Hoechst Aktiengesellschaft

Aventis Pharma Deutschland, Gmbh

Sanofi-a Ventis Deutschland Gmbh

Other

Cassella Aktiengesellschaft

Hoechst Marion Roussel

Hoechst Japan Limited

Hoechst Gmbh

Cassella Aktiengessellschaft

Genentech, Inc.

Gerhard Breipohl

Jochen Knolle

Eugen Uhlmann

Wolfgang Konig

Gerhard Zoller

David William Will

Melitta Just

Otmar Klingler

Bernd Jablonka

Stephan Henke

Klaus Wirth

Anuschirwan Peyman

Bernward Scholkens

Thomas Gadek

Denis Carniato

Jean-Francois Gourvest

Werner Stuber

Hermann J Gerhards

Max Hropot

Hans-Ulrich Stilz

J&uuml;rgen Michalowsky

Robert S McDowell

Martin Bickel

Volkmar Wehner

Rolf Geiger

Gerhard Beck

Holger Heitsch

Hans Ulrich Stilz

Sarah Catherine Bodary

Hans-Wolfram Fehlhaber

Jean-Marie Ruxer

Holger Wallmeier

Irvin Winkler

Wolfgang Holla

Hiristo Anagnostopulos

Franz Hock

Heiner Jendralla

Gabriele Wiemer

Karl-Heinz Scheunemann

Hans-Georg Alpermann

Robert Andrew Cuthbertson

Theodor Andreas Wollmann

Steven Albert Benner

Yoko Otawara-Hamamoto

Stefan M Ullner

Jens Stechl

Reiko Kikuno

Karin Molling

Anuschirwam Peyman

Napoleane Ferrara

Wolfgang K Onig

Michael Lutz

G Unter M Uller

Wendelin Frick

Fred Lembeck

Tomoaki Matsumoto

Takashi Kurita

Robert Mcdowell

Jean-François Gourvest

The present invention relates to PNA derivatives which carry, at the C terminus, or at both the C and N termini of the PNA backbone, one or more phosphoryl radicals. The phosphoryl radicals carry, where appropriate, one or more labeling groups, groups for crosslinking, groups which promote intracellular uptake, or groups which increase the binding affinity of the PNA derivative for nucleic acids. The invention furthermore relates to a process for preparing the above-mentioned PNA derivatives and to their use as pharmaceuticals or diagnostic agents.

Polymide nucleic acid derivatives, and agents and processes for preparing them

Polyamide nucleic acid derivatives and agents, and processes for preparing them

Polyamide-oligonucleotide derivatives of the formulaF[(DNA-Li)(PNA-Li)(DNA-Li)(PNA)]F'wherein q, r, s, t are, independently of one another, zero or 1, where the total of two or more adjacent q, r, s and t&#x2267;2; x is 1 to 20; DNA is a nucleic acid such as DNA or RNA or a known derivative thereof; Li is a covalent linkage between DNA and PNA, where the covalent linkage comprises a bond or an organic radical with at least one atom from the series consisting of C, N, O or S; PNA is a polyamide structure which contains at least one nucleotide base which is different from thymine; and F and F&#x2032; are end groups and/or are linked together by a covalent bond, and the physiologically tolerated salts thereof, a process for their preparation and their use as pharmaceutical, as gene probe and as primer, are described.

Polyamide-oligonucleotide derivatives, their preparation and use

The present invention relates to PNA derivatives which carry, at the N terminus of the PNA backbone, a phosphoryl radical. The phosphoryl radical can be, for example, a phosphate radical, or a substituted phosphoryl radical, with substituted phosphoryl derivatives carrying, where appropriate, one or more labeling groups, groups for crosslinking, groups which promote intracellular uptake, or groups which increase the binding affinity of the PNA derivative for nucleic acids. The invention furthermore relates to a process for preparing the abovementioned PNA derivatives and to their use as pharmaceuticals and diagnostic agents.

Polyamide nucleic acid derivatives, and agents, and processes for preparing them

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 invention provides polyamide-oligonucleotide derivatives of the formula:F[(DNA-Li)(PNA-Li)(DNA-Li)(PNA)]F'.In the formula, q, r, s, and t are, independently of one another, zero or 1, where the total of two or more adjacent q, r, s, and t is greater than or equal to 2; and x is 1 to 20. In the formula, DNA is a nucleic acid such as DNA or RNA or a known derivative thereof. Li is a covalent linkage between DNA and PNA, where the covalent linkage comprises a bond or an organic radical with at least one atom from the series consisting of C, N, O, or S. PNA is a polyamide structure which contains at least one nucleotide base that is different from thymine. F and F&#x2032; are end groups and/or are linked together by a covalent bond. The invention also provides physiologically tolerated salts of the above formula. The invention further provides a process for preparation of the polyamide-oligonucleotide derivatives of the invention as well as their use as pharmaceuticals, as gene probes, and as primers.

Polyamide nucleic acid derivatives, and agents and processes for preparing them

The present invention relates to ethyl (2S)-2-(naphthalene-1-sulfonylamino)-3-(4-(2-(1,4,5,6-tetrahydropyrimidin-2-ylcarbamoyl)ethyl)benzoylamino)propionate hemifumarate of formula (I), and to a process for its preparation comprising reacting 4-(2-(1,4,5,6-tetrahydropyrimidin-2-ylcarbamoyl)ethyl)benzoic acid or a derivative thereof and ethyl (2S)-3-amino-2-(naphthalene-1-sulfonylamino)propionate. The compound of formula (I) is a valuable pharmaceutical which can be used, for example, in the treatment or prophylaxis of diseases which can be influenced by inhibiting the vitronectin receptor, in particular of bone diseases such as osteoporosis. The invention furthermore relates to chemical intermediates useful for the preparation of the compound of formula (I).

1,4,5,6-tetrahydropyrimidine derivative as a vitronectin inhibitor

Polyamide nucleic acid derivatives and agents and processes for preparing them

Substituted purine derivatives, processes for their preparation, their use, and compositions comprising them

The present invention relates to acylguanidine derivatives of formula (I) in which R , R , R , R , R , A, m and n have the meanings indicated in the patent claims, their physiologically tolerable salts and their prodrugs. The compounds of formula (I) are valuable pharmaceutical active ingredients. They are vitronectin receptor antagonists and inhibitors of bone resorption by osteoclasts and are suitable, for example, for the therapy or prophylaxis of diseases which are caused at least partially by an undesired extend of bone resorption, for example of osteoporosis. The invention furthermore relates to processes for the preparation of compounds of formula (I), their use, in particular as pharmaceutical active ingredients, and pharmaceutical preparations comprising them.

Acylguanidine derivatives as inhibitors of bone resorption and as vitronectin receptor antagonists

Substituted N-ethylglycine derivatives for preparing PNA and PNA/DNA hybrids

Disclosed is a method for producing (&minus;)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-piperidine characterized in that 1-methyl-piperidine-4-one is converted into hydrobromide, subsequently transformed with bromine into 3(R,S)-bromine-1-methyl-4-oxo-piperidine-hydrobromide and reacted with 1,3,5-trimethoxybenzol to form 3(R,S)-bromine-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydro-pyridine-hydrobromide. By stirring the reaction solution into an organic solvent, 3(R,S)-bromine-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydro-pyridine-hydrobromide is initially isolated as a solid and subsequently the product is mixed with water and converted into 3(R,S)-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydro-pyridine by means of stirring. The product thus prepared is catalytically hydrogenated into a racemic 3,4-cis-alcohol and subsequently, enantiomerically pure (&minus;)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-piperidine is obtained by separation of racemic mixtures with chiral auxiliary reagents from racemic 3,4-cis alcohol.

Process for the preparation of (&minus;)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)piperidine

The invention provides compounds and processes for synthesis of peptide nucleic acids (PNA). The compounds include temporary amino protecting groups that are base-labile, and protection groups for the exocyclic amino function of the nucleotide base that is compatible with the base-labile amino protecting group. Cleavage of an oligomer comprising these compounds from a solid support can be achieved using weak or medium strength acids.

PNA synthesis using a base-labile amino protecting group

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Frankfurt-am-Main, Germany

Gerhard Breipohl