Synthesis and in vivo evaluation of 3,4-disubstituted gababutins

David C Blakemore; Justin S Bryans; Pauline Carnell; Mark J Field; Natasha Kinsella; Jack K Kinsora; Leonard T Meltzer; Simon A Osborne; Lisa R Thompson; Sophie C Williams

doi:10.1016/j.bmcl.2009.10.121

Synthesis and in vivo evaluation of 3,4-disubstituted gababutins

Bioorg Med Chem Lett. 2010 Jan 1;20(1):248-51. doi: 10.1016/j.bmcl.2009.10.121. Epub 2009 Oct 30.

Authors

David C Blakemore¹, Justin S Bryans, Pauline Carnell, Mark J Field, Natasha Kinsella, Jack K Kinsora, Leonard T Meltzer, Simon A Osborne, Lisa R Thompson, Sophie C Williams

Affiliation

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

PMID: 19910190
DOI: 10.1016/j.bmcl.2009.10.121

Abstract

A range of 3,4-alkylated five-membered ring derivatives of gabapentin were synthesised. One compound (21) had an excellent level of potency against alpha(2)delta and was profiled in in vivo models of pain and anxiety.

MeSH terms

Amines / chemical synthesis
Amines / chemistry*
Amines / pharmacokinetics
Amino Acids / chemical synthesis*
Amino Acids / chemistry
Amino Acids / pharmacology
Animals
Anti-Anxiety Agents / chemical synthesis*
Anti-Anxiety Agents / chemistry
Anti-Anxiety Agents / pharmacokinetics
Cyclohexanecarboxylic Acids / chemical synthesis
Cyclohexanecarboxylic Acids / chemistry*
Cyclohexanecarboxylic Acids / pharmacokinetics
Cyclopentanes / chemical synthesis*
Cyclopentanes / chemistry
Cyclopentanes / pharmacology
Disease Models, Animal
Gabapentin
Hyperalgesia / chemically induced
Hyperalgesia / drug therapy
Rats
gamma-Aminobutyric Acid / chemical synthesis
gamma-Aminobutyric Acid / chemistry*
gamma-Aminobutyric Acid / pharmacokinetics

Substances

Amines
Amino Acids
Anti-Anxiety Agents
Cyclohexanecarboxylic Acids
Cyclopentanes
gamma-Aminobutyric Acid
Gabapentin