448906-97-6Relevant academic research and scientific papers
Novel S1P1 receptor agonists - Part 4: Alkylaminomethyl substituted aryl head groups
Lescop, Cyrille,Müller, Claus,Mathys, Boris,Birker, Magdalena,De Kanter, Ruben,Kohl, Christopher,Hess, Patrick,Nayler, Oliver,Rey, Markus,Sieber, Patrick,Steiner, Beat,Weller, Thomas,Bolli, Martin H.
, p. 222 - 238 (2016/04/20)
In a previous communication we reported on the discovery of alkylamino pyridine derivatives (e.g. 1) as a new class of potent, selective and efficacious S1P1 receptor (S1PR1) agonists. However, more detailed profiling revealed that this compound class is phototoxic in vitro. Here we describe a new class of potent S1PR1 agonists wherein the exocyclic nitrogen was moved away from the pyridine ring (e.g. 11c). Further structural modifications led to the identification of novel alkylaminomethyl substituted phenyl and thienyl derivatives as potent S1PR1 agonists. These new alkylaminomethyl aryl compounds showed no phototoxic potential. Based on their in vivo efficacy and ability to penetrate the brain, the 5-alkyl-aminomethyl thiophenes appeared to be the most interesting class. Potent and selective S1PR1 agonist 20e, for instance, maximally reduced the blood lymphocyte count (LC) for 24 h after oral administration of 10 mg/kg to rat and its brain concentrations reached >500 ng/g over 24 h.
PYRIDINE DERIVATIVES AS S1P1/EDG1 RECEPTOR MODULATORS
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Page/Page column 14, (2011/09/20)
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.
PYRIDINE DERIVATIVES AS S1P1/EDG1 RECEPTOR MODULATORS
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Page/Page column 37, (2009/04/25)
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.
