Indole-3-carbinol, diindolylmethane and substituted analogs as antiestrogens

• US 5,948,808 A
• Filed: 03/07/1997
• Issued: 09/07/1999
• Est. Priority Date: 03/07/1997
• Status: Expired due to Term

• Current Assignee: Texas A&M University System
• Original Assignee: Texas A&M University System
• Inventors: Safe, Stephen H.
• Primary Examiner(s): Shah, Mukund J.
• Assistant Examiner(s): COLEMAN, BRENDA LIBBY
• Application Number:
  US08/813,365
• Time in Patent Office: 914 Days
• Field of Search: 514/414, 514/415, 514/418, 548/455, 548/483, 548/484, 548/485, 548/486, 548/509
• US Class Current: 514/415
• CPC Class Codes: C07D 209/12 Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 209/14 Radicals substituted by nitrogen atoms, not forming part of a nitro radical

Abstract

Provided in the present invention are compounds and compositions of substituted indole-3-carbinols and diindolylmethane suitable for treating estrogen-dependent tumors. Also provided are methods of treating such cancerous-conditions.

Claims

1. A method of treating estrogen-dependent tumors comprising administering a biologically active amount of a compound of the formula:

##STR13## where R₁, R₂, R₄, R₅, R₆ and R₇, individually and independently, is a hydrogen, or a substituent selected from the group consisting of a halogen, a linear or branched alkyl or alkoxy group of one to ten carbons, and a nitro group, said compound having at least one substituent.

2. The method of claim 1 wherein said linear or branched alkyl or alkoxy group is one to five carbons.

3. The method of claim 1 wherein said halogen is selected from the group consisting of chlorine, bromine and fluorine.

4. The method of claim 1 wherein said compound is selected from the group consisting of 5-methyl-indole-3-carbinol, 5-ethyl-indole-3-carbinol, 5-propyl-indole-3-carbinol, 5-butyl-indole-3-carbinol, 5-pentyl-indole-3-carbinol, 5-methoxy-indole-3-carbinol, 5-ethoxy-indole-3-carbinol, 5-propyloxy-indole-3-carbinol, 5-butyloxy-indole-3-carbinol, 5-amyloxy-indole-3-carbinol, N-methyl-indole-3-carbinol, N-ethyl-indole-3-carbinol, N-propyl-indole-3-carbinol, N-butyl-indole-3-carbinol, N-pentyl-indole-3-carbinol, 2-methyl-indole-3-carbinol, 2-ethyl-indole-3-carbinol, 2-propyl-indole-3-carbinol, 2-butyl-indole-3-carbinol and 2-pentyl-indole-3-carbinol.

5. The method according to claim 1, wherein said estrogen dependent tumor is selected from the group consisting of breast cancer and endometrial cancer.

6. The method of claim 1 wherein the compound further comprises a pharmaceutically acceptable carrier.

7. The method of claim 6 wherein the pharmaceutically acceptable carrier is selected from the group consisting of corn oil, dimethylsulfoxide and gelatin capsule.

8. A method of treating estrogen-dependent tumors comprising administering a biologically active amount of a compound of the formula:

##STR14## where R₁, R₂, R₄, R₅, R₆, R₇, R₁ '"'"', R₂ '"'"', R₄ '"'"', R₅ '"'"', R₆ '"'"' and R₇ '"'"' individually and independently, is a hydrogen, or a substituent selected from the group consisting of a halogen, a linear or branched alkyl or alkoxy group of one to ten carbons, and a nitro group, said compound having at least one substituent.

9. The method of claim 8 wherein said linear or branched alkyl or alkoxy group is one to five carbons.

10. The method of claim 8 wherein said halogen is selected from the group consisting of chlorine, bromine and fluorine.

11. The method of claim 8 wherein said compound is selected from the group consisting of 5,5'"'"'-dichloro-diindolylmethane;

5,5'"'"'-dibromo-diindolylmethane;

5,5'"'"'-difluoro-diindolylmethane;

5,5'"'"'-dimethyldiindolyl-methane;

5,5'"'"'-diethyl-diindolylmethane;

5,5'"'"'-dipropyl-diindolylmethane;

5,5'"'"'-dibutyl-diindolylmethane;

5,5'"'"'-dipentyl-diindolylmethane;

5,5'"'"'-dimethoxy-diindolylmethane;

5,5'"'"'-diethoxy-diindolylmethane;

5,5'"'"'-dipropyloxy-diindolylmethane;

5,5'"'"'-dibutyloxydiindolyl-methane;

5,5'"'"'-diamyloxy-diindolylmethane;

N,N'"'"'-dimethyldiindolyl-methane;

N,N'"'"'-diethyldiindolylmethane;

N,N'"'"'-dipropyl-diindolylmethane;

N,N'"'"'-dibutyl-diindolylmethane;

N,N'"'"'-dipentyl-diindolylmethane;

2,2'"'"'-dimethyl-diindolylmethane;

2,2'"'"'-dimethyldiindolyl-methane;

2,2'"'"'-dipropyldiindolylmethane;

2,2'"'"'-dibutyldiindolylmethane and 2,2'"'"'-dipentyl-diindolylmethane.

12. The method according to claim 8, wherein said estrogen dependent tumor is selected from the group consisting of breast cancer and endometrial cancer.

13. The method of claim 8 wherein the compound further comprises a pharmaceutically acceptable carrier.

14. The method of claim 13 wherein the pharmaceutically acceptable carrier is selected from the group consisting of corn oil, dimethylsulfoxide and gelatin capsule.