Patent EA-002988-B1 (EA)
Title: (R)-N-[[4-[[(2-METHYLPHENYLAMINO)CARBONYL]AMINO]PHENYL]ACETYL]-L-PROPYL-3-METHYL)-BETA-ALANINE AND ITS USE AS A CELL ADHESION INHIBITOR MEDIATED BY INTEGRIN alpha4beta1 INHIBITORS
Inventor: LEE WEN-CHENG
IPC: A61K31/40
Filed: 1999-05-28
Abstract: 1. (R)-N-[[4-[[(2-methylphenylamino)carbonyl]amino]phenyl] acetyl]-L-prolyl-3-methyl-β alanine inhibiting a cell adhesion   or a pharmaceutically acceptable derivative, prodrug, or salt thereof. 2. The compound according to claim 1, wherein the prodrug is an ester derivative. 3. The compound according to claim 2, which is the ester derivative prepared by reacting (R)-N-[ [4-[ [ (2-methylphenylamino)carbonyl]amino]phenyl]acetyl]-L-prolyl-3-methyl-β-alanine with a straight or branched C1-10 alcohol. 4. The compound according to claim 2, which is the ester derivative prepared by reacting (R)-N-[[4- [ [ (2-methylphenylamino)carbonyl]amino]phenyl]acetyl]-L-prolyl-3-methyl-β-alanine with a straight or blanched C1-4 alcohol. 5. The compound according to claim 2, which is the ester derivative of the following formula:   wherein R is a straight or branched C1-10 alkyl. 6. The compound according to claim 5, wherein R is a straight or branched C1-4 alkyl. 7. The compound according to claim 1, wherein the compound is   8. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutical acceptable carrier. 9. A pharmaceutical composition according to claim 8, wherein the adhesion inhibitory compound is in a salt form. 10. The pharmaceutical composition according to claim 8, additionally comprising a second agent selected from the group consisting of corticosteroids, bronchodilators, antiasthmatics, antiinflammatories, antirheumatics, immunosuppressants, antimetabolites, immunomodulators, antipsoriatics and antidiabetics. 11. A pharmaceutical composition of claim 8, further comprising one or more cell adhesion inhibitor compounds. 12. The pharmaceutical composition of claim 11, wherein said one or more cell adhesion inhibitor compounds are integrin α4β1 inhibitors. 13. The pharmaceutical composition according to claim 8, wherein the compound is an ester prodrug. 14. A method for preventing, inhibiting or suppressing cell adhesion in a mammal comprising the step of administering to said mammal an effective amount of the pharmaceutical composition of claim 8 or 9. 15. The method of claim 14 wherein said method is used for preventing, inhibiting, or suppressing inflammation. 16. A method for treating asthma, allergic rhinitis, multiple sclerosis, atherosclerosis, inflammatory bowel disease or multiple myeloma in a mammal comprising administering to said mammal a therapeutically effective amount of a compound of claim 1 or pharmaceutical composition of claim 8 or 9. 17. A method for treating multiple sclerosis in a mammal comprising administering to said mammal a therapeutically effective amount of a compound of claim 1 or pharmaceutical composition of claim 8 or 9. 18. A method for treating inflammatory bowel disorders in a mammal comprising administering to said mammal a therapeutically effective amount of a compound of claim 1 or pharmaceutical composition of claim 8 or 9. 19. A method for treating preventing or ameliorating the symptoms of asthma comprising administration to a patient suffering from asthma a therapeutically effective amount of a compound of claim 1. 20. The use of the compound of any of claims 1-7 for the manufacture of medicament for treating a disorder mediated by cell adhesion. 21. The use according to claim 19, wherein the disorder is selected from the group consisting of asthma, multiple sclerosis, allergic rhinitis, allergic conjunctivitis, inflammatory lung diseases, rheumatoid arthritis, multiple myeloma, septic arthritis, type 1 diabetes, organ transplant rejection, and an inflammatory bowel disorder. 22. The use according to claim 21, wherein the disorder is multiple sclerosis. 23. The use according to claim 21, wherein the disorder is an inflammatory bowel disorder.