Substituted 1-heteroaryl-4-substituted piperazine and piperidine analogues

A compound of the formula

• or a pharmaceutically acceptable salt thereof, wherein:
• V is absent or —(C═O)—.
• W is nitrogen, CH, or C—OH.
• Y1 and Y5 are independently CR or nitrogen.
• Y3 and Y4 are independently CR1 or nitrogen.
• Z is CR2 or nitrogen;
• such that no more than three of Y1, Y3, Z, Y4, and Y5 are nitrogen;
• Each R, R1, and R2 is independently
• (i) hydrogen, halogen, nitro, cyano, amino, carboxamide, imino, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C2-C6alkanoyl, C2-C6alkyloxime, C1-C6alkoxy, (C1-C6alkoxy)C1-C4alkyl, (C1-C6alkoxy)C1-C4alkoxy, C1-C6alkoxycarbonyl, C1-C6alkoxycarbonyl, mono- or di-C1-C6alkylcarboxamide, C1-C6alkylthio,C1-C6alkylsulfonyl, haloC1-C6alkyl, haloC1-C6alkoxy, hydroxyC1-C6alkyl, aminoC1-C6alkyl, or mono- or di-(C1-C6alkyl)aminoC0-C6alkyl, or
• (ii) (C3-C7cycloalkyl)C0-C6alkyl, (heterocycloalkyl)C0-C6alkyl, (phenyl)C0-C2alkyl, (phenyl)C0-C2alkoxy, (pyrrolyl)C0-C2alkyl, (thienyl)C0-C2alkyl, or (pyridyl)C0-C2alkyl;
• each of which is substituted with from 0 to 3 substituents independently chosen from halogen, C1-C2alkoxy, and C1-C2alkyl;
• or any two R1 and R2 may be taken together to form a fused 5- or 6-membered carbocycle or heterocycle, each of which is substituted with from 0 to 3 substituents independently chosen from halogen, hydroxy, nitro, cyano, amino, C1-C4alkyl, C1-C4alkoxy, haloC1-C4alkyl, and haloC1-C4alkoxy;
• n is 1 or 2;
• R3 is:
• (i) hydrogen, C1-C6alkyl, C2-C6alkenyl, or haloC1-C6alkyl;
• or
• (ii) taken together with one or both of R6 and R10 to form a fused carbocycle or heterocycle having one or two rings, wherein each ring contains from 5 to 8 ring members and 0, 1 or 2 heteroatoms.
• R4 is hydrogen, C1-C6alkyl, or haloC1-C6alkyl;
• Each R5 is independently:
• (i) hydrogen, halogen, hydroxy, nitro, cyano, amino, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, haloC1-C6alkyl, haloC1-C6alkoxy, mono- or di(C1-C6alkyl)amino, or aminoC1-C6alkyl;
• or
• (ii) taken together with R6 to form a fused 5- to 8-membered carbocycle or heterocycle or a methylene or ethylene bridge.
• R6 is:
• (i) hydrogen, halogen, hydroxy, nitro, cyano, amino, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, haloC1-C6alkyl, haloC1-C6alkoxy, mono- or di-(C1-C6alkyl)amino or aminoC1-C6alkyl, or
• (ii) taken together with R3 taken together with to form a fused carbocycle or heterocycle;
• or
• (iii) taken together with R5 to form a fused carbocycle or heterocycle or a methylene or ethylene bridge;
• P is N or CR7;
• Q is N or CR8;
• U is N or CR9;
• T is N or CR10;
• X is N or CR11;
• wherein at least one of P, Q, U, T, and X is nitrogen;
• when U or T is nitrogen at least one of P, Q, or X is also nitrogen, and
• when P or Q is nitrogen, at least one of U, T, and X is also nitrogen;
• R7 is:
• (i) hydrogen, halogen, hydroxy, nitro, cyano, —COOH, or a group of the formula L-M;
• or
• (ii) taken together with R8 or R12 to form a fused 5- or 6-membered carbocycle or heterocycle.
• R8 is:
• (i) hydrogen, halogen, hydroxy, nitro, cyano, —COOH, or a group of the formula L-M;
• or
• (ii) taken together with R7 to form a fused 5- or 6-membered carbocycle or heterocycle;
• R9 is:
• (i) hydrogen, halogen, hydroxy, nitro, cyano, —COOH, or a group of the formula L-M;
• or
• (ii) taken together with R10 or R11 to form a fused 5- to 10-membered carbocycle or heterocycle;
• R10 is:
• (i) hydrogen, halogen, hydroxy, nitro, cyano, —COOH, or a group of the formula L-M;
• or
• (ii) taken together with R3 or R9 to form a fused carbocycle or heterocycle;
• R11 is:
• (i) hydrogen, halogen, hydroxy, nitro, cyano, —COOH, or a group of the formula L-M;
• or
• (ii) taken together with R9 to form a fused carbocycle or heterocycle;
• R12 is:
• (i) hydrogen, halogen, hydroxy, nitro, cyano, amino, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, haloC1-C6alkyl, haloC1-C6alkoxy, mono- or di(C1-C6alkyl)amino, or aminoC1-C6alkyl;
• or
• (ii) taken together with R7 to form a fused carbocycle or heterocycle.
• Each L is independently a single covalent bond, N(R13), O, C(═O), SO2, SO2NH, C(═O)N(R13) or N(R13)C(═O) wherein each R13 is independently hydrogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, or haloC1-C6alkyl;
• and
• Each M is independently hydrogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, haloC1-C6alkyl, aminoC1-C6alkyl, or a 5- to 10-membered cycloalkyl or heterocycloalkyl;
• preferably M is other than hydrogen if L is a single covalent bond.