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

Hassan Pajouhesh, Zhong Ping Feng, Yanbing Ding, Lingyun Zhang, Hossein Pajouhesh, Jerrie Lynn Morrison, Francesco Belardetti, Elizabeth Tringham, Eric Simonson, Todd W. Vanderah, Frank Porreca, Gerald W. Zamponi, Lester A. Mitscher, Terrance P. Snutch

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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 10-150 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.

Original languageEnglish (US)
Pages (from-to)1378-1383
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number4
DOIs
StatePublished - Feb 15 2010

Keywords

  • Calcium channel
  • Diphenylpiperazine
  • L-type
  • N-type
  • Pain

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Structure-activity relationships of diphenylpiperazine N-type calcium channel inhibitors'. Together they form a unique fingerprint.

Cite this