Patent HU-9902914-A3 (HU)
Title: Substituted 6,6-heterobicyclic derivatives as corticotropin releasing factor (hormone) crf (crh) antogonists and use thereof
Filed: 1997-07-21
Abstract: Pyrido- and pyrimido- fused azinones of formula (I) and their salts are new. The DEKG ring is 6 or 7 membered, contains 1-3 double bonds, 0-2 heteroatoms from O, N, S, and 0-2 CO or CS groups, provided that there are not two adjacent double bonds; A = N or CR7; B = NR1R2, CR1R2R10, C(=CR2R11)R1, NHCR1R2R10, OCR1R2R10, SCR1R2R10, CR2R10NHR1, CR2R10OR1, CR2R10SR1, or COR2; G = N or CR4 when singly bonded to all atoms, or C when doubly bonded to K; K = N or CR6 when doubly bonded to G or E; or O, S, CO, CS, CR6R12 or NR8 when singly bonded to adjacent ring atoms; or K = a two atom spacer, one unit of which is O, N, S, CO, CS, CR6R12, NR6, or CR6, the other is CR6R12 or CR9; D, E = CO, CS, S, O, CR4R6, or NR8 when singly bonded to adjacent ring atoms, or N or CR4 when doubly bonded to adjacent ring atoms; R1 = 1-6C alkyl (optionally substituted by 1 or 2 OH, halo, 1-4C alkoxy or alkylthio, CF3, 2-5C alkylcarbonyl, alkoxycarbonyl, or alkylcarbonyloxy, (1-4C alkyl)(1-2C alkyl)aminocarbonyloxy(2-5C alkanoylamido), COOH, CONH(1-4C alkyl), CON(1-4C alkyl)(1-2C alkyl), CN, NO2, 1-4C alkylsulphinyl or alkylsulphonyl, SO2NH(1-4C alkyl), or SO2NH(1-4C alkyl)(1-2C alkyl)), in which all alkyl groups optionally contain 1 or 2 double or triple bonds; halo = Br, Cl, I or F; R2 = 1-12C alkyl, optionally containing 1-3 double or triple bonds, aryl or 1-4C alkylene(aryl); 3-8C cycloalkyl, or 3-8C cycloalkyl(1-6C alkylene) (all optionally substituted by 1-3 of Cl, F, OH or 1-4C alkyl, or one of 1-6C alkoxy or alkylthio, 2-7C alkoxycarbonyl or OCON(1-4C alkyl)(1-2C alkyl), amino, 1-2C alkylamino, (1-4C alkyl)(1-2C alkyl)amino, 2-5C alkanoylamido, N-(1-4C alkyl)-(2-5C alkanoyl)amido, carboxy, 2-5C alkoxycarbonyl or alkylaminocarbonyl, N-(1-2C alkyl)(2-5C alkylaminocarbonyl), thiol, CN, NO2, 1-4C alkylsulphinyl, alkylsulphonyl, or alkylamino-sulphonyl, or N,N-(1-2C alkyl)(1-4C alkyl)aminosulphonyl; aryl = phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl, pyrimidinyl, imidazolyl, furanyl, benzofuranyl, benzothiazolyl, isothiazolyl, pyrazolyl, pyrrolyl, indolyl, pyrrolo-pyridyl, oxazolyl, or benzoxazolyl; cycloalkyl optionally has one or two C atoms replaced by O, S, or NZ; or NR1R2 or CR1R2R10 = a 3-8 membered ring radical, of which the 5-8 membered rings optionally contain 1 or 2 double bonds and/or one or two ring C atoms can be replaced by O, S or NZ; Z = H, 1-4C alkyl, or benzyl; R3 = H, 1-4C alkyl, alkoxy, alkylthio, or alkylsulphonyl, or halo; R8, R9, R12 = H or 1-2C alkyl; R6 attached to N = H or 1-4C alkyl; R4, and R6 attached to C = H, 1-6C alkyl, halo, hydroxy, 1-2C hydroxyalkyl, CF3, CN, NO2, amino, 1-4C alkoxy or alkylthio, N,N-(1-2C alkyl)(1-4C alkyl)amino, CH2SMe, CHO, or 2-5C alkylcarbonyl or alkoxycarbonyl, and in which all 1-2C alkyl optionally contain one double or triple bond; R5 = phenyl, naphthyl, pyridyl, or pyrimidyl (all substituted by 2-4 substituents, of which 1-3 are selected from Cl, 1-6C alkyl or alkoxy, or 1-6C alkylene-O-1-6C alkyl, and one from Br, I, CN, NO2, formyl, CF3, amino, 1-4C alkylamino, N,N-(1-2C alkyl)(1-6C alkyl)amino, 2-5C alkylcarbonyl or alkoxycarbonyl, carboxy, aminosulphonyl, 1-4C alkylamino-sulphonyl, N,N-(1-2C alkyl)(1-4C alkyl)aminosulphonyl, 1-4C alkyl-sulphonamido, (1-2C alkylthio, alkylsulphinyl, or alkylsulphonyl)-J, or 1-4C hydroxyalkylene, in which all 1-4C and 1-6C alkyl optionally contain 1 or 2 substituents from F, OH, amino, methylamino, dimethylamino or acetyl; J = 0-1C alkylene; R7 = H, Me, halo, OH, MeO, 2-3C alkylcarbonyl or alkoxycarbonyl, hydroxymethyl, CF3 or formyl; R10 = H, OH, MeO or F; and R11 = H or 1-4C alkyl. Also new are quinolines either (a) having at the 4-position a hydroxy group, of formula (IVA); or (b) a leaving group, of formula (IIA). T = Cl, Br, I, or triflyl-oxy.