SU1558915A1 - 2-(5ъ-nitrofuryl)-2,3-dihydro-5h-1,3,4-thiaziazolo/2,3-b/-quinazoline-5 showing antimicrobic activity - Google Patents

Abstract

The invention relates to heterocyclic compounds, in particular to 2- (5n-nitrofuryl) -2,3-dihydro-5H-1,3,4-thiadiazolo [2,3-b] quinazolinone 5, which has antimicrobial activity. The goal is the detection of compounds with the indicated activity. The preparation is carried out by the reaction of equimolar amounts of 5-nitrofurfurylidene hydrazide anthranilic acid and potassium rhodanide in the presence of hydrochloric acid. Yield 47.3%. M.p. 147 ° C (decomposition). Gross for-la: C ₁₃ H ₈ N ₄ SO ₄ ^. LD ⁵ ° = 800 Mg / Kg (for intraperitoneal administration). 1 tab.

Description

The invention relates to organic chemistry, namely to 2- (5'-nitrofuryl) -2,3-dihydro-5Ht1,3,4-thiadiazolo [2, 3-bJ-quinazolinone-5 of the formula

About exhibiting high antimicrobial activity, which suggests the possibility of its use in medicine as an antimicrobial drug.

The aim of the invention is the synthesis of 2- (5 ^{f —} nitrofuryl) —2,3 — dihydro — 5H—

1,3,4-thiadiazolo [2,3-b] -quinazolinone5, which has high antimicrobial activity with low toxicity in a series of quinazolinone derivatives.

Example. 2t (5'-Nitrofuryl) -2,3-dihydro-5H-1,3,4-thiadiazolo (2, 3-bJ quinazolinone-5.

0.11 mol of potassium rhodanide is added to a solution of 0.01 mol of anthranilic acid 5-nitrofurfurilidenehydhydrazine in 2 mp hydrochloric acid and 10 ml of ethanol. The reaction mixture is heated in a water bath for 20 minutes, after cooling, 50 ml of water are added, the precipitate formed is filtered off, dried, and recrystallized from alcohol. Yield 47.3%, mp.

Found,%: С C, ₃ H _S H ₄ SO ₄ .

Calculated,%:

IR spectrum, cm ^-1 (liquid paraffin): 3400, 1600, 1480, 1348, 1293, 1250, 1143.

The compound of the proposed formula is a crystalline

SU, 1558915

a brown-brown substance, insoluble in water, slightly soluble in ethanol, well soluble in dimethyl sulfoxide, mineral acids. L ·

Acute toxicity of LD _{5 <>} (mg / kg)! the proposed compounds are determined by the method of G.N. The peak when administered intraperitoneally to white mice weighing 16-20 g in the form of suspension in 2% starch mucus "

To determine the bacteriostatic activity, the test substance is dissolved in ethanol 1: 100 and diluted with meat. Peptone broth (MPB) 15 to a ratio of 1: 500. Escherichia coli, capsule-forming and spore-forming cultures ”. At the same time, a daily culture flush grown on meat and peptone jarape using a sterile physiological 25 solution of sodium chloride is used and prepared using direct dilution with a concentration of 500 million "microbial bodies in 1 ml of washout. The resulting mixture was diluted with sterile BCH 100 times. ”This is a dilution of a bacterial culture with a concentration of 5 min. . Thus, the bacterial load per 1 ml of liquid is 250,000 microbial bodies. After 18-20 hours (36-37 ° C), the presence or absence of growth of bacterial cultures due to the bacteriostatic effect of the drug is recorded.

The current dose is taken as the minimum inhibitory concentration (MIC) of the drug in μg / ml, which inhibits the growth of bacterial cultures, i

The research results are presented in the table.

As can be seen from the table, the proposed compound exhibits high antimicrobial activity in relation to the reference strains of Staphi aureus: gcocca at a dilution of 1: 256000, which cc is 3.9 μg / mp and a spore-forming culture at a dilution of 1: 2 million, which is 0 5 µg / ml, exceeding the drug furatsilin by this indicator. So, in relation to Staphylococcus aureus, the proposed compound is 64 times superior to the known one, and 4 times superior in toxicity.

Thus, the proposed compound has a pronounced antimicrobial effect in relation to the reference strains ’Staphylococcus aureus and spore-bearing cultures (you. Antracoides and you. Fridlend), superior in this indicator to the drug furatsilin, with low toxicity of the compound.

Claims (2)

Claim 2- (5’-Nitrofuryl) -2,3-dihydro ~ 5H1,3; 4-thiadiazolo (2,3-b] -quinazolinone-5 of the formula _ exhibiting antimicrobial activity. Compound The minimum inhibitory concentration, mcg / ml Staphy- Escherilococ. chia coli aereus You. Fridlen dera Acute toxicity of LD _Co , mg / kg You. antracoides Furatsilin 125 125 0.5 800 (740.7-864.0) 125 220 (180 - 268.0)