| Literature DB >> 15012998 |
Dong-Ming Shen1, Min Shu, Christopher A Willoughby, Shrenik Shah, Christopher L Lynch, Jeffrey J Hale, Sander G Mills, Kevin T Chapman, Lorraine Malkowitz, Martin S Springer, Sandra L Gould, Julie A DeMartino, Salvatore J Siciliano, Kathy Lyons, James V Pivnichny, Gloria Y Kwei, Anthony Carella, Gwen Carver, Karen Holmes, William A Schleif, Renee Danzeisen, Daria Hazuda, Joseph Kessler, Janet Lineberger, Michael D Miller, Emilio A Emini.
Abstract
Modifications of the alkyl acetic acid portion and the phenyl on pyrrolidine in our lead pyrazole compound 1 afforded the isopropyl compound 9. This compound is a potent CCR5 antagonist showing good in vitro antiviral activity against HIV-1, an excellent selectivity profile, and good oral bioavailability in three animal species. During this investigation, a new method for the preparation of alpha-(pyrrolidin-1-yl)-alpha,alpha-dialkyl acetic acid from a pyrrolidine and alpha-bromo-alpha,alpha-dialkyl acetic acid using silver triflate was discovered. This allowed us to prepare compounds such as 24 and 25 for the first time. A novel Pd-mediated N-dealkylation of alpha-(pyrrolidin-1-yl)acetic acid was also uncovered.Entities:
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Year: 2004 PMID： 15012998 DOI： 10.1016/j.bmcl.2003.12.005
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823