Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Patent
1998-09-22
2000-08-15
Killos, Paul J.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
560 51, 560 76, 560 21, 560118, 560127, 562500, 562509, 564156, 564169, 564191, 514532, 514533, 514545, 514574, C07C 6976
Patent
active
06103925&
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to dimethyl-substituted cyclohexanediene derivatives, to a process for their preparation and to their use as pharmaceuticals.
It has already been disclosed that 3,6-cyclohexanediene-2-phenyl-1,3-dicarboxylic esters have a muscle contraction-inhibiting effect [compare in this connection Chem. Pharm. Bull., 39 (11), 2915-23, 1991; GB 87-18906 870810/GB 87-19441 870817].
The invention relates to dimethyl-substituted cyclohexanediene derivatives of the general formulae (Ia,b) ##STR1## in which A represents cycloalkyl having 3 to 6 carbon atoms or substituted up to 3 times, identically or differently, by nitro, cyano, cycloalkyl having 3 to 7 carbon atoms, halogen, trifluoromethyl or by straight-chain or branched alkylthio, alkyl or alkoxy, each having up to 6 carbon atoms, having up to 8 carbon atoms, hydroxyl or represent a group of the formula --NR.sup.3 R.sup.4, branched alkyl having up to 4 carbon atoms,
Preferred salts are physiologically acceptable salts. These are generally salts of the compounds according to the invention with inorganic or organic acids. Preferred salts are those with inorganic acids such as, for example, hydrochloric acid, hydrobromic acid, phosphoric acid or sulphuric acid, or salts with organic carboxylic or sulphonic acids such as, for example, acetic acid, maleic acid, fumaric acid, malic acid, citric acid, tartaric acid, lactic acid, benzoic acid, or methanesulphonic acid, ethanesulphonic acid, phenylsulphonic acid, toluenesulphonic acid or naphthalenedisulphonic acid.
The compounds according to the invention may exist in stereoisomeric forms which are related either as image and mirror image (enantiomers), or which are not related as image and mirror image (diastercomers). The invention relates both to the antipodes and to the racemic forms, and to the mixtures of diastereomers. The racemic forms can, just like the diastereomers, be separated in a known manner into the stereoisomerically pure constituents.
Compounds of the general formula (la,b) substituted up to 3 times, identically or differently, by nitro, cyano, fluorine, chlorine, bromine, iodine, cyclopentyl, cyclohexyl, trifluoromethyl or by straight-chain or branched alkylthio, alkyl or alkoxy each having up to 4 carbon atoms, having up to 6 carbon atoms, hydroxyl or represent a group of the formula --NR.sup.3 R.sup.4, carbon atoms,
Compounds of the general formula (Ia,b) up to 3 times, identically or differently, by nitro, cyano, fluorine, chlorine, bromine, iodine, trifluoromethyl, cyclohexyl, methyl, methoxy or by methylthio, having up to 5 carbon atoms, hydroxyl or represent a group of the formula --NR.sup.3 R.sup.4,
In addition, a process for preparing the compounds according to the invention of the general formulae (Ia) and (Ib) has been found, characterized in that ##STR2## in which A and R.sup.1 have the abovementioned meanings are reacted with compounds of the general formula (III) ##STR3## in which R.sup.2 has the abovementioned meanings, --P(O)(OR.sup.5)(OR.sup.6), branched alkyl having up to 4 carbon atoms, R.sup.1 /R.sup.2 .noteq.OH the esters are hydrolysed by customary methods, reacted with ammonium or the appropriate amines (NHR.sup.3 R.sup.4), derivatives of the general formula (Ia,b) an aluminium trimethyl-mediated aminolysis is carried out by the amines (NHR.sup.3 R.sup.4) or their hydrochlorides.
The resulting double-bond isomers can be separated by chromatography and/or crystallization.
The process according to the invention can be explained by way of example by the following formula diagram: ##STR4##
Suitable solvents are all inert organic solvents which are not changed under the reaction conditions. These preferably include alcohols such as methanol, ethanol, propanol or isopropanol, or ethers such as diethyl ether, dioxane, tetrahydrofuran, glycol dimethyl ether, or diethylene glycol dimethyl ether, acetonitrile, or amides such as hexamethylphosphoramide or dimethylformamide, or halogenated hydrocarbons such as methylene chloride, tetrachloromethane or hydrocarbons su
REFERENCES:
Abstract of JP 02-00129A.
Chemical and Pharmaceutical Bulletin, vol. 39, No. 11, Nov. 1991, Tokyo JP, pp. 2915-2923, XP002033122; Kazuhiko Take et al.: Agents for the Treatment of Overactive Detrusor.I.Synthesis and Structure-Activity Relationships of 1,1'-Biphenyl Derivatives.
Mauler Frank
Urbahns Klaus
Bayer Aktiengesellschaft
Killos Paul J.
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