Benzothiazole and benzothiophene compounds

A compound of Formula I:

• or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein:
• the dashed lines represent double-bonds with the proviso that only one of the two dashed line double bonds exists at the same time;
• X2 is S and X1 is N or CR1a;
• or X2 is O and X1 is N;
• or X2 is NR1b and X1 is N or CR1a;
• or X2 is N and X1 is NR1b;
• or X2 is CR1a and X1 is NR1b;
• X3, X4, and X5 are independently selected from CR1d and N;
• R1a is selected from the group consisting of H, halo, cyano, C1-C3 alkyl, C3-C5 cycloalkyl, halo-C1-C2alkyl, and C1-C3 alkoxy;
• R1b is selected from the group consisting of H, C1-C3 alkyl, and halo-C1-C2alkyl;
• R1d is selected from the group consisting of H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, C1-C4 alkylthio, halo, OH, CN, OCF3, OCHF2, OCH2F, C1-C2-alkoxy-C1-C2-alkoxy, halo-C1-C3-alkyl, halo-C1-2-alkoxy, halo-C1-2-alkylthio, benzyloxy substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano, and —(CH2)n-phenyl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano;
• Y is S or —CR1e═CR1f—;
• R1e is independently at each occurrence selected from the group consisting of H, halo, cyano, C1-C3 alkyl, C3-C5 cycloalkyl, halo-C1-C2alkyl, and C1-C3 alkoxy;
• R1f is independently at each occurrence selected from the group consisting of H, halo, cyano, C1-C3 alkyl, C3-C5 cycloalkyl, halo-C1-C2alkyl, and C1-C3 alkoxy;
• R2 is H, halo, C1-C4 alkyl, halo-C1-C2alkyl, C1-C4 alkoxy, CN or C3-C5 cycloalkyl;
• R3 is selected from the group consisting of C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, C1-2 haloalkyl, C1-2 haloalkoxy, C1-2 haloalkylthio, C3-4 cycloalkyl, halo-C3-4 cycloalkyl, C1-4 alkylamino, di-C1-4 alkylamino, (C1-2 alkoxy) C1-2 alkyl, C2-3 alkenyl, C2-3 alkynyl, tetrahydrofuran-2-yl, and halo;
• W is O or S;
• R4 and R5 are independently selected from H, C1-C6 alkyl, C1-C4 fluoroalkyl, and C1-C4 hydroxyalkyl, or R4 and R5 can be taken together with the carbon to which they are attached to form a C3-C7 cycloalkyl ring;
• is selected from the group consisting of a phenyl ring, a 5-membered heteroaryl ring containing at least one O, N or S atom, or a 6-membered heteroaryl ring containing at least one nitrogen atom;
• wherein
• (i) when ring
• is a 5-membered heteroaryl ring, then either
• (a) R6 is selected from the group consisting of H, halo, OCF3, OCHF2, OH, CN, NO2, NR11R12, COOH, C1-C4 alkoxycarbonyl, (C═O)NR11R12, C1-C4 alkylsulfonyl, S(═O)2NR11R12, and C1-C5 alkyl substituted by 0 to 7 groups independently selected from halo, CF3, OCF3, OH, hydroxy-C1-C4-alkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkoxy, di-C1-C4-alkylaminophenyl-C1-C4-alkyl, (di-C1-C4-alkoxy-C1-C4-alkyl)-C1-C4-alkyl, di-C1-C4-alkylamino, C3-C6-cycloalkyl, and C1-C4 alkylthio, or
• (b) R6 is B—D—, where B is selected from the group consisting of a C6-C10 aryl, a 5- to 10-membered heteroaryl, a 4- to 10-membered heterocyclyl containing carbon atoms and 1 to 4 additional heteroatoms selected from N, O, and S, a C3-C8 cycloalkyl which may contain unsaturation, and a C5-C11 spirocycloalkyl which may contain unsaturation and optionally containing 1 to 3 heteroatoms selected from O, N or S, all of which may be optionally substituted with one or more Rb, Rc, Rd and Re;
• and D is a linker selected from a single bond, —O—, —S—,
• C1-C4 alkylene substituted by 0 to 4 groups independently selected from halo or OH, C1-C4 alkyleneoxy, C1-C4 alkylenethio, C1-C4 alkyleneoxy-C1-C4-alkylene, C1-C4-alkylenethio-C1-C4-alkylene, —S—C1-C4-alkylene, —O—C1-C4-alkylene, —NHC(═O), —C(═O)NH—, SO2NH—, and —NHSO2—, and C2-C6 alkenylene;
• and
• (ii) when ring
• is phenyl or 6-membered heteroaryl, then
• R6 is B—D, where B is selected from the group consisting of a C6-C10 aryl, a 5- to 10-membered heteroaryl, a 4- to 10-membered heterocyclyl containing carbon atoms and 1 to 4 additional heteroatoms selected from N, O, and S, a C3-C8 cycloalkyl which may contain unsaturation, and a C5-C11 spirocycloalkyl which may contain unsaturation and optionally containing 1 to 3 heteroatoms selected from O, N or S, all of which may be optionally substituted with one or more Rb, Rc, Rd and Re;
• and D is a single bond;
• each of Rb, Rc, Rd and Re, at each occurrence, is independently selected from the group consisting of halo, halo-C1-C4 alkoxy, OH, CN, NO2, ═O, NR11R12, COOH, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkoxycarbonyl, (C═O)NR11R12, C1-C4 alkoxy-C1-C4 alkoxy, C1-C4 alkylsulfonyl, C1-C4 alkylsulfinyl, S(═O)2NR11R12, N(R13)(C═O)NR11R12, N(R13)(C═O)OR14, SO2R14, N(R13)(C═O)R14, NR13S(O)R14, NR13SO2R14, O(C═O)NR11R12, O(C═O)OR14, O(C═O)R14, (C═O)OR14, C3-C6 cycloalkyl, a 4- to 10-membered heterocyclyloxy;
• a C1-C5 alkyl substituted by 0 to 7 groups independently selected from halo, CF3, OCF3, OH, CN, hydroxy-C1-C4-alkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkoxy, di-C1-C4-alkylaminophenyl-C1-C4-alkyl, (di-C1-C4-alkoxy-C1-C4-alkyl)C1-C4-alkyl, di-C1-C4-alkylamino, C3-C6-cycloalkyl, phenyl, C1-C4-alkoxyphenyl-C1-C4-alkoxy, 4- to 10-membered heterocyclyloxy, C1-C4-alkylcarbonyloxy and C1-C4 alkylthio;
• —(CHR13)n-5- or 6-membered heteroaryl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, and CF2CH3;
• —(CHR13)n-4- to 10-membered-heterocyclyl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, and CF2CH3-, hydroxy-C1-C4-alkyl, halo-C1-C4 alkoxy, di-C1-C4-alkylamino-C1-C4-alkyl, halo-C1-C4 alkyl, C1-C4-alkoxy-C1-C4-alkyl, C3-C6 cycloalkyl-C1-C4-alkylcarbonyl, C6-C10 arylcarbonyl, C1-C4-alkylcarbonyloxy-C1-C4-alkyl, and a C6-C10 aryl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, C1-C4-alkoxycarbonyl, (C═O)NR11R12, CF3, OCF3, and CF2CH3;
• R11 and R12 are independently, at each occurrence, selected from the group consisting of H;
• C1-C4 alkyl;
• halo-C1-C4-alkyl;
• hydroxy-C1-C4-haloalkyl;
• C1-C4 alkyleneoxy-C1-C4-alkylene;
• C2-C4 alkenyl;
• C2-C4 alkynyl;
• di-C1-C4-alkylamino-C1-C4-alkyl;
• C1-C4-alkylcarbonylamino-C1-C4-alkyl;
• di-C1-C4-alkoxy-C1-C4-alkyl;
• di-C1-C4-alkylaminophenyl;
• hydroxy-C1-C4-alkyl;
• cyano-C1-C4-alkyl;
• C1-C4-alkoxy-C1-C4-alkyl;
• C1-C4 alkoxycarbonyl-C1-C4-alkyl;
• C1-C4-alkoxycarbonyl;
• C1-C4-alkylcarbonyl;
• phenylcarbonyl;
• C1-C4-alkoxycarbonylamino-C1-C4-alkylcarbonyl;
• di-C1-C4-alkylamino-C1-C4-alkylcarbonyl;
• amino-C1-C4-alkylcarbonyl;
• 4- to 10-membered-heterocyclyl-carbonyl;
• —(CR14R14)n-phenyl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano;
• —(CHR13)n—C3-C6-cycloalkyl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, hydroxy-C1-C4-alkyl, and C1-C4 alkyl;
• —(CHR13)n-4- to 10-membered-heterocyclyl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, oxo, hydroxy-C1-C4-alkyl, and C1-C4 alkyl;
• and —(CHR13)n-5- to 10-membered-heteroaryl substituted by 0 to 3 groups independently selected from the group consisting of halo, CF3, OCF3, 5- or 6-membered heteroaryl, OH, hydroxy-C1-C4-alkyl, and C1-C4 alkyl;
• or
• alternatively, R11 and R12, when attached to the same nitrogen, can be combined to form a 4- to 10-membered mono- or bicyclic heterocyclic ring containing carbon atoms substituted by 0 to 3 groups independently selected from the group consisting of halo, cyano, CF3, CHF2, OCF3, OCHF2, OCH2F, 5- or 6-membered heteroaryl, OH, oxo, hydroxy-C1-C4-alkyl, C1-C4 alkyl and C1-C4 alkoxy, and 0 to 2 additional heteroatoms selected from N, NR13, O and S(O)p;
• R13 is independently, at each occurrence, selected from the group consisting of H, C1-C6 alkyl and —(CH2)phenyl;
• R14 is independently, at each occurrence, selected from the group consisting of H, C1-C6 alkyl, halo-C1-C4-alkyl, C1-C4-alkoxycarbonylamino, (C6-C10 arylcarbonylamino), (a 5- to 10-membered heteroarylcarbonylamino) and —(CH2)n phenyl substituted by 0 to 3 groups independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyclopropyl, CF3, OCF3, 5- or 6-membered heteroaryl, OH, OCHF2, di-C1-C4-alkylamino, and cyano;
• R7 is selected from the group consisting of H, halo, hydroxyl, cyano, oxo, C1-C4 alkyl, hydroxy-C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkyl, halo-C1-C4-alkyl, C3-C6-cycloalkyl, halo-C3-C6-cycloalkyl, C1-C4-alkoxy, and halo-C1-C4-alkoxy;
• or
• R6 and R7 can be taken together with the carbons to which they attach to form a 5-7 membered heterocyclyl, heteroaryl, or aryl ring;
• n, at each occurrence, is independently selected from 0, 1, 2, 3, 4 or 5;
• and
• p, at each occurrence, is selected from 0, 1 and 2.