Substituted 6-amino-4H-[1,2]dithiolo[4,3-b]pyrrol-5-ones: Synthesis, structure-activity relationships, and cytotoxic activity on selected human cancer cell lines

Document Type

Article

Publication Date

7-1-2007

Abstract

An efficient synthesis and the cytotoxic activity of a series of substituted 6-amino-4H-[1,2]dithiolo[4,3-b]pyrrol-5-ones 1a-q is described. The synthesis was accomplished in an expedient manner (seven-steps) from commercially available starting materials. Several of the derivatives tested demonstrated significant in vitro cytotoxic activity against the human cancer cell lines H460 (≥7 nM) and LCC6 (≥28 nM). Following SAR and pharmacokinetic studies a derivative was further evaluated for its in vivo anti-tumor activity against a highly angiogenic human melanoma xenograft where it demonstrated significant efficacy as a mono-therapy and in combination with Taxol and Cisplatin. © 2007 Elsevier Ltd. All rights reserved.

Publication Source (Journal or Book title)

Bioorganic and Medicinal Chemistry

First Page

4601

Last Page

4608

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