Studies On The Synthesis Of3-(2-(4-isobutylpheny) Propionyl) Imidazolidinyl-2,4-dione Derivatives And Its Pharmacological Activities

3-(2-(4-isobutylpheny)propionyl)imidazolidinyl-2,4-dione derivatives is a series ofnovel compound which takes Ibuprofen as prodrug and is formed by the reaction with thehydantoin compounds.Hydantoin (1,3-imidazolidinedione) was discovered in1861by Baeyer, who isolated itas one of the reduction products of allantoin by studying uric acid. Hydantoin derivativesdisplay diverse and interesting pharmacological properties. Several such derivatives such asphenytoin, mephenytoin, norantoin, methetoin, ethotoin, fosphenytoin and some5-substituted hydantoins are well-known anticonvulsive drugs. Hydantoins also exhibitantidepressant, antiviral, antitumoral and antithrombotic activities, as well as inhibitoryactivity against some enzymes such as human aldose reductase and human leucocyteelastase.Ibuprofen is a kind of non-steroidal and anti-inflammatory drug that is commonly usedfor the treatment of chronic inflammatory diseases. It always shows several undesired sideeffects such as gastro-intestinal irritation and ulceration which still represent an unsolvedtherapeutic problem. Considerable attention has been focused on the development ofbioreversible derivatives, such as amidation and acetification of carboxyl of ibuprofen due totheir character tics of stability low toxicity and small side effectsThis study designed a new synthetic route of3-(2-(4-isobutylphenyl) propionyl)--imidazolidinyl2,4-diketone compoundssynthetic with references of the study of ibuprofenderivatives at home and abroad. The route first selects amino acid or amino acid estercompounds and cyanate as raw material due to their charactistic of short route, high yieldand short reaction time rather than adopting the traditional methods of using cyanide. As aresult, the study is low toxic and causes less pollution. Then the chloride reaction ofcarboxylic acid, ibuprofen was conducted which selected thiony halide as reagent because it is simple, high yield, and simple post-processing. One thing that should be paid specialattention to is that hydrogen chloride gas was produced during the process and should berecycled to prevent pollution of the environment. Finally, with the amidation reaction ofhydantoin compounds and ibuprofen chloride, the final target product3-(2-(4-isobutylpheny)propionyl)imidazolidinyl-2,4-dione derivatives were generated whichare brand new.There are abundant studies on hydantoin compounds at home and abroad more butmostly focus on the treatment of diabetes, anti-inflammatory, bactericidal, and other aspects.This study shows that a large number of hydantoin compounds are antitussive whileibuprofen is a traditional non-steroidal anti-inflammatory drug. This article focus on theantitussive effect and anti-inflammatory of the3-(2-(4-isobutylphenyl) propionyl)-imidazolidinyl2,4-diketone compound. Taking two common drugs of ibuprofen andcodeine phosphate as positive control, this study adopted the ear edema method in mice andammonia induced cough. The study results show that all the four derivatives possess varyingdegrees of anti-inflammatory activity, among which Methylhydantoin has the strongestanti-inflammatory effect that is stronger than ibuprofen. All the four derivatives significantlyprolonged the cough latency and inhibiedt the cough. Due to the reason that ammoniainduced cough method is peripheral cough model, the antitussive effect of this fourderivatives can be classified as peripheral antitussive properties.This article mainly studied the synthesis and preliminary efficacy of imidazole alkyl3-(2-(4-isobutylpheny)propionyl)imidazolidinyl-2,4-dione derivatives and it finalized a short,productive, less polluting synthetic route. At the same time, four kinds of new compoundswere successfully synthesized. Then it studied the anti-inflammatory and antitussive activityof the synthetic derivatives, which the foundation on the development of new ibuprofenderivatives with low toxicity, small side effects and high efficacy.