An anomalous effect of N-isopropyl substitution in determining beta-adrenergic activity.
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.
Macchia
B
B
Istituto di Chimica Farmaceutica, Facoltá di Farmacia, Universitá di Pisa, Italy.
Balsamo
A
A
Lapucci
A
A
Macchia
F
F
Manera
C
C
Nencetti
S
S
Breschi
M C
MC
Lucacchini
A
A
Martini
C
C
Martinotti
E
E
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
D000318:Adrenergic beta-Agonists; D007202:Indicators and Reagents; D011943:Receptors, Adrenergic, beta; D000433:1-Propanol