CS239438B1 - 2-alyftio-benzoylamino-672 / benzothiazole - Google Patents

Abstract

The previously unknown 2-allylthio-6-(2-chlorobenzylamine)-2-mercaptobenzenethiol of the formula is prepared by alkylation of the potassium salt of 6-(2-chlorobenzylamine)-2-mercaptobenzenethiol with allyl bromide. The compound of the invention is antimycobacterially effective against tuberculosis mycobacteria, especially against atypical strains of M. fertuitum, M. avium and M. canasli; it can be used as an effective component of antimycobacterial preparations or as an intermediate for further syntheses.

Description

(54) 2-Allyphthio-672-chlorobenzoylamino / benzothiazole

So far unknown 2-allythio-6- (2-chlorobenzylaminobenzetiassl)

The compound is prepared by alkylating potassium sele of 6- (2-chloro-benzylamine) -2-mercaptebensetlazel with allyl bromide. The compound of the invention is antimycobacterially active against tuberculous mycebactaria, in particular the atypical strain of M. fertuitum,

11. avium and M. kanaasli; Use it as an effective blend of entimycebecterial preparations or as a medsipreduct for other syntheses.

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The present invention provides 2-allylthio-6- (2-chlorobenzoyl) benzothiazole. Non-chlorinated analogue of the compound of the invention, 2-slythio-4-benzoylominobenzothiazole (Sidrf, a and Odler, 2nd, ref. AO 225015 (1983)), as well as the starting material for eynthase, 6- (2-chlorobenzoylamino) -2- benzothiazolinone (Sldó, X. and Odlar, 2nd, Fac. AO PV 4606-84) are antimycobacterially active. *

The compound of the formula is not yet known

CO — NH Cl

is active against the typical · tuberculous · mycobacteria Uycobacterlum (M.) tuborculosis ^H 37 ^H v> ^and 3 against atypical teburculo-mycobacteria II. Kansasii, II. avlum and M. fortuitum

At the same time, a process for the preparation of said compound based on 6- (2-chlorobenzoylamino) -2-benzothiasolinethione was found. The reaction is carried out by alkylation of potassium aol of 6- (2-chlorobenzoylamino) -2-mercaptobenzotlazole, resulting in the dissolution of 6- (2-chlorobenzoylamino) -2-benzothiasolinethione in a potassium hydroxide solution, allylbrould in a 5: 1 ethanol / water mixture. boil for 5 to 15 minutes.

The following examples illustrate, but do not limit, the preparation of a compound of the invention.

EXAMPLE

Preparation of 2-allylthio-6- (2-chloro-yoylamino) -bensothiazole

6- (2-Chlorobenzoylaaino) -2-benzotlasolinethion (9.6 g, 0.030 mol) and dissolved in boiling in a solution of potassium hydroxide (2.0 g, 0.036 mol) in a mixture of water (20 ml) and ethanol (100 ml) . To the reaction mixture was added allyl bromide (3.65 g, 0.030 mol) and the mixture was kept at reflux for 0 minutes, then decolorized with activated charcoal and filtered through a funnel. After cooling to 5 ° C, crystalline 2-allyltlo-6- (2-chlorobenzoylamino) benzothiazole of m.p. t. 115.5-117.5 ° C in an amount of 6.7 g. Concentration of the mother liquor reduced the pressure without heating to give a salt of 1.6 g of the same quality product. The total yield of the substance according to the invention was 8.3 g (76.9%).

For analysis, the material was purified by crystallization with ethanol: water (4: 1, v / v) using charcoal. Pure 2-allyl-6- (2-chloro-benzoylamino) -benzothiazole was obtained as a yellowish-bioloy crystals of m.p. 117.5-119.5 ° C.

M. h: 360.89

For C ₇ H ₁₃ C1N ₂ OS ₂ calculated: 56.58 »C, 3.63% H, 9.82% C, 7.76% N Found: 56.37 * 0, 3.57 H, 9.86 * Cl, 7.66 * N,

17,77 «S 17,80» S.

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Example 1 a d 2

The antimycobacterial activity of a compound of the invention in comparison and efficacy of known antituberculosis agents

substance MIC vs. Mycobaeterlum tbc. «37 ^H v kansasii PKO 8 avium 80/72 fortuitum 1021 A compound of the invention 10 25 25 10 Isoniazid (INH) 0.5 25 50 50 Ethionamide (ETA) 1 25 50 100

MIC * minimum inhibitory concentration in µg / ml

The anti-mycobacterial activity against tuberculous mycobacteria was monitored in liquid granules by dilution teeters. Dimethylsulfoxide was used as solvent.

The final concentration of the substances in the oil was 0.25, 0.5, 1, 5, 10, 25, 50 and 100 µg / ml.

Significantly, the compound of the invention outweighs the known antituberculotics (Isoniazid 5-fold and Etionamide 10-fold) by its activity against atypical tuberculous mycobacteria M. fortuitum, while being twice as potent against M.avium as said antituberculotics. At the same time, the compound of the invention is comparable to known antituberculotics (Izoniazide and Etionamide) against M. kanaas11 and is highly active at a concentration of 10 µg / ml and also against typical tuberculous mycobacteria M. tuberculoals H RR ^.

The compound of the invention may be used as an active ingredient of antimycobacterial preparations or as an intermediate for further synthesis.

Claims (2)

OBJECT OF THE INVENTION 1. 2-Allythio-6- (2-chlorobenzoylamino) benzothiazole of the formula Ct '- ^H XX> - ^s - ^ch ' - ^ch - ^ch > 2. A process for the preparation of a compound according to item 1, which comprises reacting the potassium salt of 6- (2-chlorobenzoylamino) -2-mercaptobenzothiazole with allyl bromide in an ethanol-water mixture (5: 1 by volume) at boiling point.