Substituted oximes and hydrazones as neurokinin antagonists

A compound represented by the structural formula

• or a pharmaceutically acceptable salt thereof, wherein:
• a is 0, 1, 2 or 3;
• b and d are independently 0, 1 or 2;
• R is H, C1-6 alkyl, —OR6 or —F;
• A is ═N—OR1;
• when d is not 0, X is a bond, —C(O)—, —O—, —NR9—, —S(O)e—, —N(R6)C(O)—, —C(O)N(R6)—, —OC(O)NR6—, —OC(═S)NR6—, —N(R6)C(═S)O—, —S(O)2N(R6)—, —N(R6)S(O)2—, —N(R6)C(O)O—, —OC(O)— or —N(R6)C(O)NR7—;
• and
• when d is 0, X is a bond or —NR6—;
• T is H, R4-aryl or R4-heteroaryl;
• Q is R5-phenyl, or R5-naphthyl;
• R1 is H, C1-6 alkyl, —(C(R6)(R7))n—G, —G2, or —(C(R6)(R7))p—M—(C(R13)(R14))n—G;
• R4 and R5 are independently 1-3 substituents independently selected from the group consisting of H, halogeno, —OR6, —OC(O)R6, —OC(O)N(R6)(R7), —N(R6)(R7), C1-6 alkyl, —CF3, —C2F5, —COR6, —CO2R6, —CON(R6)(R7), —S(O)eR13, —CN, —OCF3, —OCHF2, —NR6CO2R16, —NR6COR7, —NR8CON(R6)(R7), NO2, —N(R6)S(O)2R13 or —S(O)2N(R6)(R7);
• or adjacent R4 substituents or adjacent R5 substituents can form a —O—CH2—O— group;
• R6, R7, R8, R13 and R14 are independently selected from the group consisting of H, C1-6 alkyl, C2-C6 hydroxyalkyl, C1-C6 alkoxy-C1-C6 alkyl, R15-phenyl, and R15-benzyl;
• R9 is independently selected from the group consisting of R6 and —OR6;
• or R6 and R7, or R7 and R9, together with the nitrogen to which they are attached, form a ring of 5 to 6 members, wherein 0, 1 or 2 ring members are selected from the group consisting of —O—, —S— and —N(R19)—;
• R6a, R7a, R8a, R9a, R10 and R10a are independently selected from the group consisting of H and C1-6 alkyl;
• R15 is 1 to 3 substituents independently selected from the group consisting of H, —OH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, halogeno, —CF3, —C2F5, —COR10, —CO2R10, —C(O)N(R10)2, —S(O)eR10a, —CN, —N(R10)COR10, —N(R10)CON(R10)2 and —NO2;
• R16 is C1-6 alkyl, R15-phenyl or R15-benzyl;
• R19 is H, C1-C6 alkyl, —C(O)N(R10)2 or —CO2R10;
• n and p are independently 1-6;
• G is selected from the group consisting of H, R4-aryl, R4-heterocycloalkyl, R4-heteroaryl, R4-cycloalkyl, —CH2F, —CHF2, —CF3, —OR6, —N(R6)(R7), —COR6, —CO2R6, —CON(R7)(R9), —S(O)eR13, —NR6CO2R16, —NR6COR7, —NR8CON(R6)(R7), —N(R6)S(O)2R13, —N(R6)S(O)2N(R33)(R34), —S(O)2N(R6)(R7), —OC(O)R6, —OC(O)N(R6)(R7), —C(═NOR8)N(R6)(R7), —C(═NR25)N(R6)(R7), —N(R8)C(═NR25)N(R6)(R7), —CN, —C(O)N(R6)OR7, and —C(O)N(R9)-(R4-heteroaryl), provided that when n is 1, G is not —OH or —N(R6)(R7);
• M is selected from the group consisting of a double bond, —O—, —N(R6)—, —C(O)—, —C(R6)(0R7)—, —C(R8)(N(R6)(R7))—, —C(═NOR6)N(R7)—, —C(N(R6)(R7))═NO—, —C(═NR25)N(R6)—, —C(O)N(R9)—, —N(R9)C(O)—, —C(═S)N(R9)—, —N(R9)C(═S)— and —N(R6)C(O)N(R7)—, provided that when n is 1, G is not OH or —NH(R6);
• and when p is 2-6, M can also be —N(R6)C(═NR25)N(R7)— or —OC(O)N(R6)—;
• G2 is R4-aryl, R4-heterocycloalkyl, R4-heteroaryl, R4-cycloalkyl, —COR6, —CO2R16, —S(O)2N(R6)(R7) or —CON(R6)(R7);
• e is 0, 1 or 2, provided that when e is 1 or 2, R13 and R10a are not H;
• R25 is H, C1-C6 alkyl, —CN, R15-phenyl or R15-benzyl;
• Z is
• g, h and j are independently 0-2;
• k is 1-4;
• J is ═O, ═S, ═NR9, ═NCN or ═NOR1;
• R26, is H, C1-6 alkyl, —(C(R6)(R7))n—G, —G2, —C(O)—(C(R8)(R9))n—G, OH, —OC(O)NH2 or —S(O)eR13;
• R28 is H, —(C(R6)(R7))t—G or —CON(R6)(R7);
• t is 0, 1, 2 or 3, provided that when j is 0, t is 1, 2 or 3;
• R30 is 1-3 substituents independently selected from the group consisting of H, halogeno, —OR6, —OC(O)R6, —OC(O)N(R6)(R7), —N(R6)(R7), C1-6 alkyl, —CF3, —C2F5, —COR6, —CO2R6, —CON(R6)(R7), —S(O)eR13, —CN, —OCF3, —NR6CO2R16, —NR6COR7, —NR8CON(R6)(R7), NO2, —N(R6)S(O)2R13 or —S(O)2N(R6)(R7);
• or adjacent R30 substituents can form a —O—CH2—O— group;
• and
• R33 and R34 are independently selected from the group consisting of H, C1-C6 alkyl, R15-phenyl and R15-benzyl;
• wherein heterocycloalkyl is a 4- to 6-membered saturated ring comprising 1 to 3 heteroatoms independently selected from the group consisting of —O—, —S— and —N(R19)—, with the remaining ring members being carbon, and heteroarvl is a 5- to 10 membered single or benzofused aromatic ring comprising 1 to 4 heteroatoms independently selected from —O—, —S— and —N═, provided that the rinas do not include adiacent oxygen or sulfur atoms.