Synthesis and evaluation of furo[3,4-d]pyrimidinones as selective alpha1a-adrenergic receptor antagonists.
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.
Lagu
B
B
Department of Chemistry, Synaptic Pharmaceutical Corporation, Paramus, NJ 07652, USA.
Tian
D
D
Chiu
G
G
Nagarathnam
D
D
Fang
J
J
Shen
Q
Q
Forray
C
C
Ransom
R W
RW
Chang
R S
RS
Vyas
K P
KP
Zhang
K
K
Gluchowski
C
C
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
D000317:Adrenergic alpha-Antagonists; D011744:Pyrimidinones; D018340:Receptors, Adrenergic, alpha-1; D011224:Prazosin