CS276195B6 - 2-Alkylthio-6-maleimidobenzothiazoles and methods for their preparation - Google Patents

Abstract

Previously unknown 2-alkylthio-6-maleinimidobenzothiazoles were prepared, where R is ethyl or n-butyl. The synthesis of the mentioned compounds is carried out by the reaction of the respective 2-alkylthio-Saminobenzothiazoles with a several-fold excess of maleic anhydride in the melt. Compounds that are antibacterially effective against acrobic gram-positive and gram-negative bacteria.

Description

The present invention relates to 2-alkylthio-6-maleimidobenzothiazoles. So far he has been known

6-formalimido-2-n-propylthiobenzothiazole, effective antifungal and antibacterial against anaerobic sporulating bacteria of the genus Clostridium.

We have now found that the compounds of the formula are not yet known

\ -S-B where R is ethyl or n-butyl, are antibacterially active against gram-positive and gram-negative bacteria.

At the same time, a process for the preparation of said compounds based on 6-amino-2-ethylthiobenzothiazole, reap. 6-amino-2-n-butylthiobenzothiazole, characterized in that the corresponding 2-alkylthio-6-aminobenzothiazole is reacted with a 2 to 10-fold excess of maleic anhydride in the melt at 150 to 220 ° C for 5 to 60 minutes.

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

Example 1

Preparation of 2-ethylthio-6-maleimidobenzothiazole? The mixture was melted at 160-175 ° C for 30 minutes. The melt was poured into saturated sodium bicarbonate solution and washed repeatedly with stirring until no more carbon dioxide escaped from the mixture. After washing with water, the product was recrystallized from ethanol: water 3: 1 using the active compound

coal. Pure 2-ethylthio-6-maleimidobenzothiazole was obtained with m.p. 136.0 to 133.0 ° C v amount of 5.9 □ / 40.1% /. Mh = 290.37 For C ₁₃ H _{10 N 2} ° ₂ S ₂ calculated%: C 53.77 H 3.47 N 9.65 S 22.03 found%: 53.89 3.64 9.92 22.43

Example?

Preparation of 2-n-butylthio-6-maleimidobenzothiazole

The preparation was carried out according to Example 1, except that 6-amino-2-n-butylthiobenzothiazole (11.9 g, 0.05 mol) was used. The product was obtained with m.p. 65.0 to 67.0 ° C in an amount of 7.1 g / 44.6 V.

Mh = 310.42 For C ₁₅ H ₁₄ N ₂ 0 ₂ calculated%: found%:

C 56.53

56.29

4.43

4.24

M 3.80 S 20.14

8.55 19.94

Example 3

Antibacterial activity of the compounds according to the invention against aerobic gram-positive and gram-positive substances

The microorganisms were cultured in masopeptane broth under intense seration and at an optimum temperature of 37 ° C and 37 ° C, respectively. 25 ° C. The microorganisms were in constant contact with the compound of the invention, which was added in a concentration I.IÓ ^- ^ 2-10 "\ 4.10 ^- ^ B.IO _and ⁶ moles of di ~ \ dissolved in an amount of dimethylsulfoxide to this does not exceed the

CS 276 195 B6% of the culture medium. The effect was assessed by influencing cell growth and proliferation by photometric measurement of turbidity versus control, at regular time intervals. Growth curves were constructed from the measured values and the values ED ^ g and ΕΟ ^ θθ were obtained mathematically and graphically, which represents the inhibition of growth and cell proliferation to 50 resp. 100%.

Table a / k of example 3

Antihacterial activity of the compounds according to the invention against gram-positive bacteria (MIC, mol dm ^-3 / .mu.g cm ^- · *)

The compound of the example Micrococcus lutcus Staphylococcus aureus Bacillus subtilis 1 2.10 ~ ⁴ 2.ΙΟ “ ⁴ <1.10 ^-3 50.10 58.10 <290.37 2 2.10 ^-4 2.10 ^-4 <1.I0 ^-3 63.60 63.63 <310.42

MIC = the lowest of the concentrations tested which still completely inhibits the growth of the test micro-organisms.

Table b / k of example 3

Antibacterial activity of the compounds according to the invention against gram-negative bacteria (MIC, mol dm ^-3 / yug cm ³ )

The compound of the example Pseudomonas aeruginosa Proteus vulgaris Escherichia coli 1 1.10 ^-3 1.10 ^-3 '> 1.10 ^-3 290.37 290.37 290.37 2 2.10 ^-4 1.10 ^-3 1.10 ^-3 63.68 318.42 313.42

Significantly, the compounds of the invention are of a novel, hitherto unknown structure and have shown antibacterial activity against some of the tested representatives of gram-positive and gram-negative bacteria. Further significant is the fact that the compound of Example 2 is effective at a concentration of 63.60 .mu.g cm- ³ against Pseudomonas aeruginosa, a microorganism which has recently been a pathogen and has low susceptibility to antibiotics.

The compounds of the invention can be used as an active ingredient of antibacterial preparations, or as an intermediate for further syntheses.

Claims (2)

PATENT CLAIMS 2-Alkylthio-6-maleimidobenzothiazoles of the general formula wherein R is style or n-butyl. 2. A process for the preparation of the compounds according to item 1, characterized in that 2-alkylthio-6-aminobenzothiazole, wherein alkyl has the meaning given in item 1, is reacted with a 2 to 10-fold excess of maleic anhydride in the melt at 150 to 220 ° C for 5 up to 60 minutes.