86780-90-7

Basic information

• Product Name: ARANIDIPINE
• Synonyms: ARANIDIPINE;2，6-Dimethyl-4-(2-nitrophenyl)-1，4-dihydro-3，5-pyridinedicarboxylic acid methyl 2-oxopropyl ester;MPC-1304;Sapresta;1,4-Dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic acid 3-methyl 5-(2-oxopropyl) ester;Asanidipine;3,5-Pyridinedicarboxylicacid, 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-, 3-methyl 5-(2-oxopropyl)ester;3-Methyl 5-(2-oxopropyl) 2,6-diMethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• CAS NO: 86780-90-7
• Molecular Formula: C₁₉H₂₀N₂O₇
• Molecular Weight: 388.37
• Mol File: 86780-90-7.mol
• Article Data: 5

Chemical Properties

• Melting Point: 155°
• Boiling Point: 530 °C at 760 mmHg
• Flash Point: 274.3 °C
• Appearance: /
• Density: 1.284 g/cm³
• Vapor Pressure: 2.56E-11mmHg at 25°C
• Refractive Index: 1.555
• Storage Temp.: 2-8°C
• PKA: 2.56±0.70(Predicted)
• CAS DataBase Reference: ARANIDIPINE(CAS DataBase Reference)
• NIST Chemistry Reference: ARANIDIPINE(86780-90-7)
• EPA Substance Registry System: ARANIDIPINE(86780-90-7)

Safety Data

• Hazardous Substances Data: 86780-90-7(Hazardous Substances Data)

Usage

Description

Aranidipine is a potent and long-lasting dihydropyridine calcium channel blocker, used as an antihypertensive agent. It selectively blocks L-type voltage-gated calcium channels, leading to decreased intracellular calcium levels and enhanced relaxation of smooth and cardiac muscles. Its initial metabolite is just as effective as the parent compound, making it more potent than other dihydropyridine derivatives like nefidipine. Aranidipine is also a selective α2-adrenoreceptor antagonist, inhibiting vasoconstrictive responses. It can be synthesized via a modified Hantsch synthesis, and while sold as a racemate, the (S)-enantiomer is 150 times more active than the (R)-antipode.

Uses

Used in Pharmaceutical Industry:
Aranidipine is used as an antihypertensive agent for the treatment of hypertension. Its potent and long-lasting effects, along with its selective action on L-type voltage-gated calcium channels and α2-adrenoreceptors, make it an effective medication for managing high blood pressure.
Used in Cardiovascular Applications:
Aranidipine is used as a calcium channel blocker for the management of cardiovascular diseases, such as angina pectoris and arrhythmias. Its ability to block calcium entry during depolarization and inhibit vasoconstrictive responses helps in improving blood flow and reducing the workload on the heart.
Used in Drug Synthesis:
Aranidipine can be synthesized via a modified Hantsch synthesis, which is useful for the production of this potent antihypertensive agent. The selective activity of the (S)-enantiomer over the (R)-antipode highlights the importance of stereochemistry in drug development and synthesis.
Brand Name:
Aranidipine is marketed under the brand names Bec/Sapresta.

Originator

Maruko Seiyaku (Japan)

Manufacturing Process

100.0 mg of 50% sodium hydride was added to a mixture of 20.0 g of 2,2- ethylenedioxypropanol and 100 ml of benzene, and 20.0 g of diketene was added dropwise to the mixture while refluxing the mixture. After refluxing the mixture for 2 h, the solvent was distilled off and the resulting residue was distilled under reduced pressure to obtain 21.5 g (70% yield) of 2,2- ethylenedioxypropyl acetoacetate as a colorless oil, boiling point of 90°C (6 mm Hg). Ammonia gas was passed through a mixture of 19.0 g of 2,2- ethylenedioxypropyl acetoacetate and 100 ml of methanol for 2.5 h under icecooling while stirring. The solvent was then distilled off and the residue was distilled under reduced pressure to obtain 16.0 g (84% yield) of 2,2- ethylenedioxypropyl 3-aminocrotonate as a pale yellow oil, boiling point of 120°C (5 mm Hg). A mixture of methyl 2'-nitrobenzylidene acetoacetate, 2,2-ethylenedioxypropyl 3-aminocrotonate and ethanol was refluxed for 10 h. The resulting reaction solution was allowed to stand overnight, and the precipitated crystals were collected by filtration and recrystallized from ethanol to obtain methyl 2,2- ethylenedioxypropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5- dicarboxylate. Methyl 2,2-ethylenedioxypropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4- dihydropyridine-3,5-dicarboxylate was refluxed in an ethanol solution containing 10% hydrochloric acid for 6 h. The solvent was then distilled off and the residue was crystallized from diethyl ether to give methyl 2-oxopropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate as yellow prisms, melting point 155°C (recrystallized from a mixture of ethyl acetate and hexane).

Therapeutic Function

Antihypertensive

InChI:InChI=1/C19H20N2O7/c1-10(22)9-28-19(24)16-12(3)20-11(2)15(18(23)27-4)17(16)13-7-5-6-8-14(13)21(25)26/h5-8,17,20H,9H2,1-4H3

Upstream product

• 86780-89-4 2,2-ethylenedioxypropyl methyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate 
• 39562-27-1 methyl 2-(2'-nitrobenzylidene)acetoacetate 
• 86780-81-6 3-amino-2-crotonic acid 2,2-ethylenedioxy propyl ester 
• 552-89-6 2-nitro-benzaldehyde 
• 103785-52-0 2,2-ethylenedioxypropyl 2-(2-nitrophenylmethylene)acetoacetate 
• 86780-80-5 2,2-ethylenedioxypropyl acetoacetate 
• 105-45-3 acetoacetic acid methyl ester 

Relevant articles and documents

A process for preparing went horizontal method

The invention discloses a method for synthesizing aranidipine. The method comprises the following steps: performing addition on propargyl alcohol and ethylene glycol, performing reaction on propargyl alcohol and ethylene glycol which are subjected to addition and ketene dimer to obtain acetoacetic acid 2,2-ethylenedioxy propyl ester, then performing amination and performing condensation and hydrolysis on acetoacetic acid 2,2-ethylenedioxy propyl ester and 2-(2-nitro benzal)-3-oxo-methyl butyrate to obtain aranidipine serving as an anti-hypertension medicine. According to the preparation method for aranidipine, NiCl2 replaces mercury bichloride, is used as a promoter for preparing 2,2-ethylenedioxy propyl alcohol, non-toxic and is good in catalysis effect; ethanediamine is used as a catalyst for preparing acetoacetic acid 2,2-ethylenedioxy propyl ester and is high in catalytic yield; moreover, a product can be put into the next reaction step without being purified; by the use of NiCl2 and ethanediamine, the speed of the whole reaction process is increased, and the method is environment-friendly and is high in economical benefit.

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.

1,4-Dihydropyridine compounds

1,4-Dihydropyridine compounds having excellent coronary and vertebral vasodilation, blood pressure depression and anti-hypertensive activities are disclosed. These compounds are low toxic and stable to light, and are very useful for pharmaceutical agents.