Synthesis of gamma-Aminobutyric Acid (GABA) Analogues Conformationally Restricted by Bicyclo[3.1.0]hexane/hexene or [4.1.0]Heptane/heptene Backbones as Potent Betaine/GABA Transporter Inhibitors
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Synthesis of gamma-Aminobutyric Acid (GABA) Analogues Conformationally Restricted by Bicyclo[3.1.0]hexane/hexene or [4.1.0]Heptane/heptene Backbones as Potent Betaine/GABA Transporter Inhibitors. / Mitsui, Keisuke; Lie, Maria E. K.; Saito, Naoki; Fujiwara, Koichi; Watanabe, Mizuki; Wellendorph, Petrine; Shuto, Satoshi.
In: Organic Letters, Vol. 24, No. 23, 2022, p. 4151-4154.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Synthesis of gamma-Aminobutyric Acid (GABA) Analogues Conformationally Restricted by Bicyclo[3.1.0]hexane/hexene or [4.1.0]Heptane/heptene Backbones as Potent Betaine/GABA Transporter Inhibitors
AU - Mitsui, Keisuke
AU - Lie, Maria E. K.
AU - Saito, Naoki
AU - Fujiwara, Koichi
AU - Watanabe, Mizuki
AU - Wellendorph, Petrine
AU - Shuto, Satoshi
PY - 2022
Y1 - 2022
N2 - Novel gamma-aminobutyric acid (GABA) analogues 3-5, 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 2 with a bicyclo[3.1.0]hexane backbone. Compounds 3-5 and 2 were synthesized from a common 1,7-diene intermediate 6 using ring-closing metathesis (RCM) to construct the key bicyclo backbones. Compounds 3-5 strongly inhibit betaine/GABA transporter 1 (BGT1) uptake, but compound 4 stands out with its selective low micromolar potency.
AB - Novel gamma-aminobutyric acid (GABA) analogues 3-5, 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 2 with a bicyclo[3.1.0]hexane backbone. Compounds 3-5 and 2 were synthesized from a common 1,7-diene intermediate 6 using ring-closing metathesis (RCM) to construct the key bicyclo backbones. Compounds 3-5 strongly inhibit betaine/GABA transporter 1 (BGT1) uptake, but compound 4 stands out with its selective low micromolar potency.
KW - ISOMERIZATION
KW - CYCLOISOMERIZATION
KW - CARBENE
U2 - 10.1021/acs.orglett.2c01346
DO - 10.1021/acs.orglett.2c01346
M3 - Journal article
C2 - 35674784
VL - 24
SP - 4151
EP - 4154
JO - Organic Letters
JF - Organic Letters
SN - 1523-7060
IS - 23
ER -
ID: 315267054