Studies on the structure-activity relationship of 1,3,3,4-tetra-substituted pyrrolidine embodied CCR5 receptor antagonists. Part 1: Tuning the N-substituents.
A novel series of CCR5 antagonists has been identified, utilizing the lead, nifeviroc, which were further modified based on bioisosteric principles. Lead optimization was pursued by balancing potential toxicity and potency. Potent analogues with low toxic properties were successfully developed by formation of urea and amide bonds at the nitrogen at position 4- of the pyrrolidine ring.
Ben
Li
L
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 319 Yueyang Lu, Shanghai 200031, China.
Jones
Eric Dale
ED
Zhou
Enkun
E
Li
Chen
C
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; D065100:CCR5 Receptor Antagonists; D016466:CHO Cells; D018938:Caco-2 Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D065100:CCR5 Receptor Antagonists; D011759:Pyrrolidines