Synthesis And Quality Research Of Fingolimod

Immunosuppressant is inhibited immune response of drugs, can inhibit theproliferation and function related reactions and immune cells, reducing the role of theantibody immune response. Immunosuppressant is a class of immunosuppressantcombination of theory-based immune pathology, clinical immunology and otherdisciplines evolved new drugs. Because of their unique immune responses andsuppress immune function, can be widely used in organ transplantation anti-rejectiontreatment response and autoimmune diseases. Immunosuppressant used mainly fivecategories:(1) glucocorticoid, such as prednisone and cortisone;(2) microbialproducts, such as cyclosporin and tacrolimus;(3) antimetabolites material, such asazathioprine and6-mercaptopurine;(4) polyclonal and monoclonal anti-lymphocyteantibodies, such as OKT3and other anti-lymphocyte globulin;(5) alkylating agentssuch as cyclophosphamide. Further development of new immunosuppressive agents,and also the type of medicine class of small molecule immunosuppressants.Fingolimod is Mitsubishi developed by the pharmaceutical company. ProfessorFujita et cultivate a new immunosuppressive liquid extract obtained from the Divisionworm summer grass suppression agents, antibiotics ISP-1synthesis by chemicalmodification. Can be administered orally for the treatment of relapsing-remittingmultiple sclerosis (MS). Studies have shown that immune suppression mechanism iscompletely different with other drugs, can change lymphocytes tend to promoteretention in the lymphoid tissue lymphocytes, lymphocytes leave the lymphoid tissueprobability is lowered, the effect of immunosuppressive activity.In this paper, access to a large literature related to fingolimod synthetic methods,citing the country’s two synthetic routes and foreign literature in the three syntheticroutes. The test process research synthesis, combined with the need of industrialproduction, the design of synthetic routes to β-phenyl ethanol as raw material,halogenation, Friedel-Crafts acylation reaction, condensation, carbonyl reduction,ester reduction, hydrolysis desacetyl the final salt formation target molecule. The totalyield of22.4%. Compared with the literature synthesis route, the synthetic routeobtained by the process of the trial simplify, reduce costs, mild reaction conditions, high yield, suitable for industrial scale production. Key intermediate structure by UVproduct with the ultimate goal of spectroscopy, infrared spectroscopy, nuclearmagnetic resonance spectra of hydrogen and carbon spectra etc. corroborated.This paper established a method for determining the content of Fingolimodhydrochloride drug substance and related substances by HPLC. HPLC method for thedetermination of test results showed that: Fingolimod hydrochloride in the range of0.055~0.165mg/mL good linear regression equation was Y＝158490160X－51837.4，r2＝0.9998; precision RSD was0.11%, indicating that the instrument goodprecision; repeatability RSD0.09%, indicating good reproducibility determination;stability RSD was0.13%, indicating that the test solution at least stable within12h;recoveries and RSD was1.37%, indicating that this method is feasible; sample welltolerated. Related substances by HPLC test results showed that: the stability of RSD is0.022%, indicating that the test solution at least stable within12h; tolerated. From theabove data display measurement results are accurate, reliable, and show that theestablished HPLC method can effectively control the quality of the product.