Synthesis and in vivo evaluation of bicyclic gababutins

David C Blakemore; Justin S Bryans; Pauline Carnell; Christopher L Carr; Nicola E A Chessum; Mark J Field; Natasha Kinsella; Simon A Osborne; Andrew N Warren; Sophie C Williams

doi:10.1016/j.bmcl.2009.11.118

Synthesis and in vivo evaluation of bicyclic gababutins

Bioorg Med Chem Lett. 2010 Jan 15;20(2):461-4. doi: 10.1016/j.bmcl.2009.11.118. Epub 2009 Nov 27.

Authors

David C Blakemore¹, Justin S Bryans, Pauline Carnell, Christopher L Carr, Nicola E A Chessum, Mark J Field, Natasha Kinsella, Simon A Osborne, Andrew N Warren, Sophie C Williams

Affiliation

¹ Sandwich Laboratories, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. david.blakemore@pfizer.com

PMID: 20005103
DOI: 10.1016/j.bmcl.2009.11.118

Abstract

Synthesis of a number of bicyclic five-membered ring derivatives of gabapentin led to the identification of two compounds, (-)-(11A) and (20A) which both had an excellent level of potency against alpha(2)delta and were profiled in an in vivo model of neuropathic pain.

MeSH terms

Amines / chemical synthesis*
Amines / chemistry
Amines / pharmacokinetics
Amino Acids / chemical synthesis*
Amino Acids / chemistry
Amino Acids / pharmacokinetics
Animals
Blood-Brain Barrier / metabolism
Bridged Bicyclo Compounds / chemical synthesis*
Bridged Bicyclo Compounds / chemistry
Bridged Bicyclo Compounds / pharmacokinetics
CHO Cells
Cricetinae
Cricetulus
Cyclohexanecarboxylic Acids / chemical synthesis*
Cyclohexanecarboxylic Acids / chemistry
Cyclohexanecarboxylic Acids / pharmacokinetics
Gabapentin
Neuralgia / drug therapy
Pain Measurement
Rats
Stereoisomerism
Structure-Activity Relationship
gamma-Aminobutyric Acid / chemical synthesis*
gamma-Aminobutyric Acid / chemistry
gamma-Aminobutyric Acid / pharmacokinetics

Substances

Amines
Amino Acids
Bridged Bicyclo Compounds
Cyclohexanecarboxylic Acids
gamma-Aminobutyric Acid
Gabapentin