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The design, synthesis and structure-activity relationships of novel isoindoline-based histone deacetylase inhibitors

Shultz, Michael and Fan, Jianmei and Chen, Christine and Cho, Young and Davis, Nicole and Bickford, Shari and Buteau, Kristen and Cao, Xueying and Holmqvist, Mats and Hsu, Meier and Jiang, Lei and Liu, Gang and Lu, Qiang and Patel, Chetan and Suresh, Joghee and Selvaraj, Mannangatti and Urban, Laszlo and Wang, Ping and Yan-Neale, Yan and Whitehead, Lewis and Zhang, Haiyan and Zhou, Liping and Atadja, Peter (2011) The design, synthesis and structure-activity relationships of novel isoindoline-based histone deacetylase inhibitors. Bioorganic & Medicinal Chemistry Letters, 21 (16). pp. 4909-4912. ISSN 0960-894X

Abstract

The design, synthesis and biological evaluation of a novel series of isoindoline-based hydroxamates is described. Several analogs were shown to inhibit HDAC1 with IC50 values in the low nanomolar range and inhibit cellular proliferation of HCT116 human colon cancer cells in the sub-micromolar range. The cellular potency of compound 17e was found to have greater in vitro anti-proliferative activity than several compounds in late stage clinical trials for the treatment of cancer. The in vitro safety profiles of selected compounds were assessed and shown to be suitable for further lead optimization.

Item Type: Article
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Keywords: HDAC, hydroxamate, cancer
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Date Deposited: 13 Oct 2015 13:15
Last Modified: 13 Oct 2015 13:15
URI: https://oak.novartis.com/id/eprint/3997

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