Pyrazolone-derivatives as PDE4 inhibitors (Thu, 05 Jan 2012)
Fixed combination, non-fixed combination or kit of parts comprising 1-(2-{4-[3-(3,4-dimethoxyphenyl)-4,4-dimethyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]piperidin-1-yl}-2-oxoethyl)pyrrolidine-2,5-dione, metformin or a pharmaceutically acceptable salt of metformin, and at least one pharmaceutically acceptable auxiliary.
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Triazolophthalazines (Fri, 10 Jun 2011)
<p id="p-0001" num="0000">The compounds of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="40.13mm" wi="55.88mm" file="US20110136803A1-20110609-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">in which R1, R2 and R3 have the meanings as given in the description are novel effective PDE2 inhibitors.</p>
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METHYLPYRROLOPYRIDINECARBOXAMIDES (Fri, 04 Mar 2011)
The compounds of formula (I) wherein R1, R21, R22, R23, R24, Y and R3 have the meanings as given in the description, the salts thereof, and the stereoisomers of the compounds and the salts thereof are effective inhibitors of the type 5 phosphodiesterase.
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METHYLPYRROLOPYRIMIDINECARBOXAMIDES (Fri, 04 Mar 2011)
The compounds of formula (I) wherein R1, R2, R21, R22, R23, R24, Y and R3 have the meanings as given in the description, the salts thereof, and the stereoisomers of the compounds and the salts thereof are effective inhibitors of the type 5 phosphodiesterase.
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METHYLPYRROLOPYRIDINECARBOXAMIDES (Fri, 04 Mar 2011)
The compounds of formula (I) wherein R1, R21, R22, R23, R24, Y and R3 have the meanings as given in the description, the salts thereof, and the stereoisomers of the compounds and the salts thereof are effective inhibitors of the type 5 phosphodiesterase.</p>
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METHYLPYRROLOPYRIMIDINECARBOXAMIDES (Fri, 04 Mar 2011)
The compounds of formula (I) wherein R1, R2, R21, R22, R23, R24, Y and R3 have the meanings as given in the description, the salts thereof, and the stereoisomers of the compounds and the salts thereof are effective inhibitors of the type 5 phosphodiesterase.</p>
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TETRAHYDROBENZOTHIOPHENE DERIVATIVES (Fri, 25 Feb 2011)
<p id="p-0001" num="0000">Compounds of a certain formula I, in which Ra and Rb have the meanings indicated in the description, are novel effective compounds with anti-proliferative and apoptosis inducing activity.</p>
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BENZYL-SUBSTITUTED TETRACYCLIC HETEROCYCLIC COMPOUNDS (Fri, 11 Feb 2011)
The present invention pertains to Benzyl-substituted tetracyclic heterocyclic compounds, as well as the resulting pharmaceutical compositions, and their use in the treatment or prophylaxis of diseases alleviated by inhibition of type 5 phosphodiesterases. Furthermore, the present invention pertains to the methods of manufacturing these Benzyl-substituted tetracyclic heterocyclic compounds.
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NOVEL PYRAZOLONE-DERIVATIVES AND THEIR USE AS PD4 INHIBITORS (Fri, 21 May 2010)
The compounds of formula (1) wherein R1 represents a phenyl derivative of formulae (a), (b) or (c) R10 is 1-3C-alkyl and R11 is 1-3C-alkyl, or R10 and R11 together with the carbon atom, to which they are bonded, form a spiro-linked 3-, 4-, 5- or 6-membered hydrocarbon ring, A is C(O) or S(O)2, and R12 is phenyl, naphthalenyl, pyridinyl, quinolinyl, isoquinolinyl, quinoxalinyl, 1,6-naphthyridinyl, 1,8-naphthyridinyl, indolyl, phenyl substituted by R13, R14, R15 and R16, pyridinyl substituted by R17 and R18, naphthalenyl substituted by R19 and R20, quinolinyl substituted by R21 or indolyl substituted by R22, are novel effective inhibitors of the type 4 phosphodiesterase.
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NOVEL PYRAZOLONE-DERIVATIVES AND THEIR USE AS PD4 INHIBITORS (Fri, 21 May 2010)
The compounds of formula (1) wherein R1 represents a phenyl derivative of formulae (a), (b) or (c) R10 is 1-3C-alkyl and R11 is 1-3C-alkyl, or R10 and R11 together with the carbon atom, to which they are bonded, form a spiro-linked 3-, 4-, 5- or 6-membered hydrocarbon ring, A is C(O) or S(O)2, and R12 is phenyl, naphthalenyl, pyridinyl, quinolinyl, isoquinolinyl, quinoxalinyl, 1,6-naphthyridinyl, 1,8-naphthyridinyl, indolyl, phenyl substituted by R13, R14, R15 and R16, pyridinyl substituted by R17 and R18, naphthalenyl substituted by R19 and R20, quinolinyl substituted by R21 or indolyl substituted by R22, are novel effective inhibitors of the type 4 phosphodiesterase. </p>
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Pyrazolone derivatives as PDE4 inhibitors (Fri, 14 May 2010)
<p id="p-0001" num="0000">The compounds of a certain formula 1,</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="39.37mm" wi="63.16mm" file="US08304436-20121106-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> in which R1, R7, R8, R9 and n have the meanings as given in the description, are novel effective inhibitors of the type 4 phosphodiesterase. </p>
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5-BENZYL-1,2,3,6-TETRAHYDRO-4,6-DIAZA-CYCLOPENTA[C]FLUORENE COMPOUNDS AND 5-BENZYL-1,2,3,6-TETRAHYDRO-4,6-DIAZA-CYCLOHEPTA[C]FLUORENE COMPOUNDS (Fri, 12 Feb 2010)
The present invention pertains to 5 -Benzyl-1, 2, 3, 6- tetrahydro-4, 6-diazacyclopenta [c] fluorene compounds and 5 -Benzyl-1, 2, 3, 6- tetrahydro-4, 6-diaza-cyclohepta [c] fluorene compounds of formula (I), as well as the resulting pharmaceutical compositions, and their use in the treatment or prophylaxis of diseases alleviated by inhibition of type 5 phosphodiesterases. Furthermore, the present invention pertains to the methods of manufacturing these 5-Benzyl-1, 2, 3, 6- tetrahydro-4, 6-diaza-cyclopenta [c] fluorene compounds and 5-Benzyl-1, 2, 3, 6- tetrahydro-4, 6-diaza-cyclohepta [c] fluorene compounds.
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BENZYL-SUBSTITUTED TETRACYCLIC HETEROCYCLIC COMPOUNDS (Fri, 12 Feb 2010)
The present invention pertains to Benzyl-substituted tetracyclic heterocyclic compounds of formula (I), as well as the resulting pharmaceutical compositions, and their use in the treatment or prophylaxis of diseases alleviated by inhibition of type 5 phosphodiesterases. Furthermore, the present invention pertains to the methods of manufacturing these Benzyl -substituted tetracyclic heterocyclic compounds.
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6-BENZYL-2,3,4,7-TETRAHYDRO-INDOLO[2,3-C]QUINOLINE COMPOUNDS (Fri, 12 Feb 2010)
The present invention pertains to 6-benzyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinoline compounds of formula (I), as well as the resulting pharmaceutical compositions, and their use in the treatment or prophylaxis of diseases alleviated by inhibition of type 5 phosphodiesterases. Furthermore, the present invention pertains to the methods of manufacturing these 6-benzyl-2,3,4,7-tetrahydro-indolo[2,3-c]quinoline compounds.
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BENZYL-SUBSTITUTED TETRACYCLIC HETEROCYCLIC COMPOUNDS AS PDE5 INHIBITORS (Fri, 12 Feb 2010)
The present invention pertains to Benzyl-substituted tetracyclic heterocyclic compounds, as well as the resulting pharmaceutical compositions, and their use in the treatment or prophylaxis of diseases alleviated by inhibition of type 5 phosphodiesterases. Furthermore, the present invention pertains to the methods of manufacturing these Benzyl-substituted tetracyclic heterocyclic compounds.
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2,3,4,7-TETRAHYDRO-INDOLO[2,3-C]QUINOLINE COMPOUNDS (Fri, 12 Feb 2010)
The present invention pertains to 2,3,4,7-tetrahydro-indolo[2,3-c]quinoline compounds, as well as the resulting pharmaceutical compositions, and their use in the treatment or prophylaxis of diseases alleviated by inhibition of type 5 phosphodiesterases. Furthermore, the present invention pertains to the methods of manufacturing these 2,3,4,7-tetrahydro-indolo[2,3-c]quinoline compounds.
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PYRAZOLONE DERIVATIVES AS PDE4 INHIBITORS (Thu, 04 Feb 2010)
The compounds of a certain formula (1), in which R1, R7, R8, R9 and n have the meanings as given in the description, are novel effective inhibitors of the type 4 phosphodiesterase.
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Isotopically substituted proton pump inhibitors (Fri, 29 Jan 2010)
<p id="p-0001-en" num="0000">The invention relates to compounds of formula 1</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="24.98mm" wi="66.12mm" file="us20100022779a1-20100128-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">and formula 10</p> <p id="p-0004-en" num="0000"> <chemistry id="chem-us-00002-en" num="00002"> <img id="emi-c00002" he="25.57mm" wi="69.17mm" file="us20100022779a1-20100128-c00002.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0005-en" num="0000">and to compositions comprising these compounds and methods of treating gastrointestinal disorders by administering these compounds.</p>
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TRICYCLIC IMIDAZOPYRIDINE PRODRUG DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME (Thu, 19 Nov 2009)

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3-thia-10-aza-phenanthrene derivatives (Fri, 25 Sep 2009)
<p id="p-0001" num="0000">The compounds of formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.97mm" wi="69.85mm" file="US08324404-20121204-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> in which A, R1, R2 and R3 have the meanings as given in the description, are novel effective PDE4 inhibitors. </p>
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PYRROLOPYRIMIDINECARBOXAMIDES (Fri, 04 Sep 2009)
The compounds of Formula (I) wherein R1, R21, R22, R23, R24, Y and R3 have the meanings as given in the description, the salts thereof, the N-oxides of the compounds and the salts thereof and the stereoisomers of the compounds, the salts, the N-oxides of the compounds and the N-oxides of the salts thereof are effective inhibitors of the type 5 phosphodiesterase.
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PYRROLOPYRIMIDINECARBOXAMIDES (Fri, 04 Sep 2009)
The compounds of Formula (I) where in R1, R21, R22, R23, R24, Y and R3 have the meanings as given in the description, the salts thereof, the N-oxides of the compounds and the salts thereof and the stereoisomers of the compounds, the salts, the N--oxides of the compounds and the N-oxides of the salts thereof are effective inhibitors of the type 5 phospho--diesterase. </p>
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Amorphous ciclesonide (Thu, 12 Feb 2009)
The present invention relates to amorphous ciclesonide, methods to prepare the same, pharmaceutical compositions comprising amorphous ciclesonide as active ingredient, and methods of treatment using amorphous ciclesonide.
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6-N-SUBSTITUTED BENZ IMIDAZOLE DERIVATIVES AS ACID PUMP ANTAGONISTS (Fri, 19 Dec 2008)
The invention provides compounds of the formula (0), in which the substituents and symbols are as defined in the description. The compounds inhibit the secretion of gastric acid.
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PYRAZOLONE DERIVATIVES AS PDE4 INHIBITORS (Fri, 21 Nov 2008)
The compounds of a certain formula (1), in which R1, R7, R8, R9 and n have the meanings as given in the description, are novel effective inhibitors of the type 4 phosphodiesterase.
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PYRAZOLONE DERIVATIVES AS PDE4 INHIBITORS (Fri, 21 Nov 2008)
The compounds of a certain formula (1), in which R1, R7, R8, R9 and n have the meanings as given in the description, are novel effective inhibitors of the type 4 phosphodiesterase.</p>
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Process For the Production of Intermediates For the Preparation of Tricyclic Benzimidazoles (Fri, 14 Nov 2008)
<p id="p-0001-en" num="0000">The invention relates to a process for the synthesis of compounds of the formula 1-a and compounds of the formula 1-b.</p> <p id="p-0002-en" num="0000"/> <p id="p-0003-en" num="0000">The compounds of the formula 1-a and the compounds of the formula 1-b, in which the substituents R1, R2, R3, and Ar have the meanings indicated in the description, are valuable intermediates for the preparation of pharmaceutically active compounds.</p>
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Triazolophthalazines (Fri, 14 Nov 2008)
<p id="p-0001-en" num="0000">The compounds of formula (I)</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="39.96mm" wi="69.85mm" file="US07671050-20100302-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> in which R1, R2 and R3 have the meanings as given in the description are novel effective PDE2 inhibitors. </p>
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ENANTIOPURE PHARMACOLOGICALLY ACTIVE TRICYCLIC BENZIMIDAZOLES (Fri, 15 Aug 2008)
The invention provides compounds of the formula (1) in which the substituents and symbols are as de fined in the description. The compounds inhibit the secretion of gastric acid.
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6-BENZYL-2,3,4,7-TETRAHYDRO-INDOLO [2, 3-C] QUINOLINE COMPOUNDS USEFUL AS PDE5 INHIBITORS (Fri, 15 Aug 2008)
The compounds of Formula (I) wherein R1 to R8 and R11 have the meanings as given in the description, the salts thereof, the N-oxides of the compounds and the salts thereof, and the stereoisomers of the compounds, the salts, the N-oxides of the compounds and the N-oxides of the salts thereof are effective inhibitors of the type 5 phosphodiesterase.
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6-BENZYL-2,3,4,7-TETRAHYDRO-INDOLO [2, 3-C] QUINOLINE COMPOUNDS USEFUL AS PDE5 INHIBITORS (Fri, 15 Aug 2008)
The compounds of Formula (I) wherein R1 to R8 and R11 have the meanings as given in the description, the salts thereof, the N-oxides of the compounds and the salts thereof, and the stereoisomers of the compounds, the salts, the N-oxides of the compounds and the N-oxides of the salts thereof are effective inhibitors of the type 5 phosphodiesterase.</p>
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PHARMACEUTICALLY ACTIVE DIHYDROBENZOFURANE-SUBSTITUTED BENZIMIDAZOLE DERIVATIVES (Fri, 18 Jul 2008)
The invention provides compounds of the formula (1), in which the substituents and symbols are as defined in the description. The compounds inhibit the secretion of gastric acid.
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INTERMEDIATES AND PROCESS FOR THE PRODUCTION OF 5-SUBSTITUTED TRICYCLIC BENZIMIDAZOLES (Fri, 27 Jun 2008)
The invention relates to compoun ds of the formula 1-a and 1-b, in which R1, R2, R3, Ar and PG have the meanings as indicated in the description. These compounds are valuable intermediates for the preparation of pharmaceutically active compounds.
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Isotopically substituted proton pump inhibitors (Fri, 20 Jun 2008)
<p id="p-0001-en" num="0000">The invention relates to compounds of formula 1</p> <p id="p-0002-en" num="0000"> <br/> and formula 10 </p> <p id="p-0003-en" num="0000"> <br/> and to compositions comprising these compounds and methods of treating gastrointestinal disorders by administering these compounds. </p>
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PHARMACEUTICALLY ACTIVE SPIRO-SUBSTITUTED BENZIMIDAZOLE DERIVATIVES (Fri, 20 Jun 2008)
The invention provides compounds of the formula (1), in which the substituents and symbols are as defined in the description. The compounds inhibit the secretion of gastric acid.
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SPIRO-INDENE SUBSTITUTED IMIDAZONAPHYTHYRIDINE AND PYRANOIMIDAZOPYRIDINE DERIVATIVES AS INHIBITORS OF GASTRIC ACID SECRETION (Fri, 20 Jun 2008)
The invention provides compounds of the formula (1), in which the substituents and symbols are as defined in the description. The compounds inhibit the secretion of gastric acid.
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AMINO-HALOGEN-IMIDAZOPYRIDINES AS PROTON PUMP INHIBITORS (Thu, 29 May 2008)

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7,7-DISUBSTITUTED PYRANO-[2,3-C]-IMIDAZO-[1,2-A]-PYRIDINE DERIVATIVES AND THEIR USE AS GASTRIC ACID SECRETION INHIBITORS (Fri, 23 May 2008)
The invention provides compounds of the formula (1), in which the substituents and symbols are as defined in the description. The compounds inhibit the secretion of gastric acid.
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3-thia-10-aza-phenanthrene derivatives (Fri, 02 May 2008)
<p id="p-0001-en" num="0000">The compounds of formula I</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="29.72mm" wi="55.80mm" file="US07589205-20090915-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> in which A, R1, R2 and R3 have the meanings as given in the description, are novel effective PDE4 inhibitors. </p>
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PHARMACEUTICALLY ACTIVE TETRAHYDROISOQUINOLINE-SUBSTITUTED BENZIMIDAZOLE DERIVATIVES (Fri, 15 Feb 2008)
The invention provides compounds of the formula (1), in which the substituents and symbols are as defined in the description. The compounds inhibit the secretion of gastric acid.
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5-,7-BIS-SUBSTITUTED IMIDAZO[1,2-A]PYRIDINES (Fri, 08 Feb 2008)
The invention provides compounds of the formula (1), in which the substituents and symbols are as defined in the description. The compounds inhibit the secretion of gastric acid.
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PROCESS FOR THE PRODUCTION OF INTERMEDIATES FOR THE PREPARATION OF TRICYCLIC IMIDAZOPYRIDINES (Fri, 14 Dec 2007)
The invention relates to a process for the synthesis of compounds of the formula (1-a) and compounds of the formula (1-b). The compounds of the formula 1-a and the compounds of the formula 1-b, in which the substituents R1, R2, R3, and Arom have the meanings indicated in the description, are valuable intermediates for the preparation of pharmaceutically active compounds.
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3-oxa-10-aza-phenanthrenes (Fri, 09 Nov 2007)
<p id="p-0001-en" num="0000">The compounds of formula I</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="29.80mm" wi="69.85mm" file="US07838521-20101123-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> in which R1, R2 and R3 have the meanings as given in the description, are novel effective PDE4 inhibitors. </p>
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3-OXA-10-AZA-PHENANTHRENES AS PDE4 OR PDE3/4 INHIBITORS (Thu, 21 Jun 2007)
Compounds of a certain formula 1, in which R1, R2 and R3 have the meanings indicated in the description, are novel effective PDE4 inhibitors.
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PHENYLPHENANTHRIDINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME (Wed, 16 May 2007)

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ISOTOPICALLY SUBSTITUTED IMIDAZOPYRIDINE DERIVATIVES FOR THE TREATMENT OF GASTROINTESTINAL DISORDERS (Fri, 13 Apr 2007)
The invention provides deuterated compounds of the formula (1), in which the substituents and symbols are as defined in the description. The compounds inhibit the secretion of gastric acid.
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NOVEL SULPHONYLPYRROLES AS INHIBITORS OF HDAC S NOVEL SULPHONYLPYRROLES (Fri, 13 Apr 2007)
Compounds of a certain formula (I), in which R1, R2, R3, R4, R5, R6 and R7 have the meanings indicated in the description, as well as salts thereof are novel effective HDAC inhibitors.
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SULPHONYLPYRROLE HYDROCHLORIDE SALTS AS HISTONE DEACETYLASES INHIBITORS (Fri, 13 Apr 2007)
Compounds of formula I, in which R1, R2, R3, R4, R5, R6 and R7 have the meanings indicated in the description, as well as salts thereof are novel effective HDAC inhibitors. In more detail, this invention refers to salts of a compound selected from (E)-(E)-N-hydroxy-3-(1-[4-(([2-(1H-indol-2yl)-ethyl]-methyl-amino)-methyl)-benzene sulfonyl]-1H-pyrrol-3-yl)-acrylamide, (E)-3-[1-(4-dimetylaminomethyl-benzenesulfonyl)-1H-pyrrol-3-yl]-N-hydroxy-acrylamide, and (E)-N-hydroxy-3-[1-(5-pyridin-2-yl-thiophene-2-sulfonyl)-1H-pyrrol-3-yl]-acrylamide with hydrochloric acid, their hydrates and to crystalline forms of these salts and hydrates.
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SULPHONYLPYRROLE HYDROCHLORIDE SALTS AS HISTONE DEACETYLASES INHIBITORS (Fri, 13 Apr 2007)
Compounds of formula I, in which R1, R2, R3, R4, R5, R6 and R7 have the meanings indicated in the description, as well as salts thereof are novel effective HDAC inhibitors. In more detail, this invention refers to salts of a compound selected from (E)-(E)-N-hydroxy-3-(1-[4-(([2-(1H-indol-2yl)-ethyl]- methyl-amino)-methyl)-benzene sulfonyl]-1H-pyrrol-3-yl)-acrylamide, (E)-3-[1- (4-dimetylaminomethyl-benzenesulfonyl)-1H-pyrrol-3-yl]-N-hydroxy-acrylamide, and (E)-N-hydroxy-3-[1-(5-pyridin-2-yl-thiophene-2-sulfonyl)-1H-pyrrol-3-yl]- acrylamide with hydrochloric acid, their hydrates and to crystalline forms of these salts and hydrates. </p>
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SULPHONYLPYRROLES AND USE THEREOF AS INHIBITORS OF HDAC S (Fri, 13 Apr 2007)
Compounds of a certain formula (I), in which R1, R2, R3, R4, R5, R6 and R7 have the meanings indicated in the description, as well as salts thereof are novel effective HDAC inhibitors. </p>
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ISOTOPICALLY SUBSTITUTED BENZIMIDAZOLE DERIVATIVES (Fri, 02 Mar 2007)
The invention provides deuterated compounds of the formula (1), in which the substituents and symbols are as defined in the description. The compounds inhibit the secretion of gastric acid.
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ISOTOPICALLY SUBSTITUTED BENZIMIDAZOLE DERIVATIVES (Fri, 02 Mar 2007)
The invention provides deuterated compounds of the formula (1), in which the substituents and symbols are as defined in the description. The compounds inhibit the secretion of gastric acid. </p>
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ISOTOPICALLY SUBSTITUTED PANTOPRAZOLE (Fri, 02 Feb 2007)
The invention relates to compounds of formula 1 and to medicaments comprising these compounds, further to intermediates of formula 2 and 3.
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ISOTOPICALLY SUBSTITUTED PROTON PUMP INHIBITORS (Fri, 02 Feb 2007)
The invention relates to benzimidazoles of Formula (1) and to pharmaceutical compositions comprising these compounds, further to intermediates of Formula (2 and 3).
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ISOTOPICALLY SUBSTITUTED PROTON PUMP INHIBITORS (Fri, 02 Feb 2007)
The invention relates to benzimidazoles of Formula (1) and to pharmaceutical compositions comprising these compounds, further to intermediates of Formula (2 and 3). </p>
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ISOTOPICALLY SUBSTITUTED PANTOPRAZOLE (Fri, 02 Feb 2007)
The invention relates to compounds of formula 1 and to medicaments comprising these compounds, further to intermediates of formula 2 and 3. </p>
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PROCESS FOR THE PRODUCTION OF INTERMADIATES FOR THE PREPARATION OF TRICYCLIC BENZIMIDAZOLES (Fri, 29 Dec 2006)
The invention relates to a process for the synthesis of compounds of the formula 1-a and compounds of the formula 1-b. The compounds of the formula 1-a and the compounds of the formula 1-b, in which the substituents R1, R2, R3, and Ar have the meanings indicated in the description, are valuable intermediates for the preparation of pharmaceutically active compounds.
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PROCESS FOR THE PRODUCTION OF INTERMEDIATES FOR THE PREPARATION OF TRICYCLIC BENZIMIDAZOLES (Fri, 29 Dec 2006)
The invention relates to a process for the synthesis of compounds of the formula 1-a and compounds of the formula 1-b. The compounds of the formula 1-a and the compounds of the formula 1-b, in which the substituents R1, R2, R3, and Ar have the meanings indicated in the description, are valuable intermediates for the preparation of pharmaceutically active compounds. </p>
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SPIRO-BENZIMIDAZOLES AS INHIBITORS OF GASTRIC ACID SECRETION (Fri, 22 Dec 2006)
The invention provides compounds of the formula (1), in which the substituents and symbols are as defined in the description. The compounds inhibit the secretion of gastric acid.
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SPIRO-IMIDAZNAPHTHYRIDINE DERIVATIVES AS GASTRIC ACID SECRETION INHIBITORS (Fri, 22 Dec 2006)
The invention provides compounds of the formula (I), in which the substituents and symbols are as defined in the description. The compounds inhibit the secretion of gastric acid.
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SPIRO-BENZIMIDAZOLES AS INHIBITORS OF GASTRIC ACID SECRETION (Fri, 22 Dec 2006)
The invention provides compounds of the formula (1), in which the substituents and symbols are as defined in the description. The compounds inhibit the secretion of gastric acid. </p>
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SPIRO-IMIDAZNAPHTHYRIDINE DERIVATIVES AS GASTRIC ACID SECRETION INHIBITORS (Fri, 22 Dec 2006)
The invention provides compounds of the formula (I), in which the substituents and symbols are as defined in the description. The compounds inhibit the secretion of gastric acid. </p>
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MUTUAL PRODRUG COMPOUNDS FOR USE US ANTIINFLAMMATORY AGENTS WITH GASTROINTESTINAL PROTECTIVE ACTIVITY (Fri, 10 Nov 2006)
The invention relates compounds of the formula I in which the substituents and symbols have the meanings as indicated in the description. The compounds are prodrugs and exhibit in the human and/or animal body antipyretic, analgesic, antiphlogistic and/or anti-inflammatory activity as well as gastric acid secretion inhibiting and therefore gastro and intestinal protective activity.
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MUTUAL PRODRUG COMPOUNDS FOR USE AS ANTIINFLAMMATORY AGENTS WITH GASTROINTESTINAL PROTECCTIVE ACTIVITY (Fri, 10 Nov 2006)
The invention relates compounds of the formula I, in which the substituents and symbols have the meanings as indicated in the description. The compounds are prodrugs and exhibit in the human and/or animal body antipyretic, analgesic, antiphlogistic and/or anti-inflammatory activity as well as gastric acid secretion inhibiting and therefore gastro and intestinal protective activity. Formula (I)
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MUTUAL PRODRUG COMPOUNDS FOR USE AS ANTIINFLAMMATORY AGENTS WITH GASTROINTESTINAL PROTECTIVE ACTIVITY (Fri, 10 Nov 2006)
The invention relates compounds of the formula I in which the substituents and symbols have the meanings as indicated in the description. The compounds are prodrugs and exhibit in the human and/or animal body antipyretic, analgesic, antiphlogistic and/or anti-inflammatory activity as well as gastric acid secretion inhibiting and therefore gastro and intestinal protective activity. </p>
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MUTUAL PRODRUG COMPOUNDS FOR USE AS ANTIINFLAMMATORY AGENTS WITH GASTROINTESTINAL PROTECTIVE ACTIVITY (Fri, 10 Nov 2006)
The invention relates compounds of the formula I, in which the substituents and symbols have the meanings as indicated in the description. The compounds are prodrugs and exhibit in the human and/or animal body antipyretic, analgesic, antiphlogistic and/or anti-inflammatory activity as well as gastric acid secretion inhibiting and therefore gastro and intestinal protective activity. Formula (I) </p>
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SULFONYLPYRROLES AS HISTONE DEACETYLASE INHIBITORS (Fri, 13 Oct 2006)
The invention thus relates to compounds of formula (I) which are effective inhibitors of histone deacetylases.
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SULFONYLPYRROLES AS HISTONE DEACETYLASE INHIBITORS (Fri, 13 Oct 2006)
The invention thus relates to compounds of formula (I) which are effective inhibitors of histone deacetylases. </p>
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THIOAMIDE-SUBSTITUTED TRICYCLIC BENZIMIDAZOLES USEFUL FOR THE TREATMENT OF GASTROINTESTINAL DISEASES (Fri, 29 Sep 2006)
The invention relates to cyclic benzimidazoles of formula (I), in which the substituents and symbols have the meanings indicated in the description. The compounds have gastric secretion inhibiting and excellent gastric and intestinal protective action properties.
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THIOAMIDE-SUBSTITUTED TRICYCLIC BENZIMIDAZOLES USEFUL FOR THE TREATMENT OF GASTROINTESTINAL DISEASES (Fri, 29 Sep 2006)
The invention relates to cyclic benzimidazoles of formula (I), in which the substituents and symbols have the meanings indicated in the description. The compounds have gastric secretion inhibiting and excellent gastric and intestinal protective action properties. </p>
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N-SULPHONYLPYRROLES AND THEIR USE AS HISTONE DEACETYLASE INHIBITORS (Fri, 22 Sep 2006)
Compounds of a certain formula (I), in which R1 , R2, R3, R4, R5, R6 and R7 have the meanings indicated in the description, are novel effective HDAC inhibitors.
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N-SULPHONYLPYRROLES AND THEIR USE AS HISTONE DEACETYLASE INHIBITORS (Fri, 22 Sep 2006)
Compounds of a certain formula (I), in which R1 , R2, R3, R4, R5, R6 and R7 have the meanings indicated in the description, are novel effective HDAC inhibitors. </p>
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Diagnostic/therapeutic agents (Fri, 23 Jul 2004)
<p id="p-a-0001-en">Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, having reporters comprising gas-filled microbubbles stabilised by monolayers of film-forming surfactants, the reporter being coupled or linked to at least one vector. </p>
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Contrast agents (Fri, 09 Jul 2004)
<p id="p-a-0001-en">The invention relates to ultrasound contrast agents comprising vesicles comprising a protein capable of formation of gas-containing vesicles, wherein the vesicles contain gas which comprises sulphur hexafluoride or a low molecular weight fluorinated hydrocarbon. These contrast agents exhibit stability in vivo upon administration so as to permit ultrasound visualization while allowing rapid subsequent elimination from the system. </p>
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PHENYLPHENANTHRIDINES WITH PDE 1V INHIBITING ACTIVITY (Thu, 26 Jun 2003)
Compounds of formula (I), in which Rl, R2, R3, R31, R4, R5, R51, R6, R13 and R20 has the meanings indicated in the description, are novel active bronchial therapeutics.
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Separation processes (Fri, 06 Jun 2003)
<p id="p-a-0001-en">Separation of target material from a liquid sample is achieved by coupling the target to targetable encapsulated gas microbubbles, allowing the microbubbles and coupled target to float to the surface of the sample to form a floating microbubble/target layer, and separating this layer from the sample. In a positive separation process the microbubbles are then removed from the target, e.g. by bursting. In a negative separation process target-free sample material is recovered following separation of the floating layer. The method may also be used diagnostically to detect the presence of a disease marker in a sample. Novel separation apparatus is also described. </p>
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Base analogues (Fri, 28 Mar 2003)
<p id="p-00001-en">Nucleoside analogues or base analogues having structure (I), where X=O or NH or S, Y=N or CHR<sup>6</sup>or CR<sup>6</sup>, W=N or NR<sup>6</sup>or CHR<sup>6</sup>or CR<sup>6</sup>or S, n=1 or 2; each R<sup>6</sup>is independently H or O or alkyl or alkenyl or alkoxy or aryl or a reporter moiety; where necessary (i.e. when Y and/or W is N or CR<sup>6</sup>where R<sup>6</sup>is not O) a double bond is present between Y and W or W and W, and Q is H or a sugar or a sugar analogue or a nucleic acid backbone or backbone analogue.<chemistry id="chem-us-00001-en"><img he="N/A" wi="N/A" img-format="tif" id="emi-c00001-en" file="US06605611-20030812-C00001.TIF" img-content="chem" alt="embedded image"/></chemistry></p>
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Contrast agents (Fri, 14 Feb 2003)
<p id="p-a-0001-en">The invention relates to ultrasound contrast agents comprising vesicles comprising a protein capable of formation of gas-containing vesicles, wherein the vesicles contain gas which comprises sulphur hexafluoride or a low molecular weight fluorinated hydrocarbon. These contrast agents exhibit stability in vivo upon administration so as to permit ultrasound visualization while allowing rapid subsequent elimination from the system. </p>
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Contrast agents (Fri, 22 Nov 2002)
<p id="p-a-0001-en">The present invention provides contrast agents for use in diagnostic ultrasound studies comprising microbubbles of gas or a gas precursor encapsulated by non-proteinaceous crosslinked or polymerised amphiphilic moieties. </p>
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Dye intermediate and method (Wed, 02 Oct 2002)
<p id="p-00001-en">Various classes of dyes are provided having acid, ester or amide groups for covalent linking to biomolecules. The dyes may be prepared by use of a compound of formula (I)<chemistry id="chem-us-00001-en"><img he="N/A" wi="N/A" img-format="tif" id="emi-c00001-en" file="US06458966-20021001-C00001.TIF" img-content="chem" alt="embedded image"/></chemistry></p> <p id="p-00002-en">where R<sup>1</sup>comprises a linker and a carboxy including acid, salt, ester including N-hydroxysuccinimide, activated ester or amide group; R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>and R<sup>5</sup>are H, C<sub>1</sub>-C<sub>10</sub>alkyl or aralkyl or a group to modify solubility or electronic or spectral properties or a functional linking group: or R<sup>4</sup>-R<sup>5</sup>and/or R<sup>2</sup>-R<sup>4</sup>and/or R<sup>2</sup>-R<sup>3</sup>are linked to form an extended ring system; and R<sup>6</sup>is H or CHO or NO.</p>
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Base analogues (Wed, 04 Sep 2002)
<p id="p-00001-en">Nucleotide or base analogues having structure (3) or (4)<chemistry id="chem-us-00001-en"><img he="N/A" wi="N/A" img-format="tif" id="emi-c00001-en" file="US06444682-20020903-C00001.TIF" img-content="chem" alt="embedded image"/></chemistry></p> <p id="p-00002-en">wherein X═O or NH or S and</p> <p id="p-00003-en">each R<sup>6</sup>is independently H or alkyl or alkenyl or alkoxy or aryl or a reporter moiety.</p>
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Diagnostic/therapeutic agents (Fri, 02 Aug 2002)
<p id="p-a-0001-en">Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, having reporters comprising gas-filled microbubbles stabilized by monolayers of film-forming surfactants, the reporter being coupled or linked to at least one vector. </p>
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Paramagnetic material-containing magnetic resonance external marker or calibration composition (Fri, 02 Aug 2002)
<p id="p-a-0001-en">This invention relates to a set of aqueous marker compositions, each composition having a selected 1/T<sub>i </sub>value which is substantially invariant over an at least 10° C. temperature range between 15 and 40° C. and preferably over an at least ±2% magnetic field strength range about a selected field strength value between 0.01 and 5T and comprising an aqueous matrix material having a non-zero 1/T<sub>i </sub>temperature dependence within said temperature range with distributed therein a first paramagnetic material having a T<sub>i </sub>relaxivity which is substantially invariant within said range(s) and/or a second paramagnetic material having within said ranges(s) and T<sub>1 </sub>relaxivity which has a non-zero temperature dependence of opposite polarity to the temperature dependence of 1/T<sub>i </sub>of said matrix material, said set containing a plurality of said compositions with different selected 1/T<sub>i </sub>values preferably encompassing at least the range 1.0 to 2.5 s<sup>−1</sup>, said set preferably comprising at least one said composition containing said second paramagnetic material and at least one said composition containing said first paramagnetic material, where i in T<sub>i </sub>is 1 or 2. </p>
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PHTHALAZINONE COMPOUNDS AND MEDICAMENTS CONTAINING THEM (Fri, 26 Jul 2002)
Comppunds of the formula in which R1 is 1-4C-alkoxy or 1-4C-alkoxy which is completely or predominantly substituted by fluorine, R2 is 1-8C-alkoxy, 3-7C-cycloalkoxy, 1964 ט" ז באב התשס" ב - July 25, 2002 3-7C-cycloalkylmethoxy or 1-4C-alkoxy which is completely or predominantly substituted by fluorine, R3 and R4 are both hydrogen or together form an additional bond, R5 is R6, -CmH2m-R7, -CnH2n-C(O)R8, -CH(R9)2 or -CpH2p-Ar, in which R6 is hydrogen (H), 1-8C-alkyl, 3-10C-cycloalkyl, 3-7C-cycloalkylmethyl, 3-7C-alkenyl, 3-7C-alkinyl, phenyl-3-4C- alkenyl, 7-10C-polycycloalkyl, naphthyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidyl, quinazolinyl, quinoxalinyl, cinnolinyl, isoquinolyl, quinolyl, indanyl, benzoxazolyl, benzothiazolyl, oxazolyl, thiazolyl, N-methylpiperidyl, tetrahydropyranyl, tetrahydrothiapyranyl, or an unsubstituted or by R61 and/or R62 substituted phenyl radical, in which R61 is 1-4C-alkyl, 1-4C-alkoxy, nitro, halogen, carboxyl, carboxy1-4C-alkyl, 1-4C-alkoxycarbonyl, hydroxy1-4C-alkyl, amino, mono or di-1-4C-alkylamino, 1-4C- alkylcarbonylamino, aminocarbonyl, mono- or di1-4C-alkylaminocarbonyl, aminosulfonyl, mono- or di1-4C- alkylaminosulfonyl, 4-methylphenylsulfonamido, tetrazol-5-yl, 2-(1-4C-alkyl) tetrazol-5-yl or 2-benzyl- tetrazol-5-yl and R62 is 1-4C-alkyl, 1-4C-alkoxy, nitro or halogen, R7 is hydroxyl, halogen, cyano, nitro, nitroxy (-O-NO2), carboxyl, carboxyphenyloxy, phenoxy, 1-4C-alkoxy- 3-7C-cycloalkoxy, 3-7C- cycloalkylmethoxy, 1-4C-alkylcarbonyl, 1-4C-alkylcarbonyloxy, 1-4C- alkylcarbonylamino, 1-4C-alkoxycarbonyl, aminocarbonyl, mono- or di 1-4C- alkylaminocarbonyl, amino, mono or di- 1-4C-alkylamino, or an unsubstituted or by R71 and/or R72 substituted piperidnyl, piperazinyl, pyrrolidinyl or morpholinyl radical, where R71 is hydroxyl, 1-4C-alkyl, hydroxy- 1-4C-alkyl or 1-4C-alkoxycarbonyl, and R72 is 1-4C-alkyl, carboxyl, aminocarbonyl or 1-4C-alkoxycarbonyl, R8 is an unsubstituted or by R81 and/or R82 substituted phenyl, naphthyl, phenanthrenyl or anthracenyl radical, in which R81 is hydroxyl, halogen, cyano, 1-4C- alkyl, 1-4C-alkoxy carboxyl, aminocarbonyl, mono- or di1-4C- alkylaminocarbonyl, 1-4C- alkylcarbonyloxy, 1-4C-alkoxycarbonyl, amino, mono- or di1-4C-alkylamino, 1-4C-alkylcarbonylamino, or 1-4C-alkoxy which is completely or predominantly substituted by fluorine, and R82 is hydroxyl, halogen, 1-4C- alkyl, 1-4C- alkoxy or 1-4C-alkoxy which is completely or predominantly substituted by fluorine, R9 is -CqH2q-phenyl, Ar is an unsubstituted phenyl, naphthyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, quinazolinyl, quinoxalinyl, cinnolinyl, isoquinolyl, quinolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzotriazolyl, N-benzosucinimidyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, furyl, thienyl, pyrrolyl, a 2-(1-4C-alkyl) -thiazolyl- 4-yl radical, or a phenyl radical substituted by R10 and/or R11, in which R10 is hydroxyl, halogen, nitro, 1-4C alkyl, trifluoromethyl, 1-4C-alkoxy, carboxyl, carboxy1-4C-alkyl, 1-4C- alkylcarbonyloxy, 1-4C-alkoxycarbonyl, amino, mono or di-1-4C-alkyl-amino, 1-4C-alkylcarbonylamino, aminocarbonyl or mono- or di1-4C-alkylamino-carbonyl, and R11 is hydroxyl, halogen, nitro, 1-4C-alkyl or 1-4C-alkoxy, m is an integer from 1 to 8, n is an integer from 1 to 4, p is an integer from 1 to 6, q is an integer from 0 to 2, and the salts of these compounds. 1965 ט" ז באב התשס" ב - July 25, 2002
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Polymers (Fri, 21 Jun 2002)
<p id="p-a-0001-en">The invention provides compounds comprising a linear, branched or dendrimeric polymer backbone with linked thereto at least one reporter moiety, said polymer backbone comprising a plurality of amine-containing acids. Such compounds may be linked to one or more targeting agents and are useful as therapeutic and diagnostic agents, in particular in medical imaging techniques. </p>
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Compounds (Wed, 27 Feb 2002)
<p id="p-00001-en">This invention provides a physiologically tolerable light imaging contrast agent compound having a molecular weight in the range 500 to 5000000 and containing at least two chromophores having delocalized electron systems as well as at least one polyalkylene oxide (PAO) moiety having a molecular weight in the range 60 to 100000.</p>
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Targeted diagnostic/therapeutic agents having more than one different vectors (Wed, 19 Dec 2001)
<p id="p-00001-en">Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, comprising a suspension in an aqueous carrier liquid of a reporter comprising gas-containing or gas-generating material, said agent being capable of forming at least two types of binding pairs with a target.</p>
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Cores for technetium radiopharmaceuticals (Wed, 12 Dec 2001)
<p id="p-00001-en">A<sup>99m</sup>Tc complex which contains the moiety Tc═NR, Tc—N═NY or Tc(—N═NY)<sub>2</sub>, and as a synthetic organic ligand which confers biological target-seeking properties on the technetium complex,</p> <p id="p-00002-en">where:</p> <p id="p-00003-en">R is an aryl group, a substituted or unsubstituted alkyl group or the group —NR<sup>1</sup>R<sup>2</sup>;</p> <p id="p-00004-en">Y is an aryl group or a substituted or unsubstituted alkyl group;</p> <p id="p-00005-en">R<sup>1</sup>and R<sup>2</sup>are H, aryl groups or substituted or unsubstituted aliphatic or cyclic alkyl groups, and are the same or different provided that both are not hydrogen;</p> <p id="p-00006-en">where at least one of the R or Y groups comprises an aryl group which chelates the<sup>99m</sup>Tc.</p>
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Overhauser magnetic resonance imaging (ORMI) method comprising ex vivo polarization of a magnetic resonance (MR) imaging agent (Wed, 31 Oct 2001)
<p id="p-00001-en">This invention provides a method of MR investigation of a sample, the method comprising: (i) placing in a uniform magnetic field a composition comprising an OMRI contrast agent and an MR imaging agent containing nuclei (MR imaging nuclei) capable of emitting magnetic resonance signals (e.g. the primary magnetic field B<sub>0</sub>) and capable of exhibiting a T<sub>1</sub>relaxation time of 6 s or more (at 37° C. in D<sub>2</sub>O in a field of 7T); (ii) exposing the composition to a first radiation of a frequency selected to excite electron spin transitions in the OMRI contrast agent; (iii) optionally but preferably separating the whole, substantially the whole, or a portion of said OMRI contrast agent from said MR imaging agent; (iv) administering said MR imaging agent to said sample, (v) exposing the sample to a second radiation of a frequency selected to excite nuclear spin transitions; (vi) detecting magnetic resonance signals from the sample; and (vii) optionally, generating an image or dynamic flow data from the detected signals.</p>
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Iodinated x-ray contrast media (Wed, 31 Oct 2001)
<p id="p-00001-en">The invention provides low viscosity iodinated aryl compounds, useful as X-ray contrast agents, of formula C<sub>6</sub>R<sub>6</sub>wherein three non-adjacent R groups are iodine and the remaining R groups are non-ionic, hydrophilic moieties, said compound being water soluble at 20° C. to a concentration of at least 350 mgl/ml and which in aqueous solution at 20° C. at a concentration of 350 mgl/ml has a viscosity no greater than 13.8 mPas.</p>
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Bismuth compounds (Wed, 17 Oct 2001)
<p id="p-00001-en">The use in diagnostic imaging, in particular X-ray, MRI, ultrasound and scintigraphy, of contrast agents comprising bismuth clusters and/or organic bismuth compounds, and contrast media containing such bismuth compounds. The bismuth compounds are also useful in therapy, in particular as antimicrobial agents and antiulcer agents. Novel bismuth compounds are also disclosed.</p>
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NMR SPECTROSCOPY METHOD (Thu, 11 Oct 2001)
The invention relates to an $i(in vitro )method which comprises labelling a biological molecule with hyperpolarised xenon, and observing a magnetic resonance spectrum and/or image of the hyperpolarised xenon in the environment of the biological molecule. The spectrum/image provides information about the environment(s) at which atoms of xenon are bound to the biological molecule.
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NMR SPECTROSCOPIC IN VITRO ASSAY USING HYPERPOLARIZATION (Thu, 11 Oct 2001)
An $i(in vitro) assay method which comprises the use of an assay reagent containing at least one NMR active nucleus, and hyperpolarising at least one NMR active nucleus of the assay reagent; and analysing the assay reagent and/or the assay by NMR spectroscopy and/or NMR imaging. The assay reagent may contain an artificially high concentration of an NMR active nucleus.
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Preparation of n-arylmethyl aziridine derivatives, 1,4,7,10-tetraazacyclododecane derivatives obtained therefrom and n-arylethyl-ethanolamine sulphonate esters as intermediates (Wed, 12 Sep 2001)
<p id="p-00001-en">Aziridines may be subjeted to a cyclooligomerization reaction to produce polyazacycloalkane compounds useful for example in the preparation of chelating agents for use in diagnostic imaging contrast agents. N-benzyl-aziridine in particular is useful as it can be cyclotetramerized and debenzylated to yield cyclen, a key intermediate in chelating agent preparation. The invention provides a particularly attractive route to production of N-benzyl and other N-arylmethyl aziridines of formula (I)<chemistry id="chem-us-00001-en"><img he="N/A" wi="N/A" img-format="tif" id="emi-c00001-en" file="US06288224-20010911-C00001.TIF" img-content="chem"/></chemistry></p> <p id="p-00002-en">where each R<sub>1</sub>is independently hydrogen or a group AR and Ar is an optionally substituted phenyl group. The process comprises reacting a purified N-arylmethylethanolamine-sulphonate sulphonate ester with a base. N-aryimethyl-ethanolamine sulphonate ester of the formula R′NHCH<sub>2</sub>CH<sub>2</sub>OSO<sub>3</sub>H, wherein the N-arylmethyl group R′ is an N-(bisarylmethyl) or N-(triarylmethyl) group, as intermediates. In a further aspect, the invention provides compounds of formula (II)<chemistry id="chem-us-00002-en"><img he="N/A" wi="N/A" img-format="tif" id="emi-c00002-en" file="US06288224-20010911-C00002.TIF" img-content="chem"/></chemistry></p> <p id="p-00003-en">where Ar and R<sub>1</sub>are as hereinabove defined and at least two differing ArCHR<sub>21</sub>moieties are present.</p>
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Preparation of allylic aromatic compounds (Wed, 05 Sep 2001)
<p id="p-00001-en">A process for the preparation of an allylic aromatic compound in which an aromatic amine is reacted first with a nitrite and then with an allylic olefin having an eliminatable terminal substituent. Novel allylic derivatives of disubstituted benzene compounds are also described.</p>
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Chelating agents (Wed, 29 Aug 2001)
<p id="p-00001-en">The invention provides a complexant compound of formula I</p> <p id="p-00002-en">R<sup>3</sup>S(CR<sup>1</sup><sub>2</sub>)<sub>n</sub>N(R<sup>2</sup>)<sub>i</sub>(CR<sup>1</sup><sub>2</sub>)<sub>n</sub>X(CR<sup>1</sup><sub>2</sub>)<sub>n</sub>N(R<sup>2</sup>)<sub>i</sub>(CR<sup>1</sup><sub>2</sub>)<sub>n</sub>SR<sup>3</sup>  (I)</p> <p id="p-00003-en">(wherein</p> <p id="p-00004-en">each n, which may be the same or different, is an integer 2, 3 or 4 (preferably 2);</p> <p id="p-00005-en">each i, which may be the same or different, represents 0 or 1;</p> <p id="p-00006-en">each R<sup>3</sup>, which may be the same or different, is H or a thiol protecting group, preferably a protecting group;</p> <p id="p-00007-en">X is O, S, N, NR<sup>4</sup>or a substituted phosphorus (eg. oxo substituted phosphorus), preferably S or N;</p> <p id="p-00008-en">each R<sup>4</sup>, which may be the same or different, is hydrogen or an optionally substituted organic group;</p> <p id="p-00009-en">each R<sup>1</sup>, which may be the same or different, is hydrogen or an optionally substituted organic group, or a moiety CR<sup>1</sup><sub>2</sub>may represents a carbonyl group or two, three or four R<sup>1</sup>s on two different carbons together with those carbons and any intervening atoms may represent an optionally substituted saturated or unsaturated homocyclic or heterocyclic ring; and preferably, at least one CR<sup>1</sup><sub>2</sub>moiety is other than CH<sub>2</sub>or CH(CH<sub>3</sub>)) or a salt or complex thereof, wherein optionally at least one of the R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>and R<sup>4</sup>moieties is coupled directly or indirectly to a vector moiety.</p>
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Method of magnetic resonance imaging of a sample with ex vivo polarization of an MR imaging agent (Wed, 22 Aug 2001)
<p id="p-00001-en">The present invention provides a method of magnetic resonance investigation of a sample, preferably of a human or non-human animal body, said method comprising the step of ex vivo polarisation of a high T<sub>1</sub>agent and wherein the polarising agent is optionally seperated from the high T<sub>1</sub>agent before the high T<sub>1</sub>agent is administered to the sample.</p>
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Dry microparticles for use as a contrast agent (Wed, 15 Aug 2001)
<p id="p-00001-en">Microparticulate contrast agents comprising gas or a gas precursor encapsulated by a non-polymeric and non-polymerisable wall-forming material are readily characterisable materials exhibiting surprising structural integrity and stability.</p>
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IMPROVEMENTS IN OR RELATING TO DIAGNOSTIC THERAPEUTIC AGENTS (Thu, 26 Jul 2001)
</p> <p>Novel membrane-forming amphiphilic lipopeptides comprising one or more peptide moietie containing 2-50 aminoacyl residues and one or more hydrocarbon chains containing 5-50 carbo atoms. Such lipopeptides may be used in the formation of stabilised gas microbubble dispersion suitable for use as diagnostic and/or therapeutic agents, for example as ultrasound contrast agents.
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Contrast agents (Wed, 25 Jul 2001)
<p id="p-00001-en">The invention provides a composition of matter of the formula (I): V-L-R where V is an organic group having binding affinity for an angiotensin II receptor site, L is a linker moiety or a bond, and R is a moiety detectable in in vivo imaging of a human or animal body, with the provisos that where V is angiotension or a peptidic angiotensin derivative or analog then V-L-R is other than a non-metal radionuclide substituted peptide (e.g.<sup>125</sup>I substituted angiotensin II) and L-V is other than simply a peptide with a chelating agent amide bonded to a side chain thereof. This composition of matter may be used to image cardiovascular diseases and disorders.</p>
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Targeted ultrasound contrast agents (Wed, 25 Jul 2001)
<p id="p-00001-en">Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, having reporters comprising gas-filled microbubbles stabilised by monolayers of film-forming surfactants, the reporter being coupled or linked to at least one vector.</p>
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Diagnostic/therapeutic agents having microbubbles coupled to one or more vectors (Wed, 18 Jul 2001)
<p id="p-00001-en">Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, having reporters comprising gas-filled microbubbles stabilised by monolayers of film-forming surfactants, the reporter being coupled or linked to at least one vector.</p>
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Method for determining oxygen concentration (Wed, 04 Jul 2001)
<p id="p-00001-en">A method for determining the oxygen concentration of a sample using electron spin resonance enhanced magnetic resonance imaging.</p>
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Unsymmetrical complexing agents and targeting immunoreagents useful in therapeutic and diagnostic compositions and methods (Wed, 20 Jun 2001)
<p id="p-00001-en">A method for diagnostic imaging a site in a patient. The method involves the use of an immunoreactive group which is linked to an unsymmetrical oligo-2,6-pyrimidine complexing agent.</p>
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Method of contrast enhanced magnetic resonance imaging using carbohydrate particles (Wed, 21 Mar 2001)
<p id="p-00001-en">In a method of contrast MR imaging, using parenterally administered contrast agents, the improvement comprising using as the contrast agent, e.g. to achieve a negative contrast effect, composite particles comprising a biotolerable, carbohydrate or carbohydrate derivative, preferably polymeric, matrix material containing magnetically responsive particles, eg. of magnetite.</p>
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Hemoregulatory compounds (Wed, 07 Mar 2001)
<p id="p-00001-en">Novel compounds of general formula (I) which have homoregulatory activities and can be used to stimulate haematopoiesis and for the treatment of viral, fungal and bacterial infectious diseases.<chemistry id="chem-us-00001-en"><img he="N/A" wi="N/A" img-format="tif" id="emi-c00001-en" file="US06197793-20010306-C00001.TIF" img-content="chem"/></chemistry></p>
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Hemoregulatory compounds (Wed, 21 Feb 2001)
<p id="p-00001-en">The present invention relates to novel compounds which have hemoregulatory activities and can be used to stimulate hematopoiesis and for the treatment of viral, fungal and bacterial infectious diseases.</p>
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Light imaging contrast agents (Wed, 13 Dec 2000)
<p>The present invention relates to the use of particulate materials as contrast agents in vivo light imaging.</p>
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METHODS OF MAGNETIC RESONANCE IMAGING (MRI) USING CONTRACT AGENT SOLUTIONS FORMED FROM THE DISSOLUTION OF HYPERPOLARISED MATERIALS (Fri, 01 Dec 2000)
The present invention provides a method of magnetic resonance investigation of a sample, preferably of a human or non-human animal body, said method comprising: (i) nuclear spin polarising a solid MR imaging agent (i.e. a material containing in its molecular structure a non-zero nuclear spin nucleus) by (a) spin refrigeration, or by, (b) irradiating with circularly polarised light; (ii) administering the nuclear spin polarised MR imaging agent to said sample, preferably after dissolution in a physiologically tolerable solvent and also preferably after separation form some or all of the paramagnetic species or chromophores; (iii) exposing said sample to a radiation at a frequency selected to excite nuclear spin transitions in selected nuclei therein, e.g. the spin polarised nuclei of the MR imaging agent; (iv) detecting magnetic resonance signals form said sample; and (v) optionally generating an image, dynamic flow data, diffusion data, perfusion data, physiological data (e.g. pH, pO2, pCO2, temperature or ionic concentrations) or metabolic data from said detected signals.
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Polydentate imines and their metal complexes (Wed, 29 Nov 2000)
<p>Tripodal chelating agents incorporating imine C.dbd.N bonds are disclosed for the formation of lanthanide and other metal complexes which are relatively stable in the presence of water at neutral pH.</p>
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Intermediates for the preparation of iodinated contrast agents (Wed, 29 Nov 2000)
<p>5-Substituted isophthalic acid bis(allylamides) and bis(allylamide epoxides) in which said 5-substituent is --NO.sub.2, --NH.sub.2, --NHR.sup.1 or --NR.sup.1 R.sup.2 where R.sup.1 and R.sup.2 are independently optionally substituted alkyl, alkenyl, acyl, aryl, aralkyl or alkaryl groups.</p>
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Reflective microspheres for ultrasonic imaging (Wed, 29 Nov 2000)
<p>The present invention provides a method of contrast enhanced ultrasonic diagnostic imaging comprising administering to a subject a contrast enhancing amount of spheres or particles comprising a matrix enclosing a contrast agent which reflects sound waves, and generating an ultrasonic image of said subject wherein the matrix comprises a polymer held together by chemical bonds and wherein the polymer is selected from the group consisting of acrylates, polystyrene and derivatives thereof.</p>
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CONTRAST MEDIA (Fri, 10 Nov 2000)
The invention provides low viscosity iodinated aryl compounds, useful as X-ray contrast agents of formula (I) wherein n is 0 or 1, and where n is 1 each C6R5 moiety may be the same or different; X denotes a bond or a group providing a 1 to 7 atom chain linking two C6R5 moieties or, where n is 0, X denotes a group R; each group R is a hydrogen atom, an iodine atom or a hydrophilic moiety M or M1, two or three non-adjacent R groups in each C6R5 moiety being iodine and at least one R group in each C6R5 moiety being an M or M1 moiety; each M which may be the same or different, is a non-ionic hydrophilic moiety; and each M1 independently represents a -CHOHCON (R1)2 group wherein each R1, which may be the same or different, is a hydrogen atom, an OH group or a C1-6 alkoxy or optionally hydroxylated C1-5 alkyl group; at least one R group in the molecule being an M1 moiety; and isomers thereof.
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Superparamagnetic contrast media coated with starch and polyalkylene oxides (Wed, 27 Sep 2000)
<p>The invention relates to MR contrast media containing composite nanoparticles, preferably comprising a superparamagnetic iron oxide core provided with a coating comprising an oxidatively cleaved starch coating optionally together with a functionalized polyalkyleneoxide which serves to prolong blood residence.</p>
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Pyrazinedicarboxylic-acid derivatives as cell proliferation regulators (Wed, 27 Sep 2000)
<p>The present invention relates to novel pyrazine compounds and their use in the regulation of haematopoiesis, in particular in the stimulation of haematopoiesis, and in the treatment of bacterial, viral and fungal diseases.</p>
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Cores for technetium radiopharmaceuticals (Wed, 27 Sep 2000)
<p>.sup.99m Tc complexes of formula L.sub.n Tc.dbd.NR, L.sub.n Tc--N.dbd.NY, or L.sub.n Tc--(N.dbd.NY).sub.2 wherein each L is independently a monodentate or multidentate ligand; PA0 Y is a substituted or unsubstituted aryl group or substituted or unsubstituted alkyl group; PA0 R is Y or the grouping --NR.sup.1 R.sup.2 ; PA0 n is 1-4; PAL where at least one of R or Y is combined with one or more of the L groups; R.sup.1 and R.sup.2 are H, substituted or unsubstituted aryl groups or substituted or unsubstituted aliphatic or cyclic alkyl groups, and are the same or different, provided that both are not hydrogen.</p>
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Non-cluster type bismuth compounds (Wed, 13 Sep 2000)
<p>A method of generating an image of a human or non-human animal body which comprises administering to said body a physiologically tolerable contrast enhancing amount of a non-cluster type bismuth compound, and methods of treating gastrointestinal disorders using the same. Diagnostic imaging contrast media comprising non-cluster type bismuth compounds are also disclosed, together with novel covalent non-cluster type bismuth compounds.</p>
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Hemoregulatory compounds (Wed, 23 Aug 2000)
<p>The present invention relates to novel compounds which have hemoregulatory activities and can be used to stimulate hematopoiesis and for the treatment of viral, fungal and bacterial infectious diseases.</p>
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Microbubble-containing contrast agents having a non-proteinaceous crosslinked or polymerised amphiphilic shell (Wed, 23 Aug 2000)
<p>Ultrasound contrast agents having microbubbles of gas or a gas precursor encapsulated by non-proteinaceous crosslinked or polymerised amphiphilic moieties, e.g. in the form of micelles, exhibit good stability in vivo upon administration and may if desired incorporate biodegradable linkages so as to possess particular desired levels of biodegradability.</p>
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NMR SPECTROSCOPY METHOD (Fri, 14 Jul 2000)
The invention relates to an in vitro method which comprises labelling a biological molecule with hyperpolarised xenon, and observing a magnetic resonance spectrum and/or image of the hyperpolarised xenon in the environment of the biological molecule. The spectrum/image provides information about the environment(s) at which atoms of xenon are bound to the biological molecule.
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NMR SPECTROSCOPIC IN VITRO ASSAY USING HYPERPOLARIZATION (Fri, 14 Jul 2000)
An in vitro assay method which comprises the use of an assay reagent containing at least one NMR active nucleus, and hyperpolarising at least one NMR active nucleus of the assay reagent; and analysing the assay reagent and/or the assay by NMR spectroscopy and/or NMR imaging. The assay reagent may contain an artificially high concentration of an NMR active nucleus.
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NMR SPECTROSCOPIC IN VITRO ASSAY USING HYPERPOLARIZATION (Fri, 14 Jul 2000)
An in vitro assay method which comprises the use of an assay reagent containing at least one NMR active nucleus, and hyperpolarising at least one NMR active nucleus of the assay reagent; and analysing the assay reagent and/or the assay by NMR spectroscopy and/or NMR imaging. The assay reagent may contain an artificially high concentration of an NMR active nucleus. </p>
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WATER-SOLUBLE CONTRAST MEDIA FOR X-RAY IMAGING (Fri, 30 Jun 2000)
The invention provides low viscosity iodinated aryl compounds, useful as X-ray contrast agents, of formula (I) wherein n is 0 or 1; X is an amide group linked to the phenyl ring either by the nitrogen atom or by the carbon of the carbonyl group; R is H or a C1-4 alkyl group substituted by two or more -OH groups; R' is a C1-4 alkyl group optionally substituted by one or more -OH groups; R'' is a C2-4 alkyl group which may be straight chained or branched and is substituted by two or more -OH groups and isomers thereof.
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Hemoregulatory compounds (Wed, 21 Jun 2000)
<p>Novel compounds of the general formula (I) which have hemoregulatory activities and can be used to stimulate haematopoiesis and for the treatment of viral, fungal and bacterial infectious diseases. ##STR1##</p>
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Free radicals comprising benzodithiole derivatives (Wed, 17 May 2000)
<p>The present invention relates to certain novel triaryl methyl free radicals and their use as image enhancing agents in magnetic resonance imaging (MRI) as well as to contrast media containing such radicals and to the use of such radicals and their non-radical precursors in the manufacture of MRI contrast media.</p>
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COMPOUND (Fri, 05 May 2000)
The invention relates to the use as a contrast agent in MR imaging of a physiologically tolerable lanthanide compound or salt thereof having first and second oxidation states which differ in relaxivity by a factor of at least 5, and which is convertible in vivo from said first to said second oxidation state whereby contrast is enhanced in a body region in which conversion to said second state does or does not occur.
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COMPOSITIONS (Fri, 21 Apr 2000)
Water-soluble iodinated X-ray contrast agents can stabilise certain particulate compositions comprising vesicles or liquid droplets for thermal sterilisation. Such contrast agents also enhance the physical stability of particulate compositions to settling during storage.
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Hemoregulatory compounds (Wed, 19 Apr 2000)
<p>Novel compounds of the general formula (I) which have hemoregulatory activities and can be used to stimulate haematopolesis and for the treatment of viral, fungal and bacterial infectious diseases ##STR1##</p>
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Contrast agents (Wed, 19 Apr 2000)
<p>The invention provides a composition of matter of the formula (I): V-L-R where V is a non-peptidic organic group having binding affinity for an endothelin receptor site, L is a linker moiety or a bond, and R is a moiety detectable in in vivo imaging of a human or animal body. This composition of matter may be used to image diseases and disorders, particularly of the cardiovascular system.</p>
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Preparation of N-arylmethyl aziridine derivatives, 1,4,7,10-tetraazacyclododecane derivatives obtained therefrom and N-arylmethyl-ethanol-amine sulphonate esters as intermediates (Wed, 12 Apr 2000)
<p>Aziridines may be subjected to a cyclooligomerization reaction to produce polyazacycloalkane compounds useful for example in the preparation of chelating agents for use in diagnostic imaging contrast agents. N-benzyl-aziridine in particular is useful as it can be cyclotetramerized and debenzylated to yield cyclen, a key intermediate in chelating agent preparation. The invention provides a particularly attractive route to production of N-benzyl and other N-arylmethyl aziridines of formula (I) where each R.sub.1 is independently hydrogen or a group AR and Ar is an optionally substituted phenyl group. The process comprises reacting a purified N-arylmethylethanolaminesulphonate ester with a base. N-arylmethyl-ethanolamine sulphonate ester of the formula R'NHCH.sub.2 CH.sub.2 OSO.sub.3 H, wherein the N-arylmethyl group R' is an N-(bisarylmethyl) or N-(triarylmethyl) group, as intermediates. In a further aspect, the invention provides compounds of formula (II) ##STR1## where Ar and R.sub.1 are as hereinabove defined and at least two differing ArCHR.sub.21 moieties are present.</p>
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METHOD OF MAGNETIC RESONANCE IMAGING (Fri, 07 Apr 2000)
The invention provides a method of magnetic resonance imaging of regional blood oxygenation which comprises administering into the vasculature of a vascularised human or non-human animal subject a T2 blood pool contrast agent, detecting a magnetic resonance signal from at least part of the vasculature of said subject into which said contrast agent distributes, and manipulating said signal to generate an indication of the partial pressure of oxygen (pO2) in at least part of said vasculature.
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Parenteral administration of positive and negative contrast agents for MRI (Wed, 05 Apr 2000)
<p>This invention relates to improvements in and relating to magnetic resonance imaging of the human or non-human body. The invention particularly relates to a method in which positive and negative contrast agents are administered to enhance image contrast.</p>
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Liposomal agents (Wed, 05 Apr 2000)
<p>The present invention relates to a liposomal agent comprising liposomes having bound to a membrane thereof a chelated diagnostically or therapeutically effective metal ion. The chelating agent binding the metal ion has a macrocyclic chelant moiety with, attached to a single ring atom thereof, a lipophilic membrane associating moiety.</p>
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NMR IMAGE COMPOUNDS (Thu, 10 Feb 2000)
The invention relates to the use as a contrast agent in MR imaging of a substance which has a first and a second relaxivity state, which has relaxivities differing by a factor of at least 5 in said first and second states, and which is convertible $i(in vivo) from said first to said second state whereby contrast is enhanced in a body region in which conversion to said second electronic state does or does not occur.
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Free radicals (Wed, 12 Jan 2000)
<p>Novel triarylmethyl free radicals, their use as image enhancing agents in MRI, in particular to their use in Overhauser enhanced MRI of a sample for determining oxygen concentration of said sample.</p>
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Biodegradable blood-pool contrast agents (Wed, 05 Jan 2000)
<p>The invention provides a blood pool contrast agent having an overall molecular weight of at least 10KD comprising a macrostructure which has bound thereto a plurality of opsonization inhibiting moieties and carries chelated ionic paramagnetic or heavy metal moieties, the chelant groups for said chelated moieties being macrocyclic where said macrostructure is liposomal.</p>
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Nuclear Polarization Enhanced Nuclear Magnetic Resonance Imaaging (Wed, 29 Dec 1999)
<p>This invention relates to a method of electron spin resonance enhanced magnetic resonance imaging which relies on ex vivo dynamic nuclear polarisation of an MR imaging agent.</p>
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Derivatives of benzosulphonamides as inhibitors of the enzyme cyclooxygenase II (Wed, 22 Dec 1999)
<p>Compounds of the formula (I) in which A is oxygen, sulphur or NH; B is a group of the formula (IIa) or (IIb); and the other variables have the meaning given in claim 1, may be used as inhibitors of the enzyme cyclooxygenase II ##STR1##</p>
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Metal chelating compounds having an SNNN donor set (Wed, 22 Dec 1999)
<p>Ligands for radiopharmaceutical use are capable of chelating radiometal species and of being bound to biological targeting molecules. The ligands have formula (a) and (b), where A, A'=--SZ or Y, B.dbd.O or S, Y.dbd. (c), Z.dbd.H or a thiol protecting group, m=2 or 3, n=2 or 3, q=0 or 1, R.dbd.H or unsubstituted or substituted hydrocarbon and pharmaceutically acceptable salts, provided that at least one CR.sub.2 group represents CO and forms, together with an adjacent N atom, a --CONR-- amide group. ##STR1##</p>
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Cores for technetium radiopharmaceuticals (Wed, 15 Dec 1999)
<p>A synth .sup.99m Tc complex which contains the moiety Tc.dbd.NR, Tc--N.dbd.NY or Tc(--N.dbd.NY).sub.2 and an organic ligand which confers biological target-seeking properties on the technetium complex, where R is an aryl group, a substituted or unsubstituted alkyl group or the group --NR.sup.1 R.sup.2 ; Y is an aryl group or a substituted or unsubstituted alkyl group; and R.sup.1 and R.sup.2 are H, aryl groups or substituted or unsubstituted aliphatic or cyclic alkyl groups, and are the same or different provided that both are not hydrogen. Radiopharmaceuticals comprising this complex are also described, together with methods for the preparation of the complex.</p>
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Contrast media (Wed, 01 Dec 1999)
<p>The invention provides low viscosity iodinated aryl compounds, useful as X-ray contrast agents, of formula I ##STR1## (wherein n is 0 or 1, and where n is 1 each C.sub.6 R.sub.5 moeity may be the same or different; each group R is a hydrogen atom, an iodine atom or a hydrophilic moiety M or M.sub.1, two or three non-adjacent R groups in each C.sub.6 R.sub.5 moiety being iodine and at least one, and preferably two or three, R groups in each C.sub.6 R.sub.5 moiety being M or M.sub.1 moieties; X denotes a bond or a group providing a 1 to 7 atom chain linking two C.sub.6 R.sub.5 moieties or, where n is 0, X denotes a group R; each M independently is a non-ionic hydrophilic moiety; and each M.sub.1 independently represents a C.sub.1-4 alkyl group substituted by at least one hydroxyl group and optionally linked to the phenyl ring via a carbonyl, sulphone or sulphoxide group, at least one R group being an M.sub.1 moiety; with the proviso that where n is zero either at least one M.sub.1 group other than a hydroxymethyl or 1,2-dihydroxyethyl group is present or then if one hydroxymethyl or 1,2-dihydroxyethyl M.sub.1 group is present at least one nitrogen-attached or hydroxylated-C.sub.3-4 alkyl moiety-containing M group is also present) and isomers thereof.</p>
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Contrast agents (Wed, 24 Nov 1999)
<p>Novel extended polymer surfactants comprising a methoxy-terminated polyethylene glycol hydrophilic block acylated with a hydrophobic moiety comprising a chain of at least two fatty acid units, e.g. an acyloxyacyl group such as 16-hexadecanoyloxyhexadecanoyl, are useful in the preparation of polymer-based gas-containing contrast agents by emulsion techniques.</p>
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SELECTION OF CONTRAST AGENT FROM A COMBINATORIAL LIBRARY (Fri, 12 Nov 1999)
A method for the selection of a candidate contrast agent, comprising the steps of: (i) obtaining a library of test substances in admixture; (ii) screening said library for a first selected property; and either (iii) screening said library for a second selected property and selecting one or more said substances which satisfy the screening criteria for said first and second properties; or (iv) screening for a second selected property a fraction of said library which satisfies the screening criteria for said first property and selecting one or more substances which satisfy the screening criteria for said second property.
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SELECTION OF CONTRAST AGENT DRUG FROM A COMBINATORIAL LIBRARY (Fri, 12 Nov 1999)
The invention provides a method of contrast agent drug candidate selection which involves: (i) obtaining a combinatorial library comprising an admixture of potential contrast agent drug candidates each incorporating a reporter moiety which is detectable in the animate human or non-human animal body (e.g. mammalian, avian or reptilian body), said library comprising a plurality of said reporter moieties which are interdistinguishably detectable in said body; (ii) administering said library to an animate human or non-human animal body; (iii) identifying in vivo one or more of said reporter moieties which has a desired distribution and/or elimination pattern in said body and thereby identifying a member of said library which has said pattern site or a sub-set of said library which contains a member of said library which has said pattern.
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IMPROVEMENTS IN OR RELATING TO DIAGNOSTIC/THERAPEUTIC AGENTS (Fri, 05 Nov 1999)
Novel membrane-forming amphiphilic lipopeptides comprising one or more peptide moieties containing 2-50 aminoacyl residues and one or more hydrocarbon chains containing 5-50 carbon atoms. Such lipopeptides may be used in the formation of stabilised gas microbubble dispersions suitable for use as diagnostic and/or therapeutic agents, for example as ultrasound contrast agents.
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IMPROVEMENTS IN OR RELATING TO SEPARATION PROCESSES (Fri, 05 Nov 1999)
Separation of target material from a liquid sample is achieved by coupling the target to targetable encapsulated gas microbubbles, allowing the microbubbles and coupled target to float to the surface of the sample to form a floating microbubble/target layer, and separating this layer from the sample. In a positive separation process the microbubbles are then removed from the target, e.g. by bursting. In a negative separation process target-free sample material is recovered following separation of the floating layer. The method may also be used diagnostically to detect the presence of a disease marker in a sample. Novel separation apparatus is also described.
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IMPROVEMENTS IN OR RELATING TO SEPARATION PROCESSES (Fri, 05 Nov 1999)
Separation of target material from a liquid sample is achieved by coupling the target to targetable encapsulated gas microbubbles, allowing the microbubbles and coupled target to float to the surface of the sample to form a floating microbubble/target layer, and separating this layer from the sample. In a positive separation process the microbubbles are then removed from the target, e.g. by bursting. In a negative separation process target-free sample material is recovered following separation of the floating layer. The method may also be used diagnostically to detect the presence of a disease marker in a sample. Novel separation apparatus is also described. </p>
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IMPROVEMENTS IN OR RELATING TO DIAGNOSTIC/THERAPEUTIC AGENTS (Fri, 05 Nov 1999)
Novel membrane-forming amphiphilic lipopeptides comprising one or more peptide moieties containing 2-50 aminoacyl residues and one or more hydrocarbon chains containing 5-50 carbon atoms. Such lipopeptides may be used in the formation of stabilised gas microbubble dispersions suitable for use as diagnostic and/or therapeutic agents, for example as ultrasound contrast agents. </p>
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Dichelants (Wed, 27 Oct 1999)
<p>This invention relates to dichelants, in particular compounds having two macrocyclic chelant groups linked by a bridge containing an ester or amide bond, especially compounds of formula Vb ##STR1## (wherein each X which may be the same or different is NZ, O or S, at least two Xs being NZ; PA1 each Z is a group R.sup.1 or a group CR.sup.1.sub.2 Y, at least one Z, and preferably 2 or 3 Zs, on each macrocyclic ring being a group CR.sup.1.sub.2 Y; PA1 each Y is a group CO.sub.2 H, PO.sub.3 H, SO.sub.3 H, CONR.sup.1.sub.2, CON(OR.sup.1)R.sup.1, CNS or CONR.sup.1 NR.sup.1.sub.2, preferably COOH; PA1 m is 0 or 1 or 2, preferably 1; each n is 2 or 3, preferably 2; q is 1 or 2, preferably 1; PA1 each R.sup.1 which may be the same or different is a hydrogen atom or an alkyl group optionally substituted by one or more hydroxy and/or alkoxy groups; PA1 and D is a bridging group having a molecular weight of less than 1000, preferably less than 500, joining two macrocyclic rings via at least one amide or ester bond) and salts and metal chelates thereof.</p>
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Pyrazine fused to a cyclic peptide (Wed, 27 Oct 1999)
<p>The present invention relates to pyrazine fused to a cyclic peptide which is capable of regulating, in particular stimulating, haematopoiesis.</p>
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USE OF PARTICULATE CONTRAST AGENTS IN DIAGNOSTIC IMAGING FOR STUDYING PHYSIOLOGICAL PARAMETERS (Fri, 22 Oct 1999)
The present invention relates to a method of imaging of an animate human or non-human animal body, which method comprises: administering parenterally to said body a particulate material comprising a matrix or membrane material and at least one contrast generating species, which matrix or membrane material is responsive to a pre-selected physiological parameter whereby to alter the contrast efficacy of said species in response to a change in the value of said parameters; generating image data of at least part of said body in which said species is present; and generating therefrom a signal indicative of the value or variation of said parameter in said part of said body. The invention also relates to contrast media for imaging a physiological parameter.
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METHOD (Fri, 22 Oct 1999)
This invention relates to a method of measuring magnetic properties of water-insoluble particulate materials, in particular particulate magnetic resonance (mr) contrast agents. The method comprises disposing said sedimentable agent in a flowable aqueous solution of a polyalkyleneoxide-based matrix forming agent, optionally cooling the resulting dispersion to form a non-flowable aqueous dispersion of said sedimentable agent, measuring a magnetic property of said dispersion, and if desired calculating from the measured magnetic property a magnetic property of said agent or said dispersion. The method is useful in mr imaging applications.
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USE OF PARTICULATE CONTRAST AGENTS IN DIAGNOSTIC IMAGING FOR STUDYING PHYSIOLOGICAL PARAMETERS (Fri, 22 Oct 1999)
The present invention relates to a method of imaging of an animate human or non-human animal body, which method comprises: administering parenterally to said body a particulate material comprising a matrix or membrane material and at least one contrast generating species, which matrix or membrane material is responsive to a pre-selected physiological parameter whereby to alter the contrast efficacy of said species in response to a change in the value of said parameters; generating image data of at least part of said body in which said species is present; and generating therefrom a signal indicative of the value or variation of said parameter in said part of said body. The invention also relates to contrast media for imaging a physiological parameter. </p>
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Surfactants (Wed, 06 Oct 1999)
<p>The present invention provides a polyethylene glycol (PEG) ester surfactant comprising at least one polyethylene glycol moiety and at least one fatty acyl moiety characterized in that said moieties are linked by a linkage incorporating a biodegradable methylene diester unit of formula (I) EQU --CO.O.C(R.sup.1)(R.sup.2).O.CO-- (I) PAL where R.sup.1 and R.sup.2 may, for example, each be a hydrogen atom or a monovalent organic group attached through a carbon atom or R.sup.1 and R.sup.2 together may, for example, form a divalent organic group attached through carbon atoms.</p>
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Urea-linked, iodinated bis phenyl compounds for X-ray contrast media (Wed, 29 Sep 1999)
<p>The invention provides iodinated bis phenyl compounds, useful as X-ray contrast agents, of formula I ##STR1## (wherein each C.sub.6 R.sub.5 moeity may be the same or different; each R denotes a hydrogen or iodine atom or a group M, two or three non-adjacent R groups on each C.sub.6 R.sub.5 moiety denoting iodine atoms and one, two or three R groups on each C.sub.6 R.sub.5 moiety denoting M groups; PAL X denotes a group providing a 1, 2 or 3 atom chain linking the two C.sub.6 R.sub.5 groups, preferably where X is or contains in the bridging chain a carbonyloxy group each C.sub.6 R.sub.5 group being a triodophenyl group or a group in which each R is other than hydrogen; and each M is independently a non-ionic hydrophilic moiety, M preferably being a non-ionic hydrophilic moiety comprising a monohydroxy- or polyhydroxy-alkyl group) and isomers, especially stereoisomers and rotamers, thereof.</p>
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Iodinated X-ray contrast media (Wed, 29 Sep 1999)
<p>The invention provides iodinated bis phenyl compounds, useful as X-ray contrast agents, of formula (I) (wherein each C.sub.6 R.sub.5 moiety may be the same or different; each denotes a hydrogen or iodine atom or a group M, two or three non-adjacent R groups on each C.sub.6 R.sub.5 moiety denoting iodine atoms and one, two or three R groups on each C.sub.6 R.sub.5 moiety denoting M groups; X denotes a group providing a 1, 2 or 3 atom chain linking the two C.sub.6 R.sub.5 groups, preferably where X is or contains in the bridging chain a carbonyloxy group each C.sub.6 R.sub.5 group being a triodophenyl group or a group in which each R is other than hydrogen; and each M is independently a non-ionic hydrophilic moiety, M preferably being a non-ionic hydrophilic moiety comprising a monohydroxy- or polyhydroxy-alkyl group) and isomers, especially stereoisomers and rotamers, thereof. ##STR1##</p>
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Polychelants as contrast enhancing agents (Wed, 29 Sep 1999)
<p>The present invention provides a polychelant compound of formula (VII), (wherein each X which may be the same or different is NZ, O or S, at least two Xs being NZ; B is (CR.sup.1 Y) or --N(CR.sup.1.sub.2 Y)--; each Z is a group R.sup.1 or a group CR.sup.1.sub.2 Y, at least one Z being a group CR.sup.1.sub.2 Y; each Y is a group CO.sub.2 H, PO.sub.3 H, SO.sub.3 H, CONR.sup.1.sub.2, CON(OR.sup.1)R.sup.1, CNS or CONR.sup.1 NR.sup.1.sub.2 ; m is 0 or 1 or 2; each n is 2 or 3; q is 0 or 1 when B is (CR.sup.1 Y) and 2 when B is N(CR.sup.1.sub.2 Y); p is an integer having a value of at least 2; each R.sup.1 which may be the same or different is a hydrogen atom or an alkyl, aryl or aralkyl group optionally substituted by one or more hydroxy or alkoxy groups, or two R.sup.1 groups on ring atoms or in Z groups together represent a linker group L; each L which may be the same or different represents a bond or an organic linker group having a molecular weight of less than 1000 and salts and chelates thereof. These compounds, especially the diand trichelates with paramagnetic or heavy metal ions are especially useful as diagnostic imaging contrast agents.</p>
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Multinuclear complexes for X-ray imaging (Wed, 04 Aug 1999)
<p>An x-ray contrast medium containing a multinuclear complex of the formula (M.sub.6 (.mu..sub.3 B).sub.8 A.sub.v).sub.x L.sub.w, wherein M is Mo, W, Re Tc, V, Nb, Ta, Ru, or Fe; .mu..sub.3 B represent a tridentate bridging atom; A is a non-bridging atom; L is a ligand coordinately bonded to at least one M atom; x is a positive integer; and v and w are independently zero or positive integers.</p>
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Thioether-containing metal chelating compounds (Wed, 04 Aug 1999)
<p>Ligands for radiopharmaceutical use are capable of chelating radiometal species and of being bound to biological targeting molecules. The ligands have the formula (a) and (b), where A, A'=--SZ or Y, B=O or S, Y=(c), Z=H or a thiol protecting group, m=2 or 3, n=2 or 3, q=0 or 1, R=H or unsubstituted or substituted hydrocarbon and pharmaceutically acceptable salts, provided that at least one CR.sub.2 group represents CO and forms, together with an adjacent N atom; a --CONR-- amide group. ##STR1##</p>
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METHOD OF MAGNETIC RESONANCE INVESTIGATION (Fri, 16 Jul 1999)
This invention provides a method of magnetic resonance investigation of a sample, preferably of a human or non-human animal body, said method comprising: (i) producing a hyperpolarised solution of a high T1 agent by dissolving in a physiologically tolerable solvent a hyperpolarised solid sample of said high T1 agent; (ii) where the hyperpolarisation of the solid sample of said high T1 agent in step (i) is effected by means of a polarising agent, optionally separating the whole, substantially the whole, or a portion of said polarising agent from said high T1 agent; (iii) administering said hyperpolarised solution to said sample; (iv) exposing said sample to a second radiation of a frequency selected to excite nuclear spin transitions in selected nuclei e.g. the MR imaging nuclei of the high T1 agent; (v) detecting magnetic resonance signals from said sample; and (vi) optionally, generating an image, dynamic flow data, diffusion data, perfusion data, physiological data (e.g. pH, pO2, pCO2, temperature or ionic concentrations) or metabolic data from said detected signals, wherein said high T1 agent in said hyperpolarised solution has a T1 value (at a field strength in the range 0.01-5T and a temperature in the range 20-40 °C) of at least 5 seconds.
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METHOD OF MAGNETIC RESONANCE INVESTIGATION (Fri, 16 Jul 1999)
This invention provides a method of magnetic resonance investigation of a sample, preferably of a human or non-human animal body, said method comprising: (i) producing a hyperpolarised solution of a high Ti agent by dissolving in a physiologically tolerable solvent a hyperpolarised solid sample of said high Ti agent; (ii) where the hyperpolarisation of the solid sample of said high T1 agent in step (i) is effected by means of a polarising agent, optionally separating the whole, substantially the whole, or a portion of said polarising agent from said high T1 agent; (iii) administering said hyperpolarised solution to said sample; (iv) exposing said sample to a second radiation of a frequency selected to excite nuclear spin transitions in selected nuclei e.g. the MR imaging nuclei of the high T1 agent; (v) detecting magnetic resonance signals from said sample; and (vi) optionally, generating an image, dynamic flow data, diffusion data, perfusion data, physiological data (e.g. pH, pO2, pCO2, temperature or ionic concentrations) or metabolic data from said detected signals, wherein said high T1 agent in said hyperpolarised solution has a T1 value (at a field strength in the range 0.01-5T and a temperature in the range 20-40 °C) of at least 5 seconds. </p>
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Cross-linking agent (Wed, 07 Jul 1999)
<p>A method of crosslinking a crosslinkable protein or carbohydrate substrate to form a crosslinked substrate in which the crosslinking groups are biodegradable. The crosslinking groups may comprise methylene diacrylate and the substrate can be galactose.</p>
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Polymeric surfactant-encapsulated microbubbles and their use in ultrasound imaging (Wed, 07 Jul 1999)
<p>The present invention relates to polymer-based gas-containing contrast agents in which microbubbles of gas are encapsulated by non-polymerizable wall-forming block or graft copolymer surfactants. The polymer surfactants are preferably biodegradable and include block and graft copolymers containing linkages of formula (I): EQU --(O).sub.m --CO--O--C(R.sup.1 R.sup.2)--O--CO--(O).sub.n --(I) PAL where R.sup.1 and R.sup.2 each represent a hydrogen atom or a carbon-attached monovalent organic group, or R.sup.1 and R.sup.2 together form a carbon-attached divalent organic group and m and n are each zero or 1.</p>
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PARA-HYDROGEN LABELLED AGENTS AND THEIR USE IN MAGNETIC RESONANCE IMAGING (Fri, 21 May 1999)
The invention provides a method of magnetic resonance investigation of a sample, said method comprising: (i) reacting para-hydrogen enriched hydrogen with a hydrogenatable MR imaging agent precursor containing a non-hydrogen non-zero nuclear spin nucleus to produce a hydrogenated MR imaging agent; (ii) administering said hydrogenated MR imaging agent to said sample; (iii) exposing said sample to radiation of a frequency selected to excite nuclear spin transitions of said non-zero nuclear spin nucleus in said hydrogenated MR imaging agent; (v) detecting magnetic resonance signals of said non-zero nuclear spin nucleus from said sample; and (vi) optionally, generating an image or biological functional data or dynamic flow data from said detected signals.
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FACTORS VII FRAGMENTS AND ANALOGS THEREOF AND THEIR USE IN THE TREATMENT OF BLOOD CLOTTING DISORDERS (Fri, 19 Mar 1999)
This invention provides a compound which is capable of interacting with the internal receptor in the catalytic domain of FIXa or FX defined by the residues Ile?290, Ala291, Asp292, Tyr293, Thr294, Glu374¿, and Phe378 in FIXa and Leu?300, Pro301, Glu302, Trp305, Ala306, Lys385¿ and Phe389 in FXa or the ligand defined by residues Cys?95 to Cys99¿ in FIXa or Cys?96 to Cys100¿ in FXa to prevent the formation of a functional FVIIIa/FIXa complex or FXa/FV complex respectively.
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FACTOR VII FRAGMENTS AND ANALOGS THEREOF AND THEIR USE IN THE TREATMENT OF BLOOD CLOTTNG DISORDERS (Fri, 19 Mar 1999)
The invention provides a compound which is capable of interacting with the internal receptor in the catalytic domain of FVII defined by the residues Leu?263, Pro264, Glu265, Phe268, Ser269, Tyr357¿ and Arg353 or the ligand defined by residues Cys?98-Cys102¿ of the EGF-2 domain of FVII to prevent the formation of a functional FVIIa/TF complex, with the exclusion of the peptide from amino acids 82-128 of FVII and functional equivalents thereof in which amino acids in the sequence are modified or absent, and disulphide-cycle-[H-Cys-Glu-Gln-Tyr-Cys-OH].
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Contrast media (Wed, 17 Mar 1999)
<p>The invention provides low viscosity iodinated aryl compounds, useful as X-ray contrast agents, of formula I ##STR1## (wherein n is 0 or 1, and where n is 1 each C.sub.6 R.sub.5 moeity may be the same or different; each group R is a hydrogen atom, an iodine atom or a hydrophilic moiety M or M.sub.1, two or three non-adjacent R groups in each C.sub.6 R.sub.5 moiety being iodine and at least one, and preferably two or three, R groups in each C.sub.6 R.sub.5 moiety being M or M.sub.1 moieties; X denotes a bond or a group providing a 1 to 7 atom chain linking two C.sub.6 R.sub.5 moieties or, where n is 0, X denotes a group R; each M independently is a non-ionic hydrophilic moiety; and each M.sub.1 independently represents a C.sub.1-4 alkyl group substituted by at least one hydroxyl group and optionally linked to the phenyl ring via a carbonyl, sulphone or sulphoxide group, at least one R group being an M.sub.1 moiety; with the proviso that where n is zero either at least one M.sub.1 group other than a hydroxymethyl or 1,2-dihydroxyethyl group is present or then if one hydroxymethyl or 1,2-dihydroxyethyl M.sub.1 group is present at least one nitrogen-attached or hydroxylated-C.sub.3-4 alkyl moiety-containing M group is also present) and isomers thereof.</p>
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DYE INTERMEDIATE AND METHOD TO MANUFACTURE DYES (Fri, 19 Feb 1999)
Various classes of dyes are provided having acid, ester or amide groups for covalent linking to biomolecules. The dyes may be prepared by use of a compound of formula (I) where R1 comprises a linker and a carboxy including acid, salt, ester including N-hydroxysuccinimide, activated ester or amide group; R?2, R3, R4 and R5¿ are H, C¿1?-C10 alkyl or aralkyl or a group to modify solubility or electronic or spectral properties or a functional linking group: or R?4-R5¿ and/or R2-R4 and/or R2-R3 are linked to form an extended ring system; and R6 is H or CHO or NO.
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DYE INTERMEDIATE AND METHOD (Fri, 19 Feb 1999)
Various classes of dyes are provided having acid, ester or amide groups for covalent linking to biomolecules. The dyes may be prepared by use of a compound of formula (I) where R1 comprises a linker and a carboxy including acid, salt, ester including N-hydroxysuccinimide, activated ester or amide group; R2, R3, R4 and R5 are H, C1-C10 alkyl or aralkyl or a group to modify solubility or electronic or spectral properties or a functional linking group: or R4-R5 and/or R2-R4 and/or R2-R3 are linked to form an extended ring system; and R6 is H or CHO or NO. </p>
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BASE ANALOGUES (Fri, 12 Feb 1999)
Nucleoside analogues or base analogues having structure (I), where X = O or NH or S, Y = N or CHR?6 or CR6¿, W = N or NR?6 or CHR6 or CR6¿ or S, n = 1 or 2; each R6 is independently H or O or alkyl or alkenyl or alkoxy or aryl or a reporter moiety; where necessary (i.e. when Y and/or W is N or CR6 where R6 is not O) a double bond is present between Y and W or W and W, and Q is H or a sugar or a sugar analogue or a nucleic acid backbone or backbone analogue.
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BASE ANALOGUES (Fri, 12 Feb 1999)
Nucleoside analogues or base analogues having structure (I), where X = O or NH or S, Y = N or CHR6 or CR6, W = N or NR6 or CHR6 or CR6 or S, n = 1 or 2; each R6 is independently H or O or alkyl or alkenyl or alkoxy or aryl or a reporter moiety; where necessary (i.e. when Y and/or W is N or CR6 where R6 is not O) a double bond is present between Y and W or W and W, and Q is H or a sugar or a sugar analogue or a nucleic acid backbone or backbone analogue. </p>
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Hydrazide derivatives of polyamides and their medical use as chelating agents (Wed, 10 Feb 1999)
<p>The invention relates to certain substituted derivatives of aminopolycarboxylic acids and metal chelates thereof. The compounds are particularly suitable for use as diagnostic agent. For example, the compounds can be used as radiodiagnostic agents, detoxification agents and contrast agents for diagnostic imaging processes. In particular, the high relaxivity paramagnetic metal chelates of substituted aminopolycarboxylic acids are especially suited for use as magnetic resonance imaging contrast agents.</p>
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Composition for MRI comprising both a positive and a negative contrast agent (Wed, 10 Feb 1999)
<p>This invention relates to improvements in and relating to magnetic resonance imaging of the human or non-human body. The invention particularly relates to a method in which positive and negative contrast agents are administered to enhance image contrast.</p>
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PROCESS FOR THE PREPARATION OF POLYETHER PHOSPHATES (Fri, 05 Feb 1999)
The invention provides an improved process for the synthesis of compounds carrying at least one phosphate group, especially polyalkylene glycol phosphate compounds, said process comprising the steps of: (a) reacting a compound containing at least one primary alcohol moiety with a diaryl- or diaralkyl- halophosphate whereby to form the corresponding diaryl- or diaralkyl-phosphate ester; (b) reductively cleaving the resulting product; and (c) if desired, repeating steps (a) and (b) with the product of step (b) whereby to produce a compound carrying two or more phosphate groups. Advantages of the process in accordance with the invention are that this avoids the production of by-products and results in products which are low in impurities. Also provided are novel diaryl- and diaralkyl-phosphate ester compounds, in particular polyethylene glycol diphenylphosphate ester and derivatives thereof.
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Magnetic-polymer particles (Wed, 03 Feb 1999)
<p>A magnetic-polymer particle, useful in immunoassay techniques and various other biological/medical applications is produced by coprecipitation of transition metals in the presence of a polymer having available coordination sites. These particles are capable of forming stable aqueous suspensions and may be easily resuspended after agglomeration.</p>
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Method of T.sub.1 -weighted resonance imaging of RES organs (Wed, 06 Jan 1999)
<p>The invention provides a method of contrast enhanced MR angiography of the human or non-human animal body, said method comprising administering into the vasculature thereof a contrast effective amount of a contrast agent composition comprising magnetic particles having a r.sub.2 /r.sub.1 ratio of no more than 5, and, at a time when sufficient of said magnetic particles remain in the vasculature to provide positive contrast enhancement thereof in a T.sub.1 -weighted image while sufficient magnetic particles have been taken up into an organ of the reticuloendothelial system to provide negative contrast enhancement thereof in said T.sub.1 -weighted image, generating a T.sub.1 -weighted image magnetic resonance image of at least said organ.</p>
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OVERHAUSER MAGNETIC RESONANCE IMAGING (ORMI) METHOD COMPRISING EX VIVO POLARIZATION OF A MAGNETIC RESONANCE (MR) IMAGING AGENT (Thu, 24 Dec 1998)
This invention provides a method of MR investigation of a sample, said method comprising: (i) placing in a uniform magnetic field a composition comprising an OMRI contrast agent and an MR imaging agent containing nuclei (MR imaging nuclei) capable of emitting magnetic resonance signals (e.g. the primary magnetic field B0) and capable of exhibiting a T1 relaxation time of 6s or more (at 37 °C in D20 in a field of 7T); (ii) exposing said composition to a first radiation of a frequency selected to excite electron spin transitions in said OMRI contrast agent; (iii) optionally but preferably separating the whole, substantially the whole, or a portion of said OMRI contrast agent from said MR imaging agent; (iv) administering said MR imaging agent to said sample; (v) exposing said sample to a second radiation of a frequency selected to excite nuclear spin transitions; (vi) detecting magnetic resonance signals from said sample; and (vii) optionally, generating an image or dynamic flow data from said detected signals.
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OVERHAUSER MAGNETIC RESONANCE IMAGING (ORMI) METHOD COMPRISING EX VIVO POLARIZATION OF A MAGNETIC RESONANCE (MR) IMAGING AGENT (Thu, 24 Dec 1998)
This invention provides a method of MR investigation of a sample, said method comprising: (i) placing in a uniform magnetic field a composition comprising an OMRI contrast agent and an MR imaging agent containing nuclei (MR imaging nuclei) capable of emitting magnetic resonance signals (e.g. the primary magnetic field B0) and capable of exhibiting a T1 relaxation time of 6s or more (at 37 ~C in D20 in a field of 7T); (ii) exposing said composition to a first radiation of a frequency selected to excite electron spin transitions in said OMRI contrast agent; (iii) optionally but preferably separating the whole, substantially the whole, or a portion of said OMRI contrast agent from said MR imaging agent; (iv) administering said MR imaging agent to said sample; (v) exposing said sample to a second radiation of a frequency selected to excite nuclear spin transitions; (vi) detecting magnetic resonance signals from said sample; and (vii) optionally, generating an image or dynamic flow data from said detected signals. </p>
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SONODYNAMIC THERAPY USING AN ULTRASOUND SENSITIZER COMPOUND (Fri, 27 Nov 1998)
The invention provides a method of treatment of the human or animal body by sonodynamic therapy in which a sensitizer agent is administered to said body and said body is exposed to ultrasound to achieve a cytopathogenic effect at a site therein, wherein the said sensitizer agent is a physiologically tolerable substance which is capable of enhancing the cytopathogenic efficacy of said sonodynamic therapy. Preferably, the sensitizer agent is a water-soluble polymer compound or a conjugate thereof.
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Dendrimeric compounds (Wed, 11 Nov 1998)
<p>The invention provides a dendrimeric compound comprising a dendrimeric bioactive moiety with linked thereto a plurality of diagnostically or therapeutically active moieties characterized in that the molecular skeleton of said compound contains at least one biodegradable cleavage site such that on cleavage thereof said active moieties are released in renally excretable form.</p>
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METHOD OF DEMARCATING TISSUE (Fri, 06 Nov 1998)
This invention provides a method of treatment of the human or animal body to remove tumorous tissue therefrom, wherein an effective amount of a dye compound is administered to said body and allowed to accumulate at tumorous tissues or cells therein and wherein tumorous tissue or cells at which said dye compound has accumulated is removed or destroyed in situ, the improvement comprising using as said dye compounds a physiologically tolerable dye compound being a polysulphonic acid the molecular structure whereof comprises at least one chromophore and at least 5 sulphonic acid groups, or a derivative thereof.
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LIGHT IMAGING CONTRAST AGENTS (Fri, 06 Nov 1998)
The present invention relates to the use of materials as contrast agents in in vivo light imaging using optical microscopy.
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COMPOUNDS (Fri, 06 Nov 1998)
This invention provides a physiologically tolerable light imaging contrast agent compound having a molecular weight in the range 500 to 500000 and containing at least two chromophores having delocalized electron systems as well as at least one polyalkylene oxide (PAO) moiety having a molecular weight in the range 60 to 100000.
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Hemoregulatory peptides for stimulating the myelopoietic system (Wed, 04 Nov 1998)
<p>The invention provides compounds of the general formula (I): EQU A.sup.1 --B.sup.1 --X.sup.1 --(CH.sub.2).sub.m --(CON(R.sub.1)).sub.r --(CH.sub.2).sub.s --Y.sup.1 --(CH.sub.2).sub.s --(N(R.sub.1)CO).sub.r --(CH.sub.2).sub.n --X.sup.1 --B.sup.1 --A.sup.1 PAL The compounds of this invention are also illustrated by the Formula (II): EQU A.sup.2 --B.sup.2 --X.sup.2 --(CH.sub.2).sub.m --(N(R.sub.1)CO).sub.r --(CH.sub.2).sub.s --Y.sup.2 --(CH.sub.2).sub.s --(CON(R.sub.1)).sub.r --(CH.sub.2).sub.n --X.sup.2 --B.sup.2 --A.sup.2 PAL The compounds have hemoregulatory activities and can be used to stimulate haematopoiesis and for the prevention and treatment of viral, fungal and bacterial infectious diseases.</p>
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CONTRAST AGENTS (Fri, 30 Oct 1998)
The invention provides a composition of matter of the formula (I): V - L - R, where V is a vector moiety having affinity for an angiogenesis-related endothelias cell receptor, L is a linker moiety or a bond and R is a detectable moiety, characterised in that V is a non-peptidic organic group, or V is peptidic and R is a macromolecular or particulate species providing a multiplicity of labels detectable in in vivo imaging.
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NMR IMAGE COMPOUNDS (Fri, 30 Oct 1998)
The invention relates to the use as a contrast agent in MR imaging of a substance which has a first and a second relaxivity state, which has relaxivities differing by a factor of at least 5 in said first and second states, and which is convertible in vivo from said first to said second state whereby contrast is enhanced in a body region in which conversion to said second electronic state does or does not occur.
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Microparticulate microbubble-generating contrast agents (Wed, 28 Oct 1998)
<p>The present invention relates to contrast agents comprising microbubble-generating carbohydrate particles having a surfactant admixed within the microparticulate structure, wherein the microbubbles generated by the microparticles comprise a biocompatible low molecular weight fluorinated hydrocarbon. The contrast agents exhibit useful levels of contrast efficiency and/or stability and may be used in diagnostic applications such as ultrasound and MR imaging.</p>
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Use of free radicals in ESR and ESREMR imaging (Wed, 28 Oct 1998)
<p>The present invention relates to a method of generating an electron spin resonance enhanced magnetic resonance image of a sample which comprises introducing into the sample a magnetic resonance signal enhancing amount of a free radical and generating an enhanced electron spin resonance image of the sample. The method comprises using as the free radical an inert triarylmethyl free radical, wherein each aryl moiety of said triarylmethyl radical, which may be identical or different, comprises an optionally substituted 6-membered carbocyclic or thienyl ring. The invention also relates to the use of trityls in ESR imaging.</p>
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CHELATING AGENTS (Fri, 23 Oct 1998)
The invention provides a complexant compound of formula (I): R3S(CR12)nN(R2)i(CR12)nX(CR12)nN(R2)i(CR12)nSR3, (wherein each n, which may be the same or different, is an integer 2, 3 or 4 (preferably 2); each i, which may be the same or different, represents 0 or 1; each R3, which may be the same or different, is H or a thiol protecting group, preferably a protecting group; X is O, S, N, NR4 or a substituted phosphorus (e.g. oxo substituted phosphorus), preferably S or N; each R4, which may be the same or different, is hydrogen or an optionally substituted organic group; each R2, which may be the same or different, is hydrogen or an optionally substituted organic group; each R1, which may be the same or different, is hydrogen or an optionally substituted organic group, or a moiety CR12 may represent a carbonyl group or two, three or four R1S on two different carbons together with those carbons and any intervening atoms may represent an optionally substituted saturated or unsaturated homocyclic or heterocyclic ring; and preferably, at least one CR12 moiety is other than CH2 or CH(CH3)) or a salt or complex thereof, wherein optionally at least one of the R?1, R2, R3 and R4¿ moieties is coupled directly or indirectly to a vector moiety.
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CHELATING AGENTS (Fri, 23 Oct 1998)
The invention provides a complexant compound of formula (I): R3S(CR12)nN(R2)i(CR12)nX(CR12)nN(R2)i(CR12)nSR3, (wherein each n, which may be the same or different, is an integer 2, 3 or 4 (preferably 2); each i, which may be the same or different, represents 0 or 1; each R3, which may be the same or different, is H or a thiol protecting group, preferably a protecting group; X is O, S, N, NR4 or a substituted phosphorus (e.g. oxo substituted phosphorus), preferably S or N; each R4, which may be the same or different, is hydrogen or an optionally substituted organic group; each R2, which may be the same or different, is hydrogen or an optionally substituted organic group; each R1, which may be the same or different, is hydrogen or an optionally substituted organic group, or a moiety CR12 may represent a carbonyl group or two, three or four R1S on two different carbons together with those carbons and any intervening atoms may represent an optionally substituted saturated or unsaturated homocyclic or heterocyclic ring; and preferably, at least one CR12 moiety is other than CH2 or CH(CH3)) or a salt or complex thereof, wherein optionally at least one of the R1, R2, R3 and R4 moieties is coupled directly or indirectly to a vector moiety. </p>
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Process for the preparation of iodinated contrast agents and intermediates therefor (Wed, 21 Oct 1998)
<p>The invention provides a process for the production of a 2,3-dihydroxypropylamino compound, said process comprising the reaction steps of: PA1 (i) obtaining an allylamino compound; PA1 (ii) epoxidizing said allylamino compound to yield an epoxypropylamino compound; and PA1 (iii) hydrolysing said epoxypropylamino compound to yield a 2,3-dihydroxypropylamino compound. PAL This process may be used to produce simple 2,3-dihydroxypropylamino compounds such as APD or complex ones such as BAPD (an intermediate in the production of iohexol).</p>
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Method of ultrasonic imaging comprising administering biocompatible spheres or particles (Wed, 07 Oct 1998)
<p>A method of contrast enhanced ultrasonic diagnostic imaging comprising administering to a subject a contrast enhancing amount of spheres or particles comprising a matrix enclosing a contrast agent which reflects sound waves, said matrix being a biocompatible, biodegradable, non-immunogenic, non-polyamino acid polymer; and generating an ultrasonic image of said subject.</p>
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RADIOLABELLED SOMATOSTATIN RECEPTOR LIGANDS FOR DIAGNOSIS AND THERAPY (Fri, 25 Sep 1998)
The invention relates to a carrier substance for radionuclides used in the diagnosis and/or radiotherapy of somatostatin receptor-positive tumors or target cells. Said conjugate consists of somatostatin 14 agonists, lanreotide and a macrocyclic chelating agent former which forms stable chelates with metallic radionuclides in physiological conditions. </p>
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POLYDENTATE IMINES AND THEIR METAL COMPLEXES (Sat, 12 Sep 1998)
Novel neutral, water soluble metal complexes, particularly those containing lanthanide metals, yttrium, indium or gallium, processes for their preparation, ligands involved in their preparation, pharmaceutical formulations containing them, and their use in diagnostic methods are disclosed. The compounds are represented by Formula (I) where: A is N, CR1, P, P=O, cis,cis,cis-1,3,5-trisubstituted-cyclohexane or an N,N',N''-trisubstituted-triaza 9 to 14 membered macrocyclic ring; L?1, L2, L3¿ are linker groups which are independently chosen from C¿1-4? alkylene, C4-6 cycloalkylene or C4-6 o-arylene; Y?1, Y2, Y3¿ are independently chosen from -NH¿2?, -B(=O)OZ, -N=CR-B(=O)OZ, -NR-CR2-B(=O)OZ, -N[CR2-B(=O)Q]2 and -O-CR2-B(=O)OZ, where B is C or PR?2¿, each Q is independently -OZ or -NR¿2? and Z is H or a counter-ion; each R and R?1¿ group is independently chosen from H, C¿1-5? alkyl, C1-5 alkoxyalkyl, C1-5 hydroxyalkyl, C1-5 aminoalkyl, C5-10 aryl or C1-6 fluoroalkyl; R?2¿ is OH, C¿1-6? alkyl, C1-6 alkoxyalkyl, C1-6 fluoroalkyl, C1-10 alkoxy or C5-10 aryl; with the proviso that at least one of Y?1, Y2, and Y3¿ is -N=CR-B(=O)OZ.
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TRIARYLMETHYL FREE RADICALS AS IMAGE ENHANCING AGENTS (Sat, 12 Sep 1998)
Novel triarylmethyl free radicals, their use as image enhancing agents in MRI, in particular to their use in Overhauser enhanced MRI of a sample for determining oxygen concentration of said sample.
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Polymeric contrast agents for medical imaging (Wed, 02 Sep 1998)
<p>The invention provides polymeric polychelants containing polymer repeat units of formula L--Ch--L--B! (where Ch is a polydentate chelant moiety; L is an amide or ester linkage; B is a hydrophobic group providing a carbon chain of at least 4 carbon atoms between the L linkages it interconnects) or a salt or chelate thereof, with the proviso that where Ch is 2,5-biscarboxymethyl-2,5-diazahex-1,6-diyl, the polychelant is metallated with lanthanide or manganese ions or B provides a carbon chain of at least 10 carbon atoms between the L linkages it interconnects and their salts and chelates. The paramagnetic polychelates of the polychelants of the invention have remarkably high R.sub.1 relaxivities.</p>
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Chelant moieties linked to an aryl moiety by an interrupted alkylene linker (Wed, 26 Aug 1998)
<p>The invention provides amphiphilic compounds of the formula (I) Ch--(--L--Ar--(--AH).sub.n).sub.m (where Ch is a hydrophilic chelant moiety or a salt or a chelate thereof); each L is an optionally oxo substituted C.sub.2-25 -alkylene linker wherein at least one CH.sub.2 moiety is replaced by a group X.sup.1 (e.g. L may include a chain sequence, an X.sup.1 (CH.sub.2 CH.sub.2 X.sup.1).sub.u (where u is a positive integer) such as X.sup.1 (CH.sub.2 CH.sub.2 X.sup.1).sub.u, CH.sub.2 X.sup.1 CH.sub.2 CH.sub.2 X.sup.1 CH.sub.2 CH.sub.2 X.sup.1, CH.sub.2 X.sup.1 CH.sub.2 CH.sub.2 X.sup.1 CH.sub.2 CH.sub.2 X.sup.1 CH.sub.2 CH.sub.2 X.sup.1, etc.), and wherein L is optionally interrupted by a metabolizable group M but with the provisos that the terminus of L adjacent Ch is CH.sub.2 and that the terminus of L adjacent Ar is X.sup.1 or a CH.sub.2 group adjacent or separated by one CH.sub.2 from a group X.sup.1 (thus, for example the L--Ar linkage may be L.sup.1 --X.sup.1 --Ar, L.sup.1 --CH.sub.2 --Ar, L.sup.1 --X.sup.1 CH.sub.2 --Ar or L.sup.1 --X.sup.1 CH.sub.2 CH.sub.2 --Ar, where L.sup.1 is the residue of L; each Ar is an aryl ring optionally substituted by or having fused thereto a further aryl ring; each AH is a protic acid group, preferably an oxyacid, e.g. a carbon, sulphur or phosphorus oxyacid or a salt thereof; each X.sup.1 is O, S, NR.sup.1 or PR.sup.1, preferably no more than 3 X.sup.1 groups being present in L; each R.sup.1 is hydrogen, alkyl or aryl; and m and n are positive integers, m being for example 1 to 4, especially 1 or 2 and n being for example, 1, 2 or 3) which are especially suited for use in diagnostic imaging of the hepatobiliary system.</p>
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Contrast agents comprising gas-containing or gas-generating microparticles or microballoons (Wed, 19 Aug 1998)
<p>The present invention relates to contrast agents comprising gas-containing or gas-generating polymer microparticles and/or microballoons, in which the polymer is a biodegradable polymer containing units of formula ---(O).sub.m --CO--O--C(R.sup.1 R.sup.2)--O--CO--(O).sub.n --!- . R.sup.1 and R.sup.2 each represent hydrogen or a carbon-attached monovalent organic group, or together form a carbon-attached divalent organic group, and m and n are each independently zero or one. The contrast agents may be used in diagnostic applications such as ultrasound and MR imaging.</p>
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PROCESS FOR THE PREPARATION OF IODINATED CONTRAST AGENTS AND INTERMEDIATES THEREFOR (Fri, 14 Aug 1998)
The invention provides a process for the production of a 2,3-dihydroxypropylamino compound, said process comprising the reaction steps of: (i) obtaining an allylamino compound; (ii) epoxidizing said allylamino compound to yield an epoxypropylamino compound; and (iii) hydrolysing said epoxypropylamino compound to yield a 2,3-dihydroxypropylamino compound. This process may be used to produce simple 2,3-dihydroxypropylamino compounds such as APD or complex ones such as BAPD (an intermediate in the production of iohexol).
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PROCESS FOR THE PREPARATION OF IODINATED CONTRAST AGENTS AND INTERMEDIATES THEREFOR (Fri, 14 Aug 1998)
The invention provides a process for the production of a 2,3- dihydroxypropylamino compound, said process comprising the reaction steps of: (i) obtaining an allylamino compound; (ii) epoxidizing said allylamino compound to yield an epoxypropylamino compound; and (iii) hydrolysing said epoxypropylamino compound to yield a 2,3-dihydroxypropylamino compound. This process may be used to produce simple 2,3-dihydroxypropylamino compounds such as APD or complex ones such as BAPD (an intermediate in the production of iohexol). </p>
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SUBSTITUTED DERIVATIVES OF BENZOSULPHONAMIDES AS INHIBITORS OF THE ENZYME CYCLOOXYGENASE II (Fri, 07 Aug 1998)
The present application relates to compounds of formula (I) wherein A represents oxygen, sulfur or -NH-, m is 0-2, and R1, R2, R3, R6 and R7 have the meanings given in the specification, to a process for their preparation, as well as to their use in the inhibition of cyclooxygenase II.
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POLYMERS (Fri, 31 Jul 1998)
The invention provides compounds comprising a linear, branched or dendrimeric polymer backbone with linked thereto at least one reporter moiety, said polymer backbone comprising a plurality of amine-containing acids. Such compounds may be linked to one or more targeting agents and are useful as therapeutic and diagnostic agents, in particular in medical imaging techniques.
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POLYMERS (Fri, 31 Jul 1998)
The invention provides compounds comprising a linear, branched or dendrimeric polymer backbone with linked thereto at least one reporter moiety, said polymer backbone comprising a plurality of amine-containing acids. Such compounds may be linked to one or more targeting agents and are useful as therapeutic and diagnostic agents, in particular in medical imaging techniques. </p>
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HEMOREGULATORY COMPOUNDS (Thu, 30 Jul 1998)
The present invention relates to novel compounds which have hemoregulatory activities and can be used to stimulate hematopoiesis and for the treatment of viral, fungal and bacterial infectious diseases.
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METHOD OF MAGNETIC RESONANCE IMAGING (Fri, 17 Jul 1998)
The invention relates to a method of magnetic resonance imaging (MRI) of a living sample comprising the steps of hyperpolarising a hyperpolarisable gas ex-vivo and transferring the nuclear polarisation from the hyperpolarised gas to the nuclei of an MR imaging agent, that is not hyperpolarisable, that is exposed to a uniform magnetic field and that is introduced in contact to the hyperpolarisable gas, separating the hyperpolarisable gas from the MR imaging agent, administering the MR imaging agent to the living sample, exciting NMR transitions in the nuclei of the imaging agent and detecting an NMR signal thereof.
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Contrast agents (Wed, 17 Jun 1998)
<p>The invention relates to compounds of formula (I): ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are independently selected from: (i) saturated or unsaturated fatty acyl groups, preferably having from 14 to 24 carbon atoms, more preferably of a type found in nature; or PA0 (ii) groups of formula (II): ##STR2## wherein R.sup.4 and R.sup.5 are independently selected from hydrogen atoms, C.sub.1-4 alkyl groups and aryl groups, preferably C.sub.6-10 aryl groups; n represents the integers 0 or 1; A represents either a chemical bond or a straight or branched C.sub.1-6 alkylene chain and R.sup.6 is a triiodinated phenyl group which may also carry other substituents. The invention also relates to X-ray contrast media containing these compounds, as well as methods of enhancing X-ray images of a human subject wherein the contrast media are administered to the subject prior to imaging.</p>
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Method for determining oxygen concentration using magnetic resonance imaging (Wed, 17 Jun 1998)
<p>A method for determining the oxygen concentration of a sample using electron spin resonance enhanced magnetic resonance imaging.</p>
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Macrocyclic complexing agents and targeting immunoreagents useful in therapeutic and diagnostic compositions and methods (Wed, 03 Jun 1998)
<p>A metal chelate comprising a compound having the following formula and one or more metal ions which metal ions are a radionucleotide or a paramagnetic metal ion: ##STR1##</p>
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Polyoxyethylene fatty acid ester surfactants and use thereof (Thu, 28 May 1998)
The present invention provides a polyethylene glycol (PEG) ester surfactant comprising at least one polyethylene glycol moiety and at least one fatty acyl moiety characterised in that said moieties are linked by a linkage incorporating a biodegradable methylene diester unit of formula (I) -CO.O.C(R<1>)(R<2>).O.CO- where R<1> and R<2> may, for example, each be a hydrogen atom or a monovalent organic group attached through a carbon atom or R<1> and R<2> together may, for example, form a divalent organic group attached through carbon atoms.
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IMPROVEMENTS IN OR RELATING TO DIAGNOSTIC/THERAPEUTIC AGENTS (Fri, 08 May 1998)
Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, having reporters comprising gas-filled microbubbles stabilised by monolayers of film-forming surfactants, the reporter being coupled or linked to at least one vector.
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IMPROVEMENTS IN OR RELATING TO DIAGNOSTIC/THERAPEUTIC AGENTS (Fri, 08 May 1998)
Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, comprising a suspension in an aqueous carrier liquid of a reporter comprising gas-containing or gas-generating material, said agent being capable of forming at least two types of binding pairs with a target.
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CONTRAST AGENTS (Fri, 08 May 1998)
The invention provides a composition of matter of the formula (I): V - L - R where V is a non-peptidic organic group having binding affinity for an endothelin receptor site, L is a linker moiety or a bond, and R is a moiety detectable in in vivo imaging of a human or animal body. This composition of matter may be used to image diseases and disorders, particularly of the cardiovascular system.
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CONTRAST AGENTS (Fri, 08 May 1998)
The invention provides a composition of matter of the formula (I): V-L-R where V is an organic group having binding affinity for an angiotensin II receptor site, L is a linker moiety or a bond, and R is a moiety detectable in in vivo imaging of a human or animal body, with the provisos that where V is angiotension or a peptidic angiotensin derivative or analog then V-L-R is other than a non-metal radionuclide substituted peptide (e.g. 125I substituted angiotensin II) and L-V is other than simply a peptide with a chelating agent amide bonded to a side chain thereof. This composition of matter may be used to image cardiovascular diseases and disorders.
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IMPROVEMENTS IN OR RELATING TO DIAGNOSTIC/THERAPEUTIC AGENTS (Fri, 08 May 1998)
Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, comprising a suspension in an aqueous carrier liquid of a reporter comprising gas-containing or gas-generating material, said reporter being conjugated to one or more non-proteinaceous, non-peptide and non-polysaccharide vectors.
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IMPROVEMENTS IN OR RELATING TO DIAGNOSTIC/THERAPEUTIC AGENTS (Fri, 08 May 1998)
Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, comprising a suspension in an aqueous carrier liquid of a reporter comprising gas-containing or gas-generated material, in which the reporter is coupled or linked to one or more non-bioactive vectors.
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IMPROVEMENTS IN OR RELATING TO DIAGNOSTIC/THERAPEUTIC AGENTS (Fri, 08 May 1998)
Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, comprising a suspension in an aqueous carrier liquid of a reporter comprising gas-containing or gas-generating material, said agent being capable of forming at least two types of binding pairs with a target. </p>
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IMPROVEMENTS IN OR RELATING TO DIAGNOSTIC/THERAPEUTIC AGENTS (Fri, 08 May 1998)
Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, having reporters comprising gas-filled microbubbles stabilised by monolayers of film-forming surfactants, the reporter being coupled or linked to at least one vector. </p>
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Double-chain hemoregulatory peptides (Wed, 25 Mar 1998)
<p>The present invention relates to peptide compounds comprising two single-chain hemoregulatory, for example haemopoiesis-inhibiting, peptides linked by a bridging group terminally attached to the C.alpha. atoms of non-terminal amino acids wherein at least one of the C.alpha. atoms is independently substituted by an alkyl group. The bridged dipeptide compounds have a stimulating activity on cell division, especially in myelopoietic and bone marrow cells.</p>
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MARKER COMPOSITIONS (Fri, 20 Mar 1998)
This invention relates to a set of aqueous marker compositions, each composition having a selected 1/Ti value which is substantially invariant over an at least 10 °C temperature range between 15 and 40 °C and preferably over an at least ± 2 % magnetic field strength range about a selected field strength value between 0.01 and 5T and comprising an aqueous matrix material having a non-zero 1/Ti temperature dependence within said temperature range with distributed therein a first paramagnetic material having a Ti relaxivity which is substantially invariant within said range(s) and/or a second paramagnetic material having within said range(s) a Ti relaxivity which has a non-zero temperature dependence of opposite polarity to the temperature dependence of 1/Ti of said matrix material, said set containing a plurality of said compositions with different selected 1/Ti values preferably encompassing at least the range 1.0 to 2.5 s-1, said set preferably comprising at least one said composition containing said second paramagnetic material and at least one said composition containing said first paramagnetic material, where i in T¿i? is 1 or 2.
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Free Radicals (Wed, 18 Mar 1998)
<p>The present invention relates to certain novel triaryl methyl free radicals and their use as image enhancing agents in magnetic resonance imaging (MRI) as well as to contrast media containing such radicals and to the use of such radicals and their non-radical precursors in the manufacture of MRI contrast media.</p>
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Steroidal ester contrast media for x-ray and magnetic resonance imaging (Wed, 11 Mar 1998)
<p>The present invention relates to metabolically labile esters, and to contrast media for X-ray and magnetic resonance imaging comprising these esters. The esters have formula (I): ##STR1## in which R.sup.3 is asteroid residue. The esters contain at least one iodine atom and/or heavy metal atom. The compound are metabolizable to products which are soluble in body fluids and are physiologically acceptable.</p>
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Method of contrast enhanced magnetic resonance imaging using magnetically responsive-particles (Wed, 25 Feb 1998)
<p>In a method of contrast MR imaging, using parenterally administered contrast agents, the improvement comprising using as the contrast agent, e.g. to achieve a negative contrast effect, composite particles comprising a biotolerable, carbohydrate or carbohydrate derivative, preferably polymeric, matrix material containing magnetically responsive particles, eg. of magnetite.</p>
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METHOD OF ELECTRON SPIN RESONANCE ENHANCED MAGNETIC RESONANCE IMAGING (ESREMRI) WITH EX VIVO DYNAMIC NUCLEAR POLARISATON OF AN MR IMAGING AGENT (Fri, 16 Jan 1998)
The invention relates to a method of electron spin resonance enhanced magnetic resonance imaging comprising the steps of: (i) placing a composition comprising a contrast agent and an MR imaging agent in a first magnetic field; (ii) exciting ESR transitions in the contrast agent to generate dynamic nuclear polarisation of th e MR imaging agent; (iii) separating the contrast agent from the MR imaging agent; (iv) administering the MR imaging agent to the sample; (v) exciting NMR transitions of the MR imaging agent is a second magnetic field; and (vi) detecting MR response signals from the sample.
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Pyridine complexing agents and targeting immunoreagents useful in therapeutic and diagnostic compositions (Wed, 14 Jan 1998)
<p>The invention provides targeting radioactive immunoreagents comprising a metal radionuclide ion, a complexing agent having structure A-I, as defined in the specification, and an immunoreactive group covalently bonded to the complexing agent. The present invention also provides novel complexing agents having the structure A-I, as defined in the specification. The targeting radioactive immunoreagents are particularly useful in therapeutic and diagnostic imaging compositions and methods.</p>
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Polyazacycloalkane compounds (Wed, 07 Jan 1998)
<p>The present invention relates to tribenzylcyclen compounds of formula I ##STR1## (where R is hydrogen, or a C.sub.1-12 alkyl group optionally substituted by hydroxy, alkoxy or aryl groups or R is an amphiphilic aralkyl group comprising a N, S, O or P interrupted C.sub.2-25 alkylene chain, e.g. a polyalkylene oxide chain or R provides a bridge to a second tribenzylcyclen group, but with the proviso that R is other than benzyl; X is CHR.sub.1, or where R is hydrogen two X groups may each represent CO groups; and R.sub.1 is hydrogen, a C.sub.1-6 alkyl group optionally substituted by hydroxy, alkoxy or carboxy groups or an aralkyl group having 1 to 6 carbons in the alkyl moiety and optionally. substituted in the aryl moiety by alkyl, alkoxy, hydroxy or isothiocyanate groups). These compounds are useful in the preparation of DO3A, N-substituted-1,4,7,10-tetraazacyclododecane-N',N",N'"-triacetic acids, and the phosphonic acid analogs.</p>
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Use of persistent free-radicals in magnetic resonance imaging (Wed, 24 Dec 1997)
<p>The present invention relates to the use of persistent free radicals, in particular persistent free radicals having a carbon-based .pi.-bonded electronic system available for delocalization of the unpaired electrons as image enhancing agents in magnetic resonance imaging (MRI), in particular electron spin resonance enhanced magnetic resonance imaging (ESREMRI). The invention also relates to contrast media containing such radicals and to the use of such radicals and their non-radical precursors in the manufacture of MRI and ESREMRI contrast media.</p>
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SYNTHESIS OF FERROCENYL PHENYLTROPANE ANALOGS AND THEIR RADIO-TRANSFORMATION TO TECHNETIUM NEUROPROBES FOR MAPPING MONOAMINE REUPTAKE SITES (Fri, 19 Dec 1997)
Neuroprobes that include rhenium, manganese, and technetium for use in mapping monoamine reuptake sites are disclosed. Non-radioactive tricarbonylrheniumcyclopentadienyl (TRCp) or non-radioactive tricarbonylmanganesecyclopentadienyl (TMCp) phenyltropane analogs are synthesized for use as testing surrogates for radioactive technetium congeners. Ferrocenyl analogs of phenyltropane are disclosed as useful precursors for the preparation of novel tricarbonyltechnetiumcyclopentadienyl (TTCp) phenyltropane analogs in radioactive form.
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Polymers containing diester units (Wed, 03 Dec 1997)
<p>The present invention relates to the process for the preparation of a biodegradable polymer comprising diester units of the formula (III) EQU --(O)--CO--O--C(R.sup.1 R.sup.2)--O--CO--(O)--R.sup.3 !--; PAL where R.sup.1 and R.sup.2 each represents a hydrogen atom or a carbon-attached monovalent organic group or R.sup.1 and R.sup.2 together form a carbon-attached divalent organic group; m and n, which may be the same or different, are 0 or 1; and R.sup.3 is a carbon-attached divalent organic grouping.</p>
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Improvements in or relating to contrast agents (Thu, 20 Nov 1997)
Ultrasound contrast agents comprising microbubbles of gas or a gas precusor encapsulated in a protein shell, e.g. of human serum albumin, the protein being crosslinked with biodegradable crosslinking groups, exhibit stability in vivo upon administration so as to permit ultrasound visualisation while allowing rapid subsequent elimination from the system.
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Use of fullerenes in diagnostic and/or therapeutic agents (Wed, 19 Nov 1997)
<p>Compounds including tight molecular meshes, preferably curved in one or two directions, such as fullerenes and met-cars, can be used as carriers for diagnostic or therapeutic agents, especially diagnostic contrast agents.</p>
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Contrast agents comprising gas-containing or gas-generating polymer microparticles or microballoons (Wed, 15 Oct 1997)
<p>Contrast agents comprising gas-containing or gas-generating polymer microparticles and/or microballoons, in which the polymer is a biodegradable polymer containing units of formula EQU --(O).sub.m --CO--O--C(R.sup.1 R.sup.2)--O--CO--(O).sub.n -- PAL (wherein R.sup.1 and R.sup.2 each represent hydrogen or a carbon-attached monovalent organic group or together form a carbon-attached divalent organic group, and m and n are each independently zero or one) may be used in diagnostic applications such as ultrasound and MR imaging.</p>
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Polyazacycloalkane compounds (Wed, 15 Oct 1997)
<p>The present invention relates to tribenzylcyclen compounds of formula I ##STR1## (where R is hydrogen, or a C.sub.1-12 alkyl group optionally substituted by hydroxy, alkoxy or aryl groups or R is an amphiphilic aralkyl group comprising a N, S, O or P interrupted C.sub.2-25 alkylene chain, e.g. a polyalkylene oxide chain or R provides a bridge to a second tribenzylcyclen group, but with the proviso that R is other than benzyl; X is CHR.sub.1, or where R is hydrogen two X groups may each represent CO groups; and R.sub.1 is hydrogen, a C.sub.1-6 alkyl group optionally substituted by hydroxy, alkoxy or carboxy groups or an aralkyl group having 1 to 6 carbons in the alkyl moiety and optionally. substituted in the aryl moiety by alkyl, alkoxy, hydroxy or isothiocyanate groups). These compounds are useful in the preparation of DO3A, N-substituted-1,4,7,10-tetraazacyclododecane-N',N",N"'-triacetic acids, and the phosphonic acid analogs.</p>
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Polycyclic complexing agents (Wed, 15 Oct 1997)
<p>A compound of formula ##STR1## where the two R.sup.2 groups, taken together, represent the atoms necessary to complete a macrocyclic ring structure containing at least one heteroatom coordinating site and at least one alkylene group forming part of the ring structure; R.sup.3 represents hydrogen, alkyl, alkoxy, alkylthio, alkylamino, alkylformamido, aryl, aryloxy, heterocyclyl or a protein reactive group; and R.sup.4 represents hydrogen or a protein reactive group, provided that at least one of the R.sup.4 groups is a protein reactive group, and salts, complexes and protein conjugates thereof.</p>
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METHOD OF T1-WEIGHTED MAGNETIC RESONANCE IMAGING OF RES ORGANS (Fri, 10 Oct 1997)
The invention provides a method of contrast enhanced MR angiography of the human or non-human animal body, said method comprising administering into the vasculature thereof a contrast effective amount of a contrast agent composition comprising magnetic particles having an r2/r1 ratio of no more than 5, and, at a time when sufficient of said magnetic particles remain in the vasculature to provide positive contrast enhancement thereof in a T1-weighted image while sufficient magnetic particles have been taken up into an organ of the reticuloendothelial system to provide negative contrast enhancement thereof in said T1-weighted image, generating a T1-weighted image magnetic resonance image of at least said organ.
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METHOD OF T1-WEIGHTED MAGNETIC RESONANCE IMAGING OF RES ORGANS (Fri, 10 Oct 1997)
The invention provides a method of contrast enhanced MR angiography of the human or non-human animal body, said method comprising administering into the vasculature thereof a contrast effective amount of a contrast agent composition comprising magnetic particles having an r2/r1 ratio of no more than 5, and, at a time when sufficient of said magnetic particles remain in the vasculature to provide positive contrast enhancement thereof in a T1- weighted image while sufficient magnetic particles have been taken up into an organ of the reticuloendothelial system to provide negative contrast enhancement thereof in said T1-weighted image, generating a T1-weighted image magnetic resonance image of at least said organ. </p>
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Contrast agents comprising gas-containing or gas-generating polymer microparticles or microballoons (Wed, 08 Oct 1997)
<p>Contrast agents comprising gas-containing or gas-generating polymer microparticles and/or microballoons, in which the polymer is a biodegradable polymer containing units of formula EQU --(O).sub.m --CO--O--C(R.sup.1 R.sup.2)--O--CO--(O).sub.n -- PAL (wherein R.sup.1 and R.sup.2 each represent hydrogen or a carbon-attached monovalent organic group or together form a carbon-attached divalent organic group, and m and n are each independently zero or one) may be used in diagnostic applications such as ultrasound and MR imaging.</p>
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CONTRAST AGENTS COMPRISING METHYLENE DISTRER UNIT-CONTAINING BIODEGRADABLE POLYMERS (Wed, 01 Oct 1997)

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Ultrasonic contrast agent comprising carbohydrate particles (Wed, 24 Sep 1997)
<p>A method of contrast enhanced ultrasonic diagnostic imaging comprising: administering to a subject a contrast enhancing amount of spheres or particles comprising a matrix enclosing a contrast agent which reflects sound waves, said matrix being a biocompatible, biodegradable, non-immunogenic non-polyamino acid synthetic polymer; and generating an ultrasonic image of said subject.</p>
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CONTRAST MEDIA (Fri, 01 Aug 1997)
Diagnostic imaging contrast media comprising an image contrast enhancing physiologically tolerable complex, said complex comprising a pair of interconjugated multinuclear clusters, for example of formula (I) or a salt thereof: (M3)2 L3, wherein M3 is a multinuclear cluster containing three metal atoms and L is a ligand, together with at least one pharmaceutical carrier or excipient.
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CONTRAST MEDIA (Fri, 01 Aug 1997)
Diagnostic imaging contrast media comprising an image contrast enhancing physiologically tolerable complex, said complex comprising a pair of interconjugated multinuclear clusters, for example of formula (I) or a salt thereof: (M3)2 L3, wherein M3 is a multinuclear cluster containing three metal atoms and L is a ligand, together with at least one pharmaceutical carrier or excipient. </p>
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Macrocyclic polyaza dichelates linked through ring nitrogens via an amide or ester functionality (Wed, 23 Jul 1997)
<p>This invention relates to dichelants, in particular compounds having two macrocyclic chelant groups linked by a bridge containing an ester or amide bond, especially compounds of formula Vb ##STR1## (wherein each X which may be the same or different is NZ, O or S, at least two Xs being NZ; PA1 each Z is a group R.sup.1 or a group CR.sup.1.sub.2 Y, at least one Z, and preferably 2 or 3 Zs, on each macrocyclic ring being a group CR.sup.1.sub.2 Y; PA1 each Y is a group CO.sub.2 H, PO.sub.3 H, SO.sub.3 H, CONR.sup.1.sub.2, CON(OR.sup.1)R.sup.1, CNS or CONR.sup.1 NR.sup.1.sub.2, preferably COOH; PA1 m is 0 or 1 or 2, preferably 1; each n is 2 or 3, preferably 2; q is 1 or 2, preferably 1; PA1 each R.sup.1 which may be the same or different is a hydrogen atom or an alkyl group optionally substituted by one or more hydroxy and/or alkoxy groups; PA1 and D is a bridging group having a molecular weight of less than 1000, preferably less than 500, joining two macrocyclic rings via at least one amide or ester bond) and salts and metal chelates thereof.</p>
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CONTRAST MEDIA (Fri, 18 Jul 1997)
The invention relates to MR contrast media containing composite nanoparticles, preferably comprising a superparamagnetic iron oxide core provided with a coating comprising an oxidatively cleaved starch coating optionally together with a functionalized polyalkyleneoxide which serves to prolong blood residence.
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CONTRAST MEDIA (Fri, 18 Jul 1997)
The invention relates to MR contrast media containing composite nanoparticles, preferably comprising a superparamagnetic iron oxide core provided with a coating comprising an oxidatively cleaved starch coating optionally together with a functionalized polyalkyleneoxide which serves to prolong blood residence. </p>
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Process for the preparation of substituted diamino-dicarboxylic acid derivatives (Wed, 02 Jul 1997)
<p>The invention relates to a new process for the preparation of substituted diaminodicarboxylic acid derivatives of the formula ##STR1## in a high yield by a modified Kolbe synthesis.</p>
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MORPHINE DERIVATIVES WITH ANALGESIC ACTIVITY (Fri, 27 Jun 1997)
Morphine derivatives of formula (I), process for preparing them and their use as analgesics.
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MORPHINE DERIVATIVES WITH ANALGESIC ACTIVITY (Fri, 27 Jun 1997)
Morphine derivatives of formula (T), process for preparing them and their use as analgesics. </p>
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HEMOREGULATORY COMPOUNDS (Fri, 23 May 1997)
The present invention relates to novel compounds which have hemoregulatory activities and can be used to stimulate hematopoiesis and for the treatment of viral, fungal and bacterial infectious diseases.
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HEMOREGULATORY COMPOUNDS (Fri, 23 May 1997)
Novel compounds of general formula (I) which have hemoregulatory activities and can be used to stimulate haematopoiesis and for the treatment of viral, fungal and bacterial infectious diseases.
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HEMOREGULATORY COMPOUNDS (Fri, 23 May 1997)
The present invention relates to novel compounds which have hemoregulatory activities and can be used to stimulate hematopoiesis and for the treatment of viral, fungal and bacterial infectious diseases.
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HEMOREGULATORY COMPOUNDS (Fri, 23 May 1997)
Novel compounds of general formula (I) which have hemoregulatory activities and can be used to stimulate haematopoiesis and for the treatment of viral, fungal and bacterial infectious diseases.
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HEMOREGULATORY COMPOUNDS (Fri, 23 May 1997)
Novel compounds of general formula (I) which have hemoregulatory activities and can be used to stimulate haematopoiesis and for the treatment of viral, fungal and bacterial infectious diseases.
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HEMOREGULATORY COMPOUNDS (Fri, 23 May 1997)
Novel compounds of general formula (I) which have hemoregulatory activities and can be used to stimulate haematopoiesis and for the treatment of viral, fungal and bacterial infectious diseases.
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HEMOREGULATORY COMPOUNDS (Fri, 23 May 1997)
The present invention relates to novel compounds which have hemoregulatory activities and can be used to stimulate hematopoiesis and for the treatment of viral, fungal and bacterial infectious diseases. </p>
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Polyazacycloalkane compounds (Wed, 21 May 1997)
<p>The present invention relates to tribenzylcyclen compounds of formula I ##STR1## (where R is hydrogen, or a C.sub.1-12 alkyl group optionally substituted by hydroxy, alkoxy or aryl groups or R is an amphiphilic aralkyl group comprising a N, S, O or P interrupted C.sub.2-25 alkylene chain, e.g. a polyalkylene oxide chain or R provides a bridge to a second tribenzylcyclen group, but with the proviso that R is other than benzyl; X is CHR.sub.1, or where R is hydrogen two X groups may each represent CO groups; and R.sub.1 is hydrogen, a C.sub.1-6 alkyl group optionally substituted by hydroxy, alkoxy or carboxy groups or an aralkyl group having 1 to 6 carbons in the alkyl moiety and optionally substituted in the aryl moiety by alkyl, alkoxy, hydroxy or isothiocyanate groups). These compounds are useful in the preparation of DO3A, N-substituted-1,4,7,10-tetraazacyclododecane-N',N",N"'-triacetic acids, and the phosphonic acid analogs.</p>
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Single chain peptide compounds having hemoregulatory activity (Wed, 14 May 1997)
<p>There is disclosed single chain peptide compounds, substituted at a C.alpha.-atom of a non-terminal amino acid by a group--A which is defined in claim 1. The native .alpha.-side chain of the C.alpha. atom bonded group to group --A absent. The peptide derivatives according to the invention are useful for inhibiting cell proliferation, especially myelopoietic and bone marrow cells.</p>
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Heterocyclic amides (Wed, 07 May 1997)
<p>The invention relates to heterocyclic amides of the formula ##STR1## in which the radicals A, Z, A.sub.1, R.sub.1, R.sub.2 and R.sub.3 are as defined in the description, to a process for the preparation of these amides and to their use as active substances for the curing and amelioration of disorders and diseases which can be treated by exerting influence on potassium channels.</p>
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DERIVATIVES OF BENZENESULFONIC ACIDS (Thu, 01 May 1997)
Compounds of the formula I <br> ? A' <br> </p> <p>R<sub>s</sub> N <br> H T</p> <p>their preparation, their use and pharmaceutical composition comprising compounds of the formula I or their pharmaceutically tolerable salts.
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Diagnostic and contrast agent (Wed, 09 Apr 1997)
<p>A method of contrast enhanced ultrasonic diagnostic imaging comprising: administering to a subject a contrast enhancing amount of spheres or particles comprising a matrix enclosing a contrast agent which reflects sound waves, said matrix being a biocompatible, biodegradable, nonimmunogenic non-polyamino acid synthetic polymer; and generating an ultrasonic image of said subject.</p>
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Multinuclear complexes for X-ray imaging (Wed, 26 Mar 1997)
<p>The invention relates to the use as contrast enhancing agents in medical imaging, especially X-ray imaging, of multinuclear complexes, i.e. complexes, such as those of W202 (U20) 2, in which the complexed entity comprises at least two contrast enhancing atoms.</p>
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A METHOD OF DETERMINING OXYGEN CONCENTRATION IN A SAMPLE (Fri, 14 Mar 1997)
A method for determining the oxygen concentration of a sample using electron spin resonance enhanced magnetic resonance imaging.
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A METHOD OF DETERMINING OXYGEN CONCENTRATION IN A SAMPLE (Fri, 14 Mar 1997)
A method for determining the oxygen concentration of a sample using electron spin resonance enhanced magnetic resonance imaging. </p>
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Double chain peptide compounds having hemoregulatory activity (Wed, 12 Mar 1997)
<p>Dipeptide compounds are disclosed, the two peptide chains being joined together at a C.alpha.-atom of a non-terminal amino acid by a divalent bridging group --A--. The C.alpha.-atoms joined to group --A-- are located in equivalent positions in each peptide and each lack their native .alpha.-side chain. The bridged dipeptide compounds disclosed have a stimulating activity on cell division, especially for myelopoietic and bone marrow cells.</p>
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DERIVATIVES OF BENZOSULPHONAMIDES AS INHIBITORS OF THE ENZYME CYCLOOXYGENASE II (Fri, 07 Feb 1997)
Compounds of the formula (I) in which A is oxygen, sulphur or NH; B is a group of the formula (IIa) or (IIb); and the other variables have the meaning given in claim 1, may be used as inhibitors of the enzyme cyclo-oxygenase II. </p>
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DENDRIMERIC COMPOUNDS (Thu, 06 Feb 1997)
The invention provides a dendrimeric compound comprising a dendrimeric backbone moiety with linked thereto a plurality of diagnostically or therapeutically active moieties, characterised in that the molecular skeleton of said compound contains at least one biodegradable cleavage site such that on cleavage thereof said active moieties are released in renally excretable form.
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Triarylmethyl radicals and the use of inert carbon free radicals in MRI (Wed, 05 Feb 1997)
<p>A radical compound of formula Ia EQU .C(Ar.sup.12).sub.3 (Ia) PAL wherein: PA1 each Ar.sup.12, which may be the same or different, represents a 6-membered carbocyclic, at least one group Ar.sup.12 being a group Ar.sup.1 ; PA1 each group Ar.sup.1 represents a 6-membered ring optionally substituted at the or any ortho carbon by a group R.sup.1, R.sup.2, R.sup.3 or R.sup.4, at the or any meta carbon by a group R.sup.2 or R.sup.3, and at any para carbon by a group R.sup.1, R.sup.2, R.sup.3 or R.sup.4, PA1 with the proviso that no more than two ring carbons are unsubstituted; PA1 each of R.sup.1, R.sup.2, R.sup.3 or R.sup.4, which may be the same or different, independently represents a group of formula --M, --XM, --XAr.sup.2 or --Ar.sup.2 ; PA1 M represents a water solubilizing group, each group X, which may be the same or different, represents an oxygen or sulphur atom or a NH or CH.sub.2 group.</p>
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Diazine chelating agents for diagnostic imaging (Wed, 25 Dec 1996)
<p>Heterocyclic chelating agents and salts thereof of formula I: ##STR1## wherein X represents a bond, O or S, or a group CHR.sup.1 or NR.sup.3 ; each R.sup.1 represents H, a group OR.sup.3 or NR.sup.3 R.sup.3, or an alkyl or alkoxyalkyl group optionally substituted by a hydroxyl group or by a group NR.sup.3 R.sup.3 or CON.sup.3 R.sup.3 ; PA1 each R.sup.2 represents H, or an alkyl or alkoxy group optionally substituted by a hydroxyl or alkoxy group; PA1 each R.sup.3 represents H, an optionally hydroxylated alkyl group or a group CH.sub.2 Y; PA1 Y represents a group COZ, CON(OH)R.sup.4, POZ.sub.2 or SO.sub.2 Z, PA1 Z represents a group OR.sup.4, NR.sup.4 R.sup.4 or ##STR2## where each R.sup.11 is H, a hydroxyl group or an optionally hydroxylated alkyl group, s is 0, 1 or 2, and W is CHR.sup.11, NR.sup.11 or an oxygen atom; and PA1 each R.sup.4 represents H, or an optionally mono- or poly-hydroxylated alkyl, alkoxyalkyl or polyalkoxyalkyl group; PAL with the provisos that where s is 0 then W is CHR.sup.11 and that where X represents a bond or CHR.sup.1, at least one group R.sup.1 or R.sup.2 represents other than H or an unsubstituted alkyl group, A process for preparing these agents and methods of heavy metal detoxification using these agents are also described.</p>
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CHELATING POLYMERS AS CONTRAST AGENTS FOR MEDICAL IMAGING (Fri, 20 Dec 1996)
The invention provides polymeric polychelants containing polymer repeat units of the formula [L-Ch-L-B] (where Ch is a polydentate chelant moiety; L is an amide or ester linkage; B is a hydrophobic group providing a carbon chain of at least 4 carbon atoms between the L linkages it interconnects) or a salt or chelate thereof, with the proviso that where Ch is 2,5-biscarboxymethyl-2,5-diazahex-1,6-diyl, the polychelant is metallated with lanthanide or manganese ions or B provides a carbon chain of at least 10 carbon atoms between the L linkages it interconnects and their salts and chelates. The paramagnetic polychelates of the polychelants of the invention have remarkably high R1 relaxivities.
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CHELATING POLYMERS AS CONTRAST AGENTS FOR MEDICAL IMAGING (Fri, 20 Dec 1996)
The invention provides polymeric polychelants containing polymer repeat units of the formula [L-Ch-L-B] (where Ch is a polydentate chelant moiety; L is an amide or ester linkage; B is a hydrophobic group providing a carbon chain of at least 4 carbon atoms between the L linkages it interconnects) or a salt or chelate thereof, with the proviso that where Ch is 2,5-biscarboxymethyl-2,5- diazahex-1,6-diyl, the polychelant is metallated with lanthanide or manganese ions or B provides a carbon chain of at least 10 carbon atoms between the L linkages it interconnects and their salts and chelates. The paramagnetic polychelates of the polychelants of the invention have remarkably high R1 relaxivities. </p>
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HETEROCYCLIC METHYL FREE RADICALS AS IMAGE ENHANCING AGENTS (Fri, 13 Dec 1996)
The invention provides novel persistent free radicals useful in Overhauser MRI being triarylmethyl radicals having as at least one aryl group a group of formula (1) or (2), wherein each X which may be the same or different is an oxygen or sulphur atom or a group CO or S(O)n (where n is 1 to 3) with the proviso that at least one group X is a sulphur atom or an S(O)n group; R1 is a hydrogen atom or group of formula -M, -XM, -X-Ar2 where M is a water solubilising group, and Ar2 represents a 5-10 membered aromatic ring optionally substituted by a water solubilising group M; and each of the groups R7, which may be the same or different, is a hydrogen atom, or a hydrocarbon group or a water solubilising group M, or two groups R7 together with the atom to which they are bound represent a carbonyl group or a 5 to 8 membered cycloalkylidene, mono- or di-oxacycloalkylidene, mono or di-azacycloalkylidene or mono- or di-thiacycloalkylidene group optionally wit the ring attachment carbon replaced by a silicon atom, and R7 where it is other than hydrogen, is optionally substituted by a hydroxyl group, an optionally alkoxylated, optionally hydroxylated acyloxy or alkyl group or a water solubilising group M. The novel radicals have good stability, long relaxation times and good relaxivity.
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HETEROCYCLIC METHYL FREE RADICALS AS IMAGE ENHANCING AGENTS (Fri, 13 Dec 1996)
The invention provides novel persistent free radicals useful in Overhauser MRI being triarylmethyl radicals having as at least one aryl group a group of formula (1) or (2), wherein each X which may be the same or different is an oxygen or sulphur atom or a group CO or S(O)n (where n is 1 to 3) with the proviso that at least one group X is a sulphur atom or an S(O)n group; R1 is a hydrogen atom or group of formula -M, -XM, -X-Ar2 where M is a water solubilising group, and Ar2 represents a 5-10 membered aromatic ring optionally substituted by a water solubilising group M; and each of the groups R7, which may be the same or different, is a hydrogen atom, or a hydrocarbon group or a water solubilising group M, or two groups R7 together with the atom to which they are bound represent a carbonyl group or a 5 to 8 membered cycloalkylidene, mono- or di-oxacycloalkylidene, mono or di-azacycloalkylidene or mono- or di-thiacycloalkylidene group optionally wit the ring attachment carbon replaced by a silicon atom, and R7 where it is other than hydrogen, is optionally substituted by a hydroxyl group, an optionally alkoxylated, optionally hydroxylated acyloxy or alkyl group or a water solubilising group M. The novel radicals have good stability, long relaxation times and good relaxivity. </p>
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IODINATION PROCESS (Fri, 29 Nov 1996)
The invention provides a process for the preparation of a 2,4,6-triiodinated or 2,4,6,2',4',6'-hexaiodinated 3,5-disubstituted-aniline or 3,3'-disubstituted-5,5'-linked bisaniline, which process comprises electrochemically iodinating a 3,5-disubstituted-aniline or a 3,3'-disubstituted-5,5'-linked bisaniline in an acidic solvent which comprises water and optionally at least one water-miscible organic solvent.
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Iodination process (Wed, 20 Nov 1996)
<p>The invention provides a process for the preparation of a 2,4,6-triiodinated or 2,4,6,2',4',6'-hexaiodinated 3,5-disubstituted-aniline or 3,3'-disubstituted-5,5'-linked bisaniline, which process comprises electrochemically iodinating a 3,5-disubstituted-aniline or a 3,3'-disubstituted-5,5'-linked bisaniline in an acidic solvent which comprises water and optionally at least one water-miscible organic solvent.</p>
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Chemical compounds (Wed, 13 Nov 1996)
<p>The invention relates to non-crosslinked non-polypeptide polymers containing biodegradable lipophilic side chains incorporating methylene diester units of the formula --[--CO--O--C(R.sup.1 R.sup.2)--O--CO--]--, where R.sup.1 and R.sup.2 each represents a hydrogen atom or a carbon-attached monovalent organic group or R.sup.1 and R.sup.2 together form a carbon-attached divalent organic group. The lipophilic moieties are biodegradatively cleavable to yield a water-soluble polymer.</p>
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Gaseous microparticles as ultrasound contrast agents (Wed, 30 Oct 1996)
<p>This invention relates to ultrasound contrast agents in the form of microparticles comprising a biotolerable matrix (e.g. of a carbohydrate or an X-ray contrast agent) in association with a gas or a precursor therefor. The contrast agents are stabilized to enhance their in vivo stability and/or echogenicity by covalently modifying the structure of the matrix, e.g. to introduce crosslinking groups or to attach lipophilic groups and/or molecules. The covalent moieties may include biodegradable linkages to assist rapid subsequent elimination of the contrast agents from the system.</p>
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Flexible amphiphilic microbubbles for ultrasound (Wed, 23 Oct 1996)
<p>The invention relates to diagnostic ultrasound contrast agents comprising vesicles comprising an amphiphilic phospholipid material capable of formation of gas-containing vesicles wherein the vesicles contain gas which comprises a low molecular weight fluorinated hydrocarbon.</p>
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CONTRAST AGENTS (Thu, 26 Sep 1996)
Contrast agents comprising gas-containing polymer microparticles and/or microballoons in which the polymer is a biodegradable polymer comprising repeating units of formula (II)</p> <p>CH<sub>3</sub> <br> I <br> -0- (CH<sub>2</sub>) <sub>a</sub>-C0-0-CH-0-C0- (CH<sub>2</sub>) <sub>a</sub>-0-C0- (CH<sub>2</sub>)<sub>b</sub>-CO- (II)</p> <p>(where a is an integer of 9-19 and b is an integer of 1-8) may be used in diagnostic applications such as ultrasound and MR imaging. The polymers are novel and are also claimed per se.
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Contrast agents (Wed, 25 Sep 1996)
<p>This invention relates to ultrasound contrast agents in the form of microparticles comprising a biotolerable matrix (e.g. of a carbohydrate or an X-ray contrast agent) in association with a gas or a precursor therefor. The contrast agents are stabilized to enhance their in vivo stability and/or echogenicity by covalently modifying the structure of the matrix, e.g. to introduce crosslinking groups or to attach lipophilic groups and/or molecules. The covalent moieties may include biodegradable linkages to assist rapid subsequent elimination of the contrast agents from the system.</p>
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Microbubble-generating contrast agents for ultrasound and magnetic resonance imaging (Wed, 25 Sep 1996)
<p>The present invention relates to contrast agents comprising microbubble-generating carbohydrate particles having a surfactant admixed within the microparticulate structure, with the proviso that the surfactant is not a saturated C.sub.10-20 fatty acid. The contrast agents exhibit useful levels of contrast efficiency and/or stability and may be used in diagnostic applications such as ultrasound and MR imaging.</p>
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Iodinated esters (Wed, 25 Sep 1996)
<p>Water-insoluble iodinated esters of the formula (I) ##STR1## useful in X-ray and ultrasound imaging, are disclosed.</p>
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POLYAZACYCLOALKANE COMPOUNDS (Fri, 20 Sep 1996)
The present invention relates to tribenzylcyclen compounds of formula (I) (where R is hydrogen, or a C1-12 alkyl group optionally substituted by hydroxy, alkoxy or aryl groups or R is an amphiphilic aralkyl group comprising a N, S, O or P interrupted C2-25alkylene chain, e.g. a polyalkylene oxide chain or R provides a bridge to a second tribenzylcyclen group, but with the proviso that R is other than benzyl; X is CHR1, or where R is hydrogen two X groups may each represent CO groups; and R1 is hydrogen, a C1-6alkyl group optionally substituted by hydroxy, alkoxy or carboxy groups or an aralkyl group having 1 to 6 carbons in the alkyl moiety and optionally substituted in the aryl moiety by alkyl, alkoxy, hydroxy or isothiocyanate groups). These compounds are useful in the preparation of DO3A, N-substituted-1,4,7,10-tetraazacyclododecane-N',N',N'''-triacetic acids, and the phosphonic acid analogs.
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PREPARATION OF N-ARYLMETHYL AZIRIDINE DERIVATIVES, 1,4,7,10-TETRAAZACYCLODODECANE DERIVATIVES OBTAINED THEREFROM AND N-ARYLMETHYL-ETHANOL-AMINE SULPHONATE ESTERS AS INTERMEDIATES (Fri, 20 Sep 1996)
Aziridines may be subjected to a cyclooligomerization reaction to produce polyazacycloalkane compounds useful for example in the preparation of chelating agents for use in diagnostic imaging contrast agents. N-benzyl-aziridine in particular is useful as it can be cyclotetramerized and debenzylated to yield cyclen, a key intermediate in chelating agent preparation. The invention provides a particularly attractive route to production of N-benzyl and other N-arylmethyl aziridines of formula (I), (where each R1 independently is hydrogen or a group Ar and Ar is an optionally substituted phenyl group), said process comprising reacting a purified N-arylmethylethanolamine-sulphonate ester with a base. N-arylmethyl-ethanolamine sulphonate ester of the formula: R'NHCH2CH2OSO3H, wherein the N-arylmethyl group R' is an N-(bisarylmethyl) or N-(triarylmethyl) group, as intermediates. In a further aspect the invention provides compounds of formula (II), where Ar and R1 are as hereinbefore defined and at least two differing ArCHR1 moieties are present.
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PREPARATION OF N-ARYLMETHYL AZIRIDINE DERIVATIVES, 1,4,7,10-TETRAAZACYCLODODECANE DERIVATIVES OBTAINED THEREFROM AND N-ARYLMETHYL-ETHANOL-AMINE SULPHONATE ESTERS AS INTERMEDIATES (Fri, 20 Sep 1996)
Aziridines may be subjected to a cyclooligomerization reaction to produce polyazacycloalkane compounds useful for example in the preparation of chelating agents for use in diagnostic imaging contrast agents. N-benzyl- aziridine in particular is useful as it can be cyclotetramerized and debenzylated to yield cyclen, a key intermediate in chelating agent preparation. The invention provides a particularly attractive route to production of N-benzyl and other N-arylmethyl aziridines of formula (I), (where each R1 independently is hydrogen or a group Ar and Ar is an optionally substituted phenyl group), said process comprising reacting a purified N- arylmethylethanolamine-sulphonate ester with a base. N-arylmethyl-ethanolamine sulphonate ester of the formula: R'NHCH2CH2OSO3H, wherein the N-arylmethyl group R' is an N-(bisarylmethyl) or N-(triarylmethyl) group, as intermediates. In a further aspect the invention provides compounds of formula (II), where Ar and R1 are as hereinbefore defined and at least two differing ArCHR1 moieties are present. </p>
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POLYAZACYCLOALKANE COMPOUNDS (Fri, 20 Sep 1996)
The present invention relates to tribenzylcyclen compounds of formula (I) (where R is hydrogen, or a C1-12 alkyl group optionally substituted by hydroxy, alkoxy or aryl groups or R is an amphiphilic aralkyl group comprising a N, S, O or P interrupted C2-25alkylene chain, e.g. a polyalkylene oxide chain or R provides a bridge to a second tribenzylcyclen group, but with the proviso that R is other than benzyl; X is CHR1, or where R is hydrogen two X groups may each represent CO groups; and R1 is hydrogen, a C1-6alkyl group optionally substituted by hydroxy, alkoxy or carboxy groups or an aralkyl group having 1 to 6 carbons in the alkyl moiety and optionally substituted in the aryl moiety by alkyl, alkoxy, hydroxy or isothiocyanate groups). These compounds are useful in the preparation of DO3A, N-substituted-1,4,7,10- tetraazacyclododecane-N',N",N'''-triacetic acids, and the phosphonic acid analogs. </p>
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Polyazamacrocycle chelating agents with amide linkages (Wed, 18 Sep 1996)
<p>Macrocyclic chelating agents, optionally possessing more than one macrocyclic ring having at least two peptide linkages within the macrocyclic skeleton. The chelating agents are used for the preparation of paramagnetic metal chelates for use as MRI contrast agents.</p>
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Adducts of macrocyclic chelants (Wed, 11 Sep 1996)
<p>There are provided polychelants and their metal chelates which are useful in diagnostic imaging and in radiotherapy and which comprise a plurality of macrocyclic chelant moieties, e.g. DOTA residues, conjugated to a polyamine backbone molecule, e.g. polylysine. To produce a site-specific polychelate, one or more of the macrocyclic chelant carrying backbone molecules may be conjugated to a site-directed macromolecule, e.g. a protein. For example, adducts of a macrocyclic chelant can be formed by the process of (a) dispersing a carboxylic macrocyclic chelant in a polar, anhydrous solvent, (b) adding a base with a pKa sufficient to remove all carboxyl protons to create an amine salt of the chelant soluble in the solvent, (c) chilling the reaction mixture to between about 5.degree. C. and 55.degree. C. above the freezing point of the solvent, and (d) adding substantial equimolar amount of chilled alkylhaloformate under anhydrous conditions so as to form a slurry containing the mixture carboxycarbonic anhydride of the chelant.</p>
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CONTRAST MEDIA FOR IN VIVO IMAGING BASED ON LIGHT TRANSMISSION ON REFLECTION (Fri, 09 Aug 1996)
The present invention relates to the use of particulate materials as contrast agents in in vivo light imaging.
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CONTRAST MEDIA FOR IN VIVO IMAGING BASED ON LIGHT TRANSMISSION ON REFLECTION (Fri, 09 Aug 1996)
The present invention relates to the use of particulate materials as contrast agents in in vivo light imaging. </p>
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BISMUTH COMPOUNDS (Fri, 02 Aug 1996)
The use in diagnostic imaging, in particular X-ray, MRI, ultrasound and scintigraphy, of contrast agents comprising bismuth clusters and/or organic bismuth compounds, and contrast media containing such bismuth compounds. The bismuth compounds are also useful in therapy, in particular as antimicrobial agents and antiulcer agents. Novel bismuth compounds are also disclosed.
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BISMUTH COMPOUNDS (Fri, 02 Aug 1996)
The use in diagnostic imaging, in particular X-ray, MRI, ultrasound and scintigraphy, of contrast agents comprising bismuth clusters and/or organic bismuth compounds, and contrast media containing such bismuth compounds. The bismuth compounds are also useful in therapy, in particular as antimicrobial agents and antiulcer agents. Novel bismuth compounds are also disclosed. </p>
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Contrast agents (Wed, 17 Jul 1996)
<p>The invention relates to diagnostic ultrasound contrast agents comprising vesicles comprising an amphiphilic phospholipid material capable of formation of gas-containing vesicles wherein the vesicles contain gas which comprises sulphur hexafluoride. The contrast agents and vesicles exhibit good stability in vivo upon administration and may if desired incorporate biodegradable linkages so as to possess particularly desired levels of biodegradability.</p>
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Aminopolycarboxylic acids and derivatives thereof (Wed, 03 Jul 1996)
<p>There are provided chelating agents particularly useful for the preparation of diagnostic and therapeutic agents for magnetic resonance imaging, scintigraphy, ultrasound imaging, radiotherapy and heavy metal detoxification, said agents being compounds of formula I EQU X--CHR.sub.1 --NZ--(CHR.sub.1).sub.n --A--(CHR.sub.1).sub.m --NZ--CHR.sub.1 --X (I) PAL wherein n and m are 2, 3 or 4; and A, X, R.sub.1 and Z are as defined in the specification.</p>
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PYRIDINE AND PYRAZINEDICARBOXYLIC-ACID DERIVATIVES AS CELL PROLIFERATION REGULATORS (Fri, 28 Jun 1996)
The present invention relates to pyridine and pyrazine-containing compounds capable of regulating, in particular stimulating, haematopoiesis.
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CHELANTS AS CONTRAST ENHANCING AGENTS (Thu, 27 Jun 1996)
The present invention provides a polychelant compound of formula (VII), (wherein each X which may be the same or different is NZ, O or S, at least two Xs being NZ; B is (CR?1¿Y) or -N(CR?1¿¿2?Y)-; each Z is a group R?1¿ or a group CR?1¿¿2?Y, at least one Z being a group CR?1¿¿2?Y; each Y is a group CO¿2?H, PO¿3?H, SO¿3?H, CONR?1¿¿2?, CON(OR?1¿)R?1¿, CNS or CONR?1¿NR?1¿¿2?; m is 0 or 1 or 2; each n is 2 or 3; q is 0 or 1 when B is (CR?1¿Y) and 2 when B is N(CR?1¿¿2?Y); p is an integer having a value of at least 2; each R?1¿ which may be the same or different is a hydrogen atom or an alkyl, aryl or aralkyl group optionally substituted by one or more hydroxy or alkoxy groups, or two R?1¿ groups on ring atoms or in Z groups together represent a linker group L; each L which may be the same or different represents a bond or an organic linker group having a molecular weight of less than 1000 and salts and chelates thereof. These compounds, especially the di- and trichelates with paramagnetic or heavy metal ions are especially useful as diagnostic imaging contrast agents.
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Contrast agents (Wed, 26 Jun 1996)
<p>The invention relates to ultrasound contrast agents comprising vesicles comprising a protein capable of formation of gas-containing vesicles, wherein the vesicles contain gas which comprises sulphur hexafluoride or a low molecular weight fluorinated hydrocarbon. These contrast agents exhibit stability in vivo upon administration so as to permit ultrasound visualization while allowing rapid subsequent elimination from the system.</p>
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Free radicals (Wed, 26 Jun 1996)
<p>The invention provides novel persistent free radicals useful in Overhauser MRI being triarylmethyl radicals having as at least one aryl group a group of formula ##STR1## (wherein each X which may be the same or different is an oxygen or sulphur atom or a group CO or S(O).sub.n, (where n is 1 to 3) with the proviso that at least one group X is a sulphur atom or a S(O).sub.n group; R.sup.1 is a hydrogen atom or group of formula --M, --XM, --X--Ar.sup.2, or --Ar.sup.2 where M is a water solubilizing group, and Ar.sup.2 represents a 5-10 membered aromatic ring optionally substituted by a water solubilizing group M; and each of the groups R.sup.7, which may be the same or different, is a hydrogen atom, or a hydrocarbon group or a water solubilizing group M, or two groups R.sup.7 together with the atom to which they are bound represent a carbonyl group or a 5 to 8 membered cycloalkylidene, mono- or di-oxacycloalkylidene, mono- or di-azacycloalkylidene or mono- or di-thiacycloalkylidene group optionally with the ring attachment carbon replaced by a silicon atom, and R.sup.7 where it is other than hydrogen, is optionally substituted by a hydroxyl group, an optionally alkoxylated, optionally hydroxylated acyloxy or alkyl group or a water solubilizing group M)). The novel radicals have good stability, long relaxation times and good relaxivity.</p>
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METHODS AND COMPOSITIONS FOR IMAGE CONTRAST ENHANCING (Thu, 02 May 1996)
This invention relates to improvements in and relating to magnetic resonance imaging of the human or non-human body, in particular to a method in which positive and negative contrast agents are administered to enhance image contrast.
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PROCESS FOR THE PREPARATIONS OF SUBSTITUTED DIAMINODICARBOXYLIC ACID DERIVATIVES (Thu, 25 Apr 1996)
The invention relates to a new process for the preparation of substituted diaminodicarboxylic acid derivatives of the formula <br> 0 0 <br> R<sup>3</sup>0 - C 1 - CH - <sup>"</sup>(tH<sub>2</sub>)<sub>n</sub> - CH - C8 - OR<sup>3</sup> ( I ) <br> R!-N IH R,<sup>2</sup>-NIH</p> <p>in a high yield by a modified Kolbe synthesis.
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LIPOSOMAL AGENTS (Fri, 19 Apr 1996)
There is provided a liposomal agent comprising liposomes having bound to a membrane thereof a chelated diagnostically or therapeutically effective metal ion, the chelating agent binding said metal ion having a macrocyclic chelant moiety with attached to a single ring atom thereof a lipophilic membrane associating moiety.
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LIPOSOMAL AGENTS (Fri, 19 Apr 1996)
There is provided a liposomal agent comprising liposomes having bound to a membrane thereof a chelated diagnostically or therapeutically effective metal ion, the chelating agent binding said metal ion having a macrocyclic chelant moiety with attached to a single ring atom thereof a lipophilic membrane associating moiety. </p>
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IODINATED X-RAY-CONTRAST MEDIA (Fri, 29 Mar 1996)
The invention provides iodinated bis phenyl compounds, useful as X-ray contrast agents, of formula (I) (wherein each C6R5 moiety may be the same or different; each R denotes a hydrogen or iodine atom or a group M, two or three non-adjacent R groups on each C6R5 moiety denoting iodine atoms and one, two or three R groups on each C6R5 moiety denoting M groups; X denotes a group providing a 1, 2 or 3 atom chain linking the two C6R5 groups, preferably where X is or contains in the bridging chain a carbonyloxy group each C6R5 group being a triodophenyl group or a group in which each R is other than hydrogen; and each M is independently a non-ionic hydrophilic moiety, M preferably being a non-ionic hydrophilic moiety comprising a monohydroxy- or polyhydroxy-alkyl group) and isomers, especially stereoisomers and rotamers, thereof.
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