Combinatorial synthesis of CCR5 antagonists.
Herein we report the preparation of a combinatorial library of compounds with potent CCR5 binding affinity. The library design was aided by SAR generated in a traditional medicinal chemistry effort. Compounds with novel combinations of subunits were discovered that have high binding affinity for the CCR5 receptor. A potent CCR5 antagonist from the library, compound 11 was found to have moderate anti-HIV-1 activity.
Willoughby
C A
CA
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. christopher_willoughby@merck.com
Berk
S C
SC
Rosauer
K G
KG
Degrado
S
S
Chapman
K T
KT
Gould
S L
SL
Springer
M S
MS
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 A
EA
D065100:CCR5 Receptor Antagonists; D020650:Combinatorial Chemistry Techniques; D015497:HIV-1 / Q000187:drug effects; D013329:Structure-Activity Relationship
D065100:CCR5 Receptor Antagonists