Design, synthesis, and SAR of heterocycle-containing antagonists of the human CCR5 receptor for the treatment of HIV-1 infection.
Replacement of the large hydantoin-indole moiety from our previous work with a variety of smaller heterocyclic analogues gave rise to potent CCR5 antagonists having binding affinity comparable to the hydantoin analogues. The synthesis, SAR, and biological profiles of this class of antagonists are described.
Kim
D
D
Department of Medicinal Chemistry, Merck Research Laboratories, RY 121-240, PO Box 2000, Rahway, NJ 07065, USA. dooseop_kim@merck.com
Wang
L
L
Caldwell
C G
CG
Chen
P
P
Finke
P E
PE
Oates
B
B
MacCoss
M
M
Mills
S G
SG
Malkowitz
L
L
Gould
S L
SL
DeMartino
J A
JA
Springer
M S
MS
Hazuda
D
D
Miller
M
M
Kessler
J
J
Danzeisen
R
R
Carver
G
G
Carella
A
A
Holmes
K
K
Lineberger
J
J
Schleif
W A
WA
Emini
E A
EA
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D065100:CCR5 Receptor Antagonists; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000302:isolation & purification; D006367:HeLa Cells; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D006571:Heterocyclic Compounds