title: An anomalous effect of N-isopropyl substitution in determining beta-adrenergic activity.
abstract: We report unexpected results in an investigation of cyclic analogues of dopamine and norepinephrine possessing the structures 1-(aminomethyl)-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene (3) and 1-(aminomethyl)-5,6-dihydroxy-1,2,3,4-tetrahydro-1-naphthalenol (7). N-Isopropyl substitution of these compounds, providing 4 and 8, brings about the total disappearance of their stimulant activity on beta-adrenergic receptors. On the basis of current knowledge about the structure-activity relationship of adrenergic drugs, it is difficult to provide an explanation for these results; however a tentative rationalization based on conformational considerations is suggested.
authors.affiliation: Istituto di Chimica Farmaceutica, Facoltá di Farmacia, Universitá di Pisa, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Macchia
authors.forename: A
authors.initials: A
authors.lastname: Balsamo
authors.forename: A
authors.initials: A
authors.lastname: Lapucci
authors.forename: F
authors.initials: F
authors.lastname: Macchia
authors.forename: C
authors.initials: C
authors.lastname: Manera
authors.forename: S
authors.initials: S
authors.lastname: Nencetti
authors.forename: M C
authors.initials: MC
authors.lastname: Breschi
authors.forename: A
authors.initials: A
authors.lastname: Lucacchini
authors.forename: C
authors.initials: C
authors.lastname: Martini
authors.forename: E
authors.initials: E
authors.lastname: Martinotti
mesh_terms: D000433:1-Propanol; D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D015195:Drug Design; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000318:Adrenergic beta-Agonists; D007202:Indicators and Reagents; D011943:Receptors, Adrenergic, beta; D000433:1-Propanol