Synthesis and evaluation of CCR5 antagonists containing modified 4-piperidinyl-2-phenyl-1-(phenylsulfonylamino)-butane.
Synthesis of analogs containing more rigid bicyclic piperidine replacements for the 4-benzyloxycarbonyl-(ethyl)amino-piperidine moiety of the CCR5 antagonist structure, 1, is described. Although similar binding affinity to the lead was achieved with some analogs they were overall less potent anti-HIV agents suggesting that other features besides CCR5 binding are required for good anti-viral activity.
Shah
Shrenik K
SK
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. shrenik_shah@merck.com
Chen
Natalie
N
Guthikonda
Ravindra N
RN
Mills
Sander G
SG
Malkowitz
Lorraine
L
Springer
Martin S
MS
Gould
Sandra L
SL
Demartino
Julie A
JA
Carella
Anthony
A
Carver
Gwen
G
Holmes
Karen
K
Schleif
William A
WA
Danzeisen
Renee
R
Hazuda
Daria
D
Kessler
Joseph
J
Lineberger
Janet
J
Miller
Michael
M
Emini
Emilio A
EA
MacCoss
Malcolm
M
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002073:Butanes / Q000138:chemical synthesis / Q000494:pharmacology; D065100:CCR5 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000494:pharmacology; D014780:Viruses / Q000187:drug effects
D019380:Anti-HIV Agents; D002073:Butanes; D065100:CCR5 Receptor Antagonists; D010880:Piperidines; D013450:Sulfones