Synthesis and biological evaluation of homopiperazine derivatives with beta-aminoacyl group as dipeptidyl peptidase IV inhibitors
作者
Ahn, JH; Park, WS; Jun, MA; Shin, MS; Kang, SK; Kim, KY; Dal Rhee, S; Bae, MA; Kim, KR; Kim, SG; Kim, SY; Sohn, SK; Kang, NS; Lee, JO; Lee, DH; Cheon, HG; Kim, SS
[摘要]：Compounds with homopiperazine skeleton are designed to find a potent DPP-IV inhibitor without inhibiting CYP. Thus a series of beta-aminoacyl-containing homopiperazine derivatives was synthesized and evaluated. Compounds with acid moiety were found to be potent inhibitors of DPP-IV without inhibiting CYP 3A4. More specifically, compound 7m showed nanomolar activity with no inhibition towards five sub-types of CYPs, was considered as a prototype for further derivatization. Based on its X-ray co-crystal structure with human DPP-IV, we identified compounds 7s and 7t which showed good in vitro activity, no CYP inhibition, and good selectivity. (C) 2008 Elsevier Ltd. All rights reserved.
