ChemInform Abstract: Azetidine Derivatives as Novel γ‐Aminobutyric Acid Uptake Inhibitors: Synthesis, Biological Evaluation, and Structure—Activity Relationship.

Abstract

Azetidine Derivatives as Novel γ-Aminobutyric Acid Uptake Inhibitors: Synthesis, Biological Evaluation, and Structure-Activity Relationship. -Azetidines, e.g. (I)-(III), are synthesized as structural analogues of four known GABA-uptake inhibitors. Their activities strongly depend on both the position of the carboxylic acid moiety and the nature of the lipophilic groups. The highest affinity at GAT-1 is observed for azetidinylacetic acid derivative (I) with a selectivity of 48:1 for GAT-1 over GAT-3. Azetidinecarboxylic acid derivative (II) is the most potent inhibitor of GAT-3 with IC50 of 15.3 μM and a selectivity greater than 7:1 for GAT-3 over GAT-1. Derivative (III) reveals moderate potency at and subtype selectivity for GAT-3. -(FAUST, M. R.; HOEFNER, G.; PABEL, J.; WANNER*, K. T.; Eur.

Access to Enantiomerically Enriched cis-2,3-Disubstituted Azetidines via Diastereoselective Hydrozirconation

“…The introduction of an alkoxy group at the α carbon of the chain (in R 1 , entry 6) opens the way for further functionalizations. The presence of an azetidine-2-carboxylic acid moiety in a number of natural products and derivatives, and the recent use of such acids for preparing the conformationally constrained peptides has to be underlined . Rapid access to nonracemic azetidine-2-carboxylic acids is exemplified here by a simple preparation of the amino acid 5 , a rigid valine analogue, from 4f through alcohol deprotection and ruthenium-based oxidation (Scheme ).…”