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Bioorg Med Chem Lett. 2014 Aug 15;24(16):3739-43. doi: 10.1016/j.bmcl.2014.07.001. Epub 2014 Jul 5.

Synthesis and biological evaluation of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors.

Author information

  • 1Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China.
  • 2Department of Traditional Chinese Materia Medica and Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China.
  • 3Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China. Electronic address: wxkcaptain@aliyun.com.
  • 4Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China. Electronic address: zhengzb@bmi.ac.cn.

Abstract

We have developed a series of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors. Preliminary biological evaluation indicated that most compounds possessed inhibitory potencies comparable to, or higher than AZD-2281. Among these compounds, 18q appeared to be the most notable one, which displayed an 8-fold improvement in enzymatic activity compared to AZD-2281. These efforts lay the foundation for our further investigation.

Copyright © 2014 Elsevier Ltd. All rights reserved.

KEYWORDS:

4-(Thiophen-2-ylmethyl)-2H-phthalazin-1-ones; Antitumor; Biological evaluation; PARP-1 inhibitor; Synthesis

PMID:
25086680
[PubMed - in process]
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