Synthesis and ocular antihypertensive activity of new imidazolidine derivatives containing a beta-blocking side chain.
The syntheses of new phenylimidazolidine derivatives (3-6)1 containing a propanolamine oxime or an oxypropanolamine moiety attached either to the aromatic or to the imidazolidine ring are described. These compounds were evaluated for potential ocular antihypertensive activity in alpha-chymotrypsin-induced ocular hypertension in rabbits. These compounds represent a unique series of effective ocular antihypertensive agents that despite possessing structural characteristics of beta-blockers and of imidazolidine derivatives, exhibit weak alpha- and beta-adrenergic agonist and antagonist activities. These findings may be of significant therapeutic importance in the medical management of glaucoma.
Huber
D
D
Institut de Pharmacologie (UA 589 CNRS), Equipe de Pharmacochimie, Faculté de Médecine, Strasbourg, France.
Ehrhardt
J D
JD
Decker
N
N
Himber
J
J
Andermann
G
G
Leclerc
G
G
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D005901:Glaucoma / Q000139:chemically induced / Q000188:drug therapy; D006168:Guinea Pigs; D006973:Hypertension / Q000188:drug therapy; D007093:Imidazoles / Q000138:chemical synthesis* / Q000627:therapeutic use; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D007093:Imidazoles; D011941:Receptors, Adrenergic