Benidipine hydrochloride Chemical Properties

Melting point:

199-201°C

storage temp. 

Inert atmosphere,Store in freezer, under -20°C

solubility 

DMSO: ≥20mg/mL

pka

7.34(at 25℃)

form 

powder

color 

yellow

InChIKey

DGVVISBYHUXFIU-UHFFFAOYSA-N

SMILES

C(C1=C(NC(=C([C@H]1C1C=CC=C(C=1)N(=O)=O)C(=O)OC)C)C)(=O)O[C@@H]1CCCN(C1)CC1C=CC=CC=1.Cl

CAS DataBase Reference

91599-74-5(CAS DataBase Reference)

Safety Information

Hazard Codes 

T

Risk Statements 

25

Safety Statements 

45

RIDADR 

UN 2811 6.1 / PGIII

WGK Germany 

3

RTECS 

US7975657

HS Code 

2933.99.5300

HazardClass 

6.1

Toxicity

LD50 orally in male mice: 218 mg/kg (Muto, 1988)

Benidipine hydrochloride Usage And Synthesis

Description

Benidipine hydrochloride is a new, long acting dihydropyridine calcium antagonist useful in the treatment of hypertension and angina pectoris. In experimental animals, benidipine hydrochloride dose dependently induced hypotension with a potency of 6 and 12 times more than nifedipine and nicardipine, respectively. It also exhibited a slow onset of action.

Description

Benidipine is an orally bioavailable blocker of L-, T-, and N-type calcium channels. In guinea pig ventricular cells benidipine has an IC₅₀ of 2.7 nM for calcium currents, determined using whole cell voltage clamp electrophysiology. It prevents oxidative stress dose-dependently in vitro, decreases blood pressure in spontaneously hypertensive rats (at 3 and 10 mg/kg), and is neuroprotective for neural stem cells after oxidative stress-induced injury. Benidipine is also a competitive antagonist at mineralocorticoid receptors.

Chemical Properties

Yellow Crystalline Powder

Originator

Kyowa Hakko (Japan)

Uses

A dihydropyridine calcium channel blocker. Antihypertensive.

brand name

Coniel

Biological Activity

Orally active antihypertensive agent which displays a wide range of activities in vitro and in vivo . Inhibits L-, N- and T-type Ca 2+ channels. Also inhibits aldosterone-induced mineralocorticoid receptor activation. Exhibits cardioprotective and antiartherosclerotic effects.

Safety Profile

A poison by ingestion,intraperitoneal, and intravenous routes. When heated todecomposition it emits toxic vapors of NOx and HCl.

Synthesis

Under sonication conditions, 10 g of monomethyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate was placed in a 200 mL reaction flask, to which 14 mL of N,N-dimethylformamide (DMF) and 56 mL of dichloromethane were added. Under ice bath conditions, 2.4 mL of thionyl chloride was slowly added to the resulting homogeneous suspension, followed by stirring the reaction mixture for 1 hour until a clarified solution was formed. Next, 6.3 g of 1-benzyl-3-piperidinol was added and stirring was continued for 2.5 hours under ice bath conditions. Upon completion of the reaction, the reaction solution was washed with 40 mL of water (repeated 4 times) and 40 mL of saturated brine solution (1 time). The organic phase was dried by adding 4 g of anhydrous sodium sulfate for 2 hours. After drying, the sodium sulfate solid was removed by filtration and the dichloromethane was recovered by distillation under reduced pressure to give the crude yellow to red (R)-rel-3-((R)-1-benzylpiperidin-3-yl)5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride. The crude product was dissolved in 100 mL of acetone and sonicated at 150 W and 40 kHz for 7 min, followed by filtration under reduced pressure and drying to give 5.9 g of yellow powdery product in 36.2% yield.

storage

room temperature (desiccate)

References

[1] Patent: WO2012/142815, 2012, A1. Location in patent: Page/Page column 5; 6

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