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Discovery of super soft-drug modulators of sphingosine-1-phosphate receptor 1.
Bell, Mark; Foley, David; Naylor, Claire; Robinson, Colin; Riley, Jennifer; Epemolu, Ola; Scullion, Paul; Shishikura, Yoko; Katz, Elad; McLean, W H Irwin; Wyatt, Paul; Read, Kevin D; Woodland, Andrew.
Afiliación
  • Bell M; The Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK. Electronic address: m.u.bell@dundee.ac.uk.
  • Foley D; The Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
  • Naylor C; The Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
  • Robinson C; The Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
  • Riley J; The Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
  • Epemolu O; The Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
  • Scullion P; The Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
  • Shishikura Y; The Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
  • Katz E; The Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
  • McLean WHI; Dermatology and Genetic Medicine, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, UK.
  • Wyatt P; The Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
  • Read KD; The Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
  • Woodland A; The Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK. Electronic address: awoodland@dundee.ac.uk.
Bioorg Med Chem Lett ; 28(19): 3255-3259, 2018 10 15.
Article en En | MEDLINE | ID: mdl-30143424
The oral S1PR1 agonist ponesimod demonstrated substantial efficacy in a phase II clinical trial of psoriasis. Unfortunately, systemic side effects were observed, which included lymphopenia and transient bradycardia. We sought to develop a topical soft-drug S1PR1 agonist with an improved therapeutic index. By modifying ponesimod, we discovered an ester series of S1PR agonists. To increase metabolic instability in plasma we synthesised esters described as specific substrates for paraoxonase and butyrylcholinesterases, esterases present in human plasma.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tiazoles / Receptores de Lisoesfingolípidos / Descubrimiento de Drogas Límite: Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2018 Tipo del documento: Article Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tiazoles / Receptores de Lisoesfingolípidos / Descubrimiento de Drogas Límite: Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2018 Tipo del documento: Article Pais de publicación: Reino Unido