1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 3: polar functionality and its effect on anti-HIV-1 activity.
Incorporation of acidic functional groups into a lead CCR5 antagonist identified from a targeted combinatorial library resulted in compounds with enhanced anti-HIV-1 activity and attenuated L-type calcium channel affinity.
Hale
Jeffrey J
JJ
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. jeffrey_hale@merck.com
Budhu
Richard J
RJ
Mills
Sander G
SG
MacCoss
Malcolm
M
Gould
Sandra L
SL
DeMartino
Julie A
JA
Springer
Martin S
MS
Siciliano
Salvatore J
SJ
Malkowitz
Lorraine
L
Schleif
William A
WA
Hazuda
Daria
D
Miller
Michael
M
Kessler
Joseph
J
Danzeisen
Renee
R
Holmes
Karen
K
Lineberger
Janet
J
Carella
Anthony
A
Carver
Gwen
G
Emini
Emilio A
EA
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D016466:CHO Cells; D020746:Calcium Channels, L-Type / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D054407:Chemokine CCL4; D006224:Cricetinae; D015497:HIV-1 / Q000187:drug effects*; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000037:antagonists & inhibitors; D051381:Rats; D019713:Receptors, CCR5 / Q000737:chemistry; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D020746:Calcium Channels, L-Type; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5