DILAZEP DIHYDROCHLORIDE

Originator

Cormelian,Asta-Werke,W. Germany,1972

The Uses of DILAZEP DIHYDROCHLORIDE

Dilazep Dihydrochloride is a research product for neuroscience. This compound may exhibit neuroprotective properties. Angiotensin converting, adenosine reuptake inhibitor. Antiplatelet agent. Dilazep acts as a cerebral vasodialator.

The Uses of DILAZEP DIHYDROCHLORIDE

vasodilator, platelet aggregation inhibitor

Definition

ChEBI: Dilazep is a member of the class of diazepanes that is 1,4-diazepane substituted by 3-[(3,4,5-trimethoxybenzoyl)oxy]propyl groups at positions 1 and 4. It is a potent adenosine uptake inhibitor that exhibits antiplatelet, antianginal and vasodilator properties. It has a role as a vasodilator agent, a platelet aggregation inhibitor and a cardioprotective agent. It is a member of methoxybenzenes, a benzoate ester, a diester and a diazepane. It is a conjugate base of a dilazep(2+).

Manufacturing Process

528.8 grams of bis-(3-hydroxypropyl)-ethylene diamine [K. Schlgl and R. Schlgl, Monatschefte der Chemie 95 (1964) page 935] are dissolved in a mixture of 1,500 cc of anhydrous ethyl alcohol and 1,250 grams of triethylamine. 520 grams of 1,3-chlorobromopropane are added thereto dropwise over a period of about 3 hours while stirring and heating the reaction mixture in an oil bath of 50°C. After completion of the addition, the oil bath is heated to 60°C for 20 minutes while stirring of the reaction mixture is continued. With increasing reaction time, triethylamine hydrochloride is precipitated. After completion of the reaction, the mixture is allowed to cool to room temperature.
Triethylamine hydrochloride is separated by filtration and the filter cake is washed with 100 cc of anhydrous ethyl alcohol. The alcohol and the excess of triethylamine is distilled off in a vacuum of a water pump. The residue represents a light-yellowish brown viscous oil which is extracted 3 times with 500 cc of anhydrous benzene each time with stirring at 40° to 60°C. The benzene is distilled off on a water bath at 60°C. Thus, an oil is obtained which solidifies to a hard mass after some hours. This mass is crushed and dried over P2O5 in an exsiccator. The compound represents N,N'-bis-(3- hydroxypropyl)homopiperazine. Yield: 128.5 grams. FP: 46°-47°C; BP0.02mm: 141°-142°C.
21.6 grams of N,N'-bis-(3-hydroxypropyl)homopiperazine obtained as described and 63.8 grams of 3,4,5-trimethoxy benzoic acid chloride are dissolved in 600 parts by volume of anhydrous chloroform. The solution is heated to boiling for 5 hours. Thereafter, chloroform is distilled off in a vacuum. The residue is dissolved in water and the aqueous solution is washed with ether. Thereafter, the aqueous phase is rendered alkaline by the addition of soda lye and the separated oil base is extracted with ether. The ethereal solution is dried over Na2SO4. Ether is separated in a vacuum and the highly viscous residue is dissolved in 150 parts by volume of ethyl alcohol. The calculated equivalent amount of ethereal HCl is added thereto.
The soon crystallizing dihydrochloride is separated by filtration, dried and recrystallized from 120 parts by volume of ethanol. Thus, after drying for 3 days over P2O5, 40-50 grams (66-70% of the theoretical) of N,N'-bis-[(3,4,5- trimethoxy benzoloxy)propyl] homopiperazine dihydrochloride containing 1 mol of water of crystallization is obtained. This product has a melting point at 194°-198°C.

Therapeutic Function

Coronary vasodilator

Biological Activity

Coronary and cerebral vasodilator, suppresses the effects of ischemia. Inhibitor of platelet aggregation and of membrane transport of nucleosides. Inhibits adenosine uptake.