Lead optimisation of selective non-zinc binding inhibitors of MMP13. Part 2

…, I Nash, G Karoutchi, K Page, A Ting, S Gerhardt

Index: De Savi, Chris; Morley, Andrew D.; Nash, Ian; Karoutchi, Galith; Page, Ken; Ting, Attilla; Gerhardt, Stefan Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 1 p. 271 - 277

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Citation Number: 7

Abstract

Directed screening has identified a novel series of non-zinc binding MMP13 inhibitors that possess good levels of activity whilst demonstrating excellent selectivity over related MMPs. A lead optimisation campaign has delivered compounds with enhanced MMP13 potency, good selectivity and acceptable bioavailability profiles leading to a predicted twice-a-day dosing regimen in man.