WO2010007027 Selective hydroxamic acid based MMP-12 and MMP-13 inhibitors

WO2010007027.pdf
Adobe Acrobat Document 3.7 MB

Biological target:

Collagenase 3: MMP13

Activity:

Inhibitor

Steps Conditions Reactions
a

1. Oxalyl chloride  / DMF

2. NH2-OH / THF


b

O-tritylhydroxylamine 


c HCl 3N / EtOH

d O-tritylhydroxyamine / NMP / EDCI / HOBt / DCM
e TFA / triethylsilane / DCM
Steps Conditions Reactions
a Et3N / dioxane / H2O Sulfonamide synthesis
b 1-bromo-3-methyl butane / K2CO3 / DMF Nucleophilic substitution
c HCl 4N / EtOAc Terbutyl deprotection
Steps Conditions Reactions
a SOCl2 / MeOH Ester synthesis (Esterification)
b Et3N / Dioxane / H2O Sulfonamide synthesis (coupling reaction)
c K2CO3 / DMF Nucleophilic substitution
d LiOH / THF / H2O Carboxylic acid synthesis (Ester Hydrolysis)
Steps Conditions Reactions
a n-BuLi / CuBr-Me2S / THF
b 0.25 N HCl / THF Hydrolysis
c

1. ArSO2Cl / TEA / Dioxane / Water

2. NaBH4 / EtOH / THF

3.MsCl / TEA / DMAP / DCM

Sulfonamide synthesis / Ketone reduction / Mesyl synthesis
d Cs2CO3 / LiI / DMF Cyclisation
e

LiOH / THF / Water

Carboxylic acid synthesis (Ester hydrolysis)

Site Search