Amino alcohol derivatives or phosphoric acid derivatives and pharmaceutical compositions containing specified derivatives

FIELD: medicine; pharmacology.

SUBSTANCE: invention refers to new compositions of general formula (I): where R1 and R2 mean H; R3 means H; R4 means lower alkyl; n is equal to 1-6; X means O; formula group =N-D (where D means H, lower alkyl); Y means ethylene group, ethynylene group, formula group -E-CH2 - (where E means carbonyl, formula group -CH(OH)-), C6-C10arylen C6-C10arylen group substituted with 1-3 substitutes, selected from Group (a) of substitutes; Z means single bond, C1-C10alkylen group or C1-C10alkylen group containing oxygen atom in specified carbon chain or on the end of specified carbon chain; R5 means H, C3-C10cycloalkyl group, C6-C10aryl, C6-C10aryl group substituted with 1-3 substitutes selected from Group (a) of substitutes; R6 and R7 are identical or different and represent each H, lower alkyl; Group (a) of substitutes represents group consisting of halogen, lower alkyl group, halogenated lower alkyl group, lower alkoxy group, lower alkylthio group; provided when R5 represents H, Z represents branched C1-C10alkylen group or C1-C10alkylen group containing oxygen atom in specified carbon chain or on the end of specified carbon chain, or it pharmacologically acceptable salt.

EFFECT: high immunosuppressive activity of compounds and their effective application for pharmaceutical compositions and for methods of preventive rheumatoid arthritis treatment.

51 cl, 13 tbl, 91 ex

 

The technical field to which the invention relates

The present invention relates to the derivatives of aminoalcohols or derivatives of phosphonic acids with high immunosuppressive activity, pharmacologically acceptable salts of the derivatives of aminoalcohols or derivatives of phosphonic acids, pharmacologically acceptable esters derivatives of aminoalcohols or derivatives of phosphonic acids and to pharmaceutical compositions containing these compounds as the active component.

The present invention relates also to pharmaceutical compositions containing as active ingredients one or more immunosuppressants and one or more compounds selected from the group consisting of derivatives of aminoalcohols or derivatives of phosphonic acids with high immunosuppressive activity, their pharmacologically acceptable salts and their pharmaceutically acceptable esters. These compositions are useful as preventive or therapeutic agents against autoimmune diseases such as rejection of transplanted tissues or cells, rheumatoid arthritis or other autoimmune diseases associated with immune activity.

Background of invention

Earlier against inflammatory reactions, the mod is emich pathological immune response in the treatment of diseases, associated with the immune system such as rheumatoid arthritis and other autoimmune diseases have already used anti-inflammatory drugs, such as steroids. But these tools treat the symptoms and not the disease itself.

In addition, there were reports that disturbances in the immune system also contribute to the development of diabetes and nephritis, but the means to treat these disorders have not yet been developed.

On the other hand, is important to create a method of suppressing immune response to prevent rejection of transplanted tissues or cells, as well as for treatment and prevention of various autoimmune diseases.

It is known, however, that existing immunosuppressants, such as cyclosporine A (CsA) and tacrolimus (TRL), toxic to the kidneys and liver. Although to get rid of these adverse reactions usually used steroids, but these tools do not always give satisfactory immunosuppressive effect without any adverse reactions.

Given these prerequisites, many attempts were made to find less toxic compounds with high immunosuppressive effects.

As immunosuppressants, the following known compounds.

(1) compounds of General formula (a)disclosed in the description of the WO94/08943 (page 371):

{pointed to by the x connections:

Rxrepresents an unbranched or branched carbon chain which may be optionally substituted by one or more substituents [the chain may contain a double bond, a triple bond, an oxygen atom, a sulfur atom, a group of the formula-N(Rx6)- (where R26represents a hydrogen atom), Allenova group which may be optionally substituted by one or more substituents, or heteroarenes group which may be optionally substituted by one or more substituents, and may contain, at its end, aryl group which may be optionally substituted by one or more substituents, cycloalkyl group which may be optionally substituted by one or more substituents, or an aromatic heterocyclic group which may be optionally substituted by one or more substituents], and

Rx2, Rx3, Rx4and Rx5are the same or different and represent each a hydrogen atom or alkyl group} known as immunosuppressants.

These compounds (a) prior art contain two oxymethylene group (-CH2ORx4and CH2ORx5in quality the ve essential groups, substituted at the same carbon atom. And compounds of the present invention contain one group-CH2OR3and one lower alkyl group as significant groups, substituted at the same carbon atom, and differ from the compounds (a) specified substituents.

(2) compounds of General formula (b)disclosed in the description of the WO96/06068 (page 271):

[in the above compounds (b):

Ry1, Ry2and Ry3represent each a hydrogen atom or the like, W is a hydrogen atom, alkyl group or the like, Zyrepresents a single bond or alkilinity group, Xyrepresents a hydrogen atom or alkoxygroup and Yyrepresents a hydrogen atom, alkyl, alkoxy, acyl, acyloxy-, amino-, alluminare or the like] is known as immunosuppressants.

These compounds (b) contain a phenyl group as a significant group in the basic skeleton. Compounds of the present invention contain, instead of the phenyl group of compounds (b), a heterocyclic group, such as furilla group, pyrrolidine group or pyrrolidine group with the Deputy at the nitrogen atom, and differ from the compounds (c).

However, compounds having the chemical structure of the ur, similar to the structure of the compounds of formula (I) according to the present invention, in the aforementioned publication does not specifically disclosed.

(3) compounds of General formula (C)disclosed in the description to WO98/45249:

[in the above compounds (C):

Rz1, Rz2, Rz3and Rz4are the same or different and represent each a hydrogen atom or an acyl group] known as immunosuppressants.

These compounds (C) contain two oxymethylene group (-CH2ORz3and CH2ORz4as significant (important) groups, substituted at the same carbon atom. And compounds of the present invention contain one group-CH2OR3and one lower alkyl group as significant groups, substituted at the same carbon atom, and differ from the compounds (a) specified substituents.

In addition, these compounds (C) include phenyl group between the group -(CH2)2- and group-CO-(CH2)4as a significant group in the basic skeleton. Compounds of the present invention contain, instead of the phenyl groups of the compounds (C), a heterocyclic group, such as furilla group, pyrrolidine group or pyrrolidine group having is I Deputy at the nitrogen atom, and differ from the compounds (c).

On the other hand, the compound having the below General formula (II) according to the present invention, where X represents a sulfur atom, as disclosed in the description of WO 02/06268 in the form of joint in which the protective group of the hydroxyl group is the residue of ester of phosphoric acid.

In addition, with regard to combinations of immunosuppressants, in the publication (Kokai) Japan patent No. Hei 11-80026 disclosed combination of immunosuppressants, such as FTY-720 and cyclosporine a or FTY-720 and tacrolimus.

In light of these assumptions is desirable to find a pharmaceutical composition with high immunosuppressive effects that would be less toxic.

Disclosure of the invention

The creators of the present invention intensively researched new compounds with high immunosuppressive activity with low toxicity, and find new compounds which are useful as preventive or therapeutic agents against autoimmune diseases or other immune-related diseases such as rejection caused by transplantation of various organs or skin, systemic lupus erythematosus, rheumatoid arthritis, polymyositis, fibrositis, inflammation of the skeletal muscles, epiphyseal osteomyelitis, osteoarthritis, dermatomyositis, scleroderma syndrome B is chcete, Crohn's disease, ulcerative colitis, autoimmune hepatitis, aplastic anemia, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, multiple sclerosis, autoimmune bullet, psoriasis vulgaris, vasculitis syndrome, granuloma Wegener, uveitis, Sjogren syndrome, idiopathic interstitial pneumonia syndrome?, sarcoidosis, allergic granulomatous of anyit, bronchial asthma, myocarditis, cardiomyopathy syndrome aortica, postinfarction syndrome, primary pulmonary hypertension, nephrotic syndrome with minimal change, membranous nephropathy, membrane-proliferative glomerulonephritis, focal glomerular sclerosis, sickle glomerulonephritis, myasthenia gravis heavy psevdomatematicheskoe, inflammatory neuropathy, atopic dermatitis chronic actinic dermatitis, photosensitivity, bedsores, chorea of Sydenham, sclerosis, diabetes mellitus in adults, insulin-dependent diabetes mellitus, juvenile diabetes, atherosclerosis, glomerular nephritis, IgA nephropathy, canalave-interstitial nephritis, primary biliary cirrhosis, primary sclerosing cholangitis, fulminant hepatitis, viral hepatitis, GVHD (illness "graft versus host"), contact dermatitis and sepsis; infectious diseases caused by fungus, Mycoplasma, what irusa and the simplest and the like; cardiovascular diseases such as heart failure, cardiac hypertrophy, arrhythmia, angina, cardiac ischemia, arterial embolism, aneurysm, varicose blood vessels and circulatory disorders; brain diseases such as Alzheimer's disease, dementia, Parkinson's disease, stroke, heart attack, brain, cerebral ischemia, depression, manic-depressive psychosis, schizophrenia, Huntington's chorea, epilepsy, convulsion, attention deficit disorder, encephalitis, cerebral meningitis, loss of appetite and hyperphagia; and various diseases such as lymphoma, leukemia, diuresis, and diabetic pollakiuria retinopathy (particularly, autoimmune diseases such as rejection caused by transplantation of various organs or skin, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, atopic dermatitis), which led to the creation of the present invention.

In addition, the creators of the present invention intensively studied pharmaceutical composition having immunosuppressive activity, and found that the pharmaceutical compositions of the present invention containing as active ingredients one or more immunosuppressants and one or more compounds of the present invention, exhibit high immunosuppressive and the efficiency with low toxicity. The pharmaceutical compositions according to the invention increase the activity more than the individual immunosuppressants, and reduce the number of side reactions, resulting in them becomes smaller than when using individual immunosuppressants. Therefore, the pharmaceutical compositions of the present invention are useful as preventive or therapeutic agents against autoimmune diseases or other immune-related diseases such as rejection caused by transplantation of various organs or skin, systemic lupus erythematosus, rheumatoid arthritis, polymyositis, fibrositis, inflammation of the skeletal muscles, epiphyseal osteomyelitis, osteoarthritis, dermatomyositis, scleroderma syndrome behceta, Crohn's disease, ulcerative colitis, autoimmune hepatitis, aplastic anemia, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, multiple sclerosis, autoimmune bullet, psoriasis vulgaris, vasculitis syndrome, granuloma Wegener, uveitis syndrome Sjogren's syndrome, idiopathic interstitial pneumonia syndrome?, sarcoidosis, allergic granulomatous of anyit, bronchial asthma, myocarditis, cardiomyopathy syndrome aortica, postinfarction syndrome, primary pulmonary hypertension, nephrotic syndrome with minimal change, membranous nephropathy is Atiyah, membranosa-proliferative glomerulonephritis, focal glomerular sclerosis, sickle glomerulonephritis, myasthenia gravis heavy psevdomatematicheskoe, inflammatory neuropathy, atopic dermatitis, chronic actinic dermatitis, photosensitivity, bedsores, chorea of Sydenham, sclerosis, diabetes mellitus in adults, insulin-dependent diabetes mellitus, juvenile diabetes, atherosclerosis, glomerular nephritis, IgA nephropathy, canalave-interstitial nephritis, primary biliary cirrhosis, primary sclerosing cholangitis, fulminant hepatitis, viral hepatitis, GVHD (illness "graft versus host"), contact dermatitis and sepsis; infectious diseases caused by fungus, Mycoplasma, virus and simplest and the like; cardiovascular diseases such as heart failure, cardiac hypertrophy, arrhythmia, angina, cardiac ischemia, arterial embolism, aneurysm, varix advanced vessel and circulatory disorders; brain diseases such as Alzheimer's disease, dementia, Parkinson's disease, stroke, heart attack, brain, cerebral ischemia, depression, manic-depressive psychosis, schizophrenia, Huntington's chorea, epilepsy, convulsion, attention deficit disorder, encephalitis, cerebral meningitis, loss of appetite and hyperphagia; and various Zab the diseases, such as lymphoma, leukemia, diuresis, pollakiuriya and diabetic retinopathy (particularly, autoimmune diseases such as rejection caused by transplantation of various organs or skin, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, atopic dermatitis), which led to the creation of the present invention.

The following is a more detailed description of the present invention.

(1) the Derivatives of aminoalcohols of the present invention are compounds of General formula (I)shown below:

[where

R1and R2are the same or different and represent each a hydrogen atom, a lower alkyl group or a protective group of amino group;

R3represents a hydrogen atom, a lower alkyl group or a protective group of hydroxyl group;

R4represents a lower alkyl group;

n represents an integer from 1 to 6;

X represents an oxygen atom or a group of formula =N-D (where D represents a hydrogen atom, a C6-C10aryl group, a lower alkylsulfonyl group6-C10arylsulfonyl group or a group selected from the Group of substituents);

Y represents an ethylene group, vanilinovoi group, ethynylene group, a group of the formula-is-CH 2- (where E represents a carbonyl group or a group of the formula-CH(OH) -),6-C10Allenova group or6-C10Allenova group substituted by 1-3 substituents selected from Group (a) deputies;

Z represents a single bond, C1-C10alkylenes group1-C10alkylenes group substituted by 1-3 substituents selected from the Group of substituents and the Group (b) alternates With1-C10alkylenes group containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain, or With1-C10alkylenes group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) substituents and containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain;

R5represents a hydrogen atom, a C3-C10cycloalkyl group6-C10aryl group, a 5-7-membered heterocyclic group containing 1-3 heteroatoms selected from the group consisting of a sulfur atom, oxygen atom and nitrogen atom, With3-C10cycloalkyl group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) alternates With6-C10aryl group, a substituted 1 - substituents, selected from the group consisting of Groups (a) of substituents and the Group (b) substituents, or a 5-7-membered heterocyclic group containing 1-3 heteroatoms selected from the group consisting of a sulfur atom, oxygen atom and nitrogen atom and is substituted by 1-3 substituents selected from the Group of substituents and the Group (b) deputies;

R6and R7are the same or different and represent each a hydrogen atom or a group selected from the Group (a) deputies;

Group (a) of the substituents is a group consisting of a halogen atom, a lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup, low allylthiourea, carboxyl group, lower alkoxycarbonyl group, a hydroxyl group, a lower aliphatic acyl group, amino group, mono-lower alkylamino, di-lower alkylamino, lower aliphatic alluminare, ceanography and nitro; and

Group (b) of the substituents is a group consisting of C3-C10cycloalkyl group6-C10aryl group, a 5-7-membered heterocyclic group containing 1-3 heteroatoms selected from the group consisting of a sulfur atom, oxygen atom and nitrogen atom, With3-C10cycloalkyl group substituted by 1-3 substituents selected from Group (a) Zam is stitely, With6-C10aryl group substituted by 1-3 substituents selected from Group (a) deputies, and 5-7-membered heterocyclic group containing 1-3 heteroatoms selected from the group consisting of a sulfur atom, oxygen atom and nitrogen atom and is substituted by 1-3 substituents selected from Group (a) deputies;

provided that when R5represents a hydrogen atom, Z represents a branched C1-C10alkylenes group1-C10alkylenes group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) alternates With1-C10alkylenes group containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain, or With1-C10alkylenes group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) substituents and containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain].

In accordance with the present invention provides compounds of formula (I), their pharmacologically acceptable salts and their pharmaceutically acceptable esters.

Of these preferred compounds are:

(2) the compound according to item (1)where the specified connection forms the crystals (I) has the formula (Ia):

(where R1, R2, R3, R4, R5, R6, R7, X, Y, Z and n have the same meanings as mentioned above), its pharmacologically acceptable salt or a pharmacologically acceptable ester;

(3) the compound according to item (1), where the aforementioned compound of formula (I) has the formula (Ib):

(where R1, R2, R3, R4, R5, R6, R7, X, Y, Z and n have the same meanings as mentioned above), its pharmacologically acceptable salt or a pharmacologically acceptable ester;

(4) a pharmacologically acceptable ester of the compound of formula (I) in paragraph (1), where the aforementioned compound of formula (I) has the formula (II):

(where R1, R2, R4, R5, R6, R7, X, Y, Z and n have the same meanings as above, R10and R11are the same or different and represent each a hydrogen atom or a protective group of phosphoric acid), or its pharmacologically acceptable salt;

(5) a pharmacologically acceptable ester of the compound of formula (II) in paragraph (4), where the specified ester of the formula (II) has the formula (IIa):

(where R1, R2, R4, R5, R6, R7, X, Y, Z and n have so the e same values as mentioned above, R10and R11are the same or different and represent each a hydrogen atom or a protective group of phosphoric acid), or its pharmacologically acceptable salt and

(6) a pharmacologically acceptable ester of the compound of formula (II) in paragraph (4), where the specified ester of the formula (II) has the formula (IIb):

(where R1, R2, R4, R5, R6, R7, X, Y, Z and n have the same meanings as above, R10and R11are the same or different and represent each a hydrogen atom or a protective group of phosphoric acid), or its pharmacologically acceptable salt.

(7) Derivatives of phosphonic acids of the present invention are compounds of General formula (III)shown below:

(where R1, R2, R4, R5, R6, R7, R10, R11, X, Y, Z and n have the same meanings as above).

In accordance with the present invention provides compounds of formula (III), their pharmacologically acceptable salts and their pharmaceutically acceptable esters.

Of these preferred compounds are:

(8) the compound according to item (7), where the aforementioned compound of formula (III) has the formula (IIIa):

(where R1, R2, R4, R5, R6, R7, R10, R11, X, Y, Z and n have the same meanings as mentioned above), its pharmacologically acceptable salt or a pharmacologically acceptable ester and

(9) the compound according to item (7), where the aforementioned compound of formula (III) has the formula (IIIb):

(where R1, R2, R4, R5, R6, R7, R10, R11, X, Y, Z and n have the same meanings as mentioned above), its pharmacologically acceptable salt or a pharmacologically acceptable ester.

Of these preferred compounds are:

(10) the compound according to any one of items (1)to(9), where R1and R2are the same or different and represent each a hydrogen atom, a lower aliphatic acyl group, a lower alkoxycarbonyl group, aracelikarsaalyna group or aracelikarsaalyna group substituted by 1-3 substituents selected from Group (a) substituents, or pharmacologically acceptable salt;

(11) the compound according to any one of items (1)to(9), where R1and R2are the same or different and represent each a hydrogen atom, a lower aliphatic acyl group or a lower alkoxycarbonyl group, or its pharmaceutically acceptable salt;

(12) soy is inania according to any one of items (1)to(9), where R1and R2are the same or different and represent each a hydrogen atom, a C1-C4aliphatic acyl group, or With1-C4alkoxycarbonyl group, or its pharmaceutically acceptable salt;

(13) the compound according to any one of items (1)to(9), where R1and R2are the same or different and represent each a hydrogen atom, a C1-C2aliphatic acyl group, or With1-C2alkoxycarbonyl group, or its pharmaceutically acceptable salt;

(14) the compound according to any one of items (1)to(9), where R1and R2are the same or different and represent each a hydrogen atom, acetyl group or methoxycarbonyl group, or its pharmaceutically acceptable salt;

(15) the compound according to any one of items (1)to(9), where each of R1and R2represents a hydrogen atom, or a pharmacologically acceptable salt;

(16) the compound according to any one of items (1)to(3) and (10)-(15), where R3represents a hydrogen atom, a lower alkyl group, a lower aliphatic acyl group, aromatic acyl group, aromatic acyl group substituted by 1-3 substituents selected from the Group of substituents, or a silyl group, or a pharmacologically acceptable salt;

(17) the compound according to any one of p is nchow (1)-(3) and (10)-(15), where R3represents a hydrogen atom or a lower alkyl group, or a pharmacologically acceptable salt;

(18) the compound according to any one of items (1)to(3) and (10)-(15), where R3represents a hydrogen atom or a C1-C4alkyl group, or a pharmacologically acceptable salt;

(19) the compound according to any one of items (1)to(3) and (10)-(15), where R3represents a hydrogen atom, methyl group or ethyl group, or its pharmaceutically acceptable salt;

(20) the compound according to any one of items (1)to(3) and (10)-(15), where R3represents a hydrogen atom, or a pharmacologically acceptable salt;

(21) the compound according to any one of items (1)to(20), where R4represents a C1-C4alkyl group, or a pharmacologically acceptable salt;

(22) the compound according to any one of items (1)to(20), where R4represents a C1-C2alkyl group, or a pharmacologically acceptable salt;

(23) the compound according to any one of items (1)to(20), where R4represents a methyl group, or its pharmaceutically acceptable salt;

(24) the compound according to any one of items (1)to(23), where n is an integer 2 or 3, or its pharmacologically acceptable salt;

(25) the compound according to any one of items (1)to(23), where n is an integer 2 or its pharmacologically pickup is acceptable salt;

(26) the compound according to any one of items (1)to(25), where X represents an oxygen atom, or a pharmacologically acceptable salt;

(27) the compound according to any one of items (1)to(25), where X represents a group of formula =N-D (where D represents a hydrogen atom, a C1-C4alkyl group or phenyl group), or its pharmacologically acceptable salt;

(28) the compound according to any one of items (1)to(25), where X represents a group of formula =N-CH3or its pharmacologically acceptable salt;

(29) the compound according to any one of items (1)to(28), where Y represents an ethylene group, ethynylene group, a group of the formula-CO-CH2-, a group of the formula-CH(OH)-CH2-, fenelonov group or fenelonov group substituted by 1-3 substituents selected from the group consisting of a halogen atom and a lower alkyl group, or a pharmacologically acceptable salt;

(30) the compound according to any one of items (1)to(28), where Y represents an ethylene group, ethynylene group, a group of the formula-CO-CH2or fenelonov group, or its pharmaceutically acceptable salt;

(31) the compound according to any one of items (1)to(30), where Z represents a C1-C10alkylenes group or1-C10alkylenes group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the group is s (b) Deputy or its pharmacologically acceptable salt;

(32) the compound according to any one of items (1)to(30), where Z represents a C1-C6alkylenes group or1-C6alkylenes group substituted by 1-3 hydroxyl groups, or a pharmacologically acceptable salt;

(33) the compound according to any one of items (1)to(30), where Z represents a C1-C5alkylenes group or1-C5alkylenes group substituted by 1-3 hydroxyl groups, or a pharmacologically acceptable salt;

(34) the compound according to any one of items (1)to(30), where Z represents an ethylene group, trimethylene group, tetramethylene group or ethylene, trimethylene or tetramethylene group substituted with one hydroxyl group, or its pharmaceutically acceptable salt;

(35) the compound according to any one of items (1)to(30), where Z represents an ethylene group, trimethylene group or tetramethylene group, or its pharmaceutically acceptable salt;

(36) the compound according to any one of items (1)to(30), where Z represents an ethylene group or trimethylene group, or its pharmaceutically acceptable salt;

(37) a compound according to any one of items (1)to(30), where Z represents a C1-C10alkylenes group containing an oxygen atom or a sulfur atom in the specified carbon chain or the finally specified carbon chain, or1-C10alkylenes group, substituted with one substituent and contains an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain (the Deputy selected from the group consisting of lower alkyl groups and a hydroxyl group), or its pharmacologically acceptable salt;

(38) the compound according to any one of items (1)to(30), where Z represents a C1-C10alkylenes group containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain, or a pharmacologically acceptable salt;

(39) the compound according to any one of items (1)to(30), where Z represents a C1-C10alkylenes group containing an oxygen atom in the specified carbon chain or at the end of the specified carbon chain, or a pharmacologically acceptable salt;

(40) the compound according to any one of items (1)to(30), where Z represents a C1-C6alkylenes group containing an oxygen atom in the specified carbon chain or at the end of the specified carbon chain, or a pharmacologically acceptable salt;

(41) the compound according to any one of items (1)to(30), where Z represents a group of formula-O-CH2-, -O-(CH2)2-, -O-(CH2)3-, -CH2-O-, -(CH2)2-O - or -(CH2)3-O-, or a pharmacologically ramlila salt;

(42) the compound according to any one of items (1)to(30), where Z represents a group of formula-CH2-O - or -(CH2)2-O-, or a pharmacologically acceptable salt;

(43) the compound according to any one of items (1)to(42), where R5represents a hydrogen atom, or a pharmacologically acceptable salt;

(44) the compound according to any one of items (1)to(42), where R5represents a C3-C10cycloalkyl group6-C10aryl group or3-C10cycloalkyl or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup and lower allylthiourea, or its pharmacologically acceptable salt;

(45) the compound according to any one of items (1)to(42), where R5represents a C3-C10cycloalkyl group6-C10aryl group or3-C10cycloalkyl or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups and lower alkoxygroup, or its pharmacologically acceptable salt;

(46) the compound according to any one of items (1)to(42), where R5represents a C5-C6cycloalkyl group, phenyl group or naftalina group, or its pharmaceutically acceptable salt;

(47) the compound according to any one of items (1)to(42), where R5is tsiklogeksilnogo group or phenyl group, or its pharmaceutically acceptable salt;

(48) the compound according to any one of items (1)to(47), where R6and R7are the same or different and represent sobby each a hydrogen atom, halogen atom, lower alkyl group, halogenated lower alkyl group, lower alkoxygroup or lower allylthiourea, or its pharmacologically acceptable salt;

(49) the compound according to any one of items (1)to(47), where each of R6and R7represents a hydrogen atom, or a pharmacologically acceptable salt;

(50) the compound according to any one of items (4)to(15) and (21)to(49), where R10and R11are the same or different and represent each a hydrogen atom or a lower alkyl group, or a pharmacologically acceptable salt;

(51) the compound according to any one of items (4)to(15) and (21)to(49), where R10and R11are the same or different and represent each a hydrogen atom or a C1-C4alkyl group, or a pharmacologically acceptable salt;

(52) the compound according to any one of items (4)to(15) and (21)to(49), where R10and R11are the same or different and are each the initial hydrogen atom, methyl group or ethyl group, or its pharmacologically acceptable salt,

(53) the compound according to any one of items (4)to(15) and (21)to(49), where each of R10and R11represents a hydrogen atom, or its pharmacologically acceptable salt.

Preferred are compounds according to paragraph (1), which include any combination of arbitrarily selected from the group consisting of (2) and(3), (10)-(15), (16)-(20), (21)-(23), (24) and(25), (26)-(28), (29) and(30), (31)-(42), (43)-(47) and (48) and (49).

Preferred are compounds according to paragraph (4), which include any combination of arbitrarily selected from the group consisting of (5) and(6), (10)-(15), (21)-(23), (24) and(25), (26)-(28), (29) and(30), (31)-(42), (43)-(47), (48) and (49) and(50)-(53).

Preferred are compounds according to paragraph (7), which include any combination of arbitrarily selected from the groups consisting of (8) and(9), (10)-(15), (21)-(23), (24) and(25), (26)-(28), (29) and(30), (31)-(42), (43)-(47), (48) and (49) and(50)-(53).

Of these compounds the most preferred are:

(54) a compound selected from the following compounds, its pharmacologically acceptable salt or a pharmacologically acceptable ester:

2-amino-2-methyl-4-[5-(5-fenilpentil)furan-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(5-cyclohexylidene-1-inyl)furan-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(5-finalment-1-inyl)furan-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(4-cyclohexyloxy the t-1-inyl)furan-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(4-cyclohexylmethanol)furan-2-yl]butane-1-ol and

2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-inyl]furan-2-yl}butane-1-ol;

(55) a compound selected from the following compounds, its pharmacologically acceptable salt or a pharmacologically acceptable ester:

2-amino-2-methyl-4-[1-methyl-5-(5-finalment-1-inyl)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[3-(4-methylphenoxy)prop-1-inyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxy-1-inyl)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-inyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentane)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylmethanol)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutane)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylmethanol)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(4-were)butanoyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentane)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylmethanol)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutane)pyrrol-2-yl]butane-1-ol and

2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylmethanol)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimetilfenil)butanoyl]-pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl--{1-methyl-5-[4-(3, 5dimethylphenyl)butanoyl]-pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3-triptoreline)-butanoyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(4-triptoreline)-butanoyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(4-methoxyphenyl)butanoyl]-pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3-were)butyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimetilfenil)butyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3, 5dimethylphenyl)butyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3-triptoreline)butyl]-pyrrol-2-yl}butane-1-ol;

(56) the compound according to item (4), where the join is selected from the following compounds, or its pharmacologically acceptable salt:

mono 2-amino-2-methyl-4-[5-(5-fenilpentil)furan-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-cyclohexylidene-1-inyl)furan-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-finalment-1-inyl)furan-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(4-cyclohexyloxy-1-inyl)furan-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-cyclohexylmethanol)furan-2-yl]-1-butylphosphate and

mono 2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-inyl]furan-2-yl}-1-butylphosphate;

(57) the compound according to item (4), where the join is selected from the following compounds, or its pharmacologically acceptable salt:

mono 2-amino-2-methyl-4-[1-methyl-5-(5-finalment-1-inyl)pyrrol-2-yl]-1-is Telfort,

mono 2-amino-2-methyl-4-{1-methyl-5-[3-(4-methylphenoxy)prop-1-inyl]pyrrol-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxy-1-inyl)pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-inyl]pyrrol-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentane)pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylmethanol)-pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutane)pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylmethanol)-pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{1-methyl-5-[4-(4-were)butanoyl]pyrrol-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentane)pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylmethanol)-pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutane)pyrrol-2-yl]-1-butylphosphate and

mono 2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylmethanol)-pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimetilfenil)-butanoyl]pyrrol-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{1-methyl-5-[4-(3, 5dimethylphenyl)-butanoyl]pyrrol-2-yl}-1-butylphosphate;

(58) the compound according to item (7), where the join is selected from the following compounds, or its pharmacologically acceptable salt:

3-amino-3-methyl-5-[5-(5-Hairdryer is lentil)furan-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-cyclohexylidene-1-inyl)furan-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-finalment-1-inyl)furan-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(4-cyclohexyloxy-1-inyl)furan-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-cyclohexylmethanol)furan-2-yl]interferonbeta acid and

3-amino-3-methyl-5-{5-[3-(3,4-dimethylphenoxy)prop-1-inyl]furan-2-yl}interferonbeta acid; and

(59) the compound according to item (7), where the join is selected from the following compounds, or its pharmacologically acceptable salt:

3-amino-3-methyl-5-[1-methyl-5-(5-finalment-1-inyl)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-{1-methyl-5-[3-(4-methylphenoxy)prop-1-inyl]pyrrol-2-yl}interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexyloxy-1-inyl)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-inyl]pyrrol-2-yl}interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(5-phenylpentane)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(5-cyclohexylmethanol)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(4-phenylbutane)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexylmethanol)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-ethyl-5-(5-phenylpentane)PI is the rol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-ethyl-5-(5-cyclohexylmethanol)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-ethyl-5-(4-phenylbutane)pyrrol-2-yl]interferonbeta acid and

3-amino-3-methyl-5-[1-ethyl-5-(4-cyclohexylmethanol)pyrrol-2-yl]interferonbeta acid.

In addition, in accordance with the present invention offers the following pharmaceutical compositions are:

(60) a pharmaceutical composition comprising at least one immunosuppressant selected from the group consisting of:

means having inhibitory effect on intracellular signaling involved in the expression of cytokines by T-cells

means having inhibitory action on the synthesis of nucleosides in the cells of the immune system,

means having inhibitory effect on cytokines of immune cells and Antirheumatic action,

alkylating agent that causes cell death by rupture of DNA chains or blocking DNA synthesis,

the antimetabolite that inhibits the metabolism of nucleic acids by blocking the production of folic acid,

protein drugs having depressing (overwhelming) effect on TNF-α,

steroid hormonal agent that binds to intracellular steroid receptors to form a complex that communicates with astami interaction (reaction sites) on chromosomes which leads to the synthesis of proteins exhibiting immunosuppressive activity,

substance that suppresses the production of prostaglandin and/or non-steroidal anti-inflammatory drugs, which is an antagonist of prostaglandin

and at least one compound selected from the group consisting of compounds of General formula (I):

[where

R1and R2are the same or different and represent each a hydrogen atom, a lower alkyl group or a protective group of amino group;

R3represents a hydrogen atom, a lower alkyl group or a protective group of hydroxyl group;

R4represents a lower alkyl group;

n represents an integer from 1 to 6;

X represents a sulfur atom, an oxygen atom or a group of formula =N-D (where D represents a hydrogen atom, aryl group, lower alkylsulfonyl group, arylsulfonyl group, or a group selected from the Group of substituents);

Y represents an ethylene group, vanilinovoi group, ethynylene group, a group of the formula-O-CH2- (where E represents a carbonyl group or a group of the formula-CH(OH) -),6-C10Allenova group or6-C10Allenova group substituted by 1-3 substituents selected from the Gr is PI (a) substituents;

Z represents a single bond, C1-C10alkylenes group1-C10alkylenes group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) alternates With1-C10alkylenes group containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain, or With1-C10alkylenes group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) substituents and containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain;

R5represents a hydrogen atom, a C3-C10cycloalkyl group6-C10aryl group, a 5-7-membered heterocyclic group containing 1-3 heteroatoms selected from the group consisting of a sulfur atom, oxygen atom and nitrogen atom, With3-C10cycloalkyl group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) alternates With6-C10aryl group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) substituents, or a 5-7-membered heterocyclic group containing 1-3 heteroatoms selected from the group consisting of at the mA sulfur, oxygen atom and a nitrogen atom and substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) deputies;

R6and R7are the same or different and represent each a hydrogen atom or a group selected from the Group (a) deputies;

Group (a) of the substituents is a group consisting of a halogen atom, a lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup, low allylthiourea, carboxyl group, lower alkoxycarbonyl group, a hydroxyl group, a lower aliphatic acyl group, amino group, mono-lower alkylamino, di-lower alkylamino, lower aliphatic alluminare, ceanography and nitro; and

Group (b) of the substituents is a group consisting of C3-C10cycloalkyl group6-C10aryl group, a 5-7-membered heterocyclic group containing 1-3 heteroatoms selected from the group consisting of a sulfur atom, oxygen atom and nitrogen atom, With3-C10cycloalkyl group substituted by 1-3 substituents selected from Group (a) alternates With6-C10aryl group substituted by 1-3 substituents selected from Group (a) deputies, and 5-7-membered heterocyclic group containing 1-3 heteroatom is a, selected from the group consisting of a sulfur atom, oxygen atom and nitrogen atom and is substituted by 1-3 substituents selected from Group (a) deputies;

provided that when R5represents a hydrogen atom, Z represents a branched C1-C10alkylenes group1-C10alkylenes group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) alternates With1-C10alkylenes group containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain, or With1-C10alkylenes group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) substituents and containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain],

its pharmacologically acceptable salt or a pharmacologically acceptable ester.

Of these pharmaceutical compositions are preferred:

(61) the pharmaceutical composition according to item (60), where the aforementioned compound of General formula (I) has the General formula (Ia)shown below:

(where R1, R2, R3, R4, R5, R6, R7, X, Y, Z and n have the same meanings as pointed to by the e above);

(62) the pharmaceutical composition according to item (60), where the aforementioned compound of General formula (I) has the General formula (Ib)shown below:

(where R1, R2, R3, R4, R5, R6, R7, X, Y, Z and n have the same meanings as above);

(63) the pharmaceutical composition according to item (60), where pharmacologically acceptable ester of the compound of formula (I) has the formula (II):

(where R1, R2, R4, R5, R6, R7, X, Y, Z and n have the same meanings as above, R10and R11are the same or different and represent each a hydrogen atom or a protective group of phosphoric acid), or its pharmacologically acceptable salt;

(64) the pharmaceutical composition according to item (63), where the ester compounds of the formula (II) has the formula (IIa):

(where R1, R2, R4, R5, R6, R7, R10, R11, X, Y, Z and n have the same meanings as above), or its pharmacologically acceptable salt and

(65) the pharmaceutical composition according to item (63), where the ester compounds of the formula (II) has the formula (IIb):

(where R1, R2, R4, R5, R6, R7, R10, R11X, Y, Z and n have the same meanings as above), or its pharmacologically acceptable salt.

In addition, in accordance with the present invention offers the following pharmaceutical compositions are:

(66) a pharmaceutical composition comprising at least one immunosuppressant selected from the group consisting of:

means having inhibitory effect on intracellular signaling involved in the expression of cytokines by T-cells

means having inhibitory action on the synthesis of nucleosides in the cells of the immune system,

means having inhibitory effect on cytokines of immune cells and Antirheumatic action,

alkylating agent that causes cell death by rupture of DNA chains or blocking DNA synthesis,

the antimetabolite that inhibits the metabolism of nucleic acids by blocking the production of folic acid,

protein drugs having depressing (overwhelming) effect on TNF-α,

steroid hormonal agent that binds to intracellular steroid receptors to form a complex that communicates with the places of interaction (reaction sites) on the chromosomes, which leads to the synthesis of proteins exhibiting immunosuppressive activity, and

substances, the overwhelmingly what about the production of prostaglandin, and/or non-steroidal anti-inflammatory drugs, which is an antagonist of prostaglandin

and at least one compound selected from the group consisting of compounds of General formula (III)shown below:

[where

R1and R2are the same or different and represent each a hydrogen atom, a lower alkyl group or a protective group of amino group;

R4represents a lower alkyl group;

n is an integer from 1 to 6;

X represents a sulfur atom, an oxygen atom or a group of formula =N-D (where D represents a hydrogen atom, a C6-C10aryl group, a lower alkylsulfonyl group6-C10arylsulfonyl group, or a group selected from the Group of substituents);

Y represents an ethylene group, vanilinovoi group, ethynylene group, a group of the formula-O-CH2- (where E represents a carbonyl group or a group of the formula-CH(OH) -),6-C10Allenova group or6-C10Allenova group substituted by 1-3 substituents selected from Group (a) deputies;

Z represents a single bond, C1-C10alkylenes group1-C10alkylenes group substituted by 1-3 substituents selected and the group, consisting of Groups (a) of substituents and the Group (b) alternates With1-C10alkylenes group containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain, or With1-C10alkylenes group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) substituents and containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain;

R5represents a hydrogen atom, a C3-C10cycloalkyl group6-C10aryl group, a 5-7-membered heterocyclic group containing 1-3 heteroatoms selected from the group consisting of a sulfur atom, oxygen atom and nitrogen atom, With3-C10cycloalkyl group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) alternates With6-C10aryl group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) substituents, or a 5-7-membered heterocyclic group containing 1-3 heteroatoms selected from the group consisting of a sulfur atom, oxygen atom and nitrogen atom and is substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) deputies;

R6and R 7are the same or different and represent each a hydrogen atom or a group selected from the Group (a) deputies;

R10and R11are the same or different and represent each a hydrogen atom or a protective group of phosphoric acid;

Group (a) of the substituents is a group consisting of a halogen atom, a lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup, low allylthiourea, carboxyl group, lower alkoxycarbonyl group, a hydroxyl group, a lower aliphatic acyl group, amino group, mono-lower alkylamino, di-lower alkylamino, lower aliphatic alluminare, ceanography and nitro; and

Group (b) of the substituents is a group consisting of C3-C10cycloalkyl group6-C10aryl group, a 5-7-membered heterocyclic group containing 1-3 heteroatoms selected from the group consisting of a sulfur atom, oxygen atom and nitrogen atom, With3-C10cycloalkyl group substituted by 1-3 substituents selected from Group (a) alternates With6-C10aryl group substituted by 1-3 substituents selected from Group (a) deputies, and 5-7-membered heterocyclic group containing 1-3 heteroatoms selected from the group consisting of a sulfur atom, oxygen atom and a nitrogen atom and substituted by 1-3 substituents selected from Group (a) deputies;

provided that when R5represents a hydrogen atom, Z represents a branched C1-C10alkylenes group1-C10alkylenes group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) alternates With1-C10alkylenes group containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain, or With1-C10alkylenes group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) substituents and containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain],

its pharmacologically acceptable salt or a pharmacologically acceptable ester.

Of these pharmaceutical compositions are preferred:

(67) the pharmaceutical composition according to item (66)where the compound of formula (III) has the formula (IIIa):

(where R1, R2, R4, R5, R6, R7, R10, R11, X, Y, Z and n have the same meanings as above);

(68) the pharmaceutical composition according to paragraph (66), which is connected to the e of the formula (III) has the General formula (IIIb):

(where R1, R2, R4, R5, R6, R7, R10, R11, X, Y, Z and n have the same meanings as above).

Of these pharmaceutical compositions is more preferable are:

(69) the pharmaceutical composition according to any one of items (60)to(68)containing a compound wherein R1and R2are the same or different and represent each a hydrogen atom, a lower aliphatic acyl group, a lower alkoxycarbonyl group, aracelikarsaalyna group or aracelikarsaalyna group substituted by 1-3 substituents selected from Group (a) substituents, or pharmacologically acceptable salt;

(70) the pharmaceutical composition according to any one of items (60)to(68)containing a compound wherein R1and R2are the same or different and represent each a hydrogen atom, a lower aliphatic acyl group or a lower alkoxycarbonyl group, or its pharmaceutically acceptable salt;

(71) the pharmaceutical composition according to any one of items (60)to(68)containing a compound wherein R1and R2are the same or different and represent each a hydrogen atom, a C1-C4aliphatic acyl group, or With1-C4alkoxycarbonyl group, or farmacologiche the Ki acceptable salt;

(72) the pharmaceutical composition according to any one of items (60)to(68)containing a compound wherein R1and R2are the same or different and represent each a hydrogen atom, a C1-C2aliphatic acyl group, or With1-C2alkoxycarbonyl group, or its pharmaceutically acceptable salt;

(73) the pharmaceutical composition according to any one of items (60)to(68)containing a compound wherein R1and R2are the same or different and represent each a hydrogen atom, acetyl group or methoxycarbonyl group, or its pharmaceutically acceptable salt;

(74) the pharmaceutical composition according to any one of items (60)to(68)containing a compound where each of R1and R2represents a hydrogen atom, or a pharmacologically acceptable salt;

(75) the pharmaceutical composition according to any one of items (60)-(62) and (69)to(74)containing a compound wherein R3represents a hydrogen atom, a lower alkyl group, a lower aliphatic acyl group, aromatic acyl group, aromatic acyl group substituted by 1-3 substituents selected from the Group of substituents, or a silyl group, or a pharmacologically acceptable salt;

(76) the pharmaceutical composition according to any one of items (60)-(62) and (69)to(74)containing a compound wherein R3 represents a hydrogen atom or a lower alkyl group, or a pharmacologically acceptable salt;

(77) the pharmaceutical composition according to any one of items (60)-(62) and (69)to(74)containing a compound wherein R3represents a hydrogen atom or a C1-C4alkyl group, or a pharmacologically acceptable salt;

(78) the pharmaceutical composition according to any one of items (60)-(62) and (69)to(74)containing a compound wherein R3represents a hydrogen atom, methyl group or ethyl group, or its pharmaceutically acceptable salt;

(79) the pharmaceutical composition according to any one of items (60)-(62) and (69)to(74)containing a compound wherein R3represents a hydrogen atom, or a pharmacologically acceptable salt;

(80) the pharmaceutical composition according to any one of items (60)-(79)containing the compound, where R4represents a C1-C4alkyl group, or a pharmacologically acceptable salt;

(81) the pharmaceutical composition according to any one of items (60)-(79)containing the compound, where R4represents a C1-C2alkyl group, or a pharmacologically acceptable salt;

(82) the pharmaceutical composition according to any one of items (60)-(79)containing the compound, where R4represents a methyl group, or its pharmaceutically acceptable salt;

(83) the pharmaceutical composition according to any one of items (60)-(82)containing a compound where n is an integer 2 or 3, or its pharmacologically acceptable salt;

(84) the pharmaceutical composition according to any one of items (60)-(82)containing a compound where n is an integer 2 or its pharmacologically acceptable salt;

(85) the pharmaceutical composition according to any one of items (60)to(84)containing a compound where X is a sulfur atom, or a pharmacologically acceptable salt;

(86) the pharmaceutical composition according to any one of items (60)to(84)containing a compound where X represents an oxygen atom, or a pharmacologically acceptable salt;

(87) the pharmaceutical composition according to any one of items (60)to(84)containing a compound where X represents a group of formula =N-D (where D represents a hydrogen atom, a C1-C4alkyl group or phenyl group), or its pharmacologically acceptable salt;

(88) the pharmaceutical composition according to any one of items (60)to(84)containing a compound where X represents a group of formula =N-CH3or its pharmacologically acceptable salt;

(89) the pharmaceutical composition according to any one of items (60)-(88)containing the compound where Y is an ethylene group, ethynylene group, a group of the formula-CO-CH2-groups of the formula-CH(OH)-CH 2-, fenelonov group or fenelonov group substituted by 1-3 substituents selected from the group consisting of a halogen atom and a lower alkyl group, or a pharmacologically acceptable salt;

(90) the pharmaceutical composition according to any one of items (60)-(88)containing the compound where Y is an ethylene group, ethynylene group, a group of the formula-CO-CH2or fenelonov group, or its pharmaceutically acceptable salt;

(91) the pharmaceutical composition according to any one of items (60)to(90)containing a compound where Z represents a C1-C10alkylenes group or1-C10alkylenes group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) substituents, or pharmacologically acceptable salt;

(92) the pharmaceutical composition according to any one of items (60)to(90)containing a compound where Z represents a C1-C6alkylenes group or1-C6alkylenes group substituted by 1-3 hydroxyl groups, or a pharmacologically acceptable salt;

(93) the pharmaceutical composition according to any one of items (60)to(90)containing a compound where Z represents a C1-C5alkylenes group or1-C5alkylenes group substituted by 1-3 hydroxyl groups, or Farmak is logically acceptable salt;

(94) the pharmaceutical composition according to any one of items (60)to(90)containing a compound where Z represents an ethylene group, trimethylene group, tetramethylene group or ethylene, trimethylene or tetramethylene group substituted with one hydroxyl group, or its pharmaceutically acceptable salt;

(95) the pharmaceutical composition according to any one of items (60)to(90)containing a compound where Z represents an ethylene group, trimethylene group or tetramethylene group, or its pharmaceutically acceptable salt;

(96) the pharmaceutical composition according to any one of items (60)to(90)containing a compound where Z represents an ethylene group or trimethylene group, or its pharmaceutically acceptable salt;

(97) the pharmaceutical composition according to any one of items (60)to(90)containing a compound where Z represents a C1-C10alkylenes group containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain, or With1-C10alkylenes group, substituted with one substituent and contains an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain (the Deputy selected from the group consisting of lower alkyl groups and hydroxyl groups), or pharmacolo the automatic acceptable salt;

(98) the pharmaceutical composition according to any one of items (60)to(90)containing a compound where Z represents a C1-C10alkylenes group containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain, or a pharmacologically acceptable salt;

(99) the pharmaceutical composition according to any one of items (60)to(90)containing a compound where Z represents a C1-C10alkylenes group containing an oxygen atom in the specified carbon chain or at the end of the specified carbon chain, or a pharmacologically acceptable salt;

(100) the pharmaceutical composition according to any one of items (60)to(90)containing a compound where Z represents a C1-C6alkylenes group containing an oxygen atom in the specified carbon chain or at the end of the specified carbon chain, or a pharmacologically acceptable salt;

(101) the pharmaceutical composition according to any one of items (60)to(90)containing a compound where Z represents a group of formula-O-CH2-, -O-(CH2)2-, -O-(CH2)3-, -CH2-O-, -(CH2)2-O - or -(CH2)3-O-, or a pharmacologically acceptable salt;

(102) the pharmaceutical composition according to any one of items (60)to(90)containing a compound where Z represents a group of formula-CH2-O - Il is -(CH 2)2-O-, or a pharmacologically acceptable salt;

(103) the pharmaceutical composition according to any one of items (60)to(102)containing a compound wherein R5represents a hydrogen atom, or a pharmacologically acceptable salt;

(104) the pharmaceutical composition according to any one of items (60)to(102)containing a compound wherein R5represents a C3-C10cycloalkyl group6-C10aryl group or3-C10cycloalkyl or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup and lower allylthiourea, or its pharmacologically acceptable salt;

(105) the pharmaceutical composition according to any one of items (60)to(102)containing a compound wherein R5represents a C3-C10cycloalkyl group6-C10aryl group or3-C10cycloalkyl or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups and lower alkoxygroup, or its pharmacologically acceptable salt;

(106) the pharmaceutical composition according to any one of items (60)to(102)containing the I connection where R5represents a C5-C6cycloalkyl group, phenyl group or naftalina group, or its pharmaceutically acceptable salt;

(107) the pharmaceutical composition according to any one of items (60)to(102)containing a compound wherein R5is tsiklogeksilnogo group or phenyl group, or its pharmaceutically acceptable salt;

(108) the pharmaceutical composition according to any one of items (60)-(107)containing a compound wherein R6and R7are the same or different and represent each a hydrogen atom, halogen atom, lower alkyl group, halogenated lower alkyl group, lower alkoxygroup or lower allylthiourea, or its pharmacologically acceptable salt;

(109) the pharmaceutical composition according to any one of items (60)-(107)containing a compound where each of R6and R7represents a hydrogen atom, or a pharmacologically acceptable salt;

(110) the pharmaceutical composition according to any one of items (63)to(74) and (80)to(109)containing a compound wherein R10and R11are the same or different and represent each a hydrogen atom or a lower alkyl group, or a pharmacologically acceptable salt;

(111) the pharmaceutical composition according to any one of items (63)to(74) and (80)to(109)containing a compound wherein R10and R11is the tsya the same or different and represent each a hydrogen atom or a C 1-C4alkyl group, or a pharmacologically acceptable salt;

(112) the pharmaceutical composition according to any one of items (63)to(74) and (80)to(109)containing a compound wherein R10and R11are the same or different and represent each a hydrogen atom, methyl group or ethyl group, or its pharmacologically acceptable salt,

(113) the pharmaceutical composition according to any one of items (63)to(74) and (80)to(109)containing a compound where each of R10and R11represents a hydrogen atom, or its pharmacologically acceptable salt.

Of these pharmaceutical compositions are particularly preferred are:

(114) the pharmaceutical composition according to item (60)where the compound of General formula (I) or its pharmacologically acceptable salt or a pharmacologically acceptable ester selected from the group consisting of the compounds described below, pharmacologically acceptable salts and their pharmaceutically acceptable esters:

2-amino-2-methyl-4-[5-(4-cyclohexylmethyl)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(5-cyclohexylmethyl)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(5-fenilpentil)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(4-cyclohexyloxy)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-{5-[4-(4-pertenece)butyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[4-(4-netoxygen the XI)butyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-[5-(4-benzyloxybenzyl)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(4-cyclohexyl-1-inyl)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(4-phenylbut-1-inyl)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(5-cyclohexylidene-1-inyl)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(5-finalment-1-inyl)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-{5-[5-(4-forfinal)Penta-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[5-(4-methoxyphenyl)Penta-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[3-(4-methylphenoxy)prop-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[3-(4-ethylenoxy)prop-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[3-(4-methylthiophene)prop-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-[5-(4-cyclohexyloxy-1-inyl)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-{5-[4-(4-pertenece)buta-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[4-(4-methylphenoxy)buta-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-[5-(3-cyclohexylmethoxy-1-inyl)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(4-benzyloxy-1-inyl)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(4-cyclohexylmethanol)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(4-phenylbutane)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(5-cyclohexylmethanol)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(5-phenylpentane)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-{5-[5-(4-forfinal)pentanoyl]t is the dryer-2-yl}butane-1-ol,

2-amino-2-ethyl-4-[5-(5-cyclohexylmethyl)thiophene-2-yl]butane-1-ol,

2-amino-2-ethyl-4-[5-(5-cyclohexylidene-1-inyl)thiophene-2-yl]butane-1-ol,

2-amino-2-ethyl-4-[5-(5-cyclohexylmethanol)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-{5-[3-(4-chlorophenoxy)prop-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[3-(3-methylphenoxy)prop-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[3-(3-methoxyphenoxy)prop-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[3-(3,4-dimethoxyphenoxy)prop-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[3-(3,5-dimethoxyphenoxy)prop-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[3-(3-acetylphenol)prop-1-inyl]thiophene-2-yl}butane-1-ol and

2-amino-2-methyl-4-{5-[3-(4-acetylphenol)prop-1-inyl]thiophene-2-yl}butane-1-ol;

(115) the pharmaceutical composition according to item (60)where the compound of General formula (I) or its pharmacologically acceptable salt or a pharmacologically acceptable ester selected from the group consisting of the compounds described below, pharmacologically acceptable salts and their pharmaceutically acceptable esters:

2-amino-2-methyl-4-[5-(5-fenilpentil)furan-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(5-cyclohexylidene-1-inyl)furan-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(5-finalment-1-inyl)furan-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(4-cyclohexyloxy about-1-inyl)furan-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(4-cyclohexylmethanol)furan-2-yl]butane-1-ol and

2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-inyl]furan-2-yl}butane-1-ol;

(116) the pharmaceutical composition according to item (60)where the compound of General formula (I) or its pharmacologically acceptable salt or a pharmacologically acceptable ester selected from the group consisting of the compounds described below, pharmacologically acceptable salts and their pharmaceutically acceptable esters:

2-amino-2-methyl-4-[1-methyl-5-(5-finalment-1-inyl)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[3-(4-methylphenoxy)prop-1-inyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxy-1-inyl)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-inyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentane)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylmethanol)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutane)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylmethanol)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(4-were)butanoyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentane)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylmethanol)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutane)pyrrol-2-yl]buta is-1-ol and

2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylmethanol)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimetilfenil)butanoyl]-pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3, 5dimethylphenyl)butanoyl]-pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3-triptoreline)-butanoyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(4-triptoreline)-butanoyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(4-methoxyphenyl)butanoyl]-pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3-were)butyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimetilfenil)butyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3, 5dimethylphenyl)butyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3-triptoreline)butyl]-pyrrol-2-yl}butane-1-ol;

(117) the pharmaceutical composition according to item (63)where the compound of General formula (II) or its pharmacologically acceptable salt or a pharmacologically acceptable ester selected from the group consisting of the compounds described below, pharmacologically acceptable salts and their pharmaceutically acceptable esters:

mono 2-amino-2-methyl-4-[5-(4-cyclohexylmethyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-cyclohexylmethyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-fenilpentil)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-IU the Il-4-[5-(4-cyclohexyloxy)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[4-(4-pertenece)butyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[4-(4-methoxyphenoxy)butyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(4-benzyloxybenzyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(4-cyclohexyl-1-inyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(4-phenylbut-1-inyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-cyclohexylidene-1-inyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-finalment-1-inyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[5-(4-forfinal)Penta-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[5-(4-methoxyphenyl)Penta-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[3-(4-methylphenoxy)prop-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[3-(4-ethylenoxy)prop-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[3-(4-methylthiophene)prop-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(4-cyclohexyloxy-1-inyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[4-(4-pertenece)buta-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[4-(4-methylphenoxy)buta-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(3-cyclohexylmethoxy-1-inyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(4-benzyloxy-1-inyl)thiophene-2-yl]-1-butylphosphate,

mono-amino-2-methyl-4-[5-(4-cyclohexylmethanol)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(4-phenylbutane)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-cyclohexylmethanol)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-phenylpentane)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[5-(4-forfinal)pentanoyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-ethyl-4-[5-(5-cyclohexylmethyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-ethyl-4-[5-(5-cyclohexylidene-1-inyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-ethyl-4-[5-(5-cyclohexylmethanol)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[3-(4-chlorophenoxy)prop-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[3-(3-methylphenoxy)prop-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[3-(3-methoxyphenoxy)prop-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[3-(3,4-dimethoxyphenoxy)prop-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[3-(3,5-dimethoxyphenoxy)prop-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[3-(3-acetylphenol)prop-1-inyl]thiophene-2-yl}-1-butylphosphate and

mono 2-amino-2-methyl-4-{5-[3-(4-acetylphenol)prop-1-inyl]thiophene-2-yl}-1-butylphosphate;

(118) the pharmaceutical composition according to item (63)where the compound of General formula (II) or its pharmacologically acceptable salt or farmacologicas is acceptable ester selected from the group consisting of compounds described below, pharmacologically acceptable salts and their pharmaceutically acceptable esters:

mono 2-amino-2-methyl-4-[5-(5-fenilpentil)furan-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-cyclohexylidene-1-inyl)furan-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-finalment-1-inyl)furan-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(4-cyclohexyloxy-1-inyl)furan-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-cyclohexylmethanol)furan-2-yl]-1-butylphosphate and

mono 2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-inyl]furan-2-yl}-1-butylphosphate;

(119) the pharmaceutical composition according to item (63)where the compound of General formula (II) or its pharmacologically acceptable salt or a pharmacologically acceptable ester selected from the group consisting of the compounds described below, pharmacologically acceptable salts and their pharmaceutically acceptable esters:

mono 2-amino-2-methyl-4-[1-methyl-5-(5-finalment-1-inyl)pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{1-methyl-5-[3-(4-methylphenoxy)prop-1-inyl]pyrrol-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxy-1-inyl)pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-inyl]pyrrol-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentane)pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylmethanol)-pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutane)pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylmethanol)-pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{1-methyl-5-[4-(4-were)butanoyl]-pyrrol-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentane)pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylmethanol)-pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutane)pyrrol-2-yl]-1-butylphosphate and

mono 2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylmethanol)-pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimetilfenil)-butanoyl]pyrrol-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{1-methyl-5-[4-(3, 5dimethylphenyl)-butanoyl]pyrrol-2-yl}-1-butylphosphate;

(120) the pharmaceutical composition according to item (66)where the compound of General formula (III) or its pharmacologically acceptable salt or a pharmacologically acceptable ester selected from the group consisting of the compounds described below, pharmacologically acceptable salts and their pharmaceutically acceptable esters:

3-amino-3-methyl-5-[5-(4-cyclohexylmethyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-cyclohexylmethyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(phenylphenyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(4-cyclohexyloxy)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-{5-[4-(4-pertenece)butyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[4-(4-methoxyphenoxy)butyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-[5-(4-benzyloxybenzyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(4-cyclohexyl-1-inyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(4-phenylbut-1-inyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-cyclohexylidene-1-inyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-finalment-1-inyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-{5-[5-(4-forfinal)Penta-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[5-(4-methoxyphenyl)Penta-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[3-(4-methylphenoxy)prop-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[3-(4-ethylenoxy)prop-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[3-(4-methylthiophene)prop-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-[5-(4-cyclohexyloxy-1-inyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-{5-[4-(4-pertenece)buta-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[4-(4-methylphenoxy)buta-1-inyl]thiophene-2-yl}Penta is Fofanova acid,

3-amino-3-methyl-5-[5-(3-cyclohexylmethoxy-1-inyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(4-benzyloxy-1-inyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(4-cyclohexylmethanol)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(4-phenylbutane)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-cyclohexylmethanol)thiophene-2-

Il]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-phenylpentane)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-{5-[5-(4-forfinal)pentanoyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-ethyl-5-[5-(5-cyclohexylmethyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-ethyl-5-[5-(5-cyclohexylidene-1-inyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-ethyl-5-[5-(5-cyclohexylmethanol)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-{5-[3-(4-chlorophenoxy)prop-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[3-(3-methylphenoxy)prop-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[3-(3,4-dimethylphenoxy)prop-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[3-(3-methoxyphenoxy)prop-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[3-(3,4-dimethoxyphenoxy)prop-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[3-(3,5-dimethoxyphenoxy)prop-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[3-(3-acetylphenol)prop-1-inyl]thiophene-2-yl}interferonbeta acid and

3-amino-3-methyl-5-{5-[3-(4-acetylphenol)prop-1-inyl]thiophene-2-yl}interferonbeta acid;

(121) the pharmaceutical composition according to item (66)where the compound of General formula (III) or its pharmacologically acceptable salt or a pharmacologically acceptable ester selected from the group consisting of the compounds described below, pharmacologically acceptable salts and their pharmaceutically acceptable esters:

3-amino-3-methyl-5-[5-(5-fenilpentil)furan-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-cyclohexylidene-1-inyl)furan-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-finalment-1-inyl)furan-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(4-cyclohexyloxy-1-inyl)furan-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-cyclohexylmethanol)furan-2-yl]interferonbeta acid and

3-amino-3-methyl-5-{5-[3-(3,4-dimethylphenoxy)prop-1-inyl]furan-2-yl}interferonbeta acid;

(122) the pharmaceutical composition according to item (66)where the compound of General formula (III) or its pharmacologically acceptable salt or a pharmacologically acceptable ester selected from the group consisting of the compounds described below, pharmacologically acceptable salts and their pharmaceutically acceptable esters:

3-AMI is about-3-methyl-5-[1-methyl-5-(5-finalment-1-inyl)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-{1-methyl-5-[3-(4-methylphenoxy)prop-1-inyl]pyrrol-2-yl}interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexyloxy-1-inyl)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-inyl]pyrrol-2-yl}interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(5-phenylpentane)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(5-cyclohexylmethanol)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(4-phenylbutane)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexylmethanol)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-ethyl-5-(5-phenylpentane)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-ethyl-5-(5-cyclohexylmethanol)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-ethyl-5-(4-phenylbutane)pyrrol-2-yl]interferonbeta acid and

3-amino-3-methyl-5-[1-ethyl-5-(4-cyclohexylmethanol)pyrrol-2-yl]interferonbeta acid;

(123) the pharmaceutical composition according to any one of items (60)-(122)containing at least one immunosuppressant selected from the group consisting of:

means possessing inhibitory effect on intracellular signaling involved in the expression of cytokines by T-cells (these means are cyclosporin a, tackroom is with, rapamycin, gusperimus, everolimus, tresperimus, esperemos, assuming your-281-240, ABT-281, tigerinus, A-119435 or 17-ethyl-1,14-dihydroxy-12-[2-[4-(2-phenylhydrazine)-3-methoxycyclohexyl]-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octakis-18-ene-2,3,10,16-tetron),

means possessing inhibitory effect on the synthesis of nucleosides in the cells of the immune system (these means are mizoribine, azathioprine, mycophenolate Mofetil, Leflunomide, merimepodib, HMR-1279, TSK-204 or SP-100030),

means possessing inhibitory effect on cytokines of immune cells and Antirheumatic action (specified means are T-614, actarit, salazosulfapiridin or CDC-801),

alkylating substances that cause cell death by rupture of DNA chains or blocking DNA synthesis (indicated by the alkylating agent is cyclophosphamide),

antimetabolites, inhibiting the metabolism of nucleic acids by blocking the production of folic acid (specified antimetabolite is methotrexate),

protein drugs with depressing (overwhelming) effect on TNF-α (these protein drugs are Remicade, Enbrel, daclizumab, basiliximab, alemtuzumab, omalizumab, BMS-188667, CDP-571, enlimomab, ATM-027 or BTI-322),

steroid hormone among the STV, which bind to intracellular steroid receptors to form a complex that communicates with the places of interaction (reaction sites) on the chromosomes, which leads to the synthesis of proteins exhibiting immunosuppressive activity (specified steroid hormonal agent is prednisolone), and

substances that suppress the production of prostaglandin, and/or nonsteroidal anti-inflammatory drugs that are antagonists of prostaglandin (specified non-steroidal anti-inflammatory drugs are loxoprofen sodium, diclofenac sodium, meloxicam, celecoxib, or rofecoksib), and

(124) the pharmaceutical composition according to any one of items (60)-(122)containing at least one immunosuppressant selected from the group consisting of cyclosporine A, tacrolimus, rapamycin, Leflunomide, methotrexate, Remicade and Enbrel.

Another objective of the present invention is the creation of the following pharmaceutical compositions and methods:

(125) a pharmaceutical composition comprising as an active ingredient a compound, its pharmaceutically acceptable salt or a pharmacologically acceptable ester according to any one of paragraphs(1)-(59),

(126) the pharmaceutical composition according to paragraph (125) for the prevention or treatment of autoimmune diseases,

(127) in pharmaceutical preparations is practical composition according to paragraph (126), where specified autoimmune disease is rheumatoid arthritis,

the pharmaceutical composition according to paragraph (126), where the specified autoimmune disease is Crohn's disease or ulcerative colitis,

the pharmaceutical composition according to paragraph (126), where the specified autoimmune disease is multiple sclerosis,

the pharmaceutical composition according to paragraph (126), where the specified autoimmune disease is psoriasis,

the pharmaceutical composition according to paragraph (126), where the specified autoimmune disease is atopic dermatitis,

the pharmaceutical composition according to paragraph (126), where the specified autoimmune disease is insulin-dependent diabetes mellitus,

the pharmaceutical composition according to paragraph (126), where the specified autoimmune disease is glomerular nephritis,

(128) the pharmaceutical composition according to paragraph (125) to suppress rejection caused by transplantation of various organs or skin,

(129) a method of preventing or treating autoimmune diseases in a mammal, containing the introduction to the specified mammal an effective amount of the pharmaceutical composition according to any one of paragraphs(60)-(125),

(130) a method of preventing or treating rheumatoid arthritis in a mammal, containing the introduction to the specified mammal an effective amount of FA the pharmaceutical composition according to any one of items (60)to(125), and

the method of prevention or treatment pariza the mammal containing an introduction to the specified mammal an effective amount of the pharmaceutical composition according to any one of paragraphs(60)-(125),

the method of prevention or treatment of Crohn's disease or ulcerative colitis in a mammal, containing the introduction to the specified mammal an effective amount of the pharmaceutical composition according to any one of paragraphs(60)-(125),

a method of preventing or treating multiple sclerosis in a mammal, containing the introduction to the specified mammal an effective amount of the pharmaceutical composition according to any one of paragraphs(60)-(125),

the method of prevention or treatment of atopic dermatitis in a mammal, containing the introduction to the specified mammal an effective amount of the pharmaceutical composition according to any one of paragraphs(60)-(125),

the method of prevention or treatment of insulin-dependent diabetes in a mammal, containing the introduction to the specified mammal an effective amount of the pharmaceutical composition according to any one of paragraphs(60)-(125),

the method of prevention or treatment of glomerular nephritis in a mammal, containing the introduction to the specified mammal an effective amount of the pharmaceutical composition according to any one of paragraphs(60)-(125),

(131) a method of prevention or treatment of otter is to be placed, caused by transplantation of various organs or skin, of the mammal containing an introduction to the specified mammal an effective amount of the pharmaceutical composition according to any one of paragraphs(60)-(125).

In formulas (I), (II) and (III) the aryl part of "C6-C10aryl group", "C6-C10aryl group substituted by 1-3 substituents selected from Group (a) Deputy", or "C6-C10aryl group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) substitutes", in the definition of D, R5or Group (b) substituents may represent, for example, a group such as phenyl, angenlina or naftalina group preferably is phenyl or naftilos group, and most preferably phenyl group.

Allenova part "C6-C10Allenova group", "C6-C10Allenova group substituted by 1-3 substituents selected from Group (a) Deputy", or "C6-C10Allenova group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) substitutes", in the definition of Y or E, can represent, for example, a group such as fenelonov, inderena or naftalanovaja group, preferably is phenylenebis or naphthalenol the th group, and most preferably phenylenebis group.

With1-C10Allenova part "C1-C10alkalinous group" or "C1-C10Allenova group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) of the substituents in the definition of Z, consists of unbranched or branched alkylene group having 1-10 carbon atoms, and may represent, for example, a group such as methylene, methylmethyldopa, ethylene, propylene, trimethylene, 1-metilidinovy, tetramethylene, 1-methyltrienolone, 2-methyltrienolone, 3-methyltrienolone, 1-methylpropyloxy, 1,1-dimethylethylene, pentamethylene, 1-mediterraneita, 2-mediterraneita, 3-mediterraneita, 4-mediterraneita, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene, hexamethylene, 1-methylpentylamino, 2-methylpentylamino, 3-methylpentylamino, 4-methylpentylamino, 5-methylpentadiene, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene, 4,4-dimethyltrimethylene, heptamethylnonane, 1-methylhexanamine, 2-methylhexanamine, 5-methylhexanamine, 3-etilendiaminova, octamethylene, 2-methylheptacosane,

5-methylhept milenova, 2-ethylhexylamine, 2-ethyl-3-methylpentylamino, 3-ethyl-2-methylpentadiene, nonmelanoma, 2-methyloctadecane, 7-methyloctadecane, 4-ethylheptylamino, 3-ethyl-2-methylhexanamine, 2-ethyl-1-methylhexanamine or decamethylenebis group is preferably C1-C6alkalinous group, more preferably1-C5alkalinous group, even more preferably ethylene, trimethylene or tetramethylene group, and most preferably ethylene or trimethylene group.

"C1-C10Allenova part containing an oxygen atom or a sulfur atom in the carbon chain or at the end of the carbon chain" "C1-C10alkalinous group containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain", or "C1-C10Allenova group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) substituents and containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain", in the definition of Z can represent a "1-C10alkylenes group, mentioned above, contains an oxygen atom or sulfur within the carbon chain or at the end of the specified carbon chain and may represent, in the example, a group of the formula-O-CH2-, -O-(CH2)2-, -O-(CH2)3-, -O-(CH2)4-, -O-(CH2)5-, -O-(CH2)6-, -O-(CH2)7-, -O-(CH2)8-, -O-(CH2)9-, -O-(CH2)10-, -CH2-O-CH2-, -CH2-O-(CH2)2-, -CH2-O-(CH2)3-, -CH2-O-(CH2)4-, -(CH2)2-O-CH2-, -(CH2)2-O-(CH2)2-, -(CH2)2-O-(CH2)3-, -(CH2)2-O-(CH2)4-, -(CH2)3-O-CH2-, -(CH2)3-O-(CH2)2-, -(CH2)3-O-(CH2)3-, -(CH2)4-O-CH2-, -(CH2)4-O-(CH2)2-, -(CH2)5-O-CH2-, -CH2-O-, -(CH2)2-O-, -(CH2)3-O-, -(CH2)4-O-, -(CH2)5-O-, -(CH2)6-O-, -(CH2)7-O-, -(CH2)8-O-, -(CH2)9-O-, -(CH2)10-O-, -S-CH2-, -S-(CH2)2-, -S-(CH2)3-, -S-(CH2)4-, -S-(CH2)5-, -S-(CH2)6-, -S-(CH2)7-, -S-(CH2)8-, -S-(CH2)9-, -S-(CH2)10-, -CH2-S-CH2-, -CH2-S-(CH2)2-, -CH2-S-(CH2)3-, -CH2-S-(CH2)4-, -(CH2)2-S-CH2-, -(CH2)2-S-(CH2)2-, -(CH2)2-S-(CH2)3-, -(CH2)2/sub> -S-(CH2)4-, -(CH2)3-S-CH2-, -(CH2)3-S-(CH2)2-, -(CH2)3-S-(CH2)3-, -(CH2)4-S-CH2-, -(CH2)4-S-(CH2)2-, -(CH2)5-S-O-CH2-, -CH2-S-, -(CH2)2-S-, -(CH2)3-S-, -(CH2)4-S-, -(CH2)5-S-, -(CH2)6-S-, -(CH2)7-S-, -(CH2)8-S-, -(CH2)9-S - or -(CH2)10-S-, and is preferably C1-C6alkalinous group containing an oxygen atom in the carbon chain or at the end of the carbon chain, more preferably a group-O-CH2-, -O-(CH2)2-, -O-(CH2)3-, -CH2-O-, -(CH2)2-O - or -(CH2)3-O-, and most preferably a group-CH2-O - or -(CH2)2-O-.

With3-C10cycloalkyl part "C3-C10cycloalkyl group", "C3-C10cycloalkyl group substituted by 1-3 substituents selected from Group (a) Deputy", or "C3-C10cycloalkyl group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) of the substituents in the definition of R5or Group (b) substituents may be optionally condensed with other cyclic groups, and may represent, for example, g is polyurethane foam, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornyl, substituted or indanyl, preferably5-C6cycloalkyl group, and most preferably tsiklogeksilnogo group.

5-7-Membered heterocyclic part, containing 1-3 heteroatoms selected from the group consisting of a sulfur atom, oxygen atom and nitrogen atom, in "5-7-membered heterocyclic group containing 1-3 heteroatoms selected from the group consisting of a sulfur atom, oxygen atom and a nitrogen atom", or "5-7-membered heterocyclic group containing 1-3 heteroatoms selected from the group consisting of a sulfur atom, oxygen atom and nitrogen atom and is substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) substituents", for example 5-7-membered aromatic or heterocyclic, partially or completely gidrirovannoe saturated heterocyclic group containing 1-3 heteroatoms selected from the group consisting of a sulfur atom, oxygen atom and nitrogen atom.

Heterocyclic group may be follow, thienyl, pyrrolidinyl, sepanlou, pyrazolidine, imidazolidine, oxazolidine, isoxazolidine, thiazolidine, isothiazolinone, 1,2,3-oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyranyloxy, pyridyloxy, peridas nilou, pyrimidinyl, personilnya, tetrahydropyranyloxy, morpholinyl, thiomorpholine, pyrrolidinyloxy, pyrrolidino, imidazolidinyl, pyrazolidinone, piperidinyloxy, piperazinilnom, oxazolidinyl, isoxazolidinone, diazolidinyl or pyrazolidinone group and is preferably a 5 - or 6-membered aromatic heterocyclic group, more preferably furillo, thienyl or pyrrolidino group, even more preferably fouilloy or thienyl group, and most preferably thienyl group.

"Aromatic heterocyclic group"described above can be optionally condensed with other cyclic groups, and may represent, for example, benzothiazoline, isobenzofuranyl, romanello, santanello, phenoxathiin, indolizinyl, isoindolyl, indolenine, indazolinone, parinello, hyalinella, izohinolinove, pinolillo, talinolol, naphthyridinone, khinoksalinona, chinazolinei, carbazolyl, karbonilnuyu, criminology or isoindolyl group and preferably is benzothiazole group.

"Halogen atom" in the definition of Groups and the substituents may represent an atom of fluorine, chlorine, bromine or iodine, preferably fluorine atom, of which before occhialini is fluorine atom or chlorine.

"Lower alkyl group" in the definition of R1, R2, R3, R4or Groups and the substituents may represent, for example, unbranched or branched alkyl group having 1-6 carbon atoms. The specified lower alkyl group may be, for example, methyl, ethyl, sawn, ISO-propyl, bucilina, isobutylene, second-bucilina, tert-bucilina, pentilla, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, hexeline, isohexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 1-ethylbutyl or 2-ethylbutyl group, preferably1-C4alkyl group, more preferably1-C2alkyl group and most preferably a methyl group.

"Halogenated lower alkyl group" in the definition of the Group (a) of the substituents is a group in which the above-described "lower alkyl group" is substituted by a halogen atom. Specified halogenated lower alkyl group may represent, for example, halogenated1-C6alkyl group, such as triptorelin, trichlorethylene, deformational, dichlo is methyl, dibromoethylene, permetrina, 2,2,2-triptoreline, 2,2,2-trichlorethylene, 2-brometalia, 2-chloraniline, 2-florachilena, 2-itatinga, 3-chloropropylene, 4-terbutalina, 6-identily or 2,2-dibromoethylene group, and is preferably halogenated With1-C4alkyl group, more preferably triptoreline, trichlorethylene, 2,2,2-triptorelin or 2,2,2-trichlorethylene group, and most preferably triptorelin group.

"The lowest alkoxygroup" in the definition of the Group (a) of the substituents is a group to which the "lower alkyl group linked to an oxygen atom. The specified lower alkoxygroup can represent, for example, unbranched or branched alkoxygroup having 1-6 carbon atoms, such as methoxy, ethoxy-, propoxy-, isopropoxy, butoxy, isobutoxy-, second -, butoxy-, tert-butoxy, pentox, isobutoxy-, 2-methylbutoxy-, 1 ethylpropoxy-, 2-ethylpropoxy, neopentane, hexyloxy-, 4-methylpentene-, 3-methylpentane-, 2-methylpentane-, 3,3-dimethylbutene-, 2,2-Dimethylbutane-, 1,1-Dimethylbutane-, 1,2-Dimethylbutane-, 1,3-Dimethylbutane - or 2,3-dimethylbutyramide, and is preferably1-C4alkoxygroup, more preferably1-C2alkoxygroup and most preferably methoxy what uppoi.

"The lowest allylthiourea" in the definition of the Group (a) of the substituents is a group in which "the aforementioned lower alkyl group linked to a sulfur atom. The specified lower allylthiourea can represent, for example, unbranched or branched allylthiourea having 1-6 carbon atoms, such as methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylic-, second -, butylthio-, tert-butylthio, pentylthio, isopentyl-, 2-methylbutyric, neopentyl-, hexylthio-4 methylphenylthio-, 3-methylphenylthio-, 2-methylphenylthio-, 3,3-dimethylbutyl-, 2,2-dimethylbutyl-, 1,1-dimethylbutyl-, 1,2-dimethylbutyl-, 1,3-dimethylbutyl - or 2,3-dimethylbutadiene, and is preferably1-C4alkylthiol, more preferably1-C2alkylthiophene and most preferably by methylthioribose.

"Lower alkoxycarbonyl group" in the definition of the Group (a) of the substituents is a group to which the "lower alkoxygroup" is linked to the carbonyl group. The specified lower alkoxycarbonyl group can represent, for example, unbranched or branched alkoxycarbonyl group having 1-6 carbon atoms, such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butok carbonilla, solutionline, second-butoxycarbonyl, tert-butoxycarbonyl, phenoxycarbonyl, isopentenyladenosine, 2-motivationally, neopentecostals, hexyloxymethyl, 4-methylpentanedicarbonitrile, 3-methylpentanedicarbonitrile, 2-methylpentanedicarbonitrile, 3,3-dimethylethoxysilane, 2,2-dimethylethoxysilane, 1,1-dimethylethoxysilane, 1,2-dimethylethoxysilane, 1,3-dimethylethoxysilane or 2,3-dimethylethoxysilane group, and is preferably1-C4alkoxycarbonyl group, more preferably1-C2alkoxycarbonyl group, and most preferably methoxycarbonyl group.

"Lower aliphatic acyl group" in the definition of the Group (a) of the substituents is a group in which a hydrogen atom or a saturated or unsaturated aliphatic hydrocarbon group linked to a carbonyl group. The specified lower aliphatic hydrocarbon group may represent, for example, unbranched or branched lower aliphatic acyl group having 1-8 carbon atoms, such as formyl, acetyl, propylaniline, Butyrina, isobutylene, valerina, isovaleryl, bialoleka, hexanoyl, calolina, methacryloyl or CROs is onorina group, and is preferably1-C4lower aliphatic acyl group, more preferably acetyl or propionyloxy group, and most preferably acetyl group.

"Mono-lower alkylamino" in the definition of the Group (a) of the substituents is a group to which the "lower alkyl group" is associated with one amino group. The specified mono lowest alkylamino can represent, for example, mono-C1-C4alkylamino, such as methylamino, ethylamino, propylamino, isopropylamino, butylamino, isobutylamino-, second -, butylamino-, tert-butylamino, pentylamine, isopentylamine-, 2-methylbutylamine, neopentylene-, 1 ethylpropylamine, hexylamino, isohexane-, 4-methylpentylamino-, 3-methylpentylamino-, 2-methylpentylamino-, 1 methylpentylamino-, 3,3-dimethylbutylamino-, 2,2-dimethylbutylamino-, 1,1-dimethylbutylamino-, 1,2-dimethylbutylamino-, 1,3-dimethylbutylamino-, 2,3-dimethylbutylamino - or 2-ethylbutylamine, and is preferably mono-C1-C4alkylaminocarbonyl, more preferably mono-C1-C2alkylaminocarbonyl and most preferably by methylaminopropane.

"Di-lower alkylamino" in the definition of the Group (a) of the substituents is a group where two of the above "lower alkyl group is linked to the amino group. The specified di-lower alkylamino can represent, for example, di-C1-C6alkylamino, such as dimethylamino, diethylamino-, N-ethyl-N-methylamino, dipropylamino, dibutylamino, diphenhydamine or vexillaria, and is preferably CI-C1-C4alkylaminocarbonyl, more preferably CI-C1-C2alkylaminocarbonyl and most preferably by dimethylaminopropoxy.

"The lower aliphatic alluminare" in the definition of the Group (a) of the substituents is a group to which the "lower aliphatic acyl group" is associated with the amino group. Specified the lower aliphatic alluminare can represent, for example, unbranched or branched lower aliphatic alluminare having 1-7 carbon atoms, such as formylamino-, acetylamino-, propionamido, bucillamine, isobutylamino, Valeriano, isovaleramide, paulolino, hexanamine, acrylamido, methacrylamido or crotonylene, and is preferably1-C4lower aliphatic allmineral, more preferably acetylamino or propionamidoxime and most preferably by acetylaminophenol.

"Lower alkylsulfonyl group" in the definition of D is a group in which the Oh mentioned "lower alkyl group" is associated with sulfonyloxy group. The specified lower alkylsulfonyl group can represent, for example, unbranched or branched alkylsulfonyl group having 1-6 carbon atoms, such as methanesulfonyl, acanaloniidae, propanesulfonyl, isopropylaniline, butanesulfonyl, isobutylphenyl, second-butanesulfonyl, tert-butanesulfonyl, pentanesulfonate, isopentenyladenine, 2-methylbutyronitrile, neopentadactyla, hexanesulfonate, 4-methylphenylsulfonyl, 3-methylphenylsulfonyl, 2-methylphenylsulfonyl, 3,3-dimethylbutylamino, 2,2-dimethylbutylamino, 1,1-dimethylbutylamino, 1,2-dimethylbutylamino, 1,3-dimethylbutylamino or 2,3-dimethylbutylamino group, and is preferably1-C4alkylsulfonyl group, more preferably1-C2alkylsulfonyl group, and most preferably methanesulfonyl group.

"Arylsulfonyl group" in the definition of D represents a group to which the "aryl group" is associated with sulfonyloxy group. Specified arylsulfonyl group can represent, for example, arylsulfonyl group having 6-10 carbon atoms, such as benzolsulfonat, p-toluensulfonyl, o-xylene-4-alfonsina, m-xylene-4-sulfonylurea, p-xylostella or naphthalenesulfonyl group, and preferably is benzolsulfonate group.

"Protective group for the amino group" in the definition of R1and R2means a protective group for the amino group commonly used in chemistry for organic synthesis, and can be represented as:

"aliphatic acyl group", for example "lower aliphatic acyl group"described above, halogenated lower aliphatic acyl group, such as chlorocichla, dichloroacetylene, trichloroethylene or trifluoracetyl group, or a lower aliphatic acyl group, a substituted lower alkoxygroup, such as methoxyacetyl group;

"aromatic acyl group", for example an aromatic acyl group, such as benzoline, 1-indocarbocyanine, 2-indocarbocyanine or 1 - or 2-napolina group, or an aromatic acyl group substituted by 1-3 substituents selected from the above Group (a) substituents, such as 4-chlorbenzoyl, 4-tormentilla, 2,4,6-trimethylbenzoyl, 4-toluylene, 4-ansorena, 4-nitrobenzoyl, 2-nitrobenzoyl, 2-(methoxycarbonyl)benzoline or 4-phenylbenzyl group;

"alkoxycarbonyl group", for example "lower alkoxycarbonyl group"described earlier, or the bottom of the eighth alkoxycarbonyl group, substituted by one or more halogen atoms or by one or more lower trialkylsilyl groups such as 2,2,2-trichlorocarbanilide or 2-trimethylsilylethynyl group;

"altneratively group, such as vinyloxycarbonyl or allyloxycarbonyl group;

"aracelikarsaalyna group", for example aracelikarsaalyna group, such as benzyloxycarbonyl group, or aracelikarsaalyna group substituted by 1-3 substituents selected from the above Group (a) substituents, such as 4-methoxybenzylideneamino, 3,4-dimethoxybenzonitrile, 2-nitrobenzisoxazole or 4-nitrobenzisoxazole group;

"silyl group", for example lower trialkylsilyl group, such as trimethylsilyl, triethylsilyl, isopropylideneuridine, tert-butyldimethylsilyl, methyldiisopropanolamine, Matilde(tert-butyl)silyl or triisopropylsilyl group, or silyl group, substituted 3 substituents selected from aryl groups or aryl and lower alkyl groups, such as diphenylmethylsilane, diphenylmethylsilane, diphenylmethylsilane or phenyldimethylsilane group;

"Uralkaliy group", for example lower alkyl group, a substituted 1-3 aryl groups is mi, such as benzyl, fenetylline, 3-phenylpropionate, α-naphthylethylene, β-naphthylethylene, diphenylmethylene, triphenylethylene, α-afterdirectly or 9-intellilink group, or a lower alkyl group, a substituted 1-3 aryl groups, where this aryl group is a substituted lower alkyl group, lower alkoxygroup, nitrogroup, halogen or cyano, such as 4-methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl, 4-methoxybenzyl, 4-methoxyphenylethylamine, 2-nitroaniline, 4-nitroaniline, 4-chloraniline, 4-brombenzene, 4-Lebenshilfe, 4-lambertinifiorella, bis(2-nitrophenyl)methyl or piperella group; or

"substituted methylene group, forming a Schiff base", such as N,N-dimethylaminomethylene, benzylidene, 4-methoxybenzylidene, 4-nitrobenzylidene, salicylidene, 5-chlorosalicylaldehyde, diphenylmethylene or (5-chloro-2-hydroxyphenyl)phenylmethylene group.

"Protective group for the amino group" is preferably a lower aliphatic acyl group, a lower alkoxycarbonyl group, aracelikarsaalyna group or aracelikarsaalyna group substituted by 1-3 substituents selected from the Group of substituents, particularly preferably acetyl is full or tert-butoxycarbonyl group.

"Protective group of hydroxyl group" in the definition of R3means "ordinary protective group in chemical reactions", which can be removed by chemical method such as hydrogenolysis, hydrolysis, electrolysis and photolysis, or a protective group which can be removed by means of biological treatment such as hydrolysis in vivo".

"Conventional protective group in chemical reactions" can represent, for example:

aliphatic acyl group described above;

aromatic acyl group described above;

"tetrahydropyranyloxy or tetrahydropyranyloxy group, such as tetrahydropyran-2-ilen,

3-bromotetradecane-2-ilen,

4-methoxyacridine-4-ilen, tetrahydrothiopyran-2-ilen or 4-methoxytryptamine-4-ilen group;

"tetrahydrofuranyl or tetrahydropyranyl group"such as tetrahydrofuran-2-ilen or tetrahydrothiopyran-2-ilen group;

"silyl group"described above;

"alkoxymethyl group", for example lower alkoxymethyl group, such as methoxymethyl, 1,1-dimethyl-1-methoxymethyl, ethoxymethylene, propoxymethyl, isopropoxyaniline, butoxymethyl or tert-butoxymethyl group, lower alkoxycarbonyl alkoxymethyl group, such as 2-methoxyethoxymethyl group, or Galaganov is nnow lower alkoxymethyl group, such as 2,2,2-trichloroethylene or bis(2-chloroethoxy)methyl;

"substituted ethyl group such as lower alkoxycarbonyl ethyl group such as 1-amoxicilina or 1-(isopropoxy)ethyl group, or a halogenated ethyl group such as 2,2,2-trichlorethylene group;

"Uralkaliy group"described above;

"alkoxycarbonyl group"described above;

"altneratively group"described above; or

"aracelikarsaalyna group described above.

On the other hand, the "protective group which can be removed by means of biological treatment such as hydrolysis in vivo", can represent, for example:

"carboncillo group", for example aryloxyalkyl group, such as ethylcarboxylate, pivaloyloxymethyl, dimethylaminoacetonitrile or 1-acetoxyethyl group;

1-(alkoxycarbonyl)alkyl group such as 1-(methoxycarbonylamino)ethyl, 1-(ethoxycarbonyl)ethyl, ethoxycarbonylmethyl, 1-(isopropoxycarbonyl)-ethyl, 1-(tert-butoxycarbonylamino)ethyl, 1-(ethoxycarbonyl), sawn or 1-(cyclohexyloxycarbonyl-hydroxy)ethyl group;

phthalidyl group or

oksadiazoldiola group, such as 4-metronidazolegermany, 4-phenyloxazolidine Il is exodeoxyribonuclease group;

"aliphatic acyl group"described above;

"aromatic acyl group"described above;

"residual group of a complex Palmyra succinic acid";

"residual group of ester of phosphoric acid";

"residual group forming an ester of the amino acid or the like";

karbamoilnuyu group;

"protective group two hydroxyl groups, for example aralkylamines group, such as benzylidene group, alkoxyethanol group, such as methoxyacridine or amoxicillinbuy group, octamethylene group or dioximethylene group; or

"carbonylcontaining group, such as pivaloyloxymethyl group.

The suitability of such a derivative can be defined by introducing its experimental animal, such as rat or mouse, intravenous, and then measuring the body fluid of the animal and the detection of the parent compound or its pharmacologically acceptable salt.

"Protective group of hydroxyl group" is preferably a lower aliphatic acyl group, aromatic acyl group, aromatic acyl group substituted by 1-3 substituents selected from the Group of substituents, or a silyl group, especially preferably acetyl group or tert-butyldimethylsilyl is owned by the group.

"Protective group of phosphoric acid" in the definition of R10and R11can represent, for example:

lower alkyl group, for example:

the lower alkyl group such as methyl, ethyl, ISO-propyl or bucilina group,

lower alkyl group substituted by one or more cyano groups, such as 2-laitila or 2-cyano-1,1-dimethylethylene group,

lower alkyl group substituted by one or more silyl groups, where specified silyl group is substituted with 3 substituents selected from the group consisting of lower alkyl groups or aryl and lower alkyl groups such as 2-(methylvinylether)ethyl or 2-trimethylsilylethynyl group,

lower alkyl group substituted by one or more heterocyclyl groups, such as 2-(2'-pyridyl)ethyl or 2-(4'-pyridyl)ethyl group,

lower alkyl group substituted by one or more aristokratami, such as 2-phenylthiourea, 2-(4'-nitro-phenylthio)ethyl or 2-(4'-triphenylmethane)ethyl group,

lower alkyl group substituted by one or more alkylsulfonyl groups, arylsulfonyl groups or arylalkylamine groups, such as 2-(tert-butylsulfonyl)ethyl, 2-(phenylsulfonyl)ethyl or 2-(benzylmethyl)e the ilen group, or

halogenated lower alkyl group, such as 2,2,2-trichlorethylene, 2,2,2-trichlorethyl-1,1-dimethylethylene, 2,2,2-tribromaniline, 2,3-dibromopropionyl or

2,2,2-triptorelin group;

aracelio group, for example:

lower alkyl group, a substituted 1,3-aryl groups, such as benzyl, fenetylline, 3-phenylpropionate, α-naphthylethylene, β-naphthylethylene, diphenylmethylene, triphenylethylene, α-afterdirectly or 9-intellilink group,

lower alkyl group substituted by one or more aryl groups, where specified aryl portion is substituted by one or more nitro groups, halogen atoms or lower aliphatic acyl groups, such as o-nitroaniline, 4-nitroaniline, 2,4-dinitroaniline, 4-chloraniline, 4-chloro-2-nitroaniline or 4-acyloxymethyl group,

lower alkyl group substituted by one or more aryl groups having one or more substituents, such as 2-nitrophenylamino group, or

lower alkyl group substituted by one or more fluoroaniline groups, such as fluorenylmethyl group;

lower alkenylphenol group, such as allyl or protanilla group;

lower alkenylphenol group, substituted by one or more qi is nagrodami, such as 4-cyano-2-bucinellina group;

aryl group such as phenyl group;

aryl group substituted by one or more substituents selected from the group consisting of lower alkyl groups, lower alkyl groups, substituted 3 aryl groups, lower alkoxygroup, nitro and halogen atom, such as 2-methylphenylene, 2,6-dimethylaniline, 2-chloraniline, 4-chloraniline, 2,4-dichloraniline, 2,5-dichloraniline, 2,6-dichloraniline, 2-bratinella, 4-nitroaniline, 3,5-dinitroaniline, 4-chloro-2-nitroaniline or 2-methoxy-5-nitroaniline group; or

amide, such as anilide, 4-triphenyltetrazolium, [N-(2-trityloxy)ethyl]anilide, p-(N,N-dimethylamino)anilide or 3-(N,N-diethylaminomethyl)anilide.

"Protective group of phosphoric acid" is preferably a lower alkyl group, lower alkenylphenol group or methyl group is substituted by 1-3 substituents selected from the group consisting of phenyl groups and naftilos group, more preferably methyl group, ethyl group, allyl group or benzyl group, and most preferably methyl group or ethyl group.

"C3-C10cycloalkyl group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) the Deputy is", in the definition of R5may be, for example, 2-ferricopiapite, 2-chlorocyclopropane, 2 - or

3-perticipation, 2 - or 3-chlorocyclopentane, 2-,

3 - or 4-forcecoercion, 2-, 3 - or 4-chlorocyclohexanone, 2-, 3 - or 4-bromocyclohexene, 2-, 3 - or

4-godzillakilla, 2-methylcyclopropyl,

2-ethylcyclopropane, 2 - or 3-methylcyclopentanone, 2 - or

3-ethylcyclopentane, 2-, 3 - or 4-methylcyclohexyl,

2-, 3 - or 4-ethylcyclohexyl, 2-triftoratsetofenona, 2 - or 3-triftoratsetofenona, 2 - or

3-triftoratsetofenona, 2-, 3 - or

4-triftormetilfullerenov, 2-methoxycyclohexene, 2 - or 3-methoxyisobutyl, 2 - or 3-methoxycoronaridine,

2-, 3 - or 4-methoxycyclohexyl, 2-, 3 - or

4-toxicologically, 2-, 3 - or 4-propositionally, 2-, 3 - or 4-isopropylcyclohexane, 2-, 3 - or

4-(1-ethylpropoxy)tsiklogeksilnogo, 2-, 3 - or

4-(2-ethylpropoxy)tsiklogeksilnogo, 2-carboxyaniline,

2 - or 3-carboxyaniline, 2-, 3 - or

4-carboxyaniline, 2-methoxycarbonylpropionyl,

2 - or 3-methoxycarbonylmethylene, 2-, 3 - or

4-methoxycarbonylbenzyl, 2-hydroxyisopropyl,

2 - or 3-hydroxycyclopent, 2-, 3 - or

4-hydroxycyclohexyl, 2-formyltetrahydrofolate, 2 - or

<> 3-formultimedia, 2-, 3 - or 4-formylcyclohex,

2-acetylcyclopentanone, 2 - or 3-acetylcyclopentanone, 2-,

3 - or 4-acetylcyclohexanone, 2-aminocyclopropane, 2 - or 3-aminocyclopentane, 2-, 3 - or 4-aminocyclohexanone,

2-methylenecyclopropane, 2 - or 3-methylenecyclobutane, 2 - or 3-methylenecyclobutane, 2-, 3 - or

4-methylenedicyclohexyl, 2-dimethylaminoisopropyl,

2 - or 3-dimethylaminonaphthalene, 2 - or 3-dimethylaminoethyl-pencilina, 2-, 3 - or 4-dimethylaminoethylacrylate,

2-chancellorville, 2 - or 3-lanzilotta, 2-, 3 - or 4-cancilleria, 2 - or 3-cyclohexylaniline,

2-, 3 - or 4-cyclohexylcyclohexanes, 2-phenylcyclopropane, 2 - or 3-vinylcyclopentane, 2-, 3 - or

4-phenylcyclohexanone, 3,4-diverticulectomy,

3,4-dichlorocyclohexyl, 2,3-dimethoxyaniline,

3,4-dimethoxyaniline, 3,5-dimethoxyaniline or 3,4,5-trimethoxyaniline group is preferably3-C10cycloalkyl group substituted by 1-3 substituents (the substituents selected from the group consisting of halogen atoms, lower alkyl groups, halogenated lower alkyl groups, lower alkoxygroup, lower alkylthio and lower aliphatic acyl groups), more preferred is equipment With 3-C10cycloalkyl group substituted by 1-3 substituents (the substituents selected from the group consisting of halogen atoms, lower alkyl groups, halogenated lower alkyl groups, lower alkoxygroup and lower aliphatic acyl groups), more preferably3-C10cycloalkyl group substituted by 1-3 substituents (the substituents selected from the group consisting of halogen atoms, lower alkyl groups, halogenated lower alkyl groups, lower alkoxygroup and lower aliphatic acyl groups), and most preferably tsiklogeksilnogo group, substituted with one substituent (specified by the Deputy selected from the group consisting of fluorine atom, chlorine atom and methyl, triptorelin, methoxy and acetyl groups).

"C6-C10aryl group substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) substitutes", in the definition of R5may be, for example, 2-, 3 - or 4-Fortunella, 2-, 3 - or 4-chloraniline, 2-,

3 - or 4-bratinella, 2-, 3 - or 4-idfamilia, 2-, 3 - or

4-methylphenylene, 2-, 3 - or 4-ethylenimine, 2-, 3 - or

4-propylaniline, 2-, 3 - or 4-butylaniline, 2-, 3 - or

4-interphenylene, 2-, 3 - or 4-triftormetilfullerenov,

2-, 3 - or 4-metoksifenilny, 2-, 3 - or 4-ethoxyphenyl is,

2-, 3 - or 4-propoxyphenyl, 2-, 3 - or

4-isopropoxyaniline, 2-, 3 - or 4-butoxyaniline,

2-, 3 - or 4-(1-ethylpropoxy)phenyl, 2-, 3 - or

4-(2-ethylpropoxy)phenyl, 2-, 3 - or 4-methylthiophenyl,

2-, 3 - or 4-ethylthiophene, 2-, 3 - or 4-carboxyaniline, 2-, 3 - or 4-ethoxycarbonylphenyl, 2-, 3 - or

4-ethoxycarbonylphenyl, 2-, 3 - or 4-hydroxyproline,

2-, 3 - or 4-formylphenyl, 2-, 3 - or 4-acetylphenyl,

2-, 3 - or 4-aminoaniline, 2-, 3 - or 4-methylaminophenol, 2-, 3 - or 4-dimethylaminophenyl, 2-, 3 - or 4-cianfriglia, 2-, 3 - or 4-cyclopentylphenol, 2-, 3 - or

4-cyclohexylaniline, 2-, 3 - or 4-biphenylene,

2,4-differenly, 3,4-differenly, 3,5-differenly, 2,4-dichloraniline, 3,4-dichloraniline, 3,5-dichloraniline, 3,4-dibromophenyl, 2,3-dimethylaniline, 3,4-dimethylaniline, 3,5-dimethylaniline, 2,3-dimethoxyaniline,

3,4-dimethoxyphenyl, 3,5-dimethoxyaniline,

3,4,5-trimethoxyaniline, 3-fluoro-4-metoksifenilny,

4-methyl-2-metoksifenilny, 6-fluoro-4-methyl-2-metoksifenilny, 5-veringen-3-ilen, 5-methylinden-3-ilen,

5-methoxyindol-3-ilen, 5-veringen-2-ilen,

5-clarenden-2-ilen, 5-methylindene-2-ilen,

5-methoxyindol-2-ilen, 5-hydroxide-3-ilen,

5-nitrogen-3-ilen, 5-cyclohexylidene-3-ilen,

5-phenylindane-3-ilen, 5-phenoxide-3-yl) - Rev. Naya,

5-benzyloxyindole-3-ilen, 5-phenylthieno-3-ilen,

5-hydroxide-2-ilen, 5-nitrogen-2-ilen,

5-cyclohexylidene-2-ilen, 5-phenylindane-2-ilen,

5-fornatale-2-ilen, 5-methylnaphthalene-2-ilen,

5-methoxynaphthalene-2-ilen, 5-fornatale-1-ilen,

5-methylnaphthalene-1-ilen, 5-methoxynaphthalene-1-ilen,

5-hydroxynaphthalene-2-ilen, 5-nitronaphthalene-2-ilen,

5-cyclohexylmethyl-2-ilen, 5-phenylnaphthalene-2-ilen,

5-proximately-2-ilen, 5-benzyloxyindole-2-ilen,

5-ventionally-2-ilen, 5-hydroxynaphthalene-1-ilen,

5-nitronaphthalene-1-ilen, 5-cyclohexylmethyl-1-ilen, or

5-phenylnaphthalene-1-ilen group, and is preferably

With6-C10aryl group substituted by 1-3 substituents (the substituents selected from the group consisting of halogen atoms, lower alkyl groups, halogenated lower alkyl groups, lower alkoxygroup, lower alkylthio and lower aliphatic acyl groups), more preferably6-C10aryl group substituted by 1-3 substituents (the substituents selected from the group consisting of halogen atoms, lower alkyl groups, halogenated lower alkyl groups, lower alkoxygroup and lower aliphatic acyl groups), more preferably phenyl group, replacing the military 1-3 substituents (the substituents selected from the group consisting of halogen atoms, lower alkyl groups, halogenated lower alkyl groups, lower alkoxygroup and lower aliphatic acyl groups), particularly preferably a phenyl group substituted by 1 or 2 substituents (the substituents selected from the group consisting of fluorine atoms, chlorine atoms and methyl, triptorelin, methoxy and acetyl groups, but in the case of metoxygroup preferred is a phenyl group substituted by 1-3 methoxypropane) and most preferably

3-Fortunella, 4-Fortunella, 3,4-differenly,

3,5-differenly, 3-chloraniline, 4-chloraniline,

3,4-dichloraniline, 3,5-dichloraniline, 3-methylphenylene,

4-methylphenylene, 3,4-dimethylaniline, 3,5-dimethylaniline,

3-triftormetilfullerenov, 4-triftormetilfullerenov,

3,4-dateformatstring, 3,5-dateformatstring,

3-metoksifenilny, 4-metoksifenilny, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,4,5-trimethoxyaniline,

3-acetylphenyl or 4-acetylphenyl group.

"5-7-Membered heterocyclic group containing 1-3 heteroatoms selected from the group consisting of a sulfur atom, oxygen atom and nitrogen atom and is substituted by 1-3 substituents selected from the group consisting of Groups (a) of substituents and the Group (b) substitutes", in the definition of R5what may be for example, 3-, 4 - or 5-methylfuran-2-ilen, 2-, 4 - or 5-methylfuran-3-ilen, 3-, 4 - or 5-fortifed-2-ilen, 2-, 4 - or

5-perforin-3-ilen, 3-, 4 - or 5-bromothiophene-2-ilen, 2-,

4 - or 5-bromofuran-3-ilen, 3-, 4 - or 5-methylthiophene-2-ilen, 2-, 4 - or 5-methylthiophene-3-ilen, 3-, 4 - or 5-ethylthiophen-2-ilen, 2-, 4 - or 5-ethylthiophen-3-ilen, 3-, 4 - or

5-methoxythiophene-2-ilen, 2-, 4 - or 5-methoxythiophene-3-ilen, 3 - or 4-methylthiazole-5-ilen, 3-, 4 - or 5-fermentative-2-ilen, 3-, 4 - or 5-bromobenzoate-2-ilen, 3-, 4 - or

5-methylbenzofuran-2-ilen, 3-, 4 - or 5-methoxybenzamide-2-ilen, 2-, 4 - or 5-fermentation-3-ilen, 2-, 4 - or

5-bromobenzoate-3-ilen, 2-, 4 - or 5-methylbenzofuran-3-ilen, 2-, 4 - or 5-methoxybenzamide-3-ilen, 4-, 5-, 6 - or 7-methylbenzofuran-2-ilen, 3-, 4 - or 5-hydroxyfuran-2-ilen, 2-, 4 - or 5-hydroxyfuran-3-ilen, 3-, 4 - or

5-hydroxythiophene-2-ilen, 3-, 4 - or 5-nitrothiophen-2-ilen,

3-, 4 - or 5-phenylthiophene-2-ilen, 2-, 4 - or 5-hydroxythiophene-3-ilen, 2-, 4 - or 5-Tiantian-3-ilen, 1-, 2 - or

3 hydroxypyridine-4-ilen, 1-, 2 - or 3-lepirudin-4-ilen, or 1-, 2 - or 3-phenylpyridine-4-ilen group and preferably is a 3-, 4 - or 5-fortifed-2-ilen, or 2-, 4 - or

5-perforin-3-ilen group.

"Its pharmacologically acceptable salt" means a salt which, when the compounds of General formula (I), (II) or (III) this izobreteny who have coreó main group such as amino group, can be obtained by the interaction of these compounds with an acid, and when the compounds of General formula (I), (II) or (III) of the present invention have an acid group such as carboxyl group or a phosphate group, can be obtained by the interaction of these compounds with a base.

Salt, when the compounds of General formula (I), (II) or (III) have coreómain group may be a salt of an inorganic acid, such as salt halogenation acid, such as hydroptere, hydrochloride, hydrobromide or hydroiodide, nitrate, perchlorate, sulfate, phosphate or the like; a salt of an organic acid, for example lower alkanesulfonyl, such as methanesulfonate, triftorbyenzola or econsultant, arylsulfonate, such as bansilalpet or p-toluensulfonate, acetate, malate, fumarate, succinate, citrate, ascorbate, tartrate, oxalate, maleate or the like; or a salt of the amino acids, such as salt of glycine salt, lysine salt, arginine salt, ornithine salt of glutamic acid or a salt of aspartic acid. Preferred is a salt of organic acids (especially fumarate, oxalate or maleate) or salt halogenation acid (especially hydrochloride).

Salt, when the compounds of General formula (I), (II) or (III) have kislotno the th group, can be a metal salt, such as salt of an alkali metal such as sodium salt, potassium salt or lithium salt, a salt of alkaline earth metal such as calcium salt or magnesium salt, an aluminium salt, iron salt or the like; an amine salt such as an inorganic amine salt such as ammonium salt, organic amine salt such as a salt of tert-octylamine, salt dibenzylamine, salt of the research, salt of glucosamine, salt complex Olkiluoto phenylglycine ester, salt, Ethylenediamine salt, N-methylglucamine, guanidine salt, salt diethylamine, salt, triethylamine salt dicyclohexylamine, salt N,N'-dibenziletilendiaminom, salt chloroprocaine, salt of procaine, diethanolamine salt, a salt of N-benzylpenicillin, salt, piperazine salt of Tetramethylammonium, salt of Tris(hydroxymethyl)aminomethane or the like; or a salt of the amino acids, such as salt of glycine salt, lysine salt, arginine salt, ornithine salt of glutamic acid or a salt of aspartic acid. The preferred salt is a salt of an alkali metal (particularly sodium salt).

When the compounds of General formula (I), (II) or (III), their pharmacologically acceptable salts or their pharmaceutically acceptable esters of the present invention allowed to stand in contact with the atmosphere or precrystallization, they can absorb water, and the water and can be attached with the formation of hydrate. The present invention covers such hydrates.

Compounds of General formula (I), (II) or (III), their pharmacologically acceptable salts or pharmaceutically acceptable esters of the present invention have one or more asymmetric carbon atoms and thus can exist as optical isomers. In the present invention, a single optical isomer and a mixture of optical isomers represented by one of chemical formula (I), (II) or (III). The present invention includes both the individual optical isomers and mixtures thereof in any proportion.

Preferred compounds of General formula (I), (II) or (III) of the present invention have a group of formula-NR1R2attached to the asymmetric carbon atom, and the absolute configuration at the specified asymmetric carbon atom is R-configuration.

"Its ester"described above means an ester compounds of General formula (I), (II) or (III)who have a group capable of esterification. Ester can be an "ester by a hydroxyl group or an ester at the carboxyl group. Each ester residual group refers to "conventional protective group in chemical reactions" or "protective group can be removed by means of biological treatment such as hydrolysis in vivo".

"Conventional protective group in chemical reactions" is a protective group which can be split by chemical means, such as hydrogenolysis, hydrolysis, electrolysis and photolysis.

"Conventional protective group in chemical reactions" and "protective group can be removed by means of biological treatment such as hydrolysis in vivo", referring to the complicated air on the hydroxyl group have the same meanings as described above for the protective group of hydroxyl group.

"Conventional protective group in chemical reactions", related to "difficult to live on the carboxyl group, preferably represents a "lower alkyl group"described above; lower alkenylphenol group, such as ethynyl, 1-propenyl,

2-propenyl, 1-methyl-2-propenyl, 1-methyl-1-propenyl,

2-methyl-1-propenyl, 2-methyl-2-propenyl, 2-ethyl-2-propenyl,

1-butenyl, 2-butenyl, 1-methyl-2-butenyl, 1-methyl-1-butenyl,

3-methyl-2-butenyl, 1-ethyl-2-butenyl, 3-butenyl,

1-methyl-3-butenyl, 2-methyl-3-butenyl, 1-ethyl-3-butenyl,

1-pentenyl, 2-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 4-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl or 5-hexenyl; lower alkylamino group, such as ethinyl, 2-PROPYNYL, 1-methyl-2-PROPYNYL,

2-butynyl, 1-methyl-2-buten is l, 1-ethyl-2-butinyl, 3-butinyl,

1-methyl-3-butynyl, 2-methyl-3-butynyl, 1-ethyl-3-butinyl,

2-pentenyl, 1-methyl-2-pentenyl, 3-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 4-pentenyl, 1-methyl-4-pentenyl,

2-methyl-4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl or

5-hexenyl; "halogenated lower alkyl group"described above; hydroxy"lower alkyl group"such as

2-hydroxyethyl, 2,3-dihydroxypropyl, 3-hydroxypropyl,

3,4-dihydroxybutyl or 4-hydroxybutyl; the group "lower aliphatic acyl"-"lower alkyl group"such as acetylenyl; "Uralkaliy group"described above, or silyl group described above.

"Protective group can be removed by means of biological treatment such as hydrolysis in vivo"related to "difficult to live on the carboxyl group, preferably represents a "alkoxyalkyl group, such as group, lower alkoxy-lower alkyl, for example methoxyethyl, 1-ethoxyethyl,

1-methyl-1-methoxyethyl, 1-(isopropoxy)ethyl, 2-methoxyethyl,

2-ethoxyethyl, ethoxymethyl, n-propoxymethyl, isopropoxyphenyl,

n-butoxymethyl or tert-butoxymethyl, the group of lower alkoxycarbonyl alkoxy-lower alkyl, for example 2-methoxyethoxymethyl, "aryl"oxy"lower alkyl group", for example phenoxymethyl, or a halogenated group, a lower alkoxy-lower Alky is, for example 2,2,2-trichloroacetyl or

bis(2-chloroethoxy)methyl; a group of "lower alkoxy"carbonyl-"lower alkyl group"such as methoxycarbonylmethyl; group cyan"lower alkyl group"such as lanmeter or

2-Tianeti; the group "lower alkyl"thiomethyl, such as methylthiomethyl or ethylthiomethyl; "aryl"thiomethyl group such as phenylthiomethyl or Aftertime; the group "lower alkyl"sulfonyl-"lower alkyl group"which may be substituted by one or more halogen atoms, such as

2-methansulfonate or 2-triftormetilfullerenov; group "aryl"sulfonyl-"lower alkyl group"such as

2-benzosulfimide or 2-toluensulfonate;

1-(acyloxy)-"lower alkyl group"described above; "phthalidyl group"described above; the "aryl group"described above; a "lower alkyl group"described above; "carboxialkilnuyu group, such as carboxymethyl; or "amidabutsu residual group of amino acids"such as phenylalanine.

More preferred "conventional protecting group in chemical reactions" or "protective group can be removed by means of biological treatment such as hydrolysis in vivo"related to "difficult to live on the carboxyl group"is a lower alkyl or kalkilya group.

"Immunosuppressants is, which is an active component of the pharmaceutical compositions of the present invention, represent a deterrent or inhibiting the development of immune reactions, and compounds with immunosuppressive activity, and separated on the basis of the mechanism of their action on the following groups.

(1) Means having inhibitory effect on intracellular signaling involved in the expression of cytokines by T-cells, including means blocking the production of cytokines, as well as means to prevent the impact on the immune cells of the signals from cytokines by inhibiting intracellular signaling. Such funds, which have inhibitory effect on intracellular signaling involved in the expression of cytokines by T-cells include, for example:

S7481/F-1, disclosed in the description of U.S. patent number 4117118, or its pharmacologically acceptable salt [preferably cyclosporin a, the chemical name of which is cyclo[3-hydroxy-4-methyl-2-(methylamino)-6-octenoyl]-2-aminobutyryl-methylglycyl-methyl-leucyl-poured-methyl-leucyl-alanyl-alanyl-methyl-leucyl-methyl-leucyl-methyl-valil],

the compound of General formula (I)disclosed in the description of the European patent (ER) publication number 184162, or its pharmacologically acceptable salt {preferably tacrolimus, Henichesk what s the name of which is 17-allyl-1,14-dihydroxy-12-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0 4,9]octakis-18-ene-2,3,10,16-tetron},

rapamycin, disclosed in the description of U.S. patent number 3929992 [chemical name of which 9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecagon-9,27-dihydroxy-3-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-HEXAMETHYL-23,27-epoxy-3H-pyrido[2,1-c][1,4]oxazolidinediones-1,5,11,28,29(4H,6H,31H)-Penton],

the compound of General formula (II)disclosed in the description of European patent publication number 94632 (Japanese patent publication (Kokai) number Sho 58-62152), or its pharmacologically acceptable salt [preferably gusperimus, chemical name is N-[4-(3-aminopropyl)aminobutyl]carbamoyloximes-7-guanidinopentanoic, and in the present invention gusperimus includes its pharmacologically acceptable salt (trihydrochloride)],

the compound of General formula (I)disclosed in the description of U.S. patent number 5912253, or its pharmacologically acceptable salt {preferably everolimus, the chemical name of which 9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecagon-9,27-dihydroxy-3-[2-[4-hydroxyethoxy-3-methoxycyclohexyl]-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-HEXAMETHYL-23,27-epoxy-3H-pyrido[2,1-c][1,4]azacyclopentadecan-1,5,11,28,29(4H,6H,31H)-Penton},

the compound of General formula (I)disclosed in the description of European patent publication number 600762, or its pharmacologically acceptable salt {p is edocfile tresperimus, chemical name 2-[4-(3-aminopropylene)butyl]aminocarbonyl-N-[6-(aminoiminomethyl)aminohexyl]ndimethylacetamide, and in the present invention tresperimus includes its pharmacologically acceptable salt},

LF15-0195, disclosed in Int. J. Immunopharmacol., vol. 21 (5), 349-358 (1999) {esperemos, the chemical name of which is [(6-guanidinoacetic)carbarnoyl]methyl[4-(3-aminobutyl)aminobutyl]carbamate},

the compound of General formula (I)disclosed in the description of European patent publication number 626385 (Japan patent number 3076724 or U.S. patent number 5493019), or its pharmacologically acceptable salt {preferably assuming your-281-240, chemical name is 17-ethyl-1,14-dihydroxy-12-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]-octakis-18-ene-2,3,10,16-tetron, and in the present invention assuming your-281-240 includes its pharmacologically acceptable salt},

the compound of General formula (VII), disclosed in the description of the International (WO) publication number 93/04680 (European publication number 642516), or its pharmacologically acceptable salt {preferably ABT-281, chemical name is 17-ethyl-1,14-dihydroxy-12-[2-(4-tetrazolyl-3-methoxycyclohexyl)-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octakis-18-ene-2,3,10,16-tetron},

the compound of General formula (A), p is implicit in the description of European patent publication number 414632, or its pharmacologically acceptable salt {preferably tigerinus, the chemical name of which is cyclo[[3-hydroxy-4-methyl]-2-(methylamino)-6-octenoyl]-L-2-aminobutyryl-N-methylglycyl-N-methyl-L-leucyl-L-poured-N-methyl-L-leucyl-L-alanyl-[3-O-(2-hydroxyethyl)-D-seryl]-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valil],

the compound of General formula (I)disclosed in the description of International publication number 97/11080, or its pharmacologically acceptable salt {preferably A-119435, chemical name is 17-ethyl-1,14-dihydroxy-12-[2-[4-(acetamidoacrylic)-3-methoxycyclohexyl]-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octakis-18-ene-2,3,10,16-tetron}, and

17-ethyl-1,14-dihydroxy-12-[2-[4-(2-phenylhydrazine-carbonyloxy)-3-methoxycyclohexyl]-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octakis-18-ene-2,3,10,16-tetron, disclosed in Bioorg. Med. Chem. Lett., vol. 9 (2), 227-232 (1999).

Below shows a planar chemical structures of typical compounds.

(2) Funds, which have inhibitory effect on the synthesis of nucleosides in the cells of the immune system, inhibit lymphocyte proliferation by inhibiting the synthesis of nucleosides in immune cells and are respecifies the th immunosuppressive activity. Such means having inhibitory action on the synthesis of nucleosides in immune cells include, for example:

the compound having a chemical structure disclosed in item 1 description to U.S. patent number 3888843 (mizoribine, the chemical name is 5-hydroxy-1-β-D-ribofuranosyl-1H-imidazol-4-carboxamide),

the compound having the General formula disclosed in paragraph 7 of the description of U.S. patent number 3056785, or its pharmacologically acceptable salt [preferably azathioprine, chemical name 6-[(1-methyl-4-nitro-1H-imidazol-5-yl)thio]-1H-purine, and in the present invention azathioprine includes its pharmacologically acceptable salt (hydrochloride)],

the compound of General formula (A)disclosed in the description of European patent publication number 281713 (U.S. patent number 4753935), or its pharmacologically acceptable salt [preferably mycophenolat Mofetil, chemical name is 2-(4-morpholinyl)ethyl 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-(4E)-hexanoate],

the compound of General formula (I)disclosed in the description of European patent publication number 13376 (Japanese patent publication (Kokai) number Sho 62-72614 or U.S. patent number 4284786), or its pharmacologically acceptable salt [preferably Leflunomide, chemical name is 5-methyl-N-[4-(trifluoromethyl)phenyl]-4-ISOC azocarbonamide],

the compound of General formula (I)disclosed in the description of the International patent publication number 97/40028, or its pharmacologically acceptable salt {preferably of merimepodib, the chemical name is (3s)-tetrahydro-3-furanyl [[3-[[[[3-methoxy-4-(5-oxazolyl)phenyl]amino]carbonyl]amino]-phenyl]methyl]carbamate},

the compound of General formula (I)disclosed in the description of the French (FR) patent publication number 2727628, or its pharmacologically acceptable salt [preferably HMR-1279, chemical name α-cyano-N-(4-cyanophenyl)-β-oxacyclopropane],

the compound of General formula (I)disclosed in the description of the International patent publication number 93/22286 (Japanese patent publication number 2928385, European patent publication number 601191 or U.S. patent number 5371225), or its pharmacologically acceptable salt {preferably TSK-204, the chemical name of which is 6,7-dihydro-10-fluoro-3-(2-forfinal)-5H-benzo[6,7]cyclohepta[1,2-b]quinoline-8-carboxylic acid}, and

the compound of General formula (I)disclosed in the description of European patent publication number 569912 (Japanese patent publication (Kokai) number Hei 6-32784), or its pharmacologically acceptable salt {preferably SP-100030, chemical name is 2-chloro-N-[3,5-di(trifluoromethyl)phenyl]-4-(trifluoromethyl)pyrimidine-5-carboxamide},

Below is shown the flat x the economic structure of typical connections.

(3) Funds, which inhibit the action of cytokines on immune cells and possess Antirheumatic action, provide in combination suppress the production of cytokines, suppression of lymphocyte proliferation and suppress the production of immunoglobulin. In addition, these tools include a compound which has a suppressive effect on the proliferation of T cells, suppressive effect on the activity of NK-cells, an antagonistic effect with respect to TNF receptors and the like. These funds, which inhibit the action of cytokines on immune cells and possess Antirheumatic action, include, for example:

the compound having the General formula disclosed in paragraph (1) Japanese patent publication (Kokai) number Hei 2-49778, or its pharmacologically acceptable salt (preferably T-614, chemical name is N-[3-formylamino-4-oxo-6-phenoxy-4H-1-benzopyran-7-yl]methanesulfonamide),

the compound of General formula (I)disclosed in the description of U.S. patent number 4720506, or its pharmacologically acceptable salt [preferably actarit, chemical name 4-(acetylamino)phenylacetic acid],

the compound having the General formula disclosed in item 1 description to U.S. patent number 2396145, or its pharmacologically acceptable salt {preferably the fat is sulfapyridine, the chemical name is 5-[[p-(2-pyridylsulfonyl)phenyl]azo]salicylic acid}, and

the compound of General formula (I)disclosed in the description of International publication number 97/23457, or its pharmacologically acceptable salt {preferably CDC-801, the chemical name is 3-phthalimido-3-(3-cyclopentyloxy-4-methoxyphenyl)propionamide}.

Below shows a planar chemical structures of typical compounds.

(4) Funds, which are alkylating agents that cause cell death by rupture of DNA chains or blocking DNA synthesis include, for example,

the compound of General formula (IIIa), disclosed in the description of U.S. patent number 3018302, or its pharmacologically acceptable salt [preferably cyclophosphamide, chemical name 2-oxide N,N'-bis-(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine].

(5) Antimetabolites that inhibit the metabolism of nucleic acids by blocking the production of folic acid, exert an inhibitory effect on the metabolism of nucleic acids by binding to dihydrofolate-reductase and block products tetrahydrofolic acids required for the synthesis of the component parts of nucleic acids. These antimetabolites that inhibit the metabolism of nucleic acids to block the W production of folic acid, include, for example,

the compound having the General formula disclosed in item 1 description to U.S. patent number 2512572, or its pharmacologically acceptable salt {preferably methotrexate chemical name is N-[4-[[2,4-diamino-6-pteridinyl]methyl]methylamino]benzoyl-L-glutamic acid}.

(6) Group of protein drugs with depressing (overwhelming) effect on TNF-alpha, includes compounds such as antagonists of IL-1 receptors, soluble receptors of IL-1 and antibodies to anti-IL-6 receptors, which inhibit the action of TNF-alpha by inhibiting the neutralizing action of circulating TNF-alpha and receptor-mediated intracellular signaling from TNF-alpha. These protein drugs, which have an inhibitory effect on TNF-alpha include, for example:

Remicade (infliximab), disclosed in the description of U.S. patent number 5656272 and Drugs, vol. 59(6), 1341-1359 (2000),

Enbrel (etanercept), disclosed in the description of International publication number 94/06476, U.S. patent number 5605690 and Expert. Opin. Pharmacother., July vol. 2(7), 1137-1148 (2000),

daclizumab, disclosed in the description of International publication number 92/11018, U.S. patent number 5530101 and N. Engl. J. Med., vol. 338(3), 161 to 165 (1997),

basiliximab, disclosed in the description of European publication number 449769 and Clin. Pharmacol. Ther., Vol. 64(1), 66-72 (1998),

alemtuzumab, disclosed in the description of International publication number 89/07452, U.S. patent number 5846534 and J. Clin. Oncol., vol. 15(4), 1567-1574 (1997),

omalizumab, disclosed in the description of U.S. patent number 5965709 and Drugs vol. 61(2), 253-260 (2001),

BMS-188667, disclosed in the description of European publication number 613944 and J. Pharm. Sci., vol. 84(12), 1488-1489 (1995),

CDP-571, unveiled in Arthritis-Rheum., vol. 37(9), Suppl., S295 (1994),

enlimomab and ATM-027 disclosed in Transplant., June, vol. 55, 1320-1327 (1993), and

BTI-322, unveiled in Blood, Dec 1, vol. 92(11), 4066-4071 (1998).

(7) Funds, which is a steroid hormone drugs, which bind to intracellular steroid receptors to form a complex that communicates with the places of interaction (reaction sites) on the chromosomes, which leads to the synthesis of proteins exhibiting immunosuppressive activity include, for example, prednisolone (chemical name 1,4-pregnadien-3,20-dione-11β,17α-21-triol).

(8) Funds, which are substances that suppress the production of prostaglandin and/or non-steroidal anti-inflammatory drugs that are antagonists of prostaglandins include, for example:

the compound having the General formula disclosed in paragraph (1) Japanese patent publication (Kokoku) number Sho 58-4699, or its pharmacologically acceptable salt {preferably locks propen-sodium, chemical name 2-[4-(2-oxocyclopent-1-ylmethyl)phenyl]propionate sodium},

the compound of General formula I(A), disclosed in the description of U.S. patent number 3558690, or its pharmacologically acceptable salt {preferably diclofenac sodium, the chemical name of which [o-(2,6-dichloroaniline)phenyl]acetate-sodium},

the compound of General formula (I)disclosed in the description of U.S. patent number 4233299 (European patent publication number 0002482 or Japanese patent publication (Kokai) number Sho 58-92976), or its pharmacologically acceptable salt [preferably meloxicam, chemical name 1,1-dioxide 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazin-3-carboxamide],

the compound of General formula (II)disclosed in the description of the International patent publication number 95/15316 (U.S. patent number 5521207 or Japanese patent publication (Kokai) number 2000-109466), or its pharmacologically acceptable salt {preferably celecoxib chemical name is 4-[5-(4-were)-3-(trifluoromethyl)pyrazole-1-yl]benzosulfimide}

the compound of General formula (I)disclosed in the description of the International patent publication number 95/00501 (U.S. patent number 5474995), or its pharmacologically acceptable salt {preferably rofecoksib, chemical name 4-[4-(methylsulphonyl)phenyl]-3-phenyl-2(5H)-furanone}.

Of these immunosuppressants more preferred are cyclosporin a, tacrolimus, rapamycin, Leflunomide, methotrexate, Remicade and andrel.

"Its pharmacologically acceptable salt"described above means a salt that can be converted described above immunosuppressants for interaction of the compounds with cosómain group, such as amino group, with an acid or a coordination compound having an acid group such as carboxyl group with a base. Such salts are included within the scope of the present invention.

Salts formed with the baseómain group of the above immunosuppressants, preferably represent a salt of an inorganic acid, such as hydrohalogen, such as hydroptere, hydrochloride, hydrobromide or hydroiodide, nitrate, perchlorate, sulfate, phosphate or the like; a salt of an organic acid, for example lower alkanesulfonyl, such as methanesulfonate, triftorbyenzola or econsultant, arylsulfonate, such as bansilalpet or p-toluensulfonate, acetate, malate, fumarate, succinate, citrate, ascorbate, tartrate, oxalate, maleate or the like; or salts of amino acids such as glycine salt and salt , lysine salt, arginine salt, ornithine salt of glutamic acid or a salt of aspartic acid. Bol the preferred salt is the hydrochloride, acetate, fumarate, succinate or maleate.

Salt formed with an acid group of the above antidepressants, preferably is a salt of a metal, such as salt of an alkali metal such as sodium salt, potassium salt or lithium salt, a salt of alkaline earth metal such as calcium salt or magnesium salt, an aluminium salt, iron salt or the like; an amine salt such as an inorganic salt, such as ammonium salt, salt with organic acid, such as salt tert-octylamine, salt dibenzylamine, salt of the research, salt of glucosamine, salt complex Olkiluoto phenylglycine ester, salt, Ethylenediamine salt, N-methylglucamine, salt guanidine, salt diethylamine, salt, triethylamine salt of dicyclohexylamine, salt N,N'-dibenziletilendiaminom, salt chloroprocaine, salt of procaine, diethanolamine salt, a salt of N-benzylpenicillin, salt, piperazine salt of Tetramethylammonium, salt of Tris(hydroxymethyl)aminomethane or the like; or a salt of the amino acids, such as salt of glycine salt, lysine salt, arginine salt, ornithine salt of glutamic acid or a salt of aspartic acid. The preferred salt is the sodium salt, potassium salt, calcium salt, magnesium salt or an aluminum salt.

When immunosuppressants, the active components of the pharmaceutical compositions according to the present from which retenu, allowed to stand in contact with the atmosphere or precrystallization, they can absorb water, or water can join them with the formation of hydrate. The present invention covers such hydrates.

When immunosuppressants, the active components of the pharmaceutical compositions according to the present invention have asymmetric carbon atoms, they may by such asymmetric carbon atoms can exist in the form of various stereoisomers. In the present invention, those and other compounds represented by one of chemical formula. The present invention covers both the separate stereoisomers, and mixtures of two or more stereoisomers in any proportion.

The compounds shown in the following table 1, table 2, table 3, table 4, table 5 and table 6, specifically illustrated as the preferred compounds of General formula (I), (II) or (III) of the present invention. But the compounds of the present invention is not limited to these compounds.

Connection represented under the same number in table 1 and table 2 include compounds where X represents a sulfur atom (S), oxygen atom (O) or a group of formula =N-CH3.

Connection represented under the same number in table 5 and table 6 include six types of compounds in which X pre is represents a sulfur atom (S), the oxygen atom (O) or a group of formula =N-CH3and a phosphate group linked to the oxygen atom (O) or a group-CH2-.

Below shows the meaning of the abbreviations in the following tables.

Bu is boutelou group,

iBu is isobutylene group,

Bz represents a benzyl group,

Et represents an ethyl group,

cHx is a tsiklogeksilnogo group,

Me represents a methyl group,

Np(1) represents a naphthalene-1-ilen group,

Np(2) represents a naphthalene-2-ilen group,

Ph represents a phenyl group,

cPn is cyclopentyloxy group,

Pr is a various group and

iPr represents an isopropyl group.

Connection.R1R2R3R4n -Y-Z-R5R6R7
3-1HHHMe2-(CH2)4-cHxHH
3-2HHHMe2-(CH2)4-PhHH
3-3HHHMe2-(CH2)5-cHxHH
3-4HHHMe2-(CH2)5-PhHH
3-5HHHMe2-C≡C-(CH2)2-cHxHH
3-6HHHMe2-C≡C-(CH2)2-PhHH
3-7HHHMe2-C≡C-(CH2)3-cHxHH
3-8HHHMe2-C≡C-(CH2)3-PhHH
3-9 HHHMe2-CO-(CH2)3-cHxHH
3-10HHHMe2-CO-(CH2)3-PhHH
3-11HHHMe2-CO-(CH2)4-cHxHH
3-12HHHMe2-CO-(CH2)4-PhHH

4-4
Connection.R1R2R3R4n-Y-Z-R5R6R7
4-1HHHMe2-(CH2)4-cHxHH
4-2HHHMe2-(CH2)4-PhHH
4-3HHHMe2-(CH2)5-cHxHH
HHHMe2-(CH2)5-PhHH
4-5HHHMe2-C≡C-(CH2)2-cHxHH
4-6HHHMe2-C≡C-(CH2)2-PhHH
4-7HHHMe2-C≡C-(CH2)3-cHxHH
4-8HHHMe2-C≡C-(CH2)3-PhHH
4-9HHHMe2-CO-(CH2)3-cHxHH
4-10HHHMe2-CO-(CH2)3-PhHH
4-11HHHMe2-CO-(CH2)4-cHxHH
4-12HHHMe2 -CO-(CH2)4-PhHH

1. The compound of General formula (I)

where R1and R2are identical and represent each a hydrogen atom;

R3represents a hydrogen atom;

R4represents a lower alkyl group;

n represents an integer from 1 to 6;

X represents an oxygen atom or a group of formula =N-D (where D represents a hydrogen atom or a lower alkyl group);

Y represents an ethylene group, ethynylene group,a group of the formula-O-CH 2- (where E represents a carbonyl group or a group of the formula-CH(OH) -),6-C10Allenova group or6-C10Allenova group substituted by 1-3 substituents selected from group (a) deputies;

Z represents a single bond, C1-C10alkylenes group or1-C10alkylenes group containing an oxygen atom in the specified carbon chain or at the end of the specified carbon chain;

R5represents a hydrogen atom, a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of groups (a) deputies;

R6and R7are the same or different and represent each a hydrogen atom or lower alkyl;

group (a) of the substituents is a group consisting of a halogen atom, a lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup, low ancilliary;

provided that when R5represents a hydrogen atom, Z represents a branched C1-C10alkylenes group or1-C10alkylenes group containing an oxygen atom in the specified carbon chain or at the end of the specified carbon C is PI, or

its pharmacologically acceptable salt.

2. The compound according to claim 1, where the aforementioned compound of formula (I) has the formula (Ia), or its pharmacologically acceptable salt

3. The compound according to claim 2, where R1and R2are identical and represent each a hydrogen atom;

R3represents a hydrogen atom;

R4represents a C1-C4alkyl group;

n represents the integer 2 or 3;

X represents a group of formula =N-D (where D represents a hydrogen atom or a C1-C4alkyl group);

Y represents an ethylene group, ethynylene group, a group of the formula-CO-CH2-, a group of the formula-CH(OH)-CH2-, fenelonov group or fenelonov group substituted by 1-3 substituents selected from the group consisting of a halogen atom and lower alkyl groups;

Z represents a C1-With6alkylenes group;

R5represents a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup and neither is our ancilliary;

R6and R7are the same or different and represent each a hydrogen atom or a lower alkyl group;

or its pharmacologically acceptable salt.

4. The compound according to claim 2, where R1and R2are identical and represent each a hydrogen atom;

R3represents a hydrogen atom;

R4represents a C1-C2alkyl group;

n represents the integer 2 or 3;

X represents a group of formula =N-D (where D represents a hydrogen atom or a C1-C4alkyl group);

Y represents an ethylene group, ethynylene group, a group of the formula-CO-CH2-, a group of the formula-CH(OH)-CH2-, fenelonov group or fenelonov group substituted by 1-3 substituents selected from the group consisting of a halogen atom and lower alkyl groups;

Z represents a C1-C5alkylenes group;

R5represents a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup and lower ancilliary;

R6and R7are the same or different and represent each a hydrogen atom or a lower alkyl group;

or its pharmacologically acceptable salt.

5. The compound according to claim 2, where R1and R2are identical and represent each a hydrogen atom;

R3represents a hydrogen atom;

R4represents a methyl group;

n represents the integer 2;

X represents a group of formula = N-CH3;

Y represents an ethylene group, ethynylene group, a group of the formula-CO-CH2or fenelonov group;

Z represents an ethylene group, trimethylene group or tetramethylene group;

R5represents a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups and lower alkoxygroup;

each of R6and R7represents a hydrogen atom, or its pharmacologically acceptable salt.

6. The compound according to claim 2, where each of R1and R2represents a hydrogen atom;

R3represents a hydrogen atom

R4represents a methyl group;

n represents the integer 2;

X represents a group of formula = N-CH3;

Y represents a group of formula-CO-CH2-;

Z represents an ethylene group or trimethylene group;

R5represents a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups and lower alkoxygroup,

each of R6and R7represents a hydrogen atom,

or its pharmacologically acceptable salt.

7. The compound according to claim 1, where the aforementioned compound of formula (I) has the formula (Ib), or its pharmacologically acceptable salt

8. The compound according to claim 1, where the specified connection is selected from the following

compounds, or its pharmacologically acceptable salt:

2-amino-2-methyl-4-[5-(5-fenilpentil)furan-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(5-cyclohexylidene-1-inyl)furan-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(5-finalment-1-inyl)furan-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(4-cyclohexyloxy-1-inyl)furan-2-yl]Boo is EN-1-ol,

2-amino-2-methyl-4-[5-(5-cyclohexylmethanol)furan-2-yl]butane-1-ol, and

2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-inyl]furan-2-yl}butane-1-ol.

9. The compound according to claim 1, where the specified connection is selected from the following compounds or a pharmacologically acceptable salt:

2-amino-2-methyl-4-[1-methyl-5-(5-finalment-1-inyl)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[3-(4-methylphenoxy)prop-1-inyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxy-1-inyl)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-inyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentane)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylmethanol)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutane)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylmethanol)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(4-were)butanoyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentane)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylmethanol)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutane)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylmethanol)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-1-methyl-5-[4-(3,4-dimetilfenil)butanoyl]-pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3, 5dimethylphenyl)butanoyl]-pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3-triptoreline)-butanoyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(4-triptoreline)-butanoyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(4-methoxyphenyl)butanoyl]-pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3-were)butyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimetilfenil)butyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3, 5dimethylphenyl)butyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3-triptoreline)butyl]-pyrrol-2-yl}butane-1-ol.

10. The compound of formula (II)

where R1and R2are identical and represent each a hydrogen atom;

R4represents a lower alkyl group;

n represents an integer from 1 to 6;

X represents an oxygen atom or a group of formula =N-D (where D represents a hydrogen atom or a lower alkyl group);

Y represents an ethylene group, ethynylene group, a group of the formula-O-CH2- (where E represents a carbonyl group or a group of the formula-CH(OH) -),6-C10Allenova group or6-C10and Elenovo group, substituted by 1-3 substituents selected from group (a) deputies;

Z represents a single bond, C1-C10alkylenes group or a C1-C10alkylenes group containing an oxygen atom in the specified carbon chain or at the end of the specified carbon chain;

R5represents a hydrogen atom, a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of groups (a) deputies;

R6and R7are the same or different and represent each a hydrogen atom or lower alkyl;

R10and R11are identical and represent each a hydrogen atom;

group (a) of the substituents is a group consisting of a halogen atom, a lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup, low ancilliary;

provided that when R5represents a hydrogen atom, Z represents a branched C1-C10alkylenes group or1-C10alkylenes group containing an oxygen atom in the specified carbon chain or at the end of the specified carbon chain,

or its pharmacologically acceptable salt.

<> 11. The connection of claim 10, where the specified connection is selected from the following compounds, or its pharmacologically acceptable salt:

mono 2-amino-2-methyl-4-[5-(5-fenilpentil)furan-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-cyclohexylidene-1-inyl)furan-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-finalment-1-inyl)furan-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(4-cyclohexyloxy-1-inyl)furan-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-cyclohexylmethanol)furan-2-yl]-1-butylphosphate, and

mono 2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-inyl]furan-2-yl]}-1-butylphosphate.

12. The connection of claim 10, where the specified connection is selected from the following compounds, or its pharmacologically acceptable salt:

mono 2-amino-2-methyl-4-[1-methyl-5-(5-finalment-1-inyl)pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{1-methyl-5-[3-(4-methylphenoxy)prop-1-inyl]pyrrol-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxy-1-inyl)pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-inyl]pyrrol-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentane)pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylmethanol)-pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(4-shall tivotool)pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylmethanol)-pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{1-methyl-5-[4-(4-were)butanoyl]pyrrol-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentane)pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylmethanol)-pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutane)pyrrol-2-yl]-1-butylphosphate and

mono 2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylmethanol)-pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimetilfenil)-butanoyl]pyrrol-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{1-methyl-5-[4-(3, 5dimethylphenyl)-butanoyl]pyrrol-2-yl}-1-butylphosphate.

13. The compound of formula (II) of claim 10, where the aforementioned compound of formula (II) has the formula (IIa)

or its pharmacologically acceptable salt.

14. The connection indicated in paragraph 13, where R1and R2are identical and represent each a hydrogen atom;

R4represents a C1-C4alkyl group;

n represents the integer 2 or 3;

X represents a group of formula =N-D (where D represents a hydrogen atom or a C1-C4alkyl group);

Y represents an ethylene group, ethynylene the second group, a group of the formula-CO-CH2-, a group of the formula-CH(OH)-CH2-, fenelonov group or fenelonov group substituted by 1-3 substituents selected from the group consisting of a halogen atom and lower alkyl groups;

Z represents a C1-C6alkylenes group;

R5represents a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup and lower ancilliary;

R6and R7are the same or different and represent each a hydrogen atom or a lower alkyl group;

R10and R11are identical and represent each a hydrogen atom, or its pharmacologically acceptable salt.

15. The connection indicated in paragraph 13, where R1and R2are identical and represent each a hydrogen atom;

R4represents a C1-C2alkyl group;

n represents the integer 2 or 3;

X represents a group of formula =N-D (where D represents a hydrogen atom or a C1-C4alkyl group);

Y represents etileno the second group, ethynylene group, a group of the formula-CO-CH2-, a group of the formula-CH(OH)-CH2-, fenelonov group or fenelonov group substituted by 1-3 substituents selected from the group consisting of a halogen atom and lower alkyl groups;

Z represents a C1-C5alkylenes group;

R5represents a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup and lower ancilliary;

R6and R7are the same or different and represent each a hydrogen atom or a lower alkyl group;

R10and R11are identical and represent each a hydrogen atom,

or its pharmacologically acceptable salt.

16. The connection indicated in paragraph 13, where R1and R2are identical and represent each a hydrogen atom;

R4represents a methyl group;

n represents the integer 2;

X represents a group of formula = N-CH3;

Y represents an ethylene group, ethynylene group, a group of the formula-CO-CH2- what do fenelonov group;

Z represents an ethylene group, trimethylene group or tetramethylene group;

R5represents a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups and lower alkoxygroup;

each of R6and R7represents a hydrogen atom;

each of R10and R11represents a hydrogen atom,

or its pharmacologically acceptable salt.

17. The connection indicated in paragraph 13, where each of R1and R2represents a hydrogen atom;

R4represents a methyl group;

n represents the integer 2;

X represents a group of formula = N-CH3;

Y represents a group of formula-CO-CH2-;

Z represents an ethylene group or trimethylene group;

R5represents a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower alkyl group, halogenated lower Alky Inoi group and lowest alkoxygroup;

each of R6and R7represents a hydrogen atom;

each of R10and R11represents a hydrogen atom,

or its pharmacologically acceptable salt.

18. The compound of formula (II) of claim 10, where the aforementioned compound of formula (II) has the formula (IIb)

where R10and R11are identical and represent each a hydrogen atom,

or its pharmacologically acceptable salt.

19. The compound of General formula (III)

where R1and R2are identical and represent each a hydrogen atom;

R4represents a lower alkyl group;

n represents an integer from 1 to 6;

X represents an oxygen atom or a group of formula =N-D

(where D represents a hydrogen atom or a lower alkyl group);

Y represents an ethylene group, ethynylene group, a group of the formula-O-CH2- (where E represents a carbonyl group or a group of the formula-CH(OH) -),6-C10Allenova group or6-C10Allenova group substituted by 1-3 substituents selected from group (a) deputies;

Z represents a single bond, C1-C10alkyl is a new group or With 1-C10alkylenes group containing an oxygen atom in the specified carbon chain or at the end of the specified carbon chain;

R5represents a hydrogen atom, a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of groups (a) deputies;

R6and R7are the same or different and represent each a hydrogen atom or a lower alkyl group;

R10and R11are identical and represent each a hydrogen atom;

group (a) of the substituents is a group consisting of a halogen atom, a lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup, low ancilliary;

provided that when R5represents a hydrogen atom, Z represents a branched C1-C10alkylenes group or1-C10alkylenes group containing an oxygen atom in the specified carbon chain or at the end of the specified carbon chain, or

its pharmacologically acceptable salt.

20. The connection according to claim 19, where the specified connection is selected from the following compounds, or its pharmacologically acceptable salt:

3-amino-3-methyl-5-5-(5-fenilpentil)furan-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-cyclohexylidene-1-inyl)furan-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-finalment-1-inyl)furan-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(4-cyclohexyloxy-1-inyl)furan-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-cyclohexylmethanol)furan-2-yl]interferonbeta acid and

3-amino-3-methyl-5-{5-[3-(3,4-dimethylphenoxy)prop-1-inyl]furan-2-yl}interferonbeta acid.

21. The connection according to claim 19, where the specified connection is selected from the following compounds, or its pharmacologically acceptable salt:

3-amino-3-methyl-5-[1-methyl-5-(5-finalment-1-inyl)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-{1-methyl-5-[3-(4-methylphenoxy)prop-1-inyl]pyrrol-2-yl}interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexyloxy-1-inyl)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-inyl]pyrrol-2-yl}interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(5-phenylpentane)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(5-cyclohexylmethanol)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(4-phenylbutane)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexylmethanol)pyrrol-2-yl]Penta is Fofanova acid,

3-amino-3-methyl-5-[1-ethyl-5-(5-phenylpentane)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-ethyl-5-(5-cyclohexylmethanol)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-ethyl-5-(4-phenylbutane)pyrrol-2-yl]interferonbeta acid, and

3-amino-3-methyl-5-[1-ethyl-5-(4-cyclohexylmethanol)pyrrol-2-yl]interferonbeta acid.

22. The connection according to claim 19, where the aforementioned compound of formula (III) has the formula (IIIa), or its pharmacologically acceptable salt

23. Connection p.22, where R1and R2are identical and represent each a hydrogen atom;

R4represents a C1-C4alkyl group;

n represents the integer 2 or 3;

X represents a group of formula =N-D (where D represents a hydrogen atom or a C1-C4alkyl group);

Y represents an ethylene group, ethynylene group, a group of the formula-CO-CH2-, a group of the formula-CH(OH)-CH2-, fenelonov group or fenelonov group substituted by 1-3 substituents selected from the group consisting of a halogen atom and lower alkyl groups;

Z represents a C1-C6alkylenes group;

R5represents a C3-C10cycle the alkyl group, With6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup and lower ancilliary;

R6and R7are the same or different and represent each a hydrogen atom or a lower alkyl group;

R10and R11are identical and represent each a hydrogen atom, or its pharmacologically acceptable salt.

24. Connection p.22, where R1and R2are identical and represent each a hydrogen atom;

R4represents a C1-C2alkyl group;

n represents the integer 2 or 3;

X represents a group of formula =N-D (where D represents a hydrogen atom or a C1-C4alkyl group);

Y represents an ethylene group, ethynylene group, a group of the formula-CO-CH2-, a group of the formula-CH(OH)-CH2-, fenelonov group or fenelonov group substituted by 1-3 substituents selected from the group consisting of a halogen atom and lower alkyl groups;

Z represents a C1-C5alkylenes group;

R3represents a C3-the 10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup and lower ancilliary;

R6and R7are the same or different and represent each a hydrogen atom or a lower alkyl group;

each of R10and R11represents a hydrogen atom,

or its pharmacologically acceptable salt.

25. Connection p.22, where R1and R2are identical and represent each a hydrogen atom;

R4represents a methyl group;

n represents the integer 2;

X represents a group of formula = N-CH3;

Y represents an ethylene group, ethynylene group, a group of the formula-CO-CH2or fenelonov group;

Z represents an ethylene group, trimethylene group or tetramethylene group;

R5represents a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower Alky Inoi group, halogenated lower alkyl groups and lower alkoxygroup;

each of R6and R7represents a hydrogen atom;

each of R10and R11represents a hydrogen atom,

or its pharmacologically acceptable salt.

26. Connection p.22, where each of R1and R2represents a hydrogen atom;

R4represents a methyl group;

n represents the integer 2;

X represents a group of formula = N-CH3;

Y represents a group of formula-CO-CH2-;

Z represents an ethylene group or trimethylene group;

R5represents a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups and lower alkoxygroup;

each of R6and R7represents a hydrogen atom;

each of R10and R11represents a hydrogen atom,

or its pharmacologically acceptable salt.

27. The connection according to claim 19, where the aforementioned compound of formula (III) has the formula (IIIb), or its pharmacologically acceptable salt

p num="1197">

28. Pharmaceutical composition having immunodepressants activity containing at least one immunosuppressant selected from the group consisting of cyclosporine A, tacrolimus, rapamycin, Leflunomide, methotrexate, Remicade and Enbrel,

and at least one compound selected from the group consisting of compounds of General formula

where R1and R2are identical and represent each a hydrogen atom;

R3represents a hydrogen atom;

R4represents a lower alkyl group;

n represents an integer from 1 to 6;

X represents an oxygen atom or a group of formula =N-D (where D represents a hydrogen atom or a lower alkyl group);

Y represents an ethylene group, ethynylene group, a group of the formula-O-CH2- (where E represents a carbonyl group or a group of the formula-CH(OH) -),6-C10Allenova group or6-C10Allenova group substituted by 1-3 substituents selected from group (a) deputies;

Z represents a single bond, C1-C10alkylenes group, C1-C10alkylenes group containing an oxygen atom specified in the Oh-carbon chain or at the end of the specified carbon chain;

R5represents a hydrogen atom, a C3-C10cycloalkyl group6-C10aryl group6-C10aryl group substituted by 1-3 substituents selected from the group consisting of groups (a) deputies;

R6and R7are the same or different and represent each a hydrogen atom or a lower alkyl group;

group (a) of the substituents is a group consisting of a halogen atom, a lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup, low ancilliary;

provided that when R5represents a hydrogen atom, Z represents a branched C1-C10alkylenes group1-C10alkylenes group containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain, its pharmacologically acceptable salt.

29. The pharmaceutical composition according p, where the compound or its pharmacologically acceptable salt is selected from the group consisting of the compounds described below, pharmacologically acceptable salts:

2-amino-2-methyl-4-[5-(4-cyclohexylmethyl)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(5-cyclohexylmethyl)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(5-fenilpentil)type the-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(4-cyclohexyloxy)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-{5-[4-(4-pertenece)butyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[4-(4-methoxyphenoxy)butyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-[5-(4-benzyloxybenzyl)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(4-cyclohexyl-1-inyl)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(4-phenylbut-1-inyl)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(4-cyclohexylphenol-1-inyl)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(5-finalment-1-inyl)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-{5-[5-(4-forfinal)Penta-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[5-(4-methoxyphenyl)Penta-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[3-(4-methylphenoxy)prop-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[3-(4-ethylenoxy)prop-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[3-(4-methylthiophene)prop-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-[5-(4-cyclohexyloxy-1-inyl)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-{5-[4-(4-pertenece)buta-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[4-(4-methylphenoxy)buta-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-[5-(3-cyclohexylmethoxy-1-inyl)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(4-benzyloxy-1-inyl)thiophene-2-yl]Boo is EN-1-ol,

2-amino-2-methyl-4-[5-(4-cyclohexylmethanol)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(4-phenylbutane)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(5-cyclohexylmethanol)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(5-phenylpentane)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-{5-[5-(4-forfinal)pentanoyl]thiophene-2-yl}butane-1-ol,

2-amino-2-ethyl-4-[5-(5-cyclohexylmethyl)thiophene-2-yl]butane-1-ol,

2-amino-2-ethyl-4-[5-(5-cyclohexylidene-1-inyl)thiophene-2-yl]butane-1-ol,

2-amino-2-ethyl-4-[5-(5-cyclohexylmethanol)thiophene-2-yl]butane-1-ol,

2-amino-2-methyl-4-{5-[3-(4-chlorophenoxy)prop-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[3-(3-methylphenoxy)prop-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[3-(3-methoxyphenoxy)prop-1-inyl]thiophene-2-yl}butane-1-ol,

2-amino-2-methyl-4-{5-[3-(3,4-dimethoxyphenoxy)prop-1-inyl]thiophene-2-yl}butane-1-ol and

2-amino-2-methyl-4-{5-[3-(3,5-dimethoxyphenoxy)prop-1-inyl]thiophene-2-yl}butane-1-ol.

30. The pharmaceutical composition according p, where the compound or its pharmacologically acceptable salt is selected from the group consisting of the compounds described below, pharmacologically acceptable salts:

2-amino-2-methyl-4-[5-(5-fenilpentil)furan-2-yl]butane-1-ol,

2-amino--methyl-4-[5-(5-cyclohexylidene-1-inyl)furan-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(5-finalment-1-inyl)furan-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(4-cyclohexyloxy-1-inyl)furan-2-yl]butane-1-ol,

2-amino-2-methyl-4-[5-(5-cyclohexylmethanol)furan-2-yl]butane-1-ol and

2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-inyl]furan-2-yl}butane-1-ol.

31. The pharmaceutical composition according p, where the compound or its pharmacologically acceptable salt is selected from the group consisting of the compounds described below, pharmacologically acceptable salts:

2-amino-2-methyl-4-[1-methyl-5-(5-finalment-1-inyl)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[3-(4-methylphenoxy)prop-1-inyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxy-1-inyl)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-inyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentane)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylmethanol)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutane)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylmethanol)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentane)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylmethanol)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-[1-ethyl-5-(4-FeNi is butanoyl)pyrrol-2-yl]butane-1-ol and

2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylmethanol)pyrrol-2-yl]butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimetilfenil)butanoyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3, 5dimethylphenyl)butanoyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3-triptoreline)butanoyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(4-triptoreline)butanoyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(4-methoxyphenyl)butanoyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3-were)butyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimetilfenil)butyl]pyrrol-2-yl}butane-1-ol,

2-amino-2-methyl-4-{1-methyl-5-[4-(3, 5dimethylphenyl)butyl]pyrrol-2-yl}butane-1-ol, and

2-amino-2-methyl-4-{1-methyl-5-[4-(3-triptoreline)butyl]pyrrol-2-yl}butane-1-ol.

32. The pharmaceutical composition according p, where the aforementioned compound has the General formula (Ia)shown below

33. The pharmaceutical composition according p containing compound,

where R1and R2are identical and represent each a hydrogen atom;

R3represents a hydrogen atom;

R4represents a C1-C2alkyl group;

n represents the integer 2 ili;

X represents a group of formula =N-D (where D represents a hydrogen atom or a C1-C4alkyl group);

Y represents an ethylene group, ethynylene group, a group of the formula-CO-CH2-, a group of the formula-CH(OH)-CH2-, fenelonov group or fenelonov group substituted by 1-3 substituents selected from the group consisting of a halogen atom and lower alkyl groups;

Z represents a C1-C5alkylenes group;

R5represents a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup and lower ancilliary;

R6and R7are the same or different and represent each a hydrogen atom or a lower alkyl group,

or lower allylthiourea, or its pharmacologically acceptable salt.

34. The pharmaceutical composition according p containing compound,

where each of R1and R2represents a hydrogen atom;

R3represents a hydrogen atom;

R4represents a methyl group;

n represents the integer 2;

X represents a group of formula = N-CH3;

Y represents a group of formula-CO-CH2-;

Z represents an ethylene group or trimethylene group;

R5represents a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups and lower alkoxygroup;

each of R6and R7represents a hydrogen atom,

or its pharmacologically acceptable salt.

35. The pharmaceutical composition according p, where the aforementioned compound has the General formula (Ib)shown below

36. Pharmaceutical composition having immunodepressants activity containing at least one immunosuppressant selected from the group consisting of cyclosporine A, tacrolimus, rapamycin, Leflunomide, methotrexate, Remicade and Enbrel,

and at least one compound selected from the group consisting of compounds of General formula (II)

where R1and R2are the same and represent the th each a hydrogen atom;

R4represents a lower alkyl group;

n represents an integer from 1 to 6;

X represents an oxygen atom or a group of formula =N-D (where D represents a hydrogen atom or a lower alkyl group);

Y represents an ethylene group, ethynylene group, a group of the formula-O-CH2- (where E represents a carbonyl group or a group of the formula-CH(OH) -),6-C10Allenova group or6-C10Allenova group substituted by 1-3 substituents selected from group (a) deputies;

Z represents a single bond, C1-C10alkylenes group or a C1-C10alkylenes group containing an oxygen atom in the specified carbon chain or at the end of the specified carbon chain;

R5represents a hydrogen atom, a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of groups (a) deputies;

R6and R7are the same or different and represent each a hydrogen atom or lower alkyl;

R10and R11are identical and represent each a hydrogen atom;

group (a) of the substituents is from the Oh group, consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup, low ancilliary;

provided that when R5represents a hydrogen atom, Z represents a branched C1-C10alkylenes group or1-C10alkylenes group containing an oxygen atom in the specified carbon chain or at the end of the specified carbon chain, or its pharmacologically acceptable salt.

37. The pharmaceutical composition according p, where the compound of General formula (II) or its pharmacologically acceptable salt is selected from the group consisting of the compounds described below, pharmacologically acceptable salts:

mono 2-amino-2-methyl-4-[5-(4-cyclohexylmethyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-cyclohexylmethyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-fenilpentil)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(4-cyclohexyloxy)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[4-(4-pertenece)butyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[4-(4-methoxyphenoxy)butyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(4-benzyloxybenzyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(4-cyclohexyl-1-inyl)thiophene-2-yl]-1-BU is infostat,

mono 2-amino-2-methyl-4-[5-(4-phenylbut-1-inyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-cyclohexylidene-1-inyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-finalment-1-inyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[5-(4-forfinal)Penta-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[5-(4-methoxyphenyl)Penta-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[3-(4-methylphenoxy)prop-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[3-(4-ethylenoxy)prop-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[3-(4-methylthiophene)prop-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(4-cyclohexyloxy-1-inyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[4-(4-pertenece)buta-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[4-(4-methylphenoxy)buta-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(3-cyclohexylmethoxy-1-inyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(4-benzyloxy-1-inyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(4-cyclohexylmethanol)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(4-phenylbutane)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-cyclohexylmethanol)thiophene-2-yl]-1-buta is fosfat,

mono 2-amino-2-methyl-4-[5-(5-phenylpentane)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[5-(4-forfinal)pentanoyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-ethyl-4-[5-(5-cyclohexylmethyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-ethyl-4-[5-(5-cyclohexylidene-1-inyl)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-ethyl-4-[5-(5-cyclohexylmethanol)thiophene-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[3-(4-chlorophenoxy)prop-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[3-(3-methylphenoxy)prop-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[3-(3-methoxyphenoxy)prop-1-inyl]thiophene-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-{5-[3-(3,4-dimethoxyphenoxy)prop-1-inyl]thiophene-2-yl}-1-butylphosphate, and

mono 2-amino-2-methyl-4-{5-[3-(3,5-dimethoxyphenoxy)prop-1-inyl]thiophene-2-yl}-1-butylphosphate.

38. The pharmaceutical composition according p, where the compound of General formula (II) or its pharmacologically acceptable salt is selected from the group consisting of the compounds described below, pharmacologically acceptable salts:

mono 2-amino-2-methyl-4-[5-(5-fenilpentil)furan-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-cyclohexylidene-1-inyl)furan-2-yl]-1-butylphosphate,

mono 2-the Mino-2-methyl-4-[5-(5-finalment-1-inyl)furan-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(4-cyclohexyloxy-1-inyl)furan-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[5-(5-cyclohexylmethanol)furan-2-yl]-1-butylphosphate and

mono 2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-inyl]furan-2-yl}-1-butylphosphate.

39. The pharmaceutical composition according p, where the compound of General formula (II) or its pharmacologically acceptable salt is selected from the group consisting of the compounds described below, pharmacologically acceptable salts:

mono 2-amino-2-methyl-4-[1-methyl-5-(5-finalment-1-inyl)pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{1-methyl-5-[3-(4-methylphenoxy)prop-1-inyl]pyrrol-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxy-1-inyl)pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-inyl]pyrrol-2-yl}-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentane)pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylmethanol)-pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutane)pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylmethanol)-pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentane)pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexyl tanjil)-pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutane)pyrrol-2-yl]-1-butylphosphate, and

mono 2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylmethanol)-pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{1-methyl-5-[4-(methylphenyl)butanoyl]-pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimetilfenil)butanoyl]-pyrrol-2-yl]-1-butylphosphate,

mono 2-amino-2-methyl-4-{1-methyl-5-[4-(3, 5dimethylphenyl)butanoyl]-pyrrol-2-yl]-1-butylphosphate.

40. The pharmaceutical composition according p, where the compound has formula (IIa)

or its pharmacologically acceptable salt.

41. The pharmaceutical composition according p containing compound,

where R1and R2are identical and represent each a hydrogen atom;

R4represents a C1-C2alkyl group;

n represents the integer 2 or 3;

X represents a group of formula =N-D (where D represents a hydrogen atom or a C1-C4alkyl group);

Y represents an ethylene group, ethynylene group, a group of the formula-CO-CH2-, a group of the formula-CH(OH)-CH2-, fenelonov group or fenelonov group substituted by 1-3 substituents selected from the group consisting of a halogen atom and a lower alkyl GRU is dust;

Z represents a C1-C5alkylenes group;

R5represents a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup and lower ancilliary;

R6and R7are the same or different and represent each a hydrogen atom or a lower alkyl group;

R10and R11are identical and represent each a hydrogen atom,

or its pharmacologically acceptable salt.

42. The pharmaceutical composition according p containing compound,

where each of R1and R2represents a hydrogen atom;

R4represents a methyl group;

n represents the integer 2;

X represents a group of formula = N-CH3;

Y represents a group of formula-CO-CH2-;

Z represents an ethylene group or trimethylene group;

R5represents a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group, zameshano is 1-3 substituents, selected from the group consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups and lower alkoxygroup;

each of R6and R7represents a hydrogen atom;

each of R10and R11represents a hydrogen atom,

or its pharmacologically acceptable salt.

43. The pharmaceutical composition according p, where the compound has the formula (IIb)

or its pharmacologically acceptable salt.

44. Pharmaceutical composition having immunodepressants activity containing at least one immunosuppressant selected from the group consisting of cyclosporine A, tacrolimus, rapamycin, Leflunomide, methotrexate, Remicade and Enbrel,

and at least one compound selected from the group consisting of compounds of General formula (III)shown below

where R1and R2are identical and represent each a hydrogen atom;

R4represents a lower alkyl group;

n represents an integer from 1 to 6;

X represents an oxygen atom or a group of formula =N-D (where D represents a hydrogen atom or a lower alkyl group);

Y is particularly the ethylene group, ethynylene group, a group of the formula-O-CH2- (where E represents a carbonyl group or a group of the formula-CH(OH) -),6-C10Allenova group or6-C10Allenova group substituted by 1-3 substituents selected from group (a) deputies;

Z represents a single bond, C1-C10alkylenes group1-C10alkylenes group containing an oxygen atom in the specified carbon chain or at the end of the specified carbon chain;

R5represents a hydrogen atom, a C3-C10cycloalkyl group6-C10aryl group6-C10aryl group substituted by 1-3 substituents selected from the group consisting of groups (a) deputies;

R6and R7are the same or different and represent each a hydrogen atom or a lower alkyl group;

R10and R11are identical and represent each a hydrogen atom;

group (a) of the substituents is a group consisting of a halogen atom, a lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup, low ancilliary;

provided that when R5represents a hydrogen atom, Z represents a branched C1-C10alkyl is a new group, With1-C10alkylenes group containing an oxygen atom in the specified carbon chain or at the end of the specified carbon chain, or

its pharmacologically acceptable salt.

45. The pharmaceutical composition according to item 44, where the compound of General formula (III) or its pharmacologically acceptable salt is selected from the group consisting of the compounds described below, pharmacologically acceptable salts:

3-amino-3-methyl-5-[5-(4-cyclohexylmethyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-cyclohexylmethyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-fenilpentil)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(4-cyclohexyloxy)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-{5-[4-(4-pertenece)butyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[4-(4-methoxyphenoxy)butyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-[5-(4-benzyloxybenzyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(4-cyclohexyl-1-inyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(4-phenylbut-1-inyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-cyclohexylidene-1-inyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-finalment-1-inyl)thio is EN-2-yl]interferonbeta acid,

3-amino-3-methyl-5-{5-[5-(4-forfinal)Penta-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[5-(4-methoxyphenyl)Penta-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-(5-[3-(4-methylphenoxy)prop-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[3-(4-ethylenoxy)prop-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[3-(4-methylthiophene)prop-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-[5-(4-cyclohexyloxy-1-inyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-{5-[4-(4-pertenece)buta-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[4-(4-methylphenoxy)buta-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-[5-(3-cyclohexylmethoxy-1-inyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(4-benzyloxy-1-inyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(4-cyclohexylmethanol)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(4-phenylbutane)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-cyclohexylmethanol)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-phenylpentane)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-{5-[5-(4-forfinal)pentano the l]thiophene-2-yl}interferonbeta acid,

3-amino-3-ethyl-5-[5-(5-cyclohexylmethyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-ethyl-5-[5-(5-cyclohexylidene-1-inyl)thiophene-2-yl]interferonbeta acid,

3-amino-3-ethyl-5-[5-(5-cyclohexylmethanol)thiophene-2-yl]interferonbeta acid,

3-amino-3-methyl-5-{5-[3-(4-chlorophenoxy)prop-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[3-(3-methylphenoxy)prop-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[3-(3,4-dimethylphenoxy)prop-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[3-(3-methoxyphenoxy)prop-1-inyl]thiophene-2-yl}interferonbeta acid,

3-amino-3-methyl-5-{5-[3-(3,4-dimethoxyphenoxy)prop-1-inyl]thiophene-2-yl}interferonbeta acid, and

3-amino-3-methyl-5-{5-[3-(3,5-dimethoxyphenoxy)prop-1-inyl]thiophene-2-yl}interferonbeta acid.

46. The pharmaceutical composition according to item 44, where the compound of General formula (III) or its pharmacologically acceptable salt is selected from the group consisting of the compounds described below, pharmacologically acceptable salts:

3-amino-3-methyl-5-[5-(5-fenilpentil)furan-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-cyclohexylidene-1-inyl)furan-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-finalment-1-inyl)furan-2-yl]interferonbeta acid,

3-and the Ino-3-methyl-5-[5-(4-cyclohexyloxy-1-inyl)furan-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[5-(5-cyclohexylmethanol)furan-2-yl]interferonbeta acid, and

3-amino-3-methyl-5-{5-[3-(3,4-dimethylphenoxy)prop-1-inyl]furan-2-yl}interferonbeta acid.

47. The pharmaceutical composition according to item 44, where the compound of General formula (III) or its pharmacologically acceptable salt is selected from the group consisting of the compounds described below, pharmacologically acceptable salts:

3-amino-3-methyl-5-[1-methyl-5-(5-finalment-1-inyl)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-{1-methyl-5-[3-(3,4-methylphenoxy)prop-1-inyl]pyrrol-2-yl}interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexyloxy-1-inyl)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-inyl]pyrrol-2-yl}interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(5-phenylpentane)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(5-cyclohexylmethanol)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(4-phenylbutane)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexylmethanol)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-ethyl-5-(5-phenylpentane)pyrrol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-ethyl-5-(5-cyclohexylmethanol)PI is the rol-2-yl]interferonbeta acid,

3-amino-3-methyl-5-[1-ethyl-5-(4-phenylbutane)pyrrol-2-yl]interferonbeta acid and

3-amino-3-methyl-5-[1-ethyl-5-(4-cyclohexylmethanol)pyrrol-2-yl]interferonbeta acid.

48. The pharmaceutical composition according to item 44, where the compound of formula (III) has the formula (IIIa)

49. The pharmaceutical composition according p containing compound,

where R1and R2are identical and represent each a hydrogen atom;

R4represents a C1-C2alkyl group;

n represents the integer 2 or 3;

X represents a group of formula =N-D (where D represents a hydrogen atom or a C1-C4alkyl group);

Y represents an ethylene group, ethynylene group, a group of the formula-CO-CH2-, a group of the formula-CH(OH)-CH2-, fenelonov group or fenelonov group substituted by 1-3 substituents selected from the group consisting of a halogen atom and lower alkyl groups;

Z represents a C1-C5alkylenes group;

R5represents a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of atom Gal is gene lower alkyl group, halogenated lower alkyl groups, lower alkoxygroup and lower ancilliary;

R6and R7are the same or different and represent each a hydrogen atom or a lower alkyl group;

R10and R11are identical and represent each a hydrogen atom,

or its pharmacologically acceptable salt.

50. The pharmaceutical composition according p containing compound,

where each of R1and R2represents a hydrogen atom;

R4represents a methyl group;

n represents the integer 2;

X represents a group of formula =N-CH3;

Y represents a group of formula-CO-CH2-;

Z represents an ethylene group or trimethylene group;

R5represents a C3-C10cycloalkyl group6-C10aryl group or6-C10aryl group substituted by 1-3 substituents selected from the group consisting of halogen atom, lower alkyl group, halogenated lower alkyl groups and lower alkoxygroup;

each of R6and R7represents a hydrogen atom;

each of R10and R11is an atom of odor is Yes,

or its pharmacologically acceptable salt.

51. The pharmaceutical composition according to item 44, where the compound of formula (III) has the General formula (IIIb)

52. The pharmaceutical composition according to any one of p-43 containing at least one immunosuppressant selected from cyclosporin a, tacrolimus, rapamycin.

53. The pharmaceutical composition according to any one of paragraphs 44 to 51, containing at least one immunosuppressant selected from cyclosporin a, tacrolimus, rapamycin.

54. A method of preventing or treating rheumatoid arthritis in a mammal, containing the introduction to the specified mammal an effective amount of the compound or its pharmaceutically acceptable salt according to any one of claims 1 to 18.

55. A method of preventing or treating rejection in the transplantation of skin of the mammal containing an introduction to the specified mammal an effective amount of the compound or its pharmaceutically acceptable salt according to any one of claims 1 to 18.

56. A method of preventing or treating rheumatoid arthritis in a mammal, containing the introduction to the specified mammal an effective amount of the pharmaceutical composition according to any one of p-43.

57. A method of preventing or treating rejection in the transplantation of skin of the mammal containing the introduction indicated the mammal the effective amount of the pharmaceutical composition according to any one of p-43.

58. A method of preventing or treating rheumatoid arthritis in a mammal, containing the introduction to the specified mammal an effective amount of the compound or its pharmaceutically acceptable salt according to any one of PP-27.

59. A method of preventing or treating rejection in the transplantation of skin of the mammal containing an introduction to the specified mammal an effective amount of an effective amount of the compound or its pharmaceutically acceptable salt according to any one of PP-27.

60. A method of preventing or treating rheumatoid arthritis in a mammal, containing the introduction to the specified mammal an effective amount of the pharmaceutical composition according to any one of paragraphs 44 to 51.

61. A method of preventing or treating rejection in the transplantation of skin of the mammal containing an introduction to the specified mammal an effective amount of the pharmaceutical composition according to any one of paragraphs 44 to 51.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: description is given of a hetero-aromatic compounds with a phosphonate group with formula (I) and their pharmaceutical salts, radicals of which are given in the formula of invention. The compounds are inhibitors of fructose-1,6-bisphosphotase. Description is also given of pharmaceutical compositions based on compounds with formula (I) and (X) and the method if inhibiting fructose-1,6-bisphosphotase, using the compound with formula (I).

EFFECT: obtaining of new biologically active substances.

184 cl, 52 tbl, 62 ex

FIELD: chemistry.

SUBSTANCE: description is given of a hetero-aromatic compounds with a phosphonate group with formula (I) and their pharmaceutical salts, radicals of which are given in the formula of invention. The compounds are inhibitors of fructose-1,6-bisphosphotase. Description is also given of pharmaceutical compositions based on compounds with formula (I) and (X) and the method if inhibiting fructose-1,6-bisphosphotase, using the compound with formula (I).

EFFECT: obtaining of new biologically active substances.

184 cl, 52 tbl, 62 ex

FIELD: chemistry.

SUBSTANCE: description is given of a hetero-aromatic compounds with a phosphonate group with formula (I) and their pharmaceutical salts, radicals of which are given in the formula of invention. The compounds are inhibitors of fructose-1,6-bisphosphotase. Description is also given of pharmaceutical compositions based on compounds with formula (I) and (X) and the method if inhibiting fructose-1,6-bisphosphotase, using the compound with formula (I).

EFFECT: obtaining of new biologically active substances.

184 cl, 52 tbl, 62 ex

FIELD: chemistry of organophosphorus compounds, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new bisamidate phosphonate compounds that are inhibitors of fructose 1,6-bis-phosphatase. Invention describes a compound of the formula (IA): wherein compound of the formula (IA) is converted in vivo or in vitro to compound of the formula M-PO3H2 that is inhibitor of fructose 1,6-bis-phosphatase and wherein M represents R5-X- wherein R5 is chosen from a group consisting of compounds of the formula or wherein each G is chosen from the group consisting of atoms C, N, O, S and Se and wherein only one G can mean atom O, S or Se and at most one G represents atom N; each G' is chosen independently from the group consisting of atoms C and N and wherein two G' groups, not above, represent atom N; A is chosen from the group consisting of -H, -NR42, -CONR42, -CO2R3, halide, -S(O)R3, -SO2R3, alkyl, alkenyl, alkynyl, perhaloidalkyl, haloidalkyl, aryl, -CH2OH, -CH2NR42, -CH2CN, -CN, -C(S)NH2, -OR2, -SR2, -N3, -NHC(S)NR42, -NHAc, or absent; each B and D is chosen independently from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclyl, aralkyl, alkoxyalkyl, -C(O)R11, -C(O)SR11, -SO2R11, -S(O)R3, -CN, -NR92, -OR3, -SR3, perhaloidalkyl, halide, -NO2, or absent and all groups except for -H, -CN, perhaloidalkyl, -NO2 and halide are substituted optionally; E is chosen from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclyl, alkoxyalkyl, -C(O)OR3, -CONR42, -CN, -NR92, -NO2, -OR3, -SR3, perhaloidalkyl, halide, or absent; all groups except for -H, -CN, perhaloidalkyl and halide are substituted optionally; J is chosen from the group consisting of -H, or absent; X represents optionally substituted binding group that binds R5 with phosphorus atom through 2-4 atoms comprising 0-1 heteroatom chosen from atoms N, O and S with exception that if X represents urea or carbamate then there are 2 heteroatoms that determine the shortest distance between R5 and phosphorus atom and wherein atom bound with phosphorus means carbon atom and wherein X is chosen from the group consisting of -alkyl(hydroxy)-, -alkynyl-, - heteroaryl-, -carbonylalkyl-, -1,1-dihaloidalkyl-, -alkoxyalkyl-, -alkyloxy-, -alkylthioalkyl-, -alkylthio-, -alkylaminocarbonyl-, -alkylcarbonylamino-, -alkoxycarbonyl-, -carbonyloxyalkyl-, -alkoxycarbonylamino- and -alkylaminocarbonylamino- and all groups are substituted optionally; under condition that X is not substituted with -COOR2, -SO3H or -PO3R22; n means a whole number from 1 to 3; R2 is taken among the group -R3 and -H; R3 is chosen from the group consisting of alkyl, aryl, alicyclyc and aralkyl; each R4 is chosen independently from the group consisting of -H and alkyl, or R4 and R4 form cycloalkyl group; each R9 is chosen independently from the group consisting of -H, alkyl, aryl, aralkyl and alicyclyl, or R9 and R9 form in common cycloalkyl group; R11 is chosen from the group consisting of alkyl, aryl, -NR22 and -OR2; each R12 and R13 is chosen independently from the group consisting of hydrogen atom (H), lower alkyl, lower aryl, lower aralkyl wherein all groups are substituted optionally, or R12 and R13 in common are bound through 2-5 atoms comprising optionally 1-2 heteroatoms chosen from the group consisting of atoms O, N and S to form cyclic group; each R14 is chosen independently from the group consisting of -OR17, -N(R17)2, -NHR17, -NR2OR19 and -SR17; R15 is chosen from the group consisting of -H, lower alkyl, lower aryl, lower aralkyl, or in common with R16 is bound through 2-6 atoms comprising optionally 1 heteroatom chosen from the group consisting of atoms O, N and S; R16 is chosen from the group consisting of -(CR12R13)n-C(O)-R14, -H, lower alkyl, lower aryl, lower aralkyl, or in common with R15 is bound through 2-6 atoms comprising optionally 1 heteroatom chosen from the group consisting of atoms O, N and S; each R17 is chosen independently from the group consisting of lower alkyl, lower aryl and lower aralkyl and all groups are substituted optionally, or R17 and R17 at atom N are bound in common through 2-6 atoms comprising optionally 1 heteroatom chosen from the group consisting of atoms O, N and S; R18 is chosen independently among the group consisting of hydrogen atom (H), lower alkyl, aryl, aralkyl, or in common with R12 is bound through 1-4 carbon atoms forming cyclic group; each R19 is chosen independently from the group consisting of -H, lower alkyl, lower aryl, lower alicyclyl, lower aralkyl and -COR3; and under condition that when G' represents nitrogen atom (N) then the corresponding A, B, D or E are absent; at least one from A and B, or A, B, D and E is chosen from the group consisting of -H, or absent; when G represents nitrogen atom (N) then the corresponding A or B is not halide or group bound directly with G through a heteroatom; and its pharmaceutically acceptable salts. Also, invention describes a method for treatment or prophylaxis of diabetes mellitus, a method for inhibition of activity 0f fructose 1,6-bis-phosphatase, a method for decreasing blood glucose in animals, a method for treatment of diseases associated with glycogen deposition, a method for inhibition of gluconeogenesis in animal and a pharmaceutical composition based on compounds of the formula (IA).

EFFECT: valuable medicinal and biochemical properties of compounds.

69 cl, 7 tbl, 64 ex

FIELD: chemistry of organophosphorus compounds, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new bisamidate phosphonate compounds that are inhibitors of fructose 1,6-bis-phosphatase. Invention describes a compound of the formula (IA): wherein compound of the formula (IA) is converted in vivo or in vitro to compound of the formula M-PO3H2 that is inhibitor of fructose 1,6-bis-phosphatase and wherein M represents R5-X- wherein R5 is chosen from a group consisting of compounds of the formula or wherein each G is chosen from the group consisting of atoms C, N, O, S and Se and wherein only one G can mean atom O, S or Se and at most one G represents atom N; each G' is chosen independently from the group consisting of atoms C and N and wherein two G' groups, not above, represent atom N; A is chosen from the group consisting of -H, -NR42, -CONR42, -CO2R3, halide, -S(O)R3, -SO2R3, alkyl, alkenyl, alkynyl, perhaloidalkyl, haloidalkyl, aryl, -CH2OH, -CH2NR42, -CH2CN, -CN, -C(S)NH2, -OR2, -SR2, -N3, -NHC(S)NR42, -NHAc, or absent; each B and D is chosen independently from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclyl, aralkyl, alkoxyalkyl, -C(O)R11, -C(O)SR11, -SO2R11, -S(O)R3, -CN, -NR92, -OR3, -SR3, perhaloidalkyl, halide, -NO2, or absent and all groups except for -H, -CN, perhaloidalkyl, -NO2 and halide are substituted optionally; E is chosen from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclyl, alkoxyalkyl, -C(O)OR3, -CONR42, -CN, -NR92, -NO2, -OR3, -SR3, perhaloidalkyl, halide, or absent; all groups except for -H, -CN, perhaloidalkyl and halide are substituted optionally; J is chosen from the group consisting of -H, or absent; X represents optionally substituted binding group that binds R5 with phosphorus atom through 2-4 atoms comprising 0-1 heteroatom chosen from atoms N, O and S with exception that if X represents urea or carbamate then there are 2 heteroatoms that determine the shortest distance between R5 and phosphorus atom and wherein atom bound with phosphorus means carbon atom and wherein X is chosen from the group consisting of -alkyl(hydroxy)-, -alkynyl-, - heteroaryl-, -carbonylalkyl-, -1,1-dihaloidalkyl-, -alkoxyalkyl-, -alkyloxy-, -alkylthioalkyl-, -alkylthio-, -alkylaminocarbonyl-, -alkylcarbonylamino-, -alkoxycarbonyl-, -carbonyloxyalkyl-, -alkoxycarbonylamino- and -alkylaminocarbonylamino- and all groups are substituted optionally; under condition that X is not substituted with -COOR2, -SO3H or -PO3R22; n means a whole number from 1 to 3; R2 is taken among the group -R3 and -H; R3 is chosen from the group consisting of alkyl, aryl, alicyclyc and aralkyl; each R4 is chosen independently from the group consisting of -H and alkyl, or R4 and R4 form cycloalkyl group; each R9 is chosen independently from the group consisting of -H, alkyl, aryl, aralkyl and alicyclyl, or R9 and R9 form in common cycloalkyl group; R11 is chosen from the group consisting of alkyl, aryl, -NR22 and -OR2; each R12 and R13 is chosen independently from the group consisting of hydrogen atom (H), lower alkyl, lower aryl, lower aralkyl wherein all groups are substituted optionally, or R12 and R13 in common are bound through 2-5 atoms comprising optionally 1-2 heteroatoms chosen from the group consisting of atoms O, N and S to form cyclic group; each R14 is chosen independently from the group consisting of -OR17, -N(R17)2, -NHR17, -NR2OR19 and -SR17; R15 is chosen from the group consisting of -H, lower alkyl, lower aryl, lower aralkyl, or in common with R16 is bound through 2-6 atoms comprising optionally 1 heteroatom chosen from the group consisting of atoms O, N and S; R16 is chosen from the group consisting of -(CR12R13)n-C(O)-R14, -H, lower alkyl, lower aryl, lower aralkyl, or in common with R15 is bound through 2-6 atoms comprising optionally 1 heteroatom chosen from the group consisting of atoms O, N and S; each R17 is chosen independently from the group consisting of lower alkyl, lower aryl and lower aralkyl and all groups are substituted optionally, or R17 and R17 at atom N are bound in common through 2-6 atoms comprising optionally 1 heteroatom chosen from the group consisting of atoms O, N and S; R18 is chosen independently among the group consisting of hydrogen atom (H), lower alkyl, aryl, aralkyl, or in common with R12 is bound through 1-4 carbon atoms forming cyclic group; each R19 is chosen independently from the group consisting of -H, lower alkyl, lower aryl, lower alicyclyl, lower aralkyl and -COR3; and under condition that when G' represents nitrogen atom (N) then the corresponding A, B, D or E are absent; at least one from A and B, or A, B, D and E is chosen from the group consisting of -H, or absent; when G represents nitrogen atom (N) then the corresponding A or B is not halide or group bound directly with G through a heteroatom; and its pharmaceutically acceptable salts. Also, invention describes a method for treatment or prophylaxis of diabetes mellitus, a method for inhibition of activity 0f fructose 1,6-bis-phosphatase, a method for decreasing blood glucose in animals, a method for treatment of diseases associated with glycogen deposition, a method for inhibition of gluconeogenesis in animal and a pharmaceutical composition based on compounds of the formula (IA).

EFFECT: valuable medicinal and biochemical properties of compounds.

69 cl, 7 tbl, 64 ex

FIELD: synthesis of lubricant oiliness addends.

SUBSTANCE: claimed method includes reaction of equimolar amounts of 1-(N,N-dimethylaminomethyl)-benzotriazol and O-(n-butyl)-O-(3,4,5-trithiatricyclodez-8-yl-methyl))-dithiophosphoric acid at 80-100°C in toluene medium for 2-4 h to produce target product of general formula:

.

EFFECT: ash-free addend for lubricant oils processing under high pressure, in particular lubricant oiliness addend of improved antiscoring properties.

2 tbl, 1 ex

FIELD: synthesis of lubricant oil additives.

SUBSTANCE: method for production of O-(2-ethyl-n-hexil)-O-3,4,5-trithiatricyclo-dez-8-yl-methyl)-dithiophosphoric acid 1-(N,N-dimethylaminomethyl)-benzotriazole salt of general formula 2 is disclosed. 1-(N,N-dimethylaminomethyl)-benzotriazole is brought into reaction with equimolar amount of O-(2-ethyl-n-hexyl)-O-3,4,5-trithiatricyclo-dez-8-yl-methyl)-dithiophosphoric acid in toluene medium at 80-100°C for 2-4 h.

EFFECT: ash-free antiscoring lubricant oil additive operating under high pressure.

2 tbl, 1 ex

FIELD: synthesis of lubricant oil additives.

SUBSTANCE: method for production of O-(2-ethyl-n-hexil)-O-3,4,5-trithiatricyclo[5.2.1.02,6]-dez-8-yl-methyl)-dithiophosphoric acid 1-(N,N-dimethylaminomethyl)-1,2,4-triazole salt of general formula

is disclosed. 1-(N,N-dimethylaminomethyl)-1,2,4-triazole is brought into reaction with equimolar amount of O-(2-ethyl-n-hexyl)-O-3,4,5-trithiatricyclo[5.2.1.02,6]-dez-8-yl-methyl)-dithiophosphoric acid in toluene medium at 80-100°C for 2-4 h.

EFFECT: ash-free antiscoring lubricant oil additive operating under high pressure.

2 tbl, 1 ex

FIELD: synthesis of lubricant oil additives.

SUBSTANCE: method for production of O-(n-butyl)-O-3,4,5-trithiatricyclo-dez-8-yl-methyl)-dithiophosphoric acid 1-(N,N-dimethylaminomethyl)-1,2,4-triazole salt of general formula

is disclosed. 1-(N,N-dimethylaminomethyl)-1,2,4-triazole is brought into reaction with equimolar amount of O-(n-butyl)-O-3,4,5-trithiatricyclo-dez-8-yl-methyl)-dithiophosphoric acid in toluene medium at 80-100°C for 2-4 h.

EFFECT: ash-free antiscoring lubricant oil additive operating under high pressure.

2 tbl, 1 ex

The invention relates to new P,N-bidentate ligands of formula (I):

where a is S or NR,

where R represents a C1-C4alkyl,

R1and R2represent hydrogen, C1-C4alkyl, or R1and R2can be locked in the benzene ring,

R3and R4submit C1-C4alkyl or phenyl,

R5and R6submit C1-C4alkyl

FIELD: organic chemistry, biochemistry, enzymes.

SUBSTANCE: invention relates to compounds represented by the formula: wherein values of substitutes are given in the invention description. Also, invention relates to pharmaceutically acceptable salts of the compound that can be used in treatment and/or prophylaxis of cathepsin-dependent states or diseases of mammals. Proposed compound are useful in treatment of diseases wherein bone resorption inhibition is desired, such as osteoporosis, increased mineral density of bone and reducing risk of fractures. Proposed claimed compounds are designated for preparing a drug possessing the inhibitory activity with respect to cathepsin.

EFFECT: valuable medicinal and biochemical properties of compounds.

24 cl, 13 sch, 4 tbl, 15 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel α-(N-sulfonamido)acetamides of the formula (I) or their optical isomers wherein values R1, R, R2 and R3 are given in the invention claim. Proposed compounds are inhibitors of production of β-amyloid peptide and can be used for inhibition of production of β-amyloid peptide. Also, invention relates to pharmaceutical composition based on these compounds and to a method for inhibition of production of β-amyloid peptide.

EFFECT: valuable medicinal property of compounds and pharmaceutical composition.

22 cl, 23 sch, 4 tbl, 501 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel substituted derivatives of 5-amino-1-pentene-3-ol of the general formula (I)

as a free form or as their physiologically compatible salts possessing the analgesic effect. In general formula (I) each R1 and R2 means independently of one another (C1-C6)-alkyl that can be branched or unbranched, saturated or unsaturated, unsubstituted or mono- or multi-substituted; or R1 and R2 form in common -(CH2)2-9-mono- or bicyclic ring; each R3 and R4 means independently of one another (C1-C6)-alkyl, or R3 and R4 form in common a ring and mean the group -CH2CH2NR22CH2CH2 wherein R22 represents (C1-C10)-alkyl; R5 means (C1-C10)-alkyl that is saturated or unsaturated, branched or unbranched, mono- or multi-substituted or unsubstituted, (C3-C9)-cycloalkyl that is saturated or means phenyl, heteroaryl that can be condensed with benzene ring and chosen from 5-membered heteroaryl with sulfur or oxygen atom as a heteroatom bound through saturated (C1-C3)-alkyl, phenyl bound through saturated (C1-C3)-alkyl-(C3-C10)-cycloalkyl wherein each among all these alkyl, phenyl, heteroaryl and cycloalkyl residues and independently of others can be unsubstituted or mono- or multi-substituted residues chosen independently of one another from the group comprising atoms F, Cl, Br, J, groups -OR18, (C1-C3)-alkyl) that is saturated or branched or unbranched, mono- or multi-substituted halide, or unsubstituted and wherein R18 represents hydrogen atom (H), (C1-C10)-alkyl that is saturated, branched or unbranched; R6 means (C1-C10)-alkyl that is saturated or unsaturated, branched or unbranched and unsubstituted, phenyl or heteroaryl that is chosen from 5-membered heteroaryl with oxygen atom as a heteroatom wherein each of them is unsubstituted or mono- or multi-substituted as indicated above; R7 means H. Also, invention relates to a medicinal agent based on proposed compounds and to a method for their synthesis.

EFFECT: improved method of synthesis, valuable medicinal properties of compounds.

10 cl, 493 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of 1-aminobutane-3-ol of the general formula (I): and their physiologically acceptable salts possessing analgesic effect and capacity for binding habapentin-site. In the general formula (I) R1 and R2 form in common (CH2)2-9-ring; each R3 and R4 independently of one another means (C1-C6)-alkyl that is branched or direct, saturated or unsubstituted, benzyl or phenethyl that are unsubstituted; R5 means (C1-C10)-alkyl that can be saturated, unsaturated, branched or direct or unsubstituted, (C3-C9)-cycloalkyl that is saturated, phenyl or 5-membered sulfur-containing heteroaryl possibly condensed with benzene ring, (C3-C6)-cycloalkyl bound through saturated or unsaturated (C1-C3)-alkyl, 5-membered possibly condensed with benzene ring sulfur-containing heteroaryl bound through saturated or unsaturated (C1-C3)-alkyl wherein each aryl, heteroaryl and cycloalkyl residue independently of one another can be unsubstituted or mono- or multi-substituted with residues chosen independently of one another from the group comprising atoms F, Cl, Br, J, -OR18, (C1-C10)-alkyl that is saturated or unsaturated, branched or direct and can be mono- or multi-substituted with halogen atoms wherein R18 represents hydrogen atom (H), (C1-C10)-alkyl that is saturated, branched or direct or unsubstituted; R6 means H; R7 means (C1-C6)-alkyl that is branched or direct, saturated or unsaturated or unsubstituted, (C3-C9)-cycloalkyl that is saturated or unsubstituted, phenyl that is unsubstituted or mono- or multi-substituted or phenyl bound through saturated (C1-C3)-alkyl that can be unsubstituted or mono- or multi-substituted wherein these substitutes can be chosen independently from the group comprising atoms F, Cl, Br, J, -OR18, (C1-C10)-alkyl that is saturated or unsaturated, branched or direct, in free form as their physiologically acceptable salts. Proposed compounds can be used in treatment of pain and first of all neuropathic, chronic and acute pain. Also, invention relates to a method for synthesis of compounds and preparing a medicinal agent.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

9 cl, 89 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new N-(2-arylpropionyl)-sulfonamides of the formula (1): wherein R2 means phenyl, thiophenyl optionally substituted with 1-3 substitutes taken independently among halogen atom, (C1-C4)-alkyl, phenyl, phenoxy-group, benzyl, benzoyl, (C1-C7)-acyloxy-group, 2-thienoyl or 1-oxo-2-isoindolyl; R means linear or branched (C1-C16)-alkyl, trifluoromethyl, cyclohexyl, o-tolyl, 3-pyridyl, p-cyanophenylmethyl, p-aminomethylphenylmethyl, 2-cyano-1-propyl, alkoxyethylene group CH3-(CH2)ni-(OCH2CH2)mi- wherein ni and mi mean a whole number from 1 to 3, or the group P1P2N-CH2-CH2- wherein P1 and P2 represent independently hydrogen atom (H), (C1-C3)-alkyl, benzyloxycarbonyl, α-, β- or γ-pyridocarbonyl, carboxycarbonyl or carbalkoxycarbonyl; or R1 and P2 in common with nitrogen atom to which they are bound form morpholino-group; R' means hydrogen atom (H) or linear or branched (C1-C3)-alkyl, or their salts with strong or mean bases. Compounds of the formula (1) show inhibitory activity with respect to chemotaxis and degranulation of neutrophiles induced with interleukin-8 and can be used in pharmaceutical composition used for prophylaxis and treatment of tissue injures.

EFFECT: valuable medicinal properties of compounds.

13 cl, 2 dwg, 2 tbl, 18 ex

The invention relates to new derivatives of N, S-substituted N'-1-[(hetero)aryl] -N'-[(hetero)aryl] methylisothiazoline General formula I or their salts with pharmacologically acceptable acids HX in the form of a racemic mixture or in the form of a mixture of stereoisomers, which can be used for the treatment and prevention of diseases associated with dysfunction glutamatergic nanoperiodic

The invention relates to new nitromethylene formula (I)

< / BR>
in which A represents C6-C10aryl, thienyl, benzothiazyl; X denotes halogen, cyano, C1-C7alkyl, trifluoromethyl, C2-C7alkoxy, or cryptometer; p is chosen from 0, 1, 2, 3, 4, or 5; Z represents a bond, -CO-NH-, SO2-NH-, a sulfur atom, sulfinyl group or a C2-C7alkenylamine radical; R1, R2, R3and E indicated in paragraph 1

The invention relates to a method for producing derivatives of 2-aminothiazoline formula I, in which R1represents C1-5alkyl straight or branched chain, R2is1-3alkyl, by reacting the compounds of formula II in which R3represents phenyl which may be optionally mono-pentamidine independently chlorine, methoxy, ethoxy, phenoxy or nitro, with the compound of the formula III in which Y represents a leaving group, in a solvent and in the presence of a base

The invention relates to new derivatives of tamilcanadian with the General formula (I) wherein R' represents 2-thienyl or 3-thienyl radical, R represents ceanorhaditis or a radical of the formula-C(O) - and R2 is optional saturated or unsaturated cyclic hydrocarbon radical or aryl radical

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel substituted derivatives of 5-amino-1-pentene-3-ol of the general formula (I)

as a free form or as their physiologically compatible salts possessing the analgesic effect. In general formula (I) each R1 and R2 means independently of one another (C1-C6)-alkyl that can be branched or unbranched, saturated or unsaturated, unsubstituted or mono- or multi-substituted; or R1 and R2 form in common -(CH2)2-9-mono- or bicyclic ring; each R3 and R4 means independently of one another (C1-C6)-alkyl, or R3 and R4 form in common a ring and mean the group -CH2CH2NR22CH2CH2 wherein R22 represents (C1-C10)-alkyl; R5 means (C1-C10)-alkyl that is saturated or unsaturated, branched or unbranched, mono- or multi-substituted or unsubstituted, (C3-C9)-cycloalkyl that is saturated or means phenyl, heteroaryl that can be condensed with benzene ring and chosen from 5-membered heteroaryl with sulfur or oxygen atom as a heteroatom bound through saturated (C1-C3)-alkyl, phenyl bound through saturated (C1-C3)-alkyl-(C3-C10)-cycloalkyl wherein each among all these alkyl, phenyl, heteroaryl and cycloalkyl residues and independently of others can be unsubstituted or mono- or multi-substituted residues chosen independently of one another from the group comprising atoms F, Cl, Br, J, groups -OR18, (C1-C3)-alkyl) that is saturated or branched or unbranched, mono- or multi-substituted halide, or unsubstituted and wherein R18 represents hydrogen atom (H), (C1-C10)-alkyl that is saturated, branched or unbranched; R6 means (C1-C10)-alkyl that is saturated or unsaturated, branched or unbranched and unsubstituted, phenyl or heteroaryl that is chosen from 5-membered heteroaryl with oxygen atom as a heteroatom wherein each of them is unsubstituted or mono- or multi-substituted as indicated above; R7 means H. Also, invention relates to a medicinal agent based on proposed compounds and to a method for their synthesis.

EFFECT: improved method of synthesis, valuable medicinal properties of compounds.

10 cl, 493 ex

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