Methods and compositions for treating flaviviruses and pestiviruses

• US 20030060400A1
• Filed: 05/23/2001
• Published: 03/27/2003
• Est. Priority Date: 05/26/2000
• Status: Active Grant

• Current Assignee: Idenix Pharmaceuticals LLC (Merck & Co., Inc.), Universita' Degli Studi Di Bari (Repubblica Italiana), Universita' Degli Studi Di Cagliari (Repubblica Italiana)
• Original Assignee: Idenix Pharmaceuticals (Merck & Co., Inc.)
• Inventors: Sommadossi, Jean-Pierre, LaColla, Paulo
• Granted Patent: US 6,812,219 B2
• Time in Patent Office: Days
• US Class Current: 514/8
• CPC Class Codes: A61K 31/7052 having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
• CPC Class Codes: A61K 31/7056 containing five-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 31/7064 containing condensed or non-condensed pyrimidines
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: A61K 38/21 Interferons [IFN]
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/073 with 2-deoxyribosyl as the saccharide radical
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/16 Purine radicals
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/23 Heterocyclic radicals containing two or more heterocyclic rings condensed among themselves or condensed with a common carbocyclic ring system, not provided for in groups C07H19/14 - C07H19/22
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

A method and composition for treating a host infected with flavivirus or pestivirus comprising administering an effective flavivirus or pestivirus treatment amount of a described 1′, 2′ or 3′-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

Claims

1. A compound of Formula I:

25. The compound as described in any of the preceding claims 1-24, wherein the said compound is in the form of a dosage unit.

2. A compound of Formula II:

3. A compound of Formula III:

4. A compound of Formula IV:

5. A compound of Formula V:

6. A compound of Formula VI:

7. A compound selected from Formulas VII, VIII and IX:

8. A compound of Formulas X, XI and XII:

9. A compound selected from Formulas XIII, XIV and XV:

10. A compound of Formula XVI:

11. A compound of Formula XVII:

12. A compound of Formula XVIII:

13. A compound of the structure:

14. A compound of the structure:

15. A compound of the structure:

16. A compound of the structure:

17. A compound of the structure:

18. A compound of the structure:

19. A compound of the structure:

20. A compound of the structure:

21. A compound of the structure:

22. A compound of the structure:

23. A compound of the structure:

24. A compound of the structure:

26. The compound as described in claim 187, wherein the dosage unit contains 10 to 1500 mg of said compound.

27. The compound as described in claim 187 or 188, wherein said dosage unit is a tablet or capsule.

28. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula I:

76. The pharmaceutical composition as described in any of the preceding claims 28-75, wherein the said compound is in the form of a dosage unit.

77. The pharmaceutical composition as described in claim 76, wherein the dosage unit contains 10 to 1500 mg of said compound.

29. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula II:

30. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula III:

31. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula IV:

32. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula V:

33. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula VI:

34. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formulas VII, VIII or IX:

35. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula X, XI or XII:

36. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula XIII, XIV or XV:

37. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula XVI:

38. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula XVII:

39. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula XVIII:

40. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

41. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

42. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

43. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

44. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

45. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

46. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

47. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

48. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

49. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

50. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

51. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

52. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula I:

53. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula II:

54. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula III:

55. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula IV:

56. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula V:

57. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula VI:

58. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula VII, VIII or IX:

59. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula X, XI or XII:

60. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestiviras in a host, comprising an effective amount of a compound of Formula XIII, XIV or XV:

61. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula XVI:

62. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula XVII:

63. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula XVIII:

64. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

65. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

66. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

67. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

68. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

69. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

70. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

71. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

72. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

73. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

74. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

75. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of structure:

78. The pharmaceutical composition as described in claim 75 or 76, wherein said dosage unit is a tablet or capsule.

79. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula I:

80. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula II:

81. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula III:

82. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula IV:

83. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula V:

84. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula VI:

85. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula VII, VIII or IX:

86. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula X, XI or XII:

87. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula XIII, XIV or XV:

88. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula XVI:

89. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula XVII:

90. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula XVIII:

91. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

92. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

93. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

94. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

95. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

96. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

97. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

98. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

99. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

100. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

127. Method of treatment as described in any of the preceding claims 79-126, wherein the said compound is in the form of a dosage unit.

128. Method of treatment as described in claim 127, wherein the dosage unit contains 10 to 1500 mg of said compound.

129. Method of treatment as described in claim 127 or 128, wherein said dosage unit is a tablet or capsule.

101. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

102. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

103. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula I:

104. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula II:

105. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula III:

106. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula IV:

107. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula V:

108. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula VI:

109. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula VII, VIII or IX:

110. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula X, XI or XII:

111. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula XIII, XIV or XV:

112. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula XVI:

113. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula XVII:

114. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula XVIII:

115. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

116. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

117. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

118. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

119. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

120. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

121. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

122. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

123. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

124. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

125. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

126. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an antivirally effective amount of a compound of the structure: