Discovery of N-benzyl-N'-(4-pipyridinyl)urea CCR5 antagonists as anti-HIV-1 agents (II): modification of the acyl portion.
Modification of the acyl moiety in the CCR5 lead molecule 2 led to identification of several new classes of CCR5 antagonists. Antiviral activity and pharmacokinetic properties of the synthesized compounds were evaluated. Structure-activity relationship (SAR) derived from these studies further guided the optimization efforts, ultimately leading to the discovery of 36 with an acceptable drug-like profile.
Infectious Diseases Center for Excellence in Drug Discovery, GlaxoSmithKline, Research Ttriangle Park, NC 27709, USA. maosheng.a.duan@gsk.com
Maosheng
M
Duan
Jennifer
J
Peckham
Mark
M
Edelstein
Robert
R
Ferris
Wieslaw M
WM
Kazmierski
Andrew
A
Spaltenstein
Pat
P
Wheelan
Zhiping
Z
Xiong
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D065100:CCR5 Receptor Antagonists; D045744:Cell Line, Tumor; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D015497:HIV-1 / Q000187:drug effects*; D000882:Haplorhini; D006801:Humans; D011725:Pyridines / Q000737:chemistry; D051381:Rats; D019713:Receptors, CCR5 / Q000378:metabolism; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D011725:Pyridines; D019713:Receptors, CCR5; D014508:Urea; C023666:pyridine