title: Synthesis and beta-blocking activity of (R,S)-(E)-oximeethers of 2, 3-dihydro-1,8-naphthyridine and 2,3-dihydrothiopyrano[2, 3-b]pyridine:potential antihypertensive agents - part IX.
abstract: The synthesis of oximeethers of 2,3-dihydro-1,8-naphthyridine and 2, 3-dihydrothiopyrano[2,3-b]pyridine is described. These compounds exhibit a selective beta-blocking activity, with a selectivity towards beta(2)-receptors. Groups in the N(1) position giving rise to a considerable steric hindrance led to a higher beta(2)-blocking selectivity, whereas groups creating a moderate hindrance caused a weak but significant decrease in beta(2)-antagonist potency. Substitution of the N(1)-R group with a sulfur atom led to compounds possessing beta(1)-, beta(2)- and beta(3)-blocking properties. Compounds 9c(1) and 10a(1) showed a beta(3)-antagonist activity slightly lower than that of propranolol.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Pisa, via Bonanno 6, 56126, Pisa, Italy. ferrarini@farm.unipi.it
authors.forename: P L
authors.initials: PL
authors.lastname: Ferrarini
authors.forename: C
authors.initials: C
authors.lastname: Mori
authors.forename: M
authors.initials: M
authors.lastname: Badawneh
authors.forename: V
authors.initials: V
authors.lastname: Calderone
authors.forename: R
authors.initials: R
authors.lastname: Greco
authors.forename: C
authors.initials: C
authors.lastname: Manera
authors.forename: A
authors.initials: A
authors.lastname: Martinelli
authors.forename: P
authors.initials: P
authors.lastname: Nieri
authors.forename: G
authors.initials: G
authors.lastname: Saccomanni
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D020128:Inhibitory Concentration 50; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009287:Naphthyridines / Q000737:chemistry*; D011714:Pyrans / Q000138:chemical synthesis* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: C415403:2,3-dihydro-1,8-naphthyridine; C415404:2,3-dihydrothiopyran(2,3-b)pyridine; D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D009287:Naphthyridines; D011714:Pyrans; D011725:Pyridines; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; D007545:Isoproterenol