Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-10-27
1999-08-17
Higel, Floyd D.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
514398, 5483151, 5483171, 5483211, 5483241, 5483251, C07D23376, C07D23374, C07D23372, A61K 31415
Patent
active
059395567
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to hydantoin derivatives of the formula I ##STR2## which are valuable intermediates for the preparation of pharmaceutical active compounds, their preparation and their use in the preparation of the active compounds.
In German Patent Applications P 43 38 944 and P 44 27 979 and the PCT Application PCT/EP94/03491, substituted 5-membered ring heterocycles are described which inhibit cell-cell adhesion, in particular, for example, platelet aggregation. These active compounds contain a polysubstituted imidazolidine, oxazolidine, thiazolidine or pyrrolidine ring which is linked to an unsubstituted or substituted amino, amidino or guanidino group yla a bivalent group, e.g. yla an alkylene group or yla various other groups. The heterocyclic 5-membered ring has an asymmetric center. In particular for a group of these active compounds which contain a 2,5-dioxoimidazolidine ring, i.e. a hydantoin ring, which is linked yla a 1,4-phenylene unit to the amino or aminomethyl, amidino or guanidino group, it has proven advantageous, especially in the preparation of active compounds haylng a uniform configuration at the asymmetric center of the 5-membered ring, to start from the corresponding hydantoins of the formula I as intermediates.
The present invention therefore relates to hydantoin derivatives of the formula I ##STR3## in which R is cyano, C(.dbd.NH)--O--(C.sub.1 -C.sub.6)-alkyl, C(.dbd.NH)--NH--X, CH.sub.2 --NH--X or NH--X.sup.1; (C.sub.1 -C.sub.6)-alkoxycarbonyl, (C.sub.1 -C.sub.18)-alkylcarbonyloxy-(C.sub.1 -C.sub.6)-alkoxycarbonyl, optionally substituted (C.sub.6 -C.sub.14)-arylcarbonyl, optionally substituted (C.sub.6 -C.sub.14)-aryloxycarbonyl, (C.sub.6 -C.sub.14)-aryl-(C.sub.1 -C.sub.6)-alkoxycarbonyl which can also be substituted in the aryl radical, (R.sup.5 O).sub.2 P(O), cyano, hydroxyl, (C.sub.1 -C.sub.6)-alkoxy, (C.sub.6 -C.sub.14)-aryl-(C.sub.1 -C.sub.6)-alkoxy which can also be substituted in the aryl radical, or amino; and R" independently of one another have the meanings of X; -C.sub.8)-alkyl optionally substituted in the aryl radical or (C.sub.3 -C.sub.8)-cycloalkyl; (C.sub.6 -C.sub.14)-aryl, (C.sub.6 -C.sub.14)-aryl-(C.sub.1 -C.sub.8)-alkyl optionally substituted in the aryl radical or (C.sub.3 -C.sub.8)-cycloalkyl; -C.sub.14)-aryl-(C.sub.1 -C.sub.6)-alkyl optionally substituted in the aryl radical or optionally substituted (C.sub.6 -C.sub.14)-aryl; (C.sub.6 -C.sub.14)-aryl or (C.sub.6 -C.sub.14)-aryl-(C.sub.1 -C.sub.8)-alkyl, which can also be substituted in the aryl radical; CH.sub.2 --NH.sub.2 ; with respect to the asymmetric center in the hydantoin ring and at the same time R.sup.3 is methoxycarbonylmethyl, R.sup.1 is methyl and R.sup.2 is hydrogen or methyl, R cannot be CN or C(.dbd.NH)--OC.sub.2 H.sub.5 ; with respect to the asymmetric center in the hydantoin ring and at the same time R.sup.3 is methoxycarbonylmethyl or hydroxycarbonylmethyl, R.sup.1 is methyl and R.sup.2 is hydrogen or methyl, R cannot be NH.sub.2, CH.sub.2 --NH.sub.2, C(.dbd.NH)--NH.sub.2, tert-butoxycarbonyl-aminomethyl or benzyloxycarbonylguanidino; and their salts.
The present invention relates to all stereoisomeric forms of the compounds of the formula I. There are thus included, in particular if beside the asymmetric center in the hydantoin ring no other optically active centers are present, the enantiomers with R configuration and those with S configuration on the hydantoin carbon atom and, beside the pure enantiomers, also the racemate and mixtures of the enantiomers in any desired quantitative ratios. If, beside the optically active carbon atom in the hydantoin ring, other asymmetric centers are present, e.g. in alkyl, cycloalkyl or arylalkyl radicals, the optically active atoms in the molecule can independently of one another have the R or S configuration, and in each of these centers, independently of the others, a uniform configuration can be present or a mixture of the configuration-isomeric forms in the ratio 1:1 or in any desired quantitative ratio can be present. The present inve
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Connors et al., J. Chem. Soc., "Aryl-2-halogenalkylamines. Part XIX. Some NN-Di-chloroethyl-aminophenyl-- and -phenylalkylhydantoins and Related Amino-acids," pp. 2994-3007 (1960).
Derwent Abstract of DE-A-4338944.
Derwent Abstract of DE-A-4427979.
Klingler Otmar
Knolle Jochen
Stilz Hans Ulrich
Wehner Volkmar
Zoller Gerhard
Higel Floyd D.
Hoechst Aktiengesellschaft
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