Compounds useful for the treatment of cancer, compositions thereof and methods therewith

A method for treating or preventing a disease responsive to the modulation of ligase activity comprising administering to a patient in need of such treatment or prevention an effective amount of a compound of formula (I):

• wherein:
• X, W and U are at each occurrence independently H, halogen, hydroxy, carboxy, alkoxy, alkylamino, branched or unbranched C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, haloalkyl, acyloxy, thioalkyl, sulfonyl, sulfinylalkyl, sulfonylalkyl, hydroxyalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, substituted or unsubstituted cycloalkyl, —C(═O)OR1, —OC(═O)R1, —C(═O)NR1R2, —C(═O)NR1OR2, —SO2NR1R2, —NR1SO2R2, —CN, —NO2, —NR1R2, —NR1C(═O)R2, —NR1C(═O)(CH2)qOR2, —NR1C(═O)(CH2)qR2, NR1C(═O)(CH2)qNR1R2, —O(CH2)qNR1R2;
• R1 and R2 are independently H or branched or unbranched C1-C10 alkyl;
• Y at each occurrence is independently H, branched or unbranched C1-C10 alkyl, or
• when
• o is 1, Y can be (═O);
• Z is C or O;
• Q is H, branched or unbranched C1-C10 alkyl;
• m is 0-5;
• n is 0-8;
• o is 0-2;
• p is 0-2;
• q is 0-5;
• and
• r is 0-5;
• or a pharmaceutically acceptable salt thereof.

A method for treating or preventing a disease responsive to the modulation of cellular p27/Kip1 levels comprising administering to a patient in need of such treatment or prevention an effective amount of a compound of formula (I):

• wherein:
• X, W and U are at each occurrence independently H, halogen, hydroxy, carboxy, alkoxy, alkylamino, branched or unbranched C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, haloalkyl, acyloxy, thioalkyl, sulfonyl, sulfinylalkyl, sulfonylalkyl, hydroxyalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, substituted or unsubstituted cycloalkyl, —C(═O)OR1, —OC(═O)R1, —C(═O)NR1R2, —C(═O)NR1OR2, —SO2NR1R2, —NR1SO2R2, —CN, —NO2, —NR1R2, —NR1C(═O)R2, —NR1C(═O)(CH2)qOR2, —NR1C(═O)(CH2)qR2, NR1C(═O)(CH2)qNR1R2, —O(CH2)qNR1R2;
• R1 and R2 are independently H or branched or unbranched C1-C10 alkyl;
• Y at each occurrence is independently H, branched or unbranched C1-C10 alkyl, or
• when
• o is 1, Y can be (═O);
• Z is C or O;
• Q is H, branched or unbranched C1-C10 alkyl;
• m is 0-5;
• n is 0-8;
• o is 0-2;
• p is 0-2;
• q is 0-5;
• and
• r is 0-5;
• or a pharmaceutically acceptable salt thereof.

A method for modulating cell growth comprising administering to a patient in need thereof an effective amount of a compound of formula (I):

• wherein:
• X, W and U are at each occurrence independently H, halogen, hydroxy, carboxy, alkoxy, alkylamino, branched or unbranched C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, haloalkyl, acyloxy, thioalkyl, sulfonyl, sulfinylalkyl, sulfonylalkyl, hydroxyalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, substituted or unsubstituted cycloalkyl, —C(═O)OR1, —OC(═O)R1, —C(═O)NR1R2, —C(═O)NR1OR2, —SO2NR1R2, —NR1SO2R2, —CN, —NO2, —NR1R2, —NR1C(═O)R2, —NR1C(═O)(CH2)qOR2, —NR1C(═O)(CH2)qR2, NR1C(═O)(CH2)qNR1R2, —O(CH2)qNR1R2;
• R1 and R2 are independently H or branched or unbranched C1-C10 alkyl;
• Y at each occurrence is independently H, branched or unbranched C1-C10 alkyl, or
• when
• o is 1, Y can be (═O);
• Z is C or O;
• Q is H, branched or unbranched C1-C10 alkyl;
• m is 0-5;
• n is 0-8;
• o is 0-2;
• p is 0-2;
• q is 0-5;
• and
• r is 0-5;
• or a pharmaceutically acceptable salt thereof.

A method for preserving a cell, blood, tissue, an organ or an organism comprising contacting said blood, tissue or organ with an effective amount of a compound of formula (I):

• wherein:
• X, W and U are at each occurrence independently H, halogen, hydroxy, carboxy, alkoxy, alkylamino, branched or unbranched C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, haloalkyl, acyloxy, thioalkyl, sulfonyl, sulfinylalkyl, sulfonylalkyl, hydroxyalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, substituted or unsubstituted cycloalkyl, —C(═O)OR1, —OC(═O)R1, —C(═O)NR1R2, —C(═O)NR1OR2, —SO2NR1R2, —NR1SO2R2, —CN, —NO2, —NR1R2, —NR1C(═O)R2, —NR1C(═O)(CH2)qOR2, —NR1C(═O)(CH2)qR2, NR1C(═O)(CH2)qNR1R2, —O(CH2)qNR1R2;
• R1 and R2 are independently H or branched or unbranched C1-C10 alkyl;
• Y at each occurrence is independently H, branched or unbranched C1-C10 alkyl, or
• when
• o is 1, Y can be (═O);
• Z is C or O;
• Q is H, branched or unbranched C1-C10 alkyl;
• m is 0-5;
• n is 0-8;
• o is 0-2;
• p is 0-2;
• q is 0-5;
• and
• r is 0-5;
• or a pharmaceutically acceptable salt thereof.

A method for treating or preventing a side-effect of chemotherapy or radiation therapy comprising administering to a patient in need of such treatment an effective amount of a compound of formula (I):

• wherein:
• X, W and U are at each occurrence independently H, halogen, hydroxy, carboxy, alkoxy, alkylamino, branched or unbranched C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, haloalkyl, acyloxy, thioalkyl, sulfonyl, sulfinylalkyl, sulfonylalkyl, hydroxyalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, substituted or unsubstituted cycloalkyl, —C(═O)OR1, —OC(═O)R1, —C(═O)NR1R2, —C(═O)NR1OR2, —SO2NR1R2, —NR1SO2R2, —CN, —NO2, —NR1R2, —NR1C(═O)R2, —NR1C(═O)(CH2)qOR2, —NR1C(═O)(CH2)qR2, NR1C(═O)(CH2)qNR1R2, —O(CH2)qNR1R2;
• R1 and R2 are independently H or branched or unbranched C1-C0 alkyl;
• Y at each occurrence is independently H, branched or unbranched C1-C10 alkyl, or
• when
• o is 1, Y can be (═O);
• Z is C or O;
• Q is H, branched or unbranched C1-C10 alkyl;
• m is 0-5;
• n is 0-8;
• o is 0-2;
• p is 0-2;
• q is 0-5;
• and
• r is 0-5;
• or a pharmaceutically acceptable salt thereof.

A method for regulating or controlling the differentiation or maturation of a mammalian stem cell comprising administering to a patient in need of such treatment or prevention an effective amount of a compound of formula (I):

• wherein:
• X, W and U are at each occurrence independently H, halogen, hydroxy, carboxy, alkoxy, alkylamino, branched or unbranched C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, haloalkyl, acyloxy, thioalkyl, sulfonyl, sulfinylalkyl, sulfonylalkyl, hydroxyalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, substituted or unsubstituted cycloalkyl, —C(═O)OR1, —OC(═O)R1, —C(═O)NR1R2, —C(═O)NR1OR2, —SO2NR1R2, —NR1SO2R2, —CN, —NO2, —NR1R2, —NR1C(═O)R2, —NR1C(═O)(CH2)qOR2, —NR1C(═O)(CH2)qR2, NR1C(═O)(CH2)qNR1R2, —O(CH2)qNR1R2;
• R1 and R2 are independently H or branched or unbranched C1-C10 alkyl;
• Y at each occurrence is independently H, branched or unbranched C1-C10 alkyl, or
• when
• o is 1, Y can be (═O);
• Z is C or O;
• Q is H, branched or unbranched C1-C10 alkyl;
• m is 0-5;
• n is 0-8;
• o is 0-2;
• p is 0-2;
• q is 0-5;
• and
• r is 0-5;
• or a pharmaceutically acceptable salt thereof.

A pharmaceutical composition suitable for treating a disease associated with the modulation of a ligase comprising a compound of formula (I):

• wherein:
• X, W and U are at each occurrence independently H, halogen, hydroxy, carboxy, alkoxy, alkylamino, branched or unbranched C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, haloalkyl, acyloxy, thioalkyl, sulfonyl, sulfinylalkyl, sulfonylalkyl, hydroxyalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, substituted or unsubstituted cycloalkyl, —C(═O)OR1, —OC(═O)R1, —C(═O)NR1R2, —C(═O)NR1OR2, —SO2NR1R2, —NR1SO2R2, —CN, —NO2, —NR1R2, —NR1C(═O)R2, —NR1C(═O)(CH2)qOR2, —NR1C(═O)(CH2)qR2, NR1C(═O)(CH2)qNR1R2, —O(CH2)qNR1R2;
• R1 and R2 are independently H or branched or unbranched C1-C10 alkyl;
• Y at each occurrence is independently H, branched or unbranched C1-C10 alkyl, or
• when
• o is 1, Y can be (═O);
• Z is O;
• Q is H, branched or unbranched C1-C10 alkyl;
• m is 0-5;
• n is 0-8;
• o is 0-2;
• p is 0-2;
• q is 0-5;
• and
• r is 0-5;
• or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

A pharmaceutical composition suitable for treating a disease associated with the modulation of a ligase comprising a compound of formula (II):

• wherein:
• X, W and U are at each occurrence independently H, halogen, hydroxy, carboxy, alkoxy, alkylamino, branched or unbranched C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, haloalkyl, acyloxy, thioalkyl, sulfonyl, sulfinylalkyl, sulfonylalkyl, hydroxyalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, substituted or unsubstituted cycloalkyl, —C(═O)OR1, —OC(═O)R1, —C(═O)NR1R2, —C(═O)NR1OR2, —SO2NR1R2, —NR1SO2R2, —CN, —NO2, —NR1R2, —NR1C(═O)R2, —NR1C(═O)(CH2)qOR2, —NR1C(═O)(CH2)qR2, NR1C(═O)(CH2)qNR1R2, —O(CH2)qNR1R2;
• X′ is H, hydroxy, carboxy, alkoxy, alkylamino, branched or unbranched C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, haloalkyl, acyloxy, thioalkyl, sulfonyl, sulfinylalkyl, sulfonylalkyl, hydroxyalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycle, substituted or unsubstituted cycloalkyl, —C(═O)OR1, —OC(═O)R1, —C(═O)NR1R2, —C(═O)NR1OR2, —SO2NR1R2, —NR1SO2R2, —CN, —NO2, —NR1R2, —NR1C(═O)R2, —NR1C(═O)(CH2)qOR2, —NR1C(═O)(CH2)qR2, NR1C(═O)(CH2)qNR1R2, —O(CH2)qNR1R2;
• R1 and R2 are independently H or branched or unbranched C1-C10 alkyl;
• Y at each occurrence is independently H, branched or unbranched C1-C10 alkyl, or
• when
• o is 1, Y can be (═O);
• Z is C or O;
• Q is H, branched or unbranched C1-C10 alkyl;
• n is 0-8;
• o is 0-2;
• p is 0-2;
• q is 0-5;
• r is 0-5;
• and
• wherein one of X, X′, U or W is not H,
• or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.