Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1989-09-19
1991-02-19
Shen, Cecilia
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514253, 514318, 544360, 544364, 546193, 546194, A61K 31495, A61K 3144, C07D40112
Patent
active
049944614
DESCRIPTION:
BRIEF SUMMARY
FIELD OF APPLICATION OF THE INVENTION
The invention relates to novel enantiomers processes for their preparation, their use and medicaments which contain them. The compounds according to the invention are used in the pharmaceutical industry for the preparation of medicaments.
1. Known Prior Art
It is known that certain 1,4-dihydropyridine derivatives substituted in the 4-position have pharmacologically useful properties. It is also known that these 1,4-dihydropyridine derivatives, provided that they are differently (asymmetrically) substituted in positions 2 and 6 and/or in positions 3 and 5 - have a centre of chirality in position 4. It is also known that the pharmacological properties of the 1,4-dihydropyridines can be influenced by the absolute configuration in the 4-position. Because of these different pharmacological properties, various attempts have already been made to prepare pure 1,4-dihydropyridine enantiomers [see, for example, German Offenlegungsschrift 2,935,451, German Offenlegungsschrift 3,320,616, EP-A2 0166296, Shibaruma et al. Chem. Pharm. Bull. 28, 2809 (1980)]. However, either the known processes cannot be used to prepare all possible enantiomers of known 1,4-dihydropyridines or these processes give the pure 1,4-dihydropyridine enantiomers only in low yields or in insufficient purity.
2. Description of the Invention
Surprisingly, a novel process for the preparation of pure, optically active 1,4-dihydropyridine enantiomers has now been found, which gives the desired enantiomers in good yield and high purity. This process can be used for the preparation of novel enantiomers of the known 1,4-dihydropyridines.
The invention thus relates firstly to pure dihydropyridine enantiomers of the formula I ##STR2## wherein Cy represents a cyclic radical of the formula ##STR3## in which Y denotes oxygen (O), sulphur (S), vinylene (--CH.dbd.CH--), azomethine (--CH.dbd.N--) or a group of the formula ##STR4## R1 and R2 are identical or different and denote hydrogen, 1-6C-alkyl or 3-7C-alkoxyalkyl,
R3 denotes 1-6C-alkyl or 3-7C-alkoxyalkyl,
R4 and R5 are identical or different and denote hydrogen, hydroxyl, halogen, nitro, cyano, trifluoromethyl, 1-4C-alkyl, 1-4C-alkoxy, completely or partially fluorine-substituted 1-4C-alkoxy, 1-4C-alkoxycarbonyl or 2-5C-acyl or together denote methylenedioxy, or denote amino or mono- or di-1-4C-alkylamino,
E denotes straight-chain or branched 2-5C-alkylene which may be substituted by 1-4C-alkoxy or aryl,
A denotes --CH.sub.2 --C(R6)R7--CH.sub.2 -- or --CH.sub.2 --NR8--CH.sub.2 --,
R6 denotes hydrogen (H) or aryl and
R7 denotes aryl or arylcarbonyl,
R8 denotes aryl, aryl-1-4C-alkyl, aryl-2-4C-alkenyl, aryl-2-4C-alkynyl, diaryl-1-4C-alkyl, heteroaryl, heteroaryl-1-4C-alkyl, heteroaryl-aryl-1-4C-alkyl, diheteroaryl-1-4C-alkyl, arylcarbonyl, heteroarylcarbonyl, arylsulphonyl, aryl-1-4C-alkylcarbonyl or aryl-2-4C-alkenylcarbonyl, aryl representing a ring of the formula ##STR5## wherein R9 and R10 are identical or different and have the meaning of hydrogen (H), 1-4C-alkyl, 1-4C-alkoxy, halogen, hydroxyl or trifluoromethyl, and heteroaryl represents a 5-membered or 6-membered heterocylic radical having one heteroatom or two identical or different heteroatoms from the group consisting of oxygen (O), sulphur (S) or nitrogen (N), which is unsaturated or partially or completely saturated and which may carry one or two substituents from the group consisting of 1-4C-alkyl, 1-4C-alkoxy, halogen, trifluoromethyl or cyano, and the salts of these compounds, except for the (S)-enantiomer of the compound in which Cy has the meaning of 3-nitrophenyl, R1, R2 and R3 denote methyl, E denotes propylene, A represents CH.sub.2 --C(R6)R7--CH.sub.2 and R6 and R7 denote phenyl.
1-6C-Alkyl is straight-chain or branched and denotes, for example, a hexyl, neopentyl, isopentyl, butyl, isobutyl, sec-butyl, tert-butyl, propyl, isopropyl or, in particular, ethyl or methyl radical.
3-7C-Alkoxyalkyl represents, for example, an ethoxyethyl, propoxyethyl, isopropoxyethyl, butoxyethyl, methoxypropyl, 2-methox
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ByK Gulden Lomberg Chemische Fabrik GmbH
Shen Cecilia
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