Patent NZ-599860-A (NZ)
Title: Carboxamide compounds and their use as calpain inhibitors
Inventor: KLING ANDREAS
IPC: A61K31/4155
Filed: 2007-12-28
Abstract: Abstract - 599860 Disclosed are heterocyclic carboxamide compounds of the formula I, wherein R1 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, cycloalkyl, cycloalkyl-alkyl, where a CH2 group in the cycloalkyl moiety of the last two radicals mentioned may be replaced by O, NH, or S, or two adjacent C atoms may form a double bond, where the cycloalkyl moiety may be further substituted, optionally substituted aryl, optionally substituted hetaryl, optionally substituted aryl-alkyl, optionally substituted aryl-alkenyl, optionally substituted hetaryl-alkyl or optionally substituted hetaryl-alkenyl; R3a and R3b are independently of one another hydroxy or alkoxy, or together with the carbon atom to which they are bonded are C=O; X is hydrogen or a radical of the formulae C(=O)-O-Rx1, C(=O)-NRx2Rx3, C(=O)-N(Rx4)-(alkylene)-NRx2Rx3 or C(=O)-N(Rx4)NRx2Rx3; Y is a divalent, aromatic radical or a divalent 6-membered heteroaromatic radical which has 1 or 2 nitrogen atoms as ring members and where Y optionally has 1 or 2 identical or different substituents Ry; W is an optionally substituted imidazole ring connect to Y through nitrogen; R2 is selected from optionally substituted aryl and optionally substituted hetaryl; or W and R2 combine together to form a bi- or tricyclic radical which includes indazole, benzimidazole, and also further condensed indazole, benzimidazole moieties, wherein said indazole, benzimidazole ring moieties are connected to Y through nitrogen; and wherein the remaining substituents are as defined herein. Representative compounds include: N-(3-amino-1-benzyl-2,3-dioxopropyl)-2-(4-phenyl-1H-imidazol-1-yl)nicotinamide, N-{ 1-[amino(oxo)acetyl]pentyl} -2-(4-phenyl-1H-imidazol-1-yl)nicotinamide, N-{ 1-[amino(oxo)acetyl]-3-methylbutyl} -2-(4-phenyl-1H-imidazol-1-yl)nicotinamide, N-{ 1-[amino(oxo)acetyl]pentyl} -2-[4-(4-chlorophenyl)-1H-imidazol-1-yl]nicotinamide, N-(3-amino-1-benzyl-2,3-dioxopropyl)-2-[4-(4-morpholin-4-ylphenyl)-1H-imidazol-1-yl]nicotinamide, N-(3-amino-1-benzyl-2,3-dioxopropyl)-2-{ 4-[4-(trifluoromethyl)phenyl]-1H-imidazol-1-yl} nicotinamide, N-{ 1-[amino(oxo)acetyl]pentyl} -5-chloro-2-(4-phenyl-1H-imidazol-1-yl)nicotinamide, N-(3-amino-1-benzyl-2,3-dioxopropyl)-2-{ 4-[4-(morpholin-4-ylmethyl)phenyl]-1H-imidazol-1-yl} nicotinamide, N-(3-amino-1-benzyl-2,3-dioxopropyl)-2-(1H-indazol-1-yl)nicotinamide and N-(3-amino-1-benzyl-2,3-dioxopropyl)-2-(2H-indazol-2-yl)nicotinamide and the pharmaceutically suitable salts thereof. Further disclosed is a carboxamide compound as defined above for use in therapy of a disorder, an impairment or a condition, where the disorder, impairment or condition is selected from neurodegenerative disorders or impairments; epilepsy; pain; damage to the heart following cardiac ischemias; damage to the kidneys following renal ischemias; skeletal muscle damage; muscular dystrophies; damage resulting from proliferation of smooth muscle cells; coronary vasospasms; cerebral vasospasms; macular degeneration; cataracts of the eyes; or restenosis of the blood vessels following angioplasty; chemotherapy of tumors and metastasis thereof; and HIV.