New arylalkanol derivatives used for treating e.g. respiratory diseases, joint diseases, vascular inflammations, skin disorders, kidney and liver diseases and neurological diseases

摘要

Arylalkanol derivatives (I) are new. Arylalkanol derivatives of formula A-C(R 1)(R 2)-CH 2-C(OH)(R 3)-B'-NH-Q (I) and their isomers and salts are new, except for phthalazinone derivatives. A : aryl, benzyl or phenethyl (all optionally substituted by at least 1 1-5C alkyl, 1-5C alkoxy, 1-5C alkylthio, 1-5C perfluoroalkyl, halo, OH, CN, NO 2, O(CH 2) n, O(CH 2) nCH 2, OCH=CH, (CH 2) n+2 or NR 4R 5); n : 1 or 2; R 4, R 5 : H, 1-5C alkyl or 2-6C alkanoyl; R 1, R 2 : H, Me or Et, or R 1 + R 2 : 3-6C cycloalkane; R 3 : 1-8C alkyl (optionally substituted by at least 1 halo, OH or 1-3C alkoxy), optionally fluorinated 1-3C alkyl or 2-6C alkenyl, 2-6C alkynyl, 3-8C cycloalkyl, 3-7C heterocyclyl, aryl, heteroaryl, (1-8C)alkyl(3-8C)cycloalkyl, (1-8C alkyl)aryl or (1-8C alkyl)heteroaryl (all optionally substituted); B' : CH 2, CHMe, CHEt or CO, and Q : quinazolinyl, quinoxalinyl, cinnolinyl, indazolyl, phthalazinyl, naphthyridinyl, benzothiazolyl, dihydroindolonyl, dihydroisoindolonyl, benzimidazolyl or indolyl (all optionally substituted by at least 1 1-5C alkyl, 1-5C alkoxy, 1-5C alkylthio, 1-5C perfluoroalkyl, halo, OH, CN, NO 2 or NR 4R 5). An independent claim is also included for the preparation of (I). ACTIVITY : Antiinflammatory; Antiallergic; Immunosuppressive; Antiasthmatic; Antirheumatic; Antiarthritic; Dermatological; Antipsoriatic; Antipruritic; Cytostatic; Nephrotropic; Hepatotropic; Antiulcer; Vasotropic; Ophthalmological; Cerebroprotective; Neuroprotective; Thyromimetic; Antiemetic; Analgesic; Gastrointestinal-Gen.; Auditory; Hemostatic; Endocrine-Gen. MECHANISM OF ACTION : Glucocorticoid receptor (GR) ligand. In a GR binding assay, results showed that 4-(5-fluoro-2-methoxyphenyl)-4-methyl-1-(2-methyl-5-quinazolinylamino)-2-trifluoromethyl-2-pentanol (Ia) exhibited an IC 50 value of 1.8 nM.