Design and synthesis of 6-phenylnicotinamide derivatives as antagonists of TRPV1

SM Westaway, M Thompson, HK Rami, G Stemp…

Index: Westaway, Susan M.; Thompson, Mervyn; Rami, Harshad K.; Stemp, Geoffrey; Trouw, Leontine S.; Mitchell, Darren J.; Seal, Jon T.; Medhurst, Stephen J.; Lappin, Sarah C.; Biggs, James; Wright, James; Arpino, Sandra; Jerman, Jeffrey C.; Cryan, Jennifer E.; Holland, Vicky; Winborn, Kim Y.; Coleman, Tanya; Stevens, Alexander J.; Davis, John B.; Gunthorpe, Martin J. Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 20 p. 5609 - 5613

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Citation Number: 32

Abstract

6-Phenylnicotinamide (2) was previously identified as a potent TRPV1 antagonist with activity in an in vivo model of inflammatory pain. Optimization of this lead through modification of both the biaryl and heteroaryl components has resulted in the discovery of 6- (4-fluorophenyl)-2-methyl-N-(2-methylbenzothiazol-5-yl) nicotinamide (32; SB-782443) which possesses an excellent overall profile and has been progressed into pre-clinical ...