Claims for Patent: 7,326,696

Summary for Patent: 7,326,696

Title:	Amino-methyl substituted tetracycline compounds
Abstract:	Aminomethyl substituted tetracycline compounds, pharmaceutical compositions, and methods of use thereof are discussed.
Inventor(s):	Mark L. Nelson, Kwasi Ohemeng, Roger Frechette, Paul Abato, Victor Amoo, Haregewein Assefa, Joel Berniac, Beena Bhatia, Todd Bowser, Jackson Chen, Laura Honeyman, Mohamed Y. Ismail, Oak Kim, Rachid Mechiche, N. Laxma Reddy, Atul K. Verma, Peter Viski, Tadeusz Warchol, Ivan Yanachkov
Assignee:	Paratek Pharmaceuticals Inc
Application Number:	US10/737,361
Patent Claims:	1. A tetracycline compound of formula (III): wherein: J5 and J6 are each independently hydrogen, alkyl, alkenyl, alkynyl, aryl, sulfonyl, acyl, alkoxycarbonyl, alkaminocarbonyl, alkaminothiocarbonyl, substituted thiocarbonyl, substituted carbonyl, alkoxythiocarbonyl, or linked to form a ring; J7 and J8 are each alkyl, halogen, or hydrogen; X is CR6′R6; R2, R2′,R4′, and R4″ are each independently hydrogen, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, arylalkyl, aryl, heterocyclic, heteroaromatic or a prodrug moiety; R4 is NR4′R4″, alkyl, alkenyl, alkynyl, aryl, hydroxyl, halogen, or hydrogen; R3, R10, R11 and R12 are each hydrogen or a pro-drug moiety; R5 is hydroxyl, hydrogen, thiol, alkanoyl, aroyl, alkaroyl, aryl, heteroaromatic, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, arylalkyl, alkyl carbonyloxy, or aryl carbonyloxy; R6 and R6′ are each independently hydrogen, methylene, absent, hydroxyl, halogen, thiol, alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl; R7 is hydrogen, ethyl, phenyl, 4-t-butylphenyl, t-butylaminophenyl or dimethylamino; R8 is hydrogen, hydroxyl, halogen, thiol, alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl; R13 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 R4 is NR4′R4″, X is CR6R6′; R2, R2′, R6, R6′, R 8, R10, R11 , and R12 are each hydrogen; R4′ and R4″ are lower alkyl; and R5 is hydroxyl or hydrogen. 3. The tetracycline compound of claim 2, wherein R4′ and R4″ are each methyl and R5 is hydrogen. 4. The tetracycline compound of claim 1, wherein J7 and J8 are hydrogen. 5. The tetracycline compound of claim 1, wherein J5 is substituted or unsubstituted alkyl. 6. The tetracycline compound of claim 1, wherein J5 is sulfonyl. 7. The tetracycline compound of claim 1, wherein J5 and J6 are linked to form a ring. 8. The tetracycline compound of claim 1, wherein J5 is heteroaryl. 9. The tetracycline compound of claim 1, wherein J5 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 R7 is dimethylamino. 13. The compound of claim 1 or 9, wherein J6 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.