3-Substituted indoles and derivatives thereof as therapeutic agents

• US 20050004195A1
• Filed: 06/03/2004
• Published: 01/06/2005
• Est. Priority Date: 06/05/2003
• Status: Active Grant

• Current Assignee: Charles John Stankovic, Kimberly Suzanne Para, Melean Visnick
• Original Assignee: Charles John Stankovic, Kimberly Suzanne Para, Melean Visnick
• Inventors: Visnick, Melean, Para, Kimberly Suzanne, Stankovic, Charles John
• Granted Patent: US 7,074,814 B2
• Time in Patent Office: Days
• US Class Current: 514/381
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links

Abstract

The present invention provides indoles of Formula I:
wherein R¹ and R² have any of the values defined therefor in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cardiovascular diseases, and cancers. Also provided are pharmaceutical compositions comprising one or more compounds of Formula I.

Claims

1. A compound of Formula I:

2. The compound of claim 1, wherein wherein R¹ is an unsubstituted phenyl.

3. The compound of claim 1, wherein wherein R¹ is a phenyl substituted with 1, 2, or 3 substituents independently selected from the group consisting of:

C₁-C₄ alkyl, methyl, C₁-C₄ alkyl-O, methoxy, halo, Cl, Br, and I.

4. The compound of claim 1, wherein said compound is selected from the group consisting of:

5,6-Dimethoxy-3-o-tolylsulfanyl-1H-indole-2-carboxylic acid (2H-tetrazol-5-yl)-amide;

3-(3,4-Dichloro-phenylsulfanyl)-5,6-dimethoxy-1H-indole-2-carboxylic acid (2H-tetrazol-5-yl)-amide;

5,6-Dimethoxy-1-methyl-3-phenylsulfanyl-1H-indole-2-carboxylic acid (2H-tetrazol-5-yl)-amide;

5,6-Dimethoxy-3-phenylsulfanyl-1H-indole-2-carboxylic acid (2H-tetrazol-5-yl)-amide;

5,6-Dimethoxy-3-(3-methoxy-phenylsulfanyl)-1H-indole-2-carboxylic acid (2H-tetrazol-5-yl)-amide;

1-Ethyl-5,6-dimethoxy-3-phenyl-1H-indole-2-carboxylic acid (1H-tetrazol-5-yl)-amide; and

5,6-Dimethoxy-3-phenyl-1-propyl-1H-indole-2-carboxylic acid (1H-tetrazol-5-yl)-amide.

5. A method of treating a subject comprising:

administering, to a subject suffering from a disease selected from the group consisting of;

rheumatoid arthritis, psoriasis, psortiatic arthritis, osteoarthritis, inflammatory diseases, and autoimmune diseases, a pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

6. The method of claim 5, wherein said disease is rheumatoid arthritis.

7. A method of treating a subject comprising:

administering, to a subject suffering from a disease selected from the group consisting of;

cardiovascular diseases, atherosclerosis, hypertension, deep venous thrombosis, stroke, myocardial infarction, unstable angina, thromboembolism, pulmonary embolism, thrombolytic diseases, acute arterial ischemia, peripheral thrombotic occlusions, and coronary artery disease, a pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

8. A method of treating a subject comprising:

administering, to a subject suffering from a disease selected from the group consisting of;

cancer, breast cancer, gliobastoma, endometrial carcinoma, heptocellular carcinoma, colon cancer, lung cancer, melanoma, renal cell carcinoma, thyroid carcinoma, small cell lung cancer, squamous cell lung carcinoma, glioma, breast cancer, prostate cancer, ovarian cancer, cervical cancer, leukemia, cell lymphoma, and lymphoproliferative disorders, a pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

9. A method of treating a subject comprising:

administering, to a subject suffering from a type II diabetes, a pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

10. A method of treating a subject comprising:

administering, to a subject suffering from a disease selected from the group consisting of;

respiratory diseases, bronchitis, asthma, and chronic obstructive pulmonary disease, a pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

12. A pharmaceutical composition comprising:

a therapeutically effective amount of a compound of any one of claims 2-4 and a pharmaceutically acceptable carrier.

11. A pharmaceutical composition comprising:

a therapeutically effective amount of a compound of Formula I;

or a pharmaceutically acceptable salt thereof;

wherein R² is H or a C₁-C₃ alkyl; and

wherein R¹ is an unsubstituted phenyl or a phenyl substituted with 1, 2, or 3 substituents independently selected from the group consisting of;

C₁-C₄ alkyl, methyl, C₁-C₄ alkyl-O, methoxy, halo, Cl, Br, and I, and a pharmaceutically acceptable carrier.