Synthesis and evaluation of furo[3,4-d]pyrimidinones as selective alpha1a-adrenergic receptor antagonists

B Lagu; D Tian; G Chiu; D Nagarathnam; J Fang; Q Shen; C Forray; R W Ransom; R S Chang; K P Vyas; K Zhang; C Gluchowski

doi:10.1016/s0960-894x(99)00653-8

Synthesis and evaluation of furo[3,4-d]pyrimidinones as selective alpha1a-adrenergic receptor antagonists

Bioorg Med Chem Lett. 2000 Jan 17;10(2):175-8. doi: 10.1016/s0960-894x(99)00653-8.

Authors

B Lagu¹, D Tian, G Chiu, D Nagarathnam, J Fang, Q Shen, C Forray, R W Ransom, R S Chang, K P Vyas, K Zhang, C Gluchowski

Affiliation

¹ Department of Chemistry, Synaptic Pharmaceutical Corporation, Paramus, NJ 07652, USA.

PMID: 10673105
DOI: 10.1016/s0960-894x(99)00653-8

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.

MeSH terms

Adrenergic alpha-Antagonists / chemical synthesis*
Adrenergic alpha-Antagonists / pharmacology
Animals
Binding, Competitive
Molecular Structure
Muscle Contraction / drug effects
Muscle, Smooth, Vascular / drug effects
Prazosin / metabolism
Pyrimidinones / chemical synthesis*
Pyrimidinones / pharmacology
Rats
Receptors, Adrenergic, alpha-1 / drug effects*
Stereoisomerism
Structure-Activity Relationship

Substances

Adrenergic alpha-Antagonists
Pyrimidinones
Receptors, Adrenergic, alpha-1
Prazosin