27469-53-0

Basic information

• Product Name: ALMITRINE
• Synonyms: ALMITRINE;1-[2,4-Bis(allylamino)-1,3,5-triazin-6-yl]-4-[bis(4-fluorophenyl)methyl]piperazine;2,4-Bis(allylamino)-6-[4-[bis(p-fluorophenyl)methyl]-1-piperazinyl]-s-triazine;6-[4-[Bis(4-fluorophenyl)methyl]-1-piperazinyl]-N,N'-di(2-propenyl)-1,3,5-triazine-2,4-diamine;S-2620;AlMitrine Mesylate
• CAS NO: 27469-53-0
• Molecular Formula: C₂₆H₂₉F₂N₇
• Molecular Weight: 477.55
• EINECS: 248-475-5
• Mol File: 27469-53-0.mol
• Article Data: 1

Chemical Properties

• Melting Point: 181°
• Boiling Point: 606.2 °C at 760 mmHg
• Flash Point: 320.4 °C
• Appearance: /
• Density: 1.2278 (estimate)
• Vapor Pressure: 1.21E-14mmHg at 25°C
• Refractive Index: 1.633
• CAS DataBase Reference: ALMITRINE(CAS DataBase Reference)
• NIST Chemistry Reference: ALMITRINE(27469-53-0)
• EPA Substance Registry System: ALMITRINE(27469-53-0)

Safety Data

• Hazardous Substances Data: 27469-53-0(Hazardous Substances Data)

Usage

Description

ALMITRINE is a triamino-1,3,5-triazine compound with allylamino substituents at the 2and 4-positions and a 4-(bis(p-fluorophenyl)methyl)-1-piperazinyl group at the 6-position. It is a pharmaceutical compound with various applications in different industries.

Uses

Used in Pharmaceutical Industry:
ALMITRINE is used as a respiratory stimulant for the treatment of respiratory depression and hypoxia. It helps to increase the rate and depth of breathing, which can be beneficial for patients with respiratory disorders.
Used in Veterinary Medicine:
In the veterinary field, ALMITRINE is used as an anthelmintic agent to treat and control parasitic worm infections in animals. It is effective against various types of helminths, including roundworms, tapeworms, and flukes.
Used in Research Applications:
ALMITRINE is also utilized in research settings as a tool to study the effects of respiratory stimulants on the central nervous system and the mechanisms underlying respiratory control. This helps in understanding the complex interactions between the respiratory and nervous systems.
Please note that the provided materials do not mention any specific uses of ALMITRINE. The uses listed above are general applications based on the compound's properties and potential pharmaceutical relevance.

Originator

Armanor ,Les Laboratoires Servier

Manufacturing Process

A solution of 4,6-bis(allylamino)-2-chloro-s-triazine, melting point 204°C (Kofler) and dihydrochloride of 1-p,p'-difluorobenzhydryl piperazine, melting point 178°-180°C (capillary) in anhydrous dimethylformamide are heated under reflux. On completion of this operation the solvent is removed under vacuum and the residue taken up in a mixture of chloroform and of water (1:1). The organic phase is separated, and repeatedly extracted with aqueous N-methanesulphonic acid and the aqueous acidic layers separated. The aforementioned acidic solutions are then combined and rendered alkaline (pH 10) with dilute aqueous sodium hydroxide, the base extracted with ether, the extract dried over anhydrous potassium carbonate, and filtered. The etheral filtrate, upon evaporation yields the 2,4-bis(allylamino)-6-(4-(bis(pfluorophenyl) methyl)-1-piperazinyl)-s-triazine, melting point 175°-180°C.

Therapeutic Function

Respiratory stimulant

World Health Organization (WHO)

Peripheral neuropathy has been reported in a few patients receiving almitrine for long periods. The indications for treatment have consequently been restricted in the Federal Republic of Germany. Some other countries have advised doctors to maintain patients under close supervision throughout treatment and to restrict dosage to two out of every three months.

Pharmacology

Almitrine, like doxapram, increases the rate and depth of respiration. In addition, it is believed that it redistributes pulmonary blood circulation, increasing it in alveoli, which leads to relatively better pulmonary ventilation. It has a more prolonged effect than doxapram.

Safety Profile

Poison by intraperitoneal andintravenous routes. When heated to decomposition itemits very toxic fumes of F?? and NOx.

Synthesis

Almitrine, 2,4-bis (allylamino)-6-[4-[bis-(p-fluorophenyl)methyl]-1-piperazinyl]-s-triazine (8.2.6), is synthesized by reacting 1-[bis-(p-fluorophenyl)methyl]piperazine with cyanuric chloride, which gives 2,4-dichloro-6-[4-[bis-(p-fluorophenyl) methyl]-1-piperazinyl]-s-trazine (8.2.5). Reacting this with allylamine gives almitrine (8.2.6) [19–22].

InChI:InChI=1/C26H29F2N7/c1-3-13-29-24-31-25(30-14-4-2)33-26(32-24)35-17-15-34(16-18-35)23(19-5-9-21(27)10-6-19)20-7-11-22(28)12-8-20/h3-12,23H,1-2,13-18H2,(H2,29,30,31,32,33)

Upstream product

• 15468-86-7 2-chloro-4.6-bis(2-propenylamino)-1,3,5-triazine 
• 27469-60-9 1-(4-fluorophenyl)methyl-piperazine 

Relevant articles and documents

New Triazine Derivatives as Potent Modulators of Multidrug Resistance

A series of 70 triazine derivatives have been synthesized and tested for their capacity to modulate multidrug resistance (MDR) in DC-3F/AD and KB-A1 tumor cells in vitro, in comparison with verapamil (VRP), a calcium channel antagonist currently used in therapy as an antihypertensive drug, which also shows MDR modulating activity.Among the 12 selected compounds, 16 (S9788) showed high MDR reversing properties in vitro (300- and 6-fold VRP at 5μM in DC-3F/AD and KB-A1 cells, respectively) and induced a strong accumulation of adriamycin.The relationship between the increase of ADR accumulation and the fold reversal induced by these compounds and their lack of effects on the sensitive DC-3F cells suggest that they act mainly by inhibiting the P-glycoprotein (Pgp) catalyzed efflux of cytotoxic agents, as already described for a majority of MDR modulators.In vivo, in association with the antitumor drug vincristine (0.25 mg/kg), 16 (100 mg/kg) increased the T/C by 39percent in mice bearing the resistant tumor cell line P388/VCR.According to these interesting properties, 16 was selected for a clinical development because it is more bioavailable than 34, even though it was less active.