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New indazole squaric acid compounds are checkpoint kinase-1 modulators, useful to treat or prevent e.g. cancer, diabetes mellitus, microangiopathy, glaucoma, cataract, bacterial infections, cell aging, stress, and arteriosclerosis
New indazole squaric acid compounds are checkpoint kinase-1 modulators, useful to treat or prevent e.g. cancer, diabetes mellitus, microangiopathy, glaucoma, cataract, bacterial infections, cell aging, stress, and arteriosclerosis
Indazole squaric acid compounds (I) and their derivatives, tautomers, salts, solvates and/or stereoisomers, are new. Indazole squaric acid compounds of formula (I) and their derivatives, tautomers, salts, solvates and/or stereoisomers, are new. R : H, A, COOA, CONHA, CONA 2 or (CH 2) mAr; B 1, B-a : CH or N; R 1H, A, Hal, CN, NO 2, C(=O)A, CHO, CH(OH)A, NH 2, NH(C=O)A, COOH, COOA, SO 2NH 2, CONH 2, CONA 2, (CH 2) mAr or Het; R 2OH, OA, Hal, CF 3, SO 2NH 2, NHAc or NHSO 2A; R-2a, R-2b : H or Hal; R 3H, Hal, NH 2, NHA, NA 2, NHCOA, NHCONHA, NHCONHAr, NHCO(CH 2) mAr, Het 1, NHCO(CH 2) nOA, NHCO(CH 2) mHet, NHCOCH(Ar)OC(=O)A, NHCO(CH 2) mO(CH 2) nOA, NHCOCH(Ar)A, NHCOCH(Ar)OH, NHCO(CH 2) mNH 2, NHCO(CH 2) mNHA, NHCO(CH 2) nNA 2, NHCO(CH 2) nNHAc, NHCO(CH 2) nNA(CH 2) nOA, NHCO(CH 2) nN(BOC)A, NHCO(CH 2) nNH(BOC), NHCO(CH 2) nNHCHO, NHCO(CH 2) nNHOH, piperazine compound of formula (a), NHCO(CH 2) nNHA or NHCO(CH 2) nNA 2; Ac : acetyl; Ar : phenyl (optionally substituted with 1-3 substituents of Hal, A, OH, OA, NH 2, NHA, NA 2, NO 2, CN, COOH, COOA, CONH 2, NHCOA, NHCONH 2, NHSO 2A, SO 2NH2, S(O) mA, (CH 2) mHet 1, (CH 2) mNH(CH 2) nOA,(CH 2) mNH(CH 2) mNA 2, (CH 2) mNH(CH 2) mNHA and/or (CH 2)mNH(CH 2)mNH2); Het : furyl, thienyl, pyrrolyl, imidazolyl, pyridyl, pyrimidinyl, pyrazolyl, thiazolyl, piperazinyl, indolyl, piperidinyl, pyrrolidinyl, morpholinyl or triazolyl (optionally substituted with 1-3 substituents of A, Hal, OH or OA); Het 1morpholinyl, pyrrolidinyl, piperidinyl, pyrazolyl, furyl, thienyl, pyrrolyl, imidazolyl, pyridyl, piperazinyl or pyrimidinyl (optionally substituted with 1-3 substituents of A, Hal, OH or OA); A : 1-10C alkyl (where 1-7 H atoms are substituted by F); X : absent, CH 2, CHA, CA 2 or a cyclic compound of formula (b); Hal : F, Cl, Br or I; m : 0-2; and n : 1-4. Independent claims are included for: (1) the preparation of (I); and (2) a kit comprising divided packings of (I) and an active agent. [Image] ACTIVITY : Cytostatic; Antidiabetic; Anorectic; Analgesic; Antianginal; Antilipemic; Cardiant; Nephrotropic; Antiinflammatory; Neuroprotective; Anticoagulant; Ophthalmological; Antibacterial; Nootropic; Tranquilizer; Hypotensive; Antiarteriosclerotic; Hepatotropic; Respiratory-Gen.; Antirheumatic; Dermatological; CNS-Gen.; Vulnerary; Cardiovascular-Gen. MECHANISM OF ACTION : Serine-/threonine kinase signal transduction modulator; Checkpoint kinase-1 modulator; Checkpoint kinase-2 modulator; Serum and glucocorticoid-induced protein kinase inhibitor. The ability of (I) to inhibit serum and glucocorticoid-induced protein kinase was tested using biological assays. The results showed that 3-(3-benzoylamino-1H-indazol-5-ylamino)-4-[(R)-1-(3-methoxy-phenyl)-ethylamino]-cyclobut-3-en-1,2-dione (Ia) exhibited an IC 50 value of 10 nM.
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