Compounds and methods for the inhibition of the expression of VCAM-1

• US 20020169215A1
• Filed: 04/02/2002
• Published: 11/14/2002
• Est. Priority Date: 05/14/1997
• Status: Active Grant

• Current Assignee: Salutria Pharmaceuticals, LLC
• Original Assignee: Charles Q. Meng
• Inventors: Meng, Charles Q.
• Granted Patent: US 6,602,914 B2
• Time in Patent Office: Days
• US Class Current: 514/712
• CPC Class Codes: A61K 31/222 with compounds having aromatic groups, e.g. dipivefrine, ibopamine
• CPC Class Codes: A61K 31/225 Polycarboxylic acids
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• 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 9/02 Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
• 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 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07C 323/20 with singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
• CPC Class Codes: C07C 323/21 : with the sulfur atom of the thio group bound to a carbon atom of a six-membered aromatic ring being part of a condensed ring system
• CPC Class Codes: C07C 323/25 : the carbon skeleton being acyclic and saturated
• CPC Class Codes: C07C 323/56 : the carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07C 323/66 : containing sulfur atoms of sulfo, esterified sulfo or halosulfonyl groups, bound to the carbon skeleton
• CPC Class Codes: C07C 323/67 : containing sulfur atoms of sulfonamide groups, bound to the carbon skeleton

Abstract

This invention is in the area of methods and compositions for the inhibition of the expression of VCAM-1 and, in particular, for the treatment of diseases mediated by VCAM-1, including cardiovascular and inflammatory diseases.

Claims

1. A compound of the formula

2. A compound of the formula

3. A pharmaceutical composition comprising a compound of the formula

4. The pharmaceutical composition of claim 3, wherein the pharmaceutically acceptable carrier is suitable for oral administration.

5. The pharmaceutical composition of claim 3, wherein the pharmaceutically acceptable carrier is suitable for topical administration.

6. The pharmaceutical composition of claim 3, wherein the pharmaceutically acceptable carrier is suitable for intravenous administration.

7. The pharmaceutical composition of claim 3, wherein the pharmaceutically acceptable carrier is suitable for subcutaneous administration.

8. The pharmaceutical composition of claim 3, wherein the pharmaceutically acceptable carrier is suitable for intraperitoneal administration.

9. The pharmaceutical composition of claim 3, wherein the pharmaceutically acceptable carrier is suitable for intramuscular administration.

10. The pharmaceutical composition of claim 3, wherein the pharmaceutically acceptable carrier is suitable for submucosal administration.

11. The pharmaceutical composition of claim 3, wherein the pharmaceutically acceptable carrier is suitable for inhalation administration.

12. The pharmaceutical composition of claim 3, wherein the pharmaceutically acceptable carrier is suitable for transdermal administration.

14. The method of claim 13, wherein the inflammatory disorder is arthritis.

15. The method of claim 13, wherein the inflammatory disorder is rheumatoid arthritis.

16. The method of claim 13, wherein the inflammatory disorder is osteoarthritis.

17. The method of claim 13, wherein the inflammatory disorder is asthma.

18. The method of claim 13, wherein the inflammatory disorder is dermatitis.

19. The method of claim 13, wherein the inflammatory disorder is multiple sclerosis.

20. The method of claim 13, wherein the inflammatory disorder is psoriasis.

13. A method for the treatment of an inflammatory disorder, comprising administering to a host in need thereof an effective treatment amount of a compound of the formula

21. A method for the treatment of a disorder mediated by VCAM-1, comprising administering to a host in need thereof an effective treatment amount of a compound of the formula

22. A method for the treatment of a cardiovascular disorder, comprising administering to a host in need thereof an effective treatment amount of a compound of the formula

23. The method of claim 22, wherein the cardiovascular disorder is selected from the group consisting of atherosclerosis, post-angioplasty restenosis, coronary artery disease, angina and small artery disease.

25. The method of claim 24, wherein the redox-sensitive gene expresses cytokines.

24. A method for suppressing the expression of a redox-sensitive gene or activating a gene that is suppressed through a redox-sensitive pathway, comprising administering to a host in need thereof an effective treatment amount of a compound of the formula

26. A method of treating an immune response, comprising administering to a host in need thereof an effective treatment amount of a compound of the formula