Thioether triazolopyridine and triazolopyrimidine inhibitors of myeloperoxidase

The compound according to the formula (I)

• or a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a polymorph, or a solvate thereof, wherein:
• ring A is independently phenyl substituted with 0-1 R2 and 0-4 R3, or (a 5- to 6-membered heteroaryl comprising carbon atoms and 1-4 heteroatoms selected from N, NRa, O, and S(O)p, wherein said heterocycle is substituted with 0-1 R2 and 0-3 R3);
• X is independently CH or N;
• Y is independently selected from:
• a hydrocarbon linker substituted with 0-1 R1, or a hydrocarbon-heteroatom linker substituted with 0-1 R1;
• wherein said hydrocarbon linker has one to six carbon atoms and may be straight or branched;
• and said hydrocarbon-heteroatom linker has one to four carbon atoms and one group selected from O, S, NH, N(C1-4 alkyl), CONH, and NHCO;
• R1 is independently selected from:
• CN, OH, —(C1-4 alkyl substituted with 0-1 R18), C1-4 haloalkyl, Ph, Bn, COPh, CH(OH)Ph, CO2(C1-4 alkyl), and CONHBn;
• R2 is independently selected from:
• —CH(NH2)CF3, —(CH2)tOH, —O(CH2)2-3N(C1-4 alkyl)2, —(CH2)nR4, and —(CH2)n(X1)n(CH2)nR5;
• X1 is independently selected from:
• C(Me)2, O, S, CO and SO2;
• R3 is, at each occurrence, independently selected from:
• halogen, CN, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, NO2, CONH2, and SO2(C1-4 alkyl);
• alternatively, R2 and R3, together with the carbon atoms to which they are attached, combine to form a 5- to 6-membered carbocyclic or heterocyclic ring comprising carbon atoms and 0-3 heteroatoms selected from N, NRa, O, and S(O)p;
• wherein said heterocycle is substituted with 0-2 R19;
• R4 is independently selected from:
• halogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 haloalkyl, C1-4 haloalkoxy, C1-4 haloalkylthio, CN, CO2(C1-4 alkyl), NO2, NR6R7, CONR6R7, COR10, —CONH(CH2)1-2NR9R10, SO2NR9R10, and S(O)pR8;
• R5 is independently selected from:
• C3-10 carbocycle substituted with 0-2 R11, phenyl substituted with 0-3 R11 and 0-1 R12, and 5- to 10-membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, NRa, O, and S(O)p;
• wherein said heterocycle is substituted with 0-2 R11 and 0-1 R13;
• R6 is, at each occurrence, independently selected from:
• H, C1-4 haloalkyl, C1-6 alkyl substituted with 0-2 R15, —(CH2)n—(C3-6 cycloalkyl substituted with 0-1 R14), —(CH2)n-(phenyl substituted with 0-1 R16), —(CH2)n-(a 5- to 10-membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, NRa, O, and S(O)p, wherein said heterocycle is substituted with 0-1 R17);
• R7 is, at each occurrence, independently selected from:
• H and C1-4 alkyl substituted with R11;
• alternatively, R6 and R7, together with the nitrogen atom to which they are attached, combine to form a 4- to 10-membered heterocyclic ring comprising carbon atoms and 1-4 heteroatoms selected from N, NRa, O, and S(O)p;
• wherein said heterocycle is substituted with 0-1 R17;
• R8 is, at each occurrence, independently selected from:
• C1-4 alkyl, —(CH2)t—C3-6 cycloalkyl, and —(CH2)t-phenyl;
• R9 is, at each occurrence, independently selected from:
• H and C1-4 alkyl;
• R10 is, at each occurrence, independently selected from:
• R8 and H;
• R11 is, at each occurrence, independently selected from:
• OH, halogen, C1-4 alkoxy, C1-4 haloalkyl, and C1-4 haloalkoxy;
• R12 is independently selected from:
• halogen, CN, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C1-4 alkylthio, OH, CH2OH, CO2H, CO2(C1-4 alkyl), NH2, CH2NH2, N(C1-4 alkyl)2, CH2N(C1-4 alkyl)2, CONH2, CONH(C1-4 alkyl), CONHCH2CH2(C1-4 alkyl)2, CON(C1-4 alkyl)2, SO2NH2, SO2NH(C1-4 alkyl), SO2N(C1-4 alkyl)2, CONHPh, NHCOPh, —(CH2)n—(C3-6 carbocycle substituted with 0-2 Rc), and (a 5- to 6-membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, NRa, O, and S(O)p, wherein said heterocycle is substituted with 0-2 Rc);
• R13 is independently selected from:
• R12 and ═O;
• R14 and R16 are, at each occurrence, independently selected from:
• halogen, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, OH, CH2OH, N(C1-4 alkyl)2, CONH2, CONH(C1-4 alkyl), CON(C1-4 alkyl)2, OCH2CONH2, NHCO(C1-4 alkyl), NHCO2(C1-4 alkyl), SO2(C1-4 alkyl), —(CH2)n-phenyl, —O—(CH2)n-phenyl, and pyridylmethyl;
• R15 is, at each occurrence, independently selected from:
• OH, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, N(C1-4 alkyl)2, CONH2, CONH(C1-4 alkyl), and CON(C1-4 alkyl)2;
• R17 is independently selected from:
• R14 and ═O;
• R18 is independently selected from:
• OH, CN, NH2, N(C1-4 alkyl)2, NHBn, imidazolyl and morpholinyl;
• R19 is independently selected from:
• halogen and CO2(C1-4 alkyl);
• Ra is, at each occurrence, independently selected from:
• H, C1-4 alkyl, CO(C1-4 alkyl), CO2(C1-4 alkyl), SO2(C1-4 alkyl), —(CH2)n—C3-6 cycloalkyl, —(CH2)n-(phenyl substituted with 0-2 Rc), —CO(—(CH2)n-phenyl), (a 5- to 6-membered heteroaryl comprising carbon atoms and 1-4 heteroatoms selected from N, NRb, O, and S(O)p, wherein said heterocycle is substituted with 0-2 Rc);
• Rb is, at each occurrence, independently selected from:
• H and C1-4 alkyl;
• Rc is, at each occurrence, independently selected from:
• OH, CN, C1-4 alkyl, halogen, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, N(C1-4 alkyl)2, —CH2N(C1-4 alkyl)2, CONHCH2CH2N(C1-4 alkyl)2, pyrrolidinyl, piperazinyl, and
• n is, at each occurrence, independently selected from:
• 0, 1 and 2;
• p is, at each occurrence, independently selected from:
• 0, 1 and 2;
• and
• s is, at each occurrence, independently selected from:
• 1 and 2;
• provided that
• is excluded.