title: Identification and characterization of m4 selective muscarinic antagonists.
abstract: Our interest in the area of m4 muscarinic antagonists had led us to study a series of benzoxazine isoquinolines. One of the most potent and selective compounds of this series is example 1 with an IC50 value of 90.7 nM at m4 receptors, and 72-fold (m1), 38-fold (m2), 10-fold (m3), and 82-fold (m5) more selective compared to the other receptors. The synthesis and receptor binding affinity of analogs of 1 are reported.
authors.affiliation: Department of Medicinal Chemistry, Parke-Davis Pharmaceutical Research, Ann Arbor, Michigan 48105, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Augelli-Szafran
authors.forename: J C
authors.initials: JC
authors.lastname: Jaen
authors.forename: D W
authors.initials: DW
authors.lastname: Moreland
authors.forename: C B
authors.initials: CB
authors.lastname: Nelson
authors.forename: J R
authors.initials: JR
authors.lastname: Penvose-Yi
authors.forename: R D
authors.initials: RD
authors.lastname: Schwarz
mesh_terms: D007546:Isoquinolines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism
chemical_list: D007546:Isoquinolines; D018727:Muscarinic Antagonists; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic