The present invention relates to the 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) ##STR1## 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.
This is a continuation of application Ser. No. 10/073,330, filed Feb. 13, 2002, which was issued as U.S. Pat. No. 6,617,359 B2 on Sep. 9, 2003, and claims benefit under 35 U.S.C. .sctn. 119 of European Patent Application No. 01102852.9, filed Feb. 13, 2001, all of which are incorporated by reference herein.
The present invention provides novel aryl hydroxyethyl amides and related derivatives having the general Formula I ##STR00001## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7 and A are as defined in the specification, or a nontoxic pharmaceutically acceptable salt, solvate or hydrate thereof which are openers or activators of KCNQ potassium channels. The present invention also provides pharmaceutical compositions comprising said aryl hydroxyethyl amides and to the method of treatment of disorders sensitive to KCNQ potassium channel opening activity such as migraine or a migraine attack, bipolar disorders, epilepsy, acute and chronic pain and anxiety.
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) ##STR00001## 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.
The present invention relates to acylamino-substituted heteroaromatic compounds of formula I, ##STR00001## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 and X are as defined herein, to pharmaceutical compositions comprising such compounds, to methods for the stimulation of the expression of endothelial NO synthase, and methods of treatment comprising administering such compounds.
The present invention relates to acylated indanyl amines according to the general formula (I) ##STR00001## wherein R.sup.1 R.sup.4 have the meanings given in the description, A is CH.sub.2, CHOH or CH--(C.sub.1 C.sub.3-alkyl), B is CH.sub.2 or CH--(C.sub.1 C.sub.3-alkyl), and R.sup.5 is an aryl or heteroaryl group, possibly substituted by the substituents listed in the description. These compounds are useful in the upregulation of endothelial nitric oxide synthase (eNOS), and may therefore be useful for the manufacture of medicaments for the treatment of cardiovascular diseases, stable or 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, essential hypertension, pulmonary hypertension, secondary hypertension, renovascular hypertension, chronic glomerulonephritis, erectile dysfunction, ventricular arrhythmia, diabetes or diabetes complications, nephropathy or retinopathy, angiogenesis, asthma bronchiale, chronic renal failure, cirrhosis of the liver, osteoporosis, restricted memory performance, a restricted ability to learn, or for the lowering of cardiovascular risk of postmenopausal women or after intake of contraceptives.
The present invention relates to acylated arylcycloalkylamines, to pharmaceutical compositions comprising such compounds, to methods for the stimulation of the expression of endothelial NO synthase, and methods of treatment comprising administering such compounds.
