Abbvie Deutschland Gmbh and Co Kg

Abbvie Inc.

Achim Möller

Wilfried Hornberger

Andreas Kling

Helmut Mack

Katja Jantos

Gisela Backfisch

Yanbin Lao

Marjoleen Nijsen

Ulrich Ebert

Martin Schmidt

Nicole Teusch

Ralf Loebbert

Alfred Hahn

The present invention relates to the identification, functionality and use of domains from the N terminus of the receptor for Advanced Glycation End Products (AGER). These domains, called receptor multimerization epitope (RME), are highly conserved in all AGER protein sequences. They represent the mediators for AGER self-association and heteromerization with other proteins. The invention likewise relates to the identification, functionality and use of peptides derived from the C domain of AGER (AGER-CDP). The AGER RMEs and AGER-CDPs of the invention are suitable as target for identifying AGER ligands which modulate the natural ligand interaction; as immunogen for active or passive immunization of individuals, as diagnostic means for identifying immunogenic reactions, and as peptide ligands for modulating protein-protein interactions involving AGER.

AGER-peptides and use thereof

The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula (I) in which R, Rand n have the meanings mentioned in the claims and the description, Y is a radical of the formulae (Y1) or (Y2) where # indicates the point of attachment of Y to the pyridine ring, R, R, R, Rand m have the meanings mentioned in the claims and the description, A is (CH)with p being 1, 2, 3 or 4, where one or two hydrogen atoms may be replaced by a radical R, where A is attached to the 3- or 4-position of the pyrazole radical and Rhas the meaning mentioned in the claims and the description; Ais (CH)q with q being 0, 1, 2 or 3, where one or two hydrogen atoms may be replaced by halogen or C-C-alkyl; and Ais (CH)r with r being 0, 1, 2 or 3, where one or two hydrogen atoms may be replaced by halogen or C-C-alkyl, provided that that r+q is 2, 3, 4, 5 or 6; their tautomers, the hydrates thereof, the pharmaceutically suitable salts of the carbox-amide compounds (I), the prodrugs of (I) and the pharmaceutically suitable salts of the prodrugs, tautomers or hydrates of (I). 

Carboxamide compounds and their use as calpain inhibitors V

The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula (I) in which R, R, R, R, X, m and n have the meanings mentioned in the claims and the description, the tautomers thereof, the hydrates thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein Ris optionally substituted benzyl or hetaryl-methyl, X is a single bond or an oxygen atom, Ris C-C-alkyl, C-C-haloalkyl, C-C-alkenyl, C-C-cycloalkyl, C-C-cycloalkyl-C-C-alkyl, C-C-heterocycloalkyl-C-C-alkyl, phenyl, phenyl-C-C-alkyl, pyridin-2-yl-C-C-alkyl or CH&#x2014;C(O)OCH, Rand Rindependently of one another are halogen, CN, CF, CHF, CHF, C-C-alkyl or C-C-alkoxy, and m and n independently of one another are 0 or 1. 

The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula I in which R, R, RR, R, m and n have the meanings mentioned in the claims and the description, the tautomers thereof, the hydrates thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein Ris optionally substituted phenyl-C-C-alkyl or hetaryl-C-C-alkyl, Ris optionally substituted aryl, hetaryl, aryl-C-C-alkyl, aryl-C-C-alkenyl or hetaryl-C-C-alkyl, Ris C-C-alkyl, C-C-haloalkyl, C-C-alkenyl, C-C-cycloalkyl, C-C-cycloalkyl-C-C-alkyl, or phenyl-C-C-alkyl, Rand Rindependently of one another are halogen, CF, CHF, CHF, C-C-alkyl or C-C-alkoxy, and m and n independently of one another are 0 or 1.

The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula I in which R, R, RR, R, m and n have the meanings mentioned in the claims and the description, the tautomers thereof, the hydrates thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein Ris optionally substituted phenyl-C-C-alkyl or hetaryl-C-C-alkyl, Ris optionally substituted aryl, hetaryl, aryl-C-C-alkyl, aryl-C-C-alkenyl or hetaryl-C-C-alkyl, Ris C-C-alkyl, C-C-haloalkyl, C-C-alkenyl, C-C-cycloalkyl, C-C-cycloalkyl-C-C-alkyl, C-C-heterocycloalkyl-C-C-alkyl, phenyl-C-C-alkyl, pyridin-2-yl-C-C-alkyl or 1,3-benzoxazol-2-yl-methyl, Rand Rindependently of one another are halogen, CF, CHF, CHF, C-C-alkyl or C-C-alkoxy, and m and n independently of one another are 0 or 1.

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Ludwigshafen, Germany

Achim Möller