Aryloxy- and arylthiosubstituted pyrimidines and triazines and derivatives thereof

A compound of formula (I):

• 13
• or a pharmaceutically acceptable salt or prodrug thereof, wherein:
• Q═O, S(O)n;
• R1 is C1-C4-alkyl, -alkenyl, -alkynyl, C1-C2 haloalkyl, halogen, NR6R7, OR8, SR8, CN;
• R3 is C1-C8 alkyl, C1-C2 haloalkyl, halogen, NR6R7, OR8, SR8, (CH2)kNR6R7, (CH2)kOR8, CH(CHR16CHR16OR8)2, CH(CN)AR, CH(CN)2, CHR16 (CHR16)pOR8, (CHR16)pAr wherein the aryl group is substituted with 1-3 R18, (CHR16) pheteroaryl wherein the heteroaryl group is substituted with 1-3 R18, 1-tetrahydroquinolinyl, 2-tetrahydroisoquinolinyl, phenyl or heteroaryl substituted with 0-3 groups chosen from hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy, nitro, cyano, S (O)z-(C1-C6)alkyl;
• V is N;
• Y is CR2 or N;
• Z is N;
• R2 and is independently selected at each occurrence from the group consisting of hydrogen, halo, halomethyl, methyl cyano, nitro, NR6R7, NH(COR9), N(COR9)
• X and X′ are independently selected at each occurrence from the group consisting of alkyl, halogen, S(O)nR8, OR8, halomethyl, NR14R15, CN;
• R5 is H, halo, C1-C6 alkyl, C2-C6 alkenyl, C1-C3 haloalkyl, C1-C6 alkoxy, (CHR16)pOR8, (CHR16)pS(O)nR8 (CHR16)pNR14R15, C3-C6 cycloalkyl, C4-C6 cycloalkenyl, CN;
• R6 and R7 are independently selected at each occurrence from the group consisting of:
• hydrogen, C1-C6 alkyl, C3-C10 cycloalkyl,
• C3-C10 cycloalkylalkyl,
• CH(R16) (CHR16)pOR8, (CHR16)pOR8, —(C1-C6 alkyl)-aryl, heteroaryl, —(C1-C6alkyl)-heteroaryl or aryl optionally substituted with 1-3 groups selected from the following:
• hydrogen,
• halogen,
• C1-C6 alkyl,
• C1-C6 alkoxy,
• amino,
• NHC((═O) (C1C6 alkyl),
• NH(C1-C6 alkyl)
• N(C1-C6 alkyl)2,
• nitro
• CO2(C1-C6 alkyl),
• cyano,
• S(O)z—(C1-C6-alkyl), or
• R6 and R7 can be taken together to form —(CH2)qA (CH2)r—, optionally substituted with 0-3 R17,
• or, when considered with the commonly attached nitrogen, R6 and R7 can be taken together to form a heterocycle, said heterocycle being substituted on carbon with 1-3 groups consisting of:
• hydrogen,
• C1-C6 alkyl,
• (C1-C6) alkyl (C1-C4) alkoxy,
• hydroxy, or
• C1-C6 alkoxy;
• A is CH2, O, S(O)n, N(C(═O)R24), N(R19), C(H3)(NR14R15), C(H)(OR20) C(H)(C(═O)R21), N(S(O)nR 21);
• R8 is hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, (CH2)tR22, C3-C10 cycloalkyl, cycloalkylalkyl, —(C1-C6 alkyl)-aryl, heteroaryl, —(C1-C6 alkyl)-heteroaryl or aryl optionally substituted with 1-3 groups selected from the following:
• hydrogen,
• halogen,
• C1-C6 alkyl,
• C1-C6 alkoxy,
• amino,
• NHC(═O) (C1-C6 alkyl),
• NH(C1-C6 alkyl)
• N(C1-C6 alkyl)2,
• nitro
• CO2(C1-C6 alkyl),
• cyano,
• S(O)z(C1-C6-alkyl)
• R9 is independently selected at each occurrence from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, C2-C4 alkenyl, aryl substituted with 0-3 R18, and —(C1-C6 alkyl)-aryl substituted with 0-3 R18;
• R14 and R15 are independently hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, (CH2)tR22, aryl substituted with 0-3 R18;
• R16 is a hydrogen or C1-C4 alkyl
• R17 is hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halo, OR23, SR23, NR23R24, (C1-C6) alkyl, (C1-C4) alkoxy;
• R18 is hydrogen, C1-C4 alkyl, C1-C2 haloalkyl, C1-C4 alkoxy, C(═O)R24, NO2, halogen or cyano;
• R19 is C1-C6 alkyl, C3-C6 cycloalkyl, (CH2)wR22 aryl substituted with 0-3 R18;
• R20 is hydrogen, C(═O)R22, C1-C4 alkyl, C2-C4 alkenyl;
• R21 is hydrogen, C1-C4 alkoxy, NR23R24, hydroxyl or C1-C4 alkyl;
• R22 is cyano, OR24, SR24, NR23R24, C3-C6 cycloalkyl;
• R23 and R24 are independently selected at each occurrence from hydrogen or C1-C4 alkyl;
• k is 1-4;
• n is independently selected at each occurrence from 0-2;
• p is 0-3;
• q is 0-3;
• r is 1-4;
• t is independently selected at each occurrence from 1-6;
• z 0-3;
• w 1-6;
• provided, however, that when y is CR2, then R3 is(CHR16)pAr wherein the aryl group is substituted with 1-3 R18 or (CHR16)pheteroaryl wherein the heteroaryl group is substituted with 1-3 R18