Synthesis and in vivo evaluation of bicyclic gababutins.
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.
Blakemore
David C
DC
Sandwich Laboratories, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. david.blakemore@pfizer.com
Bryans
Justin S
JS
Carnell
Pauline
P
Carr
Christopher L
CL
Chessum
Nicola E A
NE
Field
Mark J
MJ
Kinsella
Natasha
N
Osborne
Simon A
SA
Warren
Andrew N
AN
Williams
Sophie C
SC
D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003509:Cyclohexanecarboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000077206:Gabapentin; D009437:Neuralgia / Q000188:drug therapy; D010147:Pain Measurement; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics
D000588:Amines; D000596:Amino Acids; D001643:Bridged Bicyclo Compounds; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin