Carboxylate bioisosteres of gabapentin.
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.
Burgos-Lepley
Carmen E
CE
Pfizer Global Research and Development, Michigan Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA.
Thompson
Lisa R
LR
Kneen
Clare O
CO
Osborne
Simon A
SA
Bryans
Justin S
JS
Capiris
Thomas
T
Suman-Chauhan
Nirmala
N
Dooley
David J
DJ
Donovan
Cindy M
CM
Field
Mark J
MJ
Vartanian
Mark G
MG
Kinsora
Jack J
JJ
Lotarski
Susan M
SM
El-Kattan
Ayman
A
Walters
Karen
K
Cherukury
Madhu
M
Taylor
Charles P
CP
Wustrow
David J
DJ
Schwarz
Jacob B
JB
D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000737:chemistry*; D003509:Cyclohexanecarboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D000077206:Gabapentin; D066298:In Vitro Techniques; D051379:Mice; D008811:Mice, Inbred DBA; D015394:Molecular Structure; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000737:chemistry*; D005680:gamma-Aminobutyric Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000588:Amines; D000927:Anticonvulsants; D002264:Carboxylic Acids; D003509:Cyclohexanecarboxylic Acids; D013777:Tetrazoles; C045574:1H-tetrazole; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin