|
|||||
|
|
Antagonists of human CCR5 receptor containing 4-(pyrazolyl)piperidine side chains. Part 1: Discovery and SAR study of 4-pyrazolylpiperidine side chains |
|
| Authors: | Shen Dong-Ming Shu Min Mills Sander G Chapman Kevin T Malkowitz Lorraine Springer Martin S Gould Sandra L DeMartino Julie A Siciliano Salvatore J Kwei Gloria Y Carella Anthony Carver Gwen Holmes Karen Schleif William A Danzeisen Renee Hazuda Daria Kessler Joseph Lineberger Janet Miller Michael D Emini Emilio A |
| Affiliation: | Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. dongming_shen@merck.com |
| Abstract: | Replacement of the flexible connecting chains between the piperidine moiety and an aromatic group in previous CCR5 antagonists with heterocycles, such as pyrazole and isoxazole, provided potent CCR5 antagonists with excellent anti-HIV-1 activity in vitro. SAR studies revealed optimal placement of an unsubstituted nitrogen atom in the heterocycle to be meta to the bond connected to the 4-position of piperidine. Truncation of a benzyl group to a phenyl group afforded compounds with dramatically improved oral bioavailability, albeit with reduced activity. |
| Keywords: | |
| 本文献已被 PubMed 等数据库收录！ | |