1-aryl-7-methyl-2-[-(5'-nitro-2'-furyl)vinyl]-pyrido[2,3-d] pyrimidine-4-ones exhibiting antimicrobial activity

 

(57) Abstract:

1-Aryl-7-methyl-2-[-(5'-nitro-2'-furyl)vinyl] -pyrido[2,3-d] -pyrimidine-4-ones of General formula I

< / BR>
where R is CH3THE CO3, VG, possess bacteriostatic activity. table 2.

The claimed compounds are organic chemistry, to the class of pyrido[2,3-d] pyrimidines, namely to new biologically active 1-aryl-7-methyl-2- [- (5'-nitro-2'-furyl)vinyl]-pyrido[2,3-d]pyrimidine-4-Onam formula (I-b),

< / BR>
where Ia R=CH3, IB, R=OCH3, IB, R=Br,

which can find use as a drug of antimicrobials.

The closest structural analogue of the claimed compounds is 1-metalorganic-2,7-dimethyl-1,4-dihydropyrido[2,3-d]pyrimidine-4-one formula

< / BR>
possessing analgesic activity [1] . (Author's certificate. USSR N 1783801).

Known and used in medical practice antimicrobial drugs furatsilin [2] and perfloxacin [3]. (Mokrushina, A., Charushin R. N., Chupakhin, O. N. Chem. Pharm. zhurn., N 9, s 5-19 (1995)), which is taken by us as standards for comparison of antimicrobial action.

The aim of the invention is to obtain new derivatives of 1-aryl-7-methyl-2- [- (5'-nitro-2'-furyl)W reaction-type aldol condensation between the methyl group in the second position of the 1-aryl-2,7-dimethylpyridin[2,3-d] pyrimidine-4-ones, exhibiting acid properties [3], and 5-nitrofurfural when heated in glacial acetic acid.

< / BR>
An example of obtaining the claimed compounds. 1-Aryl-7-methyl-2- [- (5'-nitro-2'-furyl)vinyl] -pyrido[2,3-d] pyrimidine-4-ones (Ia-in). The solution equimolecular quantities (0.01 mol) of 1-aryl-2,7-dimethylpyridin[2,3-d]pyrimidine-4-it 5-nitrofurfural in glacial acetic acid is heated for 10 minutes the precipitation is filtered off and crystallized from acetic acid (table. 1).

The claimed compounds are yellow crystalline substance, soluble in DMF, acetic acid, soluble in alcohols. In IR-spectra (UR-20) there are peaks at 1635 - 1645 (CO) cm-1(suspension in vaseline oil). In the PMR spectra (BS-587 A, 80,023 MHz, Tesla DMSO d6connections are In the singlet methyl group with 2.39 memorial plaques, two doublet of the vinyl protons at 6,45 and 7,97 M. D., multiplet, aromatic protons and two protons furan fragment when 7,21 - 7,82 memorial plaques, two doublet protons of the pyridine cycle when of 8.37 - of 8.47 M. D. PMR Spectra of the other compounds also comply with the existing structure.

Study of antimicrobial activity of the claimed compounds Ia-in was conducted in the Microbiology Department, you in the presence of antimicrobial activity [4, 5]. To define took out a portion of 0.05 g and was dissolved in 5 ml of the corresponding solvent. A dilution of 1:100. Source drug dilution were prepared on mesopatamia broth (BCH) in a dilution of 1: 500 by mixing (1 ml dilution of 1:100 and 4 ml BCH). For experience took a series of test tubes containing 2 ml of the BCH. The method used twofold serial dilutions by transferring 2 ml of liquid from one tube to another. As control was used tubes with the medium without drug. Research conducted in relation to two types of testmicrowave: gram positive - Staphylococcus Staphylococcus and gram - E. coli. For infection used daily agar culture that had washed in isotonic solution of sodium chloride and brought on the optical standard to a concentration of 500 million microbial cells in 1 ml of Standard breeding bred before 5 million microbial cells in 1 ml After exposure tubes were incubated at 37oC. analysis was performed at 18 to 20 h in the presence of bacterial growth (turbidity environment) or in his absence due to the antibacterial action of the drug. Indicator antibacterial activity of chemical compounds is m is Rob in the standard experiment.

Was determined acute toxicity (LD50compounds Ia-in on white mice weighing 22 to 26 g after a single intraperitoneal injection of 2% starch mucus. Eight animals were divided into four groups. Each pair was administered one dose in ascending order. The death of animals were recorded within 1 day. LD50the size of the fluctuations calculated by the Express-method at p = 0.05 [6].

The results are shown in table 2.

Compared the antimicrobial activity against Staphylococcus aureus, Escherichia coli, toxicity LD50the investigated compounds in comparison with perfloxacin [3] and furatsilinom [2].

According to the classification of the toxicity of drugs [6] compounds Ia, practically non-toxic, and IB allatoxin.

As can be seen from table 2 compounds Ia-6.4 times, IB, - 3.2 times more active than perfloxacin and compound Ia - 333 times, IB, - 166 times more active than furatsilin against Staphylococcus aureus. Antimicrobial activity of compounds In more activity perfloxacin 6.4 times that of the compounds I and more active than furatsilin 20, 40 and 640, respectively, in respect of Escherichia coli.

Thus 1-aryl-7-methyl-2- [- (low-toxic.

Therefore, the claimed compounds Ia-in can be used in medicine as an antimicrobial drugs.

Sources of information

1. Author's certificate N 1783801 (USSR) from 22.08.92.

2. Mashkovsky M Doctor of medicine (textbook of pharmacotherapy for doctors), M, "Medicine", So 2, S. 358 1993).

3. Mokrushina, A., Charushin C. R., Chupakhin, O. N. Chem. Pharm. Journe. N 9, s 5 - 19 (1995).

4. Pershin, N. Methods of experimental chemotherapy, M, S. 109 - 111, 546 - 460 (1959).

5. The order of the USSR Ministry of health N 250 from 13.03.75. About the unification of the methods of determining the sensitivity of microorganisms to chemotherapeutic drugs, M. (1975).

6. Izmerov N. P. and other Parameters toxicometric industrial poisons in a single, M, "Medicine", S. 197 (1977).

1-Aryl-7-methyl-2-[-(5'-nitro-2'-furyl)vinyl] -pyrido[2,3-d] pyrimidine-4-ones of General formula I

< / BR>
where I (R = CH3, IB, R = OCH3, IB, R = Br,

with bacteriostatic activity.

 

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