3-phenyl-6-r1-7-r2-1,2,4-benzotriaxines with antiviral activity

FIELD: bioactive compounds.

SUBSTANCE: invention relates to new 3-phenyl-1,2,4-benzotriazines and their derivatives of general formula 1

wherein R1 and R2 are independently fluorine or C1-C4-alkoxy, optionally substituted with halogen or tetrahydrofuryl. Compounds of present invention are useful in treatment and prophylaxis of diseases, induced by pathogenic for human and animals viruses including pathogenic for human orthopoxviruses, as well as postvaccinal sequelae.

EFFECT: compounds with improved antiviral activity.

1 cl, 12 ex, 7 tbl

 

The technical field

The invention relates to the field of biologically active compounds, the development of a new 3-phenyl-1,2,4-benzotriazine and their derivatives, and is intended for the treatment and prevention of diseases caused by pathogenic for human and animal viruses, including orthopoxviruses pathogenic for humans, as well as vaccine-related complications.

The problem of development of antiviral drugs is valid for the entire period of existence of mankind. Among viral infections are the causative agents of especially dangerous viral infections, as the variola virus that causes severe disease in humans with a mortality of up to 40-60%. In addition, this virus is of particular interest as it is one of the most likely agents for use in bioterroristic purposes. The most effective way to prevent smallpox is vaccination with the use of vaccinia virus, however, mass vaccination may cause a significant amount of post-vaccination complications. In addition, the nature of circulating smallpox of the cow, which is able to cause disease in humans. In addition, in Equatorial Africa in recent years among the General population there are Monkeypox outbreak with mortality up to 10-20%. Thus, the need is IMO highly effective antiviral drugs who would have had high activity, low toxicity and prolonged activity against orthopoxviruses pathogenic for humans.

Prior art

Existing drug methisazone (Marboran®) has only preventive activity, but not curative activity against variola virus. The drug cidofovir (Vistide®) is currently under investigation as a preventive or therapeutic drug, but his research is not finished. In the pharmaceutical market at present, virtually no drugs, active against viruses group of smallpox, in this regard, the development of such substances can be an important step in providing pharmacological safety of people's lives.

Known data on the biological activity of derivatives of 1,2,4-benzotriazine (J.G.Erickson, P.F.Wiley and V.P.Wystrach. The 1,2,3 - and 1,2,4-Triazines, Tetrazines and Pentazines, Interscience Publishers, Inc., New York, N.Y. 1956, p.44) [1]. It is known that 3-amino-7-chloro-1,2,4-benzotriazine 1-oxide possesses antimalarial activity (J.K.Horner, D.W.Henry. Analogs of 3-Amino-7-chloro-1,2,4-benzotriazine 1-Oxide as Antimalarial Agents. J.Medicinal Chemistry, 1968, 11, p.946-949) [2]. 3-Amino-1,2,4-benzotriazine 1,4-dioxide (Tirazone®, tirapazamine, "Tirapazamine") is an effective antineoplastic drug (..Zeman, J.M.Brown, M.J.Lemmon, V.K.Hirst and W.W.Lee. SR-4233: a new bioreductive agent with high selective toxicity for hypoxic mammalian cells. Int J Radiat Oncol Biol Phys. 1986 Jul; 12(7): 1239-42) [3]. PI is IDO[3,4-e]-1,2,4-triazine possess antibacterial activity (Reich, Marvin F.; Fabio, Paul F.; Lee, Ving J.; Kuck, Nydia A.; Testa, Ray T. Pyrido[3,4-e]-l,2,4-triazines and related heterocycles as potential antifungal agents. J.Medicinal Chemistry, 1989, 32(11), R-2485) [4].

However, the above compounds [1-4] do not possess antiviral activity.

Known for a number of triazine derivatives having antiviral activity: derivatives of 1,3,5-triazine, having activity against viral hepatitis a (international application (WO) No. 96/04914, IPC a 61 K 31/53, publ. 22.02.96) [5]; triazine derivatives having activity against retroviruses (Japan's Bid No. 6016561, IPC And 61 To 31/655, publ. 25.01.94,) [6]; derivatives of 1,3,5-triazine with activity against hepatitis b virus (U.S. Patent No. 6335339, IPC a 61 K 31/53, publ. 01.01.2002) [7].

However, these compounds have no information that they possess activity against orthopoxviruses pathogenic for humans, and these compounds do not possess property to eliminate vaccine-related complications.

The closest chemical compound - the prototype is the connection 1,2,4-benzotriazin-3-Amin-1,4-dioxide with antitumor activity (international application (WO) No. 97/11699, IPC a 61 K 31/53, publ. 03.04.1997) [8].

However, this connection does not have antiviral activity, particularly against orthopoxviruses pathogenic for humans.

Disclosure of inventions

The technical result of the invention one is to find new chemical compounds based on 1,2,4-benzotriazines, having antiviral activity, in particular against orthopoxviruses pathogenic for humans.

This technical result is achieved by the fact that according to the invention proposed new compound 3-phenyl-6-R1-7-R2-1,2,4-benzotriazine possessing antiviral activity and having the General formula (1)

where R1and R2- independently of one another denote a fluorine atom or a C1-C4-alkoxygroup, unsubstituted or substituted by halogen or tetrahydropyrazolo.

3-Phenyl-6-R1-7-R2-1,2,4-benzotriazine General formula (1) (R2- fluorine, R1- C1-C4-alkoxygroup, the remains of 2,2,2-triptoreline or tetrahydrofurfuryl alcohol) is produced by cyclization of the corresponding 1,3,5-triphenylmethanol in a mixture of acetic and sulfuric acids. In addition, 3-phenyl-6-R1-7-R2-1,2,4-benzotriazine General formula (1) (R1and R2- C1-C4-alkoxygroup) can be obtained from 3-phenyl-6-R1-7-fluoro-1,2,4-benzotriazine reaction with sodium alcoholate in an environment corresponding alcohol (scheme 1).

Scheme 1

Below are examples of the synthesis of the claimed compounds.

Example 1.

3-Phenyl-6-ethoxy-7-fluoro-1,2,4-benzotriazin (SK-29)

1-(4-ethoxy-3-forfinal)for 3,5-diphenyltriazene (10 mmol) of restore and 35 ml of acetic acid, was cooled to 0°and slowly added 10 ml of sulfuric acid. The reaction mass was heated for 10 minutes in a boiling water bath, watched the changing of the color from purple to dark brown. The reaction mass was cooled to 0°and poured into ice-cold water (50 ml). The precipitation was filtered, washed with ice water, dried and recrystallized from ethanol or a mixture of ethanol: chloroform (2:1).

Yield 55%. So pl. 164-165°C. Found, %: C 67.13, H 4.46, N 15.67. C15H12FN3O. Calculated, %: C 66.90, H 4.49, N 15.61.1H NMR in DMSO-d6that δ, ppm (JHF): 1.54 (t, 3H,), 4.42 (q, 2H,), 7.51-7.59, 8.59-at 8.62 (m, 5H, C6H5), 8.18 (d, 1H, H-8,3JHF= 10.3 Hz), at 8.62 (d, 1H, H-5,4jHF= 7.3 Hz).

Example 2.

3-Phenyl-6-methoxy-7-fluoro-1,2,4-benzotriazin (SK-277)

Is obtained analogously from 1-(4-methoxy-3-forfinal)for 3,5-diphenyltriazene. Yield 80%. So pl. 194-195°C. Found, %: C 65.84, H 3.91, N 16.71. With14H10FN3O. Calculated, %: C at 65.88, H 3.92, N 16.47.1H NMR in DMSO-d6that δ, ppm (JHF): 4.14 (s, 3H, CH3O), 7.59-7.62, 8.57-8.61 (m, 5H, C6H5), 8.27 (d, 1H, H-8,3jHF=10.9 Hz), 8.59 (d, 1H, H-5,4jHF=6.8 Hz).

Example 3.

3-Phenyl-6,7-dimethoxy-1,2,4-benzotriazin (SK-278).

Dissolved 0.24 g (10 mmol) of sodium metal in 70-80 ml of absolute methyl alcohol, to the resulting solution add the Yali 3-phenyl-6-methoxy-7-fluoro-1,2,4-benzotriazine (10 mmol), the reaction mass was heated on a water bath until complete dissolution of the precipitate (15-20 min). Then the reaction mass was left for 10-12 h at 20-25°S, sediment NaF was filtered. The solvent was evaporated in vacuum, the precipitate was filtered, washed on the filter with ice-cold water, dried and recrystallized from alcohol. Yield 40%. So pl. 203-204°C. Found,%: C 67.35, H 4.91, N 15.62. C15H13N3O2. Calculated, %: C 67.42, H 4.87, N, 15.37.1H NMR in DMSO-d6that δ, ppm: 4.07 (s, 6H, 2CH3Oh), 7.55-7.59, 8.55-8.59 (m, 5H, C6H5), 7.35 (s, 1H, H-8), 7.72 (s, 1H, H-5).

Example 4.

3-Phenyl-6-propoxy-7-fluoro-1,2,4-benzotriazin (SK-279).

Is obtained analogously from 1-(4-propoxy-3-forfinal)for 3,5-diphenyltriazene. Yield 40%. So pl. 128-129°C. Found, %: C 67.91, H 5.06, N 14.81. C16H14FN3O. Calculated, %: C 67.84, H 4.95, N 14.84.1H NMR in DMSO-d6that δ, ppm (JHF): 1.10 (t, 3H,), 1.93 (q, 2H,), 4.31 (q, 2H,), 7.55-7.60, 8.59-8.61 (m, 5H, C6H5), 8.22 (d, 1H, H-8,3jHF= 10.5 Hz), 8.61 (d, 1H, H-5,4jHF=7.3 Hz).

Example 5.

3-Phenyl-6-butoxy-7-fluoro-1,2,4-benzotriazin (SK-280).

Is obtained analogously from 1-(4-butoxy-3-forfinal)for 3,5-diphenyltriazene. Yield 65%. So pl. 124-125°C. Found, %: C 68.70, H 5.43, N 14.16. C17H16FN3O. Calculated, %: C 68.69, H 5.39, N 14.14.1H NMR in DMSO-d6that δ, pm, (JHF): 1.03 (t, 3H,), 1.57 (q, 2H,), 1.89 (q, 2H,), 4.35 (q, 2H,), 7.57-7.61, 8.59-at 8.62 (m, 5H, C6H5), 8.20 (d, 1H, H-8,3jHF=10.4 Hz), 8.61 (d, 1H, H-5,4JHF= 7.5 Hz).

Example 6.

3-Phenyl-6,7-diethoxy-1,2,4-benzotriazin (SK-281).

Is obtained analogously from 3-phenyl-6-ethoxy-7-fluoro-1,2,4-benzotriazine and ethyl alcohol. Yield 85%. So pl. 195-196°C. Found, %: C 69.17, H 5.74, N, 14.33. With17H17N3About2. Calculated, %: C 69.15, H 5.76, N 14.24.1H NMR in DMSO-d6that δ, ppm: 1.54 (m, 6N,), 4.08 (q, 4H,), 7.52-7.57, 8.57-8.59 (M, 5H, C6H5), 7.30 (s, 1H), 7.67 (s, 1H, H-5).

Example 7.

3-Phenyl-6-ethoxy-7-methoxy-1,2,4-benzotriazin (SK-282).

Is obtained analogously from 3-phenyl-6-ethoxy-7-fluoro-1,2,4-benzotriazine and methyl alcohol. Yield 70%. So pl. 184-185°C. Found, %: C 68.02, H 5.29, N at 14.88. With16H15N3O2. Calculated, %: C 68.33, H 5.34, N 14.95.1H NMR in DMSO-d6that δ, ppm: 1.53 (t, 3H,), 4.08 (s, 3H, CH3O), 4.34 (q, 2H,), 7.53-7.58, 8.57-8.59 (m, 5H, C6H3), 7.31 (s, 1H, H-8), 7.72 (s, 1H, H-5).

Example 8.

3-Phenyl-6,7-debtor-1,2,4-benzotriazin (SK-300).

1-(3,4-differenl)for 3,5-diphenyltriazene (2, R2=F) (10 mmol) was dissolved in 35 ml of acetic acid, cooled to 0&#HWS and slowly added 10 ml of sulfuric acid. The reaction mass was heated for 10 minutes in a boiling water bath, watched the changing of the color from purple to dark brown. The reaction mass was cooled to 0°and poured into ice-cold water (50 ml). The precipitation was filtered, washed with ice water, dried and recrystallized from ethanol or a mixture of ethanol: chloroform (2:1).

Yield 70%. So pl. 126°C. Found, %: C 64.18, H 2.57, N 17.14. C13H7F2N3. Calculated, %: C 64.20, H 2.88, N 17.28.1H NMR in DMSO-d6that δ, ppm: (JHF): 7.59-7.64, 8.67-8.71 (m, 5H, C6H3), [8.55 (dd, 1H), 8.70 (dd, 1H), H-8, H-5].

Example 9.

3-Phenyl-6-butoxy-7-ethoxy-1,2,4-benzotriazin (SK-301).

Is obtained analogously from 3-phenyl-6-butoxy-7-fluoro-1,2,4-benzotriazine and ethyl alcohol. A yield of 75%. So pl. 138-139°C. Found, %: C 70.51, H 6.48, N 12.94. C19H21N3O2. Calculated, %: C 70.59, H 6.50, N 13.00.1H NMR in DMSO-d6that δ, ppm: 0.98 (t, 3H,), 1.46 (t, 3H,), 1.51 (q, 2H,), 1.82 (q, 2H,), 4.33 (q, 4H,),), 7.59-7.64, 8.56-8.59 (m, 5H, C6H5), 7.41 (s, 1H, H-8), 7.75 (s, 1H, H-5).

Example 10.

3-Phenyl-6-(2-tetrahydrofuryl)methoxy-7-fluoro-1,2,4-benzotriazin (SK-302).

Is obtained analogously from 1-[4-(2-tetrahydrofuryl)methoxy-3-forfinal]for 3,5-diphenyltriazene. Yield 65%. TPL 83-84°C. Found, %: C 66.29, H 4.90, N 12.98. C18H16FN3O2. Calculated, %: C 66.46, H 4.92, N, 12.92.1H NMR in DMSO-d6, 5, ppm (JHP): [1.80-2.20 (m, 4H), 3.70-3.90 (m, 2H), 4.33-4.38 (m, 1H), tetrahydrofuran], 4.30 (q, 2H,), 7.63-7.65, 8.60-8.63 (m, 5H, C6H3), 7.64 (d, 1H, H-5,4JHP= 8.2 Hz), 8.24 (d, 1H, H-8,3JHP=10.4 Hz).

Example 11.

3-Phenyl-6-(2,2,2-Cryptor)ethoxy-7-fluoro-1,2,4-benzotriazin (SK-303).

Is obtained analogously from 1-(4-triptoreline-3-forfinal)for 3,5-diphenyltriazene. A 30%yield. So pl. 150-151°C. Found, %: C 55.68, H 2.69, N, 13.07. With15H9F4N3O. Calculated, %: C 55.73, H 2.79, N 13.00.1H NMR in DMSO-d6, 5, ppm (JHP): 5.26 (q, 2H,), 7.64-7.67, 8.61-8.63 (m, 5H, C6H3), 7.93 (d, 1H, H-54JHP=8.3 Hz), 8.52 (d, 1H, H-8,3JHP=10.6 Hz).

Example 12. The antiviral activity of the claimed compounds

To assess the antiviral activity of the claimed compounds obtained according to examples 1-11, used the following method. The culture of Vero cells or LLC MK-2 were grown in the wells of flat-bottomed 96-well plates. In culture medium were added in serial dilution of the compounds under study and the corresponding virus. After incubation for 3-5 days monolayer cells were progressively the vital dye neutral red, after removal of the of rasites and wash excess dye was made lyse solution and the amount of dye, included in the monolayer of cells was taken into account on the spectrophotometer at a wavelength of 490 nm. As controls were used wells, in which the virus did not (control of toxic compounds), which brought the virus without connections (control virus) and the wells, which were not made no virus, no connection (control cell culture). This methodology is based on the ability of test compounds to prevent the reproduction of the virus and its spread from cell to cell, and therefore the cells do not die and retain the ability to englobe neutral red.

As the study of viruses used the variola virus strains of variola major (mortality up to 30-40%) of different geographical origin India (India), 6-58 (Pakistan), Congo-9 (Africa), and strain Butler variola minor (mortality 1-2%). From other pathogenic for humans strains used smallpox cows (strain, Grisak) and Monkeypox virus (strain Zair 599). In addition, used the vaccinia virus, strain LIVP used for vaccination. In addition to orthopoxviruses pathogenic for humans to assess antiviral activity used virus ectromelia (virus of mice), the strain-To-1.

Table 1
Antiviral activity of the compounds of the For-29 against variola virus in cell culture Vero:
The virus strainCytotoxic activity, 50%, mg/mlAntiviral activity, 50%, mg/mlThe selectivity index of
India 3A>3003,28>91
6-58>3004,76>63
Congo-9>3001,36>220
Butler>3002,90>103
Table 2
Antiviral activity of compounds SC-29 against smallpox cows on the culture of Vero cells:
The virus strainCytotoxic activity, 50%, mg/mlAntiviral activity, 50%, mg/mlThe selectivity index of
Grisak>3002,23>134

Table 3
Antiviral activity of compounds SC-29 in respect of Monkeypox virus in cell culture Vero:
The virus strainCytotoxic activity, 50%, mg/ml Antiviral activity, 50%, mg/mlThe selectivity index of
Zaire 599>3003,23>92
Table 4
Antiviral activity of compounds SC-29 against vaccinia virus in cell culture Vero:
The virus strainCytotoxic activity, 50%, mg/mlAntiviral activity, 50%, mg/mlThe selectivity index of
LIIT>3000,50>600
Table 5
Antiviral activity of compounds SC-29 in respect of the virus ectromelia on the culture of Vero cells:
The virus strainCytotoxic activity, 50%, mg/mlAntiviral activity, 50%, mg/mlThe selectivity index of
K-1>3000,49>600

Table 6
Antiviral activity of derivatives SC-29 in respect of Monkeypox virus in cell culture Vero
ConnectionCytotoxic activity, 50%, mg/ml Antiviral activity, 50%, mg/mlThe selectivity index of
SC-277>1000,50>200
SC-278>1003,130
SC-279>1001,1100
SC-280>10026,44
SC-281>1001001
SC-282>100no0
SC-300the 13.4no0
SC-301>100no0
SC-3025,020,4810
SC-30328,80,4465

Table 7
Antiviral activity of derivatives SC-29 against vaccinia virus in cell culture Vero:
ConnectionCytotoxic activity, 50%, mg/mlAntiviral activity, 50%, mg/mlThe selectivity index of
SC-277>1000,39250
SC-278 >10011,358,8
SC-279>1001,7457
SC-280>10022,484
SC-281>10025,604
SC-282>100no0
SC-30013,93no0
SC-301>100no0
SC-30216,260,4735
SC-3033,50,418,5

Analysis table 1-7 shows that the proposed new chemical compounds on the basis of 1,2,4-benzotriazine possess antiviral activity, particularly against orthopoxviruses pathogenic for humans.

Industrial applicability

The invention can be used in medicine and veterinary, medical institutions, research laboratories.

3-Phenyl-6-R1-7-R2-1,2,4-benzotriazine possessing antiviral activity and having the General formula (1)

where R1and R2- independently of one another denote a fluorine atom or a C1-C4-alkoxygroup, Nezami the military or substituted by halogen or tetrahydropyrazolo.



 

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6 cl, 3 dwg, 8 ex, 1 tbl

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8 cl, 15 ex

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20 cl, 6 tbl, 192 ex

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SUBSTANCE: invention describes compound of the formula (I):

as a free form or salt wherein Ar means group of the formula (II):

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13 cl, 3 tbl, 35 ex

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The invention relates to new derivatives chromanone and chromanone selected from the group comprising: ethyl ester of (2S)-3-{2-[3-(1H-imidazol-2-ylamino)propyl]-4-oxo-4H-chromen-6-yl]-2-(2,2-dimethylpropanamide)propionic acid, (2S)-3-[2-[3-(1H-imidazol-2-ylamino)propyl]-4-oxo-4H-chromen-6-yl}-2-(2,2-dimethylpropanamide)propionic acid, (2S)-3-[2-[3-(pyridine-2-ylamino)propyl]-4-oxo-4H-chromen-6-yl}-2-(2,2-dimethylpropanamide)propionic acid, (2S)-3-{2-[3-(pyridine-2-ylamino)propyl]-4-oxo-4H-chromen-6-yl}-2-butylcyclopentadienyl acid, (2S)-3-{2-[3-(pyridine-2-ylamino)propyl]-4-oxo-4H-chromen-6-yl}-2-benzisothiazolinone acid, and also their physiologically acceptable salts, enantiomers or diastereomers

The invention relates to new derivatives of benzopyran formula (I)

where R1and R2each independently represent a hydrogen atom, a C1-6-alkyl group, where this alkyl group may be optionally substituted by a halogen atom, a C1-6-alkoxygroup or a hydroxyl group; R3represents a hydroxyl group or a C1-6-alkylcarboxylic; R4represents a hydrogen atom, or R3and R4together form a bond, m is an integer from 0 to 4, n represents an integer from 0 to 4, Y is absent or represents CR11R12where R11and R12each independently represents a hydrogen atom or a C1-6is an alkyl group, R5represents an aryl group or heteroaryl group, such as thienyl, pyridyl or indolyl, where this aryl group may be optionally substituted(R10), where R10represents a halogen atom, a hydroxyl group, a C1-6-alkyl group, where this alkyl group may be optionally substituted by atom galactography, di-C1-6-alkylamino, C1-6-alkoxycarbonyl group, carboxyl group, q is an integer from 1 to 3, and each R10may be the same or different when q is 2 or 3, R6represents a hydrogen atom or a C1-6is an alkyl group, R10represents a hydrogen atom or a C1-6is an alkyl group, X is absent or represents C=O or SO2; R8represents a hydrogen atom, a C1-6-alkyl group, where this alkyl group may be optionally substituted by a halogen atom, or WITH3-6-cycloalkyl group, and R9represents a halogen atom, a nitro-group, or cyano; or their pharmaceutically acceptable salts, as well as a drug on the basis of these compounds with anti-arrhythmic activity

FIELD: organic chemistry, pharmaceutical compositions.

SUBSTANCE: invention relates to substituted 3-oxo-1,2,3,4-tetrahydroxinoxalines of general formula 1 , wherein R1 represents substituted sulfanyl or substituted sulfonyl group, containing as substituent optionally substituted C1-C4-alkyl, optionally substituted C3-C8-cycloalkyl, aryl-(C1-C4)alkyl optionally substituted in aril or alkyl group, heterocyclyl-(C1-C4)alkyl optionally substituted in heterocycle or alkyl group; R2 and R3 independently represent hydrogen, halogen, CN, NO2, optionally substituted hydroxyl, optionally substituted amino group, optionally substituted carboxylic group, optionally substituted carbamoyl group, optionally substituted arylcarbonyl group or optionally substituted heterocyclylcarbonyl group; R4 and R5 independently represent hydrogen or inert substituent. Claimed compounds are high effective kaspase-3 inhibitors and are useful in production of pharmaceutical compositions for treatment of diseases associated with excess apoptosis activation, as well as for experimental investigations of apoptosis in vivo and in vitro. Also disclosed are pharmaceutical composition in form of tablets, capsules or injections in pharmaceutically acceptable package, as well as method for production thereof and therapy method.

EFFECT: pharmaceutical composition for apoptosis treatment and investigation.

6 cl, 3 dwg, 8 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: the present innovation deals with vaccinoprophylaxis of rubeola in girls under conditions of Fr North. The method includes immunization with Rudivax vaccine, moreover, the girls who are not 13 during March-July period should be vaccinated next year only, but during the same period, that is since March to July. The method provides protective titers of anti-rubeola antibodies during next year.

EFFECT: higher efficiency of vaccination.

12 ex, 1 tbl

FIELD: pharmaceutics.

SUBSTANCE: the present innovation deals with pharmaceutical composition of bactericidal action. The composition suggested contains ciprofloxacin in the form of hydrochloride monohydrate, maltodextrin as a binding substance, sodium carboxymethyl starch as a disintegrating agent, silica gel, a lubricant at quantities mentioned in its formula. Ciprofloxacin tablets should be obtained due to pressing technique by applying the stage of moisture granulation. If necessary, the surface of tablets should be covered with a hydroxypropylmethylcellulose-based water-soluble membrane. Simultaneous application of maltodextrin as a binding substance and sodium carboxymethyl starch as a disintegrating agent enables to obtain ciprofloxacin-containing tablets of sufficient strength and quick release of active ingredient.

EFFECT: higher efficiency of application.

6 cl, 6 ex, 9 tbl

FIELD: medicine.

SUBSTANCE: the present innovation deals with antiviral preparations that contain aliphatic alcohol C21-C28 in combination with either nucleoside or nucleotide analog or phosphoformic acid in pharmaceutically acceptable carrier. It is necessary to mention that n-docosanol is considered to be a preferable aliphatic alcohol. Concentration of aliphatic alcohol C21-C28 corresponds to 0.05% to 40% by weight. Concentration of either nucleoside or nucleotide analog or phosphoformic acid corresponds to 0.1% to 10% by weight. The innovation, also, deals with the ways to treat viral infections due to applying such compositions. Aliphatic alcohols C21-C28 synergistically intensify antiviral activity of nucleoside analogs directed against replication of several herpetic viruses and that of cow's pox.

EFFECT: higher efficiency of inhibition.

28 cl, 13 dwg, 21 ex, 6 tbl

FIELD: biotechnology, veterinary science.

SUBSTANCE: he present innovation deals with manufacturing biopreparations for oral immunization in animals. One should grow vaccinia rabic virus, TC-80 strain in a certain passage cell culture to mix it with protective components (peptone, lactose, pectin). Mixing should be carried out at 14 : 5 : 1 ratio (viral suspension : stabilizing medium, consisting of 40% peptone solution with 8% lactose solution : 4% pectin solution, correspondingly), a semifinished product obtained after mixing should be applied onto a bait (a porous briquette) to be frozen and freeze dried for 24-30 h. The method includes decreased number of stages for manufacturing necessary vaccine being more efficient and economical. The vaccine keeps immunogenic properties for 5 d, not less at environmental temperature being up to 20 C and during storage period for 6 mo at 6-8 C.

EFFECT: higher efficiency of manufacturing.

2 ex, 1 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new imidazoquinolines of the formula (1): wherein R, R1, R2 and n have values given in the description. Compounds elicit effect of immunomodulating agents inducing biosynthesis of cytokines in animals in treatment of different pathologies, among them viral and neoplastic diseases. Also, invention relates to a pharmaceutical preparation used for inducing interferon-α or tumor necrosis α-factor, to a method for inducing biosynthesis of cytokines in animals and to methods for treatment of viral diseases and neoplasm pathologies in animals. Invention provides preparing new biologically active compounds.

EFFECT: improved inducing method, valuable properties of compounds and pharmaceutical preparation.

23 cl, 10 tbl, 231 ex

FIELD: medicine, pharmaceutical industry and technology, pharmacy.

SUBSTANCE: invention relates to a composition eliciting an antiviral effect. The composition comprises hydrophilic conglomerate of immunoglobulins consortium adsorbed with polyethylene glycol 4000-6000, recombinant interferon-α2 and a special additive taken among the following substances: glycine, glucose, maltose, sodium chloride taken in the definite ratio of components. Invention provides elevating solubility of composition eliciting an antiviral effect and enhanced release of biologically active substances to solution.

EFFECT: valuable medicinal properties of composition.

5 ex

FIELD: biotechnology.

SUBSTANCE: the present innovation deals with biotechnology of viral preparations. One should apply RB-71 strain of rabies virus which should be introduced into culture reservoir (0.1-0.01 MLD50/cell) simultaneously with VNK-21 at initial cell concentration being 0.5-0.5 mln cells/ml to be grown in suspension. Cultivation should be performed in suspension medium at 37 C for 5-6 d at constant mixing and maintaining pH value of 7.2-7.4. The obtained viral raw material at infectious 6.5-6.8 lg MLD50/ml and antigenic activity being 1:90-270 should be inactivated with 1,8,36-diendomethylene-1,3,6,8-tetriasecyclodecane 0.01% at 37 C for 3 d. Ready-to-use vaccine preparation meets the requirements of the standard for veterinary preparations being of 1.5-2.0 IU activity.

EFFECT: higher efficiency.

1 ex, 1 tbl

FIELD: medicine, virology, pharmaceutical industry, pharmacy.

SUBSTANCE: invention proposes the preparation used for treatment of viral hepatitis C that comprises birch bark extract with the content of betulin above 70% and a pharmaceutically acceptable carrier. The preparation is administrated to patient by oral route. The preparation promotes to the effective treatment of viral hepatitis C. Invention can be used in treatment of viral hepatitis C.

EFFECT: valuable medicinal properties of agent.

4 cl, 2 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to biologically active compounds. Agent represents 3,6-dioxocyclohexa-1,4-diene-1,2,4,5-tetrasulfonate sodium. The new agent elicits antioxidant properties and therefore it can be used in food industry, in pharmaceutical compositions and cosmetic products. Also, the new agent elicits antiviral activity owing to it can be used as both the independent medicinal agent and in compositions with other preparations used for treatment of viral infections.

EFFECT: expanded assortment of medicinal agents and antioxidants, realization of indicated prescription.

1 tbl, 8 dwg

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