Inhibitors of inflammation and reperfusion injury and methods of use thereof

The compound of claim I wherein Y═O, R11, R12, R13, R15, R16, R17═H and R14 is selected from the group consisting of H, F, NO2, NH2, HCOCH2Cl, NHCOCH2N(CH3)2, NHCOCH2N(CH2CH3)2, NHCOCH2N(CH3)-piperazine, NHCOCH2CH2CH2N(CH3)-piperazine, NHCOCH2NH(CH2CH3), NHCOCH2-piperidine, NHCOCH21,2,3,4-tetrahydroisoquinoline, NHCOCH2N(CH3)CH2Ph, NHCOCH2(S)-prolinol, NHCOCH2-9-adenine, NHCOCH2-9-(6-chloropurine), NHCOCH2-9-(6-N,N-dimethylpurine), NHCOCH2-benzimidazole, NHCOCH2-ethylnipecotate, NHCOCH2-morpholine, NHCOCH2-pyrrolidine, NHCOCH2-1,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline, NHCOCH24-indolemethylester, NHCO-m-NO2-benzoyl, NHCOCH2CH2COOC(NH-cyclohexyl)2, OH, OCH3, OCH2COOCH3, OCH2COOH, OCH2CO-1,2,3,4-tetrahydroisoquinoline, OCO-m-NO2-benzoyl, CH2NH2, CH2NHCO-m-NO2-benzoyl, NHCOCH2CH2CH2COOH, NHCOCH═CHCOOH, NHCOCH2CH2CO-1,2,3,4-tetrahydroisoquinoline, NHCOCH2CH2CH2CO1,2,3,4-tetrahydroisoquinoline, NHCOCH2CH2OH, NHCOCH2CH2CH2OH, NHCONH-cyclohexyl, NHCO(CH2)4NHtBOC, NHCOCH2CH2CH2CH2NH2, NHCOCHNHtBoc(CH2)3-NH—C═NHNtBoc), NHCOCHNH2(CH2)3-guanidine, NHCOCHNHtBoc(5-CH2—N-tBoc-imidazole), NHCOCHNHtBoc(3-CH2-indole), NH-prolinyl, NH-nipecotyl, NH-3,4,5-trimethoxybenzoyl, NHCOCH2CH2CONH(2-CH2-benzimidazole), NHCO(CH2)2CONH(CH2)2-piperidine, NHCO(CH2)2CONH(CH2)2-piperidine, NHCO(CH2)2CONH(CH2)2-2-pyridine, NHCOCH(NHCOOC7H7)(CH2)4NHtBoc, NHCOCH(NHCOOC7H7)(CH2)4NH2, NHCOCH2COOH, NHCO(CH2)2COOH, NHCO(CH2)3COOH, NHCO(CH2)3COOH, NHCO(CH2)4COOH, NHCO(CH2)5COOH, NHCO(CH2)6COOH, NHCO(CH2)7COOH, NHCO(CH2)8COOH, NHCO(CHOAc)2COOH, NHCO(CF2)3COOH, NHCONHCH2COOH, NHCOCH2OCH2COOH, NHCOCH2NH2, NHCOCH2CH2NH2, NHCOCH(CH3)NH2, NHCOCH2NHCH3, NHCOCH2CH2NHCH3, NHCOCH2tBOC-piperazine, NHCOCH2-piperazine-HCl, NHCO(CH2)7NHCH3, NHCOCH2CO-piperazine-HCl, NHCOCH2CH2Cl, NHCOCH2CH2CH2Cl, NHCOC6H4COCH═CHCOOH, NHCO(2,5-difluorophenyl)COOH, NHCOCH2COOCH3, NHCO(CH2)2COOCH2CH3, NHCOCO COOCH3, NHCO(CH2)4COOCH3, NHCO(CH2)CH3, NHCO(CH2)6COOCH3, NHCO(P—C6H4-CH═CHCOOCH2CH3), NHCO(CH2)8COOCH3, NH(2-thiophenoyl), NH(2-furoyl), NH(m-chloromethylenebenzoyl), NH(m-N,N-diethylmethylenebenzoyl), NH(m-NHCOCH2Cl-benzoyl), NH(m-NHCOCH2N(CH2CH3)2-benzoyl), NH(m-NHCOCH2N(CH3)2-benzoyl), NH-[m-CH2-(2-hydroxymethylenepyrrolidine)-benzoyl], NH-[m-CH2-(1,2,3,4-tetrahydroisoquinoline)-benzoyl], NHCOCH2-isoindoline, NH-2-carboxybenzoyl, and NHCOCH2CH(OTBDMS)—CH2COOH.

A compound of formula I:

• A-Z1-L-Z2-G I:
• or a pharmaceutically accepted prodrug, hydrated salt, or mixtures thereof, wherein:
• A and G are connected via Z1 and Z2 respectively, to a linker, L;
• A is selected from the group consisting of Formulas II and III;
• 53
• wherein,
• X1 and X2 are, independently, N or CH,
• X3 is CR7═CR8, CHR7—CHR8, CR7═N, N═CR7, N═N, NR7—O, CHR7—O or CHR7—S, where R7 and R8 are, independently, H, alkyl, amino, substituted amino, hydroxy, or alkoxy;
• R1 and R2 are independently H, alkyl, NH2, OH, SH, Cl, NHR9, N═R9, N═NR9, or amide, where R9 is alkyl, aryl, arylalkyl, alkyl-heterocycle;
• R3 and R4 are independently H, hydroxy, C1-5 alkyl, amino, or halo;
• R5 and R6 are independently alkyl, acetyl, other acyl, or R5 and R6 taken together form a 5-or 6-membered optionally substituted heterocycle;
• Z1 is —CH2O—, —CH2NR10—, —CH2NR10C(O)—, —CONR10—, —CO2—, —CH2NHCONH—, —CH2—, —CH2NHCSNH—, —CO—, —CH2CO2—, —NHCO2, S, SO2, CH2S, or SO;
• Z2 is;
• —NR10CO—, —C(O)NR10—, —NHCONH—, —OC(O)—, —C(O)O—, NHCS, —CSNH—, NHCSNH, O, CO, OCO, OCONH, NH, CH2, CH-alkyl, NHCO2, S, SO2, CS, or SO;
• L is H, O, S, C1-15 alkylene chain optionally substituted in one or more positions, or a 5, 6 or 7 membered carbocycle or heterocycle optionally substituted in one or more positions, provided that L is not H when Z1 is O, and when L=H, Z2 and G are absent, and
• G is H, OH, SH, NH2, CO2H, unsubstituted or substituted alkyl, aryl, alkylaryl, carbocyclic, heterocyclic, bicyclic, bicyclic heterocycle, biphenyl or heterocyclic amines such as piperidine, piperazine, pyrole, imidazole, benzimidazole, tetrazoles, indole, isoquinoline, quinoline, or pyrrolidine.