Wells Gregory J, Bihovsky Ron, Hudkins Robert L, Ator Mark A, Husten Jean
Cephalon, Inc., 145 Brandywine Parkway, West Chester, PA 19380-4245, USA.
Bioorg Med Chem Lett. 2006 Mar 1;16(5):1151-5. doi: 10.1016/j.bmcl.2005.11.086. Epub 2005 Dec 15.
A series of novel pyrrolocarbazole lactams was identified as potent PARP-1 inhibitors in vitro and in a PC12 cellular NAD(+) depletion assay. The SAR trends of substituents at the 3-position, as well as the effect of blocking the indole or lactam NH-groups of the template by methylation or formylation, are discussed in relation to molecular modeling studies.
一系列新型吡咯并咔唑内酰胺在体外以及PC12细胞NAD(+)消耗试验中被鉴定为有效的PARP-1抑制剂。结合分子模拟研究，讨论了3-位取代基的构效关系趋势，以及通过甲基化或甲酰化封闭模板的吲哚或内酰胺NH基团的影响。
