title: Novel immunomodulators based on an oxazolin-2-one-4-carboxamide scaffold.
abstract: A series of oxazolidin-2-one-4-carboxylic amide compounds (1a-f) were designed and synthesized as the non-phosphate S1P(1) receptor agonists. The single crystal of 1e was prepared and solved to elucidate the structure of 1a-f. EC(50) of 1a-d were about 1.1-3.6 μM in S1P(1) Redistribution® assay, and their cytotoxicity was 8-40-fold lower than FTY720. Though its S1P(1) agonist activities in vitro were about 1000-folds weaker than (S)-FTY720-P, at a dose of 10mg/Kg, the immunosuppressive effects of 1a were comparable to FTY720. So oxazolidin-2-one-4-carboxylic amide derivatives were found as potential immunomodulator, compound 1a could be considered as a lead compound, rational modifications of 1a are anticipated using medicinal chemistry techniques and molecular modeling to obtain analogs with higher affinity and better clinical therapeutic properties.
authors: Beijing Institute of Pharmacology & Toxicology, No.27 Taiping Road, Beijing 100850, PR China. hexinhua2007@gmail.com
authors: Xinhua
authors: X
authors: He
authors: Lili
authors: L
authors: Wang
authors: Zhibing
authors: Z
authors: Zheng
authors: Junhai
authors: J
authors: Xiao
authors: Wu
authors: W
authors: Zhong
authors: Song
authors: S
authors: Li
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology*; D000596:Amino Acids / Q000737:chemistry; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology; D020134:Catalytic Domain; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D000068876:Fingolimod Hydrochloride; D006801:Humans; D006860:Hydrogen Bonding; D007155:Immunologic Factors / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D010081:Oxazolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011409:Propylene Glycols / Q000494:pharmacology; D049349:Receptors, Lysosphingolipid / Q000819:agonists; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000577:Amides; D000596:Amino Acids; D001549:Benzamides; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; C573856:oxazolin-2-one-4-carboxamide; D010081:Oxazolone; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine