Composition for prevention and treatment of hiv-1 infection and its application

 

The invention relates to the field of medicine and pharmaceutics and relates to a composition for the prevention and treatment of HIV-1 infection, including nucleoside reverse transcriptase FROM HIV-1, representing heterocyclics(ACS/thio)anilide, a second inhibitor of HIV-1, which does not choose the same HIV-1 mutant strain, or strains, select the first compound is an inhibitor of HIV-1. The invention enables to suppress the occurrence of viral resistance. 15 C.p. f-crystals, 6 PL.

Description text in facsimile form (see graphic part).

Claims

1. Composition for preventing or treating HIV-1 infections, which comprises a therapeutically effective amount of

a) the first compound is an inhibitor of HIV-1 formula

where X1is O or S;

X2is S;

Q is

or COYR5,

Y represents O or S;

R1represents halogen;

R2represents hydrogen, C1-C4alkyl;

R3represents hydrogen;

R4is3-C6alkyl;

R5is3- 1-C6alkyl;

R7and R8are hydrogen;

b) a second non-nucleoside compound is an inhibitor of HIV-1, which does not choose the same HIV-1 mutant strain, or strains, select the first compound is an inhibitor of HIV-1 (a);

where the mass ratio of the first compound is an inhibitor of HIV-1 and the second connection inhibitor of HIV-1 is from 100:1 to 1:100.

2. Composition under item 1, in which X1is O and X2is S.

3. Composition under item 1, in which Q represents COYR3.

4. The composition according to p. 3, in which Y is O.

5. Composition under item 1, in which R2is hydrogen, stands or ethyl.

6. Composition under item 1, in which R6represents a linear or branched C3-C6alkyl.

7. Composition under item 1, in which the second inhibitor AGAINST HIV-1 (b) is a PLASTIC compound of the formula

where is

i) pyrimidine of the formula

where X2represents hydrogen, C1-C4alkyl, C2-C4alkenyl,2-C4quinil, halogen, cyano, thiocyano, hydroxymethyl, C1-C2halogenated, nitro or amino;

X3is vodomodo, SH, NH2, NHCH3N(CH3)2or NHCOCH3;

ii) the purine of the formula

or the purine of the formula

where X5represents N or C1-C4alkyl;

X6represents H, HE, halogen, NH2, N3or N(CH3)2;

or (iii) triazole of the formula

where X7and X8are each independently hydrogen, C1-C4the alkyl, C1-C4halogenation, trimethylsilyl, acetyl, C1-C6alkoxycarbonyl, C1-C6alkylcarboxylic, CONH2, CONHCH3, SOPS((CH3)2, NH2, NHCH3or N(CH3)2;

R1’represents amino, C1-C4aminoalkyl,2-C4aminoalkyl or2-C4aminoalkyl;

R2’and R3’represent each independently silyl, tizamidine the same or different phenyl or linear or branched C1-C4the alkyl.

8. The composition according to p. 7, which is

i) pyrimidine of the formula

where X2represents hydrogen or C1-C4alkyl;

X3to provide the sub>;

ii) the purine of the formula

where X5is1-C4alkyl;

or (iii) triazole of the formula

where X7and X8are each independently hydrogen, C1-C4the alkyl, C1-C4halogenation, trimethylsilyl, acetyl, C1-C6alkoxycarbonyl, C1-C6alkylcarboxylic, CONH2The N3, SOP(CH3)2, NH2, NHCH3or N(CH3)2.

9. Composition under item 8, which is

i) pyrimidine of the formula

where X2represents hydrogen or C1-C4alkyl;

X3represents hydrogen or C1-C4alkyl;

ii) the purine of the formula

where X5is1-C4alkyl; or

iii) triazole of the formula

where X7and X8are each independently NH2, N3or N(CH3)2.

10. The composition according to p. 7, in which R1’is amino or1-C4aminoalkyl.

11. Composition according to any one of paragraphs.1-10, which additionally includes a third connection-inhibitor FROM Wheelie second compound is an inhibitor of HIV-1.

12. The composition according to p. 11, in which the third compound is an inhibitor of HIV is the third compound is an inhibitor of HIV-1, which does not choose the same HIV-1 mutant strain, or strains, as the first compound is an inhibitor of HIV-1 or the second compound is an inhibitor of HIV-1.

13. Composition according to any one of paragraphs.11 and 12, in which the third compound is an inhibitor of HIV is an inhibitor of HIV, which does not distinguish between HIV-1 and HIV-2.

14. The composition according to p. 11, which includes

a) the first compound is an inhibitor of HIV-1 formula

where Q represents-CR3=NOR4or COYR5;

Y represents O;

R1represents halogen;

R2represents hydrogen or C1-C4alkyl;

R3represents hydrogen;

R4is3-C6alkyl;

R5is3-C7cycloalkyl or

where R6represents a linear or branched C1-C6alkyl;

R7and R8are hydrogen;

b) the second compound is an inhibitor of HIV-1 formula

where is

i) pyrimidine of the formula

-C4alkyl;

X4represents NH2, N3or N(CH3)2;

ii) the purine of the formula

where X5is1-C4alkyl; or

iii) triazole of the formula

where X7and X8are each independently hydrogen, C1-C4the alkyl, C1-C4halogenation, trimethylsilyl, acetyl, C1-C6alkoxycarbonyl,1-C6alkylcarboxylic, CONH2The N3, SOP(CH3)2, NH2, NHCH3or N(CH3)2;

R1’represents amino or1-C4aminoalkyl;

R2’and R3’represent each independently silyl, tizamidine the same or different phenyl or linear or branched C1-C4by alkyl;

C) optional third compound is an inhibitor of HIV, which does not choose the same HIV-1 mutant strain, or strains, select either the first compound is an inhibitor of HIV-1 (a) or the second compound is an inhibitor of HIV-1 (b).

15. The composition according to p. 11, which includes

a) the first compound is an inhibitor of HIV-1 formula

where R2�2D/img_data/76/769847.gif">

where R6represents hydrogen, linear or branched C3-C6alkyl;

R7and R8are hydrogen;

b) the second compound is an inhibitor of HIV-1 formula

where is

i) pyrimidine of the formula

where X2represents hydrogen or C1-C4alkyl;

X3represents hydrogen or C1-C4alkyl;

ii) the purine of the formula

where X5is1-C4alkyl; or

iii) triazole of the formula

where X7and X8are each independently NH2, NHCH3or N(CH3)2;

R1’represents amino or1-C4aminoalkyl;

R2’and R3’represent each independently silyl, tizamidine the same or different phenyl or linear or branched C1-C4by alkyl;

C) optional third compound is an inhibitor of HIV, which does not choose the same HIV-1 mutant strain, or strains, select either the first compound is an inhibitor of HIV-1 (a) or the second compound is an inhibitor of HIV-1 (b).

16. The composition of the

 

Same patents:

The invention relates to bicyclerelated analogues of General formula (1) and the oligonucleotides on the basis thereof, containing one or more structural units of the General formula (1A), where R1represents a hydrogen atom, a protective group, the group of phosphoric acid, etc., R2is sidegroup or amino group which may be substituted, represents a purine-9-ilen, or 2-oxo-1,2-dihydropyrimidin-1-ilen group which may be substituted by one or more substituents

The invention relates to pharmaceutical compositions for inhibiting integrase, which contains as active substance a compound of the formula (I)

where X denotes a hydroxy-group; Y represents a group-COORAin which RArepresents hydrogen or ester residue, or denotes a group-CONRINRCin which RINand RCeach independently of one another denotes hydrogen or amide residue, optionally substituted aryl or optionally substituted heteroaryl, and1means optionally substituted heteroaryl, with the exception of compounds in which Y and/or AND1denote optionally substituted indol-3-yl, or contains its tautomer, prodrug, pharmaceutically acceptable salt or hydrate, compounds of formulas I, II

where X, Y described above, AND1- optional replaced heteroaryl; Z1and Z2indicate the relationship; Z2means a connection, (ness.)alkylene, -CH(OH)-, -S-, -SO2-, -O - or-CO; Z4means a connection, (ness.)alkylene, (ness.)albaniles or-CO-; R1means neobyzantine substituted heterocycle, R2denotes optionally substituted (ness.)alkyl, optionally substituted (ness.)alkyloxy, optionally substituted (ness.)allyloxycarbonyl, optionally substituted aryl, optionally substituted by alloctype, carboxy or halogen; R=0 or 1, with the exception of compounds in which (1) Y and/or AND1denotes optionally substituted indol-3-yl and (2) X denotes a hydroxy-group, Y represents 2-thienyl, AND1denotes a 1H-1,2,4-triazole-3-yl, Z1and Z3each denotes a bond, Z2denotes-NH-, R1denotes phenyl or para-tolyl and p=0; (3) X denotes a hydroxy-group, Y represents 4-methoxyphenyl, or 4-chlorophenyl, AND1means thiazol-5-yl, Z1, Z2, Z3and Z4each represents a bond, R1denotes phenyl, 4-methoxyphenyl or 4-chlorophenyl, R2denotes methyl and p=1; (4) X denotes hydroxyl, Y represents phenyl, 4-were, 4-bromophenyl or 4-chlorophenyl, AND1signifies imidazol-2-yl, Z1and Z3each denotes a bond, Z2denotes methylene, R1denotes phenyl, Z4denotes a bond, R2denotes 4-dimethylaminophenyl or 4-methoxyphenyl, and p=1; (5) X denotes hydroxyl, Y represents phenyl, 4-were-or 4-met is 1 denotes phenyl and p=0; (6) X denotes hydroxyl, Y represents-COORAwhere RAdenotes hydrogen or ethyl, AND1signifies 3-indolyl, imidazo[1,2-a]pyridine-3-yl or imidazo[2,1-b] thiazole-5-yl, Z1, Z2and Z3each represents a bond, R1denotes optionally substituted phenyl, and tautomer, prodrug, pharmaceutically acceptable salt or hydrate; various farmkompanijam, comprising as active ingredient the compound II, the drug compound having anti-HIV activity; the method of obtaining compounds of formula III

as well as the intermediate products of the formula

where Z2denotes a bond, -CO-, -O-, -CH2- or -(CH2)2and R1denotes phenyl, substituted with fluorine, and

where And denotes C-W, where W denotes hydrogen, (ness.)alkyl, (ness.)haloalkyl or halogen, or N, Q denotes trail and L denotes ethoxypropan

The invention relates to new derivatives of thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione of General formula (I) or their pharmaceutically-acceptable salts, having immunosuppressive activity

The invention relates to new derivatives of benzothiadiazole, benzoxazoles and benzodiazines formula I in free base form or in the form of a pharmaceutically acceptable acid salt additive that can be used as an anxiolytic drug in the treatment of any condition, which is associated with increased endogenous levels of CRF or in which violated the regulation of the hPa system (hypothalamic - pituitary), or various diseases that are caused by CRF1or the manifestation of which contributes CRF1such as arthritis, asthma, allergies, anxiety, depression, etc

The invention relates to peptides having the amino acid sequence of at least 5 amino acids are identical to part ner receptor, corresponding to amino acids 308-373 this receptor, excluding the peptide TEKKRRETVEREKE

The invention relates to new chemical substances, specifically to arylsubstituted the oil - and anthraquinones of formula I:

< / BR>
where (a)-g) R=H; h) R=OMe; a) X=7-hydroxy-2-methyl-1,4 - naphthoquinone-5-yl; b) X= 7-hydroxy-2-methyl-6-etoxycarbonyl-1,4-naphthoquinone-5-yl; C) X=3-hydroxy-9,10-anthraquinone-1-yl; g) X= 8-hydroxy-3-trimethyl-siloxy-2-etoxycarbonyl-and 1,1, 4,4-Tetra-hydro-9,10-anthraquinone-1-yl; d) X=8-hydroxy-3-oxo-1,2,3,4-tetrahydro-9,10-anthraquinone-1-yl; (e) X=3-hydroxy-2-taxicab-Nile-4,4-dihydro-9,10-anthraquinone-1-yl; g) X= 3,8-dihydroxy-2-etoxycarbonyl-4,4-dihydro-9,10-anthraquinone-1-yl; C) X= 3-hydroxy-2-etoxycarbonyl-4,4-dihydro-9,10-anthraquinone-1-yl, possessing anti-HIV activity

The invention relates to substituted ammonium salts of 5'-H-phosphonate 3'-azido-3'-deoxythymidine General formula (1), where RR'R N are L-alanine, ethanolamine, triethanolamine, 6-aminocaproic acid, pyridoxine or dimethylaminoethanol, which are selective inhibitors of the production of human immunodeficiency virus HIV-1 and HIV-2

The invention relates to medicine and relates to a pharmaceutical composition intended for the treatment of alcohol and drug dependence, comprising a therapeutically effective amount of (i) an opioid antagonist and (ii) a modulator of the NMDA receptor complex, and the pharmaceutical kit comprising (i) an opioid antagonist and (ii) a modulator of the NMDA receptor complex
The invention relates to medicine, in particular to the gynecologist, and for the treatment of infertility

The invention relates to technologies for water treated by electrolysis in the cathode chamber and with the ability to suppress metastasis of cancer cells
The invention relates to pharmacy
The invention relates to veterinary
Up!