1165924-06-0Relevant articles and documents
The fit for purpose development of S1P1 receptor agonist GSK2263167 using a robinson annulation and saegusa oxidation to access an advanced phenol intermediate
Harris, Robert M.,Andrews, Benjamin I.,Clark, Stacy,Cooke, Jason W. B.,Gray, John C. S.,Ng, Stephanie Q. Q.
, p. 1239 - 1246 (2013/11/06)
A fit for purpose approach has been adopted in order to develop a robust, scalable route to the S1P1 receptor agonist, GSK2263167. The key steps include a Robinson ring annulation followed by a Saegusa oxidation, providing rapid access to an ad
Discovery of a brain-penetrant S1P3-sparing direct agonist of the S1P1 and S1P5 receptors efficacious at low oral dose
Demont, Emmanuel H.,Arpino, Sandra,Bit, Rino A.,Campbell, Colin A.,Deeks, Nigel,Desai, Sapna,Dowell, Simon J.,Gaskin, Pam,Gray, James R. J.,Harrison, Lee A.,Haynes, Andrea,Heightman, Tom D.,Holmes, Duncan S.,Humphreys, Philip G.,Kumar, Umesh,Morse, Mary A.,Osborne, Greg J.,Panchal, Terry,Philpott, Karen L.,Taylor, Simon,Watson, Robert,Willis, Robert,Witherington, Jason
supporting information; experimental part, p. 6724 - 6733 (2011/12/04)
2-Amino-2-(4-octylphenethyl)propane-1,3-diol 1 (fingolimod, FTY720) has been recently marketed in the United States for the treatment of patients with remitting relapsing multiple sclerosis (RRMS). Its efficacy has been primarily linked to the agonism on
Discovery of a selective S1P1 receptor agonist efficacious at low oral dose and devoid of effects on heart rate
Demont, Emmanuel H.,Andrews, Benjamin I.,Bit, Rino A.,Campbell, Colin A.,Cooke, Jason W. B.,Deeks, Nigel,Desai, Sapna,Dowell, Simon J.,Gaskin, Pam,Gray, James R. J.,Haynes, Andrea,Holmes, Duncan S.,Kumar, Umesh,Morse, Mary A.,Osborne, Greg J.,Panchal, Terry,Patel, Bela,Perboni, Alcide,Taylor, Simon,Watson, Robert,Witherington, Jason,Willis, Robert
, p. 444 - 449 (2011/08/08)
Gilenya (fingolimod, FTY720) was recently approved by the U.S. FDA for the treatment of patients with remitting relapsing multiple sclerosis (RRMS). It is a potent agonist of four of the five sphingosine 1-phosphate (S1P) G-protein-coupled receptors (S1P1 and S1P3-5). It has been postulated that fingolimod's efficacy is due to S1P1 agonism, while its cardiovascular side effects (transient bradycardia and hypertension) are due to S1P3 agonism. We have discovered a series of selective S1P 1 agonists, which includes 3-[6-(5-{3-cyano-4-[(1-methylethyl)oxy] phenyl}-1,2,4-oxadiazol-3-yl)-5-methyl-3,4-dihydro-2(1H)-isoquinolinyl] propanoate, 20, a potent, S1P3-sparing, orally active S1P1 agonist. Compound 20 is as efficacious as fingolimod in a collagen-induced arthritis model and shows excellent pharmacokinetic properties preclinically. Importantly, the selectivity of 20 against S1P3 is responsible for an absence of cardiovascular signal in telemetered rats, even at high dose levels.
S1P1 AGONISTS COMPRISING A BICYCLIC N-CONTAINING RING
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, (2010/12/31)
The present invention relates to novel compounds of formula (I) having S1P1 agonist activity, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders.
OXADIAZOLE DERIVATIVES ACTIVE ON SPHINGOSINE-1-PHOSPHATE (S1P)
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Page/Page column 34-35, (2009/07/25)
The present application discloses oxadiazote based compounds of Formula (I) active on sphingosine-1-phosphate (S1P) in particular useful to treat lupus erythematosus. A is phenyl or a 5 or 6-membered heleroaryl ring; B is selected from one of the followin
