Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1368877 | Bioorganic & Medicinal Chemistry Letters | 2014 | 4 Pages |
Abstract
We describe the discovery of phenoxymethylbenzamide derivatives as a novel class of glycine transporter type-2 (GlyT-2) inhibitors. We found hit compound 1 (human GlyT-2, IC50 = 4040 nM) in our library and converted its 1-(1-(naphthalen-2-ylmethyl)piperidin-4-yl)pyrrolidin-3-yl group to an 1-(N,N-dimethylaminopropyl)piperidyl group and its tert-butyl group to a trifluoromethyl group to obtain N-(1-(3-(dimethylamino)propyl)piperidin-4-yl)-4-((4-(trifluoromethyl)phenoxy)methyl)benzamide (20). Compound 20 showed good inhibitory activity against human GlyT-2 (IC50 = 15.3 nM) and exhibited anti-allodynia effects in a mouse neuropathic pain model.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Eiki Takahashi, Tadamasa Arai, Masato Akahira, Mayumi Nakajima, Kazumi Nishimura, Yu Omori, Hiroki Kumagai, Tomohiko Suzuki, Ryoji Hayashi,