Hoechst Aktiengesellschaft

Sanofi-a Ventis Deutschland Gmbh

Hoechst Aktiengesellachaft

Gerhard Beck

Wilhelm Bartmann

Gunther Wess

Ulrich Lerch

Milos Babej

Hans-Hermann Lau

Heiner Jendralla

Bernward Scholkens

Hermann Teufel

Kurt Kesseler

Ernold Granzer

Wolfgang Holla

Ekkehard Baader

Bela Kerekjarto

Dieter-Bernd Reuschling

Klaus Kuhlein

Richard H Rupp

Bernhard Kammermeier

Jochen Knolle

Rudolf Kunstmann

Joachim-Heiner Jendralla

Josef Musil

Andreas Bergmann

Martin Bickel

Gerhard Breipohl

Hans Ulrich Stilz

Adolf Heinz Linkies

Karl Seeger

Peter Below

Hiristo Anagnostopulos

Elmar Konz

Berndt Kulitzscher

Ulrich Schacht

Manfred Radau

Bernward Schokens

Kurt Kebeler

Jurgen Michalowsky

The present invention relates to a process for the preparation of acetyl-amidiniophenylalanyl-cyclohexylglycyl-pyridinioalaninamides of the formula I, in which the anions X are physiologically acceptable anions, and their analogs, which are effective inhibitors of the blood coagulation factor Xa and which can be used, for example, for preventing thromboses. The process according to the invention comprises the coupling of 2-[2-acetylamino-3-(4-amidinophenyl)propionylamino]-2-cyclohexylacetic acid, which is obtained from 2-[2-acetylamino-3-(4-cyanophenyl)acryloylamino]-2-cyclohexylacetic acid by asymmetric hydrogenation and conversion of the cyano group into the amidine, or a salt thereof, with a 3-(2-amino-2-carbamoylethyl)-1-methylpyridinium salt or a salt thereof. The invention furthermore provides starting materials and intermediates for this process, processes for their preparation and acetyl-(S)-4-amidiniophenylalanyl-(S)-cyclohexylglycyl-(S)-(1-methyl-3-pyridinio)alaninamide as ditosylate salt.

Process for the preparation of acetyl-amidiniophenylalanyl-cyclohexylglycyl-pyridinioalaninamides

The present invention relates to ethyl 3-(2-(4-(4-(amino-imino-methyl)-phenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl)acetylamino)-3-phenylpropionate salts of the formula I,

Salts of ethyl 3-(2-(4-(4-amino-imino-methyl)phenyl)-4-methyl-2,5-dioxo-imidazolidin-1-yl)acetylamino)-3-phenylpropionate

The present invention relates to a process for the preparation of chiral, nonracemic compounds of the formula I ##STR1## in which R.sup.1 and R.sup.2 have the meanings indicated in claim 1 and which are useful intermediates for the preparation of pharmaceutical active compounds in which, for resolution, a salt is formed from the racemic compound of the formula I and a chiral, nonracemic amino compound. It furthermore relates to compounds of the formula I and esters thereof.

Process for the preparation of chiral, nonracemic

Process for the resolution of rac-2-oxotricyclo�2.2.1.0.sup.3,5 !heptane-7-carboxylic acid esters using lipase from candida. Compounds of the formula I ##STR1## in which R.sup.1 has the meanings mentioned, may be obtained in isomerically pure form from enantiomer mixtures or racemic mixtures by reacting the compound of the formula I in the presence of a lipase or esterase from porcine liver, porcine pancreas, bovine pancreas or from microorganisms such as Candida, Pseudomonas, Mucor, Rhizopus and Aspergillus, or proteases from Bacillus in the presence of water and, if desired, a cosolvent and separating from one another the esters and acids present in the solution obtained.

Process for the enzymatic separation of enantiomers of

Process for the stereoselective synthesis of 3-substituted

A novel process is described for preparing tert-butyl (3R, 5S ) 6-hydroxy-3,5-O-isopropylidene-3,5-dihydroxyhexanoate of the formula I ##STR1## which is a valuable structural element for preparing inhibitors of HMG-CoA reductase.

Process for preparing tert-butyl

4-Hydroxytetrahydropyran-2-ones and the corresponding dihydroxycarboxylic acid derivatives, salts and esters, process for their preparation, their use as pharmaceuticals, and pharmaceutical preparations and precursors. Compounds of the formula I ##STR1## and the corresponding open-chain dihydroxycarboxylic acids of the formula II ##STR2## in which X, Y, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 have the meanings indicated, and also their pharmacologically tolerable salts with bases and their pharmacologically tolerable esters, processes for the preparation of these compounds, their use as pharmaceuticals and pharmaceutical preparations are described. In addition, compounds of the formula III ##STR3## in which R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, X and Y have the meanings indicated are described.

4-hydroxytetrahydropyran-2-ones and the corresponding

6-Fluoro-3,5-dihydroxy carboxylic acid derivatives of the formula I and the corresponding lactones of the formula II ##STR1## in which R.sup.1 and R.sup.2 have the specified meanings, a process for the preparation of these compounds, the use thereof as medicinal agents and pharmaceutical products are described. In addition, new intermediates for the preparation of the compounds of the formula I or formula II are described.

6-fluoro-3,5-dihydroxy carboxylic acids and derivatives thereof

Substituted 3-thia- and 3-oxa-alkylflavones of formula I ##STR1## wherein R, R.sup.1, R.sup.2, R.sup.3, R.sup.4 X, m and n have the indicated meanings, a process for the preparation of these compounds and their use as medicaments and pharmaceutical preparations are described. In addition, new intermediates for the preparation of the compounds of formula I are described.

Substituted 3-thia- and 3-oxa-alkylflavones, a process for their

6-Phenoxymethyl-4-hydroxytetrahydropyran-2-ones and 6-thiophenoxymethyl-4-hydroxytetrahydropyran-2-ones and the corresponding dihydroxycarboxylic acid derivatives, salts and esters, processes for the preparation of these compounds, their use as pharmaceuticals, pharmaceutical preparations and novel phenols and thiophenols Compounds of the general formula I ##STR1## and the corresponding open-chain dihydroxycarboxylic acids of the formula II ##STR2## in which X, Y and Z have the meanings given, and pharmacologically tolerated salts thereof with bases and pharmacologically tolerated esters thereof, processes for the preparation of these compounds, their use as pharmaceuticals and pharmaceutical preparations are described. Novel phenols and thiophenols of the formula III ##STR3## in which X, Y and Z have the meanings given, are also described.

6-phenoxymethyl-4-hydroxytetrahydropyran-2-ones and

7-[1H-pyrrol-3-yl]-substituted 3,5-dihydroxyhept-6-enoic acids, 7-[1H-pyrrol-3-yl]-substituted 3,5-dihydroxyheptanoic acids of the formula I ##STR1## in which A, B, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 have the indicated meanings, and the corresponding .delta.-lactones of the formula II ##STR2## processes for the preparation of these compounds, their use as medicaments and pharmaceutical products are described. In addition, new intermediates for the preparation of the compounds of the formulae I and II are described.

7(1H-pyrrol-3-YL)-substituted 3,5-dihydroxyhept-6-enoic acids,

A process for the preparation of optically active 3-demethylmevalonic acid derivatives of the formula I ##STR1## (3,5-dihydroxy carboxylic acid derivatives) or of the formula II ##STR2## in which R, R.sup.1 and Y have the indicated meanings, is described. The invention furthermore relates to aldehydes of the formula XII ##STR3## in which M represents the indicated protective groups.

Process for the preparation of optically active 3-demethylmevalonic acid

A process for the preparation of optically active 3-de-methylmevalonic acid derivatives, and intermediates A process for the preparation of optically active 3-de-methylmevalonic acid derivatives of the formula I ##STR1## (3,5-dihydroxy carboxylic acid derivatives) or of the formula II ##STR2## (.beta.-hydroxy lactones) in which R, R.sup.1 and Y have the indicated meanings, is described. The invention furthermore relates to aldehydes of the formula XII ##STR3## in which M represents the indicated protective groups. The 3-demethylmevalonic acid derivatives of this invention are useful for lowering cholesterol levels of a host.

Optically active 3-demethylmevalonic acid derivatives, and intermediates

4(R)-Substituted 6(S)-phenyloxymethyl-, 6(S)-.beta.-phenylethyl- and 6(S)-.beta.-styryl-tetrahydropyran-2-ones of the general formula V ##STR1## in which R.sup.7, R.sup.8 and A have the meanings given, and the corresponding open-chain hydroxycarboxylic acids, pharmacologically acceptable salts and esters thereof, processes for the preparation of these compounds, their use as medicaments and pharmaceutical products are described. Novel .alpha.,.beta.-unsaturated lactones for the preparation of the compounds of the formula V are also described.

4(R)-substituted 6(S)-phenoxymethyl-, 6(S)-.beta.-phenylethyl- and

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Frankfurt am Main, Germany

Gerhard Beck