1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 2: lead optimization affording selective, orally bioavailable compounds with potent anti-HIV activity.
Investigations of the structure-activity relationships of 1,3,4-trisubstituted pyrrolidine human CCR5 receptor antagonists afforded orally bioavailable compounds with the ability to inhibit HIV replication in vitro.
Hale
J J
JJ
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. jeffrey_hale@merck.com
Budhu
R J
RJ
Holson
E B
EB
Finke
P E
PE
Oates
B
B
Mills
S G
SG
MacCoss
M
M
Gould
S L
SL
DeMartino
J A
JA
Springer
M S
MS
Siciliano
S
S
Malkowitz
L
L
Schleif
W A
WA
Hazuda
D
D
Miller
M
M
Kessler
J
J
Danzeisen
R
R
Holmes
K
K
Lineberger
J
J
Carella
A
A
Carver
G
G
Emini
E
E
D000284:Administration, Oral; D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D065100:CCR5 Receptor Antagonists; D016466:CHO Cells; D006224:Cricetinae; D006678:HIV / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D011759:Pyrrolidines