Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2 Universitetsparken, DK-2100 Copenhagen, Denmark.
Org Lett. 2022 Jun 17;24(23):4151-4154. doi: 10.1021/acs.orglett.2c01346. Epub 2022 Jun 8.
Novel γ-aminobutyric acid (GABA) analogues -, having a bicyclo[3.1.0]hexene, [4.1.0]heptane, or [4.1.0]heptene backbone, respectively, were designed from the bioactive form analysis of the previous inhibitor with a bicyclo[3.1.0]hexane backbone. Compounds - and were synthesized from a common 1,7-diene intermediate using ring-closing metathesis (RCM) to construct the key bicyclo backbones. Compounds - strongly inhibit betaine/GABA transporter 1 (BGT1) uptake, but compound stands out with its selective low micromolar potency.
新型γ-氨基丁酸（GABA）类似物-，分别具有双环[3.1.0]己烯、[4.1.0]庚烷或[4.1.0]庚烯骨架，是从前一个具有双环[3.1.0]己烷骨架的生物活性形式抑制剂分析设计的。化合物-和-是从共同的 1,7-二烯中间体-使用闭环复分解（RCM）合成的，以构建关键的双环骨架。化合物-强烈抑制甜菜碱/GABA 转运蛋白 1（BGT1）摄取，但化合物-以其选择性的低微摩尔效力脱颖而出。
