Caspase inhibitors and uses thereof

A compound of formula I:

• wherein:
• X is —OR1 or —N(R5)2,
• Y is halo, trifluorophenoxy, or tetrafluorophenoxy;
• R1 is:
• C1-6 straight chained or branched alkyl, or C2-6 straight chained or branched alkenyl or alkynyl, wherein the alkyl, alkenyl, or alkynyl is optionally substituted with phenyl or CF3, or
• C3-6 cycloalkyl, wherein 1-2 carbon atoms in the cycloalkyl is optionally replaced with —O— or —NR5—;
• R2 is C1-6 straight chained or branched alkyl;
• R3 is hydrogen, halo, OCF3, CN, or CF3;
• R4 is hydrogen, halo, OCF3, CN, or CF3;
• and
• R5 is H, C1-6 straight chained or branched alkyl, or —O—C1-6 straight chained or branched alkyl;
• provided that if:
• Y is F;
• R2 is isopropyl, R3 is hydrogen, and R4 is Cl;
• or
• R2 is ethyl, R3 is hydrogen, and R4 is Cl or CF3;
• or
• R2 is ethyl, R3 is Cl or CF3, and R4 is hydrgen;
• then
• R1 is not t-butyl;
• and if
• Y is 2,3,5,6-tetrafluorophenoxy;
• R2 is ethyl;
• and
• R3 and R4 are each hydrogen;
• or
• R3 is hydrogen and R4 is Cl or CF3;
• or
• R3 and R4 are each Cl;
• then
• R1 is not t-butyl.

A process for preparing a corn pound of formula I:

• wherein:
• X is —OR1 or —N(R5)2,
• Y is halo, trifluorophenoxy, or tetrafluorophenoxy;
• R1 is:
• C1-6 straight chained or branched alkyl, or C2-6 straight chained or branched alkenyl or alkynyl, wherein the alkyl, alkenyl, or alkynyl is optionally substituted with optionally substituted phenyl, CF3, Cl, F, OMe, OEt, OCF3, CN, or NMe2;
• C3-6 cycloalkyl, wherein 1-2 carbon atoms in the cycloalkyl is optionally replaced with —O— or —NR5—;
• R2 is C1-6 straight chained or branched alkyl;
• R3 is hydrogen, halo, OCF3, CN, or CF3;
• R4 is hydrogen, halo, OCF3, CN, or CF3;
• and
• R5 is H, C1-6 straight chained orbianched alkyl, aryl, —O—C1-6 straight chained or branched alkyl, or —O-aryl;
• comprising the step of reacting a compound of formula I′:
• wherein X, Y, R2, R3, and R4 are as defined for formula I;
• under conditions forming an ester or aniide bond to provide a compound of formula I.

A process for preparing a compound of formula I:

• wherein:
• X is —OR1 or —N(R5)2,
• Y is halo, trifluorophenoxy, or tetrafluorophenoxy;
• R1 is:
• C1-6 straight chained or branched alkyl, or C2-6 straight chained or branched alkenyl or alkynyl, wherein the alkyl, alkenyl, or alkynyl is optionally substituted with optionally substituted phenyl, CF3, Cl, F, OMe, OEt, OCF3, CN, or NMe2;
• C3-6 cycloalkyl, wherein 1-2 carbon atoms in the cycloalkyl is optionally replaced with —O— or NR5—;
• R2 is C1-6 straight chained or branched alkyl;
• R3 is hydrogen, halo, OCF3, CN, or CF3;
• R4 is hydrogen, halo, OCF3, CN, or CF3;
• and
• R5 is H, C1-6 straight chained or branched alkyl, aryl, —O—C1-6 straight chained or branched alkyl, or —O-aryl;
• comprising the step of coupling a compound of formula A and a compound of formula K:
• to provide a compound of formula L:
• wherein X, Y, R1, R2, R3, and R4 are as defined in formula I and wherein the hydroxy group in K is optionally protected.

A process for preparing a compound of formula I:

• wherein:
• X is —OR1 or —N(R5)2,
• Y is halo, trifluorophonoxy, or tetrafluorc phenoxy;
• R1 is:
• C1-6 straight chained or branched alkyl, or C2-6 straight chained or branched alkenyl or alkynyl, wherein the alkyl, alkenyl, or alkynyl is optionally substituted with optionally substituted phenyl, CF3, Cl, F, OMe, OEt, OCF3, CN, or NMe2;
• C3-6 cycloalkyl, wherein 1-2 carbon atoms in the cycloalkyl is optionally replaced with —O— or —NR5—;
• R2 is C1-6 straight chained or branched alkyl;
• R3 is hydrogen, halo, OCF3, CN, or CF3;
• R4 is hydrogen, halo, OCF3, CN, or CF3;
• and
• R5 is H, C1-6 straight chained or bianched alkyl, aryl, —O—C1-6 straight chained or branched alkyl, or —O-aryl;
• comprising the step of oxidizing a compound of fonnula L:
• wherein X, Y, R1, R2, R3, and R4 are as defined for formula I;
• to provide a compound of formula I.