Patent DE-19526678-A1 (DE)
Title: New heterocyclic substd. piperazine derivs.
Inventor: PIEPER HELMUT DIPL CHEM DR
IPC: C07D211/58
Filed: 1995-07-21
Abstract: Pyrrolidinyl-, piperidinyl- and hexamethyleneimino-substd. piperazine derivs. (I) and their tautomers, stereoisomers (including mixtures) and salts are new. Ra = 3-pyrrolidinyl, 3- or 4-piperidinyl or 3- or 4- hexamethyleneiminyl opt. monosubstd. by 1-5C alkyl or aryl-1-3C alkyl (opt. monosubstd. on or in alkyl part by COOH, 1-3C alkoxycarbonyl, CONH2, CONH(1-3C alkyl), CON(1-3C alkyl)2, vinyl or ethynyl); or, when this substit. is not on a C atom  alpha  to N, by OH, 1-3C alkoxy, NH2, NH(1-3C alkyl) or N(1-3C alkyl)2; or 1-6C alkanoyl; benzoyl; allyloxycarbonyl; 1-5C alkoxycarbonyl; or phenyl-1-3C alkoxycarbonyl; Rb, Rc = H; 1-5C alkyl; aryl; or aryl-1-5C alkyl; or together with the ethylene bridge between them form o-phenylene; and the piperazinylene gp. in (I) can contain 1 or 2 CO gps. in place of 1 or 2 CH2 gps.; Y1 = -A1-; -CO-; -CO-CO-; -A1-CO-; -CO-A1-; -SO2-A2-; -A2-SO2-; -CO-A1-CO-; -CO-NR1-CO-; -CO-NR1-A2-; -CO-NR1-A2-CO-; -CO-A2-NR1-CO-; -CO-A2-O-; or -CO-A2-NR1; R1 = H; 1-5C alkyl; aryl; or aryl-1-3C alkyl; A1 = 1-5C n-alkylene opt. monosubstd. by 1-5C alkyl, cyclohexyl-1-3C alkyl, aryl, aryl-1-3C alkyl or, when not  alpha  to a N atom, R1O; A2 = 1-4C n-alkylene opt. monosubstd. by 1-5C alkyl, aryl or aryl-1-3C alkyl; Y2= phenylene; cyclohexylene; pyridinylene; 3- or 4- piperidinylene or 1,4-piperazinylene opt. contg. 1 CO gp. in place of 1 CH2 gp. adjacent to a N atom, and in the case of 4-piperidinylene opt. 4-substd. by R1O (N, O or O,O acetal or N, O or N,N bond must not be formed in linkage with Y1 or Y3); 1,4-ketopiperazinylene opt. monosubstd.  alpha  to CO gp. by 1-5C alkyl (opt. substd. by phenyl, R1O-phenyl, 1-3C alkoxycarbonyl or COOH); -NR1-B- linked to Y1 via the N atom; or -O-B- linked to Y1 via the O atom; B = phenylene; cyclohexylene; pyridinylene; or piperidinylene linked via the 3- or 4-position with the NR1 or O of Y2 and opt contg. 1 CO gp. in place of 1 CH2 gp. adjacent to a N atom; Y3 = -CO-; -A2-CO-; -CH2-CH(NHR2)-CO-; -NR2-A3-CO-; -CH2-NR2-A3-CO-; -O-A3-CO-; -CO-A3-CO-; or -CO-NR1-A3-CO-; A3 = 1-3C n-alkylene opt. monosubstd. by 1-5C alkyl, aryl, pyridyl or aryl-1-3C alkyl; R2 = H; 1-5C alkyl; aryl-1-3C alkyl; aryl; 1-5C alkoxycarbonyl; 1-5C alkylsulphonyl; aryl-1-3C alkylsulphonyl or arylsulphonyl; formyl opt. monosubstd. by 1-4C alkyl, aryl or aryl-1-3C alkyl; and -A2-CO-, -NR2-A3-CO- and -O-A3-CO- are linked with Y2 via A2, NR2 and O, respectively, and -NR2-A3-CO-, -CH2-NR2-A3-CO- and -O-A3-CO- cannot be linked with a N atom of Y2; E = OH; 1-6C alkoxy; phenyl-1-3C alkoxy; 3-9C cycloalkoxy (in which a 5-8C cycloalkyl ring is opt. mono- or disubstd. by 1-3C alkyl); 5-8C cycloalkoxy where a CH2 gp. in the 3- or 4-position of the cycloalkyl ring is (a) replaced by O or (b) replaced by imino opt. monosubstd. by alkyl, phenyl-1-3C alkyl, phenyl-1-3C alkoxy-carbonyl or 2-6C alkanoyl (the cycloalkane ring can also be opt. mono- or disubstd. by 1-3C alkyl); 4-7C cycloalkenyloxy; or 3-5C alkenyloxy or alkynyloxy both opt. substd. by phenyl ("provided that no C-O bonds are present where the C carries a double or triple bond"); 3-8C cycloalkyl-1-3C alkoxy; 8-10C bicycloalkoxy opt. mono- or disubstd. in bicycloalkyl gp. by 1-3C alkyl; 1,3-dihydro-3-oxo-1-isobenzofuranyloxy; or R5-CO-O-C(R<3>R<4>)-O-; or alpha -amino gp. of a natural amino acid or its 1-6C alkyl, 2-6C alkenyl, 5-7C cycloalkyl, phenyl or phenyl-1-3C alkyl ester; R3 = H; 1=6C alkyl; 3-7C cycloalkyl; or phenyl; R4 = H or 1-6C alkyl; R5 = 1-5C alkyl; 1-5C alkoxy; 5-7C cycloalkyl; or 5-7C cycloalkoxy.