Piperazine and homopiperazine compounds

A compound of formula I:

• 517
• wherein
• the subscript n is 1 or 2;
• the subscript m is an integer of from 0 to 4;
• W is selected from the group consisting of N and C—R5;
• X is selected from the group consisting of S, O and N—R6;
• Y is selected from the group consisting of N and C—R7;
• Z is selected from the group consisting of N and C—R8;
• wherein
• each of R5, R6, R7 and R8 is independently selected from the group consisting of H, (C1-C6)alkyl, (C3-C7)cycloalkyl and —(CH2)n1—R11 wherein the subscript n1 is an integer of from 0 to 3 and R11 is selected from the group consisting of (C1-C6)alkoxy, (C1-C6)alkylthio, mono- or di-(C1-C6)alkylamino, amino, phenyl, pyridyl, furanyl, pyrrolyl, imidazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, thiazolyl, pyrazolyl, and thienyl, wherein each of the rings is optionally substituted with from 1 to 3 substituents selected from halogen, N3, NO2, CN, (C1-C6)alkyl, OR12, N(R12)2, CO2R12 and CON(R12)2, wherein each R12 is independently H or (C1-C6)alkyl;
• J is selected from the group consisting of a direct link, C(O), C(S), C(NR9), S(O) and S(O)2, wherein R9 is selected from the group consisting of H, CN, NO2 and (C1-C6)alkyl;
• A is selected from the group consisting of a direct link, O, S, N—R10, C(O) and CH(OH), wherein R10 is selected from the group consisting of H, (C1-C6)alkyl and C(O)—(C1-C6)alkyl;
• R is selected from the group consisting of H, halo, CN, NO2, N3, (C1-C6)alkyl, (C3-C7)cycloalkyl, —C(R13)═C(R13)2, —C≡CR13 and —(CH2)n2—R14;
• wherein each R13 is independently selected from the group consisting of H, F, Cl, Br, CN, (C—C6)alkyl, (C3-C7)cycloalkyl, (CH2)n2—R14 and C(O)—(CH2)n2—R14;
• and wherein each subscript n2 is independently an integer of from 0 to 3 and each R14 is independently selected from the group consisting of(C1-C6)alkoxy, (C1-C6)alkylthio, mono- or di-(C1-C6)alkylamino, amino, phenyl, pyridyl, furanyl, pyrrolyl, imidazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, thiazolyl, pyrazolyl, and thienyl, wherein each of the rings is optionally substituted with from 1 to 3 substituents selected from halogen, NO2, N3, CN, (C1-C6)alkyl, OR15, N(R15)2, CO2R15 and CON(R15)2, wherein each R15 is independently H or (C1-C6)alkyl;
• and wherein any alkyl or cycloalkyl portions of R1 are optionally substituted with from one to five F substituents;
• R2 is selected from the group consisting of H, halo, CN, NO2, N3, (C1-C6)alkyl, (C3-C7)cycloalkyl, —C(R16)═C(R16)2, —C≡CR16, —C(O)—(CH2)n3—R17 and —(CH2)n3—R17;
• wherein each R16 is independently selected from the group consisting of H, F, Cl, Br, CN, (C1-C6)alkyl, (CH2)n3—R17 and —(CH2)n3—C(O)—R17;
• wherein each subscript n3 is independently an integer of from 0 to 3 and each R17 is independently selected from the group consisting of (C1-C6)alkoxy, (C1-C6)alkylthio, mono- or di-(C1-C6)alkylamino, amino, hydroxy, phenyl, pyridyl, furanyl, pyrrolyl, imidazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, thiazolyl, pyrazolyl, and thienyl, wherein each of the rings is optionally substituted with from 1 to 3 substituents selected from halogen, N3, NO2, CN, (C1-C6)alkyl, OR18, N(R18)2, CO2R18 and CON(R18)2, wherein each R18 is independently H or (C1-C6)alkyl;
• and wherein any alkyl or cycloalkyl portions of R2 are optionally substituted with from one to five F substituents;
• each R3 is independently selected from the group consisting of (C1-C6)alkyl, (C3-C7)cycloalkyl, —(CH2)n4—R19 and —C(O)—(CH2)n4—R19;
• wherein the subscript n4 is an integer of from 0 to 4 and each R19 is independently selected from the group consisting of (C1-C6)alkoxy, (C1-C6)alkylthio, mono- or di-(C1-C6)alkylamino, amino, phenyl, pyridyl, furanyl, pyrrolyl, imidazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, thiazolyl, pyrazolyl, and thienyl, wherein each of the rings is optionally substituted with from 1 to 3 substituents selected from halogen, N3, NO2, CN, (C1-C6)alkyl, OR20, N(R20)2, CO2R20 and CON(R20)2, wherein each R20 is independently H or (C1-C6)alkyl;
• and wherein any alkyl or cycloalkyl portions of R3 are optionally substituted with from one to five F substituents;
• L is a direct link or a divalent linking group having a formula selected from the group consisting of
• 518
• wherein
• V1 is selected from the group consisting of a direct link, O, S and NR23;
• V2 is selected from the group consisting of a direct link, —(CR24=CR24)n8—, —(C≡C)n8—, C(O), C(S), S(O), S(O)2 and C(NR23);
• V3 is selected from the group consisting of a direct link, O, S and NR23;
• the subscript n5 is an integer of from 0 to 2;
• the subscripts n6 and n7 are each independently an integer of from 0 to 7;
• the subscript n8 is an integer of from 1 to 2;
• each R23 is independently selected from the group consisting of H and (C1-C6)alkyl;
• each R24 is independently selected from the group consisting of (C1-C6)alkyl, (C3-C7) cycloalkyl, (CH2)n9—R25 and —(CO)—(CH2)n9—R25 wherein the subscript n9 is an integer of from 0 to 3 and R25 is selected from the group consisting of (C1-C6)alkoxy, (C1-C6)alkylthio, mono- or di-(C1-C6)alkylamino, hydroxy, NH2, phenyl, pyridyl, furanyl, pyrrolyl, imidazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, thiazolyl, pyrazolyl, and thienyl, wherein each of the rings is optionally substituted with from 1 to 3 substituents selected from halogen, N3, NO2, CN, (C1-C6)alkyl, OR26, N(R16)2, CO2R26 and CON(R16)2, wherein each R26 is independently H or (C1-C6)alkyl;
• Ar1 is a 5- or 6-membered heteroaryl or phenyl group, optionally substituted with from one to three substituents independently selected from halogen, NO2, N3, CN, (C1-C6)alkyl, OR27, N(R27)2, CO2R27 and CON(R27)2, wherein each R27 is independently H or (C1-C6)alkyl;
• G is a (C3-C7)heterocycloalkyl or (C3-C7)cycloalkyl group, optionally substituted with from one to three substituents independently selected from halogen, ═O, N3, NO2, CN, (C1-C6)alkyl, OR28, N(R28)2, CO2R28 and CON(R28)2, wherein each R28 is independently H or (C1-C6)alkyl;
• each R21 and R22 is (i) independently selected from the group consisting of H, (C1-C6)alkyl, phenyl, pyridyl, furanyl, pyrrolyl, imidazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, thiazolyl, pyrazolyl, and thienyl, wherein each of the rings is optionally substituted with from 1 to 3 substituents selected from halogen, N3, NO2, CN, (C1-C6)alkyl, OR29, N(R29)2, CO2R29 and CON(R29)2, wherein each R29 is independently H or (C1-C6)alkyl;
• or (ii) combined to form —CH2—(CH2)n10—CH2—, wherein the subscript n10 is an integer of from 0 to 4;
• and
• R4 is a member selected from the group consisting of H, F, CF3, CN, N3, NO2, (C1-C6)alkyl, amino, mono- or di-(C1-C6)alkylamino, (C3-C7)cycloalkyl, (C3-C7)heterocycloalkyl, heteroaryl, fused (C8-C10)bicycloalkyl, fused (C8-C10)bicycloalkaryl, aryl and fused bicycloaryl;
• wherein any alkyl group present in R4 are unsubstituted, partially- or fully-substituted with F, and each of the rings is optionally substituted with from one to four substituents selected from halogen, NO2, N3, SO2NH2, CN, (C1-C6)alkyl, OR30, N(R30)2, CO2R30 and CON(R30)2, wherein each R30 is independently H or (C1-C6)alkyl;
• or a pharmaceutically acceptable salt or prodrug thereof.