Inhibitors of interleukin-1β Converting enzyme inhibitors

A compound represented by the formula:

• each R5 is independently selected from the group consisting of:
• —C(O)—R10,
• —C(O)O—R9,
• —C(O)—N(R10)(R10),
• —S(O)2—R9,
• —S(O)2—NH—R10,
• —C(O)—CH2—O—R9,
• —C(O)C(O)—R10,
• —R9,
• —H,
• —C(O)C(O)—OR10, and
• —C(O)C(O)—N(R9)(R10);
• X5 is
• Y2 is H2 or O;
• each R9 is independently selected from the group consisting of —Ar3 and a —C1-6 straight or branched alkyl group optionally substituted with —Ar3, wherein the —C1-6 alkyl group is optionally unsaturated;
• each R10 is independently selected from the group consisting of —H, —Ar3, a —C3-6 cycloalkyl group, and a —C1-6 straight or branched alkyl group optionally substituted with —Ar3, wherein the —C1-6 alkyl group is optionally unsaturated;
• R13 is selected from the group consisting of H, Ar3, and a —C1-6 straight or branched alkyl group optionally substituted with —Ar3, —CONH2, —OR5, —OH, —OR9, or —CO2H;
• each R51 is independently selected from the group consisting of R9, —C(O)—R9, —C(O)—N(H)—R9, or each R51 taken together forms a saturated 4-8 member carbocyclic ring or heterocyclic ring containing —O—, —S—, or —NH—;
• R21 is independently selected from the group consisting of —H or a —C1-6 straight or branched alkyl group;
• each Ar3 is a cyclic group independently selected from the set consisting of an aryl group which contains 6, 10, 12, or 14 carbon atoms and between 1 and 3 rings and an aromatic heterocycle group containing between 5 and 15 ring atoms and between 1 and 3 rings, said heterocyclic group containing at least one heteroatom group selected from —O—, —S—, —SO—, SO2, ═N—, and —NH—, said heterocycle group optionally containing one or more double bonds, said heterocycle group optionally comprising one or more aromatic rings, and said cyclic group optionally being singly or multiply substituted by —Q1;
• each Q1 is independently selected from the group consisting of —NH2, —CO2H, —Cl, —F, —Br, —I, —NO2, —CN, ═O, —OH, -perfluoro C1-3 alkyl, R5, —OR5, —NHR5, —OR9, —N(R9)(R10), —R9, —C(O)—R10, and
• provided that when —Ar3 is substituted with a Q1 group which comprises one or more additional —Ar3 groups, said additional —Ar3 groups are not substituted with another —Ar3;
• and provided that when:
• R2 is:
• R21 is H;
• and
• Y is O, then R5 cannot be —C(O)R10, wherein R10 is —CH2CH2Ar3 and Ar3 is unsubstituted phenyl;
• or —SO2R9, wherein R9 is methyl;
• and when
• Y is CH2, then R5 cannot be —CO(O)R10, wherein R10 is —CH2CH2Ar3 and Ar3 is unsubstituted phenyl.

A compound represented by the formula:

• wherein:
• m is 1 or 2;
• R1 is:
• R2 is:
• each R5 is independently selected from the group consisting of:
• —C(O)—R10,
• —C(O)O—R9,
• —C(O)—N(R10)(R10),
• —S(O)2—R9,
• —S(O)2—NH—R10,
• —C(O)—CH2—O—R9,
• —C(O)C(O)—R10,
• —R9,
• —H,
• —C(O)C(O)—OR10, and
• —C(O)C(O)—N(R9)(R10);
• Y2 is H2 or O;
• each R9 is independently selected from the group consisting of —Ar3 and a —C1-6 straight or branched alkyl group optionally substituted with —Ar3, wherein the —C1-6 alkyl group is optionally unsaturated;
• each R10 is independently selected from the group consisting of —H, —Ar3, a —C3-6 cycloalkyl group, and a —C1-6 straight or branched alkyl group optionally substituted with —Ar3, wherein the —C1-6 alkyl group is optionally unsaturated;
• R13 is selected from the group consisting of H, Ar3, and a C1-6 straight or branched alkyl group optionally substituted with —Ar3, —CONH2, —OR5, —OH, —OR9, or —CO2H;
• each R51 is independently selected from the group consisting of R9, —C(O)—R9, —C(O)—N(H)—R9, or each R51 taken together forms a saturated 4-8 member carbocyclic ring or heterocyclic ring containing —O—, —S—, or —NH—;
• R21 is —CH3;
• each Ar3 is a cyclic group independently selected from the set consisting of an aryl group which contains 6, 10, 12, or 14 carbon atoms and between 1 and 3 rings and an aromatic heterocycle group containing between 5 and 15 ring atoms and between 1 and 3 rings, said heterocyclic group containing at least one heteroatom group selected from —O—, —S—, —SO—, SO2, ═N—, and —NH—, —N(R5)—, and —N(R9)— said heterocycle group optionally containing one or more double bonds, said heterocycle group optionally comprising one or more aromatic rings, and said cyclic group optionally being singly or multiply substituted by —Q1;
• and
• each Q1 is independently selected from the group consisting of —NH2, —CO2H, —Cl, —F, —Br, —I, —NO2, —CN, ═O, —OH, -perfluoro C1-3 alkyl, R5, —OR5, —NHR5, —OR9, —N(R9)(R10), —R9, —C(O)—R10, and
• provided that when —Ar3 is substituted with a Q1 group which comprises one or more additional —Ar3 groups, said additional —Ar3 groups are not substituted with another —Ar3.

A compound represented by the formula:

• wherein:
• m is 1 or 2;
• each R5 is —C(O)C(O)—OR10;
• Y2 is H2 or O;
• each R9 is independently selected from the group consisting of —Ar3 and a —C1-6 straight or branched alkyl group optionally substituted with —Ar3, wherein the —C1-6 alkyl group is optionally unsaturated;
• each R10 is independently selected from the group consisting of —H, —Ar3, a —C3-6 cycloalkyl group, and a —C1-6 straight or branched alkyl group optionally substituted with —Ar3, wherein the —C1-6 alkyl group is optionally unsaturated;
• R13 is selected from the group consisting of H, Ar3, and a C1-6 straight or branched alkyl group optionally substituted with —Ar3, —CONH2, —OR5, —OH, —OR9, or —CO2H;
• each R51 is independently selected from the group consisting of R9, —C(O)—R9, —C(O)—N(H)—R9, or each R51 taken together forms a saturated 4-8 member carbocyclic ring or heterocyclic ring containing —O—, —S—, or —NH—;
• R21 is independently selected from the group consisting of —H or a —C1-6 straight or branched alkyl group;
• each Ar3 is a cyclic group independently selected from the set consisting of an aryl group which contains 6, 10, 12, or 14 carbon atoms and between 1 and 3 rings and an aromatic heterocycle group containing between 5 and 15 ring atoms and between 1 and 3 rings, said heterocyclic group containing at least one heteroatom group selected from —O—, —S—, —SO—, SO2, ═N—, and —NH—, —N(R5)—, and —N(R9)— said heterocycle group optionally containing one or more double bonds, said heterocycle group optionally comprising one or more aromatic rings, and said cyclic group optionally being singly or multiply substituted by —Q1;
• and
• each Q1 is independently selected from the group consisting of —NH2, —CO2H, —Cl, —F, —Br, —I, —NO2, —CN, ═O, —OH, -perfluoro C1-3 alkyl, R5, —OR5, —NHR5, —OR9, —N (R9)(R10), —R9, —C(O)—R10, and
• provided that when —Ar3 is substituted with a Q1 group which comprises one or more additional —Ar3 groups, said additional —Ar3 groups are not substituted with another —Ar3.