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ID: ALA3632469
Journal: Bioorg Med Chem Lett
Title: Discovery of dihydroquinazolinone derivatives as potent, selective, and CNS-penetrant M(1) and M(4) muscarinic acetylcholine receptors agonists.
Authors: Uruno Y, Konishi Y, Suwa A, Takai K, Tojo K, Nakako T, Sakai M, Enomoto T, Matsuda H, Kitamura A, Sumiyoshi T.
Abstract: We designed and synthesized a series of dihydroquinazolinone derivatives as selective M1 and M4 muscarinic acetylcholine receptors agonists. Introduction of the N-carbethoxy piperidine unit into a HTS hit compound followed by optimization of the amine linker and the carbamoyl moiety led to the identification of compound 1 as a potential candidate. The identified compound 1 showed high selectivity for M1 and M4 muscarinic acetylcholine receptors with M4 partial agonistic activity. In addition, compound 1 showed good brain penetration and reversed methamphetamine-induced hyperlocomotion in rats (ED50=3.0 mg/kg, sc).
CiteXplore: 26428869