CCR5 antagonists: 3-(pyrrolidin-1-yl) propionic acid analogues with potent anti-HIV activity

CL Lynch, JJ Hale, RJ Budhu, AL Gentry, PE Finke…

Index: Lynch, Christopher L.; Hale, Jeffrey J.; Budhu, Richard J.; Gentry, Amy L.; Finke, Paul E.; Caldwell, Charles G.; Mills, Sander G.; MacCoss, Malcolm; Shen, Dong-Ming; Chapman, Kevin T.; Malkowitz, Lorraine; Springer, Martin S.; Gould, Sandra L.; DeMartino, Julie A.; Siciliano, Salvatore J.; Cascierl, Margaret A.; Carella, Anthony; Carver, Gwen; Holmes, Karen; Schleif, William A.; Danzeisen, Renee; Hazuda, Daria; Kessler, Joseph; Lineberger, Janet; Miller, Michael; Emini, Emilio Organic Letters, 2003 , vol. 5, # 14 p. 2473 - 2475

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Citation Number: 21

Abstract

A novel approach to α, α-disubstituted-β-amino acids (β2, 2-amino acids) was employed in the synthesis of a series of 3-(pyrrolidin-1-yl) propionic acids possessing high affinity for the CCR5 receptor and potent anti-HIV activity. The rat pharmacokinetics for these new analogues featured higher bioavailabilities and lower rates of clearance as compared to cyclopentane 1.