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

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

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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