Mesoionic oxatriazole derivatives--a new group of NO-donors.
A number of new 3-aryl-1,2,3,4-oxatriazole-5-imine derivatives (GEA Compounds--GEAC) were synthetized. GEAC are NO-releasers as evidenced by direct measurement of NO in headspace/NO-analyzer, by cooxygenation of oxyhaemoglobin to methaemoglobin in the Werringloer's test and by generation of nitrite in the Griess' reaction. During the release of NO from GEAC the consumption of O2 could be detected only when high concentrations of GEAC were used. The mechanism of release of NO from molecules of GEAC still remains hypothetical. Some of GEAC were found to remain stable for long periods of time, even at 37 degrees C. Both mutagenic properties and the pharmacodynamic profile of GEAC can be controlled by a mindful choosing of appropriate substituents.
Karup
G
G
A/S GEA, Department of Chemistry and Biochemistry, Hvidovre, Denmark.
Preikschat
H
H
Wilhelmsen
E S
ES
Pedersen
S B
SB
Marcinkiewicz
E
E
Cieślik
K
K
Gryglewski
R J
RJ
D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006454:Hemoglobins / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008706:Methemoglobin / Q000378:metabolism; D009152:Mutagenicity Tests; D009569:Nitric Oxide / Q000378:metabolism*; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology
D006454:Hemoglobins; D010069:Oxadiazoles; D014230:Triazoles; D009569:Nitric Oxide; D008706:Methemoglobin