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Bioorg Med Chem Lett. 2010 Jan 15;20(2):488-92. doi: 10.1016/j.bmcl.2009.11.127. Epub 2009 Dec 1.

Synthesis and biological evaluation of substituted 2-phenyl-2H-indazole-7-carboxamides as potent poly(ADP-ribose) polymerase (PARP) inhibitors.

Author information

1
IRBM-Merck Research Laboratories Rome, Via Pontina km 30,600, Pomezia 00040, Rome, Italy. rita.scarpelli@iit.it

Abstract

A potent series of substituted 2-phenyl-2H-indazole-7-carboxamides were synthesized and evaluated as inhibitors of poly (ADP-ribose) polymerase (PARP). This extensive SAR exploration culminated with the identification of substituted 5-fluoro-2-phenyl-2H-indazole-7-carboxamide analog 48 which displayed excellent PARP enzyme inhibition with IC(50)=4nM, inhibited proliferation of cancer cell lines deficient in BRCA-1 with CC(50)=42nM and showed encouraging pharmacokinetic properties in rats compared to the lead 6.

PMID:
20007017
DOI:
10.1016/j.bmcl.2009.11.127
[Indexed for MEDLINE]

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