Patent HU-9903001-A2 (HU)
Title: Substituted pyrido- or pyrimido-containing 6,6- or 6,7-bicyclic derivatives
Inventor: CHEN YUHPYNG LIANG
IPC: A61K31/505
Filed: 1997-07-23
Abstract: Pyrido- and pyrimido- fused 6 or 7 membered azacyclic compounds of formula (I) and their salts are new. The dotted line = optional bond, provided that two are not adjacent; A = N or CR7; B = NR1R2, CR1R2R10, C(=CR2R11)R1, NHCR1R2R10, OCR1R2R10, SCR1R2R10, CR2R10NHR1, CR2R10OR1, CR2R10SR1, or COR2, all single bonded to D; or B = CR1R2 doubled to D which is C; D = N or CR4 single bonded to all attached atoms or D = C and is double bonded to B or to E; E = O, N, S, C(=O), C(=S), CR6R12, NR6 or CR6, or is a 2-atom spacer, being the above groups with an added CR6R12 or CR9; G, K = CO, CS, S, O, CHR8, or NR8 with both bonds to adjacent atoms single, or N or CR8 when double bonded to an adjacent atom; so that the 6 or 7-membered ring containing DEKG has 1-3 double bonds, 0-2 heteroatoms (O, N, S), and 0-2 CO or CS groups; R1 = 1-6C alkyl (optionally substituted by OH, halo, 1-4C alkoxy, CF3, COJ, COOJ, OC OJ, OCONJ(1-2C alkyl), NHCOJ, COOH, CONHJ, CONJ(1-2C alkyl), SJ, CN, NO2, SOJ, SO2J, SO2NHJ or SO2NJ(1-2C alkyl); J = 1-4C alkyl, optionally containing 1 or 2 double or triple bonds; R2 = 1-12C alkyl optionally containing 1-3 double or triple bonds, Ar, (1-4C alkylene)Ar, W or (1-6C alkylene)W (all optionally substituted by 1-3 of Cl, F, OH, or 1-4C alkyl, or one of 1-6C alkoxy, 1-6C alkylthio, 2-7C alkylcarbonyloxy, OCONJ(1-2C alkyl), S(1-6c alkyl), amino, 1-2C alkylamino, NJ(1-2C alkyl), NJCOJ, NHCOJ, N-(1-4C alkyl)-2-5C alkylcarbonyl-amido, carboxy, 2-5C alkoxycarbonyl or alkylaminocarbonyl and its N-(1-2C alkyl) derivative, thiol, CN, NO2, SOJ, SO2J, or SO2NHJ or SO2NJ(1-2C alkyl); or NR1R2 or CR1R2R10 = a 3-8 membered ring, of which the 5-8 membered rings optionally contain one or two double bonds, and one or two C atoms are optionally replaced by O, S, or NZ3; Z3 = H or 1-6C alkyl; Ar = phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl, pyrimidinyl, imidazolyl, furanyl, benzofuranyl, benzothiazolyl, isothiazolyl, pyrazolyl, pyrrolyl, indolyl, pyrrolo-pyridyl, oxazolyl or benzoxazolyl; W = 3-8C cycloalkyl, where one or two C atoms of W, or of the 5-8-membered (1-6C alkylene)W groups, may be replaced by O or S; R3 = H; 1-4C alkyl, alkoxy, alkylthio or alkylsulphonyl; or halo; R4 = H, 1-2C alkyl, OH or F; R6, R8, R9 attached to N = H or 1-4C alkyl; or attached to C = H, 1-2C alkyl, alkoxy, or alkylthio, halo, OH, hydroxymethyl, formyl, 2-3C alkylcarbonyl or alkoxycarbonyl, CF3, CN, NO2, amino, or N(1-2C alkyl)2, in which all 1-2C alkyl optionally contain one double or triple bond; R5 = phenyl, naphthyl, pyridyl, or pyrimidyl (all containing 2-4 substituents R15); one to three of R15 = Cl, 1-6C alkyl or alkoxy, or 1-6C alkylene-O-1-6C alkyl, and one = Br, I, formyl, CN, CF3, NO2, amino, NH(1-4C alkyl), N(1-6C alkyl)(1-2C alkyl), 2-5C alkylcarbonyl or alkoxycarbonyl, carboxy, SO2NH(1-4C alkyl), S(1-6C alkyl), NHSO2(1-4C alkyl), SO2NH2, SO2N(1-2C alkyl)(1-4C alkyl) or SO2(1-6C alkyl), and all alkyl in R15 optionally contain one or two substituents from F, OH, amino, NHMe, NMe2, or acetyl; R7 = H, Me, halo, OH, MeO, 2-3C alkylcarbonyl or alkoxycarbonyl, CF3, CF3, hydroxymethyl, or formyl; R10 = H, OH, MeO or F; R11 = H or 1-4C alkyl; R12 = H or Me; Z = NH, O, S, N(1-4C alkyl), or CR13R14; and R13, R14 = H or Me, or one of them = CN; provided that (a) in the 6 or 7-membered rings of (I) there can not be 2 double bonds adjacent each other; and (b) when D = carbon and is double bonded to B then B = CR1R2.