Compounds and methods for treating cancer and inflammation

A method of treating cancer, inflammation or a hyperproliferative disorder in a mammal, which method comprises administering to the mammal in need thereof a therapeutically effective amount of a compound of formula (I):

• wherein:
• a is 0 to 4;
• R1 is carbocyclyl or heterocyclyl;
• each R2 is selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, halo, haloalkyl, haloalkenyl, nitro, cyano, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —OR7, —C(O)OR7, —C(O)N(R7)2, —N(R7)2, —N(R7)C(O)N(R7)2, —N(R7)C(O)OR8, —N(R7)C(O)R7, —R9—N═N—O—R8, —S(O)pR7 (where p is 0 to 2), and —S(O)pN(R7)2 (where p is 0 to 2);
• R3 and R4 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, halo, haloalkyl, haloalkenyl, nitro, cyano, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —OR7, —C(O)OR7, —C(O)N(R7)2, —N(R7)2, —N(R7)C(O)N(R7)2, —N(R7)C(O)OR8, —N(R7)C(O)R7, —R9—N═N—O—R8, —S(O)pR7 (where p is 0 to 2), and —S(O)pN(R7)2 (where p is 0 to 2);
• R5 and R6 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, cycloalkyl, cycloalkenyl and heterocyclylalkyl;
• each R7 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl and cycloalkylalkenyl;
• each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl and cycloalkylalkenyl;
• and
• R9 is a bond or a straight or branched alkylene or alkenylene chain;
• as a single stereoisomer, a mixture of stereoisomers, or as a racemic mixture of stereoisomers;
• or as a solvate or polymorph;
• or as a pharmaceutically acceptable salt thereof.

A method of treating a mammal having a disorder or condition associated with hyperproliferation and cell survival, wherein said method comprises administering to the mammal having the disorder or condition a therapeutically effective amount of a compound of formula (I):

• wherein:
• a is 0 to 4;
• R1 is carbocyclyl or heterocyclyl;
• each R2 is selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, halo, haloalkyl, haloalkenyl, nitro, cyano, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —OR7, —C(O)OR7, —C(O)N(R7)2, —N(R7)2, —N(R7)C(O)N(R7)2, —N(R7)C(O)OR8, —N(R7)C(O)R7, —R9—N═N—O—R8, —S(O)pR7 (where p is 0 to 2), and —S(O)pN(R7)2 (where p is 0 to 2);
• R3 and R4 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, halo, haloalkyl, haloalkenyl, nitro, cyano, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —OR7, —C(O)OR7, —C(O)N(R7)2, —N(R7)2, —N(R7)C(O)N(R7)2, —N(R7)C(O)OR8, —N(R7)C(O)R7, —R9—N═N—O—R8, —S(O)pR7 (where p is 0 to 2), and —S(O)pN(R7)2 (where p is 0 to 2);
• R5 and R6 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, cycloalkyl, cycloalkenyl and heterocyclylalkyl;
• each R7 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl and cycloalkylalkenyl;
• each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl and cycloalkylalkenyl;
• and
• R9 is a bond or a straight or branched alkylene or alkenylene chain;
• as a single stereoisomer, a mixture of stereoisomers, or as a racemic mixture of stereoisomers;
• or as a solvate or polymorph;
• or as a pharmaceutically acceptable salt thereof.

A method of treating a mammalian cell with a compound of formula (I):

• wherein:
• a is 0 to 4;
• R1 is carbocyclyl or heterocyclyl;
• each R2 is selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, halo, haloalkyl, haloalkenyl, nitro, cyano, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —OR7, —C(O)OR7, —C(O)N(R7)2, —N(R7)2, —N(R7)C(O)N(R7)2, —N(R7)C(O)OR8, —N(R7)C(O)R7, —R9—N═N—O—R8, —S(O)pR7 (where p is 0 to 2), and —S(O)pN(R7)2 (where p is 0 to 2);
• R3 and R4 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, halo, haloalkyl, haloalkenyl, nitro, cyano, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —OR7, —C(O)OR7, —C(O)N(R7)2, —N(R7)2, —N(R7)C(O)N(R7)2, —N(R7)C(O)OR8, —N(R7)C(O)R7, —R9—N═N—O—R8, —S(O)pR7 (where p is 0 to 2), and —S(O)pN(R7)2 (where p is 0 to 2);
• R5 and R6 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, cycloalkyl, cycloalkenyl and heterocyclylalkyl;
• each R7 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl and cycloalkylalkenyl;
• each R8 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl and cycloalkylalkenyl;
• and
• R9 is a bond or a straight or branched alkylene or alkenylene chain;
• as a single stereoisomer, a mixture of stereoisomers, or as a racemic mixture of stereoisomers;
• or as a solvate or polymorph;
• or as a pharmaceutically acceptable salt thereof, wherein the method comprises administering the compound of formula (I) to a mammalian cell and the compound of formula (I) is capable of inhibiting the activity of SGK within the mammalian cell.