Dr. Willmar Schwabe Gmbh & Co.

Firma Willmar Schwabe

Willmar Schwabe Gmbh & Co.

Fa. Wilmar Schwabe Gmbh & Co.

Klaus Klessing

Shyam Sunder Chatterjee

Clemens Erdelmeier

Bernard L Gabard

Dieter Marme

Christoph Sch&auml;chtele

Stable hyperforin salts, method for producing same and their use in the treatment of alzheimer's disease

Amino acid esters, process for the preparation thereof and use thereof

The present invention provides 5-arylalkyl-4-alkoxy-2(5H)-furanones of the formula: ##STR1## wherein the oxygen atoms on C-5 and C-.alpha., relative to one another, are in the threo-position, with the exclusion of those compounds of the formula (I) wherein R.sup.2 is H or CH.sub.3 when n=0 or 2, R.sup.o =H, R.sup.1 =CH.sub.3, R.sup.3 =H and R.sup.4 =H. The present invention also provides processes for their preparation, as well as new 3-alkoxy-5-(subst.)-phenyl-2(E), 4(E)-pentadienoates as reactive intermediates for the preparation of the new furanone derivatives. The new furanone derivatives of the threo series are active as anticonvulsives/anti-epileptics. Therefore, the present invention also provides medicaments which contain these new furanone derivatives, as well as known furanones, the anticonvulsive/anti-epileptic effectiveness of which has been found for the first time.

5-arylalkyl-4-alkoxy-2(5H)-furanones, intermediates and processes for

1.4;3.6-Dianhydrohexitol nitrates substituted by purine bases, namely, adenyl-desoxy-1.4;3.6-dianhydrohexitol nitrates of the general formula Ia as well as theophyllinyl-desoxy-1.4;3.6-dianhydrohexitol nitrates of the general formula Ib, ##STR1## wherein R.sup.1 and R.sup.2 are the same or different and, independently of one another signify

1.4;3.6-Dianhydrohexitol nitrates substituted by purine bases, and

Alkylaminodesoxy-1.4;3.6-dianhydrohexitol nitrates substituted by purine bases of the general formula I, ##STR1## wherein R.sup.1 signifies a hydrogen atom or a lower alkyl group with 1 to 4 C-atoms, X a straight-chained or branched alkyl or hydroxyalkyl group with 1 to 7 C-atoms, Y a 1,3-dialkylxanthin-7-yl or a 3,7-dialkylxanthin-1-yl group, each with straight or branched-chained alkyl groups with 1 to 5 C-atoms, or an adenin-9-yl group, as well as their physiologically acceptable acid-addition salts. Process for the preparation of said compounds and pharmaceutical compositions containing said compounds.

Alkylaminodesoxy-1.4;3.6-dianhydrohexitol nitrates substituted by purine

Aminodesoxy-1.4;3.6-dianhydrohexitol derivatives of the general formula I, ##STR1## wherein R.sup.1 and R.sup.2 in each case independently of one another, signifies a hydrogen atom or a lower alkyl group with 1 to 4 C-atoms or wherein R.sup.1 signifies a hydrogen atom and R.sup.2 an adamant(1)yl radical or wherein R.sup.1 , and R.sup.2, together with the nitrogen atom to which they are attached, (a) signify the residue of a cyclic, non-aromatic secondary amine possibly containing a further hetero atom or (b) the aden(9)yl radical possibly mono- or disubstituted on the 6-amino group or (c) the 6-alkylmercaptopurin(9)yl radical or (d) the theophyllin-(7)yl radical or (e) the 6-chloropurin-9-yl radical or wherein R.sup.1 signifies a hydrogen atom or a lower alkyl group with 1 to 4 C-atoms and R.sup.2 an .omega.-theophyllin(7)ylalkyl radical or an .omega.-theobromin-1-ylalkyl radical or an .omega.-(N,N'-di-lower alkyl-substituted xanthin-N'-yl)alkyl radical, whereby 'lower alkyl' signifies an alkyl group with 1 to 5 C-atoms, or an .omega.-adenin-9-ylalkyl radical, whereby the alkyl radical has 2 to 7 C-atoms and can be straight-chained or branched, and wherein R.sup.3 signifies a hydrogen atom, a methanesulphonyl or toluenesulphonyl group, as well as their acid-addition salts. Processes for the preparation of said compounds and use of said compounds as reactive intermediate products for the preparation of the corresponding pharmacologically-effective amino-desoxy-1.4;3.6-dianhydrohexitol nitrates.

Optionally N-substituted aminodesoxy-1.4;3.6-dianhydrohexitol derivatives

1.4;3.6-Dianhydrohexitol nitrates substituted by purine bases, processes

Aminodesoxy-1.4;3.6-dianhydrohexitol derivatives of the general formula I, ##STR1## wherein R.sup.1 and R.sup.2, in each case independently of one another, signifies a hydrogen atom or a lower alkyl group with 1 to 4 C-atoms or wherein R.sup.1 signifies a hydrogen atom and R.sup.2 an adamant(1)yl radical or wherein R.sup.1 and R.sup.2, together with the nitrogen atom to which they are attached, (a) signify the residue of a cyclic, non-aromatic secondary amine possibly containing a further hetero atom or (b) the aden(9)yl radical possibly mono- or disubstituted on the 6-amino group or (c) the 6-alkylmercaptopurin(9)yl radical or (d) the theophyllin(7)yl radical or (e) the 6-chloropurin-9-yl radical or wherein R.sup.1 signifies a hydrogen atom or a lower alkyl group with 1 to 4 C-atoms and R.sup.2 an .omega.-theophyllin(7)ylalkyl radical or an .omega.-theobromin-1-ylalkyl radical or an .omega.-(N,N'-di-lower alkyl-substituted xanthin-N'-yl)alkyl radical, whereby 'lower alkyl' signifies an alkyl group with 1 to 5 C-atoms, or an .omega.-adenin-9-ylalkyl radical, whereby the alkyl radical has 2 to 7 C-atoms and can be straight-chained or branched, and wherein R.sup.3 signifies a hydrogen atom, a methanesulphonyl or toluenesulphonyl group, as well as their acid-addition salts. Processes for the preparation of said compounds and use of said compounds as reactive intermediate products for the preparation of the corresponding pharmacologically-effective amino-desoxy-1.4;3.6-dianhydrohexitol nitrates.

2-0- and 5-0-substituted 1.4;3.6-dianhydrohexitol mononitrates of the general formula I, ##STR1## wherein R is a halogen-substituted phenyl group, a methanesulphonyl or nicotinoyl group, as well as their physiologically acceptable acid-addition salts, insofar as R signifies the nicotinoyl group. Processes for the preparation of said compounds and pharmaceutical compositions containing said compounds.

2-0- and 5-0-Substituted 1.4;3.6-dianhydrohexitol mononitrates and

Aminodesoxy-1.4;3.6-dianhydrohexitol nitrates of the general formula I, ##STR1## wherein R.sup.1 and R.sup.2 possess the meanings given in claim 1, as well as their pharmacologically acceptable acid-addition salts; processes for the preparation of said compounds, and pharmaceutical compositions containing at least one of said compounds.

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Ettlingen, Germany

Klaus Klessing