Tricyclic-2-pyridone compounds useful as HIV reverse transcriptase inhibitors

A compound of formula (I):

• 79
• or a stereoisomeric form or mixture of stereoisomeric forms or a pharmaceutically acceptable salt form thereof, wherein:
• A is a ring selected from:
• 80
• P is O or S;
• Rb is H, F, Cl, Br, I, C1-4 alkyl, C1-4 alkenyl, C1-4 alkynyl, C1-4 alkyl—O—, or C1-4 alkyl—NH—;
• W is N or CR3;
• X is N or CR3a;
• Y is N or CR3b;
• Z is N or CR3c;
• provided that if two of W, X, Y, and Z are N, then the remaining are other than N;
• R1 is selected from the group C1-3 alkyl substituted with 0-7 halogen and cyclopropyl;
• R2 is selected from the group —R2c, —OR2c, —OCHR2aR2b, —OCH2CHR2aR2b, —O(CH2)2CHR2aR2b, OCHR2aC (R2a)═C(R2b)2, —OCHR2aC(R2a)═C(R2b)2, —OCHR2aC═C-R2b, —SR2c, —SCHR2aR2b, —SCH2CHR2aR2b, —S(CH2)2CHR2aR2b, —SCHR2aC (R2a)═C (R2b)2, —SCHR2aC(R2a)═(R2b)2, SCHR2aC≡C-R2b, NR2aR2c, —NHCHR2aR2b, —NHCH2CHR2aR2b, —NH(CH2)2CHR2aR2b, —NHCHR2aC(R2a)═C(R2b)2, —NHCHR2aC(R2a)═(R2b)2, and —NHCHR2aC≡C-R2b;
• R2a is selected from the group H, CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3;
• R2b is H or R2c;
• R2c is selected from the group methyl substituted with 0-3 R3f, C1-6 alkyl substituted with 0-2 R4, C2-5 alkenyl substituted with 0-2 R4, C2-5 alkynyl substituted with 0-1 R4, C3-6 cycloalkyl substituted with 0-2 R3d, phenyl substituted with 0-2 R3d, and 3-6 membered heterocyclic system containing 1-3 heteroatoms selected from the group O, N, and S, substituted with 0-2 R3d;
• alternatively, the group —NR2aR2c represents a 4-7 membered cyclic amine, wherein 0-1 carbon atoms are replaced by O or NR5;
• R3 is selected from the group H, C1-4 alkyl, —OH, C1-4 alkoxy, OCF3, F, Cl, Br, I, —NR5R5a, —NO2, —CN, —C(O)R6, —NHC(O)R7 —NHC(O)NR5R5a, —NHSO2R10, —SO2NR5R5a, and a 5-6 membered heteroaromatic ring containing 1-4 heteroatoms selected from the group O, N, and S;
• R3a is selected from the group H, C1-4 alkyl, —OH, C1-4 alkoxy, OCF3, F, Cl, Br, I, —NR5R5a, —NO2, —CN, —C(O)R6, —NHC(O)R7, —NHC(O)NR5R5a, —NHSO2R10, —SO2NR5R5a, and a 5-6 membered heteroaromatic ring containing 1-4 heteroatoms selected from the group O, N, and S;
• alternatively, R3 and R3a together form —OCH2O—;
• R3b is selected from the group H, C1-4 alkyl, —OH, C1-4 alkoxy, OCF3, F, Cl, Br, I, —NR5R5a, —NO2, —CN, —C(O)R6, —NHC(O)R7, —NHC(O)NR5R5a, —NHSO2R11, and —SO2NR5R5a;
• alternatively, R3a and R3b together form —OCH2O—;
• R3c is selected from the group H, C1-4 alkyl, —OH, C1-4 alkoxy, OCF3, F, Cl, Br, I, —NR5R5a, —NO2, —CN, —C(O)R6, —NHC(O)R7, —NHC(O)NR5R5a, —NHSO2R10, and —SO2NR5R5a;
• alternatively, R3b and R3c together form —OCH2O—;
• R3d, at each occurrence, is independently selected from the group H, C1-4 alkyl, —OH, C1-4 alkoxy, OCF3, F, Cl, Br, I, —NR5R5a, —NO2, —CN, —C(O)R6, —NHC(O)R7, —NHC(O)NR5R5a, —NHSO2R10, and —SO2NR5R5a;
• R3e, at each occurrence, is independently selected from the group H, C1-4 alkyl, —OH, C1-4 alkoxy, OCF3, F, Cl, Br, I, —NR5R5a, —NO2, —CN, —C(O)R6, —NHC(O)R7, —NHC(O)NR5R5a, —NHSO2R10, and —SO2NR5R5a;
• R3f, at each occurrence, is independently selected from the group H, F, Cl, Br, I, C1-4 alkyl, —OH, —O—R11, —O—C3-10 carbocycle substituted with 0-2 R3e, OCF3, —O(CO)-R13, —OS(O)2C1-4alkyl, —NR12R12a, —C(O)R13, —NHC(O)R13, —NHSO2R10, and —SO2NR12R12a;
• R4 is selected from the group H, F, Cl, Br, I, C1-6 alkyl substituted with 0-2 R3e, C3-10 carbocycle substituted with 0-2 R3e, phenyl substituted with 0-5 R3e, and a 5-10 membered heterocyclic system containing 1-3 heteroatoms selected from the group O, N, and S, substituted with 0-2 R3e;
• R5 and R5a are independently selected from the group H and C1-4 alkyl;
• alternatively, R5 and R5a, together with the nitrogen to which they are attached, combine to form a 5-6 membered ring containing 0-1 O or N atoms;
• R6 is selected from the group H, OH, C1-4 alkyl, C1-4 alkoxy, and NR5R5a;
• R7 is selected from the group H, C1-3 alkyl and C1-3 alkoxy;
• R8 is selected from the group H, (C1-6 alkyl)carbonyl, C1-6 alkoxy, (C1-4 alkoxy)carbonyl, C6-10 aryloxy, (C6-10 aryl)oxycarbonyl, (C6-10 aryl)methylcarbonyl, (C1-4 alkyl)carbonyloxy(C1-4 alkoxy)carbonyl, C6-10 arylcarbonyloxy(C1-4 alkoxy)carbonyl, C1-6 alkylaminocarbonyl, phenylaminocarbonyl, phenyl(C1-4 alkoxy) carbonyl, and NR5R5a(C1-6 alkyl) carbonyl;
• R9 is selected from H, C1-4 alkyl, C1-4 alkenyl, and C1-4 alkynyl;
• R10 is selected from the group C1-4 alkyl and phenyl;
• R11 is selected from C1-6 alkyl, C1-6 haloalkyl, C1-6 alkyl substituted with C3-6cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 carbocycle substituted with 0-2 R3e;
• R12 and R12a are independently selected from H, C1-6 alkyl, and C3-6 carbocycle substituted with 0-2 R3e;
• alternatively, R12 and R12a can join to form 4-7 membered ring;
• and
• R13 is selected from the group H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, -O-C2-6 alkenyl, —O—C2-6 alkynyl, NR12R12a, C3-6 carbocycle, and —O—C3-6carbocycle.

A compound of formula (I):

• 81
• or a stereoisomeric form or mixture of stereoisomeric forms or a pharmaceutically acceptable salt form thereof, wherein:
• A is a ring selected from:
• 82
• P is O or S;
• Rb is H, F, Cl, Br, I, C1-4 alkyl, C1-4 alkenyl, C1-4 alkynyl, C1-4 alkyl—O—, or C1-4 alkyl—NH—;
• W is N or CR3;
• X is N or CR3a;
• Y is N or CR3b;
• Z is N or CR3c;
• provided that if two of W, X, Y, and Z are N, then the remaining are other than N;
• R1 is selected from the group C1-3 alkyl substituted with 0-7 halogen and cyclopropyl;
• R2 is selected from the group —R2c, —OR2c, —OCHR2aR2b, —OCH2CHR2aR2b, —O(CH2)2CHR2aR2b, OCHR2aC(R2a)═C(R2b)2, OCHR2aC(R2a)═C(R2b)2, —OCHR2aC≡C—R2b, —SR2c, —SCHR2aR2b, —SCH2CHR2aR2b, —S(CH2)2CHR2aR2b, —SCHR2aC(R2a)═C(R2b)2, —SCHR2aC(R2a)═(R2b)2, —SCHR2aC≡C—R2b, —NR2aR2c, —NHCHR2aR2b, —NHCH2CHR2aR2b, —NH(CH2)2CHR2aR2b, —NHCHR2aC(R2a)═C(R2b)2, —NHCHR2aC(R2a)═(R2b)2, and —NHCHR2aC4 C—R2b;
• R2a is selected from the group H, CH3, CH2CH3, CH(CH3)2, and CH2CH2CH3;
• R2b is H or R2c;
• R2c is selected from the group C1-6 alkyl substituted with 0-2 R4, C2-5 alkenyl substituted with 0-2 R4, C2-5 alkynyl substituted with 0-1 R4, C3-6 cycloalkyl substituted with 0-2 R3d, phenyl substituted with 0-2 R3d, and 3-6 membered heterocyclic system containing 1-3 heteroatoms selected from the group O, N, and S, substituted with 0-2 R3d;
• alternatively, the group -NR2aR2c represents a 4-7 membered cyclic amine, wherein 0-1 carbon atoms are replaced by O or NR5;
• R3 is selected from the group H, C1-4 alkyl, -OH, C1-4 alkoxy, OCF3, F, Cl, Br, I, —NR5R5a, —NO2, —CN, —C (O) R6, —NHC(O)R7, —NHC(O)NR5R5a, —NHSO2R10, —SO2NR5R5a, and a 5-6 membered heteroaromatic ring containing 1-4 heteroatoms selected from the group O, N, and S;
• R3a is selected from the group H, C1-4 alkyl, —OH, C1-4 alkoxy, OCF3, F, Cl, Br, I, —NR5R5a, —NO2, —CN, —C(O)R6, —NHC(O)R7, —NHC(O)NR5R5a, —NHSO2R10, —SO2NR5R5a, and a 5-6 membered heteroaromatic ring containing 1-4 heteroatoms selected from the group O, N, and S;
• alternatively, R3 and R3a together form —OCH2O—;
• R3b is selected from the group H, C1-4 alkyl, —OH, C1-4 alkoxy, OCF3, F, Cl, Br, I, —NR5R5a, —NO2, —CN, —C(O)R6, —NHC(O) R7, —NHC(O)NR5R5a, —NHSO2R10, and —SO2NR5R5a;
• alternatively, R3a and R3b together form —OCH2O—;
• R3c is selected from the group H, C1-4 alkyl, —OH, C1-4 alkoxy, OCF3, F, C1, Br, I, —NR5R5a, —NO2, —CN, —C(O)R6, —NHC(O)R7, —NHC(O)NR5R5a, —NHSO2R10, and —SO2NR5R5a;
• alternatively, R3b and R3c together form —OCH2O—;
• R3d, at each occurrence, is independently selected from the group H, C1-4 alkyl, —OH, C1-4 alkoxy, OCF3, F, Cl, Br, I, —NR5R5a, —NO2, —CN, —C(O)R6, —NHC—(O)R7, —NHC(O)NR5R5a, —NHSO2R10, and —SO2NR5R5a;
• R3e, at each occurrence, is independently selected from the group H, C1-4 alkyl, —OH, C1-4 alkoxy, OCF3, F, Cl, Br, I, NR5R5a, —NO2, —CN, —C(O)R6, —NHC(O)R7, —NHC(O)NR5R5a, —NHSO2R10, and —SO2NR5R5a;
• R4 is selected from the group H, R3dF, Cl, Br, I, C1-6 alkyl substituted with 0-2 R3e, C3-10 carbocycle substituted with 0-2 R3e, phenyl substituted with 0-5 R3e, and a 5-10 membered heterocyclic system containing 1-3 heteroatoms selected from the group O, N, and S, substituted with 0-2 R3e;
• R5 and R5a are independently selected from the group H and C1-4 alkyl;
• alternatively, R5 and R5a, together with the nitrogen to which they are attached, combine to form a 5-6 membered ring containing 0-1 O or N atoms;
• R6 is selected from the group H, OH, C1-4 alkyl, C1-4 alkoxy, and NR5R5a;
• R7 is selected from the group H, C1-3 alkyl and C1-3 alkoxy;
• R8 is selected from the group H, (C1-6 alkyl)carbonyl, C1-6 alkoxy, (C1-4 alkoxy)carbonyl, C6-10 aryloxy, (C6-10 aryl)oxycarbonyl, (C6-10 aryl)methylcarbonyl, (C1-4 alkyl)carbonyloxy(C1-4 alkoxy)carbonyl, C6-10 arylcarbonyloxy(C1-4 alkoxy)carbonyl, C1-6 alkylaminocarbonyl, phenylaminocarbonyl, phenyl(C1-4 alkoxy)carbonyl, and NR5R5a(C1-6 alkyl) carbonyl;
• R9 is selected from H, C1-4 alkyl, C1-4 alkenyl, and C1-4 alkynyl;
• and
• R10 is selected from the group C1-4 alkyl and phenyl.