[4-(Benzo[B]thiophen-2-yl) Pyrimidin-2-yl]-amine derivatives as IKK-beta inhibitors for the treatment of cancer and inflammatory diseases

A compound of Formula I:

• wherein:
• R1 is hydrogen, hydroxy, halo, methylthio, aminosulfonyl, pyrid-2-ylamino, 3-methylaminocarbonylphenyl, —C(O)NR8R9, —(CH2)0-1NHSO2R12, —CH2NHCONHR13, —NHC(O)R14, or pyrrolidinonyl optionally substituted with ethyloxycarbonyl;
• R2 is hydrogen, hydroxy, halo, cyano, (C1-C4)alkyl, or (C1-C4)alkoxy;
• R3 is hydrogen, halo, or methyl;
• R4 is (a) —NR6R7 or (b) aminomethylcyclohexyl, piperidinyl, 2,2,6,6-tetramethylpiperidin-4-yl, 2,2,6,6-tetramethylpiperidin-4-ylethenyl, 4-(C1-C4)alkylpiperidin-4-yl, or pyrrolidinyl;
• wherein (b) may be optionally substituted with a substituent selected from the group consisting of (C2-C4)alkenyl, (C3-C6)cycloalkyl, C(O)R10, and (C1-C4)alkyl optionally substituted with halo, (C1-C4)alkoxy, or (C3-C6)cycloalkyl;
• R5 is hydrogen or hydroxy provided that R5 must be H when n is 1;
• R6 is hydrogen or (C1-C4)alkyl;
• R7 is selected from the group consisting of hydrogen, (C1-C4)alkyl, piperidin-4-yl optionally substituted with (C1-C4)alkyl, piperidinylcarbonyl optionally substituted with (C1-C4)alkyl, pyrrolidin-3-yl optionally substituted with (C1-C4)alkyl, and pyrrolidinylcarbonyl optionally substituted with (C1-C4)alkyl;
• alternatively R6 and R7 along with the nitrogen to which they are attached form a ring selected from the group consisting of piperazinyl, homopiperazinyl, 4-dimethylaminopiperidin-1-yl, 3-dimethylaminopyrrolidin-1-yl, or hexahydro-pyrrolo[3,4-c]pyrrolyl;
• wherein the ring may be optionally substituted one time from the group consisting of (C2-C4)alkenyl, (C3-C6)cycloalkyl, C(O)R10, and one to three (C1-C4)alkyl substituents optionally substituted with hydroxy;
• R8 is hydrogen or (C1-C4)alkyl;
• R9 is hydrogen, (C1-C4)alkyl, (C1-C4)alkoxy, (C3-C6)cycloalkyl, thiazolyl, imidazolyl, pyridyl, phenyl optionally substituted with halo, 2-hydroxy-2-phenyl-ethyl, imidazolylethyl, 6-chloropyrid-3-ylmethyl, or furan-2-yl-(C1-C4 alkyl);
• alternatively R8 and R9 along with the nitrogen to which they are attached form a heterocycle selected from the group consisting of morpholinyl and thiazinyl;
• R10 is hydrogen, (C1-C4)alkyl, or NHR11;
• R11 is hydrogen or (C1-C4)alkyl;
• R12 is (C1-C4)alkyl, trifluoro(C1-C4)alkyl, benzyl, or (C3-C6)cycloalkyl;
• R13 is (C1-C4)alkyl, (C3-C6)cycloalkyl, or benzyl optionally substituted with (C1-C4)alkyl, halo, or (C1-C4)alkoxy;
• R14 is (C3-C6)cycloalkyl, piperidinyl, indolylmethyl, or benzyl optionally substituted with 3-dimethylamino-2-hydroxypropoxy;
• provided that when R4 is piperidinyl, R1 is —C(O)NR8R9;
• and
• n is 1-7 provided that n is 1 only when R4 is -aminomethylcyclohexyl or 2,2,6,6-tetramethylpiperidin-4-ylethenyl;
• or
• a pharmaceutically acceptable salt thereof.