Synthesis, ocular effects, and nitric oxide donation of imidazole amidoximes.
Novel 1-R-imidazole-5-amidoximes and 1-R-5-cyano-imidazole-4-amidoximes (R: H, Me, Bn) were prepared from their corresponding nitriles and were tested for their efficacy to lower intraocular pressure (IOP) in rabbits. The ability of these compounds to donate nitric oxide (NO) was studied by observing the stimulation of formation of cyclic guanosine-3',5'-monophosphate (cGMP) in the incubation of porcine iris-ciliary body. In the incubation experiments, 1-methylimidazole-5-amidoxime and 1(H)-imidazole-4(5)-amidoxime stimulated formation of cGMP indicating NO donating ability of these compounds. 1-Methylimidazole-5-amidoxime lowered IOP significantly after intravitreal injection.
Oresmaa
L
L
Department of Chemistry, University of Joensuu, PO Box 111, 80101 Joensuu, Finland.
Kotikoski
H
H
Haukka
M
M
Oksala
O
O
Pohjala
E
E
Vapaatalo
H
H
Moilanen
E
E
Vainiotalo
P
P
Aulaskari
P
P
D000586:Amination; D000818:Animals; D006152:Cyclic GMP / Q000097:blood; D005123:Eye / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D007093:Imidazoles / Q000737:chemistry*; D007536:Isomerism; D008297:Male; D015394:Molecular Structure; D009566:Nitrates / Q000737:chemistry; D009569:Nitric Oxide / Q000378:metabolism*; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship; D013552:Swine
D007093:Imidazoles; D009566:Nitrates; D010091:Oximes; D009569:Nitric Oxide; C029899:imidazole; D006152:Cyclic GMP