773872-85-8Relevant academic research and scientific papers
Discovery of a potent and selective Bcl-2 inhibitor using SAR by NMR
Petros, Andrew M.,Huth, Jeffrey R.,Oost, Thorsten,Park, Cheol-Min,Ding, Hong,Wang, Xilu,Zhang, Haichao,Nimmer, Paul,Mendoza, Renaldo,Sun, Chaohong,MacK, Jamey,Walter, Karl,Dorwin, Sarah,Gramling, Emily,Ladror, Uri,Rosenberg, Saul H.,Elmore, Steven W.,Fesik, Stephen W.,Hajduk, Philip J.
scheme or table, p. 6587 - 6591 (2010/12/20)
The Bcl-2 family of proteins plays a major role in the regulation of apoptosis, or programmed cell death. Overexpression of the anti-apoptotic members of this family (Bcl-2, Bcl-xL, and Mcl-1) can render cancer cells resistant to chemotherapeutic agents and therefore these proteins are important targets for the development of new anti-cancer agents. Here we describe the discovery of a potent, highly selective, Bcl-2 inhibitor using SAR by NMR and structure-based drug design which could serve as a starting point for the development of a Bcl-2 selective anti-cancer agent. Such an agent would potentially overcome the Bcl-xL mediated thrombocytopenia observed with ABT-263.
Design, synthesis, and SAR of anthranilamide-based factor Xa inhibitors incorporating substituted biphenyl P4 motifs
Zhang, Penglie,Bao, Liang,Zuckett, Jingmei F.,Goldman, Erick A.,Jia, Zhaozhong J.,Arfsten, Ann,Edwards, Susan,Sinha, Uma,Hutchaleelaha, Athiwat,Park, Gary,Lambing, Joseph L.,Hollenbach, Stanley J.,Scarborough, Robert M.,Zhu, Bing-Yan
, p. 983 - 987 (2007/10/03)
Anthranilamides 4 and 5 were designed and synthesized as selective and orally bioavailable factor Xa inhibitors. Structural modifications aimed at lowering their lipophilicity were performed at the central phenyl ring and at the S4 binding biphenyl region by incorporating water solublizing substituents. The resulting compounds (e.g., 7, 8, 14, 30a, and 32b) are highly potent in vitro, and show improved activity in human plasma-based thrombin generation assay.
