T-type calcium channel blockers: spiro-piperidine azetidines and azetidinones-optimization, design and synthesis

Elizabeth M Smith; Steve Sorota; Hyunjin M Kim; Brian A McKittrick; Terry L Nechuta; Chad Bennett; Chad Knutson; Duane A Burnett; Jane Kieselgof; Zheng Tan; Diane Rindgen; Terry Bridal; Xiaoping Zhou; Yu-Ping Jia; Zoe Dong; Debbie Mullins; Xiaoping Zhang; Tony Priestley; Craig C Correll; Deen Tulshian; Michael Czarniecki; William J Greenlee

doi:10.1016/j.bmcl.2010.06.012

T-type calcium channel blockers: spiro-piperidine azetidines and azetidinones-optimization, design and synthesis

Bioorg Med Chem Lett. 2010 Aug 1;20(15):4602-6. doi: 10.1016/j.bmcl.2010.06.012. Epub 2010 Jun 8.

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratory, Kenilworth, NJ 07033, USA. elizabeth.m.smith@spcorp.com

PMID: 20580233
DOI: 10.1016/j.bmcl.2010.06.012

Abstract

A series of spiro-azetidines and azetidinones has been evaluated as novel blockers of the T-type calcium channel (Ca(V)3.2) which is a new therapeutic target for the potential treatment of both inflammatory and neuropathic pain. Confirmation and optimization of the potency, selectivity and DMPK properties of leads will be described.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Azetidines / chemical synthesis
Azetidines / chemistry*
Azetidines / therapeutic use
Calcium Channel Blockers / chemical synthesis*
Calcium Channel Blockers / chemistry
Calcium Channel Blockers / therapeutic use
Calcium Channels, T-Type / chemistry*
Calcium Channels, T-Type / metabolism
Drug Design
Humans
Pain / drug therapy
Piperidines / chemistry*
Protein Binding
Rats
Spiro Compounds / chemistry*
Structure-Activity Relationship

Substances

2-azetidinone
Azetidines
Calcium Channel Blockers
Calcium Channels, T-Type
Piperidines
Spiro Compounds
piperidine