2-(2-Aminothiazol-4-yl) pyrrolidine-based tartrate diamides as potent, selective and orally bioavailable TACE inhibitors

…, J Popovici-Muller, L Zhao, VM Girijavallabhan…

Index: Dai, Chaoyang; Li, Dansu; Popovici-Muller, Janeta; Zhao, Lianyun; Girijavallabhan, Vinay M.; Rosner, Kristin E.; Lavey, Brian J.; Rizvi, Razia; Shankar, Bandarpalle B.; Wong, Michael K.C.; Guo, Zhuyan; Orth, Peter; Strickland, Corey O.; Sun, Jing; Niu, Xiaoda; Chen, Shiying; Kozlowski, Joseph A.; Lundell, Daniel J.; Piwinski, John J.; Shih, Neng-Yang; Siddiqui, M. Arshad Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 10 p. 3172 - 3176

Full Text: HTML

Citation Number: 14

Abstract

Abstract TNF-α converting enzyme (TACE) inhibitors are promising agents to treat inflammatory disorders and cancer. We have investigated novel tartrate diamide TACE inhibitors where the tartrate core binds to zinc in a unique tridentate fashion. Incorporating (R)-2-(2-N-alkylaminothiazol-4-yl) pyrrolidines into the left hand side amide of the tartrate scaffold led to the discovery of potent and selective TACE inhibitors, some of which ...