Patent DE-102004009933-A1 (DE)
Title: Use of 1,3,4-thiadiazole derivatives to prepare medicaments for treating diseases in which the inhibition, regulation or modulation of kinase signal transduction plays a role
Inventor: BURGDORF LARS
IPC: C07D285/135
Filed: 2004-02-26
Abstract: 1,3,4-Thiadiazole derivatives (I) are used to prepare medicaments for preventing or treating diseases in which the inhibition, regulation or modulation of kinase signal transduction plays a role. 1,3,4-Thiadiazole derivatives of formula (I) and their derivatives, solvates, salts and stereoisomers are used to prepare medicaments for preventing or treating diseases in which the inhibition, regulation or modulation of kinase signal transduction plays a role. Ar 1>phenyl, naphthyl, biphenylyl or Het, all optionally substituted with 1-4 of R 1>; Ar 2>phenyl, naphthyl, biphenylyl or Het, all optionally substituted with 1-4 of R 2>; Y : O, S, CHNO 2, C(CN) 2 or NR 4>; Z : O, S, CH 2(CH 2) n, (CH 2) nCHA, CHA(CH 2) n; CO, CHOH, (CHA) nO, (CH 2) nO, O(CHA) n, O(CH 2) n, (CH 2) nS, S(CH 2) n, (CH 2) nNH, NH(CH 2) n, (CH 2) nNA, NA(CH 2) n, CHHal or C(Hal) 2; Het : mono- or bicyclic heteroaryl with 1-4 N, O and/or S atoms; R 1>, R 2>A, Ar', OR 3>, SR 3>, OAr', SAr', N(R 3>) 2, NHAr', Hal, NO 2, CN, (CH 2) nCOOR 3>, (CH 2) nCON(R 3>) 2, COR 3>, SO mA, SO mAr', NHCOA, NHCOAr', NHSO mA. NHSO mAr', SO mN(R 3>) 2, O(CH 2) nN(R 3>) 2, O(CH 2) nNHR 3>, O(CH 2) nNA 2, O(CH 2) nC(Me) 2(CH 2) nN(R 3>) 2, NH(CH 2) n(CH 2) 2(CH 2) nN(R 3>) 2, O(CH 2) nN(R 3>)SO mA, O(CH 2) nN(R 3>)SO mN(R 3>)A, O(CH 2) nN(R 3>)SO mAr', (CH 2) nN(R 3>)SO mA, (CH 2) nN(R 3>)SO mN(R 3>)A, (CH 2) nN(R 3>)SO mAr', O(CH 2) nSO mA, O(CH 2) nSO mN(R 3>)A, O(CH 2) nSO mAr', (CH 2) nSO mA, (CH 2) nSO mN(R 3>)A, (CH 2) nSO mAr', NH(CH 2) nNH 2, NH(CH 2) nNHA, NH(CH 2) nNA 2, NA(CH 2) nNH 2, NA(CH 2) nNHA, NA(CH 2) nNA 2, O(CH 2) nHet 1> or Het 1>; R 3>H, A or (CH 2) nAr'; R 4>H, CN, OH, A, (CH 2) nAr', COR 3>, COAr', SO mA or SO mAr'; Ar' : phenyl optionally substituted with 1-5 of A, Ph, OH, OA, SH, SA, OPh, SPh, NH 2, NHA, NA 2, NHPh, Hal, NO 2, (CH 2) nCOOH, (CH 2) nCOOA, (CH 2) nCONH 2, (CH 2) nCONHA, CHO, COA, SO mA, SO mAPh, NHCOA, NHCOPh, NHSO 2A, NHSO 2Ph or SO 2NH 2; Ph : phenyl optionally substituted with 1-3 of A, Hal, CN, COOR (R is not defined), COOH, NH 2, NO 2, OH or OA; Het 1>monocyclic saturated heterocyclyl with 1-4 N, O and/or S atoms, optionally substituted with 1-3 of Hal, A, OA, (CH 2) nOH, (CH 2) nHal, NH 2, =NH, =NOH, =NOA and/or =O; A : 1-10C alkyl or haloalkyl; Hal : F, Cl, Br or I; n : 0-5; m : 0-2. Independent claims are also included for: (1) new compounds (I), namely 1-(2-methoxy-5-trifluoromethyl-phenyl)-3-(5-pyridin-4-ylmethyl-[1,3,4]thiadiazol-2-yl}-urea, 1-(5-chloro-2-methoxy-4-methyl-phenyl)-3-[5-(3,4-dimethoxybenzyl)-[1,3,4]thiadiazol-2-yl]-urea, 1-[5-(3,4-dimethoxybenzyl)-[1,3,4]thiadiazol-2-yl]-3-(3-trifluoromethoxy-phenyl)-urea, 1-[5-(1-phenyl-ethyl)-[1,3,4]thiadiazol-2-yl]-3-(3-trifluoromethylsulfonyl-phenyl)-urea, 1-[5-(3,4-dimethoxy-benzyl)-[1,3,4]thiadiazol-2-yl]-3-(2-methoxy-5-trifluoromethyl-phenyl)-urea, 1-[5-(1-phenyl-ethyl)-(1,3,4]thiadiazol-2-yl]-3-p-tolyl-urea, 1-(2-methoxy-5-methyl-phenyl)-3-[5-(1-phenyl-ethyl)-[1,3,4]thiadiazol-2-yl]-urea, 1-(3-chloro-4-methyl-phenyl)-3-(5-(1-phenyl-ethyl)-[1,3,4]thiadiazol-2-yl]-urea, 1-(5-chloro-2-methyl-phenyl)-3-[5-(1-phenyl-ethyl)-[1,3,4]thiadiazol-2-yl]-urea, 1-(3-chloro-2-methyl-phenyl)-3-[5-(1-phenyl-ethyl)-[1,3,4]thiadiazol-2-yl]-urea, 1-(5-chloro-2-methoxy-phenyl)-3-[5-(1-phenyl-ethyl)-[1,3,4]thiadiazol-2-yl]-urea, 1-[5-(1-phenyl-ethyl)-[1,3,4]thiadiazol-2-yl]-3-(3-trifluoromethyl-phenyl)-urea, 1-[5-(1-phenyl-ethyl)-[1,3,4]thiadiazol-2-yl]-3-(4-trifluoromethyl-phenyl)-urea, 1-[5-(3,4-dimethoxy-benzyl)-[1,3,4]thiadiazol-2-yl]-3-(2-methoxy-phenyl)-urea, 1-[5-(1-phenyl-ethyl)-[1,3,4]thiadiazol-2-yl]-3-(4-trifluoromethoxy-phenyl)-urea, 1-(4-fluoro-3-trifluoromethyl-phenyl)-3-[5-(1-phenyl-ethyl)-[1,3,4]thiadiazol-2-yl]-urea, 1-(4-chloro-3-trifluoromethyl-phenyl)-3-[5-(1-phenyl-ethyl)-[1,3,4]thiadiazol-2-yl]-urea, 1-[5-(2.3-dimethoxy-benzyl)-[1,3,4]thiadiazol-2-yl]-3-(4-trifluoromethoxy-phenyl)-urea, 1-[5-(2,3-dimethoxy-benzyl)-[1,3,4]thiadiazol-2-yl]-3-(2-trifluoromethoxy-phenyl)-urea, 1-(5-chloro-2,4-dimethoxy-phenyl)-3-[5-(3,4-dimethoxy-benzyl)-[1,3,4]thiadiazol-2-yl]-urea, 1-(2,4-dimethoxy-phenyl) -3-[5-(1-phenyl-ethyl)-[1,3,4]thiadiazol-2-yl]-urea, 1-(3-chloro-4-methoxy-phenyl)-3-[5-(1-phenyl-ethyl)-[1,3,4]thiadiazol-2-yl]-urea, 1-[2-(2-dimethylamino-ethoxy)-5-trifluoromethyl-phenyl]-3-[5-(1-phenyl-ethyl)-[1,3,4]thiadiazol-2-yl]-urea; (2) a process for preparing the new compounds (I); (3) kit comprising a compound (I) and another drug in separate packaging. [Image] ACTIVITY : Cytostatic; Antipsoriatic; Gynecological; Antiinflammatory; Vulnerary; Antiarthritic; Antibacterial; Antiulcer; Virucide; Immunosuppressive; Anti-HIV. No biological data given. MECHANISM OF ACTION : Kinase inhibitor.