Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10591855 | Bioorganic & Medicinal Chemistry Letters | 2014 | 4 Pages |
Abstract
We designed and synthesized novel N-sulfonyl-7-azaindoline derivatives as selective M4 muscarinic acetylcholine receptor agonists. Modification of the N-carbethoxy piperidine moiety of compound 2, an M4 muscarinic acetylcholine receptor (mAChR)-preferring agonist, led to compound 1, a selective M4 mAChR agonist. Compound 1 showed a highly selective M4 mAChR agonistic activity with weak hERG inhibition in vitro. A pharmacokinetic study of compound 1 in vivo revealed good bioavailability and brain penetration in rats. Compound 1 reversed methamphetamine-induced locomotor hyperactivity in rats (1-10Â mg/kg, po).
Keywords
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Atsushi Suwa, Yasuko Konishi, Yoshiharu Uruno, Kentaro Takai, Tomokazu Nakako, Mutsuko Sakai, Takeshi Enomoto, Yoshiaki Ochi, Harumi Matsuda, Atsushi Kitamura, Yasuaki Uematsu, Akihiko Kiyoshi, Takaaki Sumiyoshi,