Sphingosine 1-phosphate agonists

Lynch, K. R. Macdonald, T. L. Sphingosine 1-Phosphate Agonists Comprising Cycloalkanes and 5-Membeied Heterocycles Substituted by Amino and Phenyl Groups. WO Patent 2006088944, 2006. 

Parrill AL, Sardar VM, Yuan H (2004) Sphingosine 1-phosphate and lysophosphatidic acid receptors agonist and antagonist binding and progress toward development of receptor-specific ligands. Semin Cell Dev Biol 15 467-476... 

Sphingosine-l-phosphate (= SIP) Universal likely signaller in S1P-R EDG-1 agonist... 

Mandala S, Hajdu R, Bergstrom J, Quackenbush E, Xie J, Milligan J, Thornton R, Shei GJ, Card D, Keohane C, Rosenbach M, Hale J, Lynch CL, Rupprecht K, Parsons W, Rosen H (2002) Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science 296 346-349... 

Clemens, J. J., Davis, M. D., Lynch, K. R., Macdonald, T.L. Synthesis of para-alkyl aryl amide analogues of sphingosine-l-phosphate discovery of potent SIP receptor agonists. Bioorg Med Chem Lett 13 (2003) 3401-3404. 

Fujishiro, J., Kudou, S., Iwai, S., Takahashi, M., Hakamata, Y., Kinoshita, M., Iwanami, S., Izawa, S., Yasue, T., Hashizume, K., Murakami, T., Kobayashi, E. Use of sphingosine-1-phosphate 1 receptor agonist, KRP-203, in combination with a subtherapeutic dose of cyclosporine A for rat renal transplantation. Transplantation 82 (2006) 804-812. 

Rosen, H., Alfonso, C., Surh, C. D., McHeyzer-Williams, M. G. Rapid induction of medullary thymocyte phenotypic maturation and egress inhibition by nanomolar sphingosine 1-phosphate receptor agonist. Proc Natl Acad Sci USA 100 (2003) 10907-10912. 

Sawicka, E., Zuany-Amorim, C., Manlius, C., Trifilieff, A., Brinkmann, V., Kemeny, D. M., Walker, C. Inhibition of Thl- and Th2-mediated airway inflammation by the sphingosine 1-phosphate receptor agonist FTY720. J Immunol 171 (2003) 6206-6214. 

Webb, M., Tham, C. S., Lin, F. F., Lariosa-Willingham, K., Yu, N., Hale, J., Mandala, S., Chun, J., Rao, T. S. Sphingosine 1-phosphate receptor agonists attenuate relapsing-remitting experimental autoimmune encephalitis in SJL mice. J Neuroimmunol 153 (2004) 108-121. 

Goetzl E J (2004). An IgM-kappa rat monoclonal antibody specific for the type 1 sphingosine 1-phosphate G protein-coupled receptor with antagonist and agonist activities. Immunol. Lett. 93 63-69. 

In the search for bioactive sphingosine 1-phosphate (SIP) receptor ligands, a series of 2-amino-2-heterocyclic propanols (242-245) have been synthesized. These molecules were discovered as substrates of human sphingosine kinases (SPHKl and SPHK2). The oxazole-derived structure was the most active for human SPHK2. Imidazole analogues were less active substrates for SPHKs, but more potent and selective agonists of the SI PI receptor. 

W., and Rosen, H, (2002) Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science,... 

Mandala, S, Hajdu, R, Bergstrom, J, Quackenhush, E, Xie, J, Milligan, J, Thornton, R, Shei, GJ, Card, D, Keohane, C, Rosenbach, M, Hale, J, Lynch, CL, Rupprecht, K, Parsons, W and Rosen, H (2002) Alteration of lymphocyte trafficking by sphingosine 1-phosphate receptor agonists. Science, 296, 346-349. 

VPC01091 - Sphingosine 1 -phosphate receptor-subtype 1 (SI PI) agonist... 

These mechanistic insights made the method an effective tool to be explored in organic synthesis. To illustrate its utility, we performed the total synthesis of VPC01091 (130), an agonist of the sphingosine 1-phosphate (SIP, 131) cellular receptor. Among the important biological functions of... 

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