132203-70-4

Basic information

• Product Name: Cilnidipine
• Synonyms: ATELEC;(+/-)-(e)-cinnamyl 2-methoxyethyl 1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxylate;O3-(2-Methoxyethyl) O5-[(E)-3-phenylprop-2-enyl] 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate;1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylic acid 3-(2-methoxyethyl)5-[(E)-3-phenyl-2-propenyl] ester;2,6-Dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxylic acid 3-(2-methoxyethyl)5-[(E)-3-phenyl-2-propenyl] ester;Frc 8653,1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl (2E)-3-phenyl-2-propenyl ester;1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic Acid 2-Methoxyethyl (2E)-3-Phenyl-2-propenyl Ester 2-Methoxyethyl (2E)-3-Phenyl-2-propenyl 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate;ilnidipine
• CAS NO: 132203-70-4
• Molecular Formula: C₂₇H₂₈N₂O₇
• Molecular Weight: 492.52
• EINECS: 1806241-263-5
• Product Categories: Dihydropyridine Class Chemicals;Intermediates & Fine Chemicals;Pharmaceuticals;Calcium channel;Dihydropyridine;API;FRC 8653;Active Pharmaceutical Ingredients;APIs
• Mol File: 132203-70-4.mol
• Article Data: 4

Chemical Properties

• Melting Point: 97-99°C
• Boiling Point: 652.6 °C at 760 mmHg
• Flash Point: 348.5 °C
• Appearance: light yellow/
• Density: 1.24 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.581
• Storage Temp.: Store at +4°C
• Solubility: H2O: ≤2mg/mL
• PKA: 2.61±0.70(Predicted)
• Merck: 14,2275
• CAS DataBase Reference: Cilnidipine(CAS DataBase Reference)
• NIST Chemistry Reference: Cilnidipine(132203-70-4)
• EPA Substance Registry System: Cilnidipine(132203-70-4)

Safety Data

• Hazard Codes: Xi
• Statements: 41
• Safety Statements: 26-39
• WGK Germany: 3
• RTECS: US7975550
• Hazardous Substances Data: 132203-70-4(Hazardous Substances Data)

Usage

Description

Different sources of media describe the Description of 132203-70-4 differently. You can refer to the following data:
1. Clinidipine is a kind of calcium channel blocker. It is a kind of novel calcium antagonist with the blocking effect on both L-type and N-type calcium channels. It is mainly used for the treatment of hypertension. Based on its effect on both N-type and L-type calcium channel, it can dilate both arterioles and venules, further reducing the pressure in the capillary bed. In addition, cilinidipine can attenuate the platelet activation associated with catecholamines.
2. Cilnidipine is a dihydropyridine calcium channel blocker that blocks L- and N-type high-voltage-activated calcium currents in rat hippocampal CA1 pyramidal neurons when used at a concentration of 10 μM. Cilnidipine (3 mg/kg) reduces the pressor response to acute cold stress, as well as mean blood pressure, in spontaneously hypertensive rats. It dose-dependently reduces mean blood pressure and cerebral vascular resistance without affecting cerebral blood flow in anesthetized rats at doses ranging from 3-100 μg/kg. Cilnidipine (100 μg/kg, i.p.) reduces cerebral infarction area in a rat model of focal brain ischemia.
3. Cilnidipine is a dihydropyridine calcium antagonist introduced for the treatment of essential and severe hypertension and hypertension associated with renopathy. Cilnidipine has been demonstrated to exert a potent vasodilating effect by blocking calcium influx via dihydropyridine-sensitive, voltage-dependent calcium channels. Compared to nifedipine and nicardipine, cilnidipine is superior, especially for long-term treatment, due to its characteristics of slow onset and long duration with less cardiodepressant activity. Cilnidipine is reportedly well tolerated with low toxicity. It may also be useful in ischemic heart disease.

References

https://www.drugbank.ca/drugs/DB09232 https://en.wikipedia.org/wiki/Cilnidipine

Chemical Properties

Yellow Crystalline Solid

Uses

Different sources of media describe the Uses of 132203-70-4 differently. You can refer to the following data:
1. A dihydropyridine calcium channel blocker.
2. A dihydropyridine calcium channel blocker
3. antihypertensive;dihydropyridine calcium channel blocker
4. Cilnidipine has been used:in cell viability assay of pheochromocytoma (nPC12) cellsin photoirradiation and photodegradation studies to understand effect on albuminuria in diabetic nephropathy

Definition

ChEBI: A diesterified 1,4-dihydropyridine-3,5-dicarboxylic acid. A calcium channel blocker, it is used as an antihypertensive.

Brand name

Cinalong;Siscard;Atelec

Biological Activity

Dual L- and N-type calcium channel blocker that displays antihypertensive, sympatholytic and neuroprotective activity. Lowers mean blood pressure and reduces the size of cerebral infarction in the rat model of focal brain ischemia.

Biochem/physiol Actions

Cilnidipine is a slow-acting Ca2+ channel blocker; antihypertensive; vasodilator; dual blocker of L-type voltage-gated Ca2+ channels in vascular smooth muscle and N-type Ca2+ channels in sympathetic nerve terminals that supply blood vessels. Cilnidipine may offer an advantage over nifedipine as the long term intake of the latter has been linked to increased risk of myocardial infarction and mortality in patients with coronary artery disease. Cilnidipine lowers blood pressure, but has less effect on sympathetic activity. Unlike nifedipine, cilnidipine does not inhibit PKC.

InChI:InChI=1S/C27H28N2O7/c1-18-23(26(30)35-14-8-11-20-9-5-4-6-10-20)25(21-12-7-13-22(17-21)29(32)33)24(19(2)28-18)27(31)36-16-15-34-3/h4-13,17,25,28H,14-16H2,1-3H3/b11-8+

Synthetic route

3-amino-2-butenoic acid cinnamyl ester + (E/Z)-2-methoxyethyl 2-(3-nitrobenzylidene)-acetoacetate (39562-22-6) → cilnidipine (132203-70-4)

Conditions	Yield
Stage #1: 3-amino-2-butenoic acid cinnamyl ester; (E/Z)-2-methoxyethyl 2-(3-nitrobenzylidene)-acetoacetate In ethanol for 1h; Reflux; Stage #2: With hydrogenchloride In ethanol; water for 1h; Solvent; Reagent/catalyst; Reflux;	91.5%
In ethanol for 22h; Reflux; Large scale;

3-amino-2-butenoic acid cinnamyl ester + C14H17NO6 → cilnidipine (132203-70-4)

Conditions	Yield
In ethanol at 50℃; Solvent; Temperature;	91.4%

cilnidipine (132203-70-4) → 3-(2-methoxyethyl) 5-[(2E)-3-phenyl-2-propen-1-yl] 2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In dichloromethane at 20℃; for 2h;	89%
With 1,10-Phenanthroline; cerium(IV) sulphate; sulfuric acid In acetic acid

cilnidipine (132203-70-4) → 3-(2-methoxyethyl) 5-[(2E)-3-phenyl-2-propen-1-yl] 4-(3-aminophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate

Conditions	Yield
With iron; acetic acid at 100℃; for 0.25h;	78%

heptakis-(2,3,6-tris-(2-hydroxypropyl))-β-cyclodextrin (128446-35-5) + cilnidipine (132203-70-4) → C105H196O56*C27H28N2O7

Conditions	Yield
In water at 20℃; for 24h;

Upstream product

• 103909-86-0 3-amino-2-butenoic acid cinnamyl ester 
• 39562-22-6 (E/Z)-2-methoxyethyl 2-(3-nitrobenzylidene)-acetoacetate 

Downstream Products

• 146845-34-3 3-cinnamyl 5-(2-methoxyethyl) 2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate 
• 4407-36-7 (2E)-3-phenyl-2-propen-1-ol 

Related news

Effects of Cilnidipine (cas 132203-70-4) on sympathetic nerve activity and cardiorenal function in hypertensive patients with type 2 diabetes mellitus: Association with BNP and aldosterone levels08/06/2019

AimsHypertension stimulates the sympathetic nervous system and this phenomenon is exacerbated by diabetes mellitus. We investigated the effects of cilnidipine, an N/L-type calcium channel blocker, on aspects of this system in patients with type 2 diabetes mellitus.detailed

Antialbuminuric advantage of Cilnidipine (cas 132203-70-4) compared with L-type calcium channel blockers in type 2 diabetic patients with normoalbuminuria and microalbuminuria08/05/2019

We evaluated the antialbuminuric advantage of cilnidipine, an N/L-type calcium channel blocker (CCB), compared with L-type CCBs in diabetic patients with normoalbuminuria and microalbuminuria. The study was a multicenter, non-randomized crossover trial. Participants were 90 type 2 diabetic patie...detailed

Anti-stress effects of Cilnidipine (cas 132203-70-4) and nimodipine in immobilization subjected mice08/04/2019

The present study was designed to investigate the ameliorative role of cilnidipine and nimodipine in immobilization stress-induced behavioral alterations and memory defects in the mice. Acute stress was induced by immobilizing the mice for 150 min and stress-induced behavioral changes were asses...detailed

Role of P-Glycoprotein in Regulating Cilnidipine (cas 132203-70-4) Distribution to Intact and Ischemic Brain08/03/2019

Summary:Cilnidipine is reported to show antihypertensive and neuroprotective actions in a rat brain ischemia model, but is barely distributed to normal brain, suggesting that its uptake into normal brain is inhibited by efflux transporter(s), such as P-glycoprotein (P-gp). Here, we investigated ...detailed

Investigation of inclusion complex of Cilnidipine (cas 132203-70-4) with hydroxypropyl-β-cyclodextrin08/02/2019

The objective of this study was to improve the water-solubility and photostability of cilnidipine by complexing it with hydroxypropyl-β-cyclodextrin (HP-β-CD or HP-beta-CD). The interactions of cilnidipine and HP-β-CD were characterized by ultra violet–visible (UV/VIS) spectroscopy, differen...detailed

N- and L-type calcium channels blocker Cilnidipine (cas 132203-70-4) ameliorates neuropathic pain08/01/2019

Cilnidipine is a dihydropyridine derivative that inhibits N-type and L-type voltage-gated Ca2+ channels (VDCCs). We recently reported that a selective N-type VDCC blocker attenuated the spinal long-term potentiation (LTP) of C-fiber-evoked field potentials recorded in the spinal dorsal horn of r...detailed

Relevant articles and documents

Preparation method of cilnidipine

The invention relates to a preparation method of cilnidipine. The invention provides a preparation method of cinnamyl 3-aminobut-2-enoate, which comprises the following step: carrying out amination reaction on cinnamyl acetoacetate and ammonium carbonate to obtain the cinnamyl 3-aminobut-2-enoate. On the basis, the invention further provides a method for preparing cilnidipine by taking the cinnamyl 3-aminobut-2-enoate as a raw material. The method provided by the invention is relatively low in reaction temperature, relatively short in reaction time, relatively high in product yield and purity,and simple in aftertreatment.

Cilnidipine preparation method

The invention provides a cilnidipine preparation method. The method includes the steps that 2-(3-nitrophenyl methylidene) methoxyethyl acetoacetate and 3-amino-2-butenoic acid cinnamyl ester serve as reaction raw materials and react under catalysis of concentrated hydrochloric acid to obtain cilnidipine. A common inorganic catalyst is adopted in the method for catalysis reaction so that reaction time can be effectively shortened; besides, quality of a crude product is high, the yield is high, and cilnidipine has metallic luster. The requirement for refining of reaction is low. Purity of the crude product is good, and the quality requirement can be basically met through one time of refining. The technology is reasonable in design, purity of the refined cilnidipine product is high, and the quantity of any impurity and total impurities is small.