Cell-based optimization of novel benzamides as potential antimalarial leads

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:19

Article

Wu, Tao¹  Nagle, Advait¹  Sakata, Tomoyo¹  Henson, Kerstin¹  Borboa, Rachel¹  Chen, Zhong¹  Kuhen, Kelli¹  Plouffe, David¹  Winzeler, Elizabeth¹  Adrian, Francisco¹  Tuntland, Tove¹  Chang, Jonathan¹  Simerson, Susan¹  Howard, Steven¹  Ek, Jared¹  Isbell, John¹  Deng, Xianming²  Gray, Nathanael S.²  Tully, David C.¹  Chatterjee, Arnab K.¹ 

[1] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA

[2] Harvard Univ, Sch Med, Boston, MA 02115 USA

关键词: Malaria;    Kinase;    Cellular assay;    Cyclic amines;    Pharmacokinetics;    Resistant strains;   

DOI  :  10.1016/j.bmcl.2009.10.050

来源: Elsevier

【 摘 要 】

Screening our in-house compound collection using a cell based Plasmodium falciparum proliferation assay we discovered a known pan- kinase inhibitor scaffold as a hit. Further optimization of this series led us to a novel benzamide scaffold which was devoid of human kinase activity while retaining its antiplasmodial activity. The evolution of this compound series leading to optimized candidates with good cellular potency against multiple strains as well as decent in vivo profile is described in this Letter. (C) 2009 Elsevier Ltd. All rights reserved.

【 授权许可】

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