title: Synthesis of new delta 2-isoxazoline derivatives and their pharmacological characterization as beta-adrenergic receptor antagonists.
abstract: A series of delta 2-isoxazoline derivatives structurally related to Broxaterol 1 and Falintolol 3 has been prepared and evaluated for their binding affinity to beta 1- and beta 2-adrenergic receptors. Among the tested compounds only the 3-isopropenyl anti derivative 4d is as active as the reference compounds. An electron-releasing group, probably operating through a pi-pi interaction, in the 3-position of the isoxazoline nucleus greatly enhances the affinity of the compounds. Conversely, the closest analogs of Broxaterol (3-bromo delta 2-isoxazolines 4a and 5a) are at least one order of magnitude less active than the model compound 1. Throughout the series of derivatives the anti stereoisomers are invariably more active than their syn counterparts.
authors.affiliation: Istituto di Chimica Farmaceutica e Tossicologica, Università di Milano, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Conti
authors.forename: C
authors.initials: C
authors.lastname: Dallanoce
authors.forename: M
authors.initials: M
authors.lastname: De Amici
authors.forename: C
authors.initials: C
authors.lastname: De Micheli
authors.forename: K N
authors.initials: KN
authors.lastname: Klotz
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis* / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002855:Chromatography, Thin Layer; D006224:Cricetinae; D005910:Glioma; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011412:Propanolamines / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D007555:Isoxazoles; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; C047975:cyanopindolol; C045888:falintolol; D010869:Pindolol; D000262:Adenylyl Cyclases; C045916:broxaterol