Synthesis and in vivo evaluation of 3-substituted gababutins

A range of 3-alkylated five-membered ring derivatives of Gabapentin were synthesized and several were found to have superior potency against the α2δ calcium subunit. Diastereoisomeric compounds, ( 16) and ( 22), were profiled in in vivo models of pain and anxiety and proved to have different levels...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2010, Vol.20 (1), p.362-365
Hauptverfasser: Blakemore, David C., Bryans, Justin S., Carnell, Pauline, Chessum, Nicola E.A., Field, Mark J., Kinsella, Natasha, Kinsora, Jack K., Osborne, Simon A., Williams, Sophie C.
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container_issue 1
container_start_page 362
container_title Bioorganic & medicinal chemistry letters
container_volume 20
creator Blakemore, David C.
Bryans, Justin S.
Carnell, Pauline
Chessum, Nicola E.A.
Field, Mark J.
Kinsella, Natasha
Kinsora, Jack K.
Osborne, Simon A.
Williams, Sophie C.
description A range of 3-alkylated five-membered ring derivatives of Gabapentin were synthesized and several were found to have superior potency against the α2δ calcium subunit. Diastereoisomeric compounds, ( 16) and ( 22), were profiled in in vivo models of pain and anxiety and proved to have different levels of efficacy in the two models. A range of 3-alkylated five-membered ring derivatives of Gabapentin were synthesized and several were found to have good levels of potency against the α2δ calcium subunit of a voltage-gated calcium channel. Two compounds were profiled in in vivo models of pain and anxiety.
doi_str_mv 10.1016/j.bmcl.2009.10.089
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subjects Amines - chemical synthesis
Amines - chemistry
Amines - pharmacology
Amino Acids - chemical synthesis
Amino Acids - chemistry
Amino Acids - pharmacology
Analgesics
Animals
Anti-Anxiety Agents - chemical synthesis
Anti-Anxiety Agents - chemistry
Anti-Anxiety Agents - pharmacology
Anxiety
Biological and medical sciences
Calcium Channels - metabolism
Carrageenan - pharmacology
Cyclohexanecarboxylic Acids - chemical synthesis
Cyclohexanecarboxylic Acids - chemistry
Cyclohexanecarboxylic Acids - pharmacology
Cyclopentanes - chemical synthesis
Cyclopentanes - chemistry
Cyclopentanes - pharmacology
Gababutin
Gabapentin
gamma-Aminobutyric Acid - chemical synthesis
gamma-Aminobutyric Acid - chemistry
gamma-Aminobutyric Acid - pharmacology
Hyperalgesia - chemically induced
Hyperalgesia - drug therapy
Medical sciences
Neuropharmacology
Pain
Pharmacology. Drug treatments
Pregabalin
Psycholeptics: tranquillizer, neuroleptic
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Rats
Stereoisomerism
title Synthesis and in vivo evaluation of 3-substituted gababutins
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