CS220293B1 - 1- (2-Methylthio-O-benzothiazolyl-amino-methyl) -5-phenyl-1,2,3,4-tetrazole and its preparation - Google Patents

Abstract

Anorectically effective 1-(2-methylthio-6-benzothiazolylaminomethyl)-5-phenyl-1,2,3,4-tetrazole, formula I The essence of the method for preparing the substance of formula I consists in reacting 2-methylthio-6-aminobenzothiazole with 5-phenyl-1,2,3,4-tetrazole and formaldehyde in an ethanol environment at a temperature from room temperature to 50 °C.

Description

The essence of the process for preparing the compound of formula (I) is to react 2-methylthio-6-aminobenzothiazole with 5-phenyl-1,2,3,4-tetrazole and formaldehyde in ethanol at a temperature of from room temperature to 50 ° C.

The invention relates to 1- (2-methylthio-6-benzothiazolylaminomethyl) -5-phenyl-1,2,3,4-tetrazole and a process for its preparation. The compound is a novel chemical that has not been described in the literature. 1- (2-Methylthio-6-benzothiazolylaminomethyl) -5-phenyl-1,2,3,4-tetrazole of formula I

The most commonly used medicines that can reduce excessive appetite - anorectics - are Fenmetrazine or Dexfenmetrazine. Both drugs are addictive. There is less risk of addiction when taking Mirapront. However, it sometimes causes psychological changes. There is no drug that causes weight loss (Prof. MUDr. V. Pacovský DrSc., Internal Medicine II, p. 276, 1975). A review of Chemical Abstracts on anorectics based on benzothiazole and thiazole revealed that Höchst AG filed a patent entitled: Thiazolidine derivatives - Appetite depressant by Knabe Bernd, Lang Hans Jochen and Granzer Ernoild (Ger. Offen 2,640, 368 / C1 (C07 D 277/60, 16.3.1978). Thiazolidine derivatives of types I and II are described.

The patent does not disclose efficacy values (Chemical Abstracts 88, 190 817 1978). Both of these structural types differ considerably from the structure of the claimed substance.

The synthesis of 1- (2-methylthio-6-benzothiazolyl-aminomethyl) -5-phenyl-1,2,3,4-tetrazole is accomplished by mixing 2-methylthio-6-aminobenzothiazole with 5-phenyl-1,2,3,4-tetrazole in a C 1 -C 3 alcohol medium optionally diluted with water followed by addition of formaldehyde, with stirring in the range of room temperature to 50 ° C, preferably at 40 ° Celsius.

The invention is illustrated but not limited by the following example.

Example 1 Talc-colored, odorless, white, soluble in dimethylformamide or dimethylsulfoxide, insoluble in water.

Molecular Weight: 354,46.

Summary formula: C16H1.4N6S2.

Elemental analysis:

Calculated%:

54.21 C, 3.98 H, 23.70 N, 18.09 S.

54.14 C, 3.89 H, 23.38 N, 18.47 S.

1.96 g (0.010 mol) of 2-methylthio-6-aminobenzothiazole (art. No. 189 212, 1978) is mixed at room temperature with 1.46 g (0.010 mol) of 5-phenyl-1,2,3,4 tetrazol (Collection Czech. Chem. Commun., 41, 1962, 1976). To this mixture was added 20-40 mL of ethanol (96%). The mixture was heated to 35 ° C with stirring to give a light yellow solution. To this was added dropwise 2 ml (0.025 mol) of an aqueous solution of 36-38% formaldehyde (Lachema n. P., Neratovice plant) and the mixture was heated to 40 ° C. At this temperature, after 5 to 30 minutes, the solution becomes cloudy and the reaction product crystallizes later. After 30 minutes, the mixture is cooled to room temperature, the crystalline substance is filtered off with suction and washed with 10 to 20 ml of ethanol (96%) on the filter. The final material after drying has a weight of 2.5 g, which is 71.4% yield. Melting point: 141-143 ° C.

The preparation of the substance does not require a special protective device. The substance was prepared without the use of a fume hood.

Anorectic efficacy was determined by testing at the Research Institute for Pharmacy and Biochemistry Prague, Pardubice - Rosice Branch.

Test Conclusion: Oral administration of high doses of the sample did not induce any significant toxic symptoms in mice, only 2.5 mice / kg died of only 5 mice per day until the morning of the following day. In the anorectic efficacy test in mice (Clark R .: Toxicol. Appl. Pharmacol. 15, 212, 1969), a dose of 100 mg / kg p. o., which reduced food consumption by 88% relative to controls (at a dose of 300 mg / / kg, a reduction of 85%, with a repeat of 90 percent. Anorectic effect: 50 <ED <100 mg / kg po 2500 mg / kg, starting dose 300 mg / kg.

The compound of the invention is of low toxicity and ineffective in rotating rod assays, pentet220293 razole sprays, thiopental sleep potentiation, mouse locomotor activity (CNS effect) assays, antiamphetamine and antireserpine activity assays. It can be concluded that it is essentially not effective as a psychopharmaceutical (it has no signs of neuroleptic, centrally depressing, tranquilizing, psychostimulatory or antidepressant activity).

Claims (2)

SUBJECT 1- (2-Methylthio-6-benzothiazolylaminomethyl) -5-phenyl-1,2,3,4-tetrazole of formula I INVENTION 2. A process for the preparation of a compound according to claim 1, wherein 2-methylthio-6-aminobenzothiazole is reacted with 5-phenyl-1,2,3,4-tetrazole and formaldehyde in an alcoholic medium for 5 to 30 minutes and at a temperature of from 5 to 30 minutes. up to 50 ° C.