CS242017B1 - 6-(2-chlorobenzoylamino)-2-benzothiazolintione - Google Patents

Abstract

To date unknown 6- (2-chlorobenzoylamino) -2-benzothiazolinothione of formula The compound is produced by acylation of the 6-amino- 2-benzothiazolinothione with 2-chlorobenzoyl chloride in pyridine. The compound of the invention is antimycobacterial effective against typical and atypical tuberculous mycobacteria and is also an intermediate for further syntheses

Description

The present invention provides 6- (2-chlorobenzoylamino) -2-benzothiazolinothione of the formula

Only the 6-benzoylamino-2-benzothiazolinothionone analog was prepared previously (Kuznecova, E.A., Zuravlev, S.V. and Stepanova, T.N., Chim. Geterocikl. Sojed., 1967, 261; Sido, E., Cs. AO 231 606).

We have now found that the hitherto unknown compound, 6- (2-chlorobenzoylamino) -2-benzothiazolinothionone, is antimycobacterially active against typical tuberculous mycobacteria (M.) tuberculosis H37R _v , as well as against atypical tuberculous mycobacteria and M. avannsobacteria M. avanns.

In addition, the compound of the invention is used as an intermediate in the synthesis of antimycothoacterially active compounds.

At the same time, a process for the preparation of said compound based on 6-amino-2-benzothiazolinothionone [also referred to in the literature as 6-amino-2-mercaptobenzothiazole as its tautomeric form; Blockinger, G. and Sutorls, V., Cs. No. 168,746 (1975)], which is characterized in that the acylation is carried out with 2-chlorobenzoyl chloride in pyridine.

The following examples illustrate but do not limit the preparation, properties, and uses of the compounds of the invention.

Example 1

Preparation of 6- [2-chlorobenzoylamino) -2-benzothiazolinothione

To a suspension of 6-amino-2-benzothiazolinothione (45.5 g, 0.25 mmol) in pyridine (25 mL) dried over potassium hydroxide was added 2-chlorobenzoic acid chloride (43.8 g, 0.25 mol). The reaction mixture was heated to reflux for 10 minutes, then poured into ice, made up to 1000 ml with water and acidified to pH 4-5 with hydrochloric acid. After solidification, the reaction product was aspirated, suspended in 800 ml of water. 50-60 ° C warm, acidified hydrochloric acid to pH 4-5, aspirated and washed with water, yield 77.0 g (96.0%).

For analysis, the material was purified by crystallization from acetone using activated carbon. Pure 6- (2-chlorobenzoylamino) -2-benzothiazolinethione was obtained as a crystalline solid, m.p. 249-250.5 ° C.

M. h: 320.82

For C14H9CIN2OS2 calculated%:

C 52.41, H 2.83, N 8.73, S 19.99, Cl 11.05 Found%:

H, 2.73; N, 8.55; S, 20.04; Cl, 11.00

Example 2

The antimycobacterial activity of the compound of the invention compared to that of the known antituberculotics

Compound 1 MIC vs. Mycobacterium tbc. Kansasii avium fortuitum

H37R _in PKG 8 80/72 1003

Compound of the Invention 10 25 10 100

Isoniazid (INH) 0.5 25 50 50

Ethionamide (ETA) 1 25 50 100

MiC = minimum inhibitory concentration in µg / µl

Antimycobacterial efficacy against tuberculous mycobacteria was monitored in liquid Sulla under the dilution test. Dimethyl sulfoxide was used as solvent. The final concentration of the substances in the pod was 1, 5, 10, 25, 50 and 100 µg / ml. Example 3

Use of the compound of Example 1

The compound of Example 1 is an intermediate in the synthesis of the anti-mycobacterially highly active 2-allylthio-6- (2-chlorobenzoylamino) benzothiazoil, which is prepared therefrom by alkylating its potassium salt as well as other anti-mycobacterially active compounds.

Significantly, the compound of the invention, by its activity against atypical tuberculous mycobacteria of M. avium at a concentration of 10 µg / ml, is 5-fold higher than the most well-known established preparations [Izoniazid and Etionamide] and an efficacy at 25 µg / ml against M. kansasii. im balancing. At the same time, it exhibits high efficacy at a concentration of 10 µg / ml also against typical tuberculous mycobacteria M. tuberculosis H37R _{in the} compound of the invention can be used as an active ingredient of antimycobacterial agents, or as an intermediate for further syntheses.

Claims (2)

SUBJECT 1. 6- (2-Chlorobenzoylamino) -2-benzothiazolinothione of the formula INVENTION 2. A process for the preparation of a compound according to Claim 1, which comprises reacting 6-amino-2-benzothiazolinothione with 2-chlorobenzoyl chloride in pyridine.