N-substituted-heterocycloalkyloxybenzamide compounds and methods of use

A compound having structural formula (I)

• or a pharmaceutically acceptable salt, or N-oxide thereof, wherein
• R1 is H;
• R2 is azetidinyl, pyrrolidinyl, piperidinyl, or azepanyl, each substituted at its 1-position with an optionally substituted pyridinylmethyl, an optionally substituted furanylmethyl, an optionally substituted thienylmethyl, CO—O—(C0-C6 alkyl), —CO-Het, —CO—Ar or —SO2—(C0-C6 alkyl), wherein the azetidinyl, pyrrolidinyl, piperidinyl or azepanyl groups are optionally further substituted
• each R3 is independently selected from —(C1-C6 alkyl), —(C1-C6 fluoroalkyl), —(C0-C6 alkyl)-Ar;
• —(C0-C6 alkyl)-Het, —(C0-C6 alkyl)-Cak, —(C0-C6 alkyl)-Hca, —(C0-C6 alkyl)-L-R7, —(C0-C6 alkyl)-NR8R9, —(C0-C6 alkyl)-OR10, —(C0-C6 alkyl)-S(O)0-2R10, -halogen, —NO2 and —CN;
• w is 0, 1, 2 or 3;
• n is 0, 1, 2 or 3;
• each R4 is independently selected from —(C1-C6 alkyl), —(C1-C6 fluoroalkyl), —(C0-C6 alkyl)-Ar;
• —(C0-C6 alkyl)-Het, —(C0-C6 alkyl)-Cak, —(C0-C6 alkyl)-Hca, —(C0-C6 alkyl)-L-R7, —(C0-C6 alkyl)-NR8R9, —(C0-C6 alkyl)-OR10, —(C0-C6 alkyl)-S(O)0-2R10, -halogen, —NO2 and —CN, and two R4 on the same carbon optionally combine to form oxo;
• x is 0, 1, 2, 3 or 4;
• T is —(C0-C6 alkyl)-L-R7, —(C0-C6 alkyl)-NR8R9, —(C0-C6 alkyl)-OR10, —(C0-C6 alkyl)-S(O)0-2R10;
• or
• in which
• Q is —(C0-C3 alkyl)- in which each carbon of the (C0-C3 alkyl) is optionally and independently substituted with one or two R16;
• each R16 is independently selected from —(C1-C6 alkyl), —(C1-C6 fluoroalkyl), —(C0-C6 alkyl)-Het, —(C0-C6 alkyl)-Cak, —(C0-C6 alkyl)-Hca, —(C0-C6 alkyl)-L-R7, —(C0-C6 alkyl)-NR8R9, —(C0-C6 alkyl)-OR10, —(C0-C6 alkyl)-S(O)0-2R10, -halogen, —NO2 and —CN, and two R16 on the same carbon optionally combine to form oxo;
• the ring system denoted by “A” is a monocyclic aryl or heteroaryl;
• each R5 is independently selected from —(C1-C6 alkyl), —(C1-C6 fluoroalkyl), —(C0-C6 alkyl)-Ar;
• —(C0-C6 alkyl)-Het, —(C0-C6 alkyl)-Cak, —(C0-C6 alkyl)-Hca, —(C0-C6 alkyl)-L-R7, —(C0-C6 alkyl)-NR8R9, —(C0-C6 alkyl)-OR10, —(C0-C6 alkyl)-S(O)0-2R10, -halogen, —NO2 and —CN;
• and
• y is 0, 1, 2, 3 or 4;
• in which
• each L is independently selected from —NR9C(O)O—, —NR9C(O)—NR9—, —NR9C(O)S—, —NR9C(O)—, —NR9C(S)O—, —NR9C(S)—NR9—, —NR9C(S)S—, —NR9C(S)—, —OC(O)NR9—, —SC(O)NR9—, —C(S)NR9—, —OC(S)NR9—, —SC(S)NR9—, —C(S)NR9—, —S(O)0-2—, —C(O)O, —OC(O)—, —C(S)O—, —OC(S)—, —C(O)S—, —SC(O)—, —C(S)S—, —SC(S)—, —OC(O)O—, —SC(O)O—, —OC(O)S—, —SC(S)O—, —OC(S)S—, —NR9C(NR2)NR9—, —NR9SO2—, —SO2NR9— and —NR9SO2NR9—,
• each R6, R7, R8 and R10 is independently selected from H, —(C1-C6 alkyl), —(C1-C6 fluoroalkyl), —(C0-C6 alkyl)-Ar, —(C0-C6 alkyl)-Het, —(C0-C6 alkyl)-Cak, —(C0-C6 alkyl)-Hca, —(C0-C6 alkyl)-L-(C0-C6 alkyl), —(C0-C6 alkyl)-NR9(C0-C6 alkyl), —(C0-C6 alkyl)-O—(C0-C6 alkyl) and —(C0-C6 alkyl)-S(O)0-2—(C0-C6 alkyl),
• each R9 is independently selected from —H, —(C1-C4 alkyl) and —C(O)—(C1-C4 alkyl),
• each Ar is an optionally substituted aryl,
• each Het is an optionally substituted heteroaryl,
• each Cak is an optionally substituted cycloalkyl,
• each Hca is an optionally substituted heterocycloalkyl, and
• each alkyl is optionally substituted.