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Design and Synthesis of Selective and Potent Orally Active S1P5 Agonists
Author(s) -
Mattes Henri,
Dev Kumlesh Kumar,
Bouhelal Rochdi,
Barske Carmen,
Gasparini Fabrizio,
Guerini Danilo,
Mir Anis Khusro,
Orain David,
Osinde Maribel,
Picard Anne,
Dubois Celine,
Tasdelen Engin,
Haessig Samuel
Publication year - 2010
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201000253
Subject(s) - orally active , chemistry , pharmacology , combinatorial chemistry , medicine , oral administration
Putting the brakes on demyelination: Fingolimod (FTY720) was recently shown to significantly decrease relapse rates in patients with multiple sclerosis. This drug attenuates the trafficking of harmful T‐cells entering the brain by regulating sphingosine‐1‐phosphate (S1P) receptors. We designed, synthesized, evaluated 2 H ‐phthalazin‐1‐one derivatives (e.g., 1 L ) as selective S1P5 receptor agonists; these compounds are highly potent and selective, with good PK properties, and significant activity in oligodendrocytes.