Potent 1,3,4-trisubstituted pyrrolidine CCR5 receptor antagonists: effects of fused heterocycles on antiviral activity and pharmacokinetic properties.
A series of 1,3,4-trisubstituted pyrrolidine CCR5 receptor antagonists containing a variety of fused heterocycles at the 4-position of the piperidine side chain has been discovered, which are orally bioavailable with potent anti-HIV activity.
Kim
Dooseop
D
Department of Medicinal Chemistry, Merck Research Laboratories, RY800-206, PO Box 2000, Rahway, NJ 07065, USA. dooseop_kim@merck.com <dooseop_kim@merck.com>
Wang
Liping
L
Hale
Jeffrey J
JJ
Lynch
Christopher L
CL
Budhu
Richard J
RJ
Maccoss
Malcolm
M
Mills
Sander G
SG
Malkowitz
Lorraine
L
Gould
Sandra L
SL
DeMartino
Julie A
JA
Springer
Martin S
MS
Hazuda
Daria
D
Miller
Michael
M
Kessler
Joseph
J
Hrin
Renee C
RC
Carver
Gwen
G
Carella
Anthony
A
Henry
Karen
K
Lineberger
Janet
J
Schleif
William A
WA
Emini
Emilio A
EA
D000284:Administration, Oral; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D065100:CCR5 Receptor Antagonists; D006367:HeLa Cells; D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D011759:Pyrrolidines / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D019713:Receptors, CCR5 / Q000378:metabolism
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D006571:Heterocyclic Compounds; D011759:Pyrrolidines; D019713:Receptors, CCR5