CS223441B1 - Antihelmintically active 1-/2-isobutylthio-6-benzothiazole laminimethyl/5-phenyl-1,2,3,4-tetrazole and method of making the same - Google Patents

Description

The invention relates to l- (2-isobutylthio-6-benzotiazolylaminiometyl) 5-phenyl-l, 2,3,4-tetrazole of formula I, ^CW 3 S _C> »- 'in-OGR

NH-CH 2 N 2 Z _χ

The compound is antihelinintically active on Heterakis spumosa. The essence of the process for preparing 1- (2-isobutylthio-6-benzothiazolylaminomethyl) 5-phenyl-1,2,3 4-tetrazole is characterized in that 2-isobutylthio-6-aminobenzoothiazole is reacted with formaldehyde and 5-phenyl-1,2,3,4-tetrazole by Mannich synthesis according to the reaction scheme:

The synthesis is carried out by mixing 2-isobutylthio-6-aminobenzothiazole (E. Sidóová and Ž. Odlerová: Certificate of Authorization No. 189 212-78) with 5-phenyl-1,2,3,4-tetrazole (F. Považanec, J. Kováč) and A. Krutošíková: Collection Czech. Chem. Commun., 41, 1692, 1976) in a C 1 -C 3 alcohol medium followed by the addition of fofmaldehyde with stirring ranging from a lahora temperature to 40 ° C. !

The subject of the invention is illustrated by the following example:

11.5 g (0.05 mol) of 2-isobutylthio-6-aminobenzothiazole are mixed with 7.5 g (0.05 mol) of 5-phenyl-1,2,3,4-tetrazole at ambient temperature. 100 ml of ethanol (96%) are added and the mixture is heated to 35 ° C while stirring. At this temperature, 10 ml (0.10 mol) of formaldehyde (30%) is added portionwise to the solution at a rate such that the temperature of the mixture is maintained at 35-40 ° C. After 30 minutes from prldania formaldehyde feeds the uninterrupted under stirring to the mixture at 0 ^Q C to -10 ° C, 5 mL of water followed by 20 mL of acetone and 100 ml of petroleum ether optionally. After stirring for 5 minutes at 35 to 40 ° C, the mixture was stored at -20 ° to -30 ° C for 24 hours. The crystallized product is suction filtered off with suction on a Buchner funnel, where it is washed with 20 ml of petroleum ether cooled to -20 ° C. The suction is discontinued 10 minutes after the Bichner funnel with the final substance has been brought to ambient temperature. After drying, 13.8 g of compound I is obtained, which is a 70% yield over theory.

1- (2-isobutylthio-6-benzothiazolylaminomethyl) 5-phenyl-1,2,3,4-tetrazole is a crystalline substance, light gray in color, soluble in dimethylformamide or dimethylsulfoxide, insoluble in water. Melting at 137-139 ° C.

Summary formula: C19H20N6S2.

Molecular Weight: 396,54.

Elemental analysis:

theory:

C 57.55, H 5.08, N 21.19, S 16.17, found:

% H, 5.14;% N, 21.38;% S, 16.22.

Effectiveness of 1- (2-isobutylthio-6-benzodiazolylaminomethyl) 5-phenyl-1,2,3,4-tetrazole on Heterakis spumosa:

Heterakis spumosa is a model helminth adapted to mice and rats. It serves as a model for intestinal nematodes. It is one of 6 models to test newly synthesized substances. This model is also used in the manufacture of anthelmintics such as Hoechst A. G. and Bayer A. G.

White mice of the SPF strain were experimentally invaded with 100 Heterakis spumosa eggs. On day 42 after experimental invasion, mice were treated with the compound of the invention orally at 150 mg / kg for 3 days. On day 50 p.i., the animals were sacrificed and a helminthological autopsy was performed on the animals and control animals. All 4 treated animals were negative for Heterakis spumosa while the control group was heavily invaded.

The compound of the invention showed 100% efficacy on Heterakis spumosa in the first series of experiments.

Claims (2)

An anti-helminthically active 1- (2-isobutylthio-6-benzothiazolylaminomethyl) 5-phenyl-1,2,3,4-tetrazole of formula I CHj / CH ₃ CH-CH 2 -S (I) N-N nh-ch ^ n ^ 1 2. A process for the preparation of a compound according to claim 1, wherein 2-isobutylthio-6-aminobenzothiazole is reacted with 5-phenyl-1,2,3,4-tetrazole and formaldehyde in a C1 to C3 alcohol medium to which is added at 0 ° C to -10 ^C, water and acetone and, after warming to 35 ° to 40 ° C the mixture was cooled to -20 to -30 ° C ^Q