Structure-activity relationships of diphenylpiperazine N-type calcium channel inhibitors.
A novel series of compounds derived from the previously reported N-type calcium channel blocker NP118809 (1-(4-benzhydrylpiperazin-1-yl)-3,3-diphenylpropan-1-one) is described. Extensive SAR studies resulted in compounds with IC(50) values in the range of 10-150 nM and selectivity over the L-type channels up to nearly 1200-fold. Orally administered compounds 5 and 21 exhibited both anti-allodynic and anti-hyperalgesic activity in the spinal nerve ligation model of neuropathic pain.
Pajouhesh
Hassan
H
Neuromed Pharmaceuticals Ltd, 301-2389 Health Sciences Mall, Vancouver, BC, Canada.
Feng
Zhong-Ping
ZP
Ding
Yanbing
Y
Zhang
Lingyun
L
Pajouhesh
Hossein
H
Morrison
Jerrie-Lynn
JL
Belardetti
Francesco
F
Tringham
Elizabeth
E
Simonson
Eric
E
Vanderah
Todd W
TW
Porreca
Frank
F
Zamponi
Gerald W
GW
Mitscher
Lester A
LA
Snutch
Terrance P
TP
D000284:Administration, Oral; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001559:Benzhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
C549646:1-(4-benzhydrylpiperazin-1-yl)-3,3-diphenylpropan-1-one; D000700:Analgesics; D001559:Benzhydryl Compounds; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D010879:Piperazines; D014867:Water