Modulators of Cystic Fibrosis Transmembrane Conductance Regulator
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Abstract
The present invention features a compound of formula I:
or a pharmaceutically acceptable salt thereof, where R1, R2, R3, W, X, Y, Z, n, o, p, and q are defined herein, for the treatment of CFTR mediated diseases, such as cystic fibrosis. The present invention also features pharmaceutical compositions, method of treating, and kits thereof.
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Citations
185 Claims
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1. A compound of formula I:
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185)
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2. The compound of claim 1, wherein ring A is a pyridyl, indole, indoline, isoindoline, pyrazole, pyrimidine, phenyl, quinoline, 5,6,7,8-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, pyrrolidine, aza-indole, pyrrole, oxazole, pyrazine, triazole, benzimidazole, indazole, or imidazole ring.
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3. The compound of claim 1, wherein ring A is selected from
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4. The compound of claim 1, wherein ring B is phenyl, pyridyl, pyridine-2(1H)-one, pyrazole, indole, thiophene, dihydrobenzofuran, pyrazine, indazole, thiazole, pyridine-4(1H)-one, pyrrolidinone, or quinoline.
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5. The compound of claim 1, wherein ring B is selected from
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6. The compound of claim 1, wherein ring C is phenyl, indole, cycloalkyl, pyridyl, pyrrolidine, naphthalene, piperidine, azetidine, or dihydroindene.
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7. The compound of claim 1, wherein ring C is
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8. The compound of claim 1, wherein Y is O.
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9. The compound of claim 1, wherein Y is CH2.
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10. The compound of claim 1, wherein Y is CH(C1-C6 aliphatic).
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11. The compound of claim 1, wherein Y is CH(CH3).
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12. The compound of claim 1, wherein Y is CH(CH2CH3).
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13. The compound of claim 1, wherein Y is N(C1-C6 aliphatic).
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14. The compound of claim 1, wherein Y is N(CH3).
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15. The compound of claim 1, wherein R1 is halo, CN, C1-C6 aliphatic, C1-C6 alkoxy, C3-C8 cycloalkyl, or a phenyl, pyridyl, pyrimidine, indole, aza-indole, azetidine, or thiophene ring, wherein all rings may be substituted with halo, C1-C6 aliphatic, C1-C6 alkoxy, C1-C6 fluoroaliphatic, C1-C6 fluoroalkoxy, OH, CH2OH, CH2OCH3, CN, CO2H, amino, amido, C3-C10 heteroaryl, C3-C10 heterocycloalkyl, or a (C1-C8 aliphatic)-R4 wherein up to three CH2 units may be replaced with O, CO, S, SO, SO2 or NR.
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16. The compound of claim 1, wherein R1 is selected from CH3, Cl, F, CN, OCH3, CF3, CH2CH3, tBu, CH(CH3)2,
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17. The compound of claim 1, wherein R2 is selected from halo, OH, CN, azide, amino, C1-C6 aliphatic or fluoroaliphatic, C1-C6 alkoxy or fluoroalkoxy, C3-C10 mono- or bicyclic heterocyclic ring wherein up to 4 carbon atoms may be replaced with O, S, N, or NR;
- or a (C1-C8 aliphatic)-R4 wherein up to three CH2 units may be replaced with O, CO, S, SO, SO2 or NR.
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18. The compound of claim 1, wherein R2 is selected from Cl, F, OH, CN, N3, NH2, NH(CH3), N(CH3)2, CH3, CH2OH, CH2CH3, CH(CH3)2, CHF2, OCH3, OCF3, OCHF2, OCH(CH3)2, C(O)CH3, CH2CH2OH, CH2NH2, NH(CH2)2OH, NH(CH2)2N(CH3)2, NH(CH2)2NH2, NH(CH2)3NH2, NH(CH2)2OCH3, NHCH(CH3)2,
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19. The compound of claim 1, wherein R3 is selected from halo, CN, C1-C6 aliphatic or fluoroaliphatic, C1-C6 alkoxy, or C3-C10 mono- or bicyclic heteroaryl or heterocycloalkyl wherein up to 4 carbon atoms may be replaced by O, S, N, or NR.
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20. The compound of claim 1, wherein R3 is selected from Cl, F, CN, CH3, OCH3, CF3, CH2CH3, CH2CF3, CH2CH2CH3, OCH2CH3, CH2OCH3, CH(CH3)2, CCH, CO2CH3, tBu, ═
- CH2, ═
O,
- CH2, ═
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21. The compound of claim 1, wherein o is 0.
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22. The compound of claim 1, wherein o is 1.
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23. The compound of claim 1, wherein o is 2.
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24. The compound of claim 1, wherein n is 0.
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25. The compound of claim 1, wherein n is 1.
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26. The compound of claim 1, wherein n is 2.
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27. The compound of claim 1, wherein p is 0.
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28. The compound of claim 1, wherein p is 1.
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29. The compound of claim 1, wherein p is 2.
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30. The compound of claim 1, wherein the compound is of formula Ia:
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31. The compound of claim 30, wherein ring B is phenyl, pyridyl, pyridine-2(1H)-one, pyrazole, indole, thiophene, dihydrobenzofuran, pyrazine, indazole, thiazole, pyridine-4(1H)-one, pyrrolidinone, or quinoline.
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32. The compound of claim 30, wherein ring B is selected from
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33. The compound of claim 30, wherein ring C is phenyl, indole, cycloalkyl, pyridyl, pyrrolidine, naphthalene, piperidine, or dihydroindene.
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34. The compound of claim 30, wherein ring C is
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35. The compound of claim 30, wherein Y is O.
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36. The compound of claim 30, wherein Y is CH2.
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37. The compound of claim 30, wherein Y is CH(C1-C6 aliphatic).
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38. The compound of claim 30, wherein Y is CH(CH3).
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39. The compound of claim 30, wherein Y is CH(CH2CH3).
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40. The compound of claim 30, wherein R1 is halo, CN, C1-C6 aliphatic, C1-C6 alkoxy, C3-C8 cycloalkyl, or a phenyl, pyridyl, pyrimidine, indole, aza-indole, or thiophene ring, wherein all rings may be substituted with halo, C1-C6 aliphatic, C1-C6 alkoxy, C1-C6 fluoroaliphatic, C1-C6 fluoroalkoxy, OH, CH2OH, CH2OCH3, CN, CO2H, amino, amido, C3-C10 heteroaryl, C3-C10 heterocycloalkyl, or a (C1-C8 aliphatic)-R4 wherein up to three CH2 units may be replaced with O, CO, S, SO, SO2 or NR.
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41. The compound of claim 30, wherein R1 is selected from CH3, Cl, F, CN, OCH3, CF3, CH2CH3, tBu, CH(CH3)2,
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42. The compound of claim 30, wherein R2 is selected from halo, OH, CN, azide, amino, C1-C6 aliphatic or fluoroaliphatic, C1-C6 alkoxy or fluoroalkoxy, C3-C10 mono- or bicyclic heterocyclic ring wherein up to 4 carbon atoms may be replaced with O, S, N, or NR;
- or a (C1-C8 aliphatic)-R4 wherein up to three CH2 units may be replaced with O, CO, S, SO, SO2 or NR.
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43. The compound of claim 30, wherein R2 is selected from Cl, F, OH, CN, N3, NH2, NH(CH3), N(CH3)2, CH3, CH2OH, CH2CH3, CH(CH3)2, CHF2, OCH3, OCF3, OCHF2, OCH(CH3)2, C(O)CH3, CH2CH2OH, CH2NH2, NH(CH2)2OH, NH(CH2)2N(CH3)2, NH(CH2)2NH2, NH(CH2)3NH2, NH(CH2)2OCH3, NHCH(CH3)2,
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44. The compound of claim 30, wherein R3 is selected from halo, CN, C1-C6 aliphatic or fluoroaliphatic, C1-C6 alkoxy, or C3-C10 mono- or bicyclic heteroaryl wherein up to 4 carbon atoms may be replaced by O, S, N, or NR.
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45. The compound of claim 30, wherein R3 is selected from Cl, F, CN, CH3, OCH3, CF3, CH2CH3, CH2CF3, CH2CH2CH3, OCH2CH3, CH2OCH3, CH(CH3)2, CCH, CO2CH3, tBu, ═
- CH2, ═
O,
- CH2, ═
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46. The compound of claim 30, wherein o is 0.
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47. The compound of claim 30, wherein o is 1.
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48. The compound of claim 30, wherein n is 0.
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49. The compound of claim 30, wherein n is 1.
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50. The compound of claim 30, wherein n is 2.
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51. The compound of claim 30, wherein p is 0.
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52. The compound of claim 30, wherein p is 1.
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53. The compound of claim 30, wherein p is 2.
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54. The compound of claim 30, wherein ring B is phenyl.
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55. The compound of claim 30, wherein ring B and ring C are independently phenyl or pyridyl.
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56. The compound of claim 1, wherein the compound is of formula Ib:
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57. The compound of claim 56, wherein ring B is phenyl, pyridyl, pyridine-2(1H)-one, pyrazole, indole, thiophene, dihydrobenzofuran, pyrazine, indazole, thiazole, pyridine-4(1H)-one, pyrrolidinone, or quinoline.
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58. The compound of claim 56, wherein ring B is selected from
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59. The compound of claim 56, wherein ring C is phenyl, indole, cycloalkyl, pyridyl, pyrrolidine, naphthalene, or dihydroindene.
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60. The compound of claim 56, wherein ring C is
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61. The compound of claim 56, wherein Y is O.
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62. The compound of claim 56, wherein Y is CH2.
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63. The compound of claim 56, wherein Y is CH(C1-C6 aliphatic).
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64. The compound of claim 56, wherein Y is CH(CH3).
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65. The compound of claim 56, wherein Y is CH(CH2CH3).
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66. The compound of claim 56, wherein R1 is halo, CN, C1-C6 aliphatic, C1-C6 alkoxy, C3-C8 cycloalkyl, or a phenyl, pyridyl, pyrimidine, indole, aza-indole, or thiophene ring, wherein all rings may be substituted with halo, C1-C6 aliphatic, C1-C6 alkoxy, C1-C6 fluoroaliphatic, C1-C6 fluoroalkoxy, OH, CH2OH, CH2OCH3, CN, CO2H, amino, amido, C3-C10 heteroaryl, C3-C10 heterocycloalkyl, or a (C1-C8 aliphatic)-R4 wherein up to three CH2 units may be replaced with O, CO, S, SO, SO2 or NR.
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67. The compound of claim 56, wherein R1 is selected from CH3, Cl, F, CN, OCH3, CF3, CH2CH3, tBu, CH(CH3)2,
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68. The compound of claim 56, wherein R2 is selected from halo, OH, CN, azide, amino, C1-C6 aliphatic or fluoroaliphatic, C1-C6 alkoxy or fluoroalkoxy, C3-C10 mono- or bicyclic heterocyclic ring wherein up to 4 carbon atoms may be replaced with O, S, N, or NR;
- or a (C1-C8 aliphatic)-R4 wherein up to three CH2 units may be replaced with O, CO, S, SO, SO2 or NR.
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69. The compound of claim 56, wherein R2 is selected from Cl, F, OH, CN, N3, NH2, NH(CH3), N(CH3)2, CH3, CH2OH, CH2CH3, CH(CH3)2, CHF2, OCH3, OCF3, OCHF2, OCH(CH3)2, C(O)CH3, CH2CH2OH, CH2NH2, NH(CH2)2OH, NH(CH2)2N(CH3)2, NH(CH2)2NH2, NH(CH2)3NH2, NH(CH2)2OCH3, NHCH(CH3)2,
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70. The compound of claim 56, wherein R3 is selected from halo, CN, C1-C6 aliphatic or fluoroaliphatic, C1-C6 alkoxy, or C3-C10 mono- or bicyclic heteroaryl wherein up to 4 carbon atoms may be replaced by O, S, N, or NR.
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71. The compound of claim 56, wherein R3 is selected from Cl, F, CN, CH3, OCH3, CF3, CH2CH3, CH2CF3, CH2CH2CH3, OCH2CH3, CH2OCH3, CH(CH3)2, CCH, CO2CH3, tBu, ═
- CH2, ═
O,
- CH2, ═
-
72. The compound of claim 56, wherein o is 0.
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73. The compound of claim 56, wherein o is 1.
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74. The compound of claim 56, wherein o is 2.
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75. The compound of claim 56, wherein n is 0.
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76. The compound of claim 56, wherein n is 1.
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77. The compound of claim 56, wherein n is 2.
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78. The compound of claim 56, wherein p is 0.
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79. The compound of claim 56, wherein p is 1.
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80. The compound of claim 56, wherein p is 2.
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81. The compound of claim 56, wherein ring B is pyridyl.
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82. The compound of claim 56, wherein ring B is phenyl.
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83. The compound of claim 56, wherein ring B and ring C are phenyl.
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84. The compound of claim 1, wherein the compound is of formula Ic:
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85. The compound of claim 84, wherein ring B is phenyl, pyridyl, pyridine-2(1H)-one, pyrazole, indole, thiophene, dihydrobenzofuran, pyrazine, indazole, thiazole, pyridine-4(1H)-one, pyrrolidinone, or quinoline.
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86. The compound of claim 84, wherein ring B is selected from
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87. The compound of claim 84, wherein ring C is phenyl, indole, cycloalkyl, pyridyl, pyrrolidine, naphthalene, or dihydroindene.
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88. The compound of claim 84, wherein ring C is
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89. The compound of claim 84, wherein Y is O.
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90. The compound of claim 84, wherein Y is CH2.
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91. The compound of claim 84, wherein Y is CH(C1-C6 aliphatic).
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92. The compound of claim 84, wherein Y is CH(CH3).
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93. The compound of claim 84, wherein Y is CH(CH2CH3).
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94. The compound of claim 84, wherein R1 is halo, CN, C1-C6 aliphatic, C1-C6 alkoxy, C3-C8 cycloalkyl, or a phenyl, pyridyl, pyrimidine, indole, aza-indole, or thiophene ring, wherein all rings may be substituted with halo, C1-C6 aliphatic, C1-C6 alkoxy, C1-C6 fluoroaliphatic, C1-C6 fluoroalkoxy, OH, CH2OH, CH2OCH3, CN, CO2H, amino, amido, C3-C10 heteroaryl, C3-C10 heterocycloalkyl, or a (C1-C8 aliphatic)-R4 wherein up to three CH2 units may be replaced with O, CO, S, SO, SO2 or NR.
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95. The compound of claim 84, wherein R1 is selected from CH3, Cl, F, CN, OCH3, CF3, CH2CH3, tBu, CH(CH3)2,
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96. The compound of claim 84, wherein R2 is selected from halo, OH, CN, azide, amino, C1-C6 aliphatic or fluoroaliphatic, C1-C6 alkoxy or fluoroalkoxy, C3-C10 mono- or bicyclic heterocyclic ring wherein up to 4 carbon atoms may be replaced with O, S, N, or NR;
- or a (C1-C8 aliphatic)-R4 wherein up to three CH2 units may be replaced with O, CO, S, SO, SO2 or NR.
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97. The compound of claim 84, wherein R2 is selected from Cl, F, OH, CN, N3, NH2, NH(CH3), N(CH3)2, CH3, CH2OH, CH2CH3, CH(CH3)2, CHF2, OCH3, OCF3, OCHF2, OCH(CH3)2, C(O)CH3, CH2CH2OH, CH2NH2, NH(CH2)2OH, NH(CH2)2N(CH3)2, NH(CH2)2NH2, NH(CH2)3NH2, NH(CH2)2OCH3, NHCH(CH3)2,
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98. The compound of claim 84, wherein R3 is selected from halo, CN, C1-C6 aliphatic or fluoroaliphatic, C1-C6 alkoxy, or C3-C10 mono- or bicyclic heteroaryl wherein up to 4 carbon atoms may be replaced by O, S, N, or NR.
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99. The compound of claim 84, wherein R3 is selected from Cl, F, CN, CH3, OCH3, CF3, CH2CH3, CH2CF3, CH2CH2CH3, OCH2CH3, CH2OCH3, CH(CH3)2, CCH, CO2CH3, tBu, ═
- CH2, ═
O,
- CH2, ═
-
100. The compound of claim 84, wherein o is 0.
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101. The compound of claim 84, wherein o is 1.
-
102. The compound of claim 84, wherein o is 2.
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103. The compound of claim 84, wherein n is 0.
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104. The compound of claim 84, wherein n is 1.
-
105. The compound of claim 84, wherein n is 2.
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106. The compound of claim 84, wherein p is 0.
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107. The compound of claim 84, wherein p is 1.
-
108. The compound of claim 84, wherein p is 2.
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109. The compound of claim 84, wherein ring B is phenyl.
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110. The compound of claim 84, wherein ring C is phenyl or pyridyl.
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111. The compound of claim 84, wherein ring B and ring C are phenyl.
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112. The compound of claim 1, wherein the compound is of formula Id:
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113. The compound of claim 112, wherein ring B is phenyl, pyridyl, pyridine-2(1H)-one, pyrazole, indole, thiophene, dihydrobenzofuran, pyrazine, indazole, thiazole, pyridine-4(1H)-one, pyrrolidinone, or quinoline.
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114. The compound of claim 112, wherein ring B is selected from
-
115. The compound of claim 112, wherein ring C is phenyl, indole, cycloalkyl, pyridyl, pyrrolidine, naphthalene, or dihydroindene.
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116. The compound of claim 112, wherein ring C is
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117. The compound of claim 112, wherein Y is O.
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118. The compound of claim 112, wherein Y is CH2.
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119. The compound of claim 112, wherein Y is CH(C1-C6 aliphatic).
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120. The compound of claim 112, wherein Y is CH(CH3).
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121. The compound of claim 112, wherein Y is CH(CH2CH3).
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122. The compound of claim 112, wherein R1 is halo, CN, C1-C6 aliphatic, C1-C6 alkoxy, C3-C8 cycloalkyl, or a phenyl, pyridyl, pyrimidine, indole, aza-indole, or thiophene ring, wherein all rings may be substituted with halo, C1-C6 aliphatic, C1-C6 alkoxy, C1-C6 fluoroaliphatic, C1-C6 fluoroalkoxy, OH, CH2OH, CH2OCH3, CN, CO2H, amino, amido, C3-C10 heteroaryl, C3-C10 heterocycloalkyl, or a (C1-C8 aliphatic)-R4 wherein up to three CH2 units may be replaced with O, CO, S, SO, SO2 or NR.
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123. The compound of claim 112, wherein R1 is selected from CH3, Cl, F, CN, OCH3, CF3, CH2CH3, tBu, CH(CH3)2,
-
124. The compound of claim 112, wherein R2 is selected from halo, OH, CN, azide, amino, C1-C6 aliphatic or fluoroaliphatic, C1-C6 alkoxy or fluoroalkoxy, C3-C10 mono- or bicyclic heterocyclic ring wherein up to 4 carbon atoms may be replaced with O, S, N, or NR;
- or a (C1-C8 aliphatic)-R4 wherein up to three CH2 units may be replaced with O, CO, S, SO, SO2 or NR.
-
125. The compound of claim 112, wherein R2 is selected from Cl, F, OH, CN, N3, NH2, NH(CH3), N(CH3)2, CH3, CH2OH, CH2CH3, CH(CH3)2, CHF2, OCH3, OCF3, OCHF2, OCH(CH3)2, C(O)CH3, CH2CH2OH, CH2NH2, NH(CH2)2OH, NH(CH2)2N(CH3)2, NH(CH2)2NH2, NH(CH2)3NH2, NH(CH2)2OCH3, NHCH(CH3)2,
-
126. The compound of claim 112, wherein R3 is selected from halo, CN, C1-C6 aliphatic or fluoroaliphatic, C1-C6 alkoxy, or C3-C10 mono- or bicyclic heteroaryl wherein up to 4 carbon atoms may be replaced by O, S, N, or NR.
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127. The compound of claim 112, wherein R3 is selected from Cl, F, CN, CH3, OCH3, CF3, CH2CH3, CH2CF3, CH2CH2CH3, OCH2CH3, CH2OCH3, CH(CH3)2, CCH, CO2CH3, tBu, ═
- CH2, ═
O,
- CH2, ═
-
128. The compound of claim 112, wherein o is 0.
-
129. The compound of claim 112, wherein o is 1.
-
130. The compound of claim 112, wherein o is 2.
-
131. The compound of claim 112, wherein n is 0.
-
132. The compound of claim 112, wherein n is 1.
-
133. The compound of claim 112, wherein n is 2.
-
134. The compound of claim 112, wherein p is 0.
-
135. The compound of claim 112, wherein p is 1.
-
136. The compound of claim 112, wherein p is 2.
-
137. The compound of claim 112, wherein ring B is phenyl.
-
138. The compound of claim 112, wherein ring B is pyridyl.
-
139. The compound of claim 112, wherein ring C is phenyl.
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140. The compound of claim 112, wherein ring B and ring C are phenyl.
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141. The compound of claim 112, wherein ring B is pyridyl and ring C is phenyl.
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143. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
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144. The pharmaceutical composition of claim 143, further comprising one or more additional therapeutic agent(s).
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145. The pharmaceutical composition of claim 144, wherein the additional therapeutic agent is selected from a mucolytic agent, bronchodialator, an antibiotic, an anti-infective agent, a CFTR modulator, or an anti-inflammatory agent.
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146. The pharmaceutical composition of claim 144, wherein the additional therapeutic agent is a CFTR modulator.
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147. The pharmaceutical composition of claim 144, wherein the additional therapeutic agent is a CFTR corrector.
-
148. The pharmaceutical composition of claim 144, wherein the additional therapeutic agent is
-
149. The pharmaceutical composition of claim 144, wherein the additional therapeutic agent is
-
150. The pharmaceutical composition of claim 144, wherein the additional therapeutic agent is
-
151. The pharmaceutical composition of claim 144, wherein the additional therapeutic agent is a CFTR potentiator.
-
152. The pharmaceutical composition of claim 144, wherein the additional therapeutic agent is
-
153. The pharmaceutical composition of claim 144, wherein the additional therapeutic agents are a CFTR corrector and a CFTR potentiator.
-
154. The pharmaceutical composition of claim 144, wherein the additional therapeutic agents are
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155. The pharmaceutical composition of claim 144, wherein the additional therapeutic agents are
-
156. The pharmaceutical composition of claim 144, wherein the additional therapeutic agents are
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157. A method of treating cystic fibrosis in a patient comprising administering to the patient an effective amount of the compound of claim 1.
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158. The method of claim 157, further comprising administering to the patient one or more additional therapeutic agent(s) prior to, concurrent with, or subsequent to the compound of claim 1.
-
159. The method of claim 158, wherein the additional therapeutic agent is selected from a mucolytic agent, bronchodialator, an antibiotic, an anti-infective agent, a CFTR modulator, or an anti-inflammatory agent.
-
160. The method of claim 158, wherein the additional therapeutic agent is a CFTR modulator.
-
161. The method of claim 158, wherein the additional therapeutic agent is a CFTR corrector.
-
162. The method of claim 158, wherein the additional therapeutic agent is
-
163. The method of claim 158, wherein the additional therapeutic agent is
-
164. The method of claim 158, wherein the additional therapeutic agent is
-
165. The method of claim 158, wherein the additional therapeutic agent is a CFTR potentiator.
-
166. The method of claim 158, wherein the additional therapeutic agent is
-
167. The method of claim 157, wherein the patient is homozygous in the F508del mutation.
-
168. The method of claim 157, wherein the patient is heterozygous in the F508del mutation.
-
169. A kit comprising the compound of claim 1, and instructions for use thereof.
-
170. The kit of claim 169, further comprising one or more additional therapeutic agent(s).
-
171. The kit of claim 170, wherein the additional therapeutic agent is selected from a mucolytic agent, bronchodialator, an antibiotic, an anti-infective agent, a CFTR modulator, or an anti-inflammatory agent.
-
172. The kit of claim 170, wherein the additional therapeutic agent is a CFTR modulator.
-
173. The kit of claim 170, wherein the additional therapeutic agent is a CFTR corrector.
-
174. The kit of claim 170, wherein the additional therapeutic agent is
-
175. The kit of claim 170, wherein the additional therapeutic agent is
-
176. The kit of claim 170, wherein the additional therapeutic agent is
-
177. The kit of claim 170, wherein the additional therapeutic agent is a CFTR potentiator.
-
178. The kit of claim 170, wherein the additional therapeutic agent is
-
179. The kit of claim 170, wherein the additional therapeutic agents are a CFTR corrector and a CFTR potentiator.
-
180. The kit of claim 170, wherein the additional therapeutic agents are
-
181. The kit of claim 170, wherein the additional therapeutic agents are
-
182. The kit of claim 170, wherein the additional therapeutic agents are
-
183. The kit of claim 170, wherein the compound of claim 1 and the one or more additional therapeutic agent(s) are in separate containers.
-
184. The kit of claim 170, wherein the compound of claim 1 and the one or more additional therapeutic agent(s) are in the same container.
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185. The kit of claim 170, wherein the container(s) is a bottle, vial, or blister pack, or combination thereof.
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2. The compound of claim 1, wherein ring A is a pyridyl, indole, indoline, isoindoline, pyrazole, pyrimidine, phenyl, quinoline, 5,6,7,8-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, pyrrolidine, aza-indole, pyrrole, oxazole, pyrazine, triazole, benzimidazole, indazole, or imidazole ring.
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142. A compound selected from Table 1.
Specification
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Current AssigneeVertex Pharmaceuticals Incorporated
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Original AssigneeVertex Pharmaceuticals Incorporated
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InventorsMiller, Mark Thomas, Anderson, Corey, Arumugam, Vijayalaksmi, Bear, Brian Richard, Binch, Hayley Marie, Cleveland, Thomas, Coon, Timothy Richard, Frieman, Bryan A., Grootenhuis, Peter Diederik Jan, Hadida-Ruah, Sara Sabina, McCartney, Jason, Silina, Alina, Termin, Andreas P., Uy, Johnny, Zhou, Jinglan, Clemens, Jeremy J., Conroy, Erica, Gross, Raymond Stanley, Haripada, Khatuya, Joshi, Pramod Virupax, Krenitsky, Paul John, Lin, Chun-Chieh, Marelius, Gulin Erdgogan, Melillo, Vito, Nicholls, Georgia McGaughey, Pierre, Fabrice Jean Denis
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Granted Patent
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Time in Patent OfficeDays
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Field of Search
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US Class Current1/1
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CPC Class CodesA61J 1/035 Blister-type containers bli...A61K 31/404 Indoles, e.g. pindololA61K 31/415 1,2-DiazolesA61K 31/44 Non condensed pyridines; Hy...A61K 31/4418 having a carbocyclic group ...A61K 31/4439 containing a five-membered ...A61K 31/444 containing a six-membered r...A61K 31/4525 containing a five-membered ...A61K 31/4545 containing a six-membered r...A61K 31/4709 Non-condensed quinolines an...A61K 31/496 Non-condensed piperazines c...A61K 31/497 containing further heterocy...A61K 31/506 not condensed and containin...A61P 11/00 Drugs for disorders of the ...A61P 43/00 Drugs for specific purposes...C07D 209/18 Radicals substituted by car...C07D 209/42 Carbon atoms having three b...C07D 209/49 and having in the molecule ...C07D 213/64 attached in position 2 or 6C07D 213/73 Unsubstituted amino or imin...C07D 213/82 : in position 3C07D 213/84 : NitrilesC07D 231/12 : with only hydrogen atoms, h...C07D 231/14 : with hetero atoms or with c...C07D 231/20 : One oxygen atom attached in...C07D 235/24 : with hetero atoms or with c...C07D 239/34 : One oxygen atomC07D 401/04 : directly linked by a ring-m...C07D 401/12 : linked by a chain containin...C07D 401/14 : containing three or more he...C07D 403/10 : linked by a carbon chain co...C07D 403/12 : linked by a chain containin...C07D 405/14 : containing three or more he...C07D 407/12 : linked by a chain containin...C07D 413/14 : containing three or more he...C07D 417/12 : linked by a chain containin...Y02A 50/30 : Against vector-borne diseas...