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):	Nelson; Mark L. (Norfolk, MA), Ohemeng; Kwasi (Norwood, MA), Frechette; Roger (Reading, MA), Abato; Paul (Providence, RI), Amoo; Victor (Daphne, AL), Assefa; Haregewein (Braintree, MA), Berniac; Joel (Stoneham, MA), Bhatia; Beena (Mansfield, MA), Bowser; Todd (Charlton, MA), Chen; Jackson (Brookline, MA), Honeyman; Laura (Roslindale, MA), Ismail; Mohamed Y. (Bedford, MA), Kim; Oak (Cambridge, MA), Mechiche; Rachid (South Boston, MA), Reddy; N. Laxma (Solon, OH), Verma; Atul K. (Mansfield, MA), Viski; Peter (Asharoken, NY), Warchol; Tadeusz (Northborough, MA), Yanachkov; Ivan (Newton, MA)
Assignee:	Paratek Pharmaceuticals, Inc. (Boston, MA)
Application Number:	10/737,361
Patent Claims:	1. A tetracycline compound of formula (III): ##STR00251## wherein: J.sup.5 and J.sup.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.sup.7 and J.sup.8 are each alkyl, halogen, or hydrogen; X is CR.sup.6'R.sup.6; R.sup.2, R.sup.2',R.sup.4', and R.sup.4'' are each independently hydrogen, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, arylalkyl, aryl, heterocyclic, heteroaromatic or a prodrug moiety; R.sup.4 is NR.sup.4'R.sup.4'', alkyl, alkenyl, alkynyl, aryl, hydroxyl, halogen, or hydrogen; R.sup.3, R.sup.10, R.sup.11 and R.sup.12 are each hydrogen or a pro-drug moiety; R.sup.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.sup.6 and R.sup.6' are each independently hydrogen, methylene, absent, hydroxyl, halogen, thiol, alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl; R.sup.7 is hydrogen, ethyl, phenyl, 4-t-butylphenyl, t-butylaminophenyl or dimethylamino; R.sup.8 is hydrogen, hydroxyl, halogen, thiol, alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl; R.sup.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.sup.4 is NR.sup.4'R.sup.4'', X is CR.sup.6R.sup.6'; R.sup.2, R.sup.2', R.sup.6, R.sup.6', R.sup.8, R.sup.10, R.sup.11 , and R.sup.12 are each hydrogen; R.sup.4' and R.sup.4'' are lower alkyl; and R.sup.5 is hydroxyl or hydrogen. 3. The tetracycline compound of claim 2, wherein R.sup.4' and R.sup.4'' are each methyl and R.sup.5 is hydrogen. 4. The tetracycline compound of claim 1, wherein J.sup.7 and J.sup.8 are hydrogen. 5. The tetracycline compound of claim 1, wherein J.sup.5 is substituted or unsubstituted alkyl. 6. The tetracycline compound of claim 1, wherein J.sup.5 is sulfonyl. 7. The tetracycline compound of claim 1, wherein J.sup.5 and J.sup.6 are linked to form a ring. 8. The tetracycline compound of claim 1, wherein J.sup.5 is heteroaryl. 9. The tetracycline compound of claim 1, wherein J.sup.5 is substituted carbonyl. 10. The tetracycline compound of claim 1, wherein said compound is selected from the group consisting of: ##STR00252## ##STR00253## ##STR00254## ##STR00255## ##STR00256## ##STR00257## 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: ##STR00258## ##STR00259## ##STR00260## ##STR00261## ##STR00262## ##STR00263## ##STR00264## ##STR00265## ##STR00266## ##STR00267## ##STR00268## ##STR00269## ##STR00270## ##STR00271## ##STR00272## ##STR00273## ##STR00274## ##STR00275## ##STR00276## ##STR00277## ##STR00278## ##STR00279## ##STR00280## ##STR00281## ##STR00282## ##STR00283## ##STR00284## ##STR00285## ##STR00286## ##STR00287## ##STR00288## ##STR00289## ##STR00290## ##STR00291## ##STR00292## or a pharmaceutically acceptable salt thereof. 12. The compound of claim 1, wherein R.sup.7 is dimethylamino. 13. The compound of claim 1 or 9, wherein J.sup.6 is alkyl. 14. The compound of claim 13, wherein said compound is ##STR00293## and pharmaceutically acceptable salts thereof. 15. The compound of claim 1, wherein said compound is ##STR00294## and pharmaceutically acceptable salts thereof. 16. The compound of claim 1, wherein said compound is ##STR00295## and pharmaceutically acceptable salts thereof. 17. The compound of claim 1, wherein said compound is ##STR00296## and pharmaceutically acceptable salts thereof. 18. The compound of claim 1, wherein said compound is ##STR00297## and pharmaceutically acceptable salts thereof. 19. The compound of claim 1, wherein said compound is ##STR00298## and pharmaceutically acceptable salts thereof. 20. The compound of claim 1, wherein said compound is ##STR00299## and pharmaceutically acceptable salts thereof. 21. The compound of claim 1, wherein said compound is ##STR00300## and pharmaceutically acceptable salts thereof. 22. The compound of claim 1, wherein said compound is ##STR00301## and pharmaceutically acceptable salts thereof. 23. The compound of claim 1, wherein said compound is ##STR00302## and pharmaceutically acceptable salts thereof. 24. The compound of claim 1, wherein said compound is ##STR00303## and pharmaceutically acceptable salts thereof. 25. The compound of claim 1, wherein said compound is ##STR00304## and pharmaceutically acceptable salts thereof. 26. The compound of claim 1, wherein said compound is ##STR00305## and pharmaceutically acceptable salts thereof. 27. The compound of claim 1, wherein said compound is ##STR00306## and pharmaceutically acceptable salts thereof. 28. The compound of claim 1, wherein said compound is ##STR00307## and pharmaceutically acceptable salts thereof. 29. The compound of claim 1, wherein said compound is ##STR00308## and pharmaceutically acceptable salts thereof. 30. The compound of claim 1, wherein said compound is ##STR00309## and pharmaceutically acceptable salts thereof. 31. The compound of claim 1, wherein said compound is ##STR00310## and pharmaceutically acceptable salts thereof. 32. The compound of claim 1, wherein said compound is ##STR00311## and pharmaceutically acceptable salts thereof. 33. The compound of claim 1, wherein said compound is ##STR00312## and pharmaceutically acceptable salts thereof. 34. The compound of claim 1, wherein said compound is ##STR00313## and pharmaceutically acceptable salts thereof. 35. The compound of claim 1, wherein said compound is ##STR00314## and pharmaceutically acceptable salts thereof. 36. The compound of claim 1, wherein said compound is ##STR00315## and pharmaceutically acceptable salts thereof. 37. The compound of claim 1, wherein said compound is ##STR00316## and pharmaceutically acceptable salts thereof. 38. The compound of claim 1, wherein said compound is ##STR00317## and pharmaceutically acceptable salts thereof. 39. The compound of claim 1, wherein said compound is ##STR00318## and pharmaceutically acceptable salts thereof. 40. The compound of claim 1, wherein said compound is ##STR00319## and pharmaceutically acceptable salts thereof. 41. The compound of claim 1, wherein said compound is ##STR00320## and pharmaceutically acceptable salts thereof. 42. The compound of claim 1, wherein said compound is ##STR00321## and pharmaceutically acceptable salts thereof. 43. The compound of claim 1, wherein said compound is ##STR00322## and pharmaceutically acceptable salts thereof. 44. The compound of claim 1, wherein said compound is ##STR00323## and pharmaceutically acceptable salts thereof. 45. The compound of claim 1, wherein said compound is ##STR00324## and pharmaceutically acceptable salts thereof. 46. The compound of claim 1, wherein said compound is ##STR00325## and pharmaceutically acceptable salts thereof. 47. The compound of claim 1, wherein said compound is ##STR00326## and pharmaceutically acceptable salts thereof. 48. The compound of claim 1, wherein said compound is ##STR00327## and pharmaceutically acceptable salts thereof. 49. The compound of claim 1, wherein said compound is ##STR00328## and pharmaceutically acceptable salts thereof. 50. The compound of claim 1, wherein said compound is ##STR00329## and pharmaceutically acceptable salts thereof. 51. The compound of claim 1, wherein said compound is ##STR00330## and pharmaceutically acceptable salts thereof. 52. The compound of claim 1, wherein said compound is ##STR00331## and pharmaceutically acceptable salts thereof. 53. The compound of claim 1, wherein said compound is ##STR00332## and pharmaceutically acceptable salts thereof. 54. The compound of claim 1, wherein said compound is ##STR00333## and pharmaceutically acceptable salts thereof. 55. The compound of claim 1, wherein said compound is ##STR00334## and pharmaceutically acceptable salts thereof. 56. The compound of claim 1, wherein said compound is ##STR00335## and pharmaceutically acceptable salts thereof. 57. The compound of claim 1, wherein said compound is ##STR00336## and pharmaceutically acceptable salts thereof. 58. The compound of claim 1, wherein said compound is ##STR00337## and pharmaceutically acceptable salts thereof. 59. The compound of claim 1, wherein said compound is ##STR00338## and pharmaceutically acceptable salts thereof. 60. The compound of claim 1, wherein said compound is ##STR00339## and pharmaceutically acceptable salts thereof. 61. The compound of claim 1, wherein said compound is ##STR00340## and pharmaceutically acceptable salts thereof. 62. The compound of claim 1, wherein said compound is ##STR00341## and pharmaceutically acceptable salts thereof. 63. The compound of claim 1, wherein said compound is ##STR00342## and pharmaceutically acceptable salts thereof. 64. The compound of claim 1, wherein said compound is ##STR00343## and pharmaceutically acceptable salts thereof. 65. The compound of claim 1, wherein said compound is ##STR00344## and pharmaceutically acceptable salts thereof. 66. The compound of claim 1, wherein said compound is ##STR00345## and pharmaceutically acceptable salts thereof. 67. The compound of claim 1, wherein said compound is ##STR00346## and pharmaceutically acceptable salts thereof. 68. The compound of claim 1, wherein said compound is ##STR00347## and pharmaceutically acceptable salts thereof. 69. The compound of claim 1, wherein said compound is ##STR00348## and pharmaceutically acceptable salts thereof. 70. The compound of claim 1, wherein said compound is ##STR00349## and pharmaceutically acceptable salts thereof. 71. The compound of claim 1, wherein said compound is ##STR00350## and pharmaceutically acceptable salts thereof. 72. The compound of claim 1, wherein said compound is ##STR00351## and pharmaceutically acceptable salts thereof. 73. The compound of claim 1, wherein said compound is ##STR00352## and pharmaceutically acceptable salts thereof. 74. The compound of claim 1, wherein said compound is ##STR00353## and pharmaceutically acceptable salts thereof. 75. The compound of claim 1, wherein said compound is ##STR00354## and pharmaceutically acceptable salts thereof. 76. The compound of claim 1, wherein said compound is ##STR00355## and pharmaceutically acceptable salts thereof. 77. The compound of claim 1, wherein said compound is ##STR00356## and pharmaceutically acceptable salts thereof. 78. The compound of claim 1, wherein said compound is ##STR00357## and pharmaceutically acceptable salts thereof. 79. The compound of claim 1, wherein said compound is ##STR00358## and pharmaceutically acceptable salts thereof. 80. The compound of claim 1, wherein said compound is ##STR00359## and pharmaceutically acceptable salts thereof. 81. The compound of claim 1, wherein said compound is ##STR00360## and pharmaceutically acceptable salts thereof. 82. The compound of claim 1, wherein said compound is ##STR00361## and pharmaceutically acceptable salts thereof. 83. The compound of claim 1, wherein said compound is ##STR00362## and pharmaceutically acceptable salts thereof. 84. The compound of claim 1, wherein said compound is ##STR00363## and pharmaceutically acceptable salts thereof. 85. The compound of claim 1, wherein said compound is ##STR00364## and pharmaceutically acceptable salts thereof. 86. The compound of claim 1, wherein said compound is ##STR00365## and pharmaceutically acceptable salts thereof. 87. The compound of claim 1, wherein said compound is ##STR00366## and pharmaceutically acceptable salts thereof. 88. The compound of claim 1, wherein said compound is ##STR00367## and pharmaceutically acceptable salts thereof. 89. The compound of claim 1, wherein said compound is ##STR00368## and pharmaceutically acceptable salts thereof. 90. The compound of claim 1, wherein said compound is ##STR00369## and pharmaceutically acceptable salts thereof. 91. The compound of claim 1, wherein said compound is ##STR00370## and pharmaceutically acceptable salts thereof. 92. The compound of claim 1, wherein said compound is ##STR00371## and pharmaceutically acceptable salts thereof. 93. The compound of claim 1, wherein said compound is ##STR00372## and pharmaceutically acceptable salts thereof. 94. The compound of claim 1, wherein said compound is ##STR00373## and pharmaceutically acceptable salts thereof. 95. The compound of claim 1, wherein said compound is ##STR00374## and pharmaceutically acceptable salts thereof. 96. The compound of claim 1, wherein said compound is ##STR00375## and pharmaceutically acceptable salts thereof. 97. The compound of claim 1, wherein said compound is ##STR00376## and pharmaceutically acceptable salts thereof. 98. The compound of claim 1, wherein said compound is ##STR00377## and pharmaceutically acceptable salts thereof. 99. The compound of claim 1, wherein said compound is ##STR00378## and pharmaceutically acceptable salts thereof. 100. The compound of claim 1, wherein said compound is ##STR00379## and pharmaceutically acceptable salts thereof. 101. The compound of claim 1, wherein said compound is ##STR00380## and pharmaceutically acceptable salts thereof. 102. The compound of claim 1, wherein said compound is ##STR00381## and pharmaceutically acceptable salts thereof. 103. The compound of claim 1, wherein said compound is ##STR00382## and pharmaceutically acceptable salts thereof. 104. The compound of claim 1, wherein said compound is ##STR00383## and pharmaceutically acceptable salts thereof. 105. The compound of claim 1, wherein said compound is ##STR00384## and pharmaceutically acceptable salts thereof. 106. The compound of claim 1, wherein said compound is ##STR00385## and pharmaceutically acceptable salts thereof. 107. The compound of claim 1, wherein said compound is ##STR00386## and pharmaceutically acceptable salts thereof. 108. The compound of claim 1, wherein said compound is ##STR00387## and pharmaceutically acceptable salts thereof. 109. The compound of claim 1, wherein said compound is ##STR00388## and pharmaceutically acceptable salts thereof. 110. The compound of claim 1, wherein said compound is ##STR00389## and pharmaceutically acceptable salts thereof. 111. The compound of claim 1, wherein said compound is ##STR00390## and pharmaceutically acceptable salts thereof. 112. The compound of claim 1, wherein said compound is ##STR00391## and pharmaceutically acceptable salts thereof. 113. The compound of claim 1, wherein said compound is ##STR00392## and pharmaceutically acceptable salts thereof. 114. The compound of claim 1, wherein said compound is ##STR00393## and pharmaceutically acceptable salts thereof. 115. The compound of claim 1, wherein said compound is ##STR00394## and pharmaceutically acceptable salts thereof. 116. The compound of claim 1, wherein said compound is ##STR00395## and pharmaceutically acceptable salts thereof. 117. The compound of claim 1, wherein said compound is ##STR00396## and pharmaceutically acceptable salts thereof. 118. The compound of claim 1, wherein said compound is ##STR00397## and pharmaceutically acceptable salts thereof. 119. The compound of claim 1, wherein said compound is ##STR00398## and pharmaceutically acceptable salts thereof. 120. The compound of claim 1, wherein said compound is ##STR00399## and pharmaceutically acceptable salts thereof. 121. The compound of claim 1, wherein said compound is ##STR00400## and pharmaceutically acceptable salts thereof. 122. The compound of claim 1, wherein said compound is ##STR00401## and pharmaceutically acceptable salts thereof. 123. The compound of claim 1, wherein said compound is ##STR00402## and pharmaceutically acceptable salts thereof. 124. The compound of claim 1, wherein said compound is ##STR00403## and pharmaceutically acceptable salts thereof. 125. The compound of claim 1, wherein said compound is ##STR00404## and pharmaceutically acceptable salts thereof. 126. The compound of claim 1, wherein said compound is ##STR00405## 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.