Carboxylate bioisosteres of gabapentin

Carmen E Burgos-Lepley; Lisa R Thompson; Clare O Kneen; Simon A Osborne; Justin S Bryans; Thomas Capiris; Nirmala Suman-Chauhan; David J Dooley; Cindy M Donovan; Mark J Field; Mark G Vartanian; Jack J Kinsora; Susan M Lotarski; Ayman El-Kattan; Karen Walters; Madhu Cherukury; Charles P Taylor; David J Wustrow; Jacob B Schwarz

doi:10.1016/j.bmcl.2005.05.016

Carboxylate bioisosteres of gabapentin

Bioorg Med Chem Lett. 2006 May 1;16(9):2333-6. doi: 10.1016/j.bmcl.2005.05.016. Epub 2005 Jun 8.

Affiliation

¹ Pfizer Global Research and Development, Michigan Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA.

PMID: 15946842
DOI: 10.1016/j.bmcl.2005.05.016

Abstract

A series of carboxylate bioisosteres of structures related to gabapentin 1 have been prepared. When the carboxylate was replaced by a tetrazole, this group was recognized by the alpha2-delta protein. Further characterization of alpha2-delta binding compounds 14a and 14b revealed a similar pattern of functional in vitro and in vivo activity to gabapentin 1.

Publication types

Comparative Study

MeSH terms

Amines / chemical synthesis*
Amines / chemistry
Amines / pharmacology*
Animals
Anticonvulsants / chemical synthesis
Anticonvulsants / chemistry*
Anticonvulsants / pharmacology*
Carboxylic Acids / chemistry*
Cyclohexanecarboxylic Acids / chemical synthesis*
Cyclohexanecarboxylic Acids / chemistry
Cyclohexanecarboxylic Acids / pharmacology*
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Design
Drug Evaluation, Preclinical
Gabapentin
In Vitro Techniques
Mice
Mice, Inbred DBA
Molecular Structure
Rats
Stereoisomerism
Structure-Activity Relationship
Tetrazoles / chemistry*
gamma-Aminobutyric Acid / chemical synthesis*
gamma-Aminobutyric Acid / chemistry
gamma-Aminobutyric Acid / pharmacology*

Substances

Amines
Anticonvulsants
Carboxylic Acids
Cyclohexanecarboxylic Acids
Tetrazoles
1H-tetrazole
gamma-Aminobutyric Acid
Gabapentin