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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:20

Article

Pajouhesh, Hassan²  Feng, Zhong-Ping^2,3  Ding, Yanbing²  Zhang, Lingyun²  Pajouhesh, Hossein²  Morrison, Jerrie-Lynn²  Belardetti, Francesco²  Tringham, Elizabeth²  Simonson, Eric²  Vanderah, Todd W.⁴  Porreca, Frank⁴  Zamponi, Gerald W.³  Mitscher, Lester A.⁵  Snutch, Terrance P.¹ 

[1] Univ British Columbia, Michael Smith Labs, Vancouver, BC V5Z 1M9, Canada

[2] Neuromed Pharmaceut Ltd, Vancouver, BC, Canada

[3] Univ Calgary, Dept Physiol & Pharmacol, Calgary, AB, Canada

[4] Univ Arizona, Dept Pharmacol, Tucson, AZ USA

[5] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA

关键词: Calcium channel;    N-type;    L-type;    Pain;    Diphenylpiperazine;   

DOI  :  10.1016/j.bmcl.2010.01.008

来源: Elsevier

【 摘 要 】

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 10-150 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. (C) 2010 Elsevier Ltd. All rights reserved.

【 授权许可】

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