The role of the acidity of N-heteroaryl sulfonamides as inhibitors of Bcl-2 family protein–protein interactions

BB Touré, K Miller-Moslin, N Yusuff…

Index: Toure, B. Barry; Miller-Moslin, Karen; Yusuff, Naeem; Perez, Lawrence; Dore, Michael; Joud, Carol; Michael, Walter; Dipietro, Lucian; Van Der Plas, Simon; McEwan, Michael; Lenoir, Francois; Hoe, Madelene; Karki, Rajesh; Springer, Clayton; Sullivan, John; Levine, Kymberly; Fiorilla, Catherine; Xie, Xiaoling; Kulathila, Raviraj; Herlihy, Kara; Porter, Dale; Visser, Michael ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 2 p. 186 - 190

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Citation Number: 17

Abstract

Overexpression of the antiapoptotic members of the Bcl-2 family of proteins is commonly associated with cancer cell survival and resistance to chemotherapeutics. Here, we describe the structure-based optimization of a series of N-heteroaryl sulfonamides that demonstrate potent mechanism-based cell death. The role of the acidic nature of the sulfonamide moiety as it relates to potency, solubility, and clearance is examined. This has led to the discovery ...