Design, synthesis, and SAR of novel benzimidazole based HDAC inhibitors

MEDI 575

Haishan Wang, haishan_wang@sbio.com1, Niefang Yu1, Hongyan Song1, Dizhong Chen1, Weiping Deng1, Pek Ling Lye1, Yong Zou1, Melvin Ng1, Joyce Chang1, Eric T Sun1, Kanda Sangthongpitag2, Xukun Wang2, Xiaofeng Wu2, Hwee Hoon Khng2, Siok Kun Goh2, Pauline Yeo3, Xin Liu3, Evelyn Goh3, Lee Sun New3, Kantharaj Ethirajulu3, and Michael Entzeroth2. (1) Medicinal Chemistry, S*BIO Pte Ltd, 1 Science Park Road #05-09 The Capricorn, Singapore Science Park II, Singapore 117528, Singapore, (2) Drug Discovery Biology, S*BIO Pte Ltd, Singapore 117528, Singapore, (3) Pharmacokinetics and Drug Metabolism, S*BIO Pte Ltd, Singapore 117528, Singapore
We have designed and synthesized a series of benzimidazole based hydroxamic acids (1) as HDAC inhibitors. SAR of substituents on the benzimidazole ring were explored and established. Within this series, selected compounds were evaluated in animal models for anti-tumor activity. A representative compound SB639 (2) produced significant tumor growth inhibition and tumor growth delay in HCT116 bearing nude mice xenograft model. In this presentation, the synthesis, SAR and biological profiles of this series of inhibitors will be discussed.

 

General Oral Session
1:30 PM-4:50 PM, Thursday, 14 September 2006 Moscone Center -- Room 102, Oral

Division of Medicinal Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006