title: Synthesis and in vitro evaluation of derivatives of the β₁-adrenergic receptor antagonist HX-CH 44.
abstract: Isopropyl- and fluoroisopropyl-amino derivatives of the β(1)-adrenergic receptor antagonist 2-[4-[3-(tert-butyl-amino)-2-hydroxypropoxy]phenyl]-3-methyl-6-methoxy-4(3H)-quinazolinone ((±)HX-CH 44) were synthesized, including a concise and efficient preparation of the core, 2-(4-hydroxyphenyl)-6-methoxy-3-methylquinazolin-4(3H)-one. In vitro binding assays showed that the fluorinated analog was selective towards β(1)-adrenergic receptors over β(2)-adrenergic and 5-HT(1A) receptors. An X-ray crystallographic characterization of the fluorinated analog is also reported.
authors.affiliation: PET Centre, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, 250 College St., Toronto, Ontario, Canada M5T 1R8.
authors.forename: Karin A
authors.initials: KA
authors.lastname: Stephenson
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.forename: Neil
authors.initials: N
authors.lastname: Vasdev
mesh_terms: D058665:Adrenergic beta-1 Receptor Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011412:Propanolamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D011412:Propanolamines; D052999:Quinazolinones; D018342:Receptors, Adrenergic, beta-1; C045066:HX-CH 44BS