89226-50-6

Basic information

• Product Name: Manidipine
• Synonyms: 2-(4-Diphenylmethyl-1-piperazinyl)ethyl methyl-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate;3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-, 2-(4-(diphenylmethyl)-1-piperazinyl)ethyl methyl ester;89226-75-5 (Di-hydrochloride);1-diphenylmethyl-4-(2-hydroxyethyl)piperazine;3-{2-[4-(diphenylMethyl)piperazin-1-yl]ethyl} 5-Methyl 2,6-diMethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate;Manidipine (Manyper);3-(2-(4-Benzhydrylpiperazin-1-yl)ethyl) 5-Methyl 2,6-diMethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate;3-(2-(4-Benzhydrylpiperazin-1-yl)ethyl) 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridi
• CAS NO: 89226-50-6
• Molecular Formula: C₃₅H₃₈N₄O₆
• Molecular Weight: 610.7
• EINECS: 1806241-263-5
• Product Categories: Dihydropyridine;Artedil, Iperten;Inhibitors;Dihydropyridine Class Chemicals;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 89226-50-6.mol

Chemical Properties

• Melting Point: 125-128°C
• Boiling Point: 722 °C at 760 mmHg
• Flash Point: 390.4 °C
• Appearance: /
• Density: 1.232 g/cm³
• Vapor Pressure: 1.07E-20mmHg at 25°C
• Refractive Index: 1.6
• Storage Temp.: -20°C Freezer
• PKA: 6.12±0.10(Predicted)
• CAS DataBase Reference: Manidipine(CAS DataBase Reference)
• NIST Chemistry Reference: Manidipine(89226-50-6)
• EPA Substance Registry System: Manidipine(89226-50-6)

Safety Data

• Hazardous Substances Data: 89226-50-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Manidipine is used as an antihypertensive agent for the treatment of hypertension. It causes systemic vasodilation by inhibiting the voltage-dependent calcium inward currents in smooth muscle cells, leading to a reduction in blood pressure.
Used in Cardiovascular Applications:
Manidipine is used as a calcium channel blocker for the management of cardiovascular diseases. It inhibits the influx of calcium ions into cardiac and vascular smooth muscle cells, resulting in the relaxation of these cells and the improvement of blood flow. This helps in the prevention and treatment of various cardiovascular conditions, such as angina, arrhythmias, and heart failure.
Used in Research and Development:
Manidipine is used as a research tool for studying the role of calcium channels in various physiological and pathological processes. Its ability to selectively block Land T-type calcium channels makes it a valuable compound for investigating the function and regulation of these channels in different cell types and tissues.

InChI:InChI=1/C35H38N4O6/c1-24-30(34(40)44-3)32(28-15-10-16-29(23-28)39(42)43)31(25(2)36-24)35(41)45-22-21-37-17-19-38(20-18-37)33(26-11-6-4-7-12-26)27-13-8-5-9-14-27/h4-16,23,32-33,36H,17-22H2,1-3H3

Upstream product

• 99-61-6 3-nitro-benzaldehyde 
• 89226-49-3 2-(4-diphenylmethyl-1-piperazinyl)ethyl acetoacetate 
• 14205-39-1 methyl 3-aminocrotonate 
• 90120-00-6 2-(4-diphenylmethyl-1-piperazinyl)ethyl 2-(3-nitrobenzylidene)acetoacetate 
• 10527-64-7 1-diphenylmethyl-4-(2-hydroxyethyl)piperazine 
• 39562-17-9 methyl 2-(3-nitrophenylmethylene)acetoacetate 
• 89226-75-5 Manidipine dihydrochloride 
• 74936-72-4 5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid 
• 841-77-0 diphenylmethylpiperazine 

Downstream Products

• 89226-75-5 Manidipine dihydrochloride 
• 126451-47-6 (S)-Manidipine 
• 120092-68-4 (R)-Manidipine 

Relevant articles and documents

Preparation method of calcium ion channel antagonist manidipine

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.

Preparation method of (S)-manidipine

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.

Polymorphic Forms of Manidipine

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.

POLYMORPHIC FORMS OF MANIDIPINE

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.

THERAPY FOR COMPLICATIONS OF DIABETES

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.

ANTIHYPERTENSIVE THERAPY

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.

Method for treating resistant hypertension

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.

1,4-dihydropyridine enantiomers

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

Substituted heterocyclylalkyl esters of 1,4-dihydropyridine-3,5-dicarboxylic acids

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.