4-fluoro-N-indan-2-yl benzamide and its use as a pharmaceutical
View Patent ↗A method of stimulating the expression of endothelial NO-synthase in a mammal, which method comprises administering a physiologically active amount of 4-fluoro-N-indan- 2-yl benzamide according to the formula (I) to the said mammal. Compound (I) can be used for the therapy and prophylaxis of cardiovascular diseases like stable and unstable angina pectoris, Prinzmetal angina (spasm), acute coronary syndrome, heart failure, myocardial infarction, stroke, thrombosis, peripheral artery occlusive disease PAOD, atherosclerosis, restenosis, endothelial damage after PTCA, essential hypertension, pulmonary hypertension, secondary hypertension, renovascular chronic glomerulonephritis, erectile dysfunction, ventricular arrhythmia, and the lowering of cardiovascular risk of postmenopausal women or after intake of contraceptives, the therapy and prophylaxis of diabetes and diabetes complications (nephropathy, retinopathy), angiogenesis, asthma bronchiale, chronic renal failure, cirrhosis of the liver, restricted memory performance or a restricted ability to learn.
1. A pharmaceutical preparation, comprising
an effective amount of 4-fluoro-N-indan-2-yl benzamide according to the formula (I)
at least one other pharmaceutical active compound chosen from statins, ACE-inhibitors, PDE V-inhibitors, Ca-antagonists, beta-blockers, arginine, and tetrahydrobiopterin; and
a pharmaceutically acceptable carrier, wherein the pharmaceutical preparation is for the treatment of a mammal suffering from a disease chosen from stable and unstable angina pectoris, coronary heart disease, Prinzmetal angina, acute coronary syndrome, heart failure, myocardial infarction, stroke, thrombosis, peripheral artery occlusive disease, endothelial dysfunction, atherosclerosis, restenosis, endothelial damage after PTCA, hypertension, chronic glomerulonephritis, erectile dysfunction, ventricular arrhythmia, diabetes and diabetes complications, nephropathy and retinopathy, angiogenesis, asthma bronchiale, chronic renal failure, cirrhosis of the liver, osteoporosis, restricted memory performance, and a restricted ability to learn.
2. The pharmaceutical preparation according to claim 1 , wherein the pharmaceutical preparation is for the treatment of a mammal suffering from a disease chosen from stable and unstable angina pectoris, coronary heart disease, acute coronary syndrome, heart failure, myocardial infarction, thrombosis, peripheral artery occlusive disease, endothelial dysfunction, atherosclerosis, restenosis, endothelial damage after PTCA, hypertension, and diabetes complications.
3. The pharmaceutical preparation according to claim 2 , wherein the pharmaceutical preparation is for the treatment of a mammal suffering from coronary heart disease.
4. The pharmaceutical preparation according to claim 2 , wherein the pharmaceutical preparation is for the treatment of a mammal suffering from heart failure.
5. The pharmaceutical preparation according to claim 2 , wherein the pharmaceutical preparation is for the treatment of a mammal suffering from atherosclerosis.
6. The pharmaceutical preparation according to claim 1 , wherein the pharmaceutical preparation is in the form of a pill, tablet, granule, hard or soft gelatin capsule, aqueous, alcoholic or oily solution, syrup, emulsion or suspension, suppository, solution for injection or infusion, ointment, tincture, spray, transdermal therapeutic system, nasal spray, aerosol mixture, microcapsule, implant or rod.
7. A pharmaceutical preparation, comprising
an effective amount of 4-fluoro-N-indan-2-yl benzamide according to the formula (I)
at least one other pharmaceutical active compound chosen from statins, ACE-inhibitors, PDE V-inhibitors, Ca-antagonists, beta-blockers, arginine, and tetrahydrobiopterin, and
a pharmaceutically acceptable carrier, wherein the pharmaceutical preparation is for the treatment of a mammal suffering from a cardiovascular disease.
8. The pharmaceutical preparation according to claim 7 , wherein the pharmaceutical preparation is in the form of a pill, tablet, granule, hard or soft gelatin capsule, aqueous, alcoholic or oily solution, syrup, emulsion or suspension, suppository, solution for injection or infusion, ointment, tincture, spray, transdermal therapeutic system, nasal spray, aerosol mixture, microcapsule, implant or rod.
9. A pharmaceutical preparation, comprising
4-fluoro-N-indan-2-yl benzamide according to the formula (I)
at least one other pharmaceutical active compound chosen from statins, ACE-inhibitors, AT1-antagonists, argininase-inhibitors, PDE V-inhibitors, Ca-antagonists, alpha-blockers, beta-blockers, metimazol, arginine, tetrahydrobiopterin, and vitamins, and
a pharmaceutically acceptable carrier.
10. The pharmaceutical preparation according to claim 9 , wherein the at least one other pharmaceutically active compound is chosen from statins, ACE-inhibitors, PDE V-inhibitors, Ca-antagonists, beta-blockers, arginine, and tetrahydrobiopterin.
11. The pharmaceutical preparation according to claim 9 , wherein the pharmaceutical preparation is in the form of a pill, tablet, granule, hard or soft gelatin capsule, aqueous, alcoholic or oily solution, syrup, emulsion or suspension, suppository, solution for injection or infusion, ointment, tincture, spray, transdermal therapeutic system, nasal spray, aerosol mixture, microcapsule, implant or rod.
12. The pharmaceutical preparation according to claim 1 , wherein the hypertension comprises essential hypertension, pulmonary hypertension, secondary hypertension, and renovascular hypertension.
13. The pharmaceutical preparation according to claim 6 , wherein the tablet is chosen from a lacquered tablet and a sugar-coated tablet.
14. The pharmaceutical preparation according to claim 8 , wherein the tablet is chosen from a lacquered tablet and a sugar-coated tablet.
15. The pharmaceutical preparation according to claim 11 , wherein the tablet is chosen from a lacquered tablet and a sugar-coated tablet.
16. The pharmaceutical preparation according to claim 9 , wherein the vitamins are niacin.
17. A method for treating coronary heart disease in a mammal suffering therefrom, which method comprises administering a physiologically active amount of 4-fluoro-N-indan-2-yl benzamide according to the formula (I)
to the mammal.
18. The method according to claim 17 , wherein the mammal is a human.
19. A method for treating heart failure in a mammal suffering therefrom, which method comprises administering a physiologically active amount of 4-fluoro-N-indan-2-yl benzamide according to the formula (I)
to the mammal.
20. The method according to claim 19 , wherein the mammal is a human.
21. A method for treating atherosclerosis in a mammal suffering therefrom, which method comprises administering a physiologically active amount of 4-fluoro-N-indan-2-yl benzamide according to the formula (I)
to the mammal.
22. The method according to claim 21 , wherein the mammal is a human.
23. A method of treating coronary heart disease in a mammal suffering therefrom, which method comprises administering a pharmaceutical preparation comprising an effective amount of 4-fluoro-N-indan-2-yl benzamide according to the formula (I)
and a pharmaceutically acceptable carrier, to the mammal.
24. The method according to claim 23 , wherein the mammal is a human.
25. The method according to claim 23 , wherein the pharmaceutical preparation is in the form of a pill, tablet, granule, hard or soft gelatin capsule, aqueous, alcoholic or oily solution, syrup, emulsion or suspension, suppository, solution for injection or infusion, ointment, tincture, spray, transdermal therapeutic system, nasal spray, aerosol mixture, microcapsule, implant or rod.
26. The method according to claim 25 , wherein the tablet is chosen from a lacquered tablet and a sugar-coated tablet.
27. A method of treating heart failure in a mammal suffering therefrom, which method comprises administering a pharmaceutical preparation comprising an effective amount of 4-fluoro-N-indan-2-yl benzamide according to the formula (I)
and a pharmaceutically acceptable carrier, to the mammal.
28. The method according to claim 27 , wherein the mammal is a human.
29. The method according to claim 27 , wherein the pharmaceutical preparation is in the form of a pill, tablet, granule, hard or soft gelatin capsule, aqueous, alcoholic or oily solution, syrup, emulsion or suspension, suppository, solution for injection or infusion, ointment, tincture, spray, transdermal therapeutic system, nasal spray, aerosol mixture, microcapsule, implant or rod.
30. The method according to claim 29 , wherein the tablet is chosen from a lacquered tablet and a sugar-coated tablet.
31. A method of treating atherosclerosis in a mammal suffering therefrom, which method comprises administering a pharmaceutical preparation comprising an effective amount of 4-fluoro-N-indan-2-yl benzamide according to the formula (I)
and a pharmaceutically acceptable carrier, to the mammal.
32. The method according to claim 31 , wherein the mammal is a human.
33. The method according to claim 31 , wherein the pharmaceutical preparation is in the form of a pill, tablet, granule, hard or soft gelatin capsule, aqueous, alcoholic or oily solution, syrup, emulsion or suspension, suppository, solution for injection or infusion, ointment, tincture, spray, transdermal therapeutic system, nasal spray, aerosol mixture, microcapsule, implant or rod.
34. The method according to claim 33 , wherein the tablet is chosen from a lacquered tablet and a sugar-coated tablet.
35. A method of treating a disease chosen from endothelial dysfunction, hypertension, coronary heart disease, stable angina pectoris, diabetes complications and atherosclerosis in a mammal suffering therefrom, which method comprises administering a pharmaceutical preparation comprising an effective amount of 4-fluoro-N-indan-2-yl benzamide according to the formula (I)
and a pharmaceutically acceptable carrier, to the mammal.
36. The method according to claim 35 , wherein the mammal is a human.
37. The method according to claim 35 , wherein the pharmaceutical preparation is in the form of a pill, tablet, granule, hard or soft gelatin capsule, aqueous, alcoholic or oily solution, syrup, emulsion or suspension, suppository, solution for injection or infusion, ointment, tincture, spray, transdermal therapeutic system, nasal spray, aerosol mixture, microcapsule, implant or rod.
38. The method according to claim 37 , wherein the tablet is chosen from a lacquered tablet and a sugar-coated tablet.
39. A method of treating a disease chosen from coronary heart disease, heart failure, atherosclerosis, endothelial dysfunction, hypertension, stable angina pectoris, unstable angina pectoris, acute coronary syndrome, myocardial infarction, thrombosis, peripheral artery occlusive disease, restenosis, diabetes complications and endothelial damage after PTCA, in a mammal suffering therefrom, which method comprises administering to the mammal a pharmaceutical preparation comprising
an effective amount of 4-fluoro-N-indan-2-yl benzamide according to the formula (I)
at least one other pharmaceutically active compound chosen from statins, ACE-inhibitors, AT1-antagonists, argininase-inhibitors, PDE V-inhibitors, Ca-antagonists, alpha-blockers, beta-blockers, metimazol, arginine, tetrahydrobiopterin, and vitamins and,
a pharmaceutically acceptable carrier.
40. The method according to claim 39 , wherein the disease is coronary heart disease, and the at least one other pharmaceutically active compound is chosen from statins, ACE-inhibitors, PDE V-inhibitors, Ca-antagonists, beta-blockers, arginine, and tetrahydrobiopterin.
41. The method according to claim 39 , wherein the disease is heart failure and the at least one other pharmaceutically active compound is chosen from statins, ACE-inhibitors, PDE V-inhibitors, Ca-antagonists, beta-blockers, arginine, and tetrahydrobiopterin.
42. The method according to claim 39 , wherein the disease is atherosclerosis and the at least one other pharmaceutically active compound is chosen from statins, ACE-inhibitors, PDE V-inhibitors, Ca-antagonists, beta-blockers, arginine, and tetrahydrobiopterin.
43. The method according to claim 39 , wherein the disease is chosen from endothelial dysfunction, hypertension, coronary heart disease, stable angina pectoris, diabetes complications and atherosclerosis and the at least one other pharmaceutically active compound is chosen from statins, ACE-inhibitors, PDE V-inhibitors, Ca-antagonists, beta-blockers, arginine, and tetrahydrobiopterin.
44. The method according to claim 39 , wherein the disease is chosen from unstable angina pectoris, acute coronary syndrome, myocardial infarction, thrombosis, peripheral artery occlusive disease, restenosis, and endothelial damage after PTCA and the at least one other pharmaceutically active compound is chosen from statins, ACE-inhibitors, PDE V-inhibitors, Ca-antagonists, beta-blockers, arginine, and tetrahydrobiopterin.
45. The method according to claim 39 , wherein the mammal is a human.
46. A method of treating a cardiovascular disease in a mammal suffering therefrom, which method comprises administering a pharmaceutical preparation comprising
an effective amount of 4-fluoro-N-indan-2-yl benzamide according to the formula (I)
at least one other pharmaceutical active compound chosen from statins, ACE-inhibitors, AT1-antagonists, argininase-inhibitors, PDE V-inhibitors, Ca-antagonists, alpha-blockers, beta-blockers, metimazol, arginine, tetrahydrobiopterin, and vitamins, and
a pharmaceutically acceptable carrier to the mammal.
47. The method according to claim 46 , wherein the at least one other pharmaceutically active compound is chosen from statins, ACE-inhibitors, PDE V-inhibitors, Ca-antagonists, beta-blockers, arginine, and tetrahydrobiopterin.
48. The method according to claim 39 , wherein the hypertension comprises essential hypertension, pulmonary hypertension, secondary hypertension, and renovascular hypertension.
49. The method according to claim 39 , wherein the vitamins are niacin.
50. The method according to claim 46 , wherein the vitamins are niacin.