Lomerizine hydrochloride

Base Information

• Chemical Name: Lomerizine hydrochloride
• CAS No.: 101477-54-7
• Molecular Formula: C27H32Cl2F2N2O3
• Molecular Weight: 541.465
• Hs Code.: 29335990
• European Community (EC) Number: 686-037-9
• UNII: 3W473D5LIY
• DSSTox Substance ID: DTXSID1046427
• Wikidata: Q27258118
• ChEMBL ID: CHEMBL2356978
• Mol file: 101477-54-7.mol

Synonyms:1-(bis(4-fluorophenyl)methyl)-4-(2,3,4-trimethoxybenzyl)piperazine dihydrochloride;KB 2796;KB-2796;lomerizine;lomerizine dihydrochloride

Chemical Property of Lomerizine hydrochloride

Chemical Property:

• Appearance/Colour: colourless crystalline solid
• Melting Point: 214-218 °C
• Boiling Point: 527.3 °C at 760 mmHg
• Flash Point: 272.7 °C
• PSA: 34.17000
• LogP: 6.37760
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO: ≥30mg/mL
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 8
• Exact Mass: 540.1758046
• Heavy Atom Count: 36
• Complexity: 568

Purity/Quality:

99% ^*data from raw suppliers

Lomerizine, Dihydrochloride ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn,N
• Hazard Codes: Xn,N
• Statements: 22-50
• Safety Statements: 61

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: COC1=C(C(=C(C=C1)CN2CCN(CC2)C(C3=CC=C(C=C3)F)C4=CC=C(C=C4)F)OC)OC.Cl.Cl
• 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.
• Uses: A diphenylpiperazine calcium channel blocker. A selective cerebral vasodilator. Antimigraine.

Technology Process of Lomerizine hydrochloride

There total 4 articles about Lomerizine hydrochloride which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 87.4%

4,4'-difluorobenzhydryl chloride (27064-94-4) + 1-(2,3,4-trimethoxybenzyl)piperazine (5011-34-7) → KB-2796 dihydrochloride (101477-54-7)

Guidance literature:

4,4'-difluorobenzhydryl chloride; 1-(2,3,4-trimethoxybenzyl)piperazine; With triethylamine; In methanol; at 65 - 75 ℃; for 10h;

With hydrogenchloride; In ethanol; at 45 ℃; for 2h;

Reference yield: 40.0%

1-(4-fluorophenyl)methyl-piperazine (27469-60-9) + 2,3,4-trimethoxybenzaldehyde (2103-57-3) → KB-2796 dihydrochloride (101477-54-7)

Guidance literature:

With formic acid; In melt; at 120 ℃; for 1h;

DOI:10.1248/cpb.35.3270

Reference yield:

2,3,4-trimethoxybenzyl chloride (1133-49-9) + ethanol-diethyl ether (8013-43-2) + 1-(4-fluorophenyl)methyl-piperazine (27469-60-9) → KB-2796 dihydrochloride (101477-54-7)

Guidance literature:

With hydrogenchloride; triethylamine; In ethanol; benzene;

upstream raw materials:

1-(4-fluorophenyl)methyl-piperazine

2,3,4-trimethoxybenzaldehyde

2,3,4-trimethoxybenzyl chloride

ethanol-diethyl ether

Refernces

• 1、 -. "Lomerizine hydrochloride synthesizing method". Paragraph 0016; 0018; 0022; 0024; 0030; 0031. . Retrieved 2019/05/02.
• 2、 -. "1-(2,3,4-tri-methoxybenzyl)-4[bis(4-fluorophenyl)methyl] piperazines are useful for treating cerebrovascular disease". . . Retrieved 2008/06/13.