Jean-François Arrighi

Publications (2)7.9 Total impact

• Article: Discovery of a novel series of potent S1P1 agonists.

  Stefano Crosignani, Agnes Bombrun, David Covini, Maurizio Maio, Delphine Marin, Anna Quattropani, Dominique Swinnen, Don Simpson, Wolfgang Sauer, Bernard Françon, [......], Anthony Nichols, Isabelle Martinou, Fabienne Burgat-Charvillon, Delphine Rivron, Cristina Donini, Olivier Schott, Valerie Eligert, Laurence Novo-Perez, Pierre-Alain Vitte, Jean-François Arrighi
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  ABSTRACT: The discovery of a novel series of S1P1 agonists is described. Starting from a micromolar HTS positive, iterative optimization gave rise to several single-digit nanomolar S1P1 agonists. The compounds were able to induce internalization of the S1P1 receptor, and a selected compound was shown to be able to induce lymphopenia in mice after oral dosing.
  Bioorganic & medicinal chemistry letters 01/2010; 20(5):1516-9. · 2.65 Impact Factor
• Source

  Available from: Marc Missotten

  Article: Discovery of a new class of potent, selective, and orally bioavailable CRTH2 (DP2) receptor antagonists for the treatment of allergic inflammatory diseases.

  Stefano Crosignani, Patrick Page, Marc Missotten, Véronique Colovray, Christophe Cleva, Jean-François Arrighi, John Atherall, Jackie Macritchie, Thierry Martin, Yves Humbert, [......], Maurizio Maio, Pierre-André Pittet, Lucia Golzio, Claudio Giachetti, Cynthia Rocha, Gérald Bernardinelli, Yaroslav Filinchuk, Alexander Scheer, Matthias K Schwarz, André Chollet
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  ABSTRACT: A novel chemical class of potent chemoattractant receptor-homologous expressed on Th2 lymphocytes (CRTH2 or DP2) antagonists is reported. An initial and moderately potent spiro-indolinone compound ( 5) was found during a high-throughput screening campaign. Structure-activity relationship (SAR) investigation around the carboxylic acid group revealed that changes in this part of the molecule could lead to a reversal of functional activity, yielding weakly potent agonists. SAR investigation of the succinimide functional group led to the discovery of several single-digit nanomolar antagonists. The potency of these compounds was confirmed in a human eosinophil chemotaxis assay. Moreover, compounds ( R)- 58 and ( R)- 71 were shown to possess pharmacokinetic properties suitable for development as an orally bioavailable drug.
  Journal of Medicinal Chemistry 05/2008; 51(7):2227-43. · 5.25 Impact Factor