Synthesis and alpha-adrenergic activities of 2- and 4-substituted imidazoline and imidazole analogues.
Seven analogues of medetomidine and naphazoline were synthesized and evaluated for their alpha 1 (aorta) and alpha 2 (platelet) activities. The analogues were composed of 2- and 4-substituted imidazoles and imidazolines attached through a methylene bridge to either the 1- or 2-naphthalene ring system. In general the 1-naphthalene analogues were the most potent inhibitors of epinephrine-induced platelet aggregation. Of considerable interest was the fact that the 1-naphthalene analogues (2, 5-7) were partial agonists while the 2-naphthalene analogues (3, 8, 9) were antagonists in an alpha 1-adrenergic system (aorta). Thus, appropriately substituted naphthalene analogues of medetomidine and naphthazoline provide a spectrum of alpha 1-agonist, alpha 1-antagonist, and alpha 2-antagonist activity.
Division of Medicinal Chemistry, College of Pharmacy, Ohio State University, Columbus 43210.
Y
Y
Amemiya
S S
SS
Hong
B V
BV
Venkataraman
P N
PN
Patil
G
G
Shams
K
K
Romstedt
D R
DR
Feller
F L
FL
Hsu
D D
DD
Miller
D000316:Adrenergic alpha-Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D020926:Medetomidine / Q000031:analogs & derivatives; D009278:Naphazoline / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D010975:Platelet Aggregation Inhibitors; C073198:4-(1-(1-naphthyl)ethyl)imidazole; D009278:Naphazoline; D020926:Medetomidine; D004837:Epinephrine