Indolin-2-one p38α inhibitors III: Bioisosteric amide replacement

P Eastwood, J González, E Gómez, F Caturla…

Index: Eastwood, Paul; Gonzalez, Jacob; Gomez, Elena; Caturla, Francisco; Aguilar, Nuria; Mir, Marta; Aiguade, Josep; Matassa, Victor; Balague, Cristina; Orellana, Adelina; Dominguez, Maria Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 21 p. 6253 - 6257

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Citation Number: 9

Abstract

Crystallographic structural information was used in the design and synthesis of a number of bioisosteric derivatives to replace the amide moiety in a lead series of p38α inhibitors which showed general hydrolytic instability in human liver preparations. Triazole derivative 13 was found to have moderate bioavailability in the rat and demonstrated potent in-vivo activity in an acute model of inflammation.