title: 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.
abstract: 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.
authors.affiliation: Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China.
authors.forename: Ben
authors.initials: B
authors.lastname: Li
authors.forename: Eric Dale
authors.initials: ED
authors.lastname: Jones
authors.forename: Enkun
authors.initials: E
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Dean Cameron
authors.initials: DC
authors.lastname: Baylis
authors.forename: Shanghai
authors.initials: S
authors.lastname: Yu
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.forename: Xing
authors.initials: X
authors.lastname: He
authors.forename: Jonathan Alan Victor
authors.initials: JA
authors.lastname: Coates
authors.forename: David Ian
authors.initials: DI
authors.lastname: Rhodes
authors.forename: Gang
authors.initials: G
authors.lastname: Pei
authors.forename: John Joseph
authors.initials: JJ
authors.lastname: Deadman
authors.forename: Xin
authors.initials: X
authors.lastname: Xie
authors.forename: Dawei
authors.initials: D
authors.lastname: Ma
mesh_terms: 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
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D011759:Pyrrolidines