鉴定和 SAR 新型吡咯并[1,2-a]吡嗪-1(2H)-酮衍生物作为聚（ADP-核糖）聚合酶-1（PARP-1）抑制剂。
Identification and SAR of novel pyrrolo[1,2-a]pyrazin-1(2H)-one derivatives as inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1).
机构信息
IRBM/Merck Research Laboratories, 00040 Pomezia, Italy.
出版信息
Bioorg Med Chem Lett. 2010 Feb 1;20(3):1094-9. doi: 10.1016/j.bmcl.2009.12.026. Epub 2009 Dec 6.
PMID:20031401
Abstract
Herein we describe the discovery of a novel series of pyrrolo[1,2-a]pyrazin-1(2H)-one PARP inhibitors. Optimization led to compounds that display excellent PARP-1 enzyme potency and inhibit the proliferation of BRCA deficient cells in the low double-digit nanomolar range showing excellent selectivity over BRCA proficient cancer cells.
摘要
在此，我们描述了一系列新型吡咯并[1,2-a]吡嗪-1(2H)-酮 PARP 抑制剂的发现。通过优化得到的化合物对 PARP-1 酶具有优异的抑制活性，在低双位数纳摩尔范围内抑制 BRCA 缺陷细胞的增殖，对 BRCA 功能正常的癌细胞具有优异的选择性。
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