IP Library › Granted Patent US 7,166,619
Granted Patent B2
US 7,166,619 · App. 10/636,327 · Granted Jan 23, 2007

Prenylation inhibitors and methods of their synthesis and use

Assignee: PPD Discovery , Inc.
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 7,166,619
App. No.
10/636,327
Granted
Jan 23, 2007
Kind
B2
Abstract

The present invention is directed to compounds useful in the treatment of diseases associated with prenylation of proteins and pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising same, and to methods for inhibiting protein prenylation in an organism using the same.

Claims (111)

1. A compound having the formula:

or a pharmaceutically-acceptable salt thereof, wherein:

R 1 is phenyl, benzyl, methyl, ethyl, propyl, 3,4-dimethylphenyl, 3,4-difluorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, CH 2 CF 3 , 4-trifluoromethylphenyl, 4-nitrophenyl, 4-bromophenyl, 3-bromophenyl, 4-methylphenyl, 4-methoxyphenyl, 4-chloro-2-methylphenyl, 4-fluorophenyl, 4-sulfonamidophenyl, 3-methoxyphenyl, 4-chlorophenyl, 3-chlorophenyl, 3,5-difluorophenyl, 4-aminophenyl, ethanol, or 3,4-methylenedioxyphenyl;

R 2 is pyridine or pyridine-1-oxide;

R 3 is H, CH 2 CH 2 OH, CH 2 CH 2 OCH 3 , CH 2 CH 2 N(CH 3 ) 2 , CH 2 CH 2 NHCH 3 , CH 2 OH, (CH 2 ) 3 OH, CH 2 CH 2 CO 2 H, CH 2 CO 2 H, CH 2 CH 2 SOCH 3 , CH 2 CH 2 SO 2 CH 3 , CH 2 CH 2 SH or CH 2 CH 2 SCH 3 ;

R 4 H, NH 2 , CON(CH 3 ) 2 , NH 2 CO 2 H CN, CH 2 OH, CONH 2 , CSNH 2 , CONHOH, C(NH)NH 2 , CONHNH 2 , CONHCH 3 , CH 2 OCH 3 , CONH-cyclohexyl, CO 2 CH 3 , or

R 5 is H, isopropyl, benzyl, 4-trifluoromethylbenzyl, 4-cyanobenzyl, 4-benzoylbenzyl, 3-chlorobenzyl, pentafluorobenzyl, 3,4-dichlorobenzyl, 2-fluorobenzyl, 4-methoxybenzyl, CH 2 CH 2 -phenyl, 4-fluorobenzyl, 4-phenylbenzyl, CH 2 COOH, CH 2 CH 2 COOH, (CH 2 ) 4 NH 2 , CH 2 CH 2 SCH 3 , 4-hydroxybenzyl, CH 2 -naphthyl, 4-methylbenzyl, CH 2 -cyclohexane, 4-chlorobenzyl, phenyl, 2-hydroxybenzyl, 4-tertbutoxybenzyl, 4-aminobenzyl, CH 2 OH, (CH 2 ) 3 NHC(NH)NH 2 or CH 2 CH(CH 3 ) 2 ; and,

R 6 is H, methyl, ethyl, propyl, isopropyl, CH 2 CO 2 H, CH 2 CO 2 Et, benzyl, or CH 2 -(2-methoxynaphthyl); or,

R 5 and R 6 together form:

2. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically-acceptable salt thereof, and a pharmaceutically-acceptable carrier.

3. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

4. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

5. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

6. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

7. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

8. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

9. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

10. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

11. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

12. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

13. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

14. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof wherein the compound has the formula:

15. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

16. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

17. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

18. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

19. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

20. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

21. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

22. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

23. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

24. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

25. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

26. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

27. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

28. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

29. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

30. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

31. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

32. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

33. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

34. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

35. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

36. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

37. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

38. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

39. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

40. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

41. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

42. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

43. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

44. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

45. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

46. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

47. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

48. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

49. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

50. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

51. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

52. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

53. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

54. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

55. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

56. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

57. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

58. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

59. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

60. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

61. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

62. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

63. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

64. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

65. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

66. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

67. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

68. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

69. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

70. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

71. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

72. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

73. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

74. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

75. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

76. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

77. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

78. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

79. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

80. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

81. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

82. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

83. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

84. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

85. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

86. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

87. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

88. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

89. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

90. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

91. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

92. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

93. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

94. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

95. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

96. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

97. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

98. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

99. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

100. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

101. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

102. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

103. A compound of claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound has the formula:

Assignments (5)
RELEASE OF SECURITY INTEREST Recorded Sep 2, 2015
From: CREDIT SUISSE AG, CAYMAN ISLANDS BRANCH, AS ADMINISTRATIVE AGENT
To: PHARMACEUTICAL PRODUCT DEVELOPMENT, LLC; PPD DEVELOPMENT, L.P.; PHARMACO INVESTEMENTS, INC.; X-CHEM, INC.
Reel/Frame 036481/0051 →
SECURITY AGREEMENT Recorded Dec 6, 2011
From: PHARMACEUTICAL PRODUCT DEVELOPMENT, INC.; PPD DEVELOPMENT, LP; PHARMACO INVESTMENTS INC. AND DUKE UNIVERSITY; PHARMACO INVESTMENTS INC.
To: CREDIT SUISSE AG, CAYMAN ISLANDS BRANCH, AS ADMINISTRATIVE AGENT
Reel/Frame 027334/0106 →
MERGER Recorded Feb 3, 2009
From: PPD DISCOVERY, INC.
To: PHARMACEUTICAL PRODUCT DEVELOPMENT, INC.
Reel/Frame 022191/0690 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 20, 2007
From: PHARMACEUTICAL PRODUCT DEVELOPMENT, INC.
To: PHARMACO INVESTMENTS, INC.
Reel/Frame 018907/0953 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 22, 2004
From: LI, FRANCINE FEIRONG; REHDER, KENNETH S.; CAMPBELL, MICHAEL GORDON; VISCARDI, CELESTE PATRICE; STRACHAN, JON-PAUL; GUO, ZHENGMING
To: PPD DISCOVERY, INC.
Reel/Frame 014906/0152 →
Continuity (4)
Continuation In Part 1033628500 · Jan 3, 2003
Continuation In Part 1021962800 · Aug 14, 2002
Provisional Application 6045455400 · Mar 14, 2003
Related Publication 20040116425A1 · Jun 17, 2004