Discovery and optimization of a novel series of pyrazolyltetrahydropyran N-type calcium channel (Cav 2.2) blockers for the treatment of pain

  • Bioorg Med Chem Lett. 2018 Dec 15;28(23-24):3780-3783. doi: 10.1016/j.bmcl.2018.10.007.
Mark J Wall  1 ,  Nalin L Subasinghe  2 ,  Michael P Winters  2 ,  Mary Lou Lubin  2 ,  Michael F A Finley  2 ,  Ning Qin  2 ,  Michael R Brandt  2 ,  Michael P Neeper  2 ,  Craig R Schneider  2 ,  Raymond W Colburn  2 ,  Christopher M Flores  2 ,  Zhihua Sui  2
Affiliations
  • 1. Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA. Electronic address: [email protected].
  • 2. Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA.
PMID: 30337231 DOI: 10.1016/j.bmcl.2018.10.007
Abstract

A novel series of pyrazolyltetrahydropyran N-type calcium channel blockers are described. Structural modifications of the series led to potent compounds in both a cell-based fluorescent calcium influx assay and a patch clamp electrophysiology assay. Representative compounds from the series were bioavailable and showed efficacy in the rat CFA and CCI models of inflammatory and neuropathic pain.

Keywords
CCI model; CFA model; Cav 2.2; N-type calcium channel; Pain; Pyrazoles.
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