Amino-methyl substituted tetracycline compounds
View Patent ↗Aminomethyl substituted tetracycline compounds, pharmaceutical compositions, and methods of use thereof are discussed.
1. A tetracycline compound of formula (III):
wherein:
J 5 and J 6 are each independently hydrogen, alkyl, alkenyl, alkynyl, aryl, sulfonyl, acyl, alkoxycarbonyl, alkaminocarbonyl, alkaminothiocarbonyl, substituted thiocarbonyl, substituted carbonyl, alkoxythiocarbonyl, or linked to form a ring;
J 7 and J 8 are each alkyl, halogen, or hydrogen;
X is CR 6′ R 6 ;
R 2 , R 2′ ,R 4′ , and R 4″ are each independently hydrogen, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, arylalkyl, aryl, heterocyclic, heteroaromatic or a prodrug moiety;
R 4 is NR 4′ R 4″ , alkyl, alkenyl, alkynyl, aryl, hydroxyl, halogen, or hydrogen;
R 3 , R 10 , R 11 and R 12 are each hydrogen or a pro-drug moiety;
R 5 is hydroxyl, hydrogen, thiol, alkanoyl, aroyl, alkaroyl, aryl, heteroaromatic, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, arylalkyl, alkyl carbonyloxy, or aryl carbonyloxy;
R 6 and R 6′ are each independently hydrogen, methylene, absent, hydroxyl, halogen, thiol, alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl;
R 7 is hydrogen, ethyl, phenyl, 4-t-butylphenyl, t-butylaminophenyl or dimethylamino;
R 8 is hydrogen, hydroxyl, halogen, thiol, alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl;
R 13 is hydrogen, hydroxyl, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl; and
pharmaceutically acceptable salts thereof.
2. The tetracycline compound of claim 1 , wherein R 4 is NR 4′ R 4″ , X is CR 6 R 6′ ; R 2 , R 2′ , R 6 , R 6′, R 8 , R 10 , R 11 , and R 12 are each hydrogen; R 4′ and R 4″ are lower alkyl; and R 5 is hydroxyl or hydrogen.
3. The tetracycline compound of claim 2 , wherein R 4′ and R 4″ are each methyl and R 5 is hydrogen.
4. The tetracycline compound of claim 1 , wherein J 7 and J 8 are hydrogen.
5. The tetracycline compound of claim 1 , wherein J 5 is substituted or unsubstituted alkyl.
6. The tetracycline compound of claim 1 , wherein J 5 is sulfonyl.
7. The tetracycline compound of claim 1 , wherein J 5 and J 6 are linked to form a ring.
8. The tetracycline compound of claim 1 , wherein J 5 is heteroaryl.
9. The tetracycline compound of claim 1 , wherein J 5 is substituted carbonyl.
10. The tetracycline compound of claim 1 , wherein said compound is selected from the group consisting of:
wherein
R is substituted or unsubstituted alkyl, alkenyl, alkynyl, halogen, alkoxy; and
Y is N, O, or S, or pharmaceutically acceptable salts or prodrugs thereof.
11. A tetracycline compound selected from the following:
or a pharmaceutically acceptable salt thereof.
12. The compound of claim 1 , wherein R 7 is dimethylamino.
13. The compound of claim 1 or 9 , wherein J 6 is alkyl.
14. The compound of claim 13 , wherein said compound is
and pharmaceutically acceptable salts thereof.
15. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
16. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
17. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
18. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
19. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
20. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
21. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
22. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
23. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
24. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
25. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
26. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
27. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
28. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
29. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
30. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
31. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
32. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
33. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
34. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
35. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
36. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
37. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
38. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
39. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
40. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
41. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
42. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
43. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
44. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
45. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
46. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
47. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
48. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
49. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
50. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
51. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
52. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
53. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
54. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
55. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
56. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
57. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
58. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
59. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
60. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
61. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
62. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
63. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
64. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
65. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
66. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
67. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
68. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
69. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
70. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
71. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
72. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
73. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
74. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
75. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
76. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
77. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
78. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
79. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
80. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
81. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
82. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
83. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
84. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
85. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
86. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
87. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
88. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
89. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
90. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
91. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
92. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
93. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
94. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
95. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
96. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
97. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
98. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
99. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
100. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
101. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
102. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
103. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
104. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
105. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
106. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
107. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
108. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
109. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
110. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
111. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
112. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
113. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
114. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
115. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
116. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
117. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
118. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
119. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
120. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
121. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
122. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
123. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
124. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
125. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
126. The compound of claim 1 , wherein said compound is
and pharmaceutically acceptable salts thereof.
127. A pharmaceutical composition comprising an effective amount of a tetracycline compound of any one of claims 1 , 10 or 11 , and a pharmaceutically acceptable carrier.
128. The pharmaceutical composition of claim 127 , wherein said effective amount is effective to treat a tetracycline responsive state.