30484-77-6

Basic information

• Product Name: Flunarizine dihydrochloride
• Synonyms: Flugeral;Flunarl;Fluxarten;Gradient;Issium;Flunarizine dihydrochloride,1-[Bis(4-fluorophenyl)methyl]-4-(3-phenyl-2-propenyl)piperazine dihydrochloride;Flunarizine-d8 dihydrochloride;1-[Bis(4-fluorophenyl)Methyl]-4-[(2E)-3-phenyl-2-propen-1-yl]piperazine Hydrochloride
• CAS NO: 30484-77-6
• Molecular Formula: C₂₆H₂₆F₂N₂*2ClH
• Molecular Weight: 477.42
• EINECS: 250-216-6
• Product Categories: Sodium channel;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;PROLIXIN;API;Active Pharmaceutical Ingredients
• Mol File: 30484-77-6.mol
• Article Data: 1

Chemical Properties

• Melting Point: 188-190?C
• Boiling Point: 511.3 °C at 760 mmHg
• Flash Point: 263 °C
• Appearance: White solid
• Vapor Pressure: 1.43E-10mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: chloroform/methanol (9:1): 50 mg/mL, clear, colorless
• Merck: 13,4170
• BRN: 4284243
• CAS DataBase Reference: Flunarizine dihydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Flunarizine dihydrochloride(30484-77-6)
• EPA Substance Registry System: Flunarizine dihydrochloride(30484-77-6)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 3
• RTECS: TK9187000
• Hazardous Substances Data: 30484-77-6(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Originator

Sibelium,Janssen,W. Germany,1977

Uses

Different sources of media describe the Uses of 30484-77-6 differently. You can refer to the following data:
1. Flunarizine dihydrochloride has been used to study the effect of flunarizine on epileptiform activity. It is also used to study its effect on high-potassium induced increase of intracellular free calcium.
2. antipsychotic, H1 antihistamine
3. Calcium channel blocker; fluorinated derivative of Cinnarizine. Vasodilator (cerebral and peripheral). This is the labeled analog.

Manufacturing Process

A mixture of 14.3 parts of di-(p-fluorophenyl)-chloromethane, 10.1 parts of 1- cinnamylpiperazine, 12.7 parts of sodium carbonate, a few crystals of potassium iodide in 200 parts of 4-methyl-2-pentanone is stirred and refluxed for 21 hours. The reaction mixture is cooled and 50 parts of water are added. The organic layer is separated, dried, filtered and evaporated.The oily residue is dissolved in 480 parts of anhydrous diisopropyl ether. This solution is boiled with activated charcoal, filtered and to the clear filtrate is added an excess of 2-propanol, previously saturated with gaseous hydrogen chloride. The precipitated salt is filtered off and recrystallized from a mixture of 2-propanol and ethanol, yielding 1-cinnamyl-4-(di-p-fluorobenzhydryl) piperazine dihydrochloride, MP 251.5°C.

Therapeutic Function

Vasodilator

General Description

Flunarizine has antihistamine, anticonvulsant and vestibular depressive properties. It protects endothelial cells from calcium overload-induced damage. Flunarizine is used to treat epilepsy, migraine prophylaxis, cerebral blood flow disturbances, peripheral vascular disease and vertigo.

Biological Activity

Dual Na + /Ca 2+ channel blocker; a cerebral and peripheral vasodilator. Neuroprotective.

Biochem/physiol Actions

Blocks T-type Ca2+/Na+ channels; inhibits K+-induced catecholamine release from chromaffin cells

InChI:InChI=1/C26H26F2N2/c27-24-12-8-22(9-13-24)26(23-10-14-25(28)15-11-23)30-19-17-29(18-20-30)16-4-7-21-5-2-1-3-6-21/h1-15,26H,16-20H2/p+2/b7-4+

Upstream product

• 27469-60-9 1-(4-fluorophenyl)methyl-piperazine 
• 4392-24-9 3-bromo-1-phenyl-1-propenyl bromide 
• 365-24-2 4,4'-difluorobenzhydryl alcohol 
• 27064-94-4 4,4'-difluorobenzhydryl chloride 

Relevant articles and documents

(4-(Bis(4-Fluorophenyl)Methyl)Piperazin-1-yl)(Cyclohexyl) methanone hydrochloride (LDK1229): A new cannabinoid CB1 receptor inverse agonist from the class of benzhydryl piperazine analogs

Some inverse agonists of cannabinoid receptor type 1 (CB1) have been demonstrated to be anorectic antiobesity drug candidates. However, the first generation of CB1 inverse agonists, represented by rimonabant (SR141716A), otenabant, and taranabant, are centrally active, with a high level of psychiatric side effects. Hence, the discovery of CB1 inverse agonists with a chemical scaffold distinct from these holds promise for developing peripherally active CB1 inverse agonists with fewer side effects. We generated a new CB1 inverse agonist, (4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)(cyclohexyl)methanone hydrochloride (LDK1229), from the class of benzhydryl piperazine analogs. This compound binds to CB1 more selectively than cannabinoid receptor type 2, with a Ki value of 220 nM. Comparable CB1 binding was also observed by analogs 1-[bis(4-fluorophenyl)methyl]-4-cinnamylpiperazine dihydrochloride (LDK1203) and 1-[bis(4-fluorophenyl)methyl]-4-tosylpiperazine hydrochloride (LDK1222), which differed by the substitution on the piperazine ring where the piperazine of LDK1203 and LDK1222 are substituted by an alkyl group and a tosyl group, respectively. LDK1229 exhibits efficacy comparable with SR141716A in antagonizing the basal G protein coupling activity of CB1, as indicated by a reduction in guanosine 59-O-(3-thio)triphosphate binding. Consistent with inverse agonist behavior, increased cell surface localization of CB1 upon treatment with LDK1229 was also observed. Although docking and mutational analysis showed that LDK1229 forms similar interactions with the receptor as SR141716A does, the benzhydryl piperazine scaffold is structurally distinct from the first-generation CB1 inverse agonists. It offers new opportunities for developing novel CB1 inverse agonists through the optimization of molecular properties, such as the polar surface area and hydrophilicity, to reduce the central activity observed with SR141716A.