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

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

Uses

Used in Cardiovascular Applications:
Isradipine is used as an antihypertensive and antianginal agent for the treatment of essential hypertension and stable angina. It helps in reducing the frequency of anginal attacks and the need to use nitroglycerin.
Used in Neuroprotection:
Isradipine is used as a neuroprotective agent in a rat model of focal ischemia, providing a dose-dependent sparing of dopamine neuronal fibers and cell bodies.
Used in Anti-atherosclerotic Applications:
Isradipine is used for its anti-atherosclerotic effects in animals and for improving endothelium-mediated nitric oxide (NO)-dependent vasodilation in vitro.
Used in Non-sedating H1-antihistamine Applications:
Isradipine is used as a non-sedating H1-antihistamine, which may have potential applications in treating allergic reactions with minimal sedative effects.

Originator

Sandoz (Switzerland)

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.

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.

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.