The Chemosynthesis Of A771726 And Its Effect Of Anti-psoriasis

Leflunomide is a new type of immunregulative agents, which is almost metabolized into A771726 in liver or gastrointestine to educe the pharmacological action. And it has been exerted on rheumatoid arthritis in clinical. Recently, for its antiproliferation, anti-inflammatory and immunoregulatory activity, this new drug has been payed close attention to treating dermatosis, especially for autoimmune skin disease, such as psoriasis.Part one: Chemosynthesis of A771726The α α α -trifluoro-p-toluidine and cyanoacetic acid ethyl ester were mixed to product the cyanoacet-(4-trifluoromethyl)-anilide. Then the A771726(2-betenamide, -cyano-3-hydrory-N-[(4-trifluoromethyl)phenyl] ) was obtained through mixing the cyanoacet-(4-trifluoromethyl)-anilide and the acetylchloride. The synthesis of A771726 was proved by examination of HPLC, UV, MS, HMRS, and Elemental analysis.Part two: The study of pharmacokinetics and distribution of A771726Caudal vein injection of single dose of A771726(4, 12, 36 mg·kg^-1), then calculate corresponding pharmacokinetic parameter based on the time process of blood drug concentration. The results showed that the blood drug concentration-time curve consisted with the first-order kinetics of one-compartment model, the main pharmacokinetic parameters of A771726 (4, 12, 36mg·kg^-1) were t_1/2ke(h): (18.63±1.78), (31.07±7.33), (25.41±2.76); C₀(ug·ml^-1 ): (19.92±1.20), (49.58±9.00), (182.14±22.98); AUC(ug·h·ml^-1): (533.99±41.49), (2173.88±440.21), (6621.97±584.25).For the using of intravenous injection and the blood concentration-time curve...