Studies On Synthesis And NO-release In Vitro Activity Of The New Drugs Containing Furoxanyl Moiety

Nitric oxide (NO) is an important biological messenger andeffector molecule involved in many pathological andphysiological processes which occur in the body. It has beenshown to play a key role in cardiovascular, immune, andnervous systems. Numerous scholars have focused on the studyof NO donor-drugs.There is the evidence that furoxans(1,2,5-oxadiazole 2-oxides)are able to generate NO, in the presence of thiol cofactors.Using appropriate substituents at the heteroring, it is possible tomodulate the rate and amount of NO production. Thepharmacological profile of furoxans has prompted the inclusionat the furoxan ring in the design of NO releasing drugs.At present, it is blank in researching and developing theantiatherosclerosis drugs endowed with NO donors. So, in thispaper, it has been finished as follows:â‘ 3,4-bisphenylsulfonylfuroxan was synthesized fromthiophenol by etherification, oxidation and cyclization.â‘¡Two compounds were obtained by linking furoxan moietyto nicotinic acid and clofibric acid,respectively.â‘¢Nitrosothiol group was chosen to be coupled withCaptopril, so as to get compound I3.â‘£Compound I1 , I2 , I3 and Isosorbide Mononitrate weretested for their ability of the NO-release in vitro.Objective: To synthesize new type NO donor-compounds, totest the final products'ability of the NO-release in vitro, and totry to find the lead compounds.Methods:â‘ 3,4-bisphenylsulfonylfuroxan was prepared byetherification, oxidation and cyclization from thiophenol. â‘¡Byesterification and amidation, nicotinic acid was turned intoN-(2-hydroxy-ethyl) nicotinic amide, which was then coupledwith 3,4-bisphenylsulfonylfuroxan through etherification toobtain the aim compound I1. â‘¢The clofibric acid derivativewas joined by an ether linkage to 3,4-bisphenylsulfonylfuroxan.Thus, the aim compoung I2 was obtained. â‘£Captopril andsodium nitrite dry powder (1:1 mol/mol) took placeS-nitrosylation in acidic condition to get S-nitrosocaptopril(I3).⑤A solution(10-4mmol/L) of the appropriate compound wasprepared at 37℃, using phosphate buffer(pH 7.4) in presence of5mmol/L L-cysteine. The reaction mixture was taken at differenttime and determined by Griess reagent. Absorbance wasdetected at 540nm.Results: â‘ 3,4-bisphenylsulfonylfuroxan was obtained. Itsmp. 154.4¹56.1℃was in consistent with the report in theliterature. â‘¡Two aim compounds were synthesized. The mp. ofI₁ was found in the rage of 162.2¹63.8℃. The mp. of I2 was91.9⁹3.0℃. Their structures were characterized by UV, IR,1^H-NMR and HRFAB-MS, and the analytical results were...