Methods of using benzothiophenone derivatives to treat cancer or inflammation

A pharmaceutical composition useful in treating cancer or inflammation in a human, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier, diluent or excipient and a compound of formula (I):

• wherein:
• each t is independently 0, 1 or 2;
• a is 1 to 4;
• b is 1 to 4;
• each R1 and each R2 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, halo, haloalkyl, haloalkenyl, nitro, cyano, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —OR5, —C(O)OR5, —C(O)N(R5)2, —N(R5)2, —N(R5)C(O)OR6, —N(R5)C(O)R5, —R7—N═N—O—R6, —S(O)pR5 (where p is 0 to 2), and —S(O)pN(R5)2 (where p is 0 to 2);
• R3 is hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —C(O)R5, —C(O)N(R5)2, —S(O)pR5 (where p is 0 to 2), or —S(O)pN(R5)2 (where p is 0 to 2);
• R4 is a straight or branched alkylene or alkenylene chain containing 1 to 4 carbon atoms, wherein each carbon in the chain can be replaced by a heteroatom selected from nitrogen, oxygen and sulfur, and wherein each carbon or sulfur atom in the chain can be optionally oxidized, and wherein each carbon in the chain can be optionally substituted by one or two substituents independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, halo, haloalkyl, haloalkenyl, nitro, cyano, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —OR5, —C(O)OR5, —C(O)N(R5)2, —N(R5)2, —N(R5)C(O)OR6, —N(R5)C(O)R5, —R7—N═N—O—R6, —S(O)pR5 (where p is 0 to 2), and —S(O)pN(R5)2 (where p is 0 to 2), and each nitrogen in the chain can be optionally substituted by alkyl, alkenyl, aryl, aralkyl, aralkenyl, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —C(O)R5, —C(O)N(R5)2, —S(O)pR5 (where p is 0 to 2), and —S(O)pN(R5)2 (where p is 0 to 2);
• each R5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl and cycloalkylalkenyl;
• each R6 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl and cycloalkylalkenyl;
• R7 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 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:
• each t is independently 0, 1 or 2;
• a is 1 to 4;
• b is 1 to 4;
• each R1 and each R2 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, halo, haloalkyl, haloalkenyl, nitro, cyano, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —OR5, —C(O)OR5, —C(O)N(R5)2, —N(R5)2, —N(R5)C(O)OR6, —N(R5)C(O)R5, —R7—N═N—O—R6, —S(O)pR5 (where p is 0 to 2), and —S(O)pN(R5)2 (where p is 0 to 2);
• R3 is hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —C(O)R5, —C(O)N(R5)2, —S(O)pR5 (where p is 0 to 2), or —S(O)pN(R5)2 (where p is 0 to 2);
• R4 is a straight or branched alkylene or alkenylene chain containing 1 to 4 carbon atoms, wherein each carbon in the chain can be replaced by a heteroatom selected from nitrogen, oxygen and sulfur, and wherein each carbon or sulfur atom in the chain can be optionally oxidized, and wherein each carbon in the chain can be optionally substituted by one or two substituents independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, halo, haloalkyl, haloalkenyl, nitro, cyano, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —OR5, —C(O)OR5, —C(O)N(R5)2, —N(R5)2, —N(R5)C(O)OR6, —N(R5)C(O)R5, —R7—N═N—O—R6, —S(O)pR5 (where p is 0 to 2), and —S(O)pN(R5)2 (where p is 0 to 2), and each nitrogen in the chain can be optionally substituted by alkyl, alkenyl, aryl, aralkyl, aralkenyl, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —C(O)R5, —C(O)N(R5)2, —S(O)pR5 (where p is 0 to 2), and —S(O)pN(R5)2 (where p is 0 to 2);
• each R5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl and cycloalkylalkenyl;
• each R6 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl and cycloalkylalkenyl;
• R7 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 tissue remodelling or repair, wherein said method comprises administering to the mammal having the disorder or condition a therapeutically effective amount of a compound of formula (I):

• wherein:
• each t is independently 0, 1 or 2;
• a is 1 to 4;
• b is 1 to 4;
• each R1 and each R2 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, halo, haloalkyl, haloalkenyl, nitro, cyano, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —OR5, —C(O)OR5, —C(O)N(R5)2, —N(R5)2, —N(R5)C(O)OR6, —N(R5)C(O)R5, —R7—N═N—O—R6, —S(O)pR5 (where p is 0 to 2), and —S(O)pN(R5)2 (where p is 0 to 2);
• R3 is hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —C(O)R5, —C(O)N(R5)2, —S(O)pR5 (where p is 0 to 2), or —S(O)pN(R5)2 (where p is 0 to 2);
• R4 is a straight or branched alkylene or alkenylene chain containing 1 to 4 carbon atoms, wherein each carbon in the chain can be replaced by a heteroatom selected from nitrogen, oxygen and sulfur, and wherein each carbon or sulfur atom in the chain can be optionally oxidized, and wherein each carbon in the chain can be optionally substituted by one or two substituents independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, halo, haloalkyl, haloalkenyl, nitro, cyano, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —OR5, —C(O)OR5, —C(O)N(R5)2, —N(R5)2, —N(R5)C(O)OR6, —N(R5)C(O)R5, —R7—N═N—O—R6, —S(O)pR5 (where p is 0 to 2), and —S(O)pN(R5)2 (where p is 0 to 2), and each nitrogen in the chain can be optionally substituted by alkyl, alkenyl, aryl, aralkyl, aralkenyl, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —C(O)R5, —C(O)N(R5)2, —S(O)pR5 (where p is 0 to 2), and —S(O)pN(R5)2 (where p is 0 to 2);
• each R5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl and cycloalkylalkenyl;
• each R6 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl and cycloalkylalkenyl;
• R7 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:
• each t is independently 0, 1 or 2;
• a is 1 to 4;
• b is 1 to 4;
• each R1 and each R2 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, halo, haloalkyl, haloalkenyl, nitro, cyano, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —OR5, —C(O)OR5, —C(O)N(R5)2, —N(R5)2, —N(R5)C(O)OR6, —N(R5)C(O)R5, —R7—N═N—O—R6, —S(O)pR5 (where p is 0 to 2), and —S(O)pN(R5)2 (where p is 0 to 2);
• R3 is hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —C(O)R5, —C(O)N(R5)2, —S(O)pR5 (where p is 0 to 2), or —S(O)pN(R5)2 (where p is 0 to 2);
• R4 is a straight or branched alkylene or alkenylene chain containing 1 to 4 carbon atoms, wherein each carbon in the chain can be replaced by a heteroatom selected from nitrogen, oxygen and sulfur, and wherein each carbon or sulfur atom in the chain can be optionally oxidized, and wherein each carbon in the chain can be optionally substituted by one or two substituents independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, halo, haloalkyl, haloalkenyl, nitro, cyano, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —OR5, —C(O)OR5, —C(O)N(R5)2, —N(R5)2, —N(R5)C(O)OR6, —N(R5)C(O)R5, —R7—N═N—O—R6, —S(O)pR5 (where p is 0 to 2), and —S(O)pN(R5)2 (where p is 0 to 2), and each nitrogen in the chain can be optionally substituted by alkyl, alkenyl, aryl, aralkyl, aralkenyl, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, heterocyclylalkyl, —C(O)R5, —C(O)N(R5)2, —S(O)pR5 (where p is 0 to 2), and —S(O)pN(R5)2 (where p is 0 to 2);
• each R5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl and cycloalkylalkenyl;
• each R6 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl and cycloalkylalkenyl;
• R7 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 PTPN12 and/or PTPN2 within the mammalian cell.