New carbonylamino-substituted anilino-pyrimidine compounds are tyrosine kinase-2 inhibitors, useful for treating diseases associated with inflammatory conditions e.g. bronchitis, rheumatoid arthritis, psoriasis and Guillain Barre syndrome

摘要

Carbonylamino-substituted anilino-pyrimidine compounds (I) or their salts, diastereomers and enantiomers are new. Carbonylamino-substituted anilino-pyrimidine compounds of formula (I) or their salts, diastereomers and enantiomers are new. R 11-6C alkyl, 2-6C alkenyl, 3-6C cycloalkyl or 3-6 membered heterocycloalkyl (optionally mono- or poly-substituted with halo, OH, 1-6C alkyl, 1-6C alkoxy, 1-6C alkylthio, 3-6C cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered monocyclic heteroaryl and/or phenyl); R 22-6C alkyl (mono- or poly-substituted with OH); R 3H or F; R 4, R 5H, halo, CH 3or CF 3; and R 6H or halo. An independent claim is included for the preparation of (I). [Image] ACTIVITY : Antiinflammatory; Respiratory-Gen.; Antiasthmatic; Antibacterial; Antirheumatic; Immunomodulator; Antiarthritic; Antipyretic; Vasotropic; Dermatological; Muscular-Gen.; Antiallergic; Antipsoriatic; Antipruritic; Endocrine-Gen.; Cytostatic; Nephrotropic; Hepatotropic; Gastrointestinal-Gen.; Antiulcer; Ophthalmological; Cerebroprotective; CNS-Gen.; Neuroprotective; Nootropic; Hemostatic; Antianemic; Antithyroid; Antidiabetic; Gynecological. MECHANISM OF ACTION : Tyrosine kinase-2 (Tyk2) inhibitor. The Tyk2 inhibitory activity of (I) was tested in a recombinant fusion protein using Tyk2-homogeneous time resolved fluorescence assay. The results showed that cyclobutanecarboxylic acid {3-[4-(1-hydroxymethyl-2-methyl-propylamino)-pyrimidin-2-yl-amino]-phenyl}-amide exhibited an IC 50value of 1 mole/l.