title: Proof of concept study for designed multiple ligands targeting the dopamine D2, serotonin 5-HT2A, and muscarinic M1 acetylcholine receptors.
abstract: Herein we describe the hybridization of a benzoxazinone M1 scaffold with D2 privileged structures derived from putative and clinically relevant antipsychotics to develop designed multiple ligands. The M1 mAChR is an attractive target for the cognitive deficits in key CNS disorders. Moreover, activity at D2 and 5-HT2A receptors has proven useful for antipsychotic efficacy. We identified 9 which retained functional activity at the target M1 mAChR and D2R and demonstrated high affinity for the 5-HT2AR.
authors.affiliation: Medicinal Chemistry, and ‡Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University , 381 Royal Parade, Parkville 3052, Victoria, Australia.
authors.forename: Monika
authors.initials: M
authors.lastname: Szabo
authors.forename: Herman D
authors.initials: HD
authors.lastname: Lim
authors.forename: Carmen Klein
authors.initials: CK
authors.lastname: Herenbrink
authors.forename: Arthur
authors.initials: A
authors.lastname: Christopoulos
authors.forename: J Robert
authors.initials: JR
authors.lastname: Lane
authors.forename: Ben
authors.initials: B
authors.lastname: Capuano
mesh_terms: D048588:Benzoxazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D008024:Ligands; D015394:Molecular Structure; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D048588:Benzoxazines; D065127:Dopamine D2 Receptor Antagonists; D008024:Ligands; D043643:Receptor, Muscarinic M1; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2; D058830:Serotonin 5-HT2 Receptor Antagonists