SU1135150A1 - O-acyl derivatives of treo-dl-phenylserine displaying antivira activity - Google Patents

Abstract

0-acyl derivatives of threo-DL-phenyl-serine of the general formula CO (CHg) pSN, I ABOUT .1 (CbH3-C-C-COOCgHz H NHaHCl where, possessing anti-viral S activity against the influenza A2 virus ..

Description

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The invention relates to new chemical compounds, namely, to derivatives of phenylserine, specifically to the hydrochlorides of ethyl esters 0-octanoyl Tpeo-DL-phenylserine and 0-decanoyl-threfDL-phenylserine. /.

Known ethyl hydrochloride efI jya O-miristoyl-threo-Bb-phenylserine

CO (CHJ, 2CH3

ION

iI:

1 iCgHj-C-C-COOCgHs

: H NHgHCl

which is a structural analogue of the described compounds and has fungicidal activity. However, it has an antiviral effect. DL-phenylrerin of the formula SeNSSUNSYUNSUNSHG is known to have an antiviral activity that, at a concentration of 200 µg / mp, delays the replication of the Li strain of the influenza virus in tissue culture only up to 25% of the control. Structural analogues of O-acyl p derivatives of Tpeo-DL-phenylserine, which possess antiviral activity against the influenza A2 virus, were not detected in chicken embryos. Antiviral agents are known, such as rimantadine. However, this drug delays the reproduction of the influenza A2 virus in large doses. The aim of the invention is to identify new derivatives in the range of phenylsin, which show high activity against the influenza A2 virus in small doses. The goal is achieved by 0-acyl derivatives of Tpeo-DL-phenylserine of formula I with (cn,) cn, I I-i CbH3-C-C-COOC-rH. II 5 /. H NHj-HCl (I), (II). These compounds are obtained by condensation of capric acid or capric acid chlorides, respectively, with Tpeo-DL-phenylserine ethyl ester hydrochloride in anhydrous trifluoroacetic acid medium. -.... Example. : To a solution of 2.46 g (10 mmol) of threo-DL-phenylserine ethyl ester hydrochloride in 4 ml of absolute trifluoroacetic acid, 11 mmol of alkanecarboxylic acid hydride was added with stirring. The reaction mixture is left at room temperature for 40 minutes, then 3 ml of absolute ethanol is added, and the product is added with the addition of hexane. The reaction product is recrystallized from a mixture of ethyl alcohol and hexane. The powdered Tpeo-DL-phenyl-serine derivatives O-octapoyl-threo-Bb-phenylserine ethyl ester hydrochloride and O-decanone-threo-Bb-phenylserine (II) ethyl ester hydrochloride, are white crystals, which are not soluble in hexane, petrol, II, I, in the case of white hexanes, in the case of the hexane, in petrol, petrol, II, etc., are white crystals, not soluble in hexane, in the case of petrol, II, I, in the case of hexane, in the case of white petrol, II, in the case of the hexane, in the petrol-petrolsin (II), are white crystals, not soluble in the hexane, in the case of petrol, II, I, in the case of the hexane, in the case of the white petrol, II, in the case of the hexane, in the petrol-petrol-II (II), they are white crystals, non-soluble in the hexane; soluble in water, soluble in alcohol, chloroform, dimethylformamide, IR spectrum (in tablets with KBG on a Specord 71 IR instrument): CO fluctuations at 1745 1755 for compound (I), 1740 for 1755 for compound (II). PMR spectra (in trifluoroacetic acid, on a Hitachi R-22 instrument with an operating frequency of 90 MHz, internal standard — HMDS, scale, ppm) are given in Table 1. Outputs, melting points, gross formulas and microanalysis data synthesized The compounds are listed in Table 2, - The activity of the compounds of ethyl ethyl ester 0-9ctanoyl-threo-Bb-phenylserine (I) and ethyl ester hydrochloride O-decanoyl-threo-Bb-phenylserine (II) is determined for viruses RNA-containing vesicular stomatitis, A2 flu, Coxsack A13 and A21J, and DNA adenovirus type 23 but. Compounds I and II possess antiviral activity only against influenza A2 virus. The results of testing compounds for antiviral activity as compared to etalomeremantadine are given in Table 3. The determination of antiviral activity for the influenza A2 virus was carried out on chicken embryos according to the method described by P.V. Lidina et al. As a test virus, the virus strain was used Influenza A2 - Victory (35) 72-NZ # 2, obtained from the Le Shngrad Research Institute of Influenza of the Ministry of Health of the USSR. As a control compound that delays the reproduction of the influenza A2 virus, use remantadine, which is administered at a dose of 2.5 mg / embryo simultaneously with the 100 AUD of the influenza A2 virus; in this case, a complete (100%) reproduction delay of the named test virus is observed. Determination of toxicity is carried out in cell culture FEC. To nutritional

Claims (1)

0-acyl derivatives of threo-Phenylserine of the general formula C0 (CH ₂ ) _p CH _l ' he I g С ₆ Н _Л -С-С ~ С00С _г Н ₅ Η ΝΗ ₂ · ΗίΙ where n = 6, n = o, possessing anti-viral activity against the virus ^: influenza A2, -5 and ... 1135150