7192-39-4Relevant articles and documents
Novel S1P1 receptor agonists - Part 1: From pyrazoles to thiophenes
Bolli, Martin H.,Müller, Claus,Mathys, Boris,Abele, Stefan,Birker, Magdalena,Bravo, Roberto,Bur, Daniel,Hess, Patrick,Kohl, Christopher,Lehmann, David,Nayler, Oliver,Rey, Markus,Meyer, Solange,Scherz, Michael,Schmidt, Gunther,Steiner, Beat,Treiber, Alexander,Velker, J?rg,Weller, Thomas
supporting information, p. 9737 - 9755 (2014/01/06)
From a high-throughput screening campaign aiming at the identification of novel S1P1 receptor agonists, the pyrazole derivative 2 emerged as a hit structure. Medicinal chemistry efforts focused not only on improving the potency of the compound but in particular also on resolving its inherent instability issue. This led to the discovery of novel bicyclo[3.1.0]hexane fused thiophene derivatives. Compounds with high affinity and selectivity for S1P1 efficiently reducing the blood lymphocyte count in the rat were identified. For instance, compound 85 showed EC50 values of 7 and 2880 nM on S1P1 and S1P3, respectively, had favorable pharmacokinetic properties in rat and dog, distributed well into brain tissue, and efficiently and dose dependently reduced the blood lymphocyte count in the rat. After oral administration to spontaneously hypertensive rats, the S1P 1 selective compound 85 showed no effect on mean arterial blood pressure and affected the heart rate during the wake phase of the animals only.
NEW THIADIAZOLE DERIVATIVES
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Page/Page column 34, (2011/04/24)
The present invention relates to thiadiazole derivatives of formula (I), to processes for their preparation and to pharmaceutical compositions containing them. These compounds are potent agonists of S1P1 receptors and thus, they are useful In the treatment, prevention or suppression of diseases and disorders known to be susceptible to improvement by sphingosine-1-phosphate receptors agonists (S1P1), such as autoimmune diseases, chronic immune and inflammatory diseases, transplant rejection, malignant neoplastic diseases, angiogenic-related disorders, pain, neurological diseases, viral and infectious diseases.
New 2-aminothiadiazole derivatives
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Page/Page column 23, (2011/08/03)
The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or N-oxide thereof: wherein: ? L represents a direct bond or a -S(O)2- group, ? n is an integer having a value from 0 to 2, ? R1 represents a pyridyl group or an imidazo[1,2-a]pyridinyl group, wherein the pyridyl group is substituted with one or more substituents selected from halogen atoms, a hydroxy group, a C1-4 alkyl group and a C1-4 alkoxy group, or ? R1 represents a group of formula: wherein: o Ra and Rb independently represent a hydrogen atom, halogen atom or a linear or branched C1-4 alkyl group, o Rc represents a hydroxy group, a linear or branched C1-4 alkyl group or C1-4 alkoxy group wherein the alkyl and the alkoxy groups independently are optionally substituted with one or more substituents selected from hydroxy group, cyano group and-NR'R" groups and wherein ■ R' represents a hydrogen atom or a linear or branched C1-4 alkyl group, ■ R" represents a hydrogen atom or a linear or branched C1-4 alkyl group optionally substituted with a hydroxycarbonyl group; or ■ R' and R" together with the nitrogen atom to which they are attached form a 4 to 6 membered, saturated heterocyclic ring optionally substituted with a hydroxycarbonyl group. ? R2 represents a pyridyl group, a C3-6 cycloalkyl group or a phenyl group which is optionally substituted with one or more substituents selected from halogen atoms, cyano group, and C1-4 alkoxy group; and ? R3 represents a C3-6 cycloalkyl group, a C3-6 cycloalkyl-C1-2 alkyl group or a linear or branched C2-4 alkyl group optionally substituted with one or more substituents selected from halogen atoms and C1-2 alkoxy group.
