101477-54-7

Basic information

• Product Name: Lomerizine hydrochloride
• Synonyms: 1-(4,4'-Difluorobenzhydryl)-4-(2,3,4-trimethoxybenzyl)piperazine·dihydrochloride;Flometizine hydrochloride;Piperazine, 1-[bis(4-fluorophenyl)methyl]-4-[(2,3,4-trimethoxyphenyl)methyl]-, hydrochloride (1:2);Lomerizine dihydrochloride, >=99%;1-(Bis(4-fluorophenyl)methyl)-4-(2,3,4-trimethoxybenzyl)piperazine dihydrochloride;1-(2,3,4-trimethoxybenzyl)-4-(bis(4-fluorophenyl)methyl)piperazinedihydrochl;1-(bis(4-fluorophenyl)methyl)-4-((2,3,4-trimethoxyphenyl)methyl)-piperazin;1-(bis(4-fluorophenyl)methyl)-4-((2,3,4-trimethoxyphenyl)methyl)piperazined
• CAS NO: 101477-54-7
• Molecular Formula: C₂₇H₃₀F₂N₂O₃*2ClH
• Molecular Weight: 541.46
• Product Categories: Heterocyclic Compounds;Intermediates & Fine Chemicals;Neurochemicals;Pharmaceuticals;Aromatics;Heterocycles;Inhibitors;APIs
• Mol File: 101477-54-7.mol
• Article Data: 4

Chemical Properties

• Melting Point: 214-218°C dec.
• Boiling Point: 527.3 °C at 760 mmHg
• Flash Point: 272.7 °C
• Appearance: white to tan/
• Storage Temp.: -20°C Freezer
• Solubility: DMSO: ≥30mg/mL
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 1 month.
• Merck: 14,5563
• CAS DataBase Reference: Lomerizine hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Lomerizine hydrochloride(101477-54-7)
• EPA Substance Registry System: Lomerizine hydrochloride(101477-54-7)

Safety Data

• Hazard Codes: Xn,N
• Statements: 22-50
• Safety Statements: 61
• RIDADR: UN 3077 9 / PGIII
• WGK Germany: 3
• RTECS: TK9189000
• Hazardous Substances Data: 101477-54-7(Hazardous Substances Data)

Usage

Description

Lomerizine hydrochloride was introduced as Teranas and Migsis in Japan for the treatment of migraine. It is the first in its class of dual sodium and calcium channel blockers to be marketed for this indication. It can be synthetically obtained by reductive amination of 2,3,4-trimethoxybenzaldehyde with the appropiate benzhydryl piperazine. In dogs, Lomerizine exerts a potent, selective and long-lasting vasodilation of cerebral arteries related to a combination of mechanisms, especially a functional block of L-type voltagesensitive calcium channels (L-VSCCs). Lomerizine increases cerebral blood flow compared to peripheral blood flow with only weak effects on systemic arterial blood pressure. Other mechanisms involved could be blockade of other VSCC and sodium channels, 5-HT2 and alpha-1 receptors. As a reducing agent of cortical spreading depression and neurogenic inflammation, Lomerizine was shown to be useful in migraine. In an open clinical study, it demonstrated efficacy in the treatment of cluster headache. Moreover, it may have utility in other neurological diseases such as cerebrovascular ischemia or cerebral infarction.

Chemical Properties

Colourless Crystalline Solid

Originator

Akzo Nobel (Netherlands)

Uses

A diphenylpiperazine calcium channel blocker. A selective cerebral vasodilator. Antimigraine.

Brand name

Teranas;Migsis

References

1) Ishii?et al. (2009), Inhibitory effect of lomerizine, a prophylactic drug for migraines, on serotonin-induced contraction of the basilar artery; ?J. Pharmacol. Sci. 111 221 2)?Hara et al. (2004), Clinical potential of lomerizine, a Ca2+ channel blocker as an anti-glaucoma drug: effects on ocular circulation and retinal neuronal damage; Cardiovasc.Drug Rev. 22 199 3)?Ishii et al. (2011), Neuroprotection by lomerizine, a prophylactic drug for migraine, against hydrogen peroxide-induced hippocampal neurotoxicity; Mol. Cell Biochem. 358 1 4) Savigni?et al. (2013), Three Ca2+ channel inhibitors in combination limit chronic secondary degeneration following neurotrauma; ?Neuropharmacology 75 380 5) Tran?et al. (2014), The voltage-gated calcium channel blocker lomerizine is neuroprotective in motor neurons expressing mutant SOD, but not TDP-43; ?J. Neurochem. 130 455 6) O’Hare?et al. (2016), Specific combinations of ion channel inhibitors reduce excessive Ca2+ influx as a consequence of oxidative stress and increase neuronal and glial cell viability in vitro; ?Neuroscience 339 450

InChI:InChI=1S/C27H30F2N2O3.2ClH/c1-32-24-13-8-21(26(33-2)27(24)34-3)18-30-14-16-31(17-15-30)25(19-4-9-22(28)10-5-19)20-6-11-23(29)12-7-20;;/h4-13,25H,14-18H2,1-3H3;2*1H

Upstream product

• 27064-94-4 4,4'-difluorobenzhydryl chloride 
• 5011-34-7 1-(2,3,4-trimethoxybenzyl)piperazine 
• 1133-49-9 2,3,4-trimethoxybenzyl chloride 
• 8013-43-2 ethanol-diethyl ether 
• 27469-60-9 1-(4-fluorophenyl)methyl-piperazine 
• 2103-57-3 2,3,4-trimethoxybenzaldehyde 

Relevant articles and documents

METHODS FOR TREATING CHRONIC FATIGUE SYNDROME AND MYALGIC ENCEPHALOMYELITIS

In one aspect the invention relates to a method of treatment selected from the group consisting of: (a) treating a symptom such as pain in a subject identified or diagnosed as having Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS); (b) treating a symptom such as pain in a subject having dysfunctional TRPM3 ion channel activity; (c) restoring NK cell function in a subject having dysfunctional TRPM3 ion channel activity; and (d) restoring calcium homeostasis in a subject having dysfunctional TRPM3 ion channel activity. The method comprises the step of administering to the subject a therapeutically effective amount of at least one therapeutic compound selected from the group consisting of: (i) an opioid receptor antagonist; (ii) an opioid antagonist; and (iii) a therapeutic compound that restores TRPM3 ion channel activity. In some embodiments the therapeutic compound is naltrexone hydrochloride.

1-(2,3,4-tri-methoxybenzyl)-4[bis(4-fluorophenyl)methyl] piperazines are useful for treating cerebrovascular disease

A 1-benzyl-4-benzhydrylpiperazine derivative represented by the following general formula (I) STR1 wherein R1 represents a hydrogen atom or a methoxy group, and R2 represents a hydrogen or fluorine atom, or a pharmaceutically acceptable acid addition salt thereof. The 1-benzyl-4-benzhydrylpiperazine derivative or an acid addition salt thereof is prepared by reductively condensing a benzaldehyde derivative with a fluorobenzhydrylpiperazine, or condensing a benzyl halide derivative with a fluorobenzhydrylpiperazine optionally in the presence of an acid acceptor, or condensing a benzylpiperazine with a fluorobenzhydryl halide derivative and, optionally converting the product to its acid addition salt. The 1-benzyl-4-benzhydrylpiperazine derivative is useful for improving a cerebrovascular disease.