Studies on the structure-activity relationship of 1,3,3,4-tetra-substituted pyrrolidine embodied CCR5 receptor antagonists. Part 2: Discovery of highly potent anti-HIV agents.
Modification of 1,3,3,4-tetra-substituted pyrrolidine embodied CCR5 receptor antagonists revealed that introducing a fluoro group at the 3-position of the 3-phenyl group to reduce metabolism did not adversely affect the high potency against HIV infection, and that replacing the piperidine ring with a tropane ring could deliver the most potent anti-HIV agents. Stereochemistry of the substituted tropane ring is essential for maintaining the potent anti-HIV activity because only exo-isomers displayed subnanomolar whole cell activity.
Li
Ben
B
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China.
Jones
Eric Dale
ED
Zhou
Enkun
E
Chen
Li
L
Baylis
Dean Cameron
DC
Yu
Shanghai
S
Wang
Miao
M
He
Xing
X
Coates
Jonathan Alan Victor
JA
Rhodes
David Ian
DI
Pei
Gang
G
Deadman
John Joseph
JJ
Xie
Xin
X
Ma
Dawei
D
D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D055808:Drug Discovery; D011759:Pyrrolidines / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D011759:Pyrrolidines