Compositions containing C-substituted diindolylmethane compounds

• US 20040235929A1
• Filed: 06/21/2004
• Published: 11/25/2004
• Est. Priority Date: 10/06/2000
• Status: Active Grant

• Current Assignee: Texas A&M University System
• Original Assignee: Texas A&M University System
• Inventors: Safe, Stephen H.
• Granted Patent: US 7,232,843 B2
• Time in Patent Office: Days
• US Class Current: 514/414
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: C07D 209/08 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring

Abstract

Disclosed are methods and compositions for the treatment of a wide array of cancers and tumors. In illustrative embodiments, diindolylmethanes, C-substituted diindolylmethanes, and analogs thereof have been described, which when administered either alone, or in combination with other anti-cancer or anti-tumorigenic compounds, provide new therapies for the treatment of cancer.

Claims

1-70. -70. (canceled)

71. A chemical compound of the formula:

72. A chemical compound of the formula:

73. The chemical compound of claim 72, wherein the halogen is chlorine, bromine, or fluorine.

74. The chemical compound of claim 72, wherein:

R₁, R₂, R₄, R₆, R₇, R₁′

, R₂′

, R₄′

, R₆′

, and R₇′

are each hydrogen; and

R₅ and R₅′

are each individually a halogen.

75. The chemical compound of claim 72, wherein:

R₁, R₂, R₄, R₆, R₇, R₁′

, R₂′

, R₄′

, R₆′

, and R₇′

are each hydrogen; and

R₅ and R₅′

are each individually a linear alkyl group.

76. The chemical compound of claim 72, wherein:

R₁, R₂, R₄, R₆, R₇, R₁′

, R₂′

, R₄′

, R₆′

, and R₇′

are each hydrogen; and

R₅ and R₅′

are each individually an alkoxy group.

77. The chemical compound of claim 72, wherein:

R₂, R₄, R₅, R₆, R₇, R₂′

, R₄′

, R₅′

, R₆′

, and R₇′

are each hydrogen; and

R₁ and R₁′

are each individually an alkyl group.

78. The chemical compound of claim 72, wherein:

R₂, R₄, R₅, R₆, R₇, R₂′

, R₄′

, R₅′

, R₆′

, and R₇′

are each hydrogen; and

R₁ and R₁′

are each individually an alkoxy group.

79. The chemical compound of claim 72, wherein:

R₁, R₄, R₅, R₆, R₇, R₁′

, R₄′

, R₅′

, R₆′

, and R₇′

are each hydrogen; and

R₂ and R₂′

are each individually an alkyl group.

80. The chemical compound of claim 72, wherein:

R₁, R₂, R₄, R₆, R₇, R₁′

, R₂′

, R₄′

, R₆′

, and R₇′

are hydrogen; and

R₅ and R₅′

are each a nitro group.

81. The chemical compound of claim 72, wherein at least one of R₈ and R₈′

is a linear alkyl group.

82. The chemical compound of claim 72, wherein at least one of R₈ and R₈′

is a branched alkyl group.

83. The chemical compound of claim 72, wherein at least one of R₈ and R₈′

is a cycloalkyl group.

84. The chemical compound of claim 72, wherein at least one of R₈ and R₈′

is an aryl group.

85. The chemical compound of claim 72, wherein:

R₁, R₂, R₁′

, and R₂′

are each individually hydrogen or methyl;

R_{4, R5}, R₆, R₇, R₄′

, R₅′

, R₆′

, and R₇′

are each hydrogen; and

R₈ and R₈′

are each individually hydrogen, methyl, or an aryl group selected from the group consisting of C₆H₅, C₆H₄OH, C₆H₄CH₃, C₆H₄CF₃, C₁₀H₇, C₆H₄H₅, and C₆H₄OCH₃.

86. The chemical compound of claim 72, wherein:

R₁, R₂, R₄, R₅, R₆, R₇, R₁′

, R₂′

, R₄′

, R₅′

, R₆′ and

R₈′

are each hydrogen; and

R₈ is the aryl group p-C₆H₄C₆H₅.

87. The chemical compound of claim 72, wherein:

R₁, R₂, R₄, R₅, R₆, R₇, R₁′

, R₂′

, R₄′

, R₅′

, R₆′ and

R₈′

are each hydrogen; and

R₈ is the aryl group p-C₆H₄CF₃.

88. A composition comprising a chemical compound of the formula:

89. A composition comprising a chemical compound of the formula:

90. The composition of claim 89, wherein the halogen is chlorine, bromine, or fluorine.

91. The composition of claim 89, wherein:

R₁, R₂, R₄, R₆, R₇, R₁′

, R₂′

, R₄′

, R₆′

, and R₇′

are each hydrogen; and

R₅ and R₅′

are each individually a halogen.

92. The composition of claim 89, wherein:

R₁, R₂, R₄, R₆, R₇, R₁′

, R₂′

, R₄′

, R₆′

, and R₇′

are each hydrogen; and

R₅ and R₅′

are each individually a linear alkyl group.

93. The composition of claim 89, wherein:

R₁, R₂, R₄, R₆, R₇, R₁′

, R₂′

, R₄′

, R₆′

, and R₇′

are each hydrogen; and

R₅ and R₅′

are each individually an alkoxy group.

94. The composition of claim 89, wherein:

R₂, R₄, R₅, R₆, R₇, R₂′

, R₄′

, R₅′

, R₆′

, and R₇′

are each hydrogen; and

R₁ and R₁′

are each individually an alkyl group.

95. The composition of claim 89, wherein:

R₂, R₄, R₅, R₆, R₇, R₂′

, R₄′

, R₅′

, R₆′

, and R₇′

are each hydrogen; and

R₁ and R₁′

are each individually an alkoxy group.

96. The composition of claim 89, wherein:

R₁, R₄, R₅, R₆, R₇, R₁′

, R₄′

, R₅′

, R₆′

, and R₇′

are each hydrogen; and

R₂ and R₂′

are each individually an alkyl group.

97. The composition of claim 89, wherein:

R₁, R₂, R₄, R₆, R₇, R₁′

, R₂′

, R₄′

, R₆′

, and R₇′

are hydrogen; and

R₅ and R₅′

are each a nitro group.

98. The composition of claim 89, wherein at least one of R₈ and R₈′

is a linear alkyl group.

99. The composition of claim 89, wherein at least one of R₈ and R₈′

is a branched alkyl group.

100. The composition of claim 89, wherein at least one of R₈ and R₈′

is a cycloalkyl group.

101. The composition of claim 89, wherein at least one of R₈ and R₈′

is an aryl group.

102. The composition of claim 89, wherein:

R₁, R₂, R₁′

, and R₂′

are each individually hydrogen or methyl;

R₄, R₅, R₆, R₇, R₄′

, R₅′

, R₆′

, and R₇′

are each hydrogen; and

R₈ and R₈′

are each individually hydrogen, methyl, or an aryl group selected from the group consisting of C₆H₅, C₆H₄OH, C₆H₄CH₃, C₆H₄CF₃, C₁₀H₇, C₆H₄C₆H₅, and C₆H₄OCH₃.

103. The composition of claim 89, wherein:

R₁, R₂, R₄, R₅, R₆, R₇, R′

, R₂′

, R₄′

, R₅′

, R₆′

,R₇ ′

, and R₈′

are each hydrogen; and

R₈ is the aryl group p-C₆H₄C₆H₅.

104. The composition of claim 89, wherein:

R₁, R₂, , R₅, R₆, R₇, R₁′

, R₂′

, R₄′

, R₅′

, R₆′

,R₇′

, and R₈′

are each hydrogen;

R₈ is the aryl group p-C₆H₄CF₃.