3-Aminocyclobutane-1-carboxylic acid: Synthesis and some neurochemical properties

Abstract

The paper describes synthesis of 3-amino-cyclobutane-1-carboxylic acid and its resolution into diastereoisomers. Preparations of cerebral 4-aminobutyrate: 2-oxoglutarate aminotransferase were capable of utilizing both diastereoisomers for transamination. In the uptake of (2,3-H3)-4-aminobutyric acid by slices of rat cerebral tissue the two isomers fUllction as simple competitive inhibitors. The inhibitary potency of the uptake and the utilization in transamination of the cis isomer was higher than that of the trans isomer. This reflects specific steric pre-requisites for the two processes.

Novel γ-Aminobutyric Acid ρ1Receptor Antagonists; Synthesis, Pharmacological Activity and Structure−Activity Relationships

“…It was hypothesized that the 4-aminocyclopent-1-enyl(alkyl)phosphinic acids (34)(35)(36)(37)(38)(39)(40)(41)(42) would possess the required physicochemical properties for optimal interaction with the GABA C receptor agonist binding site based on the activity of (S)-4-ACPCA (S-6). 35 It has previously been observed, for conformationally restricted analogues of GABA, that the use of phosphinic acids and alkyl phosphinic acids as a bioisostere of a carboxylic acid gives antagonists at F 1 GABA C receptors, 33,[67][68][69] with activity comparable to or greater than the parent compound.…”

“…37 However, little is known about the activity of cyclobutane analogues of GABA at GABA C receptors, with only two early reports outlining the synthesis and GABA-ergic activity of cis-and trans-3-aminocyclobutane carboxylic acid. 38,39 Thus, a series of cyclopentene and cyclobutane compounds were synthesized and their activity as selective F 1 GABA C receptor antagonists investigated. Finally, the compounds investigated were used to develop a pharmacophore model, with the potential to be utilized for the in silico screening of GABA C receptor antagonists in the future.…”

“…It has been proposed that selective activity at GABA C receptors over GABA A and GABA B receptors is achieved via a more folded conformation of the GABA ( 1 ) backbone . However, little is known about the activity of cyclobutane analogues of GABA at GABA C receptors, with only two early reports outlining the synthesis and GABA-ergic activity of cis - and trans -3-aminocyclobutane carboxylic acid. , …”