Structure–activity relationships of diphenylpiperazine N-type calcium channel inhibitors

…, Y Ding, L Zhang, H Pajouhesh, JL Morrison…

Index: Pajouhesh, Hassan; Feng, Zhong-Ping; Ding, Yanbing; Zhang, Lingyun; Pajouhesh, Hossein; Morrison, Jerrie-Lynn; Belardetti, Francesco; Tringham, Elizabeth; Simonson, Eric; Vanderah, Todd W.; Porreca, Frank; Zamponi, Gerald W.; Mitscher, Lester A.; Snutch, Terrance P. Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 4 p. 1378 - 1383

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Citation Number: 37

Abstract

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 IC50 values in the range of 10–150nM 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 ...