Compositions for treating and/or preventing cell or tissue necrosis specifically targeting cathepsin c and/or cela1 and/or cela3a and/or structurally related enzymes thereto

A method of treating, preventing, ameliorating, abrogating symptoms of or reducing the incidence of a disease or condition associated with necrosis in a subject in need thereof, said method comprising administering a therapeutically effective amount of a compound characterized by the structure of Formula I:

• wherein G1 is substituted or unsubstituted pyrrolidine, substituted or unsubstituted piperidine, substituted or unsubstituted piperazine, substituted or unsubstituted imidazolidine, or substituted or unsubstituted pyrazolidine;
• and
• G3 is characterized by the following structure:
• or G3 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl or substituted or unsubstituted cyloalkyl;
• wherein G2 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted cyloalkyl or substituted or unsubstituted heterocycle;
• or
• a compound characterized by the structure of Formula II:
• wherein G1 is substituted or unsubstituted pyrrolidine, substituted or unsubstituted pyridine, substituted or unsubstituted aryl, substituted or unsubstituted piperidine, substituted or unsubstituted piperazine, substituted or unsubstituted imidazolidine, or substituted or unsubstituted pyrazolidine;
• and
• G3 is characterized by the following structure:
• or G3 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl or substituted or unsubstituted cyloalkyl;
• wherein G2 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted cyloalkyl or substituted or unsubstituted heterocycle;
• or
• a compound characterized by the structure of Formula III:
• wherein G1 is substituted or unsubstituted pyrrolidine, substituted or unsubstituted pyridine, substituted or unsubstituted aryl, substituted or unsubstituted piperidine, substituted or unsubstituted piperazine, substituted or unsubstituted imidazolidine, or substituted or unsubstituted pyrazolidine;
• and
• G3 is characterized by the following structure:
• or G3 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl or substituted or unsubstituted cyloalkyl;
• wherein G2 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted cyloalkyl or substituted or unsubstituted heterocycle;
• or
• a compound selected from the group consisting of:
• 3,4-bis((2-(pyrrolidin-1-yl)ethyl)amino)-1,2,5-thiadiazole 1,1-dioxide;
• cyclopropyl(2-(5-isopropylisoxazol-3-yl)pyrrolidin-1-yl)methanone;
• 6-bromo-2-(3,5-dimethoxyphenyl)-4benzo[d][1,3]oxazin-4-one 6-methyl-5-((2-methylpiperidin-1-yl)sulfonyl)pyrimidine-2,4(1H,3H)-dione;
• N-methyl-4,5,6,7,8,9-hexahydro-1H-cycloocta[c]pyrazole-3-carboxamide;
• 2-(5-(13yridine-4-yl)-2H-tetrazol-2-yl)acetic acid;
• 2-(furan-2-yl)-5,6,7,8-tetrahydro-4H-benzo[4,5]thieno[2,3-d][1,3]oxazin-4-one;
• 3-((5-acetamido-1H-1,2,4-triazol-3-yl)thio)propanoic acid;
• N,N′-(oxybis(4,1-phenylene))bis(2-methylpropanamide);
• 7-(4-ethylpiperazin-1-yl)-5,6-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine;
• 7-fluoro-10-(2-(4-isopropylpiperazin-1-yl)-2-oxoethyl)-2,3-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-5,11(10H,11aH)-dione;
• 2-(tert-butyl)-3-(1-methyl-1H-benzo[d]13yridine13-2-yl)-4-oxo-4H-chromen-7-yl pivalate;
• 3-methyl-8-(piperidin-1-yl)-1H-purine-2,6(3H,7H)-dione;
• 2-(3-bromophenyl)-4-oxo-4H-benzo[d][1,3]oxazin-6-yl acetate;
• N-(1-ethyl-3,5-dimethyl-1H-pyrazol-4-yl)-3,4,5-trimethoxybenzamide;
• 5-ethyl-N-(13yridine-2-ylmethyl)-5H-[1,2,4]triazino[5,6-b]indol-3-amine;
• 3-((4-chloro-1H-pyrazol-1-yl)methyl)-N-(2-(3-fluorobenzamido)ethyl)-1,2,4-oxadiazole-5-carboxamide;
• 1-(4-(methylthio)benzyl)-4-tosylpiperazine;
• 2-(2-ethylphenylsulfonamido)-5-(4-ethylpiperazin-1-yl)benzoic acid;
• 4((2-methylindolin-1-yl)sulfonyl)benzoic acid;
• 6-bromo-2-(3,5-dimethoxyphenyl)-4H-benzo[d][1,3]oxazin-4-one;
• 2-amino-N-(2,4-difluorophenyl)pyrimidine-5-sulfonamide;
• 3-methyl-8-(piperidin-1-yl)-1H-purine-2,6(3H,7H)-dione;
• 5-chloro-N-(2-oxo-1-phenylpyrrolidin-3-yl)thiophene-2-sulfonamide;
• 3-(pyrrolidin-1-ylsulfonyl)benzoic acid;
• (3,5-dimethyl-1H-pyrazol-1-yl)(3,4,5-trimethoxyphenyl)methanone;
• N-(3,4-difluorophenyl)-2-(8-fluoro-5,11-dioxo-2,3,11,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-10(5H)-yl)acetamide;
• 5-(cyclohexylmethyl)-3-(14yridine-2-yl)-1,2,4-oxadiazole;
• ethyl 5-methyl-4-(2-((4-methylbenzyl)amino)-2-oxoethyl)-7-phenyl-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylate;
• [1,2,4]triazolo[1,5-a]pyrimidine-2-carboxylic acid;
• 1-(2-(piperidin-1-yl)-4,5-dihydro-1H-imidazol-1-yl)butan-1-one;
• (4-(6-chloro-[1,2,4]triazolo[4,3-a]14yridine-3-yl)piperazin-1-yl)(1-phenylcyclopropyl)methanone;
• N-(2,4-difluorophenyl)-2-(5,11-dioxo-2,3,11,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-10(5H)-yl)acetamide;
• and
• Ethyl-2,3-dihydro-3-oxo-1,2-benzisothiazole-2-acetate-1,1-dioxide;
• or a pharmaceutical salt thereof, or any combination thereof to said subject, thereby treating the disease or condition in said subject.

A compound of Formula VI:

• Wherein:
• G1 is optionally substituted NH-pyrrolidine, optionally substituted NH-piperidine, optionally substituted NH-piperazine, optionally substituted NH-imidazolidine, optionally substituted NH-pyrazolidine, optionally substituted NH-aryl, optionally substituted NH-cycloalkyl, optionally substituted pyrrolidine, optionally substituted piperidine, optionally substituted piperidin, optionally substituted piperazine, optionally substituted imidazolidine, or optionally substituted pyrazolidine;
• G2 is optionally substituted alkyl, optionally substituted aryl, optionally substituted cyloalkyl or optionally substituted heterocycle;
• Wherein:
• If G1 is unsubstituted pyrrolidine, then G2 is not alkyl, cyclopentyl, alkylcyclopentyl or furan;
• or
• If G1 is Piperidine then G2 is not alkyl;
• and
• If G1 is Piperazine, then G2 is not alkyl or furan;
• or a compound of Formula VII:
• Wherein:
• G1 is optionally substituted NH-pyrrolidine, optionally substituted NH-piperidine, optionally substituted NH-piperazine, optionally substituted NH-imidazolidine, optionally substituted NH-pyrazolidine, optionally substituted NH-pyridine, optionally substituted NH-aryl, optionally substituted NH-cycloalkyl, optionally substituted pyrrolidine, optionally substituted piperidine, optionally substituted piperidine, optionally substituted piperazine, optionally substituted imidazolidine, optionally substituted pyrazolidine or optionally substituted aryl;
• G2 is
• or optionally substituted alkyl, optionally substituted aryl or optionally substituted cyloalky;
• and
• G4 is optionally substituted pyrrolidine, optionally substituted piperidine, optionally substituted piperazine, optionally substituted imidazolidine or optionally substituted pyrazolidine;
• Wherein:
• If G1 is Piperidine then G4 is not pyrrolidine or G2 is not optionally substituted aryl;
• or
• If G1 is imidazolidine, then G2 is not optionally substituted aryl;
• or
• If G1 is optionally substituted NH-pyridine, then G2 is not optionally substituted aryl;
• or
• If G1 is optionally substituted NH-aryl, then G2 is not optionally substituted aryl;
• or
• If G1 is optionally substituted pyridine, then G2 is not optionally substituted aryl.