Novel Compounds and Methods of Using Them

• US 20100298270A1
• Filed: 07/23/2008
• Published: 11/25/2010
• Est. Priority Date: 07/23/2007
• Status: Abandoned Application

• Current Assignee: Syndax Pharmaceuticals, Inc.
• Original Assignee: Syndax Pharmaceuticals, Inc.
• Inventors: Goodenow, Robert, Ordentlich, Peter, Keana, John F.W.
• Application Number:
  US12/670,385
• Publication Number:
  US 20100298270A1
• Time in Patent Office: Days
• US Class Current: 514/89
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 213/30 Oxygen atoms
• CPC Class Codes: C07D 213/69 Two or more oxygen atoms
• CPC Class Codes: C07D 213/70 Sulfur atoms
• CPC Class Codes: C07D 213/79 Acids; Esters
• CPC Class Codes: C07D 213/81 Amides; Imides
• CPC Class Codes: C07D 309/40 Oxygen atoms attached in positions 3 and 4, e.g. maltol
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

Described herein are novel HDAC modulators, formulations containing them and methods of using them. In some embodiments, the HDAC modulators possess specific stereo chemistry. In other embodiments, the compounds described herein are used in the treatment or prevention of histone deacetylase mediated disorders.

Claims

1. A compound of Formula I:

3. The compound of claim 1, wherein Ar is an C₅-C₁₅ aryl or C₅-C₁₅ heteroaryl group, wherein said aryl or heteroaryl groups are optionally substituted with 1-3 substituents each independently selected from hydrogen, halogen, hydroxy, amino, carboxy, C₁-C₄ alkyl, C₁-C₄ alkoxy, C₁-C₄ aminoalkyl, C₁-C₄ alkylamino, C₁-C₄ alkylthio, C₁-C₄ haloalkyl, C₁-C₄ perfluoroalkyl, C₁-C₄ perfluoroalkoxy and C₁-C₄ alkoxycarbonyl.

4. The compound of claim 1, wherein g is I and each R¹ is independently halogen, hydroxy, or a substituted or unsubstituted group selected from amino, carboxy, C₁-C₄ alkyl, C₂-C₅ alkenyl, C₂-C₅ alkynyl, C₁-C₄ alkoxy, C₁-C₄ aminoalkyl, C₁-C₄ alkylamino, C₁-C₄ alkylthio, C₁-C₄ perfluoroalkyl, C₁-C₄ perfluoroalkoxy or C₁-C₄ alkoxycarbonyl;

and n is 0, 1 or 2.

6. The compound of claim 1, wherein Y is

7. The compound of claim 1, wherein Y is

9. The compound of claim 1, wherein n is 0.

21. The compound of claim 1, wherein Ar is:

25. The compound of claim 1, wherein Ar is an optionally substituted C₆-C₁₀ aryl or optionally substituted C₅-C₉ heteroaryl group.

26. The compound of claim 1, wherein L¹ and L² are independently —

O—

, —

N(R³)—

, wherein R³ is hydrogen or a water solubilizing group.

28. The compound of claim 1, wherein R¹ is selected from hydrogen, alkyl, alkoxy, halogen, —

CN, hydroxy and a water solubilizing group.

29. The compound of claim 1, wherein Y is selected from

48. A compound of claim 1 according to Formula

49. The compound or a pharmaceutically acceptable salt of claim 48.

80. The compound of claim 1, wherein the compound is an HDAC modulator.

81. The compound of claim 1, wherein the compound is a selective HDAC modulator.

2. (canceled)

5. (canceled)

8. (canceled)

10-20. -20. (canceled)

22-24. -24. (canceled)

27. (canceled)

30-47. -47. (canceled)

50-59. -59. (canceled)

60. A pharmaceutical composition comprising a compound of Formula I:

61. The pharmaceutical composition of claim 60, further comprising at least one pharmaceutically acceptable carrier.

62-71. -71. (canceled)

72. A method for degrading, inhibiting the growth of or killing cancer cells comprising contacting the cells with an amount of a composition effective to degrade, inhibit the growth of or kill cancer cells, the composition comprising a compound of Formula I:

73. The method of claim 72, wherein said cancer cells comprise brain, breast, lung, ovarian, pancreatic, prostate, renal, or colorectal cancer cells.

74. A method of inhibiting tumor size increase, reducing the size of a tumor, reducing tumor proliferation or preventing tumor proliferation in an individual comprising administering to said individual an effective amount of a composition to inhibit tumor size increase, reduce the size of a tumor, reduce tumor proliferation or prevent tumor proliferation, the composition comprising a compound of Formula I:

75. The method of claim 74, for inhibiting tumor size increase or reducing the size of a tumor wherein said tumor occurs in the brain, breast, lung, ovaries, pancreas, prostate, kidney, colon or rectum.

76. The method of claim 74, wherein said compound of Formula I is administered in combination with an additional cancer therapy.

77. The method of claim 76, wherein the additional cancer therapy is selected from surgery, radiation therapy, and administration of at least one chemotherapeutic agent.

78. The method of claim 76, wherein said additional cancer therapy is administration of at least one chemotherapeutic agent.

79. The method of claim 74, wherein the administration of said compound of Formula I occurs after surgery.