Discovery of N-substituted 7-azaindoline derivatives as potent, orally available M1 and M4 muscarinic acetylcholine receptors selective agonists.
We designed and synthesized novel N-substituted 7-azaindoline derivatives as selective M1 and M4 muscarinic acetylcholine receptors (mAChRs) agonists. Hybridization of compound 2 with the HTS hit compound 5 followed by optimization of the N-substituents of 7-azaindoline led to identification of compound 1, which showed highly selective M1 and M4 mAChRs agonistic activity, weak human ether-a-go-go related gene inhibition, and good bioavailability in multiple animal species.
['Takai|Kentaro|K|', 'Inoue|Yasunao|Y|', 'Konishi|Yasuko|Y|', 'Suwa|Atsushi|A|', 'Uruno|Yoshiharu|Y|', 'Matsuda|Harumi|H|', 'Nakako|Tomokazu|T|', 'Sakai|Mutsuko|M|', 'Nishikawa|Hiroyuki|H|', 'Hashimoto|Gakuji|G|', 'Enomoto|Takeshi|T|', 'Kitamura|Atsushi|A|', 'Uematsu|Yasuaki|Y|', 'Kiyoshi|Akihiko|A|', 'Sumiyoshi|Takaaki|T|']
D000284:Administration, Oral D000818:Animals D004305:Dose-Response Relationship, Drug D055808:Drug Discovery D000882:Haplorhini D006801:Humans D007211:Indoles D015394:Molecular Structure D010880:Piperidines D051381:Rats D043643:Receptor, Muscarinic M1 D043588:Receptor, Muscarinic M4 D013329:Structure-Activity Relationship
7-Azaindoline derivative Antipsychotic agents M(1) muscarinic acetylcholine receptor M(4) muscarinic acetylcholine receptor Schizophrenia Subtype-selective agonist