Derivatives of pyridinone as inhibitors for tissue transglutaminase

A compound of the following general formula (I):

• wherein
• E1 and E2 are each independently —CO— or —SO2—;
• R* is selected from the group consisting of —H, —CH3, —C2H5, —C3H7, —CH(CH3)2, and —C4H9;
• R# is selected from the group consisting of NYY′, —OH, —OY, —NH—CH2—COOH, —NH—CH(CH3)—COOH, —NH—CH(CH2CH2SCH3)—COOH, —NH—CH(CH2OH)—COOH, —NH—CH(CH2SH)—COOH, —NH—CH(CH2CONH2)—COOH, —NH—CH(CH2CH2CONH2)—COOH, —NH—CH(CH2CH(CH3)2)—CH2COOH, —NH—CH(CH2Ph)-COOH, —NH—CH(CH2COOH)—COOH, —NH—CH(CH2CH2COOH)—COOH, —NH—CH(COOH)—CH(CH3)2, —NH—CH(COOH)—CH2CH(CH3)2, —NH—CH2—COOY′, —NH—CH(CH3)—COOY′, —NH—CH(CH2CH2SCH3)—COOP′, —NH—CH(CH2OH)—COOY′, —NH—CH(CH2SH)—COOY′, —NH—CH(CH2CONH2)—COOY′, —NH—CH(CH2CH2CONH2)—COOY′, —NH—CH(CH2CH(CH3)2)—CH2COOY′, —NH—CH(CH2Ph)-COOY′, —NH—CH(CH2COOH)—COOY′, —NH—CH(CH2COOY′)—COOH, —NH—CH(CH2COOY)—COOY′, —NH—CH(CH2CH2COOY)—COOY′, —NH—CH(COOH)—CH(CH3)2, —NH—CH(COOH)—CH2CH(CH3)2,
• Y is selected from the group consisting of:
• —CH2R1, —CHR1—CH2R2, —CHR1—CHR2—CH2R3, —CHR1—CHR2—CHR3—CH2R4, —CHR1—CHR2—CHR3—CHR4—CH2R5, —CHR1—CHR2—CHR3—CHR4—CHR5—CH2R6
• Y′, R17, R18, R19, and R20 are each independently selected from the group consisting of:
• —H, —CH3, —C2H5, —C3H7, —CH(CH3)2, —C4H9, —CH2—CH(CH3)2, —CH(CH3)—C2H5, —C(CH3)3, —C5H11, —CH(CH3)—C3H7, —CH2—CH(CH3)—C2H5, —CH(CH3)—CH(CH3)2, —C(CH3)2—C2H5, —CH2—C(CH3)3, —CH(C2H5)2, and —C2H4—CH(CH3)2;
• X is selected from the group consisting of —CR7R8R9, —CH2R7, —CHR7—CH2R8, —O—CH2R7, —O—CR7R8R9, —O—CHR7—CH2R8,
• Z is selected from the group consisting of:
• —CH3, —C2H5, —C3H7, —CH(CH3)2, —C4H9, -Ph, —CH2-Ph, —OCH3, —OC2H5, —OC3H7, —OCH(CH3)2, —OC4H9, —OPh, —OCH2-Ph, —OCH═CH2, and —OCH2—CH═CH2;
• R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are each independently selected from the group consisting of:
• —H, —OH, —OCH3, —OC2H5, —OC3H7, —O-cyclo-C3H5, —OCH(CH3)2, —OC(CH3)3, —OC4H9, —OPh, —OCH2-Ph, —OCPh3, —SH, —NO2, —F, —Cl, —Br, —I, —N3, —CN, —OCN, —NCO, —SCN, —NCS, —CHO, —COCH3, —COC2H5, —COC3H7, —CO-cyclo-C3H5, —COCH(CH3)2, —COC(CH3)3, —COOH, —COCN, —COOCH3, —COOC2H5, —COOC3H7, —COO-cyclo-C3H5, —COOCH(CH3)2, —COOC(CH3)3, —CONH2, —CONHCH3, —CONHC2H5, —CONHC3H7, —CONH-cyclo-C3H5, —CONH[CH(CH3)2], —CONH[C(CH3)3], —CON(CH3)2, —CON(C2H5)2, —CON(C3H7)2, —CON(cyclo-C3H5)2, —CON[CH(CH3)2]2, —CON[C(CH3)3]2, —NHCOCH3, —NHCOC2H5, —NHCOC3H7, —NHCO-cyclo-C3H5, —NHCO—CH(CH3)2, —NHCO—C(CH3)3, —NHCO—OCH3, —NHCO—OC2H5, —NHCO—OC3H7, —NHCO—O-cyclo-C3H5, —NHCO—OCH(CH3)2, —NHCO—OC(CH3)3, —NH2, —NHCH3, —NHC2H5, —NHC3H7, —NH-cyclo-C3H5, —NHCH(CH3)2, —NHC(CH3)3, —N(CH3)2, —N(C2H5)2, —N(C3H7)2, —N(cyclo-C3H5)2, —N[CH(CH3)2]2, —N[C(CH3)3]2, —SOCH3, —SOC2H5, —SOC3H7, —SO-cyclo-C3H5, —SOCH(CH3)2, —SOC(CH3)3, —SO2CH3, —SO2C2H5, —SO2C3H7, —SO2-cyclo-C3H5, —SO2CH(CH3)2, —SO2C(CH3)3, —SO3H, —SO3CH3, —SO3C2H5, —SO3C3H7, —SO3-cyclo-C3H5, —SO3CH(CH3)2, —SO3C(CH3)3, —SO2NH2, —OCF3, —OC2F5, —O—COOCH3, —O—COOC2H5, —O—COOC3H7, —O—COO-cyclo-C3H5, —O—COOCH(CH3)2, —O—COOC(CH3)3, —NH—CO—NH2, —NH—CO—NHCH3, —NH—CO—NHC2H5, —NH—CO—NHC3H7, —NH—CO—NH-cyclo-C3H5, —NH—CO—NH[CH(CH3)2], —NH—CO—NH[C(CH3)3], —NH—CO—N(CH3)2, —NH—CO—N(C2H5)2, —NH—CO—N(C3H7)2, —NH—CO—N(cyclo-C3H5)2, —NH—CO—N[CH(CH3)2]2, —NH—CO—N[C(CH3)3]2, —NH—C S-Nh2, —NH—C S-NhCH3, —NH—C S-NhC2H5, —NH—C S-NhC3H7, —NH—CS—NH-cyclo-C3H5, —NH—C S-Nh[CH(CH3)2], —NH—C S-Nh[C(CH3)3], —NH—CS—N(CH3)2, —NH—CS—N(C2H5)2, —NH—CS—N(C3H7)2, —NH—CS—N(cyclo-C3H5)2, —NH—CS—N[CH(CH3)2]2, —NH—CS—N[C(CH3)3]2, —NH2*HOOCCF3, —CH2F, —CF2Cl, —CHF2, —CF3, —CH2Cl, —CH2Br, —CH2I, —CH2—CH2F, —CH2—CHF2, —CH2—CF3, —CH2—CH2Cl, —CH2—CH2Br, —CH2—CH2I, cyclo-C3H5, cyclo-C4H7, cyclo-c5H9, cyclo-C6H11, cyclo-C7H13, cyclo-C8H15, -Ph, —CH2-Ph, —CPh3, —CH3, —C2H5, —C3H7, —CH(CH3)2, —C4H9, —CH2—CH(CH3)2, —CH(CH3)—C2H5, —C(CH3)3, C5H11, —CH(CH3)—C3H7, —CH2—CH(CH3)—C2H5, —CH(CH3)—CH(CH3)2, —C(CH3)2—C2H5, —CH2—C(CH3)3, —CH(C2H5)2, —C2H4—CH(CH3)2, —C6H13, —C3H6—CH(CH3)2, —C2H4—CH(CH3)—C2H5, —CH(CH3)—C4H9, —CH2—CH(CH3)—C3H7, —CH(CH3)—CH2—CH(CH3)2, —CH(CH3)—CH(CH3)—C2H5, —CH2—CH(CH3)—CH(CH3)2, —CH2—C(CH3)2—C2H5, —C(CH3)2—C3H7, —C(CH3)2—CH(CH3)2, —C2H4—C(CH3)3, —CH(CH3)—C(CH3)3, —CH═CH2, —CH2—CH═CH2, —C(CH3)═CH2, —CH═CH—CH3, —C2H4—CH═CH2, —C7H15, —C8H17, —CH2—CH═CH—CH3, —CH═CH—C2H5, —CH2—C(CH3)═CH2, —CH(CH3)—CH═CH, —CH═C(CH3)2, —C(CH3)═CH—CH3, —CH═CH—CH═CH2, —C3H6—CH═CH2, —C2H4—CH═CH—CH3, —CH2—CH═CH—C2H5, CH═CH—C3H7, CH2CH═CH—CH═CH2, CH═CH CH═CH—CH3, CH2NH2, —CH2OH, —CH2SH, —CH2—CH2NH2, —CH2—CH2SH, —C6H4—OCH3, —C6H4—OH, —CH2—CH2—OCH3, —CH2—CH2OH, —CH2—OCH3, —CH2—C6H4—OCH3, —CH2—C6H4—OH, —C≡CH, —C≡C—CH3, —CH2—C≡CH, —C2H4—C≡CH, —CH2—C≡C—CH3, —C≡C—C2H5, —C3H6—C≡CH, —C2H4—C≡C—CH3, —CH2—C≡C—C2H5, —C≡C—C3H7,
• R11, R12, R13, R14, R15, and R16 are each independently selected from the group consisting of:
• —H, —NH2, —OH, —OCH3, —OC2H5, —OC3H7, —OCF3, —CF3, —F, —Cl, —Br, —I, —CH3, —C2H5, —C3H7, —CH(CH3)2, -Ph, and —CN;
• and
• stereoisomeric forms, E/Z isomers, enantiomers, mixtures of enantiomers, diastereomers, mixtures of diastereomers, racemates, tautomers, anomers, keto-enol-forms, betaine forms, prodrugs, solvates, hydrates, and pharmaceutically acceptable salts of the above mentioned compounds.