Phospho-indoles as HIV inhibitors

1. A compound of Formula (A):

or a pharmaceutically acceptable salt, N-oxide, quaternary amine, stereochemical isomer or tautomer thereof, wherein:

X is substituted or unsubstituted phenyl;

Y is O-alkyl;

W is O; S; NH; N—N(R 2 )(R 2 ); N(R 2 ); N—OH; or N—O-alkyl;

each R 2 is independently H; OH; halogen; optionally substituted, branched or unbranched alkyl; optionally substituted, branched or unbranched alkenyl; optionally substituted, branched or unbranched alkynyl; 3-14 membered carbocycle; alkylheterocycle; acyl; carboxamido; carbamoyl; alkoxy; optionally substituted aryl; optionally substituted aralkyl; optionally substituted alkylaryl; O-alkyl; O-alkenyl; O-alkynyl; O-alkaryl; O-aralkyl; O-carbocycle; O-heterocycle; O-aryl; CF 3 ; CN; S(O) n -R 3 ; N(R 3 )(R 3 ); NH—S(O) n -R 3 ; NHC(═W)-aryl; NHC(═W)-alkyl; NHC(═W)-heterocycle; CH 2 —S(O) n R 3 ; C(═W)R 3 ; C(═W)NR 3 R 3 ; C(alkyl) 2 -S(O) n R 3 ; CH(alkyl)-S(O) n R 3 ; C(alkyl) 2 -NH 2 ; CH(alkyl)-N(alkyl)R 3 ; CR 3 R 2 -NR 3 R 3 ; CH 2 N(alkyl)R 3 ; CH(alkyl)-NHR 3 ;C(alkyl) 2 -NHR 3 ; C(alkyl) 2 -N(alkyl)R 3 ; CH 2 —C(═W)H; CH 2 —C(═W)alkyl; CR 3 R 3 -C(═W)R 3 ; A-R 3 ; C(R 3 ) 2 -C(═W)R 3 ; CH 2 —C(═W)H; CH 2 —C(═W)alkenyl; CH(alkenyl)-C(═W)H; A-S(O)R 3 ; CH(NH)—S(O) n R 3 ; or A-N(NH)R 3 ; wherein said optional substitution comprises one or more of: a substituted or unsubstituted heterocycle; C(═W)O-aryl; C(═W)O-alkyl; C(═W)NH 2 ; C(═W)NH-alkyl; C(═W)NH-aryl; C(═W)N-di-alkyl; C(═W)N(alkyl)-aryl; α-amino acid; α-amino ester; α-amino-carboxamide; β-amino acid; β-amino ester; or β-amino-carboxamide;

each R 3 is independently H; OH; C 1-6 alkyl; C 2-6 alkenyl; C 2-6 alkynyl; alkoxy; CF 3 ; CN; amino; NR 2 R 2 ; O-alkyl; O-alkenyl; O-alkynyl; C(R 2 )(R 2 )-S(O) n NH 2 ; C(R 2 )(R 2 )-S(O) n CF 3 ; C(R 2 )(R 2 )-NH 2 ; A-heterocycle; C(R 2 )(R 2 )-NR 2 R 2 ; C(R 2 )(R 2 )-C(═W)R 2 ; aryl; carbocycle; heterocycle; cycloalkyl; alkaryl; alkylheterocycle; aralkyl; or heterocycle-alkyl; any of which may be unsubstituted or substituted with one or more of the following taken in any combination: halo; OH; OR 2 ; SR 2 ; COOH; carboxylic acid ester; C(═W)R 2 ; C(═W)OR 2 ; C(═W)OR 3 ; C(═W)SR 2 ; A-C(═W)NH 2 ; C(═W)NR 2 R 3 ; NR 2 R 2 ; NR 2 R 3 ; NR 2 —S(O) n R 3 ; NR 2 —C(═W)—C 1-6 alkyl; S(O) n R 3 ; C 1-6 alkoxy; C 1-6 thioether; amino acid residue; NH-A-(amino acid residue); C(═W)NH-A-(amino acid residue); and wherein when said optional substitution comprises a substituted heterocycle, then substitution is selected from the group consisting of: C(═W)O-aryl; C(═W)O-alkyl; C(═W)NH 2 ; C(═W)NH-aryl; C(═W)NH-alkyl; C(═W)N-di-alkyl; C(═W)N(alkyl)-aryl; α-amino acid; α-amino ester; α-amino-carboxamide; β-amino acid; β-amino ester; or β-amino-carboxamide; halo; or cyano; taken alone or in any combination;

each n is independently 0, 1 or 2;

A is a disubstituted spacer selected from the group consisting of: C 1-6 alkylene, branched or unbranched, and optionally having one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions in or attached to the chain; C 2-12 alkenylene, branched or unbranched, and optionally having one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions in or attached to the chain; C 2-12 alkynylene, branched or unbranched, and optionally having one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions in or attached to the chain; optionally substituted arylene; O-alkylene, branched or unbranched, and optionally having one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions in or attached to the chain; aralkylene, branched or unbranched, and optionally having one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions in or attached to the chain; optionally substituted cycloalkyl; and optionally substituted heterocycle; wherein “A” may be joined by any desired linkage or any combination of desired linkages;

R 1 , R 4 ′, R 6 ′ and R 7 ′ are each independently H;

R5′ is halogen; and

Z is carboxamide.

2. The compound of claim 1 according to Formula (A):

or a pharmaceutically acceptable salt, N-oxide, quaternary amine, stereochemical isomer or tautomer thereof, wherein:

X is substituted or unsubstituted phenyl;

Y is O-alkyl;

W is O;

R 1 , R 4 ′, R 6 ′ and R 7 ′ are each independently H;

R 5 ′ is halogen; and

Z is carboxamide.

3. The compound of claim 1 wherein R 5 ′ is chlorine.

4. The compound of claim 1 wherein Y is —O—C 1-6 alkyl.

5. The compound of claim 1 selected from the group consisting of:

6. The compound of claim 1 that is:

7. The compound of claim 1 according to Formula (B):

or a pharmaceutically acceptable salt, N-oxide, quaternary amine, stereochemical isomer or tautomer thereof, wherein:

R 2 ″, R 3 ″, R 4 ″, R 5 ″ and R 6 ″ are independently hydrogen, halogen, NO 2 , CN, OR 2 , SR 2 , NH 2 , NR 3 R 3 , NR 2 -C(═W)C 1-4 alkyl, NR 2 -S(O) 2 C 1-4 alkyl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, CF 3 , C(R 2 )(R 2 )-S(O) n -R 3 , C(R 2 )(R 2 )-NR 2 R 3 , COH, C(R 2 )(R 2 )-C(═W)R 2 , acyl, C(═W)R 2 , C(═W)OR 2 , C(═W)SR 2 , C(═W)NR 3 R 3 , C(═W)NH(CH 2 ) p -(amino acid residue), amino residue; A-(amino acid residue), cyanoalkyl, cyanoalkenyl, or cyanoalkynyl;

Y is O-alkyl;

W is O;

R 1 , R 4 ′, R 6 ′ and R 7 ′ are each independently H;

R 5 ′ is halogen;

Z is carboxamide;

p is 0-10; and

wherein R 2 , R 3 , n and A are defined as in claim 1 .

8. The compound of claim 1 according to Formula (B):

or a pharmaceutically acceptable salt, N-oxide, quaternary amine, stereochemical isomer or tautomer thereof, wherein:

R 2 ″, R 4 ″, and R 6 ″ are hydrogen; and R 3 ″ and R 5 ″ are independently halogen, NO 2 , CN, OR 2 , NHR 5 C 1-6 alkyl, NHC(O)C 1-6 alkyl, oxime, hydrazine, N(OH)C 1-6 alkyl, C 1-6 alkoxy; OH; NR 2 R 2 ; or C 1-6 alkyl, alkenyl or alkynyl optionally substituted with one or more of OH, SR, CN, halo, C(═W)H, C(═W)OH, halogen, NR 2 R 2 , C 1-6 thioether, or C 1-6 alkoxy;

Y is O-alkyl;

W is O;

R 1 , R 4 ′, R 6 ′ and R 7 ′ are each independently H;

R 5 ′ is halogen;

Z is carboxamide;

p is 0-10; and

wherein R 2 , R 3 , n and A are defined as in claim 1 .

9. The compound of claim 2 wherein R 5 ′ is chlorine.

10. The compound of claim 7 wherein R 5 ′ is chlorine.

11. The compound of claim 8 wherein R 5 ′ is chlorine.

12. The compound of claim 2 wherein Y is —O—C 1-6 alkyl.

13. The compound of claim 7 wherein Y is —O—C 1-6 alkyl.

14. The compound of claim 8 wherein Y is —O—C 1-6 alkyl.

15. A pharmaceutical composition comprising a compound of claim 1 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, optionally with a pharmaceutically acceptable carrier or diluent.

16. A pharmaceutical composition comprising a compound of claim 1 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, in combination with at least one other anti-HIV agent, optionally with a pharmaceutically acceptable carrier or diluent.

17. The pharmaceutical composition of claim 16 wherein the other anti-HIV agent is a reverse transcriptase inhibitor.

18. The pharmaceutical composition of claim 17 wherein the reverse transcriptase inhibitor induces a mutation lysine 103→asparagine and/or tyrosine 181→cysteine in HIV reverse transcriptase.

19. A method for the treatment of an HIV-infection in a host comprising administering to said host an anti-HIV effective treatment amount of a compound of claim 1 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, optionally with a pharmaceutically acceptable carrier or diluent.

20. The method of claim 19 wherein the host is human.

21. A method for the treatment of an HIV-infection in a host comprising administering to said host an anti-HIV effective treatment amount of a compound of claim 1 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, in combination and/or alternation with at least one other anti-HIV agent, optionally with a pharmaceutically acceptable carrier or diluent.

22. The method of claim 21 wherein the host is human.

23. The method of claim 21 wherein the other anti-HIV agent is a reverse transcriptase inhibitor.

24. The method of claim 23 wherein the reverse transcriptase inhibitor induces a mutation lysine 103→asparagine and/or tyrosine 181→cysteine in HIV reverse transcriptase.

25. A method for the treatment of an HIV-infection in a host, wherein the HIV has a mutation at lysine 103→asparagine and/or tyrosine 181→cysteine in HIV reverse transcriptase, comprising administering to said host an effective anti-HIV treatment amount of a compound of claim 1 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, optionally with a pharmaceutically acceptable carrier or diluent.

26. The method of claim 25 wherein the host is human.

27. A method for the treatment of an HIV-infection in a host, wherein the HIV has a mutation at lysine 103→asparagine and/or tyrosine 181→cysteine in HIV reverse transcriptase, comprising administering to said host an effective anti-HIV treatment amount of a compound of claim 1 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, in combination and/or alternation with at least one other anti-HIV agent, optionally with a pharmaceutically acceptable carrier or diluent.

28. The method of claim 27 wherein the host is human.

29. A method for the treatment of an HIV-infection in a host wherein the HIV is resistant to one or more reverse transcriptase inhibitor(s), comprising administering to said host an anti-HIV effective treatment amount of a compound of claim 1 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, optionally with a pharmaceutically acceptable carrier or diluent.

30. The method of claim 29 wherein the host is human.

31. A method for the treatment of an HIV-infection in a host wherein the HIV is resistant to one or more reverse transcriptase inhibitor(s), comprising administering to said host an anti-HIV effective treatment amount of a compound of claim 1 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, in combination and/or alternation with at least one other anti-HIV agent, optionally with a pharmaceutically acceptable carrier or diluent.

32. The method of claim 31 wherein the host is human.

33. A method for salvage therapy in the treatment of an anti-HIV infection in a host comprising administering to said host an anti-HIV effective treatment. amount of a compound of claim 1 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, optionally with a pharmaceutically acceptable carrier or diluent.

34. The method of claim 33 wherein the host is human.

35. A method for salvage therapy in the treatment of an anti-HIV infection in a host comprising administering to said host an anti-HIV effective treatment amount of a compound of claim 1 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, in combination and/or alternation with at least one other anti-HIV agent, optionally with a pharmaceutically acceptable carrier or diluent.

36. The method of claim 35 wherein the host is human.

37. A pharmaceutical composition comprising a compound of claim 5 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, optionally with a pharmaceutically acceptable carrier or diluent.

38. A pharmaceutical composition comprising a compound of claim 5 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, in combination with at least one other anti-HIV agent, optionally with a pharmaceutically acceptable carrier or diluent.

39. The pharmaceutical composition of claim 38 wherein the other anti-HIV agent is a reverse transcriptase inhibitor.

40. The pharmaceutical composition of claim 39 wherein the reverse transcriptase inhibitor induces a mutation lysine 103→asparagine and/or tyrosine 181→cysteine in HIV reverse transcriptase.

41. A method for the treatment of an HIV-infection in a host comprising administering to said host an anti-HIV effective treatment amount of a compound of claim 5 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, optionally with a pharmaceutically acceptable carrier or diluent.

42. The method of claim 41 wherein the host is human.

43. A method for the treatment of an HIV-infection in a host comprising administering to said host an anti-HIV effective treatment amount of a compound of claim 5 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, in combination and/or alternation with at least one other anti-HIV agent, optionally with a pharmaceutically acceptable carrier or diluent.

44. The method of claim 43 wherein the host is human.

45. The method of claim 43 wherein the other anti-HIV agent is a reverse transcriptase inhibitor.

46. The method of claim 45 wherein the reverse transcriptase inhibitor induces a mutation lysine 103→asparagine and/or tyrosine 181→cysteine in HIV reverse transcriptase.

47. A method for the treatment of an HIV-infection in a host, wherein the HIV has a mutation at lysine 103→asparagine and/or tyrosine 181→cysteine in HIV reverse transcriptase, comprising administering to said host an effective anti-HIV treatment amount of a compound of claim 5 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, optionally with a pharmaceutically acceptable carrier or diluent.

48. The method of claim 47 wherein the host is human.

49. A method for the treatment of an HIV-infection in a host, wherein the HIV has a mutation at lysine 103→asparagine and/or tyrosine 181→cysteine in HIV reverse transcriptase, comprising administering to said host an effective anti-HIV treatment amount of a compound of claim 5 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, in combination and/or alternation with at least one other anti-HIV agent, optionally with a pharmaceutically acceptable carrier or diluent.

50. The method of claim 49 wherein the host is human.

51. A method for the treatment of an HIV-infection in a host wherein the HIV is resistant to one or more reverse transcriptase inhibitor(s), comprising administering to said host an anti-HIV effective treatment amount of a compound of claim 5 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, optionally with a pharmaceutically acceptable carrier or diluent.

52. The method of claim 51 wherein the host is human.

53. A method for the treatment of an HIV-infection in a host wherein the HIV is resistant to one or more reverse transcriptase inhibitor(s), comprising administering to said host an anti-HIV effective treatment amount of a compound of claim 5 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, in combination and/or alternation with at least one other anti-HIV agent, optionally with a pharmaceutically acceptable carrier or diluent.

54. The method of claim 53 wherein the host is human.

55. A method for salvage therapy in the treatment of an anti-HIV infection in a host comprising administering to said host an anti-HIV effective treatment amount of a compound of claim 5 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, optionally with a pharmaceutically acceptable carrier or diluent.

56. The method of claim 55 wherein the host is human.

57. A method for salvage therapy in the treatment of an anti-HIV infection in a host comprising administering to said host an anti-HIV effective treatment amount of a compound of claim 5 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, in combination and/or alternation with at least one other anti-HIV agent, optionally with a pharmaceutically acceptable carrier or diluent.

58. The method of claim 57 wherein the host is human.

59. A pharmaceutical composition comprising a compound of claim 6 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, optionally with a pharmaceutically acceptable carrier or diluent.

60. A pharmaceutical composition comprising a compound of claim 6 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, in combination with at least one other anti-HIV agent, optionally with a pharmaceutically acceptable carrier or diluent.

61. The pharmaceutical composition of claim 60 wherein the other anti-HIV agent is a reverse transcriptase inhibitor.

62. The pharmaceutical composition of claim 61 wherein the reverse transcriptase inhibitor induces a mutation lysine 103→asparagine and/or tyrosine 181→cysteine in HIV reverse transcriptase.

63. A method for the treatment of an HIV-infection in a host comprising administering to said host an anti-HIV effective treatment amount of a compound of claim 6 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, optionally with a pharmaceutically acceptable carrier or diluent.

64. The method of claim 63 wherein the host is human.

65. A method for the treatment of an HIV-infection in a host comprising administering to said host an anti-HIV effective treatment amount of a compound of claim 6 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, in combination and/or alternation with at least one other anti-HIV agent, optionally with a pharmaceutically acceptable carrier or diluent.

66. The method of claim 65 wherein the host is human.

67. The method of claim 65 wherein the other anti-HIV agent is a reverse transcriptase inhibitor.

68. The method of claim 67 wherein the reverse transcriptase inhibitor induces a mutation lysine 103→asparagine and/or tyrosine 181→cysteine in HIV reverse transcriptase.

69. A method for the treatment of an HIV-infection in a host, wherein the HIV has a mutation at lysine 103→asparagine and/or tyrosine 181→cysteine in HIV reverse transcriptase, comprising administering to said host an effective anti-HIV treatment amount of a compound of claim 6 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, optionally with a pharmaceutically acceptable carrier or diluent.

70. The method of claim 69 wherein the host is human.

71. A method for the treatment of an HIV-infection in a host, wherein the HIV has a mutation at lysine 103→asparagine and/or tyrosine 181→cysteine in HIV reverse transcriptase, comprising administering to said host an effective anti-HIV treatment amount of a compound of claim 6 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, in combination and/or alternation with at least one other anti-HIV agent, optionally with a pharmaceutically acceptable carrier or diluent.

72. The method of claim 71 wherein the host is human.

73. A method for the treatment of an HIV-infection in a host wherein the HIV is resistant to one or more reverse transcriptase inhibitor(s), comprising administering to said host an anti-HIV effective treatment amount of a compound of claim 6 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, optionally with a pharmaceutically acceptable carrier or diluent.

74. The method of claim 73 wherein the host is human.

75. A method for the treatment of an HIV-infection in a host wherein the HIV is resistant to one or more reverse transcriptase inhibitor(s), comprising administering to said host an anti-HIV effective treatment amount of a compound of claim 6 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, in combination and/or alternation with at least one other anti-HIV agent, optionally with a pharmaceutically acceptable carrier or diluent.

76. The method of claim 75 wherein the host is human.

77. A method for salvage therapy in the treatment of an anti-HIV infection in a host comprising administering to said host an anti-HIV effective treatment amount of a compound of claim 6 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, optionally with a pharmaceutically acceptable carrier or diluent.

78. The method of claim 77 wherein the host is human.

79. A method for salvage therapy in the treatment of an anti-HIV infection in a host comprising administering to said host an anti-HIV effective treatment amount of a compound of claim 6 , or its pharmaceutically acceptable salt, stereoisomer, tautomer, N-oxide or quaternary amine, in combination and/or alternation with at least one other anti-HIV agent, optionally with a pharmaceutically acceptable carrier or diluent.

80. The method of claim 79 wherein the host is human.

81. A compound according to the formula:

or a pharmaceutically acceptable salt thereof.

82. The compound of claim 81 .