Literature

Abstract

On the basis of the three-dimensional diversity-oriented conformational restriction strategy using key chiral cyclopropane units, we previously identified 3 ((2S,3R)-4-amino-3,4-methanobutyric acid) with a chiral trans-cyclopropane structure as a γ-aminobutyric acid (GABA) transporter inhibitor selective for GABA transporter (GAT) subtypes GAT-3 and BGT-1 (betaine/GABA transporter-1). Further conformational restriction of 3 with the rigid bicyclo[3.1.0]hexane backbone led to the successful development of the first highly potent and selective BGT-1 inhibitor 4 (IC50 = 0.59 μM). The bioactive conformation of 3 for BGT-1 was also identified.

DOI： 10.1021/ml500134k

Conformationally Restricted GABA with Bicyclo[3.1.0]hexane Backbone as the First Highly Selective BGT-1 Inhibitor

ACS Medicinal Chemistry Letters 2014.0

Cyclopropane-based conformational restriction of GABA by a stereochemical diversity-oriented strategy: Identification of an efficient lead for potent inhibitors of GABA transports

Bioorganic & Medicinal Chemistry 2013.0

Synthesis of N-substituted acyclic β-amino acids and their investigation as GABA uptake inhibitors

European Journal of Medicinal Chemistry 2013.0

Selective mGAT2 (BGT-1) GABA Uptake Inhibitors: Design, Synthesis, and Pharmacological Characterization

Journal of Medicinal Chemistry 2013.0

Design, Synthesis and Evaluation of Substituted Triarylnipecotic Acid Derivatives as GABA Uptake Inhibitors: Identification of a Ligand with Moderate Affinity and Selectivity for the Cloned Human GABA Transporter GAT-3

Journal of Medicinal Chemistry 1994.0

Aminomethyltetrazoles as potential inhibitors of the γ-aminobutyric acid transporters mGAT1–mGAT4: Synthesis and biological evaluation