biostudies-otherUnknown5(8)Kobayashi TACS medicinal chemistry letters889-93https://www.ebi.ac.uk/biostudies/studies/S-EPMC4137383On 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 ?-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 ?M). The bioactive conformation of 3 for BGT-1 was also identified.biostudies-otherPMC4137383Europe PMCIgawa AKobayashi TShuto SSuemasa AArisawa MIde SAbe HFukuda HMinami MfalseConformationally Restricted GABA with Bicyclo[3.1.0]hexane Backbone as the First Highly Selective BGT-1 Inhibitor.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 ?-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 ?M). The bioactive conformation of 3 for BGT-1 was also identified.2014-01-01T00:00:00Z2014 Aug2019-03-27T01:34:20Z2019-03-27T01:34:20ZS-EPMC41373832514760910.1021/ml500134k