- Preparation method of calcium ion channel antagonist manidipine
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The invention discloses a preparation method of a calcium ion channel antagonist manidipine. The method comprises the following steps: 1) dissolving methyl beta-aminocrotonate, carring out reaction on the methyl beta-aminocrotonate and 1-diphenylmethyl-4-(2-hydroxyethyl)piperazidine in the presence of a catalyst in a 50-70-DEG C organic solvent to generate diphenylmethylpiperazinylethyl beta-aminocrotonate; and 2) adding the diphenylmethylpiperazinylethyl beta-aminocrotonate and methyl 2-(3-nitrobenzylidene)acetoacetate into a reactor filled with an alcohol solvent, carrying out gradient to 75 DEG C, continuing heating to reflux, refluxing for 3-5 hours, reacting completely to obtain a manidipine crude product, cooling to 0 DEG C, cooling over night, filtering, and recrystallizing to obtain the manidipine pure product, wherein the alcohol solvent is anhydrous ethanol. The method has the advantages of simple preparation process, short reaction period, fewer generated byproducts and simple after-treatment; the yield of the prepared product can reach 90% or above; and the method is suitable for industrial production.
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Paragraph 0018; 0020; 0022
(2017/03/08)
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- Preparation method of (S)-manidipine
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The invention relates to a preparation method of (S)-manidipine. Particularly, racemic manidipine free alkali is taken as a raw material, a resolving agent is used, and (S)-manidipine free alkali with optical activity is obtained with a chemical salting-out method. According to the preparation method, the yield is high, the process is simple to operate, the cost is lower, and (S)-manidipine is suitable for industrial production.
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Paragraph 0064; 0065; 0066
(2016/10/20)
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- Polymorphic Forms of Manidipine
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The invention relates to various new polymorphic forms of manidipine and pharmaceutically acceptable salts thereof. The invention also relates to processes for the preparation of the polymorphic forms of manidipine and pharmaceutically acceptable salts thereof.
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Page/Page column 5-6
(2012/09/22)
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- POLYMORPHIC FORMS OF MANIDIPINE
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The invention relates to various new polymorphic forms of manidipine and pharmaceutically acceptable salts thereof. The invention also relates to processes for the preparation of the polymorphic forms of manidipine and pharmaceutically acceptable salts thereof.
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Page/Page column 18
(2011/04/14)
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- THERAPY FOR COMPLICATIONS OF DIABETES
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A method for enhancing glycemic control and/or insulin sensitivity in a human subject having diabetic nephropathy and/or metabolic syndrome comprises administering to the subject a selective endothelin A (ETA) receptor antagonist in a glycemic control and/or insulin sensitivity enhancing effective amount. A method for treating a complex of comorbidities in an elderly diabetic human subject comprises administering to the subject a selective ETA receptor antagonist in combination or as adjunctive therapy with at least one additional agent that is (i) other than a selective ETA receptor antagonist and (ii) effective in treatment of diabetes and/or at least one of said comorbidities other than hypertension. A therapeutic combination useful in such a method comprises a selective ETA receptor antagonist and at least one antidiabetic, anti-obesity or antidyslipidemic agent other than a selective ETA receptor antagonist.
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- ANTIHYPERTENSIVE THERAPY
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A new use of darusentan is provided in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy with one or more drugs. The composition comprises darusentan in an amount providing a therapeutically effective daily dose; wherein (a) the composition is orally deliverable and/or (b) the daily dose of darusentan is effective to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures. Further provided is a new use of darusentan in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy, wherein the composition is administered adjunctively with at least one diuretic and at least one antihypertensive drug selected from ACE inhibitors, angiotensin II receptor blockers, beta-adrenergic receptor blockers and calcium channel blockers.
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- Method for treating resistant hypertension
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A method is provided for lowering blood pressure in a patient having clinically diagnosed resistant hypertension. The method comprises administering darusentan to the patient adjunctively with a baseline antihypertensive regimen that comprises administration of at least one diuretic and at least two antihypertensive drugs selected from at least two of (a) ACE inhibitors and angiotensin II receptor blockers, (b) beta-adrenergic receptor blockers and (c) calcium channel blockers. The darusentan is orally administered at a dose and frequency effective, in combination with the baseline regimen, to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures.
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- 1,4-dihydropyridine enantiomers
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Enantiomerically-pure dihydropyridines of formula I STR1 are effective vasodilators useful for treating coronary diseases. They have particularly advantageous properties with regard to extent and controllability of blood pressure lowering, a surprisingly
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- Substituted heterocyclylalkyl esters of 1,4-dihydropyridine-3,5-dicarboxylic acids
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Dihydropyridine derivatives and acid addition salts thereof which are of use as prophylactic or/and therapeutic drugs for cardiovascular diseases, said dihydropyridine derivatives having the formula STR1 wherein R1, R2 and R3 are the same or different and each is alkyl, cycloalkyl, cycloalkylalkyl or alkoxyalkyl; R4 and R5 are the same or different and each is hydrogen, halogen, nitro, trifluoromethyl, alkyl, cycloalkyl, alkoxy, cyano, alkoxycarbonyl or alkylthio; R6 is hydrogen, alkyl, cycloalkyl, aralkyl, aryl or a pyridyl; X is oxygen, sulfur, vinylene, azomethine or a group of the formula STR2 A is alkylene; Ar is aryl or a pyridyl; m is an integer of 1 to 3; n is an integer of 0 to 2.
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