Non-aromatic A-ring replacement in the triaryl bis-sulfone CB2 receptor inhibitors.
The triaryl bis-sulfone 1 was modified by converting the aryl A-ring to a piperidine ring. The piperidine ring was further elaborated to a spirocyclopropyl piperidine moiety. The effect on CB2 binding potency, rat calcium channel affinity, and CYP 2C9 inhibition is described.
Gilbert
Eric J
EJ
Department of Medicinal Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033-0539, USA. eric.gilbert@spcorp.com
Zhou
Guowei
G
Wong
Michael K C
MK
Tong
Ling
L
Shankar
Bandarpalle B
BB
Huang
Chunli
C
Kelly
Joseph
J
Lavey
Brian J
BJ
McCombie
Stuart W
SW
Chen
Lei
L
Rizvi
Razia
R
Dong
Youhao
Y
Shu
Youheng
Y
Kozlowski
Joseph A
JA
Shih
Neng-Yang
NY
Hipkin
R William
RW
Gonsiorek
Waldemar
W
Malikzay
Asra
A
Lunn
Charles A
CA
Favreau
Len
L
Lundell
Daniel J
DJ
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System; D054314:Drug Inverse Agonism; D006801:Humans; D010880:Piperidines / Q000737:chemistry; D051381:Rats; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000493:pharmacokinetics
D015220:Calcium Channels; D010880:Piperidines; D043885:Receptor, Cannabinoid, CB2; D013449:Sulfonamides; D013450:Sulfones; C032727:piperidine; D003577:Cytochrome P-450 Enzyme System