Abstract: The invention relates to bicyclic heterocyclic compounds of general formula ##STR1## wherein A to F, Y.sub.1 and Y.sub.2 are defined as in claim 1, the tautomers thereof, the stereoisomers thereof including their mixtures, and salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases, which have valuable pharmacological properties, preferably aggregation-inhibiting effects, pharmaceutical compositions containing the compounds and processes for preparing them as well as new intermediate products of general formula Ia.
Type:
Grant
Filed:
July 31, 1995
Date of Patent:
March 4, 1997
Assignee:
Karl Thomae GmbH
Inventors:
G unter Linz, Frank Himmelsbach, Helmut Pieper, Volkhard Austel, Thomas M uller, Johannes Weisenberger, Brian Guth
Abstract: Angiotensin-II antagonists of the formula ##STR1## wherein R.sub.1 is, other than hydrogen and, inter alia, halogen, lower alkyl or cycloalkyl; R.sub.2 is, inter alia, optionally substituted benzimidazol-2-yl, 5,6,7,8-tetrahydro-imidazo [1,2-a]pyridin-2-yl, butanesultam-1-yl, imidazol-4-yl, and tetrahydobenzimidazol-2-yl; R.sub.3 is, inter alia, lower alkyl; and, R.sub.4 is an acidic group, such as carboxyl or tetrazolyl. An exemplary compound is: 4'-[(2-n-propyl-4-methyl-6-(butanesultam-1-yl)benzimidazol-1-yl)-methyl]-b iphenyl-2-carboxylic acid.
Type:
Grant
Filed:
June 1, 1995
Date of Patent:
February 11, 1997
Assignee:
Karl Thomae GmbH
Inventors:
Norbert Hauel, Berthold Narr, deceased, Uwe Ries, Jacobus C. A. van Meel, Wolfgang Wienen, Michael Entzeroth
Abstract: The invention relates to biphenyl derivatives of general formula ##STR1## wherein A to E and X are defined as in claim 1, the stereoisomers thereof, including their mixtures and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, which have valuable properties, preferably aggregation-inhibiting effects, pharmaceutical compositions containing these compounds and processes for preparing them.
Type:
Grant
Filed:
May 16, 1994
Date of Patent:
January 28, 1997
Assignee:
Dr. Karl Thomae GmbH
Inventors:
Frank Himmelsbach, Helmut Pieper, Volkhard Austel, G unter Linz, Thomas M uller, Wolfgang Eisert, Johannes Weisenberger
Abstract: Angiotensin-II antagonists of the formula ##STR1## wherein R.sub.1 is, other than hydrogen and, inter alia, halogen, lower alkyl or cycloalkyl; R.sub.2 is, inter alia, optionally substituted benzimidazol-2-yl, 5,6,7,8-tetrahydro-imidazo[1,2-a]pyridin-2-yl, butanesultam-1-yl, imidazol-4-yl, and tetrahydobenzimidazol-2-yl; R.sub.3 is, inter alia, lower alkyl; and, R.sub.4 is an acidic group, such as carboxyl or tetrazolyl. An compound is:4'-[(2-Ethyl-4-methyl-6-(5,6,7,8-tetrahydro-imidazo[1,2-a]pyridin-2-yl)-ben zimidazol-1-yl)-methyl]-biphenyl-2-carboxylic acid.
Type:
Grant
Filed:
June 1, 1995
Date of Patent:
January 14, 1997
Assignee:
Dr. Karl Thomae GmbH
Inventors:
Norbert Hauel, Berthold Narr, deceased, Uwe Ries, Jacobus C. A. van Meel, Wolfgang Wienen, Michael Entzeroth
Abstract: Disclosed herein are angiotensin-II antagonists of the formula ##STR1## wherein R.sub.1 is, other than hydrogen and, inter alia, halogen, lower alkyl or cycloalkyl; R.sub.2 is, inter alia, optionally substituted benzimidazol-2-yl, 5,6,7,8-tetrahydro-imidazo[1,2-a]pyridin-2-yl, butanesultam-1-yl, imidazol-4-yl, and tetrahydobenzimidazol-2-yl; R.sub.3 is, inter alia, lower alkyl; and, R.sub.4 is an acidic group, such as carboxyl or tetrazolyl.An exemplary compound is:(a) 4'-[[2-n-propyl-4-methyl-6-(1-methylbenzimidazole-2-yl)-benzimidazol-1-yl] methyl]-biphenyl-2-carboxylic acid.
Type:
Grant
Filed:
June 1, 1995
Date of Patent:
January 7, 1997
Assignee:
Dr. Karl Thomae GmbH
Inventors:
Norbert Hauel, Berthold Narr, deceased, Uwe Ries, Jacobus C. A. van Meel, Wolfgang Wienen, Michael Entzeroth
Abstract: The invention relates to cyclic imino compounds which have, inter alia, valuable pharmacological properties, especially inhibitory effects on cell aggregation, pharmaceutical compositions which contain these compounds and processes for preparing them.
Type:
Grant
Filed:
June 1, 1995
Date of Patent:
January 7, 1997
Assignee:
Karl Thomae GmbH
Inventors:
Frank Himmelsbach, Volkhard Austel, Helmut Pieper, Wolfgang Eisert, Thomas Mueller, Johannes Weisenberger, Guenter Linz, Gerd Krueger
Abstract: The invention relates to benzimidazoles of general formula ##STR1## wherein R.sub.1 to R.sub.4 are as defined herein, the 1-, 3-isomer mixtures thereof and the addition salts thereof. The new compounds are useful, in particular, as angiotensin antagonists.
Type:
Grant
Filed:
September 1, 1994
Date of Patent:
December 24, 1996
Assignee:
Dr. Karl Thomae GmbH
Inventors:
Berthold Narr, Norbert Hauel, Jacques Van Meel, Wolfgang Wienen, Michael Entzeroth, Uwe Ries
Abstract: Pharmaceutical composition for prevention of adhesions to body organs or parts of body organs within a body cavity at a site of inflammation is disclosed. The pharmaceutical composition contains t-PA and an aqueous hydroxyethylcellulose hydrogel. The method involves applying the aforementioned pharmaceutical composition to a site of inflammation in a body cavity.
Type:
Grant
Filed:
November 14, 1994
Date of Patent:
November 26, 1996
Assignee:
Karl Thomae GmbH
Inventors:
Helmut Franz, Thomas Muller, Wolfgang Fisert
Abstract: Cyclic imino derivatives of the formulaB--X.sub.2 --X.sub.1 --A--Y--E (I)wherein A, B, E, X.sub.1, X.sub.2 and Y are as defined herein, the stereoisomers, tautomers, mixtures and addition salts thereof, pharmaceutical compositions containing these compounds and processes for preparing them. The cyclic imino derivatives are useful as inhibitors of cell-cell and cell-matrix interactions, e.g., thrombocyte aggregation.
Type:
Grant
Filed:
April 26, 1993
Date of Patent:
November 19, 1996
Assignee:
Dr. Karl Thomae GmbH
Inventors:
Frank Himmelsbach, Austel Volkhard, Helmut Pieper, Guenter Linz, Johannes Weisenberger, Thomas Mueller
Abstract: Heterobiaryl derivatives of the formulaR.sub.1 NH--X.sub.1 --X.sub.2 --X.sub.3 --Y.sub.1 --Y.sub.2 --Y.sub.3 --Y.sub.4 --E (I)whereinR.sub.1, X.sub.1 to X.sub.3 and Y.sub.1 to Y.sub.4 are as defined herein, the tautomers, stereoisomers and mixtures thereof, and the salts, particularly the physiologically acceptable salts, thereof with organic or inorganic acids or bases. The derivatives have valuable pharmacological properties, such as inhibiting cell-cell aggregation and cell-matrix interactions.
Type:
Grant
Filed:
January 19, 1995
Date of Patent:
October 8, 1996
Assignee:
Dr. Karl Thomae GmbH
Inventors:
Guenter Linz, Helmut Pieper, Frank Himmelsbach, Volkhard Austel, Thomas Mueller, Johannes Weisenberger, Elke Seewaldt-Becker
Abstract: The invention relates to a one-pot mixer/granulator/dryer constituting a single step or one-pot production apparatus for successively mixing, moist-granulating and drying solid pharmaceutical products, for example in the manufacture of powdered products, pellets or granules. The dryer according to the invention has a substantially improved drying performance compared with conventional production equipment. The high efficiency of drying is achieved by the simultaneous use of four different drying mechanisms.
Type:
Grant
Filed:
May 19, 1994
Date of Patent:
October 1, 1996
Assignee:
Dr. Karl Thomae GmbH
Inventors:
Kurt Bauer, Wolfram Carius, Gerold Duschler
Abstract: Low viscosity, highly concentrated surfactant suspensions for replacement therapy In diseases of the respiratory tract are described. The suspensions are characterised in that they contain calcium and/or magnesium ions bound to the surfactant and unbound in the suspension agent, as well as containing a certain amount of common salt.
Type:
Grant
Filed:
May 1, 1995
Date of Patent:
September 3, 1996
Assignee:
Dr. Karl Thomae GmbH
Inventors:
Bernd Disse, Eberhard Weller, Robert Becker
Abstract: The invention relates to benzimidazoles of the formula ##STR1## in which R.sub.1 to R.sub.2 are as defined in claim 1,1 and 3 isomer mixtures thereof and addition salts thereof which have valuable properties.In particular, the novel compounds are angiotensin II antagonists.
Type:
Grant
Filed:
April 13, 1994
Date of Patent:
July 30, 1996
Assignee:
Dr. Karl Thomae GmbH
Inventors:
Berthold Narr, Andreas Bomhard, Norbert Hauel, Jacques Van Meel, Wolfgang Wienen, Michael Entzeroth
Abstract: The invention relates to cyclic imino compounds which have, inter alia, valuable pharmacological properties, especially inhibitory effects on cell aggregation, pharmaceutical compositions which contain these compounds and processes for preparing them.
Type:
Grant
Filed:
December 28, 1994
Date of Patent:
July 30, 1996
Assignee:
Karl Thomae GmbH
Inventors:
Frank Himmelsbach, Volkhard Austel, Helmut Pieper, Wolfgang Eisert, Thomas Mueller, Johannes Weisenberger, Guenter Linz, Gerd Krueger
Abstract: The invention relates to benzimidazoles of general formula ##STR1## Exemplary compounds are: (a) 4'-[[2-Ethyl-4-methyl-6-[(2-dimethylamino-3,4-dioxo-1-cyclobuten-1-yl)amin o]-1H-benzimidazol-1-yl]-methyl]-2-(1H-tetrazol-5-yl)-biphenyl,(b) 4'-[[2-n-Propyl-4-methyl-6-(2-cyano-3,3-dimethyl-guanidino)-1H-benzimidazo l-1-yl]-methyl]-2-(1H-tetrazol-5-yl)-biphenyl,(c) 4'-[[2-n-Propyl-4-methyl-6-(2,2-dicyano-1-dimethylamino-etheneamino)-1H-be nzimidazol -1-yl]-methyl]-2-(1H-tetrazol-5-yl)-biphenyl,(d) 4'-[[2-n-Propyl-4-methyl-6-(1-morpholino-2-nitro-etheneamino)-1H-benzimida zol -1 -yl]-methyl]-2-(1H-tetrazol-5-yl)-biphenyl, and(e) 4'-[[2-n-Propyl-4-methyl-6-(1,1-dimethylamino-2-nitro-etheneamino)-1H-benz imidazol -1-yl]-methyl]-2-(1H-tetrazol-5-yl)-biphenyl.The new compounds are angiotensin-antagonists.
Type:
Grant
Filed:
October 4, 1993
Date of Patent:
May 28, 1996
Assignee:
Dr. Karl Thomae GmbH
Inventors:
Uwe Ries, Norbert Hauel, Jacques van Meel, Wolfgang Wienen, Michael Entzeroth
Abstract: The invention relates to cyclic derivatives of general formula ##STR1## wherein R.sub.a, R.sub.b, X and Y are as defined in claim 1, the tautomers, the stereoisomers including the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases, which have valuable pharmacological properties, preferably aggregation-inhibiting effects, pharmaceutical compositions containing the compounds and processes for preparing them.
Type:
Grant
Filed:
February 22, 1994
Date of Patent:
May 21, 1996
Assignee:
Karl Thomae GmbH
Inventors:
F. Himmelsbach, Helmut Pieper, Volkhard Austel, Gunter Linz, Brian Guth, Thomas Muller, Johannes Weisenberger
Abstract: A phenylalkyl derivative of the formula ##STR1## wherein R.sub.a to R.sub.f, A and B are substituents and n is the number 0 or 1.These phenylalkyl derivatives possess angiotensin antagonist activity.
Type:
Grant
Filed:
December 1, 1994
Date of Patent:
May 21, 1996
Assignee:
Dr. Karl Thomae GmbH
Inventors:
Uwe Ries, Manfred Reiffen, Wolfgang Grell, Norbert Hauel, Berthold Narr, Armin Heckel, Andreas Bomhard, Jacques van Meel, Wolfgang Wienen, Michael Entzeroth
Abstract: The use of a compound of formula ##STR1## wherein the substituents are defined herein and the physiologically acceptable acid addition salts thereof for treating high blood pressure and cardiac insufficiency.