title: Synthesis and evaluation of furo[3,4-d]pyrimidinones as selective alpha1a-adrenergic receptor antagonists.
abstract: Furo[3,4-d]pyrimidinones were found to be metabolites of dihydropyrimidinones such as 1a-b that are subtype-selective antagonists of the alpha1a-adrenergic receptor. A versatile synthesis that provides access to furo[3,4-d]pyrimidinones in high yield and in enantiomerically pure forms is described along with structure-activity relationships in the series.
authors.affiliation: Department of Chemistry, Synaptic Pharmaceutical Corporation, Paramus, NJ 07652, USA.
authors.forename: B
authors.initials: B
authors.lastname: Lagu
authors.forename: D
authors.initials: D
authors.lastname: Tian
authors.forename: G
authors.initials: G
authors.lastname: Chiu
authors.forename: D
authors.initials: D
authors.lastname: Nagarathnam
authors.forename: J
authors.initials: J
authors.lastname: Fang
authors.forename: Q
authors.initials: Q
authors.lastname: Shen
authors.forename: C
authors.initials: C
authors.lastname: Forray
authors.forename: R W
authors.initials: RW
authors.lastname: Ransom
authors.forename: R S
authors.initials: RS
authors.lastname: Chang
authors.forename: K P
authors.initials: KP
authors.lastname: Vyas
authors.forename: K
authors.initials: K
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Gluchowski
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011224:Prazosin / Q000378:metabolism; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000317:Adrenergic alpha-Antagonists; D011744:Pyrimidinones; D018340:Receptors, Adrenergic, alpha-1; D011224:Prazosin