Oxoazepanylacetamide and oxoazepanylphenoxyacetamide derivatives, compositions containing them and method for inhibiting hepatitis type c virus (hcv) replication

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new oxoazepanylacetamide and oxoazepanylphenoxyacetamide derivatives, or to their stereoisomers or pharmaceutically acceptable salts described by general formula I where Q means O, S or N(R25); R25 means H; R80 is C6arylC1-4alkyl substituted by one or two substituted independently chosen from R3 groups; each R3 is independently chosen from a group including C1-4alkyl, C1-4alkoxy group, C2-6alkenyloxy group, halogen, C6aryloxy group, N(R20)(R21), R50, heteroaryl chosen from pyridine and thiazol where each alkoxy group and heteroaryl has optionally up to three substitutes independently chosen from R61 groups; and alkyl has optionally three substitutes independently chosen from R60 groups; or two R3 groups when they are present on carbon neighbours, together can form a fragment of formula -(O)a-(CH2)b-(O)c-(CH2)d-(O)e- where a, c and e independently mean 0 or 1, and both b and d independently mean 0, 1, 2 or 3; provided the fragment does not contain two oxygen neighbors and summed a, b, c, d and e are equal to 3 at least; R1 is chosen from a group including H, C1-4alkyl, C6arylC1-4alkyl; each R60 independently is chosen from a group including C1-C6a alkoxy group, NR12R13, halogen, heterocycloalkyl, such as piperidine; each R61 independently is chosen from a group including R60 and C1-C6alkyl; X means a group of formula -(CH2)n- where n means 2 or 3; or a group of formula II where Y means CH2, S; R75 and R76 means H; Z means C6aryl or heteroaryl, such as pyridine; each of which has optionally one substitutes chosen from R2 groups; R2 is chosen from a group including H, C1-4alkyl, halogen, heterocycloalkylC1-4alkyl, C6arylC1-4alkylaminoC1-4alkyl and a group of formula -(CH2)fN(R11)-(R10); where each heterocycloalkyl, arylalkylaminoalkyl has oprtionally one substitute chosen from R61 groups; f means 1; R11 means H; R10 means C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, aryl, C6arylC1-4alkyl, heteroarylC1-4alkyl where aryl has optionally one substitute chosen from R61 groups; each R12 and R13 independently mean C1-4alkyl; each R20 and R21 independently mean C1-4alkyl where alkyl has optionally one substitute chosen from R60 groups; and provided that the compound does not represent N-(4-ethoxybenzyl)-N-(2-oxoazepane-2-yl)-2-phenoxyacetamide or N-[(2-fluorophenyl)methyl]-N-(2- oxoazepane-3-yl)-2,2-diphenylacetamide. Also, the invention refers to a pharmaceutical composition of the compound of formula I, to methods of treating HCV viral infection and methods of relieving the symptoms of HCV viral infection with using the compound of formula I.

EFFECT: there are produced new oxoazepanylacetamide and oxoazepanylphenoxyacetamide derivatives showing HCV replication inhibiting activity.

1 tbl, 9 ex

 

The technical field to which the invention relates.

The present invention relates to new methods and compositions designed for the inhibition of viruses. Specific variants of the invention are methods of inhibiting hepatitis C virus (HCV) and the virus that causes severe acute respiratory syndrome (SARS). The invention relates also to compositions that include a new containing lactam compounds that can be used for inhibiting viruses.

Background of invention

Hepatitis is a systemic disease that affects mainly the liver. The onset of the disease is characterized by symptoms such as anorexia, nausea, vomiting, fatigue, malaise, arthralgia, myalgia, and headache, followed by jaundice. The disease may also show elevated levels of aminotransferases ACT and serum ALT. Quantitative estimates of the levels of these enzymes in the serum allows you to set the degree of liver damage.

There are five General categories of viral agents associated with hepatitis: hepatitis A virus (HAV); hepatitis b virus (HBV); agents of two types, neither And nor (NUNW), one is present in the blood (hepatitis C), and the other is transmitted by enteral (hepatitis E); and associated with HBV agent Delta (hepatitis D).

With whom have two General clinical categories hepatitis, namely acute hepatitis and chronic hepatitis. For acute hepatitis is characterized by a wide range of symptoms from asymptomatic and characterized by the absence of symptoms of disease to infections, leading to death. The disease may be subclinical and persistent or rapidly progressive, passing in chronic liver disease, which is accompanied by cirrhosis, and in some cases it goes into the liver cell cancer. Adult residents of the United States Caucasian race of acute hepatitis in approximately 5-10% of cases progressing, moving in chronic hepatitis C. Among other cases, approximately 65% of the disease is asymptomatic. In the far East infection usually occurs in the perinatal period and in 50-90% of cases progresses, turning into a chronic condition. Apparently, the different rate of progression of disease is associated with the age at which infection occurs, but not with genetic differences between hosts. In the United States, approximately 0.2% of the population is chronically infected, with the highest percentage of falls in high-risk groups, such as doctors, drug addicts, and patients undergoing hemodialysis. In such countries and regions as Taiwan, Hong Kong and Singapore, the percentage of people infected with hepatitis, can be up to 10%.

p> In the United States about 20% of patients with chronic hepatitis die from liver failure, and another 5% will develop associated with hepatitis b carcinoma. In the far East, a large percentage of the population are infected with HBV, and after a long chronic infection (from 20 to 40 years) approximately 25% of these people develop liver cell carcinoma.

After the development of serological tests for hepatitis a and hepatitis b, scientists have identified other patients with symptoms similar to the symptoms of hepatitis, for which the incubation periods and the transmission path correspond to infectious disease, but have no serological evidence of infection caused by hepatitis a or B. after Almost 15 years the agent the causative agent was identified as Recovy virus. The virus (called "hepatitis C virus") has no homology with HBV, retroviruses or other hepatitis viruses.

Hepatitis C virus (HCV), apparently, is the main cause may occur after transfusion and sporadic cases of hepatitis And no, no (NANU) all over the world, and he plays a major role in the development of chronic liver disease, including renal cell carcinoma (Kuo and others, Science 244, 1989, SS-364; Choo and others, British Medical Bulletin 46 (2), 1990, SS-441). At approximately 150,000 of the estimated 3 million people at every gotranslate, develops acute hepatitis C (Davis et al., New Eng. J. Med. 321 (22), 1989, s-1506). In addition, about half of people who develop acute hepatitis C develop chronic hepatitis C.

Until recently been no effective therapy for the treatment of acute or chronic infections caused by hepatitis b or C, and, as a rule, affected by hepatitis patients had to accept the fact that the disease takes its course. Most antiviral drugs such as acyclovir, and also attempts to support the immune system through the use of corticosteroids has been found to be ineffective (Alter, "Viral hepatitis and liver disease", edited by Zuckerman, published by Alan R. Liss, New York, 1988, cc.537-542). It was found that certain antiviral activity has arabinoside adenosine (Jacyna and others, British Med. Bull.46, 1990, cc.368-382), while the toxic side effects associated with this drug, make it unacceptable for such treatment.

Another method of treatment, which leads to certain favorable action on chronic infections caused by hepatitis viruses b and C, is the use of recombinant α-interferon (Davis and others, New Eng. J. Med. 321(22), 1989, s-1506; Perrillo and others, New Eng. J. Med. 323, 1990, SS-301). However, among patients with infections caused by hepatitis b virus, only about 35% of those infected the people react to such treatment, and among people infected in the perinatal age, only about 10% respond to treatment. In the case of infections caused by hepatitis C virus, despite the apparent short-term beneficial effect of this therapy six months after the end of treatment in half of the patients reacted to therapy, there was a relapse. In addition, an additional difficulty associated with the treatment with α-interferon, is that the composition often causes toxic side effects, such as nausea and symptoms that resemble the flu, which requires reducing the dose to sensitive patients.

Liver-cell cancer is a disease associated with infections caused by viruses of hepatitis b and hepatitis C. In General, it is believed that liver cell cancer is the most common type of cancer worldwide. He is the cause of about 1,000,000 deaths each year, most of which occur in China and areas of Africa, sub-Saharan African. There is clear evidence of the etiological role of infections caused by hepatitis b virus, in the occurrence of hepatic cell carcinoma. Carriers of HBV are at risk for development of liver-cell cancer, more than 90 times higher than the risk in people who are not carriers of HBV. In many cases, DNA virus hepatitis the ITA In integrates into the cellular genome of the tumor. Recently, based on the fact that some patients with liver-cell cancer in the blood of antibodies to HCV, it was found that the hepatitis C virus is also associated with liver-cell cancer. Currently, surgical resection is the only treatment for hepatic cell cancer as chemotherapy, radiation therapy and immunotherapy are not sufficiently effective (Colombo and others, Lancet, 1989, cs-1008; Bisceglie and others, Ann. of Internal Med. 108, 1988, SS-401; Watanabe and others, Int J. Cancer 48, 1991, SS-343; Bisceglie and others, Amer. J. Gastro. 86, 1991, SS-338).

Severe acute respiratory syndrome, or SARS is a respiratory disease, often fatal, which was in recent years identified in Asia, North America and Europe. Recently it was found that the agent responsible for SARS, is a previously unknown coronavirus, which was recently sequenced at the Center for control and prevention of the disease (CDC).

Whereas a serious threat to people affected by viral infections, such as infection caused by HCV and SARS, obviously, extremely important to develop new methods of treatment of such infections. The present invention is directed to the achievement of this and other important purposes.

Summary of the invention

Some of the options that the implementation of the present invention methods of treating a viral infection in suffering from the patient, which is that the patient is administered in a therapeutically effective amount of a substituted accoutability. In some embodiments of the invention substituted accoutability is a compound of the formula I:

or a stereoisomer or pharmaceutically acceptable salt, where

Q represents O, S, SO, SO2or N(R25);

R25denotes H or alkyl;

R80denotes alkyl, optionally having up to three substituents, independently from each other selected from the group R60or arylalkyl, optionally having up to three substituents, independently from each other selected from the group R3;

R3each independently from each other selected from the group including H, HE, alkyl, alkoxygroup, alkenylacyl, halogen, alloctype, heteroaryl, N(R20)(R21), R50, carbarnoyl, carbamoylating, carbamoyloximes, NO2sidegroup, hydratherapy, hydroxylamino, sulfoxylate, sulfonyl, sulfide, disulfide, alkylsulfonyl, S-alkyl, heteroseksualci, heterocyclisation, geterotsiklicheskikh, geterotsiklicheskikh, alkoxyalkanols, geterotsiklicheskikh, aryl, arylalkyl, alkylaryl, arylalkylamines, arylalkylamines, aryl is sulfonyl, arylalkylamine-arylalkylamine, -C(=O)aryl, -OC(=O)aryl, -C(=O)-alloctype, -C(=O)arielalexisxrp, -C(=O)killingray, aryloxyalkyl, arylalkylamine,

-C(=O)arylalkyl, -OC(=O)arylalkyl, -C(=O)arylalkylamine, arylalkylamine, heteroaryl, heteroaromatic, alkylether, heteroarylboronic, heteroarylboronic, arylalkylamine and arylsulfonyl; where alkoxygroup, alkenylacyl, alloctype, heteroaryl, alkylsulfonyl, S-alkyl, heteroseksualci, heterocyclisation, geterotsiklicheskikh, geterotsiklicheskikh, alkoxyalkanols, geterotsiklicheskikh, aryl, arylalkyl, alkylaryl, arylalkylamines, arylalkylamines, arylsulfonyl, arylalkylamines, arylalkylamine,

-C(=O)aryl, -OC(=O)aryl, -C(=O)-alloctype, -C(=O)arielalexisxrp, -C(=O)killingray, aryloxyalkyl, arylalkylamine, -C(=O)arylalkyl, -OC(=O)arylalkyl, -C(=O)arylalkylamine, arylalkylamine, heteroaryl, heteroaromatic, alkylether, heteroarylboronic, heteroarylboronic, arylalkylamine and arylsulfonyl each optionally has up to five substituents, independently from each other selected from the group R61; and alkyl optionally has up to five substituents, independently of each wybran the x group R 60;

or two groups R3when they are present on adjacent carbon atoms together may form part of a formula -(O)and-(CH2)b-(O)with-(CH2)d-(O)e-where a, C and e independently of one another denote 0 or 1, and b and d independently of one another denote 0, 1, 2 or 3; provided that the fragment does not contain two adjacent oxygen atoms and that the sum of a, b, C, d and e is equal to at least 3;

R1selected from the group comprising H, alkyl, alkenyl, quinil, aryl, arylalkyl, heteroaryl and heteroallyl, where alkyl optionally has up to three substituents, independently from each other selected from the group R60and where alkenyl, quinil, aryl, arylalkyl, heteroaryl and heteroaromatic each optionally has up to three substituents, independently from each other selected from the group R61;

R60each independently from each other selected from the group comprising HE, C1-C6alkoxygroup, C1-C6hydroxyalkyl,2-C6alkenyl,2-C6quinil, CN, NO2, -S-C1-C6alkyl, NR12R13, -C(=O)NR12R13, halogen, R50heteroaryl, heteroaromatic, heteroseksualci, bergalli, pellouchoud, amidinopropane, arylalkylamine, -S-arylalkyl, asiagraph, hydratherapy, hydroxylamino is the SCP, sulfoxylate, sulfonyl, sulfide, disulfide, aryl and arylalkyl, where C1-C6alkoxygroup,2-C6alkenyl,2-C6quinil, -S-C1-C6alkyl, heteroaryl, heteroaromatic, heteroseksualci, arylalkylamine, -S-arylalkyl, aryl and arylalkyl each optionally has up to three substituents selected from the group comprising C1-C6alkyl, C1-C6alkoxygroup, halogen, HE and1-C6bergalli;

R61each independently from each other selected from the group comprising R60and C1-C6alkyl;

X represents a simple bond, a group of the formula -(CH2)n-, where n denotes 1, 2, 3, 4, or 5; or a group of formula II:

where Y denotes CH2, S, SO, SO2or N(R20);

R75and R76each independently from each other selected from the group comprising H, alkyl, alkoxygroup, alkenylacyl, halogen, alloctype, heteroaryl, N(R20)(R21and R50where alkyloxy, alkenylacyl, alloctype and heteroaryl each optionally has up to five substituents, independently from each other selected from the group R61and where alkyl optionally has up to five substituents, independently from each other selected from the group R60;

Z represents alkyl aryl, arylalkyl or heteroaryl, each of which optionally has up to two substituents, independently from each other selected from the group R2;

R2each independently from each other selected from the group including H, HE, alkyl, alkoxygroup, alkenylacyl, halogen, alloctype, heteroaryl, N(R20)(R21), R50, carbarnoyl, carbamoylating, carbamoyloximes, NO2sidegroup, hydratherapy, hydroxylamino, sulfoxylate, sulfonyl, sulfide, disulfide, alkylsulfonyl, S-alkyl, heteroseksualci, heterocyclisation, geterotsiklicheskikh, geterotsiklicheskikh, alkoxyalkanols, geterotsiklicheskikh, aryl, arylalkyl, alkylaryl, arylalkylamines, arylalkylamines, arylsulfonyl, arylalkylamine-arylalkylamine, -C(=O)aryl, -OC(=O)aryl, -C(=O)-alloctype, -C(=O)arielalexisxrp, -C(=O)killingray, aryloxyalkyl, arylalkylamine, -C(=O)arylalkyl, -OC(=O)arylalkyl, -C(=O)arylalkylamine, arylalkylamine, heteroaryl, heteroaromatic, alkylether, heteroarylboronic, heteroarylboronic, arylalkylamine, arylsulfonyl and a group of the formula -(CH2)f-N(R11)-(R10);

where alkoxygroup, alkenylacyl, alloctype, heteroaryl, alkylsulfonyl, S-alkyl, n is erotically, heterocyclisation, geterotsiklicheskikh, geterotsiklicheskikh, alkoxyalkanols, geterotsiklicheskikh, aryl, arylalkyl, alkylaryl, arylalkylamines, arylalkylamines, arylsulfonyl, arylalkylamine-arylalkylamine, -C(=O)aryl, -OC(=O)aryl, -C(=O)-alloctype, -C(=O)arielalexisxrp, -C(=O)killingray, aryloxyalkyl, arylalkylamine, -C(=O)arylalkyl, -OC(=O)arylalkyl, -C(=O)arylalkylamine, arylalkylamine, heteroaryl, heteroallyl, alkylether, heteroarylboronic, heteroarylboronic, arylalkylamine and arylsulfonyl each optionally have up to five substituents, independently from each other selected from the group R61; and where alkyl optionally has up to five substituents, independently from each other selected from the group R60;

f denotes 0, 1, 2, 3, 4, 5 or 6;

R11denotes H, alkyl or arylalkyl;

R10denotes alkyl, alkenyl, cycloalkyl, aryl, arylalkyl, heteroaromatic or cycloalkyl where arylalkyl, aryl and heteroaryl each optionally has up to three substituents, independently from each other selected from the group R61; and where alkyl optionally has up to three substituents, independently from each other selected from the group R60;

or R11and R10VM is the wall with the nitrogen atom, with which they are linked, can form a heterocyclic ring, which optionally has up to three substituents, independently from each other selected from the group R61;

R12and R13each independently of one another denotes H, alkyl or arylalkyl;

R20and R21each independently of one another denotes H, alkyl or arylalkyl where arylalkyl optionally has up to three substituents, independently from each other selected from the group R61and where alkyl optionally has up to three substituents, independently from each other selected from the group R60; and

R50denotes a group of formula III:

in which m, n, o and p each represents 0 or 1, and

R30and R31each independently from each other represents C1-C6alkyl.

In some embodiments of the invention the compound, stereoisomer or pharmaceutically acceptable salt according to claim 1 has the formula IV:

In other embodiments of the invention in the compounds proposed in the invention, R80denotes benzyl, optionally having up to two substituents, independently from each other selected from the group R3; and Z has the formula V or VI:

in which k is m each represents 0, 1 or 2, and R2all can be identical or have different values.

In some other embodiments of the invention R3each independently from each other selected from the group including H, HE, alkyl, alkoxygroup, alkenylacyl, halogen, alloctype, heteroaryl, N(R20)(R21), R50, aryl and arylalkyl; where alkoxygroup, alkenylacyl, alloctype, heteroaryl, aryl and arylalkyl each optionally has up to five substituents, independently from each other selected from the group R61; and where alkyl optionally has up to five substituents, independently from each other selected from the group R60;

or two groups R3when they are present on adjacent carbon atoms together may form part of a formula -(O)a-(CH2)b-(O)c-(CH2)d-(O)e-; and

R2each independently from each other selected from the group including H, HE, alkyl, alkoxygroup, alkenylacyl, halogen, alloctype, heteroaryl, N(R20)(R21), R50, aryl, arylalkyl and a group of the formula -(CH2)f-N(R11)-(R10);

where alkoxygroup, alkenylacyl, alloctype, heteroaryl, aryl and arylalkyl each optionally has up to five substituents, independently from each other selected from the group R61; and RG is alkyl optionally has up to five substituents, independently from each other selected from the group R60.

In the following embodiments of the invention R1selected from the group comprising H, benzyl and alkyl; R3each independently from each other selected from the group including H, HE, C1-C6alkyl, C1-C6alkoxygroup, CF3, F3alliancegroup, halogen, pyridyl, -C(O)-OS1-C6alkyl, thiazolyl, optionally substituted C1-C6alkyl group, fenoxaprop, optionally having up to three substituents selected from the group comprising halogen, C1-C6alkoxygroup, CF3and F3; and N(R40)(R41), where R40represents C1-C6alkyl, and R41stands With1-C6alkyl, optionally substituted-OS1-C6by alkyl;

or two groups R3when they are present on adjacent carbon atoms together may form part of a formula -(O)and-(CH2)b-(O)with-(CH2)d-(O)e-; and

R2each independently from each other selected from the group including H, HE, C1-C6alkyl, C1-C6alkoxygroup, and a group of the formula -(CH2)f-N(R11)(R10), in which f denotes 1; R11denotes N or C1-C6alkyl; and R10denotes optionally substituted ar is Elgiloy group of the formula -(CH 2)g-L, where g denotes 0, 1, 2, 3, 4, 5 or 6, and L is selected from the group comprising H, C3-C6cycloalkyl, allyl, pyridyl, and phenyl, where phenyl optionally has up to three substituents selected from the group comprising halogen, HE1-C6alkyl, OC1-C6alkyl, CF3, F3and N(R12)(R13);

or R11and R10together with the nitrogen atom to which they are bound, may form a piperidine, optionally substituted geteroseksualnoe group.

In some embodiments of the invention, complementary to each of the above options, Z has the formula V, or Z has the formula VI. In some other embodiments of the invention, complementary to each of the above options, Q denotes O or Q denotes N(R25), or Q denotes S, or Q denotes SO or Q denotes SO2. In the following embodiments of the invention, complementary to each of the above options, X denotes a group of the formula -(CH2)n-, in which n denotes 2 or 3. In the following embodiments of the invention X represents a group of formula II in which Y denotes CH2or Y represents S, or Y denotes SO or Y denotes SO2or Y represents N(R20). In other embodiments of the invention, complementary to the above VA is ianti, Q represents O; Z has the formula V; and X denotes a group of the formula -(CH2)n-, in which n denotes 2 or 3. In other embodiments of the invention, complementary variants described above, Q represents O; Z has the formula VI; and X denotes a group of the formula -(CH2)n-, in which n denotes 2 or 3.

In other embodiments of the invention, complementary variants described above, Q represents S; Z has the formula V; and X denotes a group of the formula

-(CH2)n-, in which n denotes 2 or 3. In other embodiments of the invention, complementary variants described above, Q represents S; Z has the formula VI; and X denotes a group of the formula -(CH2)n-, in which n denotes 2 or 3. In the following embodiments of the invention, complementary variants described above, Q represents O; Z has the formula V; and X denotes a group of formula II in which Y denotes CH2or S. In certain other embodiments of the invention, complementary variants described above, Q represents O; Z has the formula VI; and X denotes a group of formula II in which Y denotes CH2or S. In certain other embodiments of the invention, complementary variants described above, Q represents S; Z has the formula V; and X denotes a group of formula II in which Y denotes CH2or S. In some of the on the natives of the embodiments of the invention, complementary variants described above, Q represents S; Z has the formula VI; and X denotes a group of formula II in which Y denotes CH2or S.

In some other embodiments of the invention the compounds proposed in the invention are the compounds listed below in table 1.

In certain embodiments the invention, the compounds proposed in the invention, formula I or formula IV does not represent N-(4-ethoxybenzyl)-N-(2-oxazepan-3-yl)-2-phenoxyacetamide or N-[(2-forfinal)methyl]-N-(2-oxazepan-3-yl)-2,2-diphenylacetamide.

In addition, the present invention relates to a method of weakening symptom of viral infection, namely, that the patient is suffering from infection, enter the connection proposed in the invention, or a composition containing the compound, provided in the invention. In certain embodiments the invention, the viral infection is caused by HCV.

In addition, the present invention relates to a method of weakening symptom of SARS, which consists in the fact that the patient is suffering from them, enter the connection proposed in the invention, or a composition containing the compound, provided in the invention.

Other variants of implementation of the present invention are methods of treating diseases caused by HCV, the suffering they investigated the and, namely, that the patient is administered in a therapeutically effective amount of a substituted accoutability or substituted oxaazamacrocycles.

The following variants of implementation of the present invention are methods of treating SARS in them suffering of the patient, namely, that the patient is administered in a therapeutically effective amount of a substituted accoutability or substituted oxaazamacrocycles.

The present invention relates also to methods of inhibiting HCV in a patient, which consists in the fact that the patient is administered in a therapeutically effective amount of a compound proposed in the invention.

The present invention relates also to methods of inhibiting the virus that causes SARS, the patient lies in the fact that the patient is administered in a therapeutically effective amount of a compound proposed in the invention.

Objects of the present invention are also pharmaceutical compositions containing at least one connection proposed in the invention.

In some embodiments, implementation of the present invention the objects of the invention are the compounds of formula II whose ability to inhibit HCV is characterized by the value of the IC50less than 10 μm according to the analysis described below in example 83 or example 84.

The crust is ASEE the invention relates also to compositions, containing compounds proposed in the invention, and to methods of using compounds proposed in the invention. Also described methods of producing compounds proposed in the invention. Specialists in this field after reading this description it should be evident suitable for this purpose methods. These and other distinguishing features of the compounds proposed in the invention, described in more detail below.

Detailed description of the invention

One of the objects of the present invention are new methods and compositions designed for the inhibition of viral infections, particularly infections caused by HCV and SARS. In some embodiments, implementation of the present invention the objects of the invention are the way to alleviate the symptom of viral infection and methods of treating viral infections, namely, that the patient is suffering from infection, enter the connection proposed in the invention. In other embodiments of the invention objects of the invention are methods of inhibiting HCV or the virus that causes SARS, namely, that the patient is suffering from them, enter the connection proposed in the invention. In some embodiments, the methods proposed in the invention, the connection proposed in the invention is a substituted octoate arylacetamide. In other embodiments of the invention the compound is a substituted oxaazamacrocycles. In some embodiments of the invention substituted accoutability is a compound of the formula I:

or a stereoisomer or pharmaceutically acceptable salt, where

Q represents O, S, SO, SO2or N(R25);

R25denotes H or alkyl;

R80denotes alkyl, optionally having up to three substituents, independently from each other selected from the group R60or arylalkyl, optionally having up to three substituents, independently from each other selected from the group R3;

R3each independently from each other selected from the group including H, HE, alkyl, alkoxygroup, alkenylacyl, halogen, alloctype, heteroaryl, N(R20)(R21), R50, carbarnoyl, carbamoylating, carbamoyloximes, NO2sidegroup, hydratherapy, hydroxylamino, sulfoxylate, sulfonyl, sulfide, disulfide, alkylsulfonyl, S-alkyl, heteroseksualci, heterocyclisation, geterotsiklicheskikh, geterotsiklicheskikh, alkoxyalkanols, geterotsiklicheskikh, aryl, arylalkyl, alkylaryl, arylalkylamines, arylalkylamines, harilal who were radioactive, arylalkylamine-arylalkylamine, -C(=O)aryl, -OC(=O)aryl, -C(=O)-alloctype, -C(=O)arielalexisxrp, -C(=O)killingray, aryloxyalkyl, arylalkylamine, -C(=O)arylalkyl, -OC(=O)arylalkyl, -C(=O)arylalkylamine, arylalkylamine, heteroaryl, heteroaromatic, alkylether, heteroarylboronic, heteroarylboronic, arylalkylamine and arylsulfonyl; where alkoxygroup, alkenylacyl, alloctype, heteroaryl, alkylsulfonyl, S-alkyl, heteroseksualci, heterocyclisation, geterotsiklicheskikh, geterotsiklicheskikh, alkoxyalkanols, geterotsiklicheskikh, aryl, arylalkyl, alkylaryl, arylalkylamines, arylalkylamines, arylsulfonyl, arylalkylamine-arylalkylamine, -C(=O)aryl, -OC(=O)aryl, -C(=O)-alloctype, -C(=O)arielalexisxrp, -C(=O)killingray, aryloxyalkyl, arylalkylamine, -C(=O)arylalkyl, -OC(=O)arylalkyl, -C(=O)arylalkylamine, arylalkylamine, heteroaryl, heteroaromatic, alkylether, heteroarylboronic, heteroarylboronic, arylalkylamine and arylsulfonyl each optionally has up to five substituents, independently from each other selected from the group R61; and alkyl optionally has up to five substituents, independently from each other selected from the group R0 ;

or two groups R3when they are present on adjacent carbon atoms together may form part of a formula -(O)a-(CH2)b-(O)c-(CH2)d-(O)e-where a, C and e independently of one another denote 0 or 1, and b and d independently of one another denote 0, 1, 2 or 3; provided that the fragment does not contain two adjacent oxygen atoms and that the sum of a, b, C, d and e is equal to at least 3;

R1selected from the group comprising H, alkyl, alkenyl, quinil, aryl, arylalkyl, heteroaryl and heteroallyl, where alkyl optionally has up to three substituents, independently from each other selected from the group R60and where alkenyl, quinil, aryl, arylalkyl, heteroaryl and heteroaromatic each optionally has up to three substituents, independently from each other selected from the group R61;

R60each independently from each other selected from the group comprising HE, C1-C6alkoxygroup,1-C6hydroxyalkyl,2-C6alkenyl,2-C6quinil, CN, NO2, -S-C1-C6alkyl, NR12R13, -C(=O)NR12R13, halogen, R50heteroaryl, heteroaromatic, heteroseksualci, bergalli, pellouchoud, amidinopropane, arylalkylamine, -S-arylalkyl, asiagraph, hydratherapy, hydroxylamino, with whom loxiglumide, sulfonyl, sulfide, disulfide, aryl and arylalkyl, where C1-C6alkoxygroup,2-C6alkenyl,2-C6quinil, -S-C1-C6alkyl, heteroaryl, heteroaromatic, heteroseksualci, arylalkylamine, -S-arylalkyl, aryl and arylalkyl each optionally has up to three substituents selected from the group comprising From1-C6alkyl, C1-C6alkoxygroup, halogen, HE and C1-C6bergalli;

R61each independently from each other selected from the group comprising R60and C1-C6alkyl;

X represents a simple bond, a group of the formula -(CH2)n-, where n denotes 1, 2, 3, 4, or 5; or a group of formula II:

where Y denotes CH2, S, SO, SO2or N(R20);

R75and R76each independently from each other selected from the group comprising H, alkyl, alkoxygroup, alkenylacyl, halogen, alloctype, heteroaryl, N(R20)(R21and R50where alkyloxy, alkenylacyl, alloctype and heteroaryl each optionally has up to five substituents, independently from each other selected from the group R61and where alkyl optionally has up to five substituents, independently from each other selected from the group R60;

Z represents alkyl, aryl, arylalkyl and the and heteroaryl, each of which optionally has up to two substituents, independently from each other selected from the group R2;

R2each independently from each other selected from the group including H, HE, alkyl, alkoxygroup, alkenylacyl, halogen, alloctype, heteroaryl, N(R20)(R21), R50, carbarnoyl, carbamoylating, carbamoyloximes, NO2sidegroup, hydratherapy, hydroxylamino, sulfoxylate, sulfonyl, sulfide, disulfide, alkylsulfonyl, S-alkyl, heteroseksualci, heterocyclisation, geterotsiklicheskikh, geterotsiklicheskikh, alkoxyalkanols, geterotsiklicheskikh, aryl, arylalkyl, alkylaryl, arylalkylamines, arylalkylamines, arylsulfonyl, arylalkylamine-arylalkylamine, -C(=O)aryl, -OC(=O)aryl, -C(=O)-alloctype, -C(=O)arielalexisxrp, -C(=O)killingray, aryloxyalkyl, arylalkylamine, -C(=O)arylalkyl, -OC(=O)arylalkyl, -C(=O)arylalkylamine, arylalkylamine, heteroaryl, heteroaromatic, alkylether, heteroarylboronic, heteroarylboronic, arylalkylamine, arylsulfonyl and a group of the formula -(CH2)f-N(R11)-(R10);

where alkoxygroup, alkenylacyl, alloctype, heteroaryl, alkylsulfonyl, S-alkyl, heteroseksualci, heterocycle who alkylamino, geterotsiklicheskikh, geterotsiklicheskikh, alkoxyalkanols, geterotsiklicheskikh, aryl, arylalkyl, alkylaryl, arylalkylamines, arylalkylamines, arylsulfonyl, arylalkylamine-arylalkylamine, -C(=O)aryl, -OC(=O)aryl, -C(=O)-alloctype, -C(=O)arielalexisxrp, -C(=O)killingray, aryloxyalkyl, arylalkylamine, -C(=O)arylalkyl, -OC(=O)arylalkyl, -C(=O)arylalkylamine, arylalkylamine, heteroaryl, heteroaromatic, alkylglycerol, heteroarylboronic, heteroarylboronic, arylalkylamine and arylsulfonyl each optionally have up to five substituents, independently from each other selected from the group R61; and where alkyl optionally has up to five substituents, independently from each other selected from the group R60;

f denotes 0, 1, 2, 3, 4, 5 or 6;

R11denotes H, alkyl or arylalkyl;

R10denotes alkyl, alkenyl, cycloalkyl, aryl, arylalkyl, heteroaromatic or cycloalkyl where arylalkyl, aryl and heteroaryl each optionally has up to three substituents, independently from each other selected from the group R61; and where alkyl optionally has up to three substituents, independently from each other selected from the group R60;

or R11and R10together with the nitrogen atom to which of the and connected, may form a heterocyclic ring, which optionally has up to three substituents, independently from each other selected from the group R61;

R12and R13each independently of one another denotes H, alkyl or arylalkyl;

R20and R21each independently of one another denotes H, alkyl or arylalkyl where arylalkyl optionally has up to three substituents, independently from each other selected from the group R61and where alkyl optionally has up to three substituents, independently from each other selected from the group R60; and

R50denotes a group of formula III:

in which m, n, o and p each represents 0 or 1, and

R30and R31each independently from each other represents C1-C6alkyl.

In some embodiments of the invention the connection proposed in the invention, a stereoisomer or pharmaceutically acceptable salt according to claim 1 has the formula IV:

In other embodiments of the invention in the compounds of formula IV R80denotes benzyl, optionally having up to two substituents, independently from each other selected from the group R3; and Z has the formula V or VI:

in which k and m are each about who appoints 0, 1 or 2, and R2all can be identical or have different values.

In some embodiments of the invention the term "substituted accoutability" refers to the compound having the structure that is described by the formula:

where And denotes optionally substituted alkyl, aryl or arylalkyl group; ring b is an optionally substituted 5-9-membered ring, which optionally contains merged with it optionally substituted aryl or heteroaryl ring; (C denotes a group of the formula-Q-Z, as above, and D denotes a group R1as specified above. In other embodiments of the invention the term "substituted accoutability" refers to the above structure, which is described by the formula:

In the context of the present description, the term "alkyl" refers to saturated hydrocarbon groups, including hydrocarbons with straight, branched chain and cyclic hydrocarbons (i.e. "cycloalkyl" group)such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, tert-pentyl, neopentyl, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, saturated systems containing multiple rings, such as decahydro the naphthalene and adamantane and the like, including alkyl substituted derivatives of the above groups.

In the context of the present description the term "alkenyl" refers to an alkyl group that contains one or more double bonds in the carbon-carbon and is not aromatic. The concept of "quinil" refers to an alkyl group that contains one or more triple relations of carbon-carbon and is not aromatic. The concept of "bergalli" refers to an alkyl group in which all hydrogen atoms replaced by halogen atoms.

In the context of the present description the term "alkanoyl" refers to a group of the formula-C(=O)alkyl.

In the context of the present description the term "alkoxygroup" refers to a fragment of the formula-O-alkyl. The concept pellouchoud denotes alkoxygroup, in which all the hydrogen atoms replaced by halogen atoms. The concept of "alkoxyalkyl" refers to a group of the formula-alkyl-O-alkyl. The concept of "monoalkylamines" and "dialkylamino" mean respectively the group of formula-NH-alkyl and N(alkyl)2in which the fragments that represent alkyl groups may be the same or different. The concept of "acylaminoalkyl" refers to a group of the formula-alkyl-NR'r R"in which R' denotes an alkyl and R ' denotes H (i.e. "monoalkylamines") or alkyl (i.e. "dialkylaminoalkyl"). The concept of "alkoxyalkanols" seat is no acylaminoalkyl group, in which one or both alkyl groups R' and R" replaced by alkoxygroup.

In the context of the present description, the term "aryl" refers to aromatic hydrocarbon, such as phenyl, naphthyl, phenanthrene, anthracene, pyrenyl, etc. In some embodiments the invention, the aryl groups have from 6 to 10 carbon atoms.

The concept of "arielalexisxrp" refers to alkoxygroup, which contains an aryl group. The concept of "aryloxyalkyl" refers to a group of the formula-alkyl-O-aryl. The concept of "arylcarbamoyl" refers to a fragment having the formula-C(=O)aryl. The concept of "arylalkylamine" refers to a fragment having the formula alkyl-C(=O)arylalkyl. The concept of "arylalkylamine" refers to a group of the formula-O-arylalkyl, such as benzyloxy. The concept of "alkylglycerol" refers to a group of the formula heteroaryl-alkyl, such as 4-methylpiperid-2-ilen group.

In the context of the present description the term "arylalkyl" (or "aralkyl") refers to an alkyl group that is attached to the aryl group, such as benzyl and naphthalenedione group. In some embodiments of the invention arylalkyl groups have from 7 to 11 carbon atoms.

In the context of the present description the term "alkylaryl" (or "alkaryl") refers to a aryl group that is attached to one or the number of alkyl groups, such as 4-methylphen-1-ilen group or xylella group attached through a phenyl ring.

The concept of "killingray", "arylalkylamine" and "alkalinuria" mean respectively aryl, arylalkyl or alcylaryl group attached through the amino group of the formula NR ' in which R ' denotes H or alkyl. The concept of "arylalkylamines and alkylarylsulfonates" refers to an alkyl group that contains arylalkylamine or alkylarylsulfonate respectively.

In the context of the present description the term "heteroseksualci" refers to a group that contains non-aromatic ring bearing one or more ring heteroatoms (i.e. non-carbon atom), which preferably are O, N or S, and which may also contain one or more attached alkyl groups. Under the concept of "heteroseksualci" also includes fragments that contain ekzoticheskie heteroatoms, for example cycloalkyl ring, where the ring carbon atom attached to ekzoticheskom atom O or S through the double bond. Under the concept of "heteroseksualci" also includes fragments that have one or more aromatic rings fused (i.e. having a common connection with) with non-aromatic heterocyclic ring such, in the example, as phthalimide, diimides naphthalenedisulfonic acid, talani and benzoperylene saturated heterocycles, such as indolinone and isoindoline group.

The concept of "heterocyclisation" means geterotsyklicescoe group attached through the amino group of the formula NR ' in which R ' denotes H or alkyl. The concept of "geterotsiklicheskikh" means heterocyclisation attached through an alkyl group. The concept of "geterotsiklicheskikh" means geterotsyklicescoe group attached through its ekzoticheskuyu alkyl group. The concept of "geterotsiklicheskikh" refers to a group of the formula-alkyl-NR"-geterotsiklicheskikh, in which R" represents H or alkyl.

In the context of the present description the term "heteroaryl" refers to an aryl group containing one or more ring heteroatoms (i.e. non-carbon atom), which preferably are O, N or S. In some embodiments of the invention heteroaryl groups are monocyclic or bicyclic and contain up to four ring heteroatoms. Examples of some of the preferred heteroaryl groups are radicals representing derivatives of pyrrole, pyrazole, imidazole, triazoles, tetrazole, pyridine, n is Razin, pyridazine, pyrimidine, triazines, quinoline, indoles, benzimidazole, etc.

The concept of "heteroarylboronic" refers to a fragment having the formula-C(=O)-heteroaryl. The concept of "heteroaromatic" refers to a group of the formula-alkyl-heteroaryl. The concept of "alkylglycerol" refers to a group of the formula-heteroaryl-alkyl. The concept of "heteroarylboronic" refers to a group of the formula-NR"-heteroallyl, in which R" represents H or alkyl. The concept of "heteroarylboronic" refers to a group of the formula-alkyl-heteroarylboronic.

The term "halogen" denotes an element of group VII, including fluorine, chlorine, bromine and iodine.

Typically, the suffix "sulfonyl" refers to the attachment of the group through a group of the formula-S(=O)2-. Thus, the term "alkylsulfonyl" refers to a group of the formula-SO2-alkyl, the term "arylsulfonyl" refers to the fragment having the formula-S(=O)2-aryl, and the term "heteroarylboronic" refers to the fragment having the formula-S(=O)2-heteroaryl.

Generally, the term containing the suffix "hydroxy"refers to the attachment of the group through an oxygen atom. For example, the notion of "aryloxy" refers to an aryl group attached through an oxygen atom, such as fenoxaprop, and the concept of "arancelaria" or "arylalkylamine" refers to a group of the formula-O-arylalkyl to whom I is equivalent to the group arylalkyl-O-, which is equivalent to the group-O-alkylaryl.

In the context of the present description the term "aryloxyalkyl" refers to the fragment having the formula-C(=O)-O-aryl, such as phenoxycarbonyl.

In the context of the present description, the term alkoxyalkyl refers to the fragment having the formula-alkyl-O-alkyl-O-alkyl.

In the context of the present description the term "hydroxyalkyl" refers to an alkyl group in which the hydrogen atom is substituted by a group of IT.

In the context of the present description the term "alkoxycarbonyl" refers to the fragment having the formula-C(=O)-O-alkyl.

The term "side chain of naturally occurring alpha-amino acids" refers to the side chains of naturally occurring alpha amino acids, except glycine, which are known to have the formula H2N-CHR-COOH, in which R represents a side chain. Examples of such naturally occurring amino acids are the 20 so-called "essential" amino acids, such as serine and threonine. Other examples of the side chains of naturally occurring amino acids can be found in the book "Biochemistry", 3rd ed., edited by Mathews, Van Holde, and Ahern, Addison Wesley Longman, San Francisco, CA, fully incorporated into the present description by reference.

Some embodiments of the present invention relate to Conn the injuries of the formula IV:

in which R80denotes benzyl, optionally having up to two substituents, independently from each other selected from the group R3; and Z has the formula V or VI:

in which k and m each represents 0, 1 or 2, and R2all can be identical or have different values.

In some embodiments of the invention R3each independently from each other selected from the group including H, HE, alkyl, alkoxygroup, alkenylacyl, halogen, alloctype, heteroaryl, N(R20)(R21), R50, aryl and arylalkyl; where alkoxygroup, alkenylacyl, alloctype, heteroaryl, aryl and arylalkyl each optionally has up to five substituents, independently from each other selected from the group R61; and where alkyl optionally has up to five substituents, independently from each other selected from the group R60;

or two groups R3when they are present on adjacent carbon atoms together may form part of a formula -(O)a-(CH2)b-(O)c-(CH2)d-(O)e-; and

R2each independently from each other selected from the group including H, HE, alkyl, alkoxygroup, alkenylacyl, halogen, alloctype, heteroaryl, N(R20)(R1 ), R50, aryl, arylalkyl and a group of the formula -(CH2)f-N(R11)-(R10);

where alkoxygroup, alkenylacyl, alloctype, heteroaryl, aryl and arylalkyl each optionally has up to five substituents, independently from each other selected from the group R61; and where alkyl optionally has up to five substituents, independently from each other selected from the group R60.

In some other embodiments of the invention R1selected from the group comprising H, benzyl and alkyl; R3each independently from each other selected from the group including H, HE, C1-C6alkyl, C1-C6alkoxygroup, CF3, F3alliancegroup, halogen, pyridyl, -C(O)-OS1-C6alkyl, thiazolyl, optionally substituted C1-C6alkyl group, fenoxaprop, optionally having up to three substituents selected from the group comprising halogen, C1-C6alkoxygroup, CF3and F3; and N(R40)(R41), where R40represents C1-C6alkyl, and R41represents C1-C6alkyl, optionally substituted by-OC1-C6by alkyl;

or two groups R3when they are present on adjacent carbon atoms together may form a fragment having the formula -(O)and-(CH2)b-(O with-(CH2)d-(O)e-; and

R2each independently from each other selected from the group including H, HE, C1-C6alkyl, C1-C6alkoxygroup, and a group of the formula -(CH2)f-N(R11)(R10), in which f denotes 1; R11denotes N or C1-C6alkyl; and R10denotes a group of the formula -(CH2)g-L, where g denotes 0, 1, 2, 3, 4, 5 or 6, and L is selected from the group comprising H, C3-C6cycloalkyl, allyl, pyridyl, and phenyl, where phenyl optionally has up to three substituents selected from the group comprising halogen, HE, C1-C6alkyl, OC1-C6alkyl, CF3, F3and N(R12)(R13);

or R11and R10together with the nitrogen atom to which they are bound, may form a piperidine, optionally substituted geteroseksualnoe group.

In some embodiments of the invention Z is of formula V, or Z has the formula VI. In some other embodiments of the invention Q denotes O or Q denotes N(R25), or Q denotes S, or Q denotes SO or Q denotes SO2. In the following embodiments of the invention X represents a group of formula -(CH2)n-, in which n denotes 2 or 3. In the following embodiments of the invention X represents a group of formula II, to the auroy Y denotes CH 2or Y represents S, or Y denotes SO or Y denotes SO2or Y represents N(R20). In other embodiments of the invention, Q represents O; Z has the formula V; and X denotes a group of the formula -(CH2)n-, in which n denotes 2 or 3. In other embodiments of the invention, Q represents O; Z has the formula VI; and X denotes a group of the formula -(CH2)n-, in which n denotes 2 or 3.

In other embodiments of the invention, Q represents S; Z has the formula V; and X denotes a group of the formula -(CH2)n-, in which n denotes 2 or 3. In other embodiments of the invention, Q represents S; Z has the formula VI; and X denotes a group of the formula -(CH2)n-, in which n denotes 2 or 3. In some other embodiments of the invention, Q represents O; Z has the formula V; and X denotes a group of formula II in which Y denotes CH2or S. In certain other embodiments of the invention, Q represents O; Z has the formula VI; and X denotes a group of formula II in which Y denotes CH2or S. In certain other embodiments of the invention, Q represents S; Z has the formula V; and X denotes a group of formula II in which Y denotes CH2or S. In certain other embodiments of the invention, Q represents S; Z has the formula VI; and what signifies a group of formula II, in which Y denotes CH2or S.

Some other embodiments of the invention relate to compounds shown below in table 1.

Presented in the present description replaced accoutability derivatives can be easily synthesized as shown in scheme 1, which is illustrated in more detail in the "Examples"section.

Scheme 1

It should be borne in mind that by choosing as initial products appropriately substituted aminoethane and aldehyde can be obtained with a wide variety of substituted accoutability derivatives, including compounds of formulas (I) and (IV). Thus, some embodiments of the invention relate to methods of preparing compounds of formulas (I) and (IV) according to scheme 1. Furthermore, it was assumed that under the scope of the present invention are subject to intermediate products, as well as appropriate methods for their synthesis is illustrated in scheme 1 and described below in the examples. When applying these methods, variables that are included in the formulas of compounds can be any of the values specified for compounds of formulas (I) and (IV).

Assume that under the scope of the present invention is applicable to all possible protonated and diprotonirovannyye forms referred to in this description of the link is, and their solvate and a pharmaceutically acceptable salt. It is also understood that each of the specifically described in this description of the compounds includes all possible tautomers and stereoisomers.

In this description of the compounds represented by their common and individual chemical formulas and names. In all such cases it is assumed that under the scope of the present invention is applicable to all individual stereoisomers referred to in this description of the compounds, as well as their racemic forms.

Connections proposed in the present invention, and their pharmaceutically acceptable salts can be used for the treatment of viral infections in animals and humans, particularly infections caused by HCV and SARS. Connections proposed in the invention can be applied individually or in the form of pharmaceutical compositions containing one or more compounds proposed in the invention, in combination with one or more pharmaceutically acceptable carriers. Thus, other objects of the present invention are pharmaceutical compositions and methods of treating viral infections with the use as active ingredients of new compounds presented in this description.

In some embodiments of the invention the connection offer from the Britanie, you can get in the form of salts, such as amine salts (but not limited to), which may contain any one of a variety of pharmaceutically acceptable counterions. Suitable counterions for the amine salts are the acetate, adipate, aminosalitsilata, anhydrotetracycline, ascorbate, aspartate, benzoate, bansilalpet, bromide, citrate, comfort, camphorsulfonate, chloride, astolat, aconsultant, fumarate, glucoheptonate, gluconate, glutamate, lactobionate, malate, maleate, mandelate, methanesulfonate, Pantothenate, pectinate, phosphate/diphosphate, polygalacturonate, propionate, salicylate, stearate, succinate, sulfate, tartrate and tosylate. Specialist in this field must be known to other suitable types of anions.

Connections proposed in the invention can be included in pharmaceutical compositions, which may contain one or more compounds proposed in the invention, and one or more pharmaceutically acceptable carriers. Connections proposed in the invention, it is possible to enter in powder or crystalline form in the composition of the liquid solution or suspension. You can enter them in different ways, providing efficiency with the introduction of antiviral agents, including (but not limited to) local injection, or introduction oral route or parenteral with the help of the injection (for example, intravenously or intramuscularly).

With the introduction by injection of the compounds proposed in the invention is preferably introduced in the form of standard doses, in ampoules or in containers containing multiple doses. Designed for injection of the composition can be in such forms as suspensions, solutions or emulsions in oily or aqueous fillers, and they may include a variety of agents necessary for preparation of the drug. Alternatively, the active ingredient may be in powder form (lyophilized or reliabilitybased), designed to restore before making the introduction using suitable filler, such as sterile water. Intended for injection, the compositions of the media, as a rule, is a sterile water, saline or other suitable injection fluid, for example peanut oil for intramuscular injection. The composition can also include various tabularasa agents, preservatives, etc.

Compositions for topical application can be prepared using carriers, such as hydrophobic or hydrophilic bases, obtaining ointments, creams, lotions, using aqueous, oily or alcoholic liquids with obtaining medicinal substance in SCOM media (applied with a brush or using dry solvents to obtain powders.

Compositions for oral administration may be in such forms as tablets, capsules, suspensions for oral administration, and solutions for oral administration. In compositions for oral administration can be applied media, such as conventional agents necessary for preparation of the compositions, and they may have the ability to prolonged release, as well as the ability to rapidly release.

Designed for dose depends to a large extent on the condition and size of the patient to be treated, the route and frequency of administration, the sensitivity of the pathogen to a particular connection, the degree of virulence of the pathogen, and other factors. These issues, however, are the responsibility of the attending physician in accordance with the principles of treatment are well known in the treatment of viral infections. Another factor affecting the accuracy of the regimen of medicines that is not associated with the nature of the infection and specific distinctive features of the individual, is the molecular weight of the connection.

Under the amount presented in the present description, the subject invention is also a method of treating viral infections, namely, that the mammal is administered the connection proposed in the invention, in an amount effective to treat the infection. One predpochtitelnye the introduction of antiviral compounds proposed in the invention is the introduction of oral and parenteral route, for example via intravenous (i.v.) infusion, intravenous (i.v.) boles and intramuscular (i.m.) the injection.

The compounds presented in the present description, can be prepared as pharmaceutical compositions by mixing with pharmaceutically acceptable nontoxic excipients and carriers. As noted above, such compositions can be prepared in a form suitable for parenteral administration, primarily in the form of liquid solutions or suspensions; or for oral administration, primarily in the form of tablets or capsules; or intranasal, primarily in the form of powders, nose drops, or aerosols; or for insertion through the skin, for example, using transdermal plaques; or they can be prepared in any other form suitable for these and other routes of administration, as it should be obvious to specialists in this field.

The composition may be conveniently introduced in the form of standard doses, and can be prepared by any methods well known in the pharmaceutical field, for example, as described in the Handbook Remington''s Pharmaceutical Sciences (published by Mack Pub. Co., Easton, PA, 1980). Preparations for parenteral administration may contain as conventional excipients sterile water or saline, Polyak langille, such as polyethylene glycol, oils of vegetable origin, hydrogenated naphthalenes and the like as excipients to control the release of active substances can be applied, in particular, biocompatible biodegradable lacheny polymer lacheny/glycolide copolymer or copolymers of polyoxyethylene/polyoxypropylene. Other systems that can be used for parenteral administration of these active substances include particles of a copolymer of ethylene/vinyl acetate, osmotic pumps, implantable infusion systems, and liposomes. Drugs for administration via inhalation contain as excipients, for example lactose, or you can apply aqueous solutions containing, for example, a simple polyoxyethylene-9-lauric ether, glycocholate and dezoksiholatom, or oily solutions for administration in the form of nasal drops or gels intended for intranasal administration. Preparations for parenteral administration may contain also glycocholate for buccal administration, salicylate for rectal injection or citric acid for vaginal administration. Preparations for transdermal plaques preferably represent a lipophilic emulsion.

Connections proposed in the present invention, can be used as a single acting washes the VA, present in the pharmaceutical agent, or can be used in combination with other active substances, such as other agents that can be used to treat viral infections.

Concentrations presented in this description of the compounds in a therapeutic composition will vary depending on many factors, including intended for the introduction of the dose of the drug, chemical characteristics (e.g., hydrophobicity) of the compounds used and the route of administration. Compositions intended for administration to man in the form of a standard dose, both in liquid and solid form, can contain from about 0.01% to about 99% of active substance, preferably the range is from about 0.1 to 60%. For example, the compounds proposed in the present invention, can be present effective in terms of inhibitory effect of amounts designated for injecting aqueous physiological buffer solution containing about 0.1 to 10 wt./vol.%. connection.

Typical dose ranges are from about 1 mg/kg to about 1 g/kg body weight per day; a preferred dose range is from about 0.01 to 100 mg/kg of body weight per day. Such preparations usually contain possessing inhibitory effective amount of soy is inane, proposed in the invention. However, the preferred dose intended for the introduction of medicines depends on such variables as the type and extent of progression of disease or impairment, General health status of the particular patient, the relative biological efficacy of the selected compound and the composition of excipient to connect and route of administration.

Although the present invention is described with reference to specific preferred variants of its implementation, the following examples serve only to illustrate the invention and are not intended to limit its scope.

For the item the considered compounds used the program ACD Name, version 5.04 (28 may 2001), which is available from Advanced Chemistry Development, Inc., and trademark ChemInnovation NamExpert + Nomenclator™, which can be obtained from the company ChemInnovation Software, Inc. Some of the initial products were identified using standard IUPAC nomenclature.

Examples

Example 1

Obtaining 3-methyl-4-propoxybenzaldehyde

4-Hydroxy-3-methylbenzaldehyde [(1); 16,65 g; 1 equiv.], 1-bromopropane [12,2 ml; 1.1 EQ.], sodium iodide [4,58 g; 0.25 EQ.], potassium carbonate [33,8 g; 2 EQ.] and DMF (300 ml) was added to a dried round bottom flask. On top of the flask was set condenser and a rubber membrane is angelically element, then was purged with argon. The reaction mixture was heated to 75°C for 12 h in an argon atmosphere. Then the reaction mixture was poured into a separating funnel containing water (900 ml) and ethyl acetate (900 ml). The organic layer was washed twice with water and twice with brine and dried over sodium sulfate. The organic filtrate was concentrated in vacuum, obtaining 3-methyl-4-propoxybenzaldehyde in the form of crude oil. The product was used in the next stage without additional purification.

Example 2

Obtain (3S)-3-{[(3-methyl-4-propoxyphenyl)methyl]amino}superheroes-2-it

3-methyl-4-propoxybenzaldehyde (9,72 g; 1 EQ.), (S)-alpha-amino-omega-caprolactam [6,99 g; 1 equiv.], traceability sodium (34,68 g; 3 EQ.) and methylene chloride (220 ml) was added to a round bottom flask. Then the reaction mixture was stirred at room temperature for 5 hours To terminate the reaction was carefully added to saturated aqueous sodium bicarbonate solution (200 ml). The resulting mixture was diluted with ethyl acetate (200 ml) and shaken in a separating funnel. After separation of the organic layer the aqueous layer was again extracted with two additional portions of ethyl acetate (400 ml). The organic layers were combined and dried over sodium sulfate. The sodium sulfate was filtered and the organic filtrate conc the Wali in vacuum, receiving the crude product. The resulting crude oil was dissolved in methylene chloride and purified using the rapid chromatography using a gradient of methylene chloride/methanol. Purified fractions were combined and concentrated in vacuum, obtaining (3S)-3-{[(3-methyl-4-propoxyphenyl)methyl]amino}superheroes-2-it is in the form of oil.

Example 3

Obtaining N-((3S)-2-oxoazetidin-3-yl)-2-(4-carbonfinance)-N-[(3-methyl-4-propoxyphenyl)methyl]ndimethylacetamide

In a round bottom flask was added (3S)-3-{[(3-methyl-4-propoxyphenyl)methyl]amino}superheroes-2-he (4,00 g), 4-formylphenoxy acid (4,96 g; 2 EQ.), EDCI (5,28 g; 2 EQ.) and THF (30 ml). Then the reaction mixture was stirred at room temperature for 5 hours then the mixture was concentrated in vacuo and diluted with ethyl acetate (50 ml) and water (50 ml). The resulting suspension was placed in a separating funnel and was intensively shaken. Then the organic layers were isolated and dried over sodium sulfate. The sodium sulfate was filtered and the organic filtrate was concentrated in vacuum, obtaining the crude product. The resulting crude solid product was dissolved in methylene chloride and purified using the rapid chromatography using a gradient of methylene chloride/methanol. Purified fractions were combined and concentrated in HAC the mind, receiving N-((3S)-2-oxoazetidin-3-yl)-2-(4-carbonfinance)-N-[(3-methyl-4-propoxyphenyl)methyl]ndimethylacetamide in the form of a pure solid.

Example 4

Obtaining N-((3S)-2-oxoazetidin-3-yl)-2-{4-[(cyclohexylamino)methyl]phenoxy}-N-[(3-methyl-4-propoxyphenyl)methyl]ndimethylacetamide

In a round bottom flask was added N-((3S)-2-oxoazetidin-3-yl)-2-(4-carbonfinance)-N-[(3-methyl-4-propoxyphenyl)methyl]ndimethylacetamide (0,30 g; 1 EQ.), cyclohexylamine (0,30 ml, 4 EQ.) and methylene chloride (3 ml). The reaction mixture was stirred at room temperature for 10 hours To the mixture was added triacetoxyborohydride sodium (0,42 g; 3 EQ.). Then the reaction mixture was stirred at room temperature for 3 hours To terminate the reaction was carefully added to saturated aqueous sodium bicarbonate solution (3 ml). The resulting mixture was diluted with ethyl acetate (10 ml) and was shaken in a separating funnel. After separation of the organic layer the aqueous layer was again extracted with two additional portions of ethyl acetate (20 ml). The organic layers were combined and dried over sodium sulfate. The sodium sulfate was filtered and the organic filtrate was concentrated in vacuum, obtaining the crude solid product. Then the solid mixture was dissolved in DMSO and purified using preparative GHUR. Then peeled the coat is AI were combined and liofilizirovanny, receiving N-((3S)-2-oxoazetidin-3-yl)-2-{4-[(cyclohexylamino)methyl]phenoxy}-N-[(3-methyl-4-propoxyphenyl)methyl]ndimethylacetamide in the form of purified salt triperoxonane acid (TFA) in white.

Example 5

Obtaining N-((3S)-2-oxoazetidin-3-yl)-N-{[3-(N-cyclohexylcarbonyl)-4-propoxyphenyl]methyl}-2-phenoxyacetamide (8)

The specified connection was synthesized according to the following scheme 2.

Scheme 2

a) 3-Methyl-4-propoxybenzaldehyde (2)

In a dried round bottom flask was added 5-formulaicity acid (8,76 g; 1 EQ.), 1-bromopropane (10.1 ml; 2.1 EQ.), sodium iodide (3,95 g; 0.5 equiv.) potassium carbonate (21,87 g; 3 EQ.) and DMF (211 ml). On top of the flask was set condenser and a rubber membrane separation element, then purged with argon. The reaction mixture was heated to 75°C for 12 h in an argon atmosphere. Then the reaction mixture was poured into a separating funnel containing water (900 ml) and ethyl acetate (900 ml). The organic layer was washed twice with water and twice with brine and dried over sodium sulfate. The sodium sulfate was filtered and the organic filtrate was concentrated in vacuum, obtaining propyl-5-carbonyl-2-propoxybenzene (1). The crude product was used in the next stage without additional purification.

b) Propyl-5-{[((3S)-2-oxeas perseroan-3-yl)amino]methyl}-2-propoxybenzene (4)

In a round bottom flask was added 3-methyl-4-propoxybenzaldehyde (6,00 g; 1 EQ.), (S)-alpha-amino-omega-caprolactam (3,69 g; 1.2 EQ.), triacetoxyborohydride sodium (15,24 g; 3 EQ.) and methylene chloride (240 ml). The reaction mixture was stirred at room temperature for 5 hours To terminate the reaction was carefully added to saturated aqueous sodium bicarbonate solution (200 ml). The resulting mixture was diluted with ethyl acetate (200 ml) and shaken in a separating funnel. After separation of the organic layer the aqueous layer was again extracted with two additional portions of ethyl acetate (400 ml). The organic layers were combined and dried over sodium sulfate. The sodium sulfate was filtered and the organic filtrate was concentrated in vacuum, obtaining the crude product. The resulting crude oil was dissolved in methylene chloride and purified using the rapid chromatography using a gradient of methylene chloride/methanol. Purified fractions were combined and concentrated in vacuum, obtaining propyl-5-{[((3S)-2-oxoazetidin-3-yl)amino]methyl}-2-propoxybenzene in the form of oil.

in) Propyl-5-{[N-((3S)-2-oxoazetidin-3-yl)-2-phenoxyacetamide]methyl}-2-propoxybenzene (6)

In a round bottom flask was added propyl-5-{[((3S)-2-oxoazetidin-3-yl)amino]methyl}-2-prop is xiantai (4.52 g; 1 EQ.), phenoxyacetate (2.1 ml; 1.2 EQ.), the basis Hunya (2,6 ml; 1.2 EQ.) and THF (125 ml). Then the reaction mixture was stirred at room temperature for 30 minutes then the reaction was stopped by adding water (3 ml) and concentrated in vacuo to remove THF. The crude mixture was dissolved in ethyl acetate (200 ml) and washed with water (100 ml). Then the organic layer was isolated and dried over sodium sulfate. The sodium sulfate was filtered and the organic filtrate was concentrated in vacuum, obtaining the crude product. The resulting crude oil was dissolved in methylene chloride and purified using the rapid chromatography using a gradient of methylene chloride/methanol. Purified fractions were combined and concentrated in vacuum, obtaining propyl-5-{[N-((3S)-2-oxoazetidin-3-yl)-2-phenoxyacetamide]methyl}-2-propoxybenzene (6) as a pure solid.

d) 5-{[N-((3S)-2-oxoazetidin-3-yl)-2-phenoxyacetamide]methyl}-2-propoxybenzene acid (7)

In a round bottom flask was added propyl-5-{[N-((3S)-2-oxoazetidin-3-yl)-2-phenoxyacetamide]methyl}-2-propoxybenzene (1,15 g; 1 EQ.), the lithium hydroxide (0,278 g; 5 equiv.) THF (11.5 ml) and water (11.5 ml). Flask provided with a condenser and was heated to 48°C. After completion of the reaction (after about 18 hours, every hour assests is whether the monitoring of the reaction by TLC) the mixture was concentrated in vacuo to remove THF. The reaction mixture was acidified to pH 6 by addition of 0.5 M aqueous citric acid. The precipitate was filtered, washed with water and dried by suction air, receiving 5-{[N-((3S)-2-oxoazetidin-3-yl)-2-phenoxyacetamide]methyl}-2-propoxybenzene acid (7) in the form of a pure solid white color.

d) N-((35)-2-oxoazetidin-3-yl)-N-{[3-(N-cyclohexylcarbonyl)-4-propoxyphenyl]methyl}-2-phenoxyacetamide (8)

To the vessel was added 5-{[N-((3S)-2-oxoazetidin-3-yl)-2-phenoxyacetamide]methyl}-2-propoxybenzene acid (0,020 g; 1 EQ.), cyclohexylamine (10,0 ál; 2 equiv.) EDCI (0,017 g; 2 EQ.) and DMF (0.5 ml). The reaction mixture was stirred at room temperature for 10 hours Then the mixture was filtered through a plug removal nerastvorim particles. The crude solution was directly injected with in a column for preparative GHUR. Purified fractions were combined and concentrated in vacuum, obtaining N-((3S)-2-oxoazetidin-3-yl)-N-{[3-(N-cyclohexylcarbonyl)-4-propoxyphenyl]methyl}-2-phenoxyacetamide (8) as a pure solid.

Example 6

Obtaining N-((3S)-2-oxoazetidin-3-yl)-2-bromo-N-[(3-methyl-4-propoxyphenyl)methyl]ndimethylacetamide

In a dried round bottom flask was added (3S)-3-{[(3-methyl-4-propoxyphenyl)methyl]amino}superheroey the-2-he (3.00 g; 1 EQ.), the basis Hunya (2.4 ml, 1.1 EQ.) and THF (100 ml). Then the mixture was cooled in an argon atmosphere to 0°C. using a bath of ice/water. To the above cooled mixture was added dropwise within 5 min bromocatechol (1.3 ml; 1.5 EQ.). The resulting solution was stirred for another 30 min at 0°C. then the reaction was stopped by adding water (3 ml) and concentrated in vacuo to remove THF. The crude mixture was dissolved in ethyl acetate (200 ml) and washed with water (100 ml). Then the organic layer was isolated and dried over sodium sulfate. The sodium sulfate was filtered and the organic filtrate was concentrated in vacuum, obtaining the crude product. The resulting crude oil was dissolved in methylene chloride and purified using the rapid chromatography using a gradient of methylene chloride/methanol. Purified fractions were combined and concentrated in vacuum, obtaining N-((3S)-2-oxoazetidin-3-yl)-2-bromo-N-[(3-methyl-4-propoxyphenyl)methyl]ndimethylacetamide in the form of a pure solid.

Example 7

Obtaining N-((3S)-2-oxoazetidin-3-yl)-N-[(3-methyl-4-propoxyphenyl)methyl]-2-(phenylamino)ndimethylacetamide

In a round bottom flask was added N-((38)-2-oxoazetidin-3-yl)-2-bromo-N-[(3-methyl-4-propoxyphenyl)methyl]ndimethylacetamide (0,250 g; 1 EQ.), aniline (of 0.11 ml, 2 equiv.) sodium iodide (0,023 g; 0.25 EQ.), to rbonate potassium (has 0.168 g; 2 EQ.) and DMF (2.4 ml). After that the reaction mixture was heated to 75°C for 8 h in an argon atmosphere. After cooling to room temperature the mixture was filtered through a cotton plug to remove excess nerastvorim salts, such as sodium iodide and potassium carbonate. The crude solution was purified by using preparative GHUR. Purified fractions were combined and concentrated in vacuum, obtaining N-((3S)-2-oxoazetidin-3-yl)-N-[(3-methyl-4-propoxyphenyl)methyl]-2-(phenylamino)ndimethylacetamide as TFA salt.

It should be borne in mind that the General procedure described in example 7, can be used for a wide variety of compounds proposed in the invention. For example, the bromide used in example 7, can be replaced with any of the many nucleophiles, such as anilines, thiophenol, alkoxides, etc. using the same General conditions.

Examples 8-82

Representative substituted accoutability derivatives

Representative substituted accoutability derivatives proposed in the invention, presented in table 2. In table 2, MN+ refers to a molecule ion detected using mass spectrometry.

Analysis procedures

Example 83

Quantification of the RNA of the HCV replicon cell lines (analysis of HCV using cell)

Cell line Huh-11-7 or Huh-9-13 bearing HCV replicons (Lohmann and others, Science 285, 1999, SS-113), were sown at a rate of 5×103cells/well in 96-well plates and fed with medium containing DMEM (high glucose), 10% fetal calf serum, penicillin-streptomycin and non-essential amino acids. Cells were incubated in an incubator in an atmosphere containing 5% CO2at 37°C. After incubation period were extracted total RNA was purified from cells using the set Qiagen RNeasy 96 (catalog number 74182). In order by amplification of HCV RNA to obtain the product quantity sufficient for detection using specific HCV probe (see below), was used primers specific for HCV (see below), mediating as reverse transcription (FROM) HCV RNA and amplification of cDNA using polymerase chain reaction (PCR), using a set of TaqMan One-Step RT-PCR Master Mix, Applied Biosystems, catalog number 4309169). Primers for RT-PCR had the following nucleotide sequence located in the NS5B region of the HCV genome:

Direct primer "RBNS5bfor" HCV: 5'GCTGCGGCCTGTCGAGCT

Reverse primer "RBNS5Brev" HCV: 5'CAAGGTGTCTCCGCATAC

Detection of product RT-PCR was performed using the detection system of sequence Detection System (SDS)) type Applied Biosystems (ABI) Prism 7700, which allows to detect the fluorescence emitted when the probe is labeled with a fluorescent dye-reporter and dye-quencher, is subjected to processing by PCR. The increase in the level of fluorescence was measured during each PCR cycle, and it reflects the increase in the number of product RT-PCR. Specifically, the quantitative assessment is based on the determination of the threshold cycle at which the graph of amplification crosses a certain threshold level of fluorescence. Comparison of threshold cycles for the sample with a known standard is a highly sensitive method of measuring the relative concentration of the matrix in different samples (Newsletter for the user firm ABI No. 2, December 11, 1997). Data were analyzed using SDS firm ABI, version 1.7. Relative concentration of the matrix to determine the number of copies of RNA using a standard curve for HCV RNA with a known number of copies (Newsletter for the user firm ABI No. 2, December 11, 1997).

Detection of RT-PCR product was performed using the following labeled probe:

5' FAM-CGAAGCTCCAGGACTGCACGATGCT-TAMRA,

FAM is the fluorescent dye reporter

TAMRA - paint the ü-quencher.

FROM-the reaction was carried out at 48°C for 30 min, after which PCR was carried out. For PCR using the detection system sequence type ABI Prism 7700 asked the following parameters thermoacetica: one cycle at 95°C, 10 min, then 35 cycles, each of which included one incubation at 95°C for 15 s, and a second incubation at 60°C for 1 min

To standardize data is relatively used as an internal standard molecule in cellular RNA was carried out by RT-PCR using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) cellular messenger RNA. The number of copies of GAPDH is very stable in the used cell lines. RT-PCR using GAPDH was performed on exactly the same sample RNA, which determined the number of copies of HCV. GAPDH primers and probe, as well as standards for determining the number of copies included in the set ABI Pre-Developed TaqMan Assay (catalog number E). To calculate the activity of the compounds tested in respect of inhibiting the replication of HCV RNA, used the ratio of HCV RNA/GAPDH.

Example 84

The activity of compounds as inhibitors of HCV replication (analysis using cells) containing the replicon cell lines Huh-7

The influence of specific antiviral compounds on the levels of RNA of the HCV replicon cell line Huh-11-7 or 9-13 were determined by comparison to the value of the quantity of HCV RNA, normalized with respect to GAPDH (for example, the ratio of HCV/GAPDH) in cells treated with the compound, and in cells treated controls, leading to a 0%increase inhibition and 100%increase inhibition. Specifically, the method consisted in the fact that the cells were sown at a rate of 5×103cells/well in 96-well plate and incubated with: 1) media containing 1% DMSO (control, leading to a 0%increase inhibition), 2) 100 international units, IU/ml interferon-alpha 2b in the media/1% DMSO or 3) media/1% DMSO containing a fixed concentration. Then 96-well plates, as described above, incubated at 37°C for 3 days (primary screening test) or for 4 days (to determine the IC50). The percentage of inhibition was determined according to the following formula:

% inhibition = [100-((S-C2)/(C1-C2))]×100,

in which

S = the ratio of the number of copies of HCV RNA/number of copies of GAPDH RNA in the sample,

C1 = the ratio of the number of copies of HCV RNA/RNA copies GAPDH in control, leading to a 0%increase inhibition (media/1% DMSO),

C2 = the ratio of the number of copies of HCV RNA/RNA copies GAPDH in control, leading to 100%increase inhibition (100 IU/ml interferon-alpha 2b).

Curves of the response to the dose of inhibitor was obtained by adding to the wells of serial three-fold dilutions (3 log) connection starting with the most is our concentration of specific compounds component 10 μm, and ending with the lowest concentration, component of 0.01 μm. In that case, if the value of the IC50was not in the linear range changes according to used additional serial dilutions (for example, from 1 μm to 0.001 μm). The value of the IC50was determined using IDBS Activity Base using Microsoft Excel XL-Fit", in which A = the value corresponding to 100%inhibition (100 IU/ml interferon-alpha 2b), B = the value corresponding to 0%inhibition control (media/1% DMSO), and C = the average point on the curve, which is calculated as follows: C=(- A/2)+A. the Values a, b and C were expressed as the ratio of HCV RNA/PHK GAPDH for each the sample in each well of 96-hole tablet as described above. To determine values corresponding to 100%and 0%inhibition, and used the average of 4 wells for each plate.

Each of the compounds listed in table 2, which can be synthesized according to the procedures illustrated in scheme 1 and in examples 1-7, can be analyzed according to the method described above in example 83 and/or the example 84. Many of these compounds have activity against inhibition of HCV at a concentration of less than 10 μm. Some of these compounds have activity against inhibition of HCV at a concentration of less than 1 μm. More concrete is some connection example 1-82 inhibit HCV in a concentration of less than 0.1 μm. Thus, in some preferred embodiments, the implementation of the methods and compounds proposed in the invention, the variables that are included in formula (I) and (VII)are chosen from those presented in the examples 1-82. In addition, due to its very high activity it is preferable for each of these compounds individually, and it is preferred as a representative of the group, including any or all of the compounds of examples 1-82, in the application presented in the present description means. Each of these compounds is preferred for use in the preparation of medicines intended for the treatment of biological conditions.

However, because you can also use compounds that inhibit HCV in the above-described assays in higher concentrations, such as 10 μm, 20 μm or 50 μm, the present invention is not limited to compounds having activity at a concentration of 10 μm or less.

It should be borne in mind that everything mentioned in this description of the patents, patent applications and printed publications, including books, fully incorporated into the present description by reference.

Professionals in this field should be obvious that you can make numerous changes and modification preferably in the e embodiments of the invention without deviating from the invention. It is implied that all such variations fall within the scope of invention.

1. The compound of formula I:

or a stereoisomer, or a pharmaceutically acceptable salt,
where Q denotes O, S or N(R25);
R25denotes H;
R80- C6arils1-4alkyl, substituted by one or two substituents, independently from each other selected from the group R3;
R3each independently from each other selected from the group comprising From1-4alkyl, C1-4alkoxygroup,2-6alkenylacyl, halogen, C6alloctype, N(R20)(R21), R50heteroaryl selected from pyridine and thiazole, where alkoxygroup and heteroaryl each optionally has up to three substituents, independently from each other selected from the group R61; and the alkyl has three optional substituent, independently from each other selected from the group R60;
or two groups R3when they are present on adjacent carbon atoms together may form part of a formula -(O)and-(CH2)b-(O)with-(CH2)d-(O)e-where a, c and e independently of one another denote 0 or 1, and b and d independently of one another denote 0, 1, 2 or 3; provided that the fragment does not contain two adjacent oxygen atoms and that the sum of a, b, C, d and e is equal to at least 3;
R 1selected from the group including H, C1-4alkyl, C6arils1-4alkyl;
R60each independently from each other selected from the group comprising C1-C6alkoxygroup, NR12R13, halogen, heteroseksualci, such as piperidine;
R61each independently from each other selected from the group comprising R60and C1-C6alkyl;
X denotes a group of the formula -(CH2)n-where n is 2 or 3; or a group of formula II:

where Y denotes CH2, S;
R75and R76denote H;
Z represents C6aryl or heteroaryl, such as pyridine; each of which optionally has one Deputy selected from the group R2;
R2selected from the group including H, C1-4alkyl, halogen, heterocyclics1-4alkyl, C6arils1-4alkylamino1-4alkyl and a group of the formula -(CH2)fN(R11)-(R10);
where heteroseksualci, arylalkylamines each optionally have one Deputy, selected from the group R61;
f denotes 1;
R11denotes H;
R10represents C1-6alkyl, C2-6alkenyl,3-8cycloalkyl, aryl, C6arils1-4alkyl, heteroaryl1-4alkyl, where aryl optionally has one Deputy selected from the group R61;
R12and R 13each independently from each other represents C1-4alkyl;
R20and R21each independently from each other represents C1-4alkyl, where alkyl optionally has one Deputy selected from the group R60;
provided that the compound is not N-(4-ethoxybenzyl)-N-(2-oxazepan-3-yl)-2-phenoxyacetamide or N-[(2-forfinal)methyl]-N-(2-oxazepan-3-yl)-2,2-diphenylacetamide.

2. The compound, stereoisomer or pharmaceutically acceptable salt according to claim 1 of formula IV:

3. The compound, stereoisomer or pharmaceutically acceptable salt according to claim 2,
where R80denotes benzyl, with up to two substituents, independently from each other selected from the group R3;
Z has the formula V or VI:

in which k and m represent 0 or 1, and R2everything can be the same or have different meanings defined in claim 1.

4. The compound, stereoisomer or pharmaceutically acceptable salt according to claim 3,
where R3each independently from each other selected from the group comprising From1-4alkyl, C1-4alkoxygroup,2-6alkenylacyl, halogen, C6alloctype, heteroaryl selected from pyridine and thiazole, N(R20)(R21where alkoxygroup and heteroaryl each optionally has up to three Deputy is stitely, independently from each other selected from the group R61; and where alkyl has three optional substituent, independently from each other selected from the group R60;
or two groups R3when they are present on adjacent carbon atoms together may form a fragment having the formula -(O)and-(CH2)b-(O)c-(CH2)d-(O)e-; and
R2each independently from each other selected from the group including H, C1-4alkyl, halogen and a group of the formula -(CH2)f-N(R11)-(R10).

5. The compound, stereoisomer or pharmaceutically acceptable salt according to claim 2,
where R1selected from the group comprising H, benzyl and C1-4alkyl; R3each independently from each other selected from the group comprising From1-C4alkyl, C1-C4alkoxygroup, OCF3, halogen, pyridyl, thiazolyl, optionally substituted C1-C6alkyl group, fenoxaprop;
or two groups R3when they are present on adjacent carbon atoms together may form part of a formula -(O)and-(CH2)b-(O)with-(CH2)d-(O)e-; and
R2each independently from each other selected from the group including H, C1-C4alkyl and a group of the formula -(CH2)f-N(R11)(R10),
in which f denotes 1;
R11denotes the; and
R10denotes optionally substituted arylalkyl group of the formula -(CH2)g-L, where g denotes 0, 1, 2, 3, or 4 and L is selected from the group comprising a pyridyl, and phenyl, where phenyl optionally has one Deputy, selected from the group comprising halogen, C1-C6alkyl and N(R12)(R13).

6. The compound, stereoisomer or pharmaceutically acceptable salt according to one of PP, 4 or 5, where Z has the formula V.

7. The compound, stereoisomer or pharmaceutically acceptable salt according to one of PP, 4 or 5, where Z has the formula VI.

8. The compound, stereoisomer or pharmaceutically acceptable salt according to one of PP, 4 or 5, where Q denotes O.

9. The compound, stereoisomer or pharmaceutically acceptable salt according to one of PP, 4 or 5, where Q denotes N(R25).

10. The compound, stereoisomer or pharmaceutically acceptable salt according to one of PP, 4 or 5, where Q denotes S.

11. The compound, stereoisomer or pharmaceutically acceptable salt according to one of PP, 4 or 5, where X denotes the group -(CH2)n-, where n denotes 2 or 3.

12. The compound, stereoisomer or pharmaceutically acceptable salt according to one of PP, 4 or 5, where X denotes a group of formula II in which Y denotes CH2.

13. The compound, stereoisomer or pharmaceutically acceptable salt according to one of PP, 4 or 5, where X Ref is no group of formula II, in which Y represents S.

14. The compound, stereoisomer or pharmaceutically acceptable salt according to one of PP, 4 or 5, where Q represents O; Z has the formula V; and X denotes a group of the formula (CH2)nin which n denotes 2 or 3.

15. The compound, stereoisomer or pharmaceutically acceptable salt according to one of PP, 4 or 5, where Q represents O; Z has the formula VI; and X denotes a group of the formula (CH2)nin which n denotes 2 or 3.

16. The compound, stereoisomer or pharmaceutically acceptable salt according to one of PP, 4 or 5, where Q denotes S; Z has the formula V; and X denotes a group of the formula (CH2)nin which n denotes 2 or 3.

17. The compound, stereoisomer or pharmaceutically acceptable salt according to one of PP, 4 or 5, where Q denotes S; Z has the formula VI; and X denotes a group of the formula (CH2)nin which n denotes 2 or 3.

18. The compound, stereoisomer or pharmaceutically acceptable salt according to one of PP, 4 or 5, where Q represents O; Z has the formula V; and X denotes a group of formula II.

19. The compound, stereoisomer or pharmaceutically acceptable salt p, where Y represents S.

20. The compound, stereoisomer or pharmaceutically acceptable salt according to one of PP, 4 or 5, where Q represents O; Z has the formula VI; and X denotes a group of formula II.

21. The compound, stereoisomer or pharmacist who Cesky acceptable salt according to claim 20, where Y represents S.

22. The compound, stereoisomer or pharmaceutically acceptable salt according to one of PP, 4 or 5, where Q denotes S; Z has the formula V; and X denotes a group of formula II.

23. The compound, stereoisomer or pharmaceutically acceptable salt according to item 22, where Y represents S.

24. The compound, stereoisomer or pharmaceutically acceptable salt according to one of PP, 4 or 5, where Q denotes S; Z has the formula VI; and X denotes a group of formula II.

25. The compound, stereoisomer or pharmaceutically acceptable salt according to paragraph 24, where Y represents S.

26. The compound, stereoisomer or pharmaceutically acceptable salt according to claim 2, selected from the group including:
N-[(3S)-1-ethyl-2-oxazepan-3-yl]-N-(3-methyl-4-propoxyphenyl)-2-phenoxyacetamide,
N-(3-methyl-4-propoxyphenyl)-N-[(3S)-1-ethyl-2-oxazepan-3-yl]-2-phenoxyacetamide,
N-(4-ethoxy-3-methylbenzyl)-N-[(3S)-2-oxazepan-3-yl]-2-phenoxyacetamide,
N-[(3S)-1-methyl-2-oxazepan-3-yl]-N-(3-methyl-4-propoxyphenyl)-2-phenoxyacetamide,
N-(4-isobutylphenyl)-N-[(3S)-2-oxazepan-3-yl]-2-phenoxyacetamide,
N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxopiperidin-3-yl]-2-phenoxyacetamide,
2-(4-{[(2-terbisil)amino]methyl}phenoxy-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]-2-phenoxyacetamide,
N-(3-methyl-4-propoxyphenyl)-N-[(3R)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl]-2-phenoxyacetamide,
N-[(3S)-2-oxazepan-3-yl]-2-phenoxy-N-(4-propoxyphenes the l)ndimethylacetamide,
N-[(3S)-2-oxazepan-3-yl]-2-phenoxy-N-(4-phenoxybenzyl)ndimethylacetamide,
2-[4-(anilinomethyl)phenoxy]-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl] acetamide", she
2-{4-[(benzylamino)methyl]phenoxy}-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
2-(4-{[(4-terbisil)amino]methyl}phenoxy)-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
N-[(3S)-1-benzyl-2-oxazepan-3-yl]-N-(3-methyl-4-propoxyphenyl)-2-phenoxyacetamide,
N-(4-methoxy-3-methylbenzyl)-N-[(3S)-2-oxazepan-3-yl]-2-phenoxyacetamide,
2-(4-{[(3-terbisil)amino]methyl}phenoxy)-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
N-(3-(allyloxy)benzyl)-N-[(3S)-2-oxazepan-3-yl]-2-phenoxyacetamide,
N-1-(3-methyl-4-propoxyphenyl)-N-1-[(3S)-2-oxazepan-3-yl]-N-2-phenylglycine,
N-(3-methyl-4-propoxyphenyl)-2-[(6-methylpyridin-3-yl)oxy]-N-[(3S)-2-oxazepan-3-yl]acetamide", she
N-{4-[(2-methoxyethyl)(methyl)amino]benzyl)}-N-[(3S)-2-oxazepan-3-yl]-2-phenoxyacetamide,
N-(4-isopropoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]-2-phenoxyacetamide,
2-(4-{[(4-methylbenzyl)amino]methyl}phenoxy)-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]-2-(4-{[(2-phenylethyl)amino]methyl}phenoxy)ndimethylacetamide,
N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]-2-(phenylthio)ndimethylacetamide,
N-(4-ethoxybenzyl)-2-(4-pertenece)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
N-(4-ethoxybenzyl)-N-[(3S)-2-oxazepan-3-yl]-2-venexiana the amide,
N-(3,4-dichlorobenzyl)-N-[(3S)-2-oxazepan-3-yl]-2-phenoxyacetamide,
2-(4-{[(4-Chlorobenzyl)amino]methyl}phenoxy-N-(3-methyl-4-ethoxybenzyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]-2-(4-{[(pyridine-3-ylmethyl)amino]methyl}phenoxy)ndimethylacetamide,
N-[3-(3,5-dichlorophenoxy)benzyl]-N-[(3S)-2-oxazepan-3-yl]-2-phenoxyacetamide,
N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]-2-(4-{[(pyridine-4-ylmethyl)amino]methyl}phenoxy)ndimethylacetamide,
N-[(3S)-2-oxazepan-3-yl]-2-phenoxy-N-[4-trifluoromethyl)benzyl]acetamide", she
N-[(3S)-2-oxazepan-3-yl]-2-phenoxy-N-[4-triptoreline)benzyl]acetamide", she
2-[4-({[4-(dimethylamino)benzyl]amino}methyl)phenoxy]-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
N-(4-ethoxybenzyl)-N-(2-oxazepan-3-yl)-2-phenoxyacetamide,
N-(4-ethoxybenzyl)-N-(2-oxazepan-3-yl)-2-phenoxyacetamide,
2-[4-({[2-(4-chlorophenyl)ethyl]amino}methyl)phenoxy]-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
N-[(3S)-2-oxazepan-3-yl]-2-phenoxy-N-(4-pyridin-4-ylbenzyl]ndimethylacetamide,
N-(4-tert-butoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]-2-phenoxyacetamide,
N-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-N-[(3S)-2-oxazepan-3-yl]-2-phenoxyacetamide,
N-[4-(dimethylamino)benzyl]-N-[(3S)-2-oxazepan-3-yl]-2-phenoxyacetamide,
2-(4-{[2,4-dimethoxybenzyl)amino]methyl}phenoxy)-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
N - (3-methyl-4-propoxyphenyl)-N-(3S)-2-oxazepan-3-yl]-2-(pyridine-2-is lexi)ndimethylacetamide,
N-[4-(4-tert-butyl-1,3-thiazol-2-yl)benzyl]-N-[(3S)-2-oxazepan-3-yl]-2-phenoxyacetamide,
2-(4-{[methyl(phenyl)amino]methyl}phenoxy)-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
N-[(3S)-2-oxazepan-3-yl]-2-phenoxy-N-(4-pyridine-2-ylbenzyl)ndimethylacetamide,
2-(3-chlorophenoxy)-N-(4-ethoxybenzyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
N-(2,3-dihydro-1-benzofuran-5-ylmethyl)-N-[(3S)-2-oxazepan-3-yl]-2-phenoxyacetamide,
N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]-2-{[(pyridine-2-ylmethyl)amino]methyl}phenoxy)ndimethylacetamide,
2-[3-(anilinomethyl)phenoxy]-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
methyl-4-{[[(3S)-2-oxazepan-3-yl](phenoxyacetyl)amino]methyl}benzoate,
2-(4-{[methyl(2-phenylethyl)amino]methyl}phenoxy)-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
2-[(5-bromopyridin-2-yl)oxy]-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
2-[(5-chloropyridin-2-yl)oxy]-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
2-[2-(1,4'-bipiperidine-1'-ylmethyl)phenoxy]-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
2-[4-(1,4'-bipiperidine-1'-ylmethyl)phenoxy]-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
N-[(3S)-2-oxazepan-3-yl]-2-phenoxy-N-(3-phenoxybenzyl)ndimethylacetamide,
2-(4-{[(cyclohexylmethyl)amino]methyl}phenoxy)-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
2-(3-{[methyl(phenyl)amino]methyl}phenoxy)-N-(3-methyl-4-propoxyphen who yl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]-2-(4-{[(3-phenylpropyl)amino]methyl}phenoxy)ndimethylacetamide,
N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]-2-(4-{[(4-phenylbutyl)amino]methyl}phenoxy)ndimethylacetamide,
2-{4-[(hexylamino)methyl]phenoxy}-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
2-(3-{[methyl(2-phenylethyl)amino]methyl}phenoxy)-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]-2-(4-{[(2-pyridin-4-retil)amino]methyl}phenoxy)ndimethylacetamide,
2-(3-{[(cyclohexylmethyl)amino]methyl}phenoxy)-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]-2-(3-{[(3-phenylpropyl)amino]methyl}phenoxy)ndimethylacetamide,
2-(3-{[(4-terbisil)amino]methyl}phenoxy)-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
2-[3-({[2-(4-chlorophenyl)ethyl]amino}methyl)phenoxy]-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
2-{4-[(allylamino)methyl]phenoxy}-N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]acetamide", she
N-[(3S)-2-oxazepan-3-yl]-2-phenoxy-N-(4-pyridine-3-ylbenzyl)ndimethylacetamide,
N-(3-bromobenzyl)-N-[(3S)-2-oxazepan-3-yl]-2-phenoxyacetamide,
N-(3-methyl-4-propoxyphenyl)-N-[(3S)-2-oxazepan-3-yl]-2-(pyridine-4-yloxy)ndimethylacetamide,
N-(4-methoxybenzyl)-N-[(3S)-2-oxazepan-3-yl]-2-phenoxyacetamide,
N-(3,4-dimethoxybenzyl)-N-[(3S)-2-oxazepan-3-yl]-2-phenoxyacetamide and
2-[(2-yodellin-yl)oxy]-N-(4-methoxybenzyl)-N-[(3S)-2-oxazepan-3-yl]-2-phenoxyacetamide.

27. The composition having inhibitory activity against HCV replication containing compound, stereoisomer or pharmaceutically acceptable salt according to one of claims 1 to 5.

28. Pharmaceutical composition having inhibitory activity against HCV replication containing compound, stereoisomer or pharmaceutically acceptable salt according to one of claims 1 to 5.

29. A method of treating a viral infection of HCV, namely, that the patient is suffering from such infection, introducing an effective amount of a compound of formula I:

or a stereoisomer or pharmaceutically acceptable salt, where:
Q represents O, S or N(R25);
R25denotes H;
R80- C6arils1-4alkyl, substituted by one or two substituents, independently from each other selected from the group R3;
R3each independently from each other selected from the group comprising From1-4alkyl, C1-4alkoxygroup,2-6alkenylacyl, halogen, C6alloctype, N(R20)(R21), R50heteroaryl selected from pyridine and thiazole, where alkoxygroup and heteroaryl each optionally has up to three substituents, independently from each other selected from the group R61; and the alkyl has three optional substituent, independently from each other selected from the group R 60;
or two groups R3when they are present on adjacent carbon atoms together may form part of a formula -(O)and-(CH2)b-(O)with-(CH2)d-(O)e-where a, C and e independently of one another denote 0 or 1, and b and d independently of one another denote 0, 1, 2 or 3; provided that the fragment does not contain two adjacent oxygen atoms and that the sum of a, b, C, d and e is equal to at least 3;
R1selected from the group including H, C1-4alkyl, C6arils1-4alkyl;
R60each independently from each other selected from the group comprising C1-C6alkoxygroup, NR12R13, halogen, heteroseksualci, such as piperidine;
R61each independently from each other selected from the group comprising R60and C1-C6alkyl;
X denotes a group of the formula -(CH2)n-where n is 2 or 3; or a group of formula II:

where Y denotes CH2, S;
R75and R76denote H;
Z represents C6aryl or heteroaryl, such as pyridine; each of which optionally has one Deputy selected from the group R2;
R2selected from the group including H, C1-4alkyl, halogen, heterocyclics1-4alkyl, C6arils1-4alkylamino1-4alkyl and a group of the formula -(CH2
)fN(R11)-(R10);
where heteroseksualci, arylalkylamines each optionally have one Deputy, selected from the group R61;
f denotes 1;
R11denotes H;
R10stands With1-6alkyl, C2-6Balkany,3-8cycloalkyl, aryl, C6arils1-4alkyl, heteroaryl1-4alkyl, where aryl optionally has one Deputy selected from the group R61;
R12and R13each independently from each other represents C1-4alkyl;
R20and R21each independently from each other represents C1-4alkyl, where alkyl optionally has one Deputy selected from the group R60;
provided that the compound is not N-(4-ethoxybenzyl)-N-(2-oxazepan-3-yl)-2-phenoxyacetamide or N-[(2-forfinal)methyl]-N-(2-oxazepan-3-yl)-2,2-diphenylacetamide.

30. A method of treating a viral infection of HCV, namely, that the patient is suffering from such infection, introducing an effective amount of the compound, stereoisomer or pharmaceutically effective salt according to one of claims 1 to 5.

31. The method of relieving the symptoms of virus infection HCV, namely, that the patient is suffering from such infection, introducing an effective amount of a compound of formula I:

or a stereoisomer or pharmaceutically acceptable salt,
25);
R25denotes H;
R80- C6arils1-4alkyl, substituted by one or two substituents, independently from each other selected from the group R3;
R3each independently from each other selected from the group comprising From1-4alkyl, C1-4alkoxygroup,2-6alkenylacyl, halogen, C6alloctype, N(R20)(R21), R50heteroaryl selected from pyridine and thiazole, where alkoxygroup and heteroaryl each optionally has up to three substituents, independently from each other selected from the group R61; and the alkyl has three optional substituent, independently from each other selected from the group R60;
or two groups R3when they are present on adjacent carbon atoms together may form part of a formula -(O)and-(CH2)b-(O)with-(CH2)d-(O)e-where a, C and e independently of one another denote 0 or 1, and b and d independently of one another denote 0, 1, 2 or 3; provided that the fragment does not contain two adjacent oxygen atoms and that the sum of a, b, C, d and e is equal to at least 3;
R1selected from the group including H, C1-4alkyl, C6arils1-4alkyl;
R60each independently from each other selected from the group comprising C1-C6alkoxygroup, NR12R13halo is Yong, heteroseksualci, such as piperidine;
R61each independently from each other selected from the group comprising R60and C1-C6alkyl;
X denotes a group of the formula -(CH2)n-where n is 2 or 3; or a group of formula II:

where Y denotes CH2, S;
R75and R76denote H;
Z represents C6aryl or heteroaryl, such as pyridine; each of which optionally has one Deputy selected from the group R2;
R2selected from the group including H, C1-4alkyl, halogen, heterocyclics1-4alkyl, C6arils1-4alkylamino1-4alkyl and a group of the formula -(CH2)fN(R11)-(R10);
where heteroseksualci, arylalkylamines each optionally have one Deputy, selected from the group R61;
f denotes 1;
R11denotes H;
R10represents C1-6alkyl, C2-6alkenyl,3-8cycloalkyl, aryl, C6arils1-4alkyl, heteroaryl1-4alkyl, where aryl optionally has one Deputy selected from the group R61;
R12and R13each independently from each other represents C1-4alkyl;
R20and R21each independently from each other represents C1-4alkyl, where alkyl optionally has one Deputy, selected isgroup R 60;
provided that the compound is not N-(4-ethoxybenzyl)-N-(2-oxazepan-3-yl)-2-phenoxyacetamide or N-[(2-forfinal)methyl]-N-(2-oxazepan-3-yl)-2,2-diphenylacetamide.

32. Way relieve symptoms caused by HCV, which consists in the fact that the patient is suffering from such infection, introducing an effective amount of a compound of formula I:

or a stereoisomer or pharmaceutically acceptable salt,
where Q denotes O, S or N(R25);
R25denotes H;
R80- C6arils1-4alkyl, substituted by one or two substituents, independently from each other selected from the group R3;
R3each independently from each other selected from the group comprising From1-4alkyl, C1-4alkoxygroup,2-6alkenylacyl, halogen, C6alloctype, N(R20)(R21), R50heteroaryl selected from pyridine and thiazole, where alkoxygroup and heteroaryl each optionally has up to three substituents, independently from each other selected from the group R61; and the alkyl has three optional substituent, independently from each other selected from the group R60;
or two groups R3when they are present on adjacent carbon atoms together may form part of a formula -(O)and-(CH2)b-(O)with-(CH2) d-(O)e-where a, C and e independently of one another denote 0 or 1, and b and d independently of one another denote 0, 1, 2 or 3; provided that the fragment does not contain two adjacent oxygen atoms and that the sum of a, b, C, d and e is equal to at least 3;
R1selected from the group including H, C1-4alkyl, C6arils1-4alkyl;
R60each independently from each other selected from the group comprising C1-C6alkoxygroup, NR12R13, halogen, heteroseksualci, such as piperidine;
R61each independently from each other selected from the group comprising R60and C1-C6alkyl;
X denotes a group of the formula -(CH2)n-where n is 2 or 3; or a group of formula II:

where Y denotes CH2, S;
R75and R76denote H;
Z represents C6aryl or heteroaryl, such as pyridine; each of which optionally has one Deputy selected from the group R2;
R2selected from the group including H, C1-4alkyl, halogen, heterocyclics1-4alkyl, C6arils1-4alkylamino1-4alkyl and a group of the formula -(CH2)fN(R11)-(R10);
where heteroseksualci, arylalkylamines each optionally have one Deputy, selected from the group R61;
f denotes 1;
R11denotes H;
R10stands With1-6alkyl, C2-6alkenyl,3-8cycloalkyl, aryl, C6arils1-4alkyl, heteroaryl1-4alkyl, where aryl optionally has one Deputy selected from the group R61;
R12and R13each independently from each other represents C1-4alkyl;
R20and R21each independently from each other represents C1-4alkyl, where alkyl optionally has one Deputy selected from the group R60;
provided that the compound is not N-(4-ethoxybenzyl)-N-(2-oxazepan-3-yl)-2-phenoxyacetamide or N-[(2-forfinal)methyl]-N-(2-oxazepan-3-yl)-2,2-diphenylacetamide.

33. Way relieve symptoms caused by HCV, which consists in the fact that the patient is suffering from such infection, introducing an effective amount of a pharmaceutical composition comprising a compound of formula I:

or a stereoisomer or pharmaceutically acceptable salt, where:
Q represents O, S or N(R25);
R25denotes H;
R80- C6arils1-4alkyl, substituted by one or two substituents, independently from each other selected from the group R3;
R3each independently from each other selected from the group comprising From1-4alkyl, C1-4alkoxygroup,2-6alkenylacyl, halogen, C6alloctype, NR 20)(R21), R50heteroaryl selected from pyridine and thiazole, where alkoxygroup and heteroaryl each optionally has up to three substituents, independently from each other selected from the group R61; and the alkyl has three optional substituent, independently from each other selected from the group R60;
or two groups R3when they are present on adjacent carbon atoms together may form part of a formula -(O)and-(CH2)b-(O)with-(CH2)d-(O)e-where a, C and e independently of one another denote 0 or 1, and b and d independently of one another denote 0, 1, 2 or 3; provided that the fragment does not contain two adjacent oxygen atoms and that the sum of a, b, C, d and e is equal to at least 3;
R1selected from the group including H, C1-4alkyl, C6arils1-4alkyl;
R60each independently from each other selected from the group comprising C1-C6alkoxygroup, NR12R13; halogen, heteroseksualci, such as piperidine;
R61each independently from each other selected from the group comprising R60and C1-C6alkyl;
X denotes a group of the formula -(CH2)n-where n is 2 or 3; or a group of formula II:

where Y denotes CH2, S;
R75and R76denote H;
Z denotes the 6aryl or heteroaryl, such as pyridine; each of which optionally has one Deputy selected from the group R2;
R2selected from the group including H, C1-4alkyl, halogen, heterocyclics1-4,alkyl, C6arils1-4alkylamino1-4alkyl and a group of the formula -(CH2)fN(R11)-(R10);
where heteroseksualci, arylalkylamines each optionally have one Deputy, selected from the group R61;
f denotes 1;
R11denotes H;
R10represents C1-6alkyl, C2-6alkenyl,3-8cycloalkyl, aryl, C6arils1-4alkyl, heteroaryl1-4alkyl, where aryl optionally has one Deputy selected from the group R61;
R12and R13each independently from each other represents C1-4alkyl;
R20and R21each independently from each other represents C1-4alkyl, where alkyl optionally has one Deputy selected from the group R60;
provided that the compound is not N-(4-ethoxybenzyl)-N-(2-oxazepan-3-yl)-2-phenoxyacetamide or N-[(2-forfinal)methyl]-N-(2-oxazepan-3-yl)-2,2-diphenylacetamide.

34. A method of treating infection caused by HCV, in a patient suffering from this infection, namely, that the patient is administered in a therapeutically effective amount of substituted the initial accoutability formula I.

35. A method of treating infection caused by HCV, in a patient suffering from this infection, namely, that the patient is administered in a therapeutically effective amount of a substituted oxaazamacrocycles formula I.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I), where R2 denotes H, [(C1-C6) alkylene]0-1-R'; R3 denotes H; R4 denotes H, halogen or (C1-C6) alkyl; R5 denotes H or halogen; R6 denotes H, (C1-C8) alkyl, R', (C1-C6) alkylene-R'; R7 and R8 independently denote H, halogen, (C1-C6) alkyl, O-(C1-C6) alkyl, R'; R9 denotes (C1-C6)alkyl; n equals 0 or 1; L denotes O or O-(C1-C6)alkylene; where R' denotes (C3-C8) cycloalkyl; (C5-C10)heterocyclyl, which denotes an aromatic or saturated mono- or bicyclic ring system which, besides a carbon atom, includes one or more heteroatoms such as nitrogen, oxygen and sulphur atoms; or (C6-C10) aryl; where in the heterocyclyl is unsubstituted or substituted with (C1-C6)alkyl, and the aryl is unsubstituted or substituted with a halogen, (C1-C4)alkyl, -O-(C1-C4)alkyl, SO2- (C1-C4) alkyl or N[(C1-C4) alkyl]2; and where in groups R4, R6 and R7 the alkyl can be halogenised in one or more positions; or pharmaceutically acceptable salts and/or stereo isomer forms thereof. The invention also relates to use of formula (I) compounds, as well as a medicinal agent.

EFFECT: obtaining novel biologically active compounds having Rho-kinase inhibiting activity.

21 cl, 320 ex, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new compound presented by general formula (I) where values of Rx, R3, R4, X and A substitutes are described in the patent claim, inhibiting tyrosine kinase of EGF receptor and HER2 tyrosine kinase, as well as to using the compound of formula (I) and pharmaceutical composition containing this compound or its pharmaceutically acceptable salt.

EFFECT: preparation of the tyrosine kinase inhibiting compound.

14 cl, 19 ex, 53 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new pyrrolidine derivatives of general formula (1) or its pharmaceutically acceptable salts where R101 and R102 values are described by the patent claim. The compounds inhibit serotonin and/or norepinephrine and/or dopamine reabsorption thereby allowing to be used for treating depression and anxiety disorder. A method for preparing thereof is described.

EFFECT: preparation of new pyrrolidine derivatives.

10 cl, 162 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound of formula I: where Y1 and Y2 are independently selected from N and CR10, where R10 is selected from group, including hydrogen, halogen, C1-C6alkyl, halogen(C1-C6)alkyl, R1 is selected from group, including hydrogen, cyano, halogen, C1-C6alkyl, halogen(C1-C6)alkyl, C1-C6alkoxy, halogen(C1-C6)alkoxy, dimethylamino, C1-C6alkylsulfanyl, dimethylaminoethoxy and pyperasinyl, substituted up to 2 radicals C1-C6alkyl, R2 and R5 are independently selected from group, including hydrogen, cyano, halogen, C1-C6alkyl, halogen(C1-C6)alkyl, C1-C6alkoxy, halogen(C1-C6)alkoxy and dimethylamino, R3 and R4 are independently selected from group, including hydrogen, halogen, cyano, C1-C6alkyl, halogen(C1-C6)alkyl, C1-C6alkoxy, or R1 and R5 with phenyl, to which they are bound, form C5-C10heteroaryl, R6 and R7 are independently selected from group, including hydrogen, C1-C6alkyl, C1-C6alkoxy and halogen(C1-C6)alkyl, on condition that R6 and R7 both do not represent hydrogen, R8 is selected from group, including hydrogen, halogen, C1-C6alkyl, C1-C6alkoxy and halogen(C1-C6)alkoxy, R9 is selected from -S(O)2R11, -C(O)R11, -NR12aR12b and -R11, where R11 is selected from group, including aryl, cycloalkyl and heterocycloalkyl, R12a and R12b are independently selected from (C1-C6)alkyl and hydroxy(C1-C6)alkyl, and said aryl, heteroaryl, cycloalkyl and heterocycloalkyl in composition of R9 optionally contain as substituents from 1 to 3 radicals, independently selected from group, including (C1-C6)alkyl, halogen(C1-C6)alkyl, C1-C6alkoxy, halogen(C1-C6)alkoxy, C6-C10aryl(C0-C4)alkyl, C5-C10heteroaryl(C0-C4)alkyl, C3-C12cycloalkyl and C3-C8heterocycloalkyl, where said arylalkyl substituent in composition of R9 optionally contains as substituents from 1 to 3 radicals, independently selected from group, including halogen, cyano, (C1-C6)alkyl, halogen(C1-C6)alkyl, C1-C6alkoxy, halogen(C1-C6)alkoxy, dimethylamino and methyl-pyperasinyl, as well as to its pharmaceutically acceptable salts, hydrates, solvates and isomers. In addition, invention relates to method of inhibiting hedgehog pathway in cell and to method of inhibiting undesirable cell proliferation, when cell contacts with compound described above.

EFFECT: obtained and described are novel compounds, which can be applied in medicine.

13 cl, 153 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) where: R1 denotes C1-C10alkyl, C3-C10cycloalkyl; R3 denotes H, halide; R4 denotes a 6-member monocyclic heteroaryl containing 1-2 nitrogen atoms, one of which can be oxidised, optionally substituted with a halide; n ranges from 0 to 3; provided that R1 denotes C3-C10cycloalkyl and/or R4 denotes a 6-member monocyclic heteroaryl optionally substituted with a halide and containing 2 ring N heteroatoms, one of which can be oxidised or pharmaceutically acceptable salt thereof.

EFFECT: obtaining peptidyl deformylase (PDF) inhibiting compounds.

12 cl, 24 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of general formula (I-B), where values of radicals are described in formula of invention, or to its pharmaceutically acceptable salts, which possess activity of inhibiting cholesterol ester transfer protein, due to which said compounds or salts can be used for prevention and/or treatment of arteriosclerotic diseases, hyperlipemia or dislipidemia or similar diseases.

EFFECT: obtaining pharmaceutical compositions for prevention and treatment of arteriosclerosis, as well as application of formula I-B compounds for manufacturing of medication.

15 cl, 36 tbl, 252 ex

FIELD: chemistry.

SUBSTANCE: invention describes compounds of formula I

, where R1 is selected from a group comprising hydrogen, lower alkyl, lower hydroxyl, lower alkoxyalkyl, lower halogenalkyl, lower cyanoalkyl; unsubstituted or substituted phenyl; lower phenylalkyl, where the phenyl ring can be unsubstituted or substituted; and heteroaryl, selected from pyridyl and pyrimidinyl; R2 denotes hydrogen or halogen; G denotes a group selected from

, where m equals, 0, 1; R3 is selected from lower alkyl, cycloalkyl and lower cycloalkylalkyl; n equals 0, 1; R4 denotes lower alkyl, as well as pharmaceutical compositions.

EFFECT: said compounds are used to treat or prevent diseases associated with histaminase receptor modulation.

19 cl, 1 tbl, 24 ex

FIELD: chemistry.

SUBSTANCE: invention relates to N-alkylamides of formula I

, where A is selected from such groups as -CH2-CH2-, -CH2-CH2-CH2- and -Y-CH2-CH2-, where Y is selected from O, S and NR11 and Y is bonded to a Het group; Het denotes a 5-member or 6-member monocyclic aromatic group which contains one or two identical or different heterocyclic ring elements selected from N, NR13 and S, and which can be substituted with one or more identical or different substitutes R5; X denotes a single bond; R1 and R2 together with a N-CO group which contains them, form a 4-10-member monocyclic or bicyclic saturated or unsaturated ring which, besides a nitrogen ring atom which is part of the N-CO group, can contain one or two additional heterocyclic ring elements selected from N, NR12, O and S, which can be identical or different, provided that two ring elements from O and S cannot be in neighbouring positions in the ring, where the ring, formed by R1 and R2 and the N-CO group containing them, can be substituted with one or more identical or different substitutes R8; R3 is selected from phenyl, naphthalinyl and heteroaryl, which all can be substituted with one or more identical or different substitutes selected from a halogen atom, (C1-C4)alkyl, (C1-C4)alkyloxy group, which can be substituted with one or more fluorine atoms, (C1-C4)alkylamino, di((C1-C4)alkyl)amino, ((C1-C4)alkyl)-CONH-, CONH2, CN, CF3, H2NSO2- and (C1-C4)alkyl-SO2-; R5 is selected from a halogen atom and (C1-C4)alkyl; R8 is selected from a halogen atom, (C1-C4)alkyl and an oxo-group; R11 denotes a hydrogen atom; R12 is selected from a hydrogen atom and (C1-C4)alkyl; R13 is selected from a hydrogen atom and (C1-C4)alkyl; heteraryl is a 5-member or 6-member monocyclic aromatic group which contains one, two or three identical or different heterocyclic ring elements selected from N, NR13, O and S; in any of its stereoisomeric forms or mixture of stereoisomeric forms in any ratio, or its physiologically acceptable salt; provided that the -N(R2)-CO-R1 group cannot be an unsubstituted 2-oxopyrrolidin-1-yl group or unsubstituted 2-oxoimidazolin-1-yl group if the -N(R2)-CO-R1 group simultaneously denotes a group of formula

,

in which the bond through which the group is bonded to group A, is denoted by a line starting from position 2 of the pyridine ring, and in which R90 is selected from imidazol-1-yl, isoxazol-5-yl, isothiazol-5-yl, 1,2,4-thiazol-1-yl, pyrazin-2-yl and pyrazol-3-yl, which can all be substituted with (C1-C4)alkyl and which can be substituted in the pyridine ring with at most four substitutes selected from (C1-C4)alkyl and a halogen atom; and provided that the -N(R2)-CO-R1 cannot be a 1,3-dioxoisoindol-2-yl group of formula

in which the bond through which the group is bonded to group A is denoted by a line beginning from the nitrogen atom. The invention also relates to a method of producing said compounds, a pharmaceutical composition for stimulating endothelia NO synthase, as well as to use thereof in preparing a medicinal agent.

EFFECT: novel compounds which can be used in conditions where high expression of the said enzyme, high content of NO or normalisation of low content of NO is desired are obtained and described.

18 cl, 87 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula [I-D1] or pharmaceutically acceptable salt thereof,

,

where each symbol is defined in the claim. The invention also relates to pharmaceutical compositions containing said compound and having HCV polymerase inhibiting activity.

EFFECT: disclosed compound exhibits anti-HCV activity, based on HCV polymerase inhibiting activity and is useful as an agent for preventing and treating hepatitis C.

32 cl, 497 tbl, 1129 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives of formula I

or pharmaceutically acceptable salts thereof, where R1 denotes (1-6C)alkyl; R2, R3 independently denote halogen, (1-4C)alkoxy; R4 denotes phenyl or a 5-6-member heteroaryl, having one or two heteroatoms selected from nitrogen, oxygen or sulphur, phenyl or said heteroaryl, substituted with R7 and optionally substituted on the (hetero)aromatic ring with one or two substitutes selected from halogen, nitro, trifluoromethyl and (1-4C)alkyl; R7 denotes H, (1-4C)alkylthio, (1-4C)alkylsulphonyl, R8R9-amino, R10R11-aminocarbonyl, R12R13-amino(1-4C)alkylcarbonyl-amino, R14R15-amino(1-4C)alkyl, R16-oxy, R17R18-aminocarbonyl (1-4C)alkoxy, R19-oxy(1-4C)alkyl, R19-oxycarbonyl(1-4C)alkyl, R20R21-aminosulphonyl, R20-oxysulphonyl, aminoiminomethyl, (di)(1-4C)alkylaminoiminomethyl, morpholinyliminomethyl, trifluoromethylsulphonyl; R23-oxycarbonyl, or R23R24-aminocarbonyl; R8 denotes H or (1-4C)alkyl; R9 denotes (1-4C)alkylsulphonyl, (1-6C)alkylcarbonyl, (2-6C)alkenylcarbonyl, (3-6C)cycloalkylcarbonyl, (1-4C)alkoxycarbonyl, (3-4C)alkenyloxycarbonyl, (di)(1-4C)alkylaminocarbonyl, piperazinylcarbonyl, (5-8C)alkyl, (3-6C)cycloalkyl(1-4C)alkyl or phenylcarbonyl, furylcarbonyl, thiophenylsulphonyl, 5-member heteraryl(1-4C)alkyl, having one or two nitrogen atoms, optionally substituted on the heteroaromatic ring with one, two or three substitutes selected from hydroxy, amino, halogen, nitro, trifluoromethyl, (1-4C)alkoxy; R10 denotes H or (1-4C)alkyl; R11 denotes hydroxy(2-4C)alkyl, (1-4C)alkoxy(2-4C)alkyl; R12, R13 independently denote H, (1-6C)alkyl, (3-6C)-cycloalkyl, (1-4C)alkoxy(2-4C)alkyl, (3-6C)cycloalkyl-(1-4C)alkyl, pyrrolidinyl(1-4C)alkyl, amino(2-4C)alkyl, (di)(1-4C)-alkylamino(2-4C)alkyl or phenyl(1-4C)alkyl, pyridinyl (1-4C)alkyl; or R12R13 in R12R13-amino(1-4C)alkylcarbonylamino can be bonded together with the nitrogen atom to which they are bonded into a (5-6C)heterocycloalkyl ring, having one or two nitrogen atoms, optionally substituted with hydroxy(1-4C)alkyl; R14, R15 independently denote H, (1-6C)alkyl, (1-6C)alkylcarbonyl, (1-4C)alkoxycarbonyl or pyridinyl(1-4C)alkyl, optionally substituted on the aromatic ring with one substitute selected from halogen; or R16 denotes (di)(1-4C)alkylamino(2-4C)alkyl, hydroxycarbonyl(1-4C)alkyl, (1-4C)alkoxycarbonyl(1-4C)alkyl, phenyl(1-4C)alkyl or pyridinyl(1-4C)alkyl; R17, R18 independently denote H, (1-6C)alkyl, thiophenyl(1-4C)alkyl; or R17R18 in R17R18-aminocarbonyl(1-4C)alkoxy can be bonded into a morpholine or piperazine ring, R19 denotes H or (1-6C)alkyl; R20R21 independently denote H, (1-6C)alkyl or (1-4C)alkoxy(1-4C)alkyl; or R20R21 in R20R21-aminosulphonyl can be bonded into a morpholine ring; X denotes O or N-R22; Y denotes CH2 or C(O); Z denotes CN or NO2; R22 denotes H; R23, R24 independently denotes H; (1-4C)alkyl; or R23R24 in R23R24-aminocarbonyl can be bonded into a dihydropyridine ring; provided that compounds of formula I, in which X denotes O, R4 denotes phenyl and R7 is selected from H, (1-4C)alkylthio, (1-4C)alkylsulphonyl, R23-oxycarbonyl, and R23R24-aminocarbonyl, and compounds of formula I, in which X denotes O, R4 denotes (2-5C)heteroaryl and R7 denotes H are excluded. The invention also relates to use of 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives to prepare a medicinal agent for treating sterility.

EFFECT: improved useful biological properties.

12 cl, 73 ex

FIELD: synthesis of biologically active compounds.

SUBSTANCE: invention provides 1,5-benzothiazepines of general formula I (formulae presented below), in which Rv and Rw are independently selected from hydrogen and C1-C5-alkyl; one of Rx and Ry represents hydrogen or C1-C6-alkyl and the other hydroxy or C1-C6-alkoxy; Rz is selected from halogen, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, C1-C6-alkyl, and other residues indicated in claim 1 of invention; v is a number from 0 to 5; one of R4 and R5 represents group of general formula IA; R3 and R6 and the second from R4 and R5 are independently selected from hydrogen, halogen, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, C1-C6-alkyl, and other residues indicated in claim 1; R3 and R6 and the second from R4 and R5 being optionally substituted by one or several R16 groups at their carbon atoms; D represents -O-, -N(Ra)-, -S(O)b- or -CH(Ra)-, wherein Ra is hydrogen or C1-C6-alkyl; and b=0-2; ring A represents aryl or heteroaryl and is optionally substituted by one or several substituents selected from R17; R7 represents hydrogen, C1-C4-alkyl, carbocyclyl, or heterocyclyl and is optionally substituted by one or several substituents selected from R18; R8 represents hydrogen or C1-C4-alkyl; R9 represents hydrogen or C1-C4-alkyl; R10 represents hydrogen or C1-C4-alkyl, carbocyclyl, or heterocyclyl and is optionally substituted by one or several substituents selected from R19; R11 represents carboxy, sulfo, sulfino, phosphono, tetrazolyl, -P(O)(ORc)(ORd), -P(O)(OH)(ORc), -P(O)(OH)(Rd), or -(O)(ORc)(Rd), wherein Rc and Rd are independently selected from C1-C6-alkyl; or R11 represents group of general formula IB, in which X is -N(Rq)-, N(Rq)C(O)-, -O-, or -S(O)a, wherein a=0-2; and Rq is hydrogen or C1-C4-alkyl; R12 represents hydrogen or C1-C4-alkyl; R13 and R14 are independently selected from hydrogen, C1-C4-alkyl, carbocyclyl, heterocyclyl, or R23, of which C1-C4-alkyl, carbocyclyl, heterocyclyl, or R23 can be optionally independently substituted by one or several substituents selected from R20; R15 represents carboxy, sulfo, sulfino, phosphono, tetrazolyl, -P(O)(ORe)(ORf), -P(O)(OH)(ORe), -P(O)(OH)(Re), or -P(O)(ORe)(Rf), wherein Re and Rf are independently selected from C1-C6-alkyl; or R15 represents group of general formula IC, in which R24 is selected from hydrogen and C1-C4-alkyl; R24 is selected from hydrogen, C1-C4-alkyl carbocyclyl, heterocyclyl, and R27, of which C1-C4-alkyl, carbocyclyl, heterocyclyl, or R27 can be optionally independently substituted by one or several substituents selected from R28; R26 is selected from carboxy, sulfo, sulfino, phosphono, tetrazolyl, -P(O)(ORg)(ORh), -P(O)(OH)(ORg), -P(O)(OH)(Rg), or -P(O)(ORg)(Rh), wherein Rg and Rg are independently selected from C1-C6-alkyl; p=1-3; wherein meanings for R13 can be the same or different; q=0-1; r=0-3; wherein meanings for R14 can be the same or different; m=0-2; wherein meanings for R10 can be the same or different; n=1-3; wherein meanings for R7 can be the same or different; z=0-3; wherein meanings for R25 can be the same or different; R16, R17, and R18 are independently selected from halogen, nitro, cyano, hydroxy, carbamoyl, mercapto, sulfamoyl, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-alkoxy, C1-C4-alkanoyl, C1-C4-alkanoyloxy, N-(C1-C4-alkyl)amino, N,N-(di-C1-C4-alkyl)amino, C1-C4-alkyl-S(O)a (wherein a=0-2), C1-C4-alkoxycarbonyl, N-(C1-C4-alkyl)sulfamoyl, and N,N-(di-C1-C4-alkyl)sulfamoyl; wherein R16, R17, and R18 can be optionally independently substituted by one or several of R21 at their carbon atoms; R19, R20, R23, R27, and R28 are independently selected from halogen, nitro, cyano, hydroxy, carbamoyl, mercapto, sulfamoyl, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-alkoxy, C1-C4-alkanoyl, C1-C4-alkanoyloxy, N-(C1-C4-alkyl)amino, N.N-(di-C1-C4-alkyl)amino, C1-C4-alkanoylamino, N-(C1-C4-alkyl)carbamoyl, N,N-(di-C1-C4-alkyl)carbamoyl, C1-C4-alkyl-S(O)a (wherein a=0-2), C1-C4-alkoxycarbonyl, N-(C1-C4-alkyl)sulfamoyl, N,N-(di-C1-C4-alkyl)sulfamoyl, carbocyclyl, heterocyclyl, sulfo, sulfino, amidino, phosphono, -P(O)(ORa)(ORb), -P(O)(OH)(ORa), -P(O)(OH)(Ra), or -P(O)(ORa)(Rb), wherein Ra and Rb are independently selected from C1-C6-alkyl and wherein R19, R20, R23, R27, and R28 can be optionally independently substituted by one or several of R22 at their carbon atoms; R21 and R22 are independently selected from halogen, hydroxy, cyano, carbamoyl, mercapto, sulfamoyl, trifluoromethyl, trifluoromethoxy, methyl, ethyl, methoxy, ethoxy, vinyl, allyl, ethynyl, methoxycarbonyl, formyl, acetyl, formamido, acetylamino, acetoxy, methylamino, dimethylamino, N-methylcarbamoyl, N,N-dimethylcarbamoyl, methylthio, methylsulfinyl, mesyl, N-methylsulfamoyl, N,N-dimethylsulfamoyl; or pharmaceutically acceptable salt thereof, solvate, or salt solvate. Described are also method for preparing compounds of formula I, pharmaceutical compositions based on compounds I, and a method for achieving inhibiting effect relative to interscapular brown adipose tissue (IBAT), and intermediates. (I), (IA), (IB), (IC).

EFFECT: expanded synthetic possibilities in the 1,5-benzothiazepine series.

36 cl, 121 ex

FIELD: biochemistry, medicine, in particular new bioactive compounds having peptide hormone vasopressin agonistic activity.

SUBSTANCE: disclosed are compounds of general formula 1 or 2 or tautomers, or pharmaceutically acceptable salts thereof, wherein W represents N or C-R4; R1-R4 are independently H, F, Cl, Br, alkyl, O-alkyl, NH2, NH-alkyl, N(alkyl)2, NO2 or R2 and R3 together may form -CH=CH-CH=CH-; G1 represents bicyclic or tricyclic condensed azepine derivatives selected from general formulae 3-8 wherein A1, A4, A7, and A10 are independently CH3, O, and NR5; A2, A3, A9, A11, A12, A14, and A15 are independently CH and N; or A5 represents covalent bond and A6 represents S; or A5 represents N=CN and A6 represents covalent bond; A8 and A12 are independently NH, N-CH3 and S; A16 and A17 both represent CH2 or one of A16 and A17 represents CH2 and the other represents CH(OH), CF2, O, SOa, and NR5; R5 represents H, alkyl, CO-alkyl, and (CH2)bR6; R6 represents phenyl, pyridyl, OH, CO2H; a = 0-2; b = 1-4; Y represents CH or N; Z represents CH=CH or S; and G2 represents group selected from groups of formulae 9-11 wherein Ar represents phenyl, pyridyl, naphthyl, and mono- or polysubstituted phenyl, pyridyl, wherein substituents are selected from F, Cl, Br, alkyl, NO2; D represents covalent bond or NH; E1 and E2 both are H, OMe, F, or one of E1 and E2 represents OH, O-alkyl, OBn, OPh, OAc, F, Cl, Br, N2, NH2, NHBn or NHAc and the other represents H; or E1 and E2 together form =O, -O(CH2)gO- or -S(CN2)gS-; F1 and F2 both represent H or together form =O or =R; L represents OH, O-alkyl, NH2, NH-alkyl, and NR9R10; R7 represents COR8; R8 represents OH, O-alkyl, NH2, NH-alkyl, N(alkyl)2, pyrolidinyl, and piperidinyl; R9 and R10 both are alkyl or together form -(CH2)h-; V represents O, N-CN or S; c = 0 or 1; d = 0 or 1, e = 0 or 1; f = 0-4; g = 2 or 3; h = 3-5, with the proviso, that both d and e are not 0. Also disclosed are pharmaceutical composition having agonistic activity in relate to V2 receptor, method for treatment one or more diseases (e.g., enuresis, nycturia, diabetes insipidus, hemorrhage disorders, urinary incontinence.

EFFECT: new compounds with value biological characteristics.

41 cl, 19 tbl, 193 ex

The invention relates to new theatlanticwire.com General formula I, where R1means a sulfur atom, R2means hydrogen, -R3-R4-R5-R6means a chain of formula-CH2-CH2-CH2-CH2-, -CH2-CH2-CH2-CH(R8)-, -CH2-CH2-CH2-S-, -CH2-CH2-CH2-SO-, -CH2-CH2-CH2-SO2- and so on, R7means polyfluoroankyl or polyporales, R8means hydroxyl, R9means benzyl, R10means alkyl, -CH2HE-Sooma, -COOH or-CONH2their isomers, racemates, enantiomers and salts with inorganic or organic acid

The invention relates to new 1,4-benzothiazepine-1,1-dioxides of the formula (I), where R1is non-branched C1-6alkyl group, R2is non-branched C1-6alkyl group, R3is hydrogen, R4represents phenyl, R5R6and R8selected from hydrogen, R7represents a group of formula (Ia) and (IB), where the hydroxy-group may be substituted by acetyl, R16represents-COOH, -CH2-OH, -CH2-O-acetyl-Sooma, R9and R10the same or different and each represents hydrogen or C1-6alkyl group, X represents-O-, or its salt, solvate and physiologically acceptable derivative

The invention relates to new 1,4-benzothiazepine-1,1-dioxides of the formula II, where R1, R2are primocane C1-6alkyl group; R4represents unsubstituted phenyl; R5and R8represent hydrogen; R6represents methoxy or bromo; R7arepresents methoxy, hydroxy or trifluoromethyl; R9and R10represent hydrogen, salts, solvate or physiologically functional derivatives, and method of production thereof

The invention relates to a method for producing 3-hydroxy-5- [2-(dimethylamino)-ethyl] -2,3-dihydro-4-(methoxyphenyl)-1)5 - benzothiazepin-4(5H)-she and its salts, which can be used to produce pharmaceutically active compounds, such as CIS-(+)-3-acetoxy-5-[2-(dimethylamino)-ethyl] -2,3 - dihydro-4-(methoxyphenyl)-1,5-benzothiazepin-4(5H)he, who then is called diltiazem

The invention relates to a condensed heterocyclic compounds or their salts and inhibitors of squalene synthetase containing these compounds as an effective component

FIELD: chemistry.

SUBSTANCE: invention relates to derivatives of 3-aminocaprolactam of formula (I): , where X represents -CO-R1 or -SO2-R2, R1 represents alkyl (with the exception of 5-methylheptanyl and 6-methylheptanyl, where radical R1 is bonded to carbonyl in position 1), halogenalkyl, alkoxy (with the exception of tret-butyloxy), alkenyl, alkinyl or alkylamino radical from 4-20 carbon atoms (for example, from 5-20 carbon atoms, 8-20 carbon atoms, 9-20 carbon atoms, 10-18 carbon atoms, 12-18 carbon atoms, 13-18 carbon atoms, 14-18 carbon atoms, 13-17 carbon atoms) and R2 is alkyl radical from 4-20 carbon atoms (for example, from 5-20 carbon atoms, 8-20 carbon atoms, 9-20 carbon atoms, 10-18 carbon atoms, 12-18 carbon atoms, 13-18 carbon atoms, 14-18 carbon atoms, 13-17 carbon atoms); or to its pharmacologically acceptable salt. Invention also relates to application and pharmacological composition, which has anti-inflammatory activity, based on said compounds.

EFFECT: obtaining new compounds and based on them pharmacological composition, which can be applied for obtaining medications for treatment, relief or prevention of inflammatory disease symptoms.

57 cl, 62 ex

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