Cyclobutane analogs of GABA.
Both cis- and trans-3-aminocyclobutane-1-carboxylic acid have been synthesized as conformationally restricted analogs of GABA. The cis isomer displayed weak to moderate GABA-like activity with respect to (1) inhibition of GABA uptake in rat brain minislices, (2) inhibition of sodium-independent binding of GABA to rat brain membranes, (3) activity as a substrate for GABA aminotransferase. and (4) depression of the firing rate of cat spinal neurons in vivo. The trans isomer was less effective on all four assays. The results has been interpreted in terms of the conformational "pinning back" of the polar groups by the cyclobutane ring in the trans GABA analog so that unfavorable steric interactions would occur between one of the methylene groups and a region of steric hindrance at the active sites for particular GABA processes.
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000042:Absorption; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D003503:Cyclobutanes / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D008968:Molecular Conformation; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects; D013237:Stereoisomerism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology
D003503:Cyclobutanes; D005680:gamma-Aminobutyric Acid; C025236:3-aminocyclobutane-1-carboxylic acid; D000612:4-Aminobutyrate Transaminase