Syntheses and biological evaluation of 5-(piperidin-1-yl)-3-phenyl-pentylsulfones as CCR5 antagonists.
Cellular proliferation of HIV-1 requires the cooperative assistance of both the CCR5 and CD4 receptors. Our medicinal chemistry efforts in this area have resulted in the identification of N-alkyl piperidine sulfones as CCR5 antagonists. These compounds display potent binding and show antiviral properties in HIV-1 spread cell-based assays.
Shankaran
K
K
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. kothandaraman_shankaran@merck.com
Donnelly
Karla L
KL
Shah
Shrenik K
SK
Caldwell
Charles G
CG
Chen
Ping
P
Finke
Paul E
PE
Oates
Bryan
B
MacCoss
Malcolm
M
Mills
Sander G
SG
DeMartino
Julie A
JA
Gould
Sandra L
SL
Malkowitz
Lorraine
L
Siciliano
Salvatore J
SJ
Springer
Martin S
MS
Kwei
Gloria
G
Carella
Anthony
A
Carver
Gwen
G
Danzeisen
Renee
R
Hazuda
Daria
D
Holmes
Karen
K
Kessler
Joseph
J
Lineberger
Janet
J
Miller
Michael D
MD
Emini
Emilio A
EA
Schleif
William A
WA
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D065100:CCR5 Receptor Antagonists; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D010880:Piperidines / Q000737:chemistry; D019713:Receptors, CCR5 / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000494:pharmacology
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D015704:CD4 Antigens; D010880:Piperidines; D019713:Receptors, CCR5; D013450:Sulfones; C032727:piperidine