75695-93-1

Basic information

• Product Name: Isradipine
• Synonyms: PN-200-110;Presca;Prescal;4-(4-Benzofurazanyl)-2，6-dimethyl-1，4-dihydro-3，5-pyridinedicarboxylic acid methyl 1-methylethyl ester;Dynacrine;Iomir;Rebfiden;3,5-Pyridinedicarboxylic acid, 4-(2,1,3-benzoxadiazol-4-yl)-1,4-dihydro-2,6-dimethyl-, methyl 1-methylethyl ester
• CAS NO: 75695-93-1
• Molecular Formula: C₁₉H₂₁N₃O₅
• Molecular Weight: 371.39
• EINECS: 1308068-626-2
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Calcium channel;Ion Channels;ALLEGRA
• Mol File: 75695-93-1.mol
• Article Data: 3

Chemical Properties

• Melting Point: 166-1680C
• Boiling Point: 501.9 °C at 760 mmHg
• Flash Point: 257.4 °C
• Appearance: yellow/solid
• Density: 1.249 g/cm³
• Storage Temp.: 2-8°C
• Solubility: DMSO: ~26 mg/mL
• PKA: 2.56±0.70(Predicted)
• Stability: Stable for 2 years from date of purchsae as supplied. Protect from moisture. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
• Merck: 14,5240
• CAS DataBase Reference: Isradipine(CAS DataBase Reference)
• NIST Chemistry Reference: Isradipine(75695-93-1)
• EPA Substance Registry System: Isradipine(75695-93-1)

Safety Data

• Safety Statements: 22-24/25
• WGK Germany: 3
• Hazardous Substances Data: 75695-93-1(Hazardous Substances Data)

Usage

Description

Isradipine is a long-acting calcium blocker effective in the treatment of essential hypertension. The advantages of isradipine as compared with other dihydropyridine calcium antagonists include a "gentle" onset and fewer contraindications. It can be taken by patients with diabetes mellitus, chronic obstructive airway diseases, gout, congestive heart failure or ischemic heart disease.

Chemical Properties

Yellow Solid

Originator

Sandoz (Switzerland)

Uses

Different sources of media describe the Uses of 75695-93-1 differently. You can refer to the following data:
1. Isradipine is a L-type calcium channel blocker, Isradipine has anti-atherosclerotic effects in animals and improves endothelium-mediated nitric oxide (NO)-dependent vasodilation in vitro. Additional studies indicate that Isradipine may provide a neuroprotective effect in a rat model of focal ischemia and that Isradipine produces a dose-dependent sparing of dopamine neuronal fibers and cell bodies.
2. nonsedating H1-antihistamine
3. Dihydropyridine calcium channel blocker. Antihypertensive; antianginal

Brand name

Dynacirc (Reliant);Prescal.

General Description

Isradipine, 4-(4-benzofuranazyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinecarboxylic acid methyl 1-methylethyl ester (DynaCirc), is another second-generationdihydropyridine-type channel blocker. This drug, like theother second-generation analogs, is more selective for vascularsmooth muscle than for myocardial tissue. It is effectivein the treatment of stable angina, reducing the frequencyof anginal attacks and the need to use nitroglycerin.

Biological Activity

Potent and selective L-type voltage-gated Ca 2+ channel blocker. EC 50 and pA 2 values are 1.4 nM and 10.3 for relaxation of depolarization- and Ca 2+ -induced contractions of rabbit aorta respectively; EC 25 = 0.45 nM for reduction in rate of spontaneously beating guinea pig right atria. Long-acting antihypertensive agent in vivo , exerting primary effects on vascular tissue with secondary negative chronotropic action.

Biochem/physiol Actions

L-type calcium channel blocker (also referred to as dihydropyridine-type calcium channel blocker); antihypertensive.

References

1) Bracht et al. (2001), Isradipine improves endothelium-dependent vasodilation in normotensive coronary artery disease patients with hypercholesterolemia; J. Hyperten., 19 899 2) Chandra et al. (1999), Use of diffusion-weighted MRI and neurological deficit scores to demonstrate beneficial effects of isradipine in a rat model of focal ischemia ; Pharmacology, 58 292 3) Merck 14:5240

InChI:InChI=1/C19H21N3O5/c1-9(2)26-19(24)15-11(4)20-10(3)14(18(23)25-5)16(15)12-7-6-8-13-17(12)22-27-21-13/h6-9,16,20H,1-5H3

Synthetic route

2-acetyl-3-benzofurazan-4-yl-acrylic acid methyl ester (104785-90-2) + isopropyl 3-aminocrotonate (40100-28-5) → isradipine (75695-93-1)

Conditions	Yield
In ethanol at 25 - 28℃; for 5 - 7h;

isradipine (75695-93-1) → [3H]-(+)-Isradipine + (-)-Isradipine

Conditions	Yield
With α1-acid glycoprotein HPLC column resolution of racemate;

isradipine (75695-93-1) + C4H9N2O2*ClH → 4-benzo[1,2,5]oxadiazol-4-yl-2,6-dimethyl-pyridine-3,5-dicarboxylic acid 3-isopropyl ester 5-methyl ester

Conditions	Yield
With Britton-Robinson buffer In water; N,N-dimethyl-formamide at 37℃; pH=7.4; Kinetics;

Upstream product

• 104785-90-2 2-acetyl-3-benzofurazan-4-yl-acrylic acid methyl ester 
• 40100-28-5 isopropyl 3-aminocrotonate 

Downstream Products

• 131970-21-3 (+)-PN 200-110 
• 131970-21-3 (-)-(R)-isradipine 

Relevant articles and documents

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.

AN IMPROVED PROCESS FOR THE MANUFACTURE OF ISRADIPINE.

The present invention relates to an improved method for the manufacture of Isradipine, 4-(4-Benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid methyl 1-methylethyl ester. which, involves reacting 2,1,3-benzoxadiazole-4-carboxaldehyde with methyl acetoacetate in the presence of acetic acid and piperidine in diisopropyl ether. To obtain the product 2-acetyl-3-benzofurazan-4-yl-acrylic acid methyl ester which is then reacted with isopropyl-?-aminocrotonate in ethanol at 25 to 35°C to obtain the product.