Discovery of 4-{4-[3-(Pyridin-2-yl)-1 H-pyrazol-4-yl] pyridin-2-yl}-N-(tetrahydro-2 H-pyran-4-yl) benzamide (GW788388): A Potent, Selective, and Orally Active …

…, N Mathews, VL Nguyen, C Bertho-Ruault…

Index: Gellibert, Francoise; De Gouville, Anne-Charlotte; Woolven, James; Mathews, Neil; Nguyen, Van-Loc; Bertho-Ruault, Cecile; Patikis, Angela; Grygielko, Eugene T.; Laping, Nicholas J.; Huet, Stephane Journal of Medicinal Chemistry, 2006 , vol. 49, # 7 p. 2210 - 2221

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Citation Number: 61

Abstract

Inhibitors of transforming growth factor β (TGF-β) type I receptor (ALK5) offer a novel approach for the treatment of fibrotic diseases such as renal, hepatic, and pulmonary fibrosis. The optimization of a novel phenylpyridine pyrazole series (1a) led to the identification of potent, selective, and orally active ALK5 inhibitors. The cellular potency and pharmacokinetics profiles of these derivatives were improved and several compounds ...