Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Patent
1995-08-08
1999-01-19
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
514141, 514142, 514451, 514553, 514576, 514577, 514675, 514678, 514682, 514699, 514700, 514701, 549417, 558117, 560256, 562 23, C07D30910, C07C 4752, C07C 6702, C07F 902
Patent
active
058613854
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP93/03459, filed Dec. 8, 1993.
The invention relates to substituted triols, to a process for their preparation, and to their use in medicaments.
It has been disclosed that lactone derivatives isolated from fungal cultures are inhibitors of 3-hydroxy-3-methyl-glutayl coenzyme A reductase
It has additionally been disclosed that pyridine-substituted EP 307 342; EP 306 929!.
The present invention relates to substituted triols of the general formula (I)
D represents a hetero- or carbocyclic radical of the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are identical or different and denote hydrogen or methyl, or R.sup.4 denotes hydroxyl, identical or different substituents from the group consisting of halogen, trifluoromethyl and straight-chain or branched alkyl having up to 8 carbon atoms, hydrogen, straight-chain or branched alkyl having up to 8 carbon atoms or cycloalkyl having 3 to 6 carbon atoms, or form a saturated or partially saturated carbocycle having 3 to 6 carbon atoms different from this or denotes hydrogen or phenyl, 8 carbon atoms, which is optionally substituted by hydroxyl or straight-chain or branched alkoxy having up to 6 carbon atoms, or by benzyloxy which for its part can be substituted by halogen or trifluoromethyl or by straight-chain or branched alkyl having up to 4 carbon atoms, carbon atoms or a radical of the formula ##STR2## R.sup.14 and R.sup.15 are identical or different and denote hydrogen or straight-chain or branched alkyl having up to 8 carbon atoms, or denote phenyl or benzyl, each of which is optionally substituted up to 2 times by identical or different substituents from the group consisting of halogen, trifluoromethyl, cyano and nitro or by straight-chain or branched alkyl having up to 6 carbon atoms, identical to or different from this, or denotes pyridyl or a radical of the formula --CO--NH-L, wherein trifluoromethyl, and is identical to or different from these, or denotes a radical of the formula --NMM', wherein or branched alkyl having up to 6 carbon atoms or benzyl, alkyl in each case having up to 8 carbon atoms, the latter optionally being substituted by cyano or phenyl which for its part can be substituted by halogen or trifluoromethyl or by straight-chain or branched alkyl having up to 6 carbon atoms, atoms, benzoyl or the group --NMM', wherein carbon atoms or benzyl, --N--R.sup.10,
R represents a radical of the formula ##STR3## wherein X denotes the group --CH.sub.2 --CH.sub.2 --, --CH.dbd.CH-- or --C.tbd.C--, hydroxyl protective group, hydrogen or a radical of the formula --CO--R.sup.24 or --CO.sub.2 --R.sup.25, wherein straight-chain or branched alkyl having up to 8 carbon atoms or phenyl, or ##STR4##
In the context of the present invention, physiologically acceptable salts are preferred. Physiologically acceptable salts of the Quinolylmethoxyphenyl-acetic acid amides can be salts of the substances according to the invention with mineral acids, carboxyl acids or sulphonic acids. Particularly preferred salts are e.g. those with hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, ethanesulphonic acid, toluenesulphonic acid, benzenesulphonic acid, naphthalenedisulphonic acid, acetic acid, propionic acid, lactic acid, tartaric acid, citric acid, fumaric acid, maleic acid or benzoic acid.
Depending on the side chains listed under R, the compounds according to the invention in each case have 1 or 2 asymmetric carbon atoms, to which the radicals --OR.sup.21 and --OR.sup.22 are bonded. They can therefore exist in various stereochemical forms.
The invention relates both to the individual isomers and to their mixtures. Depending on the relative position of the radicals --OR.sup.21 /--OR.sup.22, the substances according to the invention can thus be present in the erythro configuration or in threo configuration. This can be illustrated by way of example: ##STR5##
In turn, two enantiomers both of the substances in the threo and in the erythro configuration in each case exist.
Moreover, t
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Angerbauer Rolf
Bischoff Hilmar
Fey Peter
Hubsch Walter
Krause Hans-Peter
Bayer Aktiengesellschaft
Rao Deepak R.
Shah Mukund J.
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