Patent ID: 6313097
Filing Date: 2001-11-06
Classification: A61K,C07D,C07K

Abstract:
A compound of the formula ##STR20##R is a 1-piperidinyl group substituted in the 4 position by a mono- or di-unsaturated 5- to 7-membered aza, diaza, or triaza heterocyclic group bound via a nitrogen atom, which contains one or two carbonyl groups linked to a nitrogen atom,wherein the mono- or di-unsaturated 5- to 7-membered aza, diaza, or triaza heterocyclic groups of R are optionally substituted at a carbon atom by an optionally substituted phenyl group,wherein an olefinic double bond of one of the mono- or di-unsaturated 5- to 7-membered aza, diaza, or triaza heterocyclic groups of R is optionally condensed with a benzene, pyridine, diazine, 1,3-oxazole, thiophene, furan, thiazole, pyrrole, N-methyl-pyrrole, quinoline, imidazole, or N-methyl-imidazole ring or two olefinic double bonds in one of the di-unsaturated 5- to 7-membered aza, diaza, or triaza heterocyclic groups of R are optionally benzocondensed, andwherein the phenyl group optionally attached to the mono- or di-unsaturated 5- to 7-membered aza, diaza, or triaza heterocyclic groups of R and the benzo-, thieno-, pyrido-, and diazino-condensed heterocyclic groups of R are optionally, additionally mono-, di-, or trisubstituted in the carbon skeleton by fluorine, chlorine, or bromine atoms, by alkyl groups, cycloalkyl groups with 3 to 8 carbon atoms, nitro, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylsulphonylamino, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxy, carboxyalkyl, dialkylaminoalkyl, hydroxy, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, hydroxyalkylaminocarbonyl, (4-morpholinyl)carbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1-azepinyl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, methylenedioxy, aminocarbonylamino, aminocarbonylaminoalkyl, alkylaminocarbonylamino, alkanoyl, cyano, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl, or trifluoromethylsulphonyl groups, wherein the substituents are identical or different;Y is a divalent group selected from ##STR21##wherein R.sup.9 is an alkyl group with 1 to 4 carbon atoms or a phenyl group optionally substituted by a halogen atom or a methyl or methoxy group;X.sup.1, X.sup.2 and X.sup.3, which are identical or different, are a hydrogen atom, a fluorine, chlorine, or bromine atom, a branched or unbranched alkyl group, an alkoxy, trifluoromethyl, dialkylaminoalkyl, dialkylaminoalkoxy, nitro, hydroxy, amino, acetylamino, methylsulphonyloxy, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkanoyl, cyano, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl, or trifluoromethylsulphonyl group;A is a bond or the divalent group ##STR22##linked via the --CO group to the NR.sup.1 R.sup.2 group of formula I, whereinR.sup.7 is a hydrogen atom or a methyl group,R.sup.8 is a hydrogen atom, or a methyl, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, or acetyl group;R.sup.1 is a hydrogen atom,an alkyl group with 1 to 7 carbon atoms, which is optionally substituted in the .omega. position by a cyclohexyl, phenyl, pyridinyl, diazinyl, hydroxy, amino, alkylamino, dialkylamino, carboxy, aminocarbonyl, aminocarbonylamino, acetylamino, 1-pyrrolidinyl, 1-piperidinyl, 4-(1-piperidinyl)-1-piperidinyl, 4-morpholinyl, hexahydro-1H-1-azepinyl, [bis-(2-hydroxyethyl)]amino, 4-alkyl-1-piperazinyl, or 4-(.omega.-hydroxyalkyl)-1-piperazinyl group,a phenyl or pyridinyl group,wherein the heterocyclic groups and phenyl groups of R.sup.1 are optionally, additionally mono-, di-, or trisubstituted in the carbon skeleton by fluorine, chlorine, or bromine atoms, by methyl, alkoxy, trifluoromethyl, hydroxy, amino, acetylamino, aminocarbonyl, cyano, methylsulphonyloxy, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl, or trifluoromethylsulphonyl groups, wherein the substituents are identical or different,R.sup.2 is a hydrogen atom or an alkyl group with 1 to 3 carbon atoms optionally substituted by a phenyl or pyridinyl group, orR.sup.1 and R.sup.2 together with the included nitrogen atom are a group of general formula III ##STR23##Y.sup.1 is a carbon atom or, if R.sup.4 is a free pair of electrons, a nitrogen atom,m is the number 0, 1, or 2,n is the number 0, 1, or 2,R.sup.3 is a hydrogen atom, or an amino, alkylamino, dialkylamino, alkyl, cycloalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aminoiminomethyl, aminocarbonylamino, alkylaminocarbonylamino, cycloalkylaminocarbonylamino, phenylaminocarbonylamino, aminocarbonylalkyl, aminocarbonylaminoalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxyalkyl, or carboxy group,a phenyl, pyridinyl, diazinyl, 1-naphthyl, 2-naphthyl, pyridinylcarbonyl, or phenylcarbonyl group, each of which is optionally mono-, di-, or trisubstituted in the carbon skeleton by fluorine, chlorine, or bromine atoms, by alkyl, alkoxy, methylsulphonyloxy, trifluoromethyl, hydroxy, amino, acetylamino, aminocarbonyl, aminocarbonylamino, aminocarbonylaminomethyl, cyano, carboxy, carbalkoxy, carboxyalkyl, carbalkoxyalkyl, alkanoyl, .omega.-(dialkylamino)alkanoyl, .omega.-(dialkylamino)alkyl, .omega.-(dialkylamino)hydroxyalkyl, .omega.-(carboxy)alkanoyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl, or trifluoromethylsulphonyl groups, wherein the optional substituents are identical or different,a 4- to 10-membered azacycloalkyl group, a 5- to 10-membered oxaza, thiaza, or diazacycloalkyl group, or a 6- to 10-membered azabicycloalkyl group, wherein the mono- and bicyclic heterocyclic groups of R.sup.3 are bound via a nitrogen or carbon atom,a 1-alkyl-4-piperidinylcarbonyl or 4-alkyl-1-piperazinylcarbonyl group,wherein the mono- and bicyclic heterocyclic groups and the 1-alkyl-4-piperidinylcarbonyl and 4-alkyl-1-piperazinylcarbonyl group of R.sup.3 are optionally substituted in the ring by an alkyl group with 1 to 7 carbon atoms, by an alkanoyl, dialkylamino, phenylcarbonyl, pyridinylcarbonyl, carboxyalkanoyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, alkylsulphonyl, cycloalkyl, or cycloalkylalkyl group, or by a cycloalkylcarbonyl, azacycloalkylcarbonyl, diazacycloalkylcarbonyl, or oxazacycloalkylcarbonyl group optionally alkyl-substituted in the ring,wherein the alicyclic moieties contained in these substituents contain 3 to 10 ring members and the heterocyclic moieties each contain 4 to 10 ring members, andwherein the phenylcarbonyl and pyridinylcarbonyl substituents are optionally mono-, di-, or trisubstituted by fluorine, chlorine, or bromine atoms, by alkyl, alkoxy, methylsulphonyloxy, trifluoromethyl, hydroxy, amino, acetylamino, aminocarbonyl, aminocarbonylamino, aminocarbonylaminomethyl, cyano, carboxy, carbalkoxy, carboxyalkyl, carbalkoxyalkyl, alkanoyl, .omega.-(dialkylamino)alkanoyl, .omega.-(carboxy)alkanoyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl, or trifluoromethylsulphonyl groups, wherein the substituents are identical or different, orR.sup.3 together with R.sup.4 and Y.sup.1 are a 4- to 7-membered cycloaliphatic ring, in which a methylene group is optionally replaced by the group --NH-- or --N(alkyl)--,wherein a hydrogen atom bound to a nitrogen atom within the group R.sup.3 is optionally replaced by a protecting group;R.sup.4 is a hydrogen atom,an alkyl group with 1 to 4 carbon atoms, wherein an unbranched alkyl group is optionally substituted in the .omega. position by a phenyl, pyridinyl, diazinyl, amino, alkylamino, dialkylamino, 1-pyrrolidinyl, 1-piperidinyl, 4-methyl-1-piperazinyl, 4-morpholinyl, or hexahydro-1H-1-azepinyl group,an alkoxycarbonyl, cyano, or aminocarbonyl group, or a free pair of electrons, if Y.sup.1 is a nitrogen atom, andR.sup.5 and R.sup.6 are each a hydrogen atom or,if Y.sup.1 is a carbon atom, R.sup.4 together with R.sup.6 also constitute another carbon-carbon bond, wherein R.sup.5 is a hydrogen atom, orif Y.sup.1 is a carbon atom, R.sup.4 together with R.sup.6 also constitute a further carbon-carbon bond and R.sup.3 together with R.sup.5 and the enclosed double bond constitute a partially hydrogenated or aromatic five- to seven-membered, mono- or bicyclic carbocyclic or heterocyclic group,wherein all the abovementioned alkyl and alkoxy groups as well as the alkyl groups present within the other groups mentioned contain 1 to 7 carbon atoms, unless otherwise specified, and all the abovementioned cycloalkyl groups as well as the cycloalkyl groups present within the other groups mentioned contain 5 to 10 carbon atoms, unless otherwise specified,or a tautomer, diastereomer, or enantiomer thereof, or a pharmaceutically acceptable salt thereof.