Carboxylate bioisosteres of pregabalin.
Several beta-amino tetrazole analogs of gabapentin 1 and pregabalin 2 were prepared by one of two convergent, highly efficient routes, and their affinity for the alpha(2)-delta protein examined. Two select compounds with potent affinity for alpha(2)-delta, 8a and 16a, were subsequently tested in vivo in an audiogenic seizure model and found to elicit protective effects.
Schwarz
Jacob B
JB
Pfizer Global Research and Development, Michigan Laboratories, 2800 Plymouth Road, Ann Arbor, 48105, USA. jacob.schwarz@pfizer.com
Colbry
Norman L
NL
Zhu
Zhijian
Z
Nichelson
Brian
B
Barta
Nancy S
NS
Lin
Kristin
K
Hudack
Raymond A
RA
Gibbons
Sian E
SE
Galatsis
Paul
P
DeOrazio
Russell J
RJ
Manning
David D
DD
Vartanian
Mark G
MG
Kinsora
Jack J
JJ
Lotarski
Susan M
SM
Li
Zheng
Z
Dickerson
Melvin R
MR
El-Kattan
Ayman
A
Thorpe
Andrew J
AJ
Donevan
Sean D
SD
Taylor
Charles P
CP
Wustrow
David J
DJ
D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002264:Carboxylic Acids / Q000737:chemistry*; D003509:Cyclohexanecarboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D020195:Epilepsy, Reflex / Q000517:prevention & control*; D000077206:Gabapentin; D051379:Mice; D008811:Mice, Inbred DBA; D015394:Molecular Structure; D000069583:Pregabalin; D021122:Protein Subunits / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000588:Amines; D000927:Anticonvulsants; D002264:Carboxylic Acids; D003509:Cyclohexanecarboxylic Acids; D021122:Protein Subunits; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin