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• 203793-60-6 4-fluorophenylazo-O-(phenoxycarbonyl)-methanamidoxime 
• 203795-11-3 C₇H₇FN₄O 

Relevant academic research and scientific papers

Arylazoamidoximes and related compounds as NO-modulators

Three amidinoarylhydrazines 1, three arylazoamidines 2, and nine arylazoamidoximes 3 have been synthesized and investigated for their potential to function as nitric oxide (NO) modulators. In-vitro studies demonstrated that 2 and 3 inhibited platelet aggregation (2c, IC50 = 3 μM) which could also be shown in vivo by inhibition of thrombus formation in arterioles (3a, 22%). Moreover, for all compounds antihypertensive effects were examined in vivo with SHR rats, with 2a being the most potent candidate by lowering blood pressure by 19%. However, no common underlying mechanism of action could be shown. Some of these compounds released HNO non-enzymatically. Incubations with NO synthase isoforms (NOSs) revealed, that compounds 1 to 3 were weak substrates for NOSs but arylazoamidoximes 3 remarkably elevated the NOSs activity in the presence of L-arginine (3h, up to fivefold). In addition, we examined effects on arginase and dimethylarginine dimethylaminohydrolase (DDAH), two further enzymes involved in the complex regulation of NO biosynthesis, to elucidate whether the observed in-vivo effects can be traced back to their modulation. Furthermore, the metabolic fate of arylazoamidoximes 3 was addressed by investigation of a possible N-reductive biotransformation. In summary, novel NO-modulating compound classes are presented, among which arylazoamidoximes 3 are potent activators of NOS isoforms, and arylazoamidines 2 exert in-vivo effects by unknown mechanisms.

New NO-Donors with antithrombotic and vasodilating activities, part 17. Arylazoamidoximes and 3-arylazo-1,2,4-oxadiazol-5-ones

Seven arylazoamidoximes (3), six phenoxycarbonyl derivatives (4), and six 1,2,4-oxadiazol-5-ones (5) have been prepared and their structure and purity etablished by spectroscopy and elemental analysis. In the EI mass spectra ready elimination of NO from the title amidoximes was observed. A new addition reaction of 3a with hydrochloric acid to 4-chlorophenylhydroazoamidoxime 7 is described. The compounds were tested for nitric oxide dependent biological properties, i.e. platelet aggregation, antithrombotic effects, and decrease in blood pressure. In arterioles of rats 5/19 compounds inhibited the formation of thrombi with a laser beam by ≤20% 2 h after oral administration of 60 mg/kg. Among these are three amidoximes (3a, 3e, 3f), one phenoxycarbonyl derivative (4a), and one oxadiazolone (5a). With the 4-chlorophenylazoamidoxime 3c a long lasting (24 h) decrease of blood pressure in spontaneously hypertensive rats was observed. Microsomal fractions of rat liver oxidize arylazoamidoximes and generate nitric oxide (e.g. 3a and 3b). NO was measured by the oxyhemoglobin assay. The influence of SOD, pretreatment of the rats with dexamethasone, as well as kinetic parameters were determined. Type 3 compounds, therefore, are a new class of NO donors. Type 4 and 5 compounds function as their prodrugs.