WO2010059552 Propyl hydroxylase inhibitors

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Biological target:

HIF prolyl-hydroxylase

Activity:

Inhibitor

Steps Conditions Reactions
a Phosphoryl trichloride reflux, 6h
b KMNO4, H2O, reflux, 24h Oxidation (Carboxylic acid formation)
c K2CO3, CH3I, DMF, 12h Esterification
d NaN3, DMF, 12h Azide formation
e H2, Pd/C, MeOH, 12h Azide Reduction (Amine formation)
f

i). Triphosgene, DMAP, CH2Cl2, -77oC

ii). NaOH 2N, 50oC, 30 min
Urea formation, intramolecular cyclization and saponification
g HATU, Et3N, DMF Amide bond formation

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