Improved Synthesis Of Novel S1P₁Receptor Agonist CYM-5442

Immunomodulators is a category of biological or chemical substances that canregulate the body’s immune response. It plays an important role in the field ofpreventing and controling the infectious diseases, autoimmune diseases and organtransplantation rejection resistance diseases. In the process of looking for newimmunomodulators which have high activities and low adverse reactions, bycontrolling the lymphocyte migration, the S1P1receptor modulators can producestrong immunomodulatory effection. Therefore, through exciting S1P1receptor andblocking lymph cell’s cycling can be used in the treatment of the immune system’sdiseases. The function of regulating the lymphocyte migration has made the S1P1receptor a immune modulator’s target which has a new mechanism.In this paper, the synthesized S1P1receptor agonist CYM-5442blongs to a newimmunomodulator, which only has selective combination for S1P1receptors in thebody, and then exerting immunoregulatory activity and improving the curativeeffection. At present, the drug is in the clinical trials of phase Ⅲ of multiple sclerosisand in the clinical trials of phase Ⅱof ulcerative colitis.In this essay, the research work includes two aspects. Firstly we improved themethod based on the existing literature of synthesizing CYM-5442. And it was tried tosynthesizethe important intermediates of4-cyano-1-indanone with o-cyanobenzylchloride and diethyl alonate as raw materials and with4-bromine-1-indanone as rawmaterial. Finally, the CYM-5442was obtained accroding to improving the method ofthe foreign literature and it was based on getting the4-cyano-1-indanone. Its structurewas confirmed by spectroscopy. The total yield of synthesis was up to11.3％. Thesynthetic amount of target compound of CYM-5442was reached to gram weight level,which was establishing foundation for enlargement in preparing the compound.Secondly, we tried to separate the structure of CYM-5442into two parts, thenconnected the two parts of the heterocyclic compound with chloride atom and thebenzene ring with boronester by Suzuki reaction, achieving the connection of twoparts and getting the target compound CYM-5442. These explorations provide animportant reference for the preparation and research of CYM-5442.