SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

• US 20160331770A1
• Filed: 07/28/2016
• Published: 11/17/2016
• Est. Priority Date: 03/21/2012
• Status: Active Grant

• Current Assignee: Janssen Biopharma, Inc. (Johnson & Johnson)
• Original Assignee: Alios Biopharma, Inc. (Johnson & Johnson)
• Inventors: Wang, Guangyi, Smith, David Bernard, Beigelman, Leonid, Deval, Jerome, Prhavc, Marija
• Granted Patent: US 10,485,815 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/706 containing six-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• 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 31/708 having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/12 Triazine radicals
• 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 19/207 the phosphoric or polyphosphoric acids being esterified by a further hydroxylic compound, e.g. flavine adenine dinucleotide or nicotinamide-adenine dinucleotide

Abstract

Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a paramyxovirus and/or an orthomyxovirus, with a nucleoside, a nucleotide and an analog thereof.

Claims

1. Use of an effective amount of a compound selected from Formula (I), Formula (II), and Formula (III), or a pharmaceutically acceptable salt of the foregoing, for amelioring or treating a viral infection caused by a virus selected from a henipavirus, a morbillivirus, a respirovirus, a rubulavirus and a metapneumovirus, wherein the compound is selected from Formula (I), Formula (II), and Formula (III) has one of the following structures:

3. The use of claim 1 or the method of claim 2, wherein the virus is a henipavirus.

4. The use or method of claim 3, wherein the henipavirus is a nipahvirus.

5. The use of claim 1 or the method of claim 2, wherein the virus is a morbillivirus.

6. The use or method of claim 5, wherein the morbillivirus is the measles virus.

7. The use of claim 1 or the method of claim 2, wherein the virus is a respirovirus.

8. The use or method of claim 7, wherein the respirovirus is human parainfluenza virus 1.

9. The use or method of claim 7, wherein the respirovirus is human parainfluenza virus 3.

10. The use of claim 1 or the method of claim 2, wherein the virus is a rubulavirus.

11. The use or method of claim 10, wherein the rubulavirus is the mumps virus.

12. The use or method of claim 10, wherein the rubulavirus is human parainfluenza virus 2.

13. The use or method of claim 10, wherein the rubulavirus is human parainfluenza virus 4.

14. The use of claim 1 or the method of claim 2, wherein the virus is a metapneumovirus.

15. The use or method of claim 14, wherein the metaphenumovirus is human metapneumovirus.

16. The use of any one of claim 1 or 3-15 or the method of any one of claims 2-15, wherein the compound is a compound of Formula (I).

17. The use or method of claim 16, wherein R^1A is

18. The use or method of claim 17, wherein R^6A and R^7A are both hydrogen.

19. The use or method of claim 17, wherein R^6A and R^7A are both absent.

20. The use or method of claim 17, wherein one of R^6A and R^7A is hydrogen, and the other of R^6A and R^7A is selected from the group consisting of an optionally substituted C_1-24 alkyl, an optionally substituted C_2-24 alkenyl, an optionally substituted C_2-24 alkynyl, an optionally substituted C_3-6 cycloalkyl, an optionally substituted C_3-6 cycloalkenyl, an optionally substituted aryl, an optionally substituted heteroaryl and an optionally substituted aryl(C_1-6 alkyl).

21. The use or method of claim 20, wherein the other of R^6A and R^7A is an optionally substituted C_1-24 alkyl.

22. The use or method of claim 17, wherein both R^6A and R^7A are independently selected from the group consisting of an optionally substituted C_1-24 alkyl, an optionally substituted C_2-24 alkenyl, an optionally substituted C_2-24 alkynyl, an optionally substituted C_3-6 cycloalkyl, an optionally substituted C_3-6 cycloalkenyl, an optionally substituted aryl, an optionally substituted heteroaryl and an optionally substituted aryl(C_1-6 alkyl).

23. The use or method of claim 22, wherein both R^6A and R^7A are an optionally substituted C_1-24 alkyl.

24. The use or method of claim 17, wherein at least one of R^6A and R^7A are selected from the group consisting of

25. The use or method of claim 17, wherein both R^6A and R^7A are independently selected from the group consisting of

26. The use or method of any one of claims 24-25, wherein both R^26A and R^27A are an optionally substituted C_2-8 organylcarbonyl.

27. The use or method of claim 26, wherein the optionally substituted C_1-8 organylcarbonyl is —

C(═

O)CH₃.

28. The use or method of any one of claims 24-25, wherein both R^26A and R^27A are an optionally substituted C_2-8 alkoxycarbonyl.

29. The use or method of claim 28, wherein the optionally substituted C_1-8 alkoxycarbonyl is —

C(═

O)OCH₂CH₃.

30. The use or method of claim 28, wherein the optionally substituted C_1-8 alkoxycarbonyl is —

C(═

O)OCH₃.

31. The use or method of any one of claims 24-30, wherein R^28A is an optionally substituted C_1-4-alkyl

32. The use or method of any one of claims 24-25, wherein

33. The use or method of claim 17, wherein R^6A and R^7A are both optionally substituted C_2-24 alkyl.

34. The use or method of claim 17, wherein R^6A and R^7A are both an optionally substituted C_2-24 alkenyl.

35. The use or method of claim 17, wherein R^6A and R^7A are both *—

(CR^15AR^16A)_p—

O—

C_1-24 alkyl.

36. The use or method of claim 17, wherein R^6A and R^7A are both *—

(CR^17AR^18A)_q—

O—

C_2-24 alkenyl.

37. The use or method of claim 17, wherein R^6A and R^7A are both an optionally substituted aryl.

38. The use or method of claim 17, wherein R^6A and R^7A are both an optionally substituted aryl(C_1-6 alkyl).

39. The use or method of claim 17, wherein R^6A and R^7A are both

40. The use or method of claim 17, wherein R^6A and R^7A are both

41. The use or method of claim 17, wherein R^6A and R^7A are both

42. The use or method of claim 17, wherein R^6A and R^7A are both

43. The use or method of claim 17, wherein R^6A and R^7A are both

44. The use or method of claim 17, wherein R^6A and R^7A can be taken together to form a moiety selected from the group consisting of an optionally substituted

45. The use or method of claim 44, wherein R^6A and R^7A can be taken together to form a moiety selected from the group consisting of

46. The use or method of any one of claims 17-45, wherein Z^1A is O.

47. The use or method of any one of claims 17-45, wherein Z^1A is S.

48. The use or method of claim 16, wherein R^1A is

49. The use or method of claim 48, wherein R^8A is selected from the group consisting of absent, hydrogen, an optionally substituted C_1-24 alkyl, an optionally substituted C_2-24 alkenyl, an optionally substituted C_2-24 alkynyl, an optionally substituted C_3-6 cycloalkyl and an optionally substituted C_3-6 cycloalkenyl;

and R^9A is independently selected from the group consisting of an optionally substituted C_1-24 alkyl, an optionally substituted C_2-24 alkenyl, an optionally substituted C_2-24 alkynyl, an optionally substituted C_3-6 cycloalkyl and an optionally substituted C_3-6 cycloalkenyl.

50. The use or method of claim 49, wherein R^8A is hydrogen, and R^9A is an optionally substituted C_1-6 alkyl.

51. The use or method of claim 48, wherein R^8A is hydrogen, and R^9A is NR^30AR^31A, wherein R³⁰ and R³¹ are independently selected from the group consisting of hydrogen, an optionally substituted C_1-24 alkyl, an optionally substituted C_2-24 alkenyl, an optionally substituted C_2-24 alkynyl, an optionally substituted C_3-6 cycloalkyl and an optionally substituted C_3-6 cycloalkenyl.

52. The use or method of claim 48, wherein R^8A is absent or hydrogen;

and R^9A is an optionally substituted N-linked amino acid or an optionally substituted N-linked amino acid ester derivative.

53. The use or method of claim 48, wherein R^8A is an optionally substituted aryl;

and R^9A is an optionally substituted N-linked amino acid or an optionally substituted N-linked amino acid ester derivative.

54. The use or method of claim 52 or 53, wherein R^9A is selected from the group consisting of alanine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, tyrosine, arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine and ester derivatives thereof.

55. The use or method of claim 54, wherein R^9A is selected from the group consisting of alanine isopropyl ester, alanine cyclohexyl ester, alanine neopentyl ester, valine isopropyl ester and leucine isopropyl ester.

56. The use or method of claim 52 or 53, wherein R^9A has the structure

57. The use or method of claim 56, wherein R^34A is an optionally substituted C_1-6-alkyl.

58. The use or method of claim 57, wherein the optionally substituted C_1-6-alkyl is methyl.

59. The use or method of any one of claims 56-58, wherein R^35A is hydrogen.

60. The use or method of any one of claims 56-59, wherein R^33A is an optionally substituted C_1-6 alkyl, an optionally substituted C_3-6 cycloalkyl or an optionally substituted benzyl.

61. The use or method of any one of claims 48-60, wherein Z^2A is O.

62. The use or method of any one of claims 48-60, wherein Z^2A is S.

63. The use or method of claim 16, wherein R^1A is

64. The use or method of claim 63, wherein R^10A and R^11A are both an optionally substituted N-linked amino acid or an optionally substituted N-linked amino acid ester derivative.

65. The use or method of claim 64, wherein R^10A and R^11A are independently selected from selected from the group consisting of alanine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, tyrosine, arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine and ester derivatives thereof.

66. The use or method of claim 65, wherein R^10A and R^11A are independently selected from the group consisting of alanine isopropyl ester, alanine cyclohexyl ester, alanine neopentyl ester, valine isopropyl ester and leucine isopropyl ester.

67. The use or method of claim 64, wherein R^10A and R^11A are independently have the structure

68. The use or method of claim 67, wherein R^42A is an optionally substituted C_1-6-alkyl.

69. The use or method of claim 68, wherein the optionally substituted C_1-6-alkyl is methyl.

70. The use or method of any one of claims 67-69, wherein R^43A is hydrogen.

71. The use or method of any one of claims 67-70, wherein R^41A is an optionally substituted C_1-6 alkyl, an optionally substituted C_3-6 cycloalkyl or an optionally substituted benzyl.

72. The use or method of any one of claims 63-71, wherein Z^3A is O.

73. The use or method of any one of claims 63-71, wherein Z^3A is S.

74. The use or method of claim 16, wherein R^1A is

75. The use or method of claim 74, wherein m is 0, and R^12A and R^13A are independently absent or hydrogen.

76. The use or method of claim 74, wherein m is 1, and R^12A, R^13A and R^14A are independently absent or hydrogen.

77. The use or method of claim 16, wherein R^1A is H.

78. The use or method of claim 16, wherein R^1A is an optionally substituted acyl.

79. The use or method of claim 78, wherein the optionally substituted acyl is —

C(═

O)R^39A, wherein R^39A is selected from the group consisting of an optionally substituted C_1-12 alkyl, an optionally substituted C_2-12 alkenyl, an optionally substituted C_2-12 alkynyl, an optionally substituted C_3-8 cycloalkyl, an optionally substituted C_5-8 cycloalkenyl, an optionally substituted C_6-10 aryl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, an optionally substituted aryl(C_1-6 alkyl), an optionally substituted heteroaryl(C_1-6 alkyl) and an optionally substituted heterocyclyl(C_1-6 alkyl).

80. The use or method of claim 79, wherein R^39A is substituted or unsubstituted C_1-12 alkyl.

81. The use or method of claim 16, wherein R^1A is an optionally substituted O-linked amino acid.

82. The use or method of claim 16, wherein R^1A is

83. The use or method of claim 82, wherein R^40A is an optionally substituted C_1-6-alkyl.

84. The use or method of claim 83, wherein the optionally substituted C_1-6-alkyl is methyl.

85. The use or method of any one of claims 82-84, wherein R^41A is hydrogen.

86. The use or method of any one of claims 16-85, wherein B^1A is selected from the group consisting of:

87. The use or method of claim 86, wherein B^1A is

88. The use or method of claim 86, wherein B^1A is

89. The use or method of claim 86, wherein B^1A is

90. The use or method of claim 86, wherein B^1A is

91. The use or method of claim 86, wherein B^1A is

92. The use or method of claim 86, wherein B^1A is

93. The use or method of any one of claims 16-92, wherein the dashed line (- - - - - -) is a single bond, R^2A is CH₂, and R^3A is O.

94. The use or method of any one of claims 16-92, wherein the dashed line (- - - - - -) is absent, R^2A is selected from the group consisting of an optionally substituted C_1-6 alkyl, an optionally substituted C_2-6 alkenyl, an optionally substituted C_2-6 alkynyl, an optionally substituted —

O—

C_1-6 alkyl, an optionally substituted —

O—

C_3-6 alkenyl, an optionally substituted —

O—

C_3-6 alkynyl and cyano, and R^3A is selected from the group consisting of OH, —

OC(═

O)R A and an optionally substituted O-linked amino acid.

95. The use or method of claim 94, wherein R^2A is an optionally substituted C_1-6 alkyl.

96. The use or method of claim 95, wherein R^2A is unsubstituted C_1-6 alkyl.

97. The use or method of claim 94, wherein R^2A is an optionally substituted C_2-6 alkenyl.

98. The use or method of claim 97, wherein R^2A is unsubstituted C_2-6 alkenyl.

99. The use or method of claim 94, wherein R^2A is an optionally substituted C_2-6 alkynyl.

100. The use or method of claim 99, wherein R^2A is unsubstituted C_2-6 alkynyl.

101. The use or method of claim 94, wherein R^2A is an optionally substituted C_3-6 cycloalkyl.

102. The use or method of claim 94, wherein R^2A is an optionally substituted —

O—

C_1-6 alkyl.

103. The use or method of claim 102, wherein R^2A is unsubstituted —

O—

C_1-6 alkyl.

104. The use or method of claim 94, wherein R^2A is an optionally substituted —

O—

C_3-6 alkenyl.

105. The use or method of claim 104, wherein R^2A is unsubstituted —

O—

C_3-6 alkenyl.

106. The use or method of claim 94, wherein R^2A is an optionally substituted —

O—

C_3-6 alkynyl.

107. The use or method of claim 106, wherein R^2A is unsubstituted —

O—

C_3-6 alkynyl.

108. The use or method of claim 94, wherein R^2A is cyano.

109. The use or method of any one of claims 16-108, wherein R^3A is OH.

110. The use or method of any one of claims 16-108, wherein R^3A is —

OC(═

O)R″

^A.

111. The use or method of claim 110, wherein R″

^A is an optionally substituted C_1-8 alkyl.

112. The use or method of any one of claims 16-108, wherein R^3A is O-linked amino acid.

113. The use or method of claim 112, wherein the O-linked amino acid is selected from the group consisting of alanine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, tyrosine, arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine. Additional examples of suitable amino acids include, but are not limited to, ornithine, hypusine, 2-aminoisobutyric acid, dehydroalanine, gamma-aminobutyric acid, citrulline, beta-alanine, alpha-ethyl-glycine, alpha-propyl-glycine and norleucine.

114. The use or method of any one of claims 16-108, wherein R^3A is

115. The use or method of claim 114, wherein R^42A is an optionally substituted C_1-6-alkyl.

116. The use or method of claim 115, wherein the optionally substituted C_1-6-alkyl is methyl.

117. The use or method of any one of claims 114-116, wherein R^43A is hydrogen.

118. The use or method of any one of claims 16-117, wherein R^5A is hydrogen.

119. The use or method of any one of claims 16-117, wherein R^5A is halogen.

120. The use or method of claim 119, wherein R^5A is fluoro.

121. The use or method of any one of claims 16-120, wherein R^4A is fluoro.

122. The use of any one of claim 1 or 3-15 or the method of any one of claims 2-15, wherein the compound is a compound of Formula (II).

123. The use or method of claim 122, wherein R^1B is O—

or OH.

124. The use or method of claim 122, wherein R^1B is

125. The use or method of claim 122, wherein R^1B is

126. The use or method of claim 122, wherein R^1B is

127. The use or method of claim 122, wherein R^1B is an optionally substituted N-linked amino acid or an optionally substituted N-linked amino acid ester derivative.

128. The use or method of claim 127, wherein R^1B is selected from the group consisting of alanine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, tyrosine, arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine and ester derivatives thereof.

129. The use or method of claim 128, wherein R^1B is selected from the group consisting of alanine isopropyl ester, alanine cyclohexyl ester, alanine neopentyl ester, valine isopropyl ester and leucine isopropyl ester.

130. The use or method of claim 127, wherein R^1B has the structure

131. The use or method of claim 130, wherein R^13B is an optionally substituted C_1-6-alkyl.

132. The use or method of claim 131, wherein the optionally substituted C_1-6-alkyl is methyl.

133. The use or method of any one of claims 130-132, wherein R^14B is hydrogen.

134. The use or method of any one of claims 130-133, wherein R^12B is an optionally substituted C_1-6 alkyl, an optionally substituted C_3-6 cycloalkyl or an optionally substituted benzyl.

135. The use or method of any one of claims 122-134, wherein R^2B is an optionally substituted C_1-6 alkyl.

136. The use or method of claim 135, wherein R^2B is unsubstituted C_1-6 alkyl.

137. The use or method of any one of claims 122-134, wherein R^2B is an optionally substituted C_2-6 alkenyl.

138. The use or method of claim 137, wherein R^2B is unsubstituted C_2-6 alkenyl.

139. The use or method of any one of claims 122-134, wherein R^2B is an optionally substituted C_2-6 alkynyl.

140. The use or method of claim 139, wherein R^2B is unsubstituted C_2-6 alkynyl.

141. The use or method of any one of claims 122-134, wherein R^2B is an optionally substituted —

O—

C_1-6 alkyl.

142. The use or method of claim 141, wherein R^2B is unsubstituted —

O—

C_1-6 alkyl.

143. The use or method of any one of claims 122-134, wherein R^2B is an optionally substituted —

O—

C_3-6 alkenyl.

144. The use or method of claim 143, wherein R^2B is unsubstituted —

O—

C_3-6 alkenyl.

145. The use or method of any one of claims 122-134, wherein R^2B is an optionally substituted —

O—

C_3-6 alkynyl.

146. The use or method of claim 145, wherein R^2B is unsubstituted —

O—

C_3-6 alkynyl.

147. The use or method of any one of claims 122-134, wherein R^2B is an optionally substituted C_3-6 cycloalkyl.

148. The use or method of any one of claims 122-134, wherein R^2B is cyano.

149. The use or method of any one of claims 122-148, wherein R^4B is hydrogen.

150. The use or method of any one of claims 122-148, wherein R^4B is halogen.

151. The use or method of claim 150, wherein R^4B is fluoro.

152. The use or method of any one of claims 122-151, wherein R^3B is fluoro.

153. The use or method of any one of claims 122-152, wherein Z^1B is O.

154. The use or method of any one of claims 122-152, wherein Z^1B is S.

155. The use or method of any one of claims 122-154, wherein B^1B is selected from the group consisting of:

156. The use or method of claim 155, wherein B^1B is

157. The use or method of claim 155, wherein B^1B is f

158. The use or method of claim 155, wherein B^1B is

159. The use or method of claim 155, wherein B^1B is

160. The use or method of claim 155, wherein B^1B is

161. The use or method of claim 155, wherein B^1B is

162. The use of any one of claim 1 or 3-15 or the method of any one of claims 2-15, wherein the compound is a compound of Formula (III).

163. The use or method of claim 162, wherein R^1C is O⁻

or OH.

164. The use or method of claim 162, wherein R^1C is an optionally substituted C_1-6 alkoxy.

165. The use or method of claim 162, wherein R^1C is

166. The use or method of claim 162, wherein R^1C is C

167. The use or method of claim 162, wherein R^1C is

168. The use or method of claim 162, wherein R^1C is an optionally substituted N-linked amino acid.

169. The use or method of claim 162, wherein R^1C is an optionally substituted N-linked amino acid ester derivative.

170. The use or method of any one of claims 162-169, wherein R^2C is O⁻

or OH.

171. The use or method of any one of claims 162-169, wherein R^2C is an optionally substituted C_1-6 alkoxy.

172. The use or method of any one of claims 162-169, wherein R^2C is

173. The use or method of any one of claims 162-169, wherein R^2C is

174. The use or method of any one of claims 162-169, wherein R^2C is

175. The use or method of any one of claims 162-169, wherein R^2C is an optionally substituted N-linked amino acid.

176. The use or method of any one of claims 162-169, wherein R^2C is an optionally substituted N-linked amino acid ester derivative.

177. The use or method of any one of claim 176, wherein R^1C is

178. The use or method of any one of claims 162-177, wherein R^3C is an optionally substituted C_1-6 alkyl.

179. The use or method of claim 178, wherein R^3C is unsubstituted C_1-6 alkyl.

180. The use or method of any one of claims 162-177, wherein R^3C is an optionally substituted C_2-6 alkenyl.

181. The use or method of claim 180, wherein R^3C is unsubstituted C_2-6 alkenyl.

182. The use or method of any one of claims 162-177, wherein R^3C is an optionally substituted C_2-6 alkynyl.

183. The use or method of claim 182, wherein R^3C is unsubstituted C_2-6 alkynyl.

184. The use or method of any one of claims 162-177, wherein R^3C is an optionally substituted —

O—

C_1-6 alkyl.

185. The use or method of claim 184, wherein R^3C is unsubstituted —

O—

C_1-6 alkyl.

186. The use or method of any one of claims 162-177, wherein R^3C is an optionally substituted —

O—

C_3-6 alkenyl.

187. The use or method of claim 186, wherein R^3C is unsubstituted —

O—

C_3-6 alkenyl.

188. The use or method of any one of claims 162-177, wherein R^3C is an optionally substituted —

O—

C_3-6 alkynyl.

189. The use or method of claim 188, wherein R^3C is unsubstituted —

O—

C_3-6 alkynyl.

190. The use or method of any one of claims 162-177, wherein R^3C is an optionally substituted C_3-6 cycloalkyl.

191. The use or method of any one of claims 162-177, wherein R^3C is cyano.

192. The use or method of any one of claims 162-191, wherein R^4C is OH.

193. The use or method of any one of claims 162-191, wherein R^4C is —

OC(═

O)R″

^C.

194. The use or method of claim 193, wherein R^C is an optionally substituted C_1-8 alkyl.

195. The use or method of any one of claims 162-191, wherein R^4C is O-linked amino acid.

196. The use or method of claim 195, wherein the O-linked amino acid is selected from the group consisting of alanine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, tyrosine, arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine. Additional examples of suitable amino acids include, but are not limited to, ornithine, hypusine, 2-aminoisobutyric acid, dehydroalanine, gamma-aminobutyric acid, citrulline, beta-alanine, alpha-ethyl-glycine, alpha-propyl-glycine and norleucine.

197. The use or method of any one of claims 162-191, wherein R^4C

198. The use or method of claim 197, wherein R^22C is an optionally substituted C_1-6-alkyl.

199. The use or method of claim 198, wherein the optionally substituted C_1-6-alkyl is methyl.

200. The use or method of any one of claims 197-199, wherein R^23C is hydrogen.

201. The use or method of any one of claims 162-200, wherein R^6C is halogen.

202. The use or method of any one of claims 162-200, wherein R^6C is hydrogen.

203. The use or method of any one of claims 162-202, wherein R^5C is fluoro.

204. The use or method of any one of claims 162-203, wherein - - - - - - - is a single bond such that Formula (III) has the structure

205. The use or method of claim 204, wherein the R^7C and the R^8C groups are all hydrogen.

206. The use or method of claim 204, wherein one R^7C is halogen, one R^7C is hydrogen and both R^8C groups are all hydrogen.

207. The use or method of claim 204, wherein one R^7C is halogen, one R^7C is hydrogen, one R^8C is halogen and one R^8C is hydrogen.

208. The use or method of any one of claims 162-203, wherein - - - - - - - is a double bond such that Formula (III) has the structure

209. The use or method of claim 208, wherein both R^8C groups are hydrogen.

210. The use or method of claim 208, wherein one R^8C is halogen and the other R^8C is hydrogen.

211. The use or method of claim 208, wherein both R^8C groups are halogen.

212. The use or method of any one of claims 162-211, wherein B^1C is selected from the group consisting of:

213. The use or method of claim 212, wherein B^1C is

214. The use or method of claim 212, wherein B^1C is

215. The use or method of claim 212, wherein B^1C

216. The use or method of claim 212, wherein B^1C is

217. The use or method of claim 212, wherein B^1C is

218. The use or method of claim 212, wherein B^1C is

219. The use or method of claim 16, wherein the compound of Formula (I) is selected from the group consisting of:

220. The use or method of claim 16, wherein the compound of Formula (I) is selected from the group consisting of:

221. The use or method of claim 16, wherein the compound of Formula (I) is selected from the group consisting of:

222. The use or method of claim 16, wherein the compound of Formula (I)

223. The use or method of claim 16, wherein the compound of Formula (I)

224. The use or method of claim 16, wherein the compound of Formula (I) is selected from the group consisting of:

225. The use or method of claim 16, wherein the compound of Formula (I) is selected from the group consisting of:

226. The use or method of claim 16, wherein the compound of Formula (I) is selected from the group consisting of:

227. The use or method of claim 16, wherein the compound of Formula (I) is selected from the group consisting of:

228. The use or method of claim 122, wherein the compound of Formula (II)

229. The use or method of claim 122, wherein the compound of Formula (II) is selected from the group consisting of:

230. The use or method of claim 162, wherein the compound of Formula (III) is selected from the group consisting of:

231. The use or method of claim 162, wherein the compound of Formula (III) is selected from the group consisting of:

2. A method for ameliorating or treating a viral infection caused by a virus comprising administering to or contacting a cell in a subject with an effective amount of a compound selected from Formula (I), Formula (II), and Formula (III), or a pharmaceutically acceptable salt of the foregoing, wherein the virus is selected from a henipavirus, a morbillivirus, a respirovirus, a rubulavirus and a metapneumovirus, and wherein the compound is selected from Formula (I), Formula (II), and Formula (III) has one of the following structures:

232. Use of an effective amount of a compound, or a pharmaceutically acceptable salt thereof, for amelioring or treating a viral infection caused by a virus selected from a henipavirus, a morbillivirus, a respirovirus, a rubulavirus and a metapneumovirus, wherein the compound is selected from:

234. The use of claim 232 or the method of claim 233, wherein the virus is a henipavirus.

235. The use or method of claim 234, wherein the henipavirus is a nipahvirus.

236. The use of claim 232 or the method of claim 233, wherein the virus is a morbillivirus.

237. The use or method of claim 236, wherein the morbillivirus is the measles virus.

238. The use of claim 232 or the method of claim 233, wherein the virus is a respirovirus.

239. The use or method of claim 238, wherein the respirovirus is human parainfluenza virus 1.

240. The use or method of claim 238, wherein the respirovirus is human parainfluenza virus 3.

241. The use of claim 232 or the method of claim 233, wherein the virus is a rubulavirus.

242. The use or method of claim 241, wherein the rubulavirus is the mumps virus.

243. The use or method of claim 241, wherein the rubulavirus is human parainfluenza virus 2.

244. The use or method of claim 241, wherein the rubulavirus is human parainfluenza virus 4.

245. The use of claim 232 or the method of claim 233, wherein the virus is a metapneumovirus.

246. The use or method of claim 245, wherein the metaphenumovirus is human metapneumovirus.

233. A method for ameliorating or treating a viral infection caused by a virus comprising administering to or contacting a cell in a subject with an effective amount of a compound, or a pharmaceutically acceptable salt of thereof, wherein the virus is selected from a henipavirus, a morbillivirus, a respirovirus, a rubulavirus and a metapneumovirus, and wherein the compound is selected from: