- Novel S1P1 receptor agonists - Part 3: From thiophenes to pyridines
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In preceding communications we summarized our medicinal chemistry efforts leading to the identification of potent, selective, and orally active S1P 1 agonists such as the thiophene derivative 1. As a continuation of these efforts, we replaced the thiophene in 1 by a 2-, 3-, or 4-pyridine and obtained less lipophilic, potent, and selective S1P1 agonists (e.g., 2) efficiently reducing blood lymphocyte count in the rat. Structural features influencing the compounds' receptor affinity profile and pharmacokinetics are discussed. In addition, the ability to penetrate brain tissue has been studied for several compounds. As a typical example for these pyridine based S1P 1 agonists, compound 53 showed EC50 values of 0.6 and 352 nM for the S1P1 and S1P3 receptor, respectively, displayed favorable PK properties, and penetrated well into brain tissue. In the rat, compound 53 maximally reduced the blood lymphocyte count for at least 24 h after oral dosing of 3 mg/kg.
- Bolli, Martin H.,Abele, Stefan,Birker, Magdalena,Bravo, Roberto,Bur, Daniel,De Kanter, Ruben,Kohl, Christopher,Grimont, Julien,Hess, Patrick,Lescop, Cyrille,Mathys, Boris,Müller, Claus,Nayler, Oliver,Rey, Markus,Scherz, Michael,Schmidt, Gunther,Seifert, Jürgen,Steiner, Beat,Velker, J?rg,Weller, Thomas
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supporting information
p. 110 - 130
(2014/02/14)
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- NOVEL PYRIMIDINE-PYRIDINE DERIVATIVES
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The invention relates to novel pyrimidine-pyridine derivatives, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunomodulating agents.
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Page/Page column 20
(2011/04/14)
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- PYRIDINE DERIVATIVES AS S1P1/EDG1 RECEPTOR MODULATORS
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The invention relates to novel pyridine derivatives of formula (D, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunomodulating agents. Formula (I) wherein A represents and the other substituents are as defined in the claims.
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Page/Page column 28
(2011/09/20)
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- PYRIDINE DERIVATIVES AS S1P1/EDG1 RECEPTOR MODULATORS
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The invention relates to novel pyridine derivatives of formula (D, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunomodulating agents. Formula (I) wherein A represents and the other substituants are as defined in the claims.
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Page/Page column 76
(2009/04/25)
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- NOVEL PYRIMIDINE-PYRIDINE DERIVATIVES
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The invention relates to novel pyrimidine-pyridine derivatives, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunomodulating agents. Formula I.
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Page/Page column 50
(2009/10/22)
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- Compounds
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Compounds of Formula (I), compositions containing them, their use in therapy, including their use as antibacterials, for example in the treatment of tuberculosis, and methods for the preparation of such compounds, are provided.
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Page/Page column 36-37
(2009/08/14)
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