Tetrahydropurinones and derivatives thereof as corticotropin releasing factor receptor ligands

A compound of Formula (I):

• 47
• or a pharmaceutically acceptable salt form thereof, wherein:
• R1 is H, C1-C4 alkyl substituted with 0-3 X1, C3-C8 cycloalkyl substituted with 0-3 X1, C2-C4 alkenyl substituted with 0-3 X1, or C2-C4 alkynyl substituted with 0-3 X1;
• each X1 is, independently at each occurrence, CN, hydroxy, halo, or C1-C4 alkoxy;
• alternatively, R1 is CN, C1-C4 haloalkyl, C1-C6 alkyl-NR1aR1b, NR1aC(O)R1b, C(O)NR1aR1b, OR1a, S(O)nR1a, or OC(O)R1a;
• each R1a and R1b is, independently, H, C1-C4 alkyl substituted with 0-3 X2, or C3-C6 cycloalkyl substituted with 0-3 X2;
• each X2 is, independently, at each occurrence, CN, hydroxy, halo, or C1-C4 alkoxy;
• n is 0, 1 or 2;
• R2 is H, C1-C6 alkyl substituted with 0 to 4 X3, C3-C7 cycloalkyl substituted with 0 to 4 X3, C3-C6-cycloalkyl-C1-C6 alkyl substituted with 0 to 4 X3, C3-C6-alkenyl substituted with 0 to 4 X3, C3-C6-alkynyl substituted with 0 to 4 X3 aryl substituted with 0 to 4 X3, heteroaryl substituted with 0 to 4×, or C5-C8 cycloalkenyl substituted with 0 to 4 X3;
• each X3 is, independently at each occurrence, halogen, OH, C2-C4 alkenyl, C2-C4 alkynyl, C2-C4 cycloalkyl, C1-C4 haloalkyl, CO2R7OC(O)R7, COR7, OC(O)OR7, CO2H, OR7, NR8R9, NR7COR9, NHR7SO2R9, OC(O)NR7R8, N(COR7)2, NR7CONR8R9, NR7CO2R9, CONR7R9, S(O)nR7, SO2NR7R9, SH, CN, aryl, heteroaryl, or heterocyclyl;
• R3 is aryl substituted with 0-5 XAr or heteroaryl substituted with 0-4 XhAr;
• each XAr is, independently at each occurrence, phenyl, C1-C6 alkyl, C3-C6 cycloalkyl, methylenedioxy, C1-C4 alkoxy-C1-C4 alkoxy, OR15, Br, Cl, F, I, C1-C4 haloalkyl, CN, NO2, SH, S(O)nR16, COR15, CO2R15, OC(O)R16, NR20COR15, N(COR15)2, NR20CONR15R17, NR20CO2R16, NR15R17, or CONR15R17;
• each XhAr is, independently at each occurrence, C1-C6 alkyl, C3-C6 cycloalkyl, Br, Cl, F, I, C1-C4 haloalkyl, CN, nitro, OR15, SH, S(O)nR16, COR15, CO2R15, OC(O)R16, NR20COR15, N(COR15)2, NR20CONR15R17, NR20CO2R16, NR15R17, CONR15R17, R20, CO2R21, COR21, or SO2R21;
• R4 is C1-C10 alkyl substituted with 0-1 X4 or 0-3 X5, C2-C10 alkenyl substituted with 0-1 X4 or 0-3 X5, C2-C10 alkynyl substituted with 0-1 X4 or 0-3 X5, C3-C8 cycloalkyl substituted with 0-1 X4 or 0-3 X5, C3-C6 cycloalkyl-C1-6 alkyl substituted with 0-1 X4 or 0-3 X5, C1-C4 alkoxy-C1-4 alkyl substituted with 0-1 X4 or 0-3 X5, aryl substituted with 0-1 X4 or 0-3 X5, heteroaryl substituted with 0-1 X4 or 0-3 X5, heterocyclyl substituted with 0-1 X4 or 0-3 X5, or aryl-C1-C4 alkyl substituted with 0-1 X4 or 0-3 X5;
• each X4 is, independently at each occurrence, CN, S(O)nR11, COR12, CO2R12, NR13COR12, N(COR12)2, NR13CONR12R14, NR13CO2R11, CONR12R14, 1-naphthalenyl, 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, or C3-8 cycloalkyl, wherein 0-1 carbon atoms in said C3-8 cycloalkyl is replaced by a group selected from the group consisting of —S(O)n—, —NR12—, —NCO2R11—, —NCOR11—and —NSO2R11—, and wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group consisting of R12, CO2R11, COR11 and SO2R11;
• each X5 is, independently at each occurrence, aryl, heteroaryl, heterocyclyl, C1-C6 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, Br, Cl, F, I, C1-4 haloalkyl, OR12, NR12R14, C1-C4 alkoxy-C1-C4 alkyl substituted with 0-1 R10, or C3-C8 cycloalkyl optionally substituted with 0-1 R11, and wherein 0-1 carbon atoms in said C3-C8 cycloalkyl is replaced by —O—;
• each R5 and R6 is, independently, H, C1-C4 alkyl, C3-C4 alkenyl, or C3-C4 alkynyl;
• each R7 is, independently at each occurrence, H, C1-C4 alkyl substituted with 0-2 X6, C3-C6 cycloalkyl substituted with 0-2 X6, C3-C4 alkenyl substituted with 0-2 X6, C3-C4 alkynyl substituted with 0-2 X6, C1-C4 haloalkyl substituted with 0-2 X6, C1-C4 alkyloxy-C1-C4 alkyl substituted with 0-2 X6, or C3-C6 cycloalkyl-C1-C4 alkyl substituted with 0-2 X6, wherein one carbon atom in any cycloalkyl ring is optionally replaced with O, S or NR8;
• each X6 is, independently at each occurrence, OH, C1-C4 alkoxy, or halogen;
• R8 is H, C1-C4 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl-C1-C4 alkyl, or C1-C4 haloalkyl;
• R9 is H, C1-C4 alkyl substituted with 0-2 X7, C3-C6 cycloalkyl substituted with 0-2 X7, C3-C4 alkenyl substituted with 0-2 X7, C3-C4 alkynyl substituted with 0-2 X7, C1-C4 haloalkyl substituted with 0-2 X7, aryl substituted with 0-2 X7, C1-C4 alkyloxy-C1-C4 alkyl substituted with 0-2 X7, or C3-C6 cycloalkyl-C1-C4 alkyl substituted with 0-2 X7, wherein one carbon in any cycloalkyl ring is optionally replaced with O, S or NR8;
• each X7 is, independently at each occurrence, C1-C4 alkoxy or halogen;
• R10 is H, C1-C4 alkyl, C3-C6 cycloalkyl-C1-C4 alkyl, or C3-C8 cycloalkyl;
• R11 is C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy-C1-C4 alkyl, C3-C6 cycloalkyl, or C3-C6 cycloalkyl-C1-6 alkyl;
• R12 is H, benzyl, aryl, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy-C1-C4 alkyl, C3-C6 cycloalkyl, or C3-C6 cycloalkyl-C1-6 alkyl;
• R13 is H, C1-C4 alkyl, C3-C7 cycloalkyl, or C3-C6 cycloalkyl-C1-C6 alkyl;
• R14 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy-C1-C4 alkyl, C3-C6 cycloalkyl, or C3-C6 cycloalkyl-C1-C6 alkyl;
• R15 is H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkoxy-C1-4 alkyl, C1-4 haloalkyl, R18S(O)n—C1-4 alkyl, or R11R12N—C2-4 alkyl;
• each R16 and R17 is, independently at each occurrence, H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkoxy-C1-2 alkyl, or C1-4 haloalkyl;
• alternatively, in an NR15R7 moiety R15 and R17 are taken together with the nitrogen atom to which they are both attached to form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl, or 1-piperazinyl, wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group consisting of R19, CO2R18, COR18 and SO2R18;
• R18 is C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, aryl, aryl-C1-4 alkyl, heteroaryl, or heteroaryl-C1-4 alkyl, wherein said aryl-C1-4 alkyl is substituted with 0-1 substituents selected from the group consisting of C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy C1-4 haloalkoxy, and dimethylamino;
• R19 is H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, aryl, aryl-C1-4 alkyl, heteroaryl, or heteroaryl-C1-4 alkyl;
• R20 is H, C1-4 alkyl, C3-7 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, aryl substituted with 0-3 X8, or aryl-C1-C4 alkyl substituted with 0-3 X8;
• each X8 is, independently at each occurrence, C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, or dimethylamino;
• R21 is C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, or aryl-C1-C4 alkyl, wherein said aryl-C1-C4 alkyl is substituted with 0-1 X9;
• and
• each X9 is, independently at each occurrence, C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, or dimethylamino.