Indole derivative and its pharmaceutical application

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound, represented by the following formula

,

or its pharmaceutically acceptable salt. In claimed formula each symbol has values, determined in formula of invention. Versions of formula [I] compound and particular compounds are also objects of invention. In addition, invention relates to pharmaceutical composition, ITK inhibitor and means for treatment or prevention of inflammatory diseases, allergic diseases, autoimmune diseases, transplant rejection and other diseases and methods of treating said diseases.

EFFECT: claimed compounds inhibit induced T-cellular kinase (ITK).

32 cl, 86 tbl, 387 ex

 

The technical field to which the invention relates

The present invention relates to indole derivative and its pharmaceutical use. More specifically, the present invention relates to a compound for the prevention or treatment of inflammatory diseases, allergic diseases, autoimmune diseases, transplant rejection and other diseases by suppressing the function of Th2 cells and/or mast cells by inhibiting inducible T-cell kinase (ITK) and its application.

Art

ITK is a receptor precepting type, belonging to the family of TES, which is important for activation of T cells, and is mainly expressed in T-cells, mast cells and natural cells killer cells. ITK is activated in T cells by stimulation of the T cell receptor (TCR) and is activated in mast cells upon activation of the receptor of the immunoglobulin (Ig) E high affinity. After receptor stimulation in T cells Lck, which is one member of the family of Src tyrosine kinases, phosphorylates Y511 in the activation loop domain of the kinase ITK. Activated ITK together with Zap-70 is required for the phosphorylation and activation of PLC-γ. PLC-γ catalyzes the formation of Inositol-1,4,5-Christoforou acid and diacylglyceride, causing the mobilization of calcium and activation of PKC, the relevant�but. These events activate many ways subsequent reactions, and, finally, induce cytokine production in T cells and degranulation in mast cells.

Studies using mice with ITK deficiency confirmed that ITK is involved in the differentiation of Th2-cells.

Th2-cell is one type of CD4-positive T-helper cells (Th-cells), which differs from the “untrained” T-cell antigenic stimulation and produces the cytokine. Cytokines, such as interleukin (IL)-4, IL-5, IL-13 and the like, produced Th2-cells, called Th2-cytokines, and it is known that they are involved in the mechanism of allergic disease and other similar diseases, because they stimulate the production of antibodies plasma cells, differentiated from b cells, and activate such cells, such as eosinophils (a type of granulocyte), and the like. Like Th2-cell, Th1 cell, which is differentiated from “untrained” T-cells, produces the so-called Th1-cytokines such as interferon (IFN)-γ and the like, and Th1-cell and Th2-cell support the balance called the balance of Th1/Th2, by suppressing the functions of each other. It is believed that the relative imbalance of any of these cytokines causes of disease that are specific to each of them. Described that mouse with ITK deficiency selectively inhibits d�fferential Th2 cells and production of Th2-cytokine.

In addition, it is described that the inhibition of ITK inhibits the activation of mast cells.

Fat cell contains various chemical mediators, such as histamine. When antigen binds to IgE bound to the surface of the cell, set cross-linking triggers activation of the cells which then causes the release of its contents (chemical mediators such as histamine, and the like) (degranulation). Of chemical mediators released from mast cells, histamine, and the like have an effect on the structure of the bronchial smooth muscle, an action that increases the permeability of blood vessels, secretory action on the mucous membrane and the like and cause asthma and allergic diseases.

It is therefore assumed that the ITK inhibitor, which inhibits the proliferation of Th2 cells and production of Th2-cytokine and/or inhibits the degranulation and the production of histamine and the like by suppressing the activation of mast cells, would be effective as a means for the treatment or prevention of diseases involving proliferation of Th2 cells producing Th2-cytokine, degranulation, production of histamine and the like, for example, inflammatory diseases, allergic diseases and other similar diseases.

In recent times suggest that ITK PR�also takes part in the activation of Th17 cells, which is one type of Th-cells, and suggest that the ITK inhibitor shows activity as a means for the treatment or prevention of diseases involving TH17-cell, such as autoimmune diseases (e.g., rheumatism and others).

In addition, it is assumed that ITK is involved in the reaction of the mixed culture of lymphocytes. It is therefore assumed that the ITK inhibitor shows activity as an inhibitor of rejection during transplantation.

In addition, it is assumed that ITK is involved in HIV infection. It is therefore assumed that the ITK inhibitor exhibits an effect as a prophylactic or therapeutic agent against HIV infection.

Description of the invention

The problems that must be solved by the invention

The object of the present invention is to provide a method for the treatment or prevention of inflammatory diseases, an agent for the treatment or prophylaxis of allergic diseases, an agent for the treatment or prevention of autoimmune diseases, an inhibitor of rejection in the transplantation and the like, which are based on ITK inhibitory action.

The only way of resolving problems

The authors of the present invention have conducted intensive studies in an attempt to develop tools for the treatment of�I or prophylaxis of inflammatory diseases, remedies for the treatment or prophylaxis of allergic diseases, for the treatment or prevention of autoimmune diseases, an inhibitor of rejection in the transplantation and the like, which are based on ITK inhibitory action, and found that the indole derivative ITK has an inhibitory effect, and reached the present invention.

Accordingly, the present invention offers the following:

[1] a Compound represented by the following formula [I] or its pharmaceutically acceptable salt

where

R1is a

(1) a hydrogen atom,

(2) a hydroxy-group or

(3) C1-6alkoxygroup, optionally substituted C6-10aryl group(s);

R2and R3are the same or different and each represents

(1) a hydrogen atom or

(2) C1-6alkyl group, optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup; and

R4is a group represented by the formula

which is associated with 5-position or 6-position of the indole ring,

where

R5is a

(1) a hydrogen atom or

(2) C1-6alkyl group, and

R6is a

(1) a hydrogen atom,/p>

(2) C1-6alkyl group, optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup,

(c) carboxypropyl,

(d) C1-6alkoxycarbonyl group,

(e) C6-10aryl group,

(f) C6-10aryloxy groups,

(g) amino group optionally mono - or disubstituted C1-6alkyl group(s)

(h) a 5 - or 6-membered unsaturated heterocyclic group, an optionally substituted C1-6alkyl group(s), and

(i) 5 - or 6-membered saturated heterocyclic group,

(3) C1-6alkoxygroup,

(4) C6-10aryl group, or

(5) a 5 - or 6-membered unsaturated heterocyclic group, optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup, or

R5and R6together with the nitrogen atom to which they are linked, form a 5 - or 6-membered cyclic amine (specified cyclic amine optionally condensed with 5 - or 6-membered unsaturated heterocycle), optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkyl group,

(c) C1-6alkoxygroup and

(d) C1-6alkoxycarbonyl group;

R7is a

(1) a hydrogen atom or

(2) C1-6alkyl group, optionally replaced�enny 1-3 substituents, selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup and

(c) amino, optionally mono - or disubstituted C1-6alkyl group(s), and

R8is a

(1) C1-6alkyl group, optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup, optionally substituted C6-10aryl group(s)

(c) C3-6cycloalkyl group, an optionally substituted C1-6alkoxygroup(AMI),

(d) C6-10aryl group,

(e) a 5 - or 6-membered unsaturated heterocyclic group optionally substituted by oxopropoxy(AMI),

(f) 5-8-membered saturated heterocyclic group, optionally substituted with 1-3 substituents selected from

(i) hydroxyl groups,

(ii) C1-6alkyl group, optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup,

(iii) C1-6alkoxygroup and

(iv) the carbonyl group,

(g) C3-6cycloalkylcarbonyl,

(h) C6-10aryloxy groups,

(i) 5 - or 6-membered unsaturated geterotsiklicheskikh,

(j) a 5 - or 6-membered saturated geterotsiklicheskie and

(k) an amino group optionally mono - or disubstituted by substituents selected from the

(i) C1-6alkyl group, optionally substituted with 1-3 substituents, �selected from hydroxy-group, carboxypropyl and carboxy-(C1-6alkoxygroup,

(ii) C1-6alkylcarboxylic group, optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup,

(iii) C1-6alkoxycarbonyl group, an optionally substituted C6-10aryl group(s), and

(iv) C3-6cycloalkylcarbonyl group, an optionally substituted C1-6alkoxygroup(AMI),

(2) C1-6alkoxygroup, optionally substituted C6-10aryl group(s)

(3) C3-6cycloalkyl group, optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup,

(4) C6-10aryl group, an optionally substituted C1-6alkyl group(s) optionally substituted by 1 to 3 halogen atoms,

(5) an amino group optionally mono - or disubstituted C1-6alkyl group(s) optionally substituted C6-10aryl group(s)

(6) a 5 - or 6-membered unsaturated heterocyclic group, an optionally substituted C1-6alkyl group(s)

(7) a 5 - or 6-membered saturated heterocyclic group, optionally substituted with 1-3 substituents selected from

(a) C1-6alkyl group,

(b) C1-6alkylcarboxylic groups and

(c) the carbonyl group,

(8) C3-6cycloalkylation or/p>

(9) C6-10arylcarbamoyl group, or

R7and R8together with the nitrogen atom and the carbon atom to which they are linked, form a 5 - or 6-membered cyclic amine substituted by exography and optionally additionally substituted by 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkyl group, optionally substituted hydroxy-group(s)

(c) C1-6alkoxygroup and

(d) C3-6cycloalkyl group.

[2] the Compound represented by the following formula [I-a], or its pharmaceutically acceptable salt

where

R1is a

(1) a hydrogen atom,

(2) a hydroxy-group or

(3) C1-6alkoxygroup, optionally substituted C6-10aryl group(s);

R2and R3are the same or different and each represents

(1) a hydrogen atom or

(2) C1-6alkyl group, optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup;

R7'represents C1-6alkyl group, optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup and

(c) amino, optionally mono - or disubstituted C1-6alkyl group(s), and

R8is a fun�

(1) C1-6alkyl group, optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup, optionally substituted C6-10aryl group(s)

(c) C3-6cycloalkyl group, an optionally substituted C1-6alkoxygroup(AMI),

(d) C6-10aryl group,

(e) a 5 - or 6-membered unsaturated heterocyclic group optionally substituted by oxopropoxy(AMI),

(f) 5-8-membered saturated heterocyclic group, optionally substituted with 1-3 substituents selected from

(i) hydroxyl groups,

(ii) C1-6alkyl group, optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup,

(iii) C1-6alkoxygroup and

(iv) the carbonyl group,

(g) C3-6cycloalkylcarbonyl,

(h) C6-10aryloxy groups,

(i) 5 - or 6-membered unsaturated geterotsiklicheskikh,

(j) a 5 - or 6-membered saturated geterotsiklicheskie and

(k) an amino group optionally mono - or disubstituted by substituents selected from the

(i) C1-6alkyl group, optionally substituted with 1-3 substituents chosen from hydroxyl groups, carboxypropyl and carboxy-(C1-6alkoxygroup,

(ii) C1-6alkylcarboxylic group, optionally substituted with 1-3 substituents selected from hydroxyprop�s and C 1-6alkoxygroup,

(iii) C1-6alkoxycarbonyl group, an optionally substituted C6-10aryl group(s) and

(iv) C3-6cycloalkylcarbonyl group, an optionally substituted C1-6alkoxygroup(AMI),

(2) C1-6alkoxygroup, optionally substituted C6-10aryl group(s)

(3) C3-6cycloalkyl group, optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup,

(4) C6-10aryl group, an optionally substituted C1-6alkyl group(s) optionally substituted by 1 to 3 halogen atoms,

(5) an amino group optionally mono - or disubstituted C1-6alkyl group(s) optionally substituted C6-10aryl group(s)

(6) a 5 - or 6-membered unsaturated heterocyclic group, an optionally substituted C1-6alkyl group(s)

(7) a 5 - or 6-membered saturated heterocyclic group, optionally substituted with 1-3 substituents selected from

(a) C1-6alkyl group,

(b) C1-6alkylcarboxylic groups and

(c) the carbonyl group,

(8) C3-6cycloalkylation or

(9) C6-10arylcarbamoyl group, or

R7'and R8together with the nitrogen atom and the carbon atom to which they are linked, form a 5 - or 6-membered cyclic amine substituted by exography and optionally additionally substituted by 1-3 substituents, selected from

(a) hydroxyl groups,

(b) C1-6alkyl group, optionally substituted hydroxy-group(s)

(c) C1-6alkoxygroup and

(d) C3-6cycloalkyl group.

[3] the Compound according to the above item [2], in which

R1represents a hydrogen atom and

R2and R3are the same or different and each represents C1-6alkyl group,

or its pharmaceutically acceptable salt.

[4] the Compound according to the above item [3], in which

R7'represents C1-6alkyl group, and

R8represents C1-6alkyl group, substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup, optionally substituted C6-10aryl group(s)

(c) C3-6cycloalkyl group, an optionally substituted C1-6alkoxygroup(AMI),

(d) C6-10aryl group,

(e) a 5 - or 6-membered unsaturated heterocyclic group optionally substituted by oxopropoxy(AMI),

(f) 5-8-membered saturated heterocyclic group, optionally substituted with 1-3 substituents selected from

(i) hydroxyl groups,

(ii) C1-6alkyl group, optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup,

(iii) C 1-6alkoxygroup and

(iv) the carbonyl group,

(g) C3-6cycloalkylcarbonyl,

(h) C6-10aryloxy groups,

(i) 5 - or 6-membered unsaturated geterotsiklicheskikh,

(j) a 5 - or 6-membered saturated geterotsiklicheskie and

(k) amino, optionally mono or disubstituted by substituents selected from the

(i) C1-6alkyl group, optionally substituted with 1-3 substituents chosen from hydroxyl groups, carboxypropyl and carboxy-(C1-6alkoxygroup,

(ii) C1-6alkylcarboxylic group, optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup,

(iii) C1-6alkoxycarbonyl group, an optionally substituted C6-10aryl group(s), and

(iv) C3-6cycloalkylcarbonyl group, an optionally substituted C1-6alkoxygroup(AMI),

or its pharmaceutically acceptable salt.

[5] the Compound selected from compounds of the following formulas:

or its pharmaceutically acceptable salt.

[6] a Pharmaceutical composition comprising a compound according to any one of the above paragraphs [1]-[5] or its pharmaceutically acceptable salt and pharmaceutically acceptable carrier.

[7] the ITK Inhibitor containing compounds�ie according to any one of the above paragraphs [1]-[5] or its pharmaceutically acceptable salt.

[8] an agent for the treatment or prevention of inflammatory diseases containing a compound according to any one of the above paragraphs [1]-[5] or its pharmaceutically acceptable salt.

[9] the Agent according to the above item [8], where the inflammatory disease is rheumatoid arthritis.

[10] an agent for the treatment or prevention of allergic diseases containing a compound according to any one of the above paragraphs [1]-[5] or its pharmaceutically acceptable salt.

[11] an agent for the treatment or prevention of autoimmune diseases containing a compound according to any one of the above paragraphs [1]-[5] or its pharmaceutically acceptable salt.

[12] the Agent according to the above item [11], where the autoimmune disease is rheumatoid arthritis.

[13] the Inhibitor of rejection in the transplantation comprising compound according to any one of the above paragraphs [1]-[5] or its pharmaceutically acceptable salt.

[14] a Method of inhibiting ITK in a mammal, comprising administering pharmaceutically effective amount of a compound according to any one of the above paragraphs [1]-[5] or its pharmaceutically acceptable salt to a mammal.

[15] a Method of treating or preventing inflammatory disease in a mammal, comprising administering a pharmaceutically effective�th number of compounds according to any one of the above paragraphs [1]-[5] or its pharmaceutically acceptable salt to a mammal.

[16] the Method according to the above item [15], where the inflammatory disease is rheumatoid arthritis.

[17] a Method of treating or preventing an allergic disease in a mammal, comprising administering pharmaceutically effective amount of a compound according to any one of the above paragraphs [1]-[5] or its pharmaceutically acceptable salt to a mammal.

[18] a Method of treating or preventing autoimmune disease in a mammal, comprising administering pharmaceutically effective amount of a compound according to any one of the above paragraphs [1]-[5] or its pharmaceutically acceptable salt to a mammal.

[19] the Method according to the above item [18], where the autoimmune disease is rheumatoid arthritis.

[20] a Method of suppressing rejection during transplantation in a mammal, comprising administering pharmaceutically effective amount of a compound according to any one of the above paragraphs [1]-[5] or its pharmaceutically acceptable salt to a mammal.

[21] use of a compound according to any one of the above paragraphs [1]-[5] or its pharmaceutically acceptable salt to obtain funds for the treatment or prevention of inflammatory diseases.

[22] the Use according to the above item [21], where the inflammatory disease is p�metody arthritis.

[23] use of a compound according to any one of the above paragraphs [1]-[5] or its pharmaceutically acceptable salt to obtain funds for the treatment or prevention of allergic diseases.

[24] use of a compound according to any one of the above paragraphs [1]-[5] or its pharmaceutically acceptable salt to obtain funds for the treatment or prevention of autoimmune diseases.

[25] the Use according to item [24], where the autoimmune disease is rheumatoid arthritis.

[26] use of a compound according to any one of the above paragraphs [1]-[5] or its pharmaceutically acceptable salt to obtain an inhibitor of rejection during transplantation.

[27] a Commercial product containing (a) a pharmaceutical composition containing a compound according to any one of the above paragraphs [1]-[5] or its pharmaceutically acceptable salt as an active ingredient, and (b) accompanied by the description associated with it, which indicates that the pharmaceutical composition can or should be used to treat or prevent inflammatory diseases, allergic diseases or autoimmune diseases.

[28] a Commercial package containing (a) a pharmaceutical composition containing a compound according to any one of the above paragraphs [1]-[5] or its Pharma�efticiency acceptable salt as an active ingredient, and (b) accompanied by the description associated with it, which indicates that the pharmaceutical composition can or should be used to treat or prevent inflammatory diseases, allergic diseases or autoimmune diseases.

[1'] a Compound represented by the following formula [I'] or its pharmaceutically acceptable salt or solvate

where

R1'is a

(1) a hydrogen atom,

(2) a hydroxy-group or

(3) C1-6alkoxygroup, optionally substituted C6-10aryl group(s);

R2'and R3'are the same or different and each represents

(1) a hydrogen atom or

(2) C1-6alkyl group, optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup; and

R4'is a group represented by the formula

which is associated with 5-position or 6-position of the indole ring,

where

R5'is a

(1) a hydrogen atom or

(2) C1-6alkyl group, and

R6'is a

(1) a hydrogen atom,

(2) C1-6alkyl group, optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup,

(c) to�of roxyrama,

(d) C1-6alkoxycarbonyl group,

(e) C6-10aryl group,

(f) C6-10aryloxy groups,

(g) amino group optionally mono - or disubstituted C1-6alkyl group(s)

(h) a 5 - or 6-membered unsaturated heterocyclic group, an optionally substituted C1-6alkyl group(s), and

(i) 5 - or 6-membered saturated heterocyclic group,

(3) C1-6alkoxygroup,

(4) C6-10aryl group, or

(5) a 5 - or 6-membered unsaturated heterocyclic group, optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup, or

R5'and R6'together with the nitrogen atom to which they are linked, form a 5 - or 6-membered cyclic amine (cyclic amine optionally condensed with 5 - or 6-membered unsaturated heterocycle, which optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkyl group,

(c) C1-6alkoxygroup and

(d) C1-6alkoxycarbonyl group;

R7"is a

(1) a hydrogen atom or

(2) C1-6alkyl group, optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup and

(c) amino, optionally mono - or disubstituted C1-6alkyl �Ruppel(s) and

R8'is a

(1) C1-6alkyl group, optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup, optionally substituted C6-10aryl group(s)

(c) C3-6cycloalkyl group, an optionally substituted C1-6alkoxygroup(AMI),

(d) C6-10aryl group,

(e) a 5 - or 6-membered unsaturated heterocyclic group optionally substituted by oxopropoxy(AMI),

(f) 5-8-membered saturated heterocyclic group, optionally substituted with 1-3 substituents selected from

(i) hydroxyl groups,

(ii) C1-6alkyl group, optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup,

(iii) C1-6alkoxygroup and

(iv) the carbonyl group,

(g) C3-6cycloalkylcarbonyl,

(h) C6-10aryloxy groups,

(i) 5 - or 6-membered unsaturated geterotsiklicheskikh,

(j) a 5 - or 6-membered saturated geterotsiklicheskie and

(k) an amino group optionally mono - or disubstituted by substituents selected from the

(i) C1-6alkyl group,

(ii) C1-6alkylcarboxylic group, optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup,

(iii) C1-6alkoxycarbonyl group, neobyazatelnostyu C 6-10aryl group(s) and

(iv) C3-6cycloalkylcarbonyl group, an optionally substituted C1-6alkoxygroup(AMI),

(2) C1-6alkoxygroup, optionally substituted C6-10aryl group(s)

(3) C3-6cycloalkyl group, optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup,

(4) C6-10aryl group, an optionally substituted C1-6alkyl group(s) optionally substituted by 1 to 3 halogen atoms,

(5) an amino group optionally mono - or disubstituted C1-6alkyl group(s) optionally substituted C6-10aryl group(s)

(6) a 5 - or 6-membered unsaturated heterocyclic group, an optionally substituted C1-6alkyl group(s)

(7) a 5 - or 6-membered saturated heterocyclic group, optionally substituted with 1-3 substituents selected from

(a) C1-6alkyl group,

(b) C1-6alkylcarboxylic groups and

(c) the carbonyl group,

(8) C3-6cycloalkylation or

(9) C6-10arylcarbamoyl group, or

R7"and R8'together with the nitrogen atom and the carbon atom to which they are linked, form a 5 - or 6-membered cyclic amine substituted by exography and optionally additionally substituted by 1-3 substituents selected�

(a) hydroxyl groups,

(b) C1-6alkyl group, optionally substituted hydroxy-group(s)

(c) C1-6alkoxygroup and

(d) C3-6cycloalkyl group.

[2'] the Connection represented by the following formula [I'-a], or its pharmaceutically acceptable salt, or its solvate

where

R1'is a

(1) a hydrogen atom,

(2) a hydroxy-group or

(3) C1-6alkoxygroup, optionally substituted C6-10aryl group(s);

R2'and R3'are the same or different and each represents

(1) a hydrogen atom or

(2) C1-6alkyl group, optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup;

R7"'represents C1-6alkyl group, optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup and

(c) amino, optionally mono - or disubstituted C1-6alkyl group(s) and

R8'is a

(1) C1-6alkyl group, optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup, optionally substituted C6-10aryl group(s)

(c) C3-6cycloalkyl group, neo�Astelin substituted C 1-6alkoxygroup(AMI),

(d) C6-10aryl group,

(e) a 5 - or 6-membered unsaturated heterocyclic group optionally substituted by oxopropoxy(AMI),

(f) 5-8-membered saturated heterocyclic group, optionally substituted with 1-3 substituents selected from

(i) hydroxyl groups,

(ii) C1-6alkyl group, optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup,

(iii) C1-6alkoxygroup and

(iv) the carbonyl group,

(g) C3-6cycloalkylcarbonyl,

(h) C6-10aryloxy groups,

(i) 5 - or 6-membered unsaturated geterotsiklicheskikh,

(j) a 5 - or 6-membered saturated geterotsiklicheskie and

(k) an amino group optionally mono - or disubstituted by substituents selected from the

(i) C1-6alkyl group,

(ii) C1-6alkylcarboxylic group, optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup,

(iii) C1-6alkoxycarbonyl group, an optionally substituted C6-10aryl group(s), and

(iv) C3-6cycloalkylcarbonyl group, an optionally substituted C1-6alkoxygroup(AMI),

(2) C1-6alkoxygroup, optionally substituted C6-10aryl group(s)

(3) C3-6cycloalkyl group, optionally substituted with 1 - substituents, selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup,

(4) C6-10aryl group, an optionally substituted C1-6alkyl group(s) optionally substituted by 1 to 3 halogen atoms,

(5) an amino group optionally mono - or disubstituted C1-6alkyl group(s) optionally substituted C6-10aryl group(s)

(6) a 5 - or 6-membered unsaturated heterocyclic group, an optionally substituted C1-6alkyl group(s)

(7) a 5 - or 6-membered saturated heterocyclic group, optionally substituted with 1-3 substituents selected from

(a) C1-6alkyl group,

(b) C1-6alkylcarboxylic groups and

(c) the carbonyl group,

(8) C3-6cycloalkylation or

(9) C6-10arylcarbamoyl group, or

R7"'and R8'together with the nitrogen atom and the carbon atom to which they are linked, form a 5 - or 6-membered cyclic amine substituted by exography and optionally additionally substituted by 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkyl group, optionally substituted hydroxy-group(s)

(c) C1-6alkoxygroup and

(d) C3-6cycloalkyl group.

[3'] a Pharmaceutical composition comprising the compound according to the above item [1'] or [2'] or farmatsevticheskii salt, or solvate and a pharmaceutically acceptable carrier.

[4'] an agent for the treatment or prevention of inflammatory diseases containing a compound according to the above item [1'] or [2'] or its pharmaceutically acceptable salt, or its solvate.

[5'] ITK Inhibitor containing the compound according to the above item [1'] or [2'] or its pharmaceutically acceptable salt, or its solvate.

[6'] an agent for the treatment or prevention of allergic diseases containing a compound according to the above item [1'] or [2'] or its pharmaceutically acceptable salt, or its solvate.

[7'] an agent for the treatment or prevention of autoimmune diseases containing a compound according to the above item [1'] or [2'] or its pharmaceutically acceptable salt, or its solvate.

[8'] the Inhibitor of rejection in the transplantation containing compound according to the above item [1'] or [2'] or its pharmaceutically acceptable salt, or its solvate.

[9'] a Method of treating or preventing inflammatory disease in a mammal, comprising administering pharmaceutically effective amount of a compound according to the above item [1'] or [2'] or its pharmaceutically acceptable salt or solvate of the mammal.

[10'] a Method of treating or preventing an allergic disease� of a mammal, comprising administering pharmaceutically effective amount of a compound according to the above item [1'] or [2'] or its pharmaceutically acceptable salt or solvate of the mammal.

[11'] Method of treating or preventing autoimmune disease in a mammal, comprising administering pharmaceutically effective amount of a compound according to the above item [1'] or [2'] or its pharmaceutically acceptable salt or solvate of the mammal.

[12'] a Method of suppressing rejection during transplantation in a mammal, comprising administering pharmaceutically effective amount of a compound according to the above item [1'] or [2'] or its pharmaceutically acceptable salt or solvate of the mammal.

[13'] use of a compound according to the above item [1'] or [2'] or its pharmaceutically acceptable salt or solvate to obtain funds for the treatment or prevention of inflammatory diseases.

Effect of the invention

Indole derivative of the present invention effectively inhibits the activity of ITK, inhibits the proliferation and activation of Th2 cells and/or inhibits mast cell activation. Therefore, it is effective as a means for the treatment or prevention of diseases associated with proliferation or activation of Th2-cells�and or activation of mast cells, for example, allergic diseases, inflammatory diseases and autoimmune diseases, or as an inhibitor of rejection during transplantation.

Description of the invention

The present invention is explained in detail below.

The definition used in the present description of the invention of the term is as described below.

The term “optionally substituted” includes both the substitution and no substitution (without replacement) in the substituted position of the group. In the context of the term “without replacement” means that each of all substitutable positions of the considered group is present, the hydrogen atom.

Examples of “halogen atom” include fluorine atom, chlorine atom, bromine atom and iodine atom.

“C1-6alkyl group” means a saturated hydrocarbon group with a straight chain or branched chain containing 1-6 carbon atoms, and examples include methyl group, ethyl group, propyl group, isopropylene group, butyl group, isobutylene group, sec-butyl group, tert-butyl group, pentelow group, isopentyl group, neopentyl group, 1,2-dimethylpropylene group, 1-ethylpropyl group, hexoloy group, isohexyl group, 1,2,2-trimethylpropyl group, 1,1-dimethylbutyl group, 2,2-dimethylbutyl gr�foam, 3,3-dimethylbutyl group, 2-ethylbutyl group and the like.

“C1-6alkoxygroup” means a hydroxyl group, the above substituted C1-6alkyl group”, and examples include a methoxy group, an ethoxy group, propoxylate, isopropoxide, butoxypropan, isobutoxide, second-butoxypropan, tert-butoxypropan, pentyloxy, isopentylamine, neopentylene, 1,2-dimethylpropylene, 1-ethylpropoxy, hexyloxy, isohexadecane, 1,2,2-trimethylpropyl, 1,1-dimethylbutylamino, 2,2-dimethylbutylamino, 3,3-dimethylbutylamino, 2-ethylbutylamine and the like.

“C3-6cycloalkyl group” means a monocyclic saturated hydrocarbon group having 3-6 carbon atoms, and examples include cyclopropyl group, cyclobutyl group, cyclopentyl group, pirazinokarbazolovogo cyclohexyl group and the like.

“C3-6cycloalkylation” means a hydroxy-group, the above substituted C3-6cycloalkyl group”, and examples include cyclopropylamino, cyclobutylamine, cyclopentyloxy, cyclohexyloxy and the like.

“C6-10aryl group” means an aromatic hydrocarbon group having 6-10 carbon atoms, and examples include computers�t phenyl group, 1-naftalina group, 2-naftalina group and the like. Preferred is phenyl group.

“C6-10alloctype” means a hydroxy-group, the above substituted C6-10aryl group, and examples include fenoxaprop, a 1-naphthyloxy, 2-naphthyloxy and the like. Preferred fenoxaprop.

“5 - or 6-membered unsaturated heterocyclic group” means a monocyclic unsaturated or partially unsaturated heterocyclic group having 5 or 6 atoms forming a ring which contains in addition to carbon atoms, 1-4 of heteroatom selected from a nitrogen atom, oxygen atom and sulfur atom. When a group contains a sulfur atom as a heteroatom, a sulfur atom optionally mono - or diocesan. Examples of such groups include follow group, dianilino group, pyrrolidino group, oxazolidinyl group, oxazolidinyl group, isoxazolyl group, isoxazolyl group, thiazolidine group, thiazolidine group, isothiazolinone group, isothiazolinone group, imidazolidinyl group, imidazolidinyl group, pyrazolidine group, personilnya group, oxadiazolyl group (1,2,5-oxadiazolyl group, 1,3,4-oxadiazolyl group, 1,2,4-oxadiazolyl group), thiadiazolyl group (1,2,5-thiadiazolidine group, 1,34-thiadiazolidine group 1,2,4-thiadiazolyl group), triazolyl group (1,2,3-triazolyl group, 1,2,4-triazolyl group), tetrazolyl group, pyridyloxy group, pyrimidinyl group, pyridazinyl group, personilnya group, triazinyl group, dihydropyridine group and the like.

“5 - or 6-membered unsaturated geterotsiklicheskikh” means a hydroxy-group, substituted with the above “5 - or 6-membered unsaturated heterocyclic group”, and examples include ferrochrome, tailorship, errollaceaply, oxazolidones, oxazolidinones, isoxazolidine, isoxazolidine, thiazoleacetate, diazolidinylurea, isothiazolinones, isothiazolinones, imidazolylalkyl, imidazolylalkyl, personalantispy, pyrazolecarboxylate, oxadiazolidine (1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-oxadiazolidine), thiadiazolidine (1,2,5-thiadiazolidine, 1,3,4-thiadiazolidine, 1,2,4-thiadiazolidine), triazolinones (1,2,3-thiazoleacetate, 1,2,4-triazolinones), tetrachlorocuprate, pyridyloxy, pyrimidinamine, pyridinylamino, personalantispy, teatinerkirhe, digidropiridinovh and the like.

“5-8-membered saturated�traveler heterocyclic group” means saturated monocyclic heterocyclic group, having 5-8 atoms constituting a ring which contains in addition to carbon atoms, 1-4 of heteroatom selected from a nitrogen atom, oxygen atom and sulfur atom. When a group contains a sulfur atom as a heteroatom, a sulfur atom optionally mono - or diocesan. Examples of such groups include pyrrolidinyl group, tetrahydrofuryl group, tetrahydropyranyl group, tetrahydrocannibinol group, tetrahydropyranyloxy group, oxazolidinyl group, isoxazolyl group, diazolidinyl group, isothiazolinone group, imidazolidinyl group, pyrazolidine group, piperidino group (including piperidino), morpholinyl group (including morpholinopropan), thiomorpholine group (including thiomorpholine), piperazinilnom group, sepanlou group, atenelol group, 1,1-deoxidization group, 1,1-dioxotetrahydrofuran group, 1,1-dioxotetrahydrofuran group, 1,1-dioxothiazolidine group (including 1,1-diocletianopolis) and such.

“5 - or 6-membered saturated heterocyclic group” means among the above “5-8-membered saturated heterocyclic group” is a group having a 5 - or 6-membered ring, and examples thereof include pyrrolidinyl group, tetrahydrofuryl group, tetrahed�pyranyloxy group tetrahydrocannibinol group, tetrahydropyranyloxy group, oxazolidinyl group, isoxazolyl group, diazolidinyl group, isothiazolinone group, imidazolidinyl group, pyrazolidine group, piperidino group (including piperidino), morpholinyl group (including morpholinopropan), thiomorpholine group (including thiomorpholine), piperazinilnom group, 1,1-deoxidization group, 1,1-dioxotetrahydrofuran group, 1,1-dioxotetrahydrofuran group, 1,1-dioxothiazolidine group (including 1,1-diocletianopolis) and the like.

“5 - or 6-membered saturated geterotsiklicheskikh” means a hydroxy-group, substituted with the above “5 - or 6-membered saturated heterocyclic group”, and examples include pyrrolidinyloxy, tetrahydropyranyloxy, tetrahydropyranyloxy, tetrahydropyranyloxy, tetrahydropyranyloxy, oxazolidinones, isoxazolidinone, diazolidinylurea, isothiazolinones, imidazolidinone, pyrazolidinone, piperidinyloxy (and including piperidineacetate), morpholinopropan (including morpholinopropan), thiomorpholine (including thiomorpholine�), piperidinyloxy, 1,1-deoxycytidylate, 1,1-, 1,1-, 1,1-diocletianopolis (including 1,1-diocletianopolis) and the like.

“C1-6alkylcarboxylic group” means a carbonyl group that is linked to the above “C1-6alkyl group”, and examples include acetyl group, propanolol group, butanoyloxy group, 2-methylpropanoyl group, 2,2-dimethylpropanoyl group, 3-methylbutanoyl group and the like.

“C1-6alkoxycarbonyl group” means a carbonyl group that is linked to the above “C1-6alkoxygroup”, and examples include methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group, butoxycarbonyl group, solutionscatalog group, Deut-butoxycarbonyl group, tert-butoxycarbonyl group, ventilatsioonile group, isopentenyladenine group, neopentylglycol group, hexyloxymethyl group and the like.

“C3-6cycloalkylcarbonyl group” means a carbonyl group that is linked to the above “C3-6cycloalkyl group”, and examples include cycloprop�carbonyloxy group cyclobutanecarbonyl group, cyclopentanecarbonyl group, cyclohexylcarbonyl group and the like.

“C6-10arylcarbamoyl group” means a carbonyl group that is linked to the above “C6-10aryl group, and examples include benzoyloxy group and the like.

“Carboxy-C1-6alkoxygroup” means the above “C1-6alkoxygroup” associated carboxypropyl, and examples include carboxymethoxy, 2-carboxymethoxy, 3-carboxypropyl, 2-carboxymethyl-1-methylethoxy, 4-carboxybutyl and the like. Preferred carboxymethoxy.

“5 - or 6-membered cyclic amine” means a saturated heterocycle having 5 or 6 atoms forming the ring, which contains at least one nitrogen atom in addition to carbon atoms, further optionally contains 1 to 3 heteroatom selected from nitrogen atom, oxygen atom and sulfur atom, which is connected through a nitrogen atom that is part of the ring. When the ring contains a sulfur atom as a heteroatom, a sulfur atom optionally mono - or diocesan. Examples of such rings include pyrrolidine, oxazolidine, isoxazolidine, thiazolidine, isothiazolin, imidazolidin, pyrazolidine, piperidine, morpholine, thiomorpholine, piperazine, 1,1-deoxidization�lidin, 1,1-diocletianopolis and the like.

“5 - or 6-membered unsaturated heterocycle” means a monocyclic unsaturated or partially unsaturated heterocyclic group having 5 or 6 atoms forming a ring which contains in addition to carbon atoms, 1-4 of heteroatom selected from a nitrogen atom, oxygen atom and sulfur atom. When the ring contains a sulfur atom as a heteroatom, a sulfur atom optionally mono - or diocesan. Examples of such rings include furan, thiophene, pyrrole, oxazole, isoxazol, thiazole, isothiazol, imidazole, pyrazole, oxadiazole, thiadiazole, triazole, tetrazol, pyridine, pyrimidine, pyridazine, pyrazine, triazine and the like.

Each group of compounds represented by formula [I] (hereinafter sometimes to reduce abbreviated as compound [I]), is explained below.

R1is a

(1) a hydrogen atom,

(2) a hydroxy-group or

(3) C1-6alkoxygroup (preferably a methoxy group, isopropoxy), optionally substituted C6-10aryl group(s) (preferably phenyl group),

and preferably a hydrogen atom.

R2and R3are the same or different and each represents

(1) a hydrogen atom or

(2) C1-6alkyl group (preferably methyl group) optionally substituted by 1-3 substituents,�from abusive

(a) hydroxyl groups and

(b) C1-6alkoxygroup (preferably, methoxy groups), and preferably are the same or different and each represents C1-6alkyl group (preferably methyl group).

R4is a group represented by the formula

which is associated with 5-position or 6-position of the indole ring.

R4preferably is a group

which is associated with 5-position or 6-position of the indole ring, or a group

which is linked to the 6-position of the indole ring, and more preferably a group

which is linked to the 6-position of the indole ring.

R5is a

(1) a hydrogen atom or

(2) C1-6alkyl group (preferably methyl group, ethyl group).

R6is a

(1) a hydrogen atom,

(2) C1-6alkyl group (preferably methyl group, ethyl group, isopropylene group, isobutylene group, a tert-butyl group, neopentyl group, 1,2-dimethylpropylene group, 1,2,2-trimethylpropyl group), optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxy�group (preferably methoxy groups, propoxylate, isopropoxide),

(c) carboxypropyl,

(d) C1-6alkoxycarbonyl group (preferably methoxycarbonyl group, tert-butoxycarbonyl group)

(e) C6-10aryl groups (preferably phenyl groups),

(f) C6-10aryloxy groups (preferably fenoxaprop),

(g) amino group optionally mono - or disubstituted C1-6alkyl groups (preferably methyl group),

(h) a 5 - or 6-membered unsaturated heterocyclic group (preferably shriley group, pyrrolidino group, thiazolidine group, tetrazolyl group, imidazolidine group), optionally substituted C1-6alkyl group(s) (preferably methyl group), and

(i) 5 - or 6-membered saturated heterocyclic group (preferably morpholinyl group)

(3) C1-6alkoxygroup (preferably a methoxy group),

(4) C6-10aryl group (preferably phenyl group), or

(5) a 5 - or 6-membered unsaturated heterocyclic group (preferably 1,3,4-thiadiazolyl group), optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup (preferably, methoxy groups).

Alternatively, R5and R6together with the nitrogen atom to which they are linked, can clicks�should be organized the 5 - or 6-membered cyclic amine (preferably pyrrolidine, the piperidine, piperazine, morpholine) (cyclic amine optionally condensed with 5 - or 6-membered unsaturated heterocycle (preferably imidazole)), which is optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkyl group (preferably methyl group, ethyl group),

(c) C1-6alkoxygroup (preferably, methoxy groups), and

(d) C1-6alkoxycarbonyl group (preferably tert-butoxycarbonyl group).

R7is a

(1) a hydrogen atom or

(2) C1-6alkyl group (preferably methyl group, ethyl group, propyl group) optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup (preferably, methoxy groups), and

(c) amino, optionally mono - or disubstituted C1-6alkyl group(s) (preferably methyl group), preferably C1-6alkyl group (preferably methyl group, ethyl group, propyl group) optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup (preferably, methoxy groups), and

(c) amino, optionally mono - or disubstituted C1-6alkyl group(s) (preferably methyl group),

and more preferably C1-6alkyl group (preferably methyl group, ethyl group, propyl group).

R8is a

(1) C1-6alkyl group (preferably methyl group, ethyl group, propyl group, isopropylene group, isobutylene group, a tert-butyl group, neopentylene group), optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup (preferably methoxy groups, ethoxypropan, propoxylate, isopropoxy), optionally substituted C6-10aryl group(s) (preferably phenyl group),

(c) C3-6cycloalkyl group (preferably cyclopentyloxy group, pirazinokarbazolovogo cyclohexyl group), an optionally substituted C1-6alkoxygroup(s) (preferably methoxy group),

(d) C6-10aryl groups (preferably phenyl groups),

(e) a 5 - or 6-membered unsaturated heterocyclic group (preferably imidazolidine group, dihydropyridine group, pyrazolidine group), optionally substituted oxopropoxy(AMI),

(f) 5-8-membered saturated heterocyclic group (preferably tetrahydrofuryl group, tetrahydropyranyl group, pyrrolidinyl group, piperidino group, sepanlou group, ALRC�juvenile group morpholinyl group (including morpholinopropan), 1,1-dioxide isothiazolinone group, oxazolidinyl group, imidazolidinyl group), optionally substituted with 1-3 substituents selected from

(i) hydroxyl groups,

(ii) C1-6alkyl group (preferably methyl group) optionally substituted by 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup (preferably, methoxy groups),

(iii) C1-6alkoxygroup (preferably, methoxy groups), and

(iv) the carbonyl group,

(g) C3-6cycloalkylation (preferably cyclopentyloxy),

(h) C6-10aryloxy groups (preferably fenoxaprop),

(i) 5 - or 6-membered unsaturated geterotsiklicheskikh (preferably pyridyloxy),

(j) a 5 - or 6-membered saturated geterotsiklicheskikh (preferably tetrahydropyranyloxy, tetrahydropyranyloxy) and

(k) an amino group optionally mono - or disubstituted by substituents selected from the

(i) C1-6alkyl group (preferably methyl group) optionally substituted by 1-3 substituents chosen from hydroxyl groups, carboxypropyl and carboxy-(C1-6alkoxygroup (preferably carboxymethoxy),

(ii) C1-6alkylcarboxylic group (preferably acetyl group, propanol�th group, 2-methylpropanoyl group, 2,2-dimethylpropanoyl group, 3-methylbutanoyl group), optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup (preferably, methoxy groups),

(iii) C1-6alkoxycarbonyl group (preferably methoxycarbonyl group, tert-butoxycarbonyl group), optionally substituted C6-10aryl group(s) (preferably phenyl group), and

(iv) C3-6cycloalkylcarbonyl group (preferably cyclopropanecarbonyl group, cyclohexylcarbonyl group), optionally substituted C1-6alkoxygroup(s) (preferably methoxy group),

(2) C1-6alkoxygroup (preferably a methoxy group), an optionally substituted C6-10aryl group(s) (preferably phenyl group),

(3) C3-6cycloalkyl group (preferably cyclopentyloxy group, pirazinokarbazolovogo cyclohexyl group) optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup (preferably, methoxy groups),

(4) C6-10aryl group (preferably phenyl group) optionally substituted C1-6alkyl group(s) (preferably methyl group) optionally substituted by 1 to 3 halogen atoms (preferably a�Ohm fluorine),

(5) an amino group optionally mono - or disubstituted C1-6alkyl group(s) (preferably methyl group), an optionally substituted C6-10aryl group(s) (preferably phenyl group),

(6) a 5 - or 6-membered unsaturated heterocyclic group (preferably isoxazolyl group), optionally substituted C1-6alkyl group(s) (preferably methyl group),

(7) a 5 - or 6-membered saturated heterocyclic group (preferably tetrahydrofuryl group, tetrahydropyranyl group, pyrrolidinyl group, piperidino group), optionally substituted with 1-3 substituents selected from

(a) C1-6alkyl group (preferably methyl group),

(b) C1-6alkylcarboxylic group (preferably acetyl group), and

(c) the carbonyl group,

(8) C3-6cycloalkylation (preferably cyclohexyloxy) or

(9) C6-10arylcarbamoyl group (preferably benzoyloxy group).

R8represents preferably C1-6alkyl group (preferably methyl group, ethyl group, propyl group, isopropylene group, isobutylene group, a tert-butyl group, neopentylene group), substituted by 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6 alkoxygroup (preferably methoxy groups, ethoxypropan, propoxylate, isopropoxy), optionally substituted C6-10aryl group(s) (preferably phenyl group),

(c) C3-6cycloalkyl group (preferably cyclopentyloxy group, pirazinokarbazolovogo cyclohexyl group), an optionally substituted C1-6alkoxygroup(s) (preferably methoxy group),

(d) C6-10aryl groups (preferably phenyl groups),

(e) a 5 - or 6-membered unsaturated heterocyclic group (preferably imidazolidine group, dihydropyridine group, pyrazolidine group), optionally substituted oxopropoxy(AMI),

(f) 5-8-membered saturated heterocyclic group (preferably tetrahydrofuryl group, tetrahydropyranyl group, pyrrolidinyl group, piperidino group, sepanlou group, atenelol group, morpholinyl group (including morpholinopropan), 1,1-dioxide isothiazolinone group, oxazolidinyl group, imidazolidinyl group), optionally substituted with 1-3 substituents selected from

(i) hydroxyl groups,

(ii) C1-6alkyl group (preferably methyl group) optionally substituted by 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup (preferably, methoxy groups),

(iii) C1-6alkoxygroup (preferably, methoxy groups), and

(iv) the carbonyl group,

(g) C3-6cycloalkylation (preferably cyclopentyloxy),

(h) C6-10aryloxy groups (preferably fenoxaprop),

(i) 5 - or 6-membered unsaturated geterotsiklicheskikh (preferably pyridyloxy),

(j) a 5 - or 6-membered saturated geterotsiklicheskikh (preferably tetrahydropyranyloxy, tetrahydropyranyloxy) and

(k) an amino group optionally mono - or disubstituted by substituents selected from the

(i) C1-6alkyl group (preferably methyl group) optionally substituted by 1-3 substituents chosen from hydroxyl groups, carboxypropyl and carboxy-(C1-6alkoxygroup (preferably carboxymethoxy),

(ii) C1-6alkylcarboxylic group (preferably acetyl group, propanolol group, 2-methylpropanoyl group, 2,2-dimethylpropanoyl group, 3-methylbutanoyl group), optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup (preferably, methoxy groups),

(iii) C1-6alkoxycarbonyl group (preferably methoxycarbonyl group, tert-butoxycarbonyl group), optionally substituted C6-10aryl group(s) (preferably �Tilney group), and

(iv) C3-6cycloalkylcarbonyl group (preferably cyclopropanecarbonyl group, cyclohexylcarbonyl group), optionally substituted C1-6alkoxygroup(s) (preferably methoxy group).

R8represents more preferably C1-6alkyl group (preferably methyl group, ethyl group, propyl group, isopropylene group), substituted by 1-3 substituents selected from

(c) C3-6cycloalkyl group (preferably cyclopentyloxy group, pirazinokarbazolovogo cyclohexyl group), an optionally substituted C1-6alkoxygroup(s) (preferably methoxy group),

(d) C6-10aryl groups (preferably phenyl groups),

(e) a 5 - or 6-membered unsaturated heterocyclic group (preferably imidazolidine group, dihydropyridine group, pyrazolidine group), optionally substituted oxopropoxy(AMI), and

(f) 5-8-membered saturated heterocyclic group (preferably morpholinyl group (including morpholinopropan)), optionally substituted with 1-3 substituents selected from

(i) hydroxyl groups,

(ii) C1-6alkyl group (preferably methyl group) optionally substituted by 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup (preferably methoxy�uppi),

(iii) C1-6alkoxygroup (preferably, methoxy groups), and

(iv) the carbonyl group.

R8represents particularly preferably C1-6alkyl group (preferably methyl group, ethyl group), substituted 5-8-membered saturated heterocyclic group(s) (preferably morpholinopropan), optionally substituted with 1-3 substituents selected from

(i) hydroxyl groups,

(ii) C1-6alkyl group (preferably methyl group) optionally substituted by 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup (preferably, methoxy groups),

(iii) C1-6alkoxygroup (preferably, methoxy groups), and

(iv) the carbonyl group.

Alternatively, R7and R8together with the nitrogen atom and the carbon atom to which they are linked, can form a 5 - or 6-membered cyclic amine substituted by oxopropoxy (preferably 2-oxopyrrolidin, 2-oxopiperidine, 2-oxoacridine) and optionally additionally substituted by 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkyl group (preferably methyl group), optionally substituted hydroxy-group,

(c) C1-6alkoxygroup (preferably, methoxy groups), and

(d) C3-6cycloalkyl group (preferably pirazinokarbazolovogo cyclohexyl group).

Concurrently�e compounds [I] preferred is the compound, which

R1is a

(1) a hydrogen atom,

(2) a hydroxy-group or

(3) C1-6alkoxygroup (preferably a methoxy group, isopropoxy), optionally substituted C6-10aryl group(s) (preferably phenyl group);

R2and R3are the same or different and each represents

(1) a hydrogen atom or

(2) C1-6alkyl group (preferably methyl group) optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup (preferably, methoxy groups); and

R4is a group

which is associated with 5-position or 6-position of the indole ring, or a group

which is linked to the 6-position of the indole ring (preferably a group

which is linked to the 6-position of the indole ring),

where

R5is a

(1) a hydrogen atom or

(2) C1-6alkyl group (preferably methyl group, ethyl group), and

R6is a

(1) a hydrogen atom,

(2) C1-6alkyl group (preferably methyl group, ethyl group, isopropylene group, isobutylene group, a tert-butyl group, neo�untilnow group 1,2-dimethylpropylene group, 1,2,2-trimethylpropyl group), optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup (preferably methoxy groups, propoxylate, isopropoxide),

(c) carboxypropyl,

(d) C1-6alkoxycarbonyl group (preferably methoxycarbonyl group, tert-butoxycarbonyl group)

(e) C6-10aryl groups (preferably phenyl groups),

(f) C6-10aryloxy groups (preferably fenoxaprop),

(g) amino group optionally mono - or disubstituted C1-6alkyl group(s) (preferably methyl group),

(h) a 5 - or 6-membered unsaturated heterocyclic group (preferably shriley group, pyrrolidino group, thiazolidine group, tetrazolyl group, imidazolidine group), optionally substituted C1-6alkyl group(s) (preferably methyl group), and

(i) 5 - or 6-membered saturated heterocyclic group (preferably morpholinyl group)

(3) C1-6alkoxygroup (preferably a methoxy group),

(4) C6-10aryl group (preferably phenyl group), or

(5) a 5 - or 6-membered unsaturated heterocyclic group (preferably 1,3,4-thiadiazolyl group), optionally substituted with 1-3 Zama�the sinks, selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup (preferably, methoxy groups), or

R5and R6together with the nitrogen atom to which they are linked, form a 5 - or 6-membered cyclic amine (preferably pyrrolidine, piperidine, piperazine, morpholine) (cyclic amine optionally condensed with 5 - or 6-membered unsaturated heterocycle (preferably imidazole)), optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkyl group (preferably methyl group, ethyl group),

(c) C1-6alkoxygroup (preferably, methoxy groups), and

(d) C1-6alkoxycarbonyl group (preferably tert-butoxycarbonyl group);

R7is a

(1) a hydrogen atom or

(2) C1-6alkyl group (preferably methyl group, ethyl group, propyl group) optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup (preferably, methoxy groups), and

(c) amino, optionally mono - or disubstituted C1-6alkyl group(s) (preferably methyl group)

[preferably C1-6alkyl group (preferably methyl group, ethyl group, propyl group) optionally substituted by 1-3 �zamestitelyami, selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup (preferably, methoxy groups), and

(c) amino, optionally mono - or disubstituted C1-6alkyl group(s) (preferably methyl group)], and

R8is a

(1) C1-6alkyl group (preferably methyl group, ethyl group, propyl group, isopropylene group, isobutylene group, a tert-butyl group, neopentylene group), optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup (preferably methoxy groups, ethoxypropan, propoxylate, isopropoxy), optionally substituted C6-10aryl group(s) (preferably phenyl group),

(c) C3-6cycloalkyl group (preferably cyclopentyloxy group, pirazinokarbazolovogo cyclohexyl group), an optionally substituted C1-6alkoxygroup(s) (preferably methoxy group),

(d) C6-10aryl groups (preferably phenyl groups),

(e) a 5 - or 6-membered unsaturated heterocyclic group (preferably imidazolidine group, dihydropyridine group, pyrazolidine group), optionally substituted oxopropoxy(AMI),

(f) 5-8-membered saturated heterocyclic group (preferably tetrahydrofuryl group, �tetrahydropyranyloxy group, pyrrolidinyloxy group, piperidino group, sepanlou group, atenelol group, morpholinyl group (including morpholinopropan), 1,1-dioxide isothiazolinone group, oxazolidinyl group, imidazolidinyl group), optionally substituted with 1-3 substituents selected from

(i) hydroxyl groups,

(ii) C1-6alkyl group (preferably methyl group) optionally substituted by 1 to 3 substituents selected from a hydroxy-group and C1-6alkoxygroup (preferably, methoxy groups),

(iii) C1-6alkoxygroup (preferably, methoxy groups), and

(iv) the carbonyl group,

(g) C3-6cycloalkylation (preferably cyclopentyloxy),

(h) C6-10aryloxy groups (preferably fenoxaprop),

(i) 5 - or 6-membered unsaturated geterotsiklicheskikh (preferably pyridyloxy),

(j) a 5 - or 6-membered saturated geterotsiklicheskikh (preferably tetrahydropyranyloxy, tetrahydropyranyloxy) and

(k) an amino group optionally mono - or disubstituted by substituents selected from the

(i) C1-6alkyl group (preferably methyl group) optionally substituted by 1-3 substituents chosen from hydroxyl groups, carboxypropyl and carboxy-(C1-6alkoxygroup (preferably carboxymethoxy),

(ii) C1-6alkylcarboxylic group (preferably acetyl group, propanolol group, 2-methylpropanoyl group, 2,2-dimethylpropanoyl group, 3-methylbutanoyl group), optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup (preferably, methoxy groups),

(iii) C1-6alkoxycarbonyl group (preferably methoxycarbonyl group, tert-butoxycarbonyl group), optionally substituted C6-10aryl group(s) (preferably phenyl group), and

(iv) C3-6cycloalkylcarbonyl group (preferably cyclopropanecarbonyl group, cyclohexylcarbonyl group), optionally substituted C1-6alkoxygroup(s) (preferably methoxy group),

(2) C1-6alkoxygroup (preferably a methoxy group), an optionally substituted C6-10aryl group(s) (preferably phenyl group),

(3) C3-6cycloalkyl group (preferably cyclopentyloxy group, pirazinokarbazolovogo cyclohexyl group) optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup (preferably, methoxy groups),

(4) C6-10aryl group (preferably phenyl group) optionally substituted C1-6an alkyl group (preferred�flax methyl group), optionally substituted by 1 to 3 halogen atoms (preferably fluorine atom),

(5) an amino group optionally mono - or disubstituted C1-6alkyl group(s) (preferably methyl group), an optionally substituted C6-10aryl group(s) (preferably phenyl group),

(6) a 5 - or 6-membered unsaturated heterocyclic group (preferably isoxazolyl group), optionally substituted C1-6alkyl group(s) (preferably methyl group),

(7) a 5 - or 6-membered saturated heterocyclic group (preferably tetrahydrofuryl group, tetrahydropyranyl group, pyrrolidinyl group, piperidino group), optionally substituted with 1-3 substituents selected from

(a) C1-6alkyl group (preferably methyl group),

(b) C1-6alkylcarboxylic group (preferably acetyl group), and

(c) the carbonyl group,

(8) C3-6cycloalkylation (preferably cyclohexyloxy) or

(9) C6-10arylcarbamoyl group (preferably benzoyloxy group) or

R7and R8together with the nitrogen atom and the carbon atom to which they are linked, form a 5 - or 6-membered cyclic amine substituted by oxopropoxy (preferably 2-oxopyrrolidin, 2-oxopiperidine, 2-oxoacridine) and niobate�till then optionally substituted with 1-3 substituents, selected from

(a) hydroxyl groups,

(b) C1-6alkyl group (preferably methyl group), optionally substituted hydroxy-group(s)

(c) C1-6alkoxygroup (preferably, methoxy groups), and

(d) C3-6cycloalkyl group (preferably pirazinokarbazolovogo cyclohexyl group).

In particular, the compound wherein

R1is a

(1) a hydrogen atom,

(2) a hydroxy-group or

(3) C1-6alkoxygroup (preferably a methoxy group, isopropoxy), optionally substituted C6-10aryl group(s) (preferably phenyl group);

R2and R3are the same or different and each represents

(1) a hydrogen atom or

(2) C1-6alkyl group (preferably methyl group) optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup (preferably, methoxy groups);

R4is a group

which is linked to the 6-position of the indole ring and

where

R7represents C1-6alkyl group (preferably methyl group, ethyl group, propyl group) optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup (premise�plant methoxy groups), and

(c) amino, optionally mono - or disubstituted C1-6alkyl group(s) (preferably methyl group), and

R8is a

(1) C1-6alkyl group (preferably methyl group, ethyl group, propyl group, isopropylene group, isobutylene group, a tert-butyl group, neopentylene group), optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup (preferably methoxy groups, ethoxypropan, propoxylate, isopropoxy), optionally substituted C6-10aryl group(s) (preferably phenyl group),

(c) C3-6cycloalkyl group (preferably cyclopentyloxy group, pirazinokarbazolovogo cyclohexyl group), an optionally substituted C1-6alkoxygroup(s) (preferably methoxy group),

(d) C6-10aryl groups (preferably phenyl groups),

(e) a 5 - or 6-membered unsaturated heterocyclic group (preferably imidazolidine group, dihydropyridine group, pyrazolidine group), optionally substituted oxopropoxy(AMI),

(f) 5-8-membered saturated heterocyclic group (preferably tetrahydrofuryl group, tetrahydropyranyl group, pyrrolidinyl group, piperidino group, sepanlou group, azo�anilino group, morpholinyl group (including morpholinopropan), 1,1-dioxide isothiazolinone group, oxazolidinyl group, imidazolidinyl group), optionally substituted with 1-3 substituents selected from

(i) hydroxyl groups,

(ii) C1-6alkyl group (preferably methyl group) optionally substituted by 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup (preferably, methoxy groups),

(iii) C1-6alkoxygroup (preferably, methoxy groups), and

(iv) the carbonyl group,

(g) C3-6cycloalkylation (preferably cyclopentyloxy),

(h) C6-10aryloxy groups (preferably fenoxaprop),

(i) 5 - or 6-membered unsaturated geterotsiklicheskikh (preferably pyridyloxy),

(j) a 5 - or 6-membered saturated geterotsiklicheskikh (preferably tetrahydropyranyloxy, tetrahydropyranyloxy) and

(k) an amino group optionally mono - or disubstituted by substituents selected from the

(i) C1-6alkyl group (preferably methyl group) optionally substituted by 1-3 substituents chosen from hydroxyl groups, carboxypropyl and carboxy-(C1-6alkoxygroup (preferably carboxymethoxy),

(ii) C1-6alkylcarboxylic group (preferably acetyl group, propanol�th group, 2-methylpropanoyl group, 2,2-dimethylpropanoyl group, 3-methylbutanoyl group), optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup (preferably, methoxy groups),

(iii) C1-6alkoxycarbonyl group (preferably methoxycarbonyl group, tert-butoxycarbonyl group), optionally substituted C6-10aryl group(s) (preferably phenyl group), and

(iv) C3-6cycloalkylcarbonyl group (preferably cyclopropanecarbonyl group, cyclohexylcarbonyl group), optionally substituted C1-6alkoxygroup(s) (preferably methoxy group),

(2) C1-6alkoxygroup (preferably a methoxy group), an optionally substituted C6-10aryl group(s) (preferably phenyl group),

(3) C3-6cycloalkyl group (preferably cyclopentyloxy group, pirazinokarbazolovogo cyclohexyl group) optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup (preferably, methoxy groups),

(4) C6-10aryl group (preferably phenyl group) optionally substituted C1-6an alkyl group (preferably methyl group) optionally substituted by 1 to 3 halogen atoms (preferably an atom of f�ora),

(5) an amino group optionally mono - or disubstituted C1-6alkyl group(s) (preferably methyl group), an optionally substituted C6-10aryl group(s) (preferably phenyl group),

(6) a 5 - or 6-membered unsaturated heterocyclic group (preferably isoxazolyl group), optionally substituted C1-6alkyl group(s) (preferably methyl group),

(7) a 5 - or 6-membered saturated heterocyclic group (preferably tetrahydrofuryl group, tetrahydropyranyl group, pyrrolidinyl group, piperidino group), optionally substituted with 1-3 substituents selected from

(a) C1-6alkyl group (preferably methyl group),

(b) C1-6alkylcarboxylic group (preferably acetyl group), and

(c) the carbonyl group,

(8) C3-6cycloalkylation (preferably cyclohexyloxy) or

(9) C6-10arylcarbamoyl group (preferably benzylcarbamoyl group) or

R7and R8together with the nitrogen atom and the carbon atom to which they are linked, form a 5 - or 6-membered cyclic amine substituted by oxopropoxy (preferably 2-oxopyrrolidin, 2-oxopiperidine, 2-oxoacridine) and optionally additionally substituted by 1-3 substituents selected from

(a) �of hydroxypropy,

(b) C1-6alkyl group (preferably methyl group), optionally substituted hydroxy-group(s)

(c) C1-6alkoxygroup (preferably, methoxy groups), and

(d) C3-6cycloalkyl group (preferably pirazinokarbazolovogo cyclohexyl group),

that is, the connection represented by the above formula [I-a], is especially preferred.

As compounds represented by the formula [I-a], a compound wherein

R1represents a hydrogen atom;

R2and R3are the same or different and each represents C1-6alkyl group (preferably methyl group);

R7'represents C1-6alkyl group (preferably methyl group, ethyl group, propyl group), and

R8represents C1-6alkyl group (preferably methyl group, ethyl group, propyl group, isopropylene group, isobutylene group, a tert-butyl group, neopentylene group), substituted by 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup (preferably methoxy groups, ethoxypropan, propoxylate, isopropoxy), optionally substituted C6-10aryl group(s) (preferably phenyl group),

(c) C3-6cycloalkyl groups� (preferably cyclopentyloxy group, pirazinokarbazolovogo cyclohexyl group), an optionally substituted C1-6alkoxygroup(s) (preferably methoxy group),

(d) C6-10aryl groups (preferably phenyl groups),

(e) a 5 - or 6-membered unsaturated heterocyclic group (preferably imidazolidine group, dihydropyridine group, pyrazolidine group), optionally substituted oxopropoxy(AMI),

(f) 5-8-membered saturated heterocyclic group (preferably tetrahydrofuryl group, tetrahydropyranyl group, pyrrolidinyl group, piperidino group, sepanlou group, atenelol group, morpholinyl group (including morpholinopropan), 1,1-dioxide isothiazolinone group, oxazolidinyl group, imidazolidinyl group), optionally substituted with 1-3 substituents selected from

(i) hydroxyl groups,

(ii) C1-6alkyl group (preferably methyl group) optionally substituted by 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup (preferably, methoxy groups),

(iii) C1-6alkoxygroup (preferably, methoxy groups), and

(iv) the carbonyl group,

(g) C3-6cycloalkylation (preferably cyclopentyloxy),

(h) C6-10aryloxy groups (preferably fenoxaprop),

(i) 5 - or 6-membered unsaturated, heterocy�of laloxirape (preferably pyridyloxy),

(j) a 5 - or 6-membered saturated geterotsiklicheskikh (preferably tetrahydropyranyloxy, tetrahydropyranyloxy) and

(k) an amino group optionally mono - or disubstituted by substituents selected from the

(i) C1-6alkyl group (preferably methyl group) optionally substituted by 1-3 substituents chosen from hydroxyl groups, carboxypropyl and carboxy-(C1-6alkoxygroup (preferably carboxymethoxy),

(ii) C1-6alkylcarboxylic group (preferably acetyl group, propanolol group, 2-methylpropanoyl group, 2,2-dimethylpropanoyl group, 3-methylbutanoyl group), optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup (preferably, methoxy groups),

(iii) C1-6alkoxycarbonyl group (preferably methoxycarbonyl group, tert-butoxycarbonyl group), optionally substituted C6-10aryl group(s) (preferably phenyl group), and

(iv) C3-6cycloalkylcarbonyl group (preferably cyclopropanecarbonyl group, cyclohexylcarbonyl group), optionally substituted C1-6alkoxygroup(s) (preferably methoxy group),

preferably.

In another embodiment, the implementation as a compound [I] �the connection, represented by the above formula [I'] (hereinafter sometimes to reduce abbreviated as compound [I']), is preferred. Each group of compound [I'] is explained below.

R1'is a

(1) a hydrogen atom,

(2) a hydroxy-group or

(3) C1-6alkoxygroup (preferably a methoxy group, isopropoxy), optionally substituted C6-10aryl group(s) (preferably phenyl group).

R2'and R3'are the same or different and each represents

(1) a hydrogen atom or

(2) C1-6alkyl group (preferably methyl group) optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup (preferably, methoxy groups).

R4'is a group represented by the formula

which is associated with 5-position or 6-position of the indole ring.

R4'represents preferably a group

which is associated with 5-position or 6-position of the indole ring, or a group

which is linked to the 6-position of the indole ring, more preferably a group

which is linked to the 6-position of the indole ring.

5'is a

(1) a hydrogen atom or

(2) C1-6alkyl group (preferably methyl group, ethyl group).

R6'is a

(1) a hydrogen atom,

(2) C1-6alkyl group (preferably methyl group, ethyl group, isopropylene group, isobutylene group, a tert-butyl group, neopentyl group, 1,2-dimethylpropylene group, 1,2,2-trimethylpropyl group), optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup (preferably methoxy groups, propoxylate, isopropoxide),

(c) carboxypropyl,

(d) C1-6alkoxycarbonyl group (preferably methoxycarbonyl group, tert-butoxycarbonyl group)

(e) C6-10aryl groups (preferably phenyl groups),

(f) C6-10aryloxy groups (preferably fenoxaprop),

(g) amino group optionally mono - or disubstituted C1-6alkyl group(s) (preferably methyl group),

(h) a 5 - or 6-membered unsaturated heterocyclic group (preferably shriley group, pyrrolidino group, thiazolidine group, tetrazolyl group, imidazolidine group), optionally substituted C1-6alkyl group(s) (preferably methyl group), and

(i) 5 - yl� 6-membered saturated heterocyclic group (preferably morpholinyl group)

(3) C1-6alkoxygroup (preferably a methoxy group),

(4) C6-10aryl group (preferably phenyl group), or

(5) a 5 - or 6-membered unsaturated heterocyclic group (preferably 1,3,4-thiadiazolyl group), optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup (preferably, methoxy groups).

Alternatively, R5'and R6'together with the nitrogen atom to which they are linked, can form a 5 - or 6-membered cyclic amine (preferably pyrrolidine, piperidine, piperazine, morpholine) (cyclic amine optionally condensed with 5 - or 6-membered unsaturated heterocycle (preferably imidazole)), which is optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups

(b) C1-6alkyl group (preferably methyl group, ethyl group),

(c) C1-6alkoxygroup (preferably, methoxy groups), and

(d) C1-6alkoxycarbonyl group (preferably tert-butoxycarbonyl group).

R7"is a

(1) a hydrogen atom or

(2) C1-6alkyl group (preferably methyl group, ethyl group, propyl group) optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup�group (preferably, methoxy groups), and

(c) amino, optionally mono - or disubstituted C1-6alkyl group(s) (preferably methyl group),

preferably C1-6alkyl group (preferably methyl group, ethyl group, propyl group) optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup (preferably, methoxy groups), and

(c) amino, optionally mono - or disubstituted C1-6alkyl group(s) (preferably methyl group).

R8'is a

(1) C1-6alkyl group (preferably methyl group, ethyl group, propyl group, isopropylene group, isobutylene group, a tert-butyl group, neopentylene group), optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup (preferably methoxy groups, ethoxypropan, propoxylate, isopropoxy), optionally substituted C6-10aryl group(s) (preferably phenyl group),

(c) C3-6cycloalkyl group (preferably cyclopentyloxy group, pirazinokarbazolovogo cyclohexyl group), an optionally substituted C1-6alkoxygroup(s) (preferably methoxy group),

(d) C6-10aryl groups (preferably phenyl groups),

(e) 5 - yl� 6-membered unsaturated heterocyclic group (preferably imidazolidine group, dihydropyridine group, pyrazolidine group), optionally substituted oxopropoxy(AMI),

(f) 5-8-membered saturated heterocyclic group (preferably tetrahydrofuryl group, tetrahydropyranyl group, pyrrolidinyl group, piperidino group, sepanlou group, atenelol group, morpholinyl group, 1,1-dioxide isothiazolinone group, oxazolidinyl group, imidazolidinyl group), optionally substituted with 1-3 substituents selected from

(i) hydroxyl groups,

(ii) C1-6alkyl group (preferably methyl group) optionally substituted by 1 to 3 substituents selected from a hydroxy-group and C1-6alkoxygroup (preferably, methoxy groups),

(iii) C1-6alkoxygroup (preferably, methoxy groups), and

(iv) the carbonyl group,

(g) C3-6cycloalkylation (preferably cyclopentyloxy),

(h) C6-10aryloxy groups (preferably fenoxaprop),

(i) 5 - or 6-membered unsaturated geterotsiklicheskikh (preferably pyridyloxy),

(j) a 5 - or 6-membered saturated geterotsiklicheskikh (preferably tetrahydropyranyloxy, tetrahydropyranyloxy) and

(k) an amino group optionally mono - or disubstituted by substituents selected from the

(i) C1-6alkyl group (Pref�Stateline methyl group),

(ii) C1-6alkylcarboxylic group (preferably acetyl group, propanolol group, 2-methylpropanoyl group, 2,2-dimethylpropanoyl group, 3-methylbutanoyl group), optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup (preferably, methoxy groups),

(iii) C1-6alkoxycarbonyl group (preferably methoxycarbonyl group, tert-butoxycarbonyl group), optionally substituted C6-10aryl group(s) (preferably phenyl group), and

(iv) C3-6cycloalkylcarbonyl group (preferably cyclopropanecarbonyl group, cyclohexylcarbonyl group), optionally substituted C1-6alkoxygroup(s) (preferably methoxy group),

(2) C1-6alkoxygroup (preferably a methoxy group), an optionally substituted C6-10aryl group(s) (preferably phenyl group),

(3) C3-6cycloalkyl group (preferably cyclopentyloxy group, pirazinokarbazolovogo cyclohexyl group) optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup (preferably, methoxy groups),

(4) C6-10aryl group (preferably phenyl group) optionally substituted C1-6alkyl group(s) (pre�occhialino methyl group), optionally substituted by 1 to 3 halogen atoms (preferably fluorine atom),

(5) an amino group optionally mono - or disubstituted C1-6alkyl group(s) (preferably methyl group), an optionally substituted C6-10aryl group(s) (preferably phenyl group),

(6) a 5 - or 6-membered unsaturated heterocyclic group (preferably isoxazolyl group), optionally substituted C1-6alkyl group(s) (preferably methyl group),

(7) a 5 - or 6-membered saturated heterocyclic group (preferably tetrahydrofuryl group, tetrahydropyranyl group, pyrrolidinyl group, piperidino group), optionally substituted with 1-3 substituents selected from

(a) C1-6alkyl group (preferably methyl group),

(b) C1-6alkylcarboxylic group (preferably acetyl group), and

(c) the carbonyl group,

(8) C3-6cycloalkylation (preferably cyclohexyloxy) or

(9) C6-10arylcarbamoyl group (preferably benzoyloxy group).

Alternatively, R7"and R8'together with the nitrogen atom and the carbon atom to which they are linked, can form a 5 - or 6-membered cyclic amine substituted by oxopropoxy (preferably 2-oxopyrrolidin, 2-oxopiperidine, 2-oxo�oxazolidin) and optionally additionally substituted by 1-3 substituents, selected from

(a) hydroxyl groups,

(b) C1-6alkyl group (preferably methyl group), optionally substituted hydroxy-group(s)

(c) C1-6alkoxygroup (preferably, methoxy groups), and

(d) C3-6cycloalkyl group (preferably pirazinokarbazolovogo cyclohexyl group).

As compound [I'] preferred is a compound wherein

R1'is a

(1) a hydrogen atom,

(2) a hydroxy-group or

(3) C1-6alkoxygroup (preferably a methoxy group, isopropoxy), optionally substituted C6-10aryl group(s) (preferably phenyl group);

R2'and R3'are the same or different and each represents

(1) a hydrogen atom or

(2) C1-6alkyl group (preferably methyl group) optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup (preferably, methoxy groups);

R4'is a group

which is associated with 5-position or 6-position of the indole ring, or a group

which is linked to the 6-position of the indole ring

(preferably a group

which is linked to the 6-position of the Indo�professional ring),

where

R5'is a

(1) a hydrogen atom or

(2) C1-6alkyl group (preferably methyl group, ethyl group), and

R6'is a

(1) a hydrogen atom,

(2) C1-6alkyl group (preferably methyl group, ethyl group, isopropylene group, isobutylene group, a tert-butyl group, neopentyl group, 1,2-dimethylpropylene group, 1,2,2-trimethylpropyl group), optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup (preferably methoxy groups, propoxylate, isopropoxide),

(c) carboxypropyl,

(d) C1-6alkoxycarbonyl group (preferably methoxycarbonyl group, tert-butoxycarbonyl group)

(e) C6-10aryl groups (preferably phenyl groups),

(f) C6-10aryloxy groups (preferably fenoxaprop),

(g) amino group optionally mono - or disubstituted C1-6alkyl group(s) (preferably methyl group),

(h) a 5 - or 6-membered unsaturated heterocyclic group (preferably shriley group, pyrrolidino group, thiazolidine group, tetrazolyl group, imidazolidine group), optionally substituted C1-6alkyl group(s) (preferably methyl groups�s) and

(i) 5 - or 6-membered saturated heterocyclic group (preferably morpholinyl group)

(3) C1-6alkoxygroup (preferably a methoxy group),

(4) C6-10aryl group (preferably phenyl group), or

(5) a 5 - or 6-membered unsaturated heterocyclic group (preferably 1,3,4-thiadiazolyl group), optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup (preferably, methoxy groups), or

R5'and R6'together with the nitrogen atom to which they are linked, form a 5 - or 6-membered cyclic amine (preferably pyrrolidine, piperidine, piperazine, morpholine) (cyclic amine optionally condensed with 5 - or 6-membered unsaturated heterocycle (preferably imidazole)), which is optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkyl group (preferably methyl group, ethyl group),

(c) C1-6alkoxygroup (preferably, methoxy groups), and

(d) C1-6alkoxycarbonyl group (preferably tert-butoxycarbonyl group);

R7"is a

(1) a hydrogen atom or

(2) C1-6alkyl group (preferably methyl group, ethyl group, propyl group) optionally zameshano� 1-3 substituents, selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup (preferably, methoxy groups), and

(c) amino, optionally mono - or disubstituted C1-6alkyl group(s) (preferably methyl group),

[preferably

C1-6alkyl group (preferably methyl group, ethyl group, propyl group) optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup (preferably, methoxy groups), and

(c) amino, optionally mono - or disubstituted C1-6alkyl group(s) (preferably methyl group)], and

R8'is a

(1) C1-6alkyl group (preferably methyl group, ethyl group, propyl group, isopropylene group, isobutylene group, a tert-butyl group, neopentylene group), optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup (preferably methoxy groups, ethoxypropan, propoxylate, isopropoxy), optionally substituted C6-10aryl group(s) (preferably phenyl group),

(c) C3-6cycloalkyl group (preferably cyclopentyloxy group, pirazinokarbazolovogo cyclohexyl group), an optionally substituted C1-6alkoxygroup(s) (ol�doctitle a methoxy group),

(d) C6-10aryl groups (preferably phenyl groups),

(e) a 5 - or 6-membered unsaturated heterocyclic group (preferably imidazolidine group, dihydropyridine group, pyrazolidine group), optionally substituted oxopropoxy(AMI),

(f) 5-8-membered saturated heterocyclic group (preferably tetrahydrofuryl group, tetrahydropyranyl group, pyrrolidinyl group, piperidino group, sepanlou group, atenelol group, morpholinyl group, 1,1-dioxide isothiazolinone group, oxazolidinyl group, imidazolidinyl group), optionally substituted with 1-3 substituents selected from

(i) hydroxyl groups,

(ii) C1-6alkyl group (preferably methyl group) optionally substituted by 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup (preferably, methoxy groups),

(iii) C1-6alkoxygroup (preferably, methoxy groups), and

(iv) the carbonyl group,

(g) C3-6cycloalkylation (preferably cyclopentyloxy),

(h) C6-10aryloxy groups (preferably fenoxaprop),

(i) 5 - or 6-membered unsaturated geterotsiklicheskikh (preferably pyridyloxy),

(j) a 5 - or 6-membered saturated geterotsiklicheskikh (preferably tetrahydrofuryl�of gruppi, tetrahydropyranyloxy) and

(k) an amino group optionally mono - or disubstituted by substituents selected from the

(i) C1-6alkyl group (preferably methyl group),

(ii) C1-6alkylcarboxylic group (preferably acetyl group, propanolol group, 2-methylpropanoyl group, 2,2-dimethylpropanoyl group, 3-methylbutanoyl group), optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup (preferably, methoxy groups),

(iii) C1-6alkoxycarbonyl group (preferably methoxycarbonyl group, tert-butoxycarbonyl group), optionally substituted C6-10aryl group(s) (preferably phenyl group), and

(iv) C3-6cycloalkylcarbonyl group (preferably cyclopropanecarbonyl group, cyclohexylcarbonyl group), optionally substituted C1-6alkoxygroup(s) (preferably methoxy group),

(2) C1-6alkoxygroup (preferably a methoxy group), an optionally substituted C6-10aryl group(s) (preferably phenyl group),

(3) C3-6cycloalkyl group (preferably cyclopentyloxy group, pirazinokarbazolovogo cyclohexyl group) optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups and

(b)C 1-6alkoxygroup (preferably, methoxy groups),

(4) C6-10aryl group (preferably phenyl group) optionally substituted C1-6alkyl group(s) (preferably methyl group) optionally substituted by 1 to 3 halogen atoms (preferably fluorine atom),

(5) an amino group optionally mono - or disubstituted C1-6alkyl group(s) (preferably methyl group), an optionally substituted C6-10aryl group(s) (preferably phenyl group),

(6) a 5 - or 6-membered unsaturated heterocyclic group (preferably isoxazolyl group), optionally substituted C1-6alkyl group(s) (preferably methyl group),

(7) a 5 - or 6-membered saturated heterocyclic group (preferably tetrahydrofuryl group, tetrahydropyranyl group, pyrrolidinyl group, piperidino group), optionally substituted with 1-3 substituents selected from

(a) C1-6alkyl group (preferably methyl group),

(b) C1-6alkylcarboxylic group (preferably acetyl group), and

(c) the carbonyl group,

(8) C3-6cycloalkylation (preferably cyclohexyloxy) or

(9) C6-10arylcarbamoyl group (preferably benzoyloxy group) or

R7"and Rsup> 8'together with the nitrogen atom and the carbon atom to which they are linked, form a 5 - or 6-membered cyclic amine substituted by oxopropoxy (preferably 2-oxopyrrolidin, 2-oxopiperidine, 2-oxoacridine) and optionally additionally substituted by 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkyl group (preferably methyl group), optionally substituted hydroxy-group(s)

(c) C1-6alkoxygroup (preferably, methoxy groups), and

(d) C3-6cycloalkyl group (preferably pirazinokarbazolovogo cyclohexyl group).

Among the above compounds, the compound wherein

R1'is a

(1) a hydrogen atom,

(2) a hydroxy-group or

(3) C1-6alkoxygroup (preferably a methoxy group, isopropoxy), optionally substituted C6-10aryl group(s) (preferably phenyl group);

R2'and R3'are the same or different and each represents

(1) a hydrogen atom or

(2) C1-6alkyl group (preferably methyl group) optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup (preferably, methoxy groups);

R4'is a group

associated with polozenie indole ring,

where

R7"represents C1-6alkyl group (preferably methyl group, ethyl group, propyl group) optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup (preferably, methoxy groups), and

(c) amino, optionally mono - or disubstituted C1-6alkyl group(s) (preferably methyl group), and

R8'is a

(1) C1-6alkyl group (preferably methyl group, ethyl group, propyl group, isopropylene group, isobutylene group, a tert-butyl group, neopentylene group), optionally substituted with 1-3 substituents selected from

(a) hydroxyl groups,

(b) C1-6alkoxygroup (preferably methoxy groups, ethoxypropan, propoxylate, isopropoxy), optionally substituted C6-10aryl group(s) (preferably phenyl group),

(c) C3-6cycloalkyl group (preferably cyclopentyloxy group, pirazinokarbazolovogo cyclohexyl group), an optionally substituted C1-6alkoxygroup(s) (preferably methoxy group),

(d) C6-10aryl groups (preferably phenyl groups),

(e) a 5 - or 6-membered unsaturated heterocyclic group (preferably imidazolidine group, dihydropyri�ilen group, pyrazolidine group), optionally substituted oxopropoxy(AMI),

(f) 5-8-membered saturated heterocyclic group (preferably tetrahydrofuryl group, tetrahydropyranyl group, pyrrolidinyl group, piperidino group, sepanlou group, atenelol group, morpholinyl group, 1,1-dioxide isothiazolinone group, oxazolidinyl group, imidazolidinyl group), optionally substituted with 1-3 substituents selected from

(i) hydroxyl groups,

(ii) C1-6alkyl group (preferably methyl group) optionally substituted by 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup (preferably, methoxy groups),

(iii) C1-6alkoxygroup (preferably, methoxy groups), and

(iv) the carbonyl group,

(g) C3-6cycloalkylation (preferably cyclopentyloxy),

(h) C6-10aryloxy groups (preferably fenoxaprop),

(i) 5 - or 6-membered unsaturated geterotsiklicheskikh (preferably pyridyloxy),

(j) a 5 - or 6-membered saturated geterotsiklicheskikh (preferably tetrahydropyranyloxy, tetrahydropyranyloxy) and

(k) an amino group optionally mono - or disubstituted by substituents selected from the

(i) C1-6alkyl group (preferably methyl group),/p>

(ii) C1-6alkylcarboxylic group (preferably acetyl group, propanolol group, 2-methylpropanoyl group, 2,2-dimethylpropanoyl group, 3-methylbutanoyl group), optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup (preferably, methoxy groups),

(iii) C1-6alkoxycarbonyl group (preferably methoxycarbonyl group, tert-butoxycarbonyl group), optionally substituted C6-10aryl group(s) (preferably phenyl group), and

(iv) C3-6cycloalkylcarbonyl group (preferably cyclopropanecarbonyl group, cyclohexylcarbonyl group), optionally substituted C1-6alkoxygroup(s) (preferably methoxy group),

(2) C1-6alkoxygroup (preferably a methoxy group), an optionally substituted C6-10aryl group(s) (preferably phenyl group),

(3) C3-6cycloalkyl group (preferably cyclopentyloxy group, pirazinokarbazolovogo cyclohexyl group) optionally substituted by 1-3 substituents selected from

(a) hydroxyl groups and

(b) C1-6alkoxygroup (preferably, methoxy groups),

(4) C6-10aryl group (preferably phenyl group) optionally substituted C1-6alkyl group(s) (pre�occhialino methyl group), optionally substituted by 1 to 3 halogen atoms (preferably fluorine atom),

(5) an amino group optionally mono - or disubstituted With1-6alkyl group(s) (preferably methyl group), an optionally substituted C6-10aryl group(s) (preferably phenyl group),

(6) a 5 - or 6-membered unsaturated heterocyclic group (preferably isoxazolyl group), optionally substituted C1-6alkyl group(s) (preferably methyl group),

(7) a 5 - or 6-membered saturated heterocyclic group (preferably tetrahydrofuryl group, tetrahydropyranyl group, pyrrolidinyl group, piperidino group), optionally substituted with 1-3 substituents selected from

(a) C1-6alkyl group (preferably methyl group),

(b) C1-6alkylcarboxylic group (preferably acetyl group), and

(c) the carbonyl group,

(8) C3-6cycloalkylation (preferably cyclohexyloxy) or

(9) C6-10arylcarbamoyl group (preferably benzoyloxy group) or

R7"and R8'together with the nitrogen atom and the carbon atom to which they are linked, form a 5 - or 6-membered cyclic amine substituted by oxopropoxy (preferably 2-oxopyrrolidin, 2-oxopiperidine, 2-oxoacridine) and optional�tive optionally substituted with 1-3 substituents, selected from

(a) hydroxyl groups,

(b) C1-6alkyl group (preferably methyl group), optionally substituted hydroxy-group(s)

(c) C1-6alkoxygroup (preferably, methoxy groups), and

(d) C3-6cycloalkyl group (preferably pirazinokarbazolovogo cyclohexyl group),

that is, the connection represented by the above formula [I'-a], is especially preferred.

Pharmaceutically acceptable salt of the compound [I] can be any salt, if it is non-toxic salt of the compounds of the present invention, and examples include salts of inorganic acids, organic acid salts, salts of inorganic bases, salts with organic bases, salts of amino acids, and the like.

Examples of salts of inorganic acids include salts of hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, Hydrobromic acid and the like.

Examples of salts with organic acids include salts of oxalic acid, maleic acid, citric acid, fumaric acid, lactic acid, malic acid, succinic acid, tartaric acid, acetic acid, trifluoroacetic acid, gluconic acid, ascorbic acid, methanesulfonic acid, the mixture of Benzenesulfonic acid, p-toluensulfonate acid and the like.

Prima�s salts of inorganic bases include the sodium salt, potassium salt, calcium salt, magnesium salt, ammonium salt and the like.

Examples of salts with organic bases include salts of methylamine, diethylamine, trimethylamine, triethylamine, ethanolamine, diethanolamine, triethanolamine, Ethylenediamine, Tris(gidroximetil)methylamine, dicyclohexylamine, N,N'-dibenziletilendiaminom, guanidine, pyridine, picoline, choline, cinchonine, meglumine and the like.

Examples of amino acid salts include salts with lysine, arginine, aspartic acid, glutamic acid and the like.

When you need the salt of compound [I] of each salt can be obtained by interaction of the compound [I] with inorganic base, organic base, inorganic acid, organic acid or amino acid according to a known method.

A “solvate” is the compound [I] or its pharmaceutically acceptable salt, which is coordinated with the solvent molecule, and such term also includes hydrates. The solvate is preferably pharmaceutically acceptable solvate, examples include hydrate, ethanolate, dimethylsulfoxide and such solvates of the compounds [I] or its pharmaceutically acceptable salt. Specific examples include hemihydrate, monohydrate, dihydrate or monoethanol compounds [I], monohydrate sodium salt or 2/3-atenolol dihydrochloride compounds�ia [I] and the like.

Solvates can be obtained in a known manner.

In addition, the compound represented by the formula [I], there are different “isomers”. For example, the CIS-form and TRANS-form are present as geometric isomers, and when there is an asymmetric carbon atom, enantiomers and diastereomers are present as stereoisomers due to asymmetric carbon atom. In addition, when there is an axis of asymmetry, the stereoisomers are present due to the axis of asymmetry. In some cases, may also be present tautomery.

Alternative, may be present as stereoisomers formed due to the orientation of the unpaired pair of electrons at the nitrogen atom. Consequently, all these isomers and mixtures thereof are included in the scope of the present invention.

In addition, the compound [I] can be observed isotope (for example,3N,14C,35S, etc.).

Deuterated compound obtained by conversion of the1N connections [I]2N (D) are also included in the compound represented by the formula [I].

As compound [I] or its pharmaceutically acceptable salt, or its solvate is preferred essentially purified compound [I] or its pharmaceutically acceptable salt, or its solvate. More preferred is the compound [I] or its pharmaceutically reception�supported salt, or a solvate, which is purified so that it had a purity of more than 80%.

In the present invention, the prodrug of compound [I] or its pharmaceutically acceptable salt, or its solvate (hereinafter sometimes to reduce abbreviated as the compound of the present invention can be also acceptable drug. “Prodrug” is a derivative of the compound of the present invention having a chemically or metabolically destroy the group, which after the introduction into the organism is regenerated into the original compound, for example, hydrolysis, solvolysis or decomposition under physiological conditions, and manifests its inherent efficiency. It includes non-covalent complex and salt. A prodrug may be used, for example, to improve absorption by oral administration or delivery to the target organ.

Examples of the modified portion in the compound of the present invention include highly reactive functional group such as hydroxyl group, carboxyl group, amino group and the like.

Specific examples hydroxymorphinone groups include acetyl group, propanolol group, 2-methylpropanoyl group, 2,2-dimethylpropanoyl group, Palmitoyl group, benzoyloxy group, 4-methylbenzoyl group, dimethylcarbamoyl group, Dima�aluminometasilicate group alfagroup, Alamillo group, fumarello group, 3-carboxybenzoyl group, 2-carboxyethylgermanium group, 3-natrocarbonatite group and the like.

Specific examples carboxymethylcelluose groups include methyl group, ethyl group, propanolol group, 2-methylpropanoyl group, butyl group, isobutylene group, a tert-butyl group, 2,2-dimethylpropyleneurea group, carboxymethyl group, dimethylaminomethyl group, 1-(acetyloxy)ethyl group, 1-(ethoxycarbonyl)ethyl group, 1-(isopropoxycarbonyl)ethyl group, 1-(cyclohexyloxycarbonyloxy)ethyl group, (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl group, benzyl group, phenyl group, about-taillow group, morpholinoethyl group, N,N-diethylcarbamoyl group, phthalidyl group and the like.

Specific examples aminoantipyrine groups include tert-butyl group, docosanol group, 2,2-dimethylphenylethylamine, Alamillo group, hexylberberine group, intelceremony group, 3-methylthio-1-(acetylamino)propellerblades group, 1-sulfo-1-(3-ethoxy-4-hydroxyphenyl)methyl group, (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl group, (5-methyl-2-oxo-1,3-dioxol-4-yl)methoxycarbonyl group, tetrahydrofuranyl �the Rupp, pyrrolidinyloxy group and the like.

When the indole derivative of the present invention is used as a medicament, particularly in the pharmaceutical composition, preferred is a chemically stable compound.

Examples of pharmaceutical compositions include oral preparations such as tablet, capsule, granule, powder, lozenge, syrup, emulsion, suspension and the like, and parenteral agents such as a drug for external application, suppository, injection, eye drops, preparations for nasal, pulmonary drugs, and the like.

The pharmaceutical composition of the present invention are prepared according to a method known in the field of pharmaceutical preparations, mixing, etc. of the compounds of the present invention with a suitable amount of at least one type of pharmaceutically acceptable carrier, and optionally similar component. Although the content of compounds of the present invention in the pharmaceutical composition varies depending on the dosage form, dose and the like, the content is, for example, 0.1 to 100 wt%. the whole composition.

Examples of “pharmaceutically acceptable carrier include various organic or inorganic substances-carriers that are commonly used as components of pre�herdsmen, for example, excipient, dezintegriruetsja substance binding substance, the substance giving the slide, a lubricant and the like for solid preparations, and solvents solubilizers agent, suspending agent, isotonic agent, buffering agent, soothing agent and the like for liquid preparations. In addition, when necessary, used additives such as preservative, antioxidant, colorant, sweetening agent and the like.

Examples of “excipient” include lactose, sucrose, D-mannitol, D-sorbitol, corn starch, dextrin, microcrystalline cellulose, crystalline cellulose, carmellose, calcium salt carmellose, the sodium salt of carboxymethylcel, slabosalenuyu hydroxypropyl cellulose, acacia gum and the like.

Examples of “dezintegriruetsja funds” include carmellose, calcium salt carmellose, sodium salt carmellose, the sodium salt of carboxymethylcel, the sodium salt of croscarmellose, polyplasdone, slabosalenuyu hydroxypropyl cellulose, hydroxypropyl methylcellulose, crystalline cellulose and the like.

Examples of binders include hydroxypropyl cellulose, hydroxypropyl methylcellulose, povidone, crystalline cellulose, sucrose, dextrin, starch, gelatin, sodium with�l carmellose, acacia gum and the like.

Examples of compounds that give the slide include light anhydrous silicic acid, magnesium stearate, and the like.

Examples of the lubricant include magnesium stearate, calcium stearate, talc and the like.

Examples of the solvent include purified water, ethanol, propylene glycol, macrogol, sesame oil, corn oil, olive oil, and the like.

Examples of “solubilizing agent include propylene glycol, D-mannitol, benzyl benzoate, ethanol, triethanolamine, sodium carbonate, sodium citrate and the like.

Examples of a suspending agent include benzalkonium chloride, carmellose, hydroxypropyl cellulose, propylene glycol, povidone, methylcellulose, glycerol monostearate and the like.

Examples of the isotonic agent include glucose, D-sorbitol, sodium chloride, D-mannitol and the like.

Examples of the buffer agent include sodium hydrogen phosphate, sodium acetate, sodium carbonate, sodium citrate and the like.

Examples of the soothing agent include benzyl alcohol and the like.

Examples of the preservative include metilparagidroksibenzoat, chlorobutanol, benzyl alcohol, dehydroacetic sodium, sorbic acid and the like.

Examples of the “antioxidant” include sodium sulfite, ascorbic �islote and the like.

Examples of the colorant include food colors (e.g., food color red No. 2 or 3, food color yellow No. 4 or 5, etc.), β-carotene and the like.

Examples of “sweetening agent” include sodium salt of saccharin, dialogization, aspartame and the like.

The pharmaceutical composition of the present invention can be administered orally or parenterally (e.g. local, rectal, intravenous administration etc.) to man and mammals, non-human (e.g., mouse, rat, hamster, Guinea pig, rabbit, cat, dog, pig, cow, horse, sheep, monkey, etc.). The dose varies depending on subject of administration, disease, symptom, dosage form, route of administration and the like. For example, the daily dose for oral administration to an adult patient (body weight: about 60 kg) is typically in the range from about 1 mg to 1 g of compound [I] as an active ingredient. This amount can be administered in one to several portions.

The compound of the present invention has inhibitory activity against inducible T-cell kinase (ITK). Therefore, the compound of the present invention can be applied as an active ingredient of an agent for treatment or prevention of inflammatory W�problems agent for the treatment or prophylaxis of allergic diseases, an agent for treating or preventing autoimmune diseases, an inhibitor of rejection in the transplantation and the like.

“Inhibition of ITK” or “possessing inhibitory activity against ITK” means the inhibition of ITK functions to eliminate or attenuate the activity or the possession of such an activity of ITK. For example, this means measuring inhibition activity against ITK based on the conditions in the following experimental example 1 and the introduction of compounds having inhibitory activity, to a mammal, including man, to inhibit the function of ITK. “Inhibition of ITK” preferably means “inhibition of ITK man.” “The ITK inhibitor” preferably is “ITK inhibitor of human rights”.

Although inflammatory disease is not specifically limited, examples include rheumatoid arthritis, inflammatory bowel disease and the like.

Although allergic disease is not specifically limited, examples include atopic dermatitis, asthma, allergic rhinitis and the like.

Although autoimmune disease is not specifically limited, examples include rheumatoid arthritis, systemic lupus erythematosus, psoriasis, inflammatory bowel disease and the like.

The compound of the present invention can be used in combination with one or more other drugs (hereinafter also referred to as concomitant drugs) according to the method conventionally used in the medical field (hereinafter called the combined use).

The period of introduction of the compounds of the present invention and a concomitant drug is not restricted, and you can enter the subject of the introduction in the form of a combination drug or both drugs may be administered simultaneously or at given intervals in the form of individual drugs. In addition, the pharmaceutical composition of the present invention and a concomitant drug can be used in the form of a set. The dose of concomitant medications similar to clinically used dose, and can appropriately be selected according to the subject of administration, disease, symptom, dosage form, route of administration, time of administration, combinations and the like. The form of the introduction of concomitant medications not specifically limited, requires only the combination of the compounds of the present invention with a concomitant drug.

Then following explains one example of methods for producing compounds for practicing the present �of subramania. However, the method of obtaining compounds of the present invention is not limited to them.

Even if direct appropriate description is in the following methods of preparation, the stage can be modified for the efficient production of compounds, such as the introduction of protective groups at the functional group with the removal of protection in the next stage, the exposure of functional groups as the precursor to the reaction conditions in each stage with the subsequent transformation into the desired functional group in a suitable stage, by a change in the ways and stages of receipt, and the like.

Treatment after the reaction in each stage can be conventional treatment, where the isolation and purification can be performed, if necessary, according to the method appropriately selected from conventional methods such as crystallization, recrystallization, distillation, distribution, chromatography on silica gel, preparative HPLC and the like, or a combination of such methods.

A method of producing 1

where R9and R10are the same or different and each represents aminosidine group, and other symbols have the meanings given above.

Examples of “aminosidine group” for R9or R10include tert-butoxycarbonyl group, �oxycarbonyl group trityloxy group, tetrahydropyranyloxy group, methoxymethyl group, 2-(trimethylsilyl)ethoxymethylene group, p-toluensulfonyl group and the like, with preference given to tert-butoxycarbonylamino the group.

(Stage 1)

Compound [3] can be obtained by reaction combinations Suzuki compounds [1] and connections [2]. For example, the compound [3] can be obtained by reaction of compound [1] with compound [2] in a solvent under heating in the presence of base and palladium catalyst. The reaction is preferably carried out by gradual addition of compounds [2] to the mixture of all other reagents when heated.

Examples of the palladium catalyst used for the reaction include tetranitropentaerithrite, complex (bis(diphenylphosphino)ferrocene)paradigalla-methylene chloride, and the like.

Examples of the base used for the reaction include potassium phosphate, sodium carbonate, sodium bicarbonate, potassium carbonate, triethylamine and the like.

Preferred examples of the solvent used for the reaction include type solvents ethers, such as 1,4-dioxane, tetrahydrofuran, diethyl ether, 1,2-dimethoxyethane and the like; alcohol solvents such as methanol, ethanol, n-propanol, isopropanol and the like; hydrocarbon solvents, �which as toluene, hexane, xylene and the like; polar solvents such as N,N-dimethylformamide, dimethylsulfoxide, acetonitrile and the like; and a mixture of such solvent with water.

Connection [1] and the compound [2] can be commercially available products or can be prepared according to the following methods for the preparation of 2 and 3 or the conventional method.

(Stage 2)

The compound [I] can be obtained by removing R9and R10compounds [3] the usual response to the removal of protection. The reaction of removing the protection can be performed in conditions suitable for the types of R9and R10or a combination of R9and R10. For example, when both of R9and R10represent tert-butoxycarbonyl group, the compound [I] can be obtained by treating compound [3] in a solvent and in the presence of base at room temperature.

Examples of the base used for the reaction include sodium hydroxide, lithium hydroxide, sodium carbonate, and the like.

Preferred examples of the solvent used for the reaction include type solvents ethers, such as 1,4-dioxane, tetrahydrofuran and the like; alcohol solvents such as methanol, ethanol, n-propanol, isopropanol and the like; polar solvents such as N,N-dimethylformamide, dimethylsulfoxide, acetonitrile and the under�training; and the mixture of such solvent with water.

The method of obtaining 2

where each symbol has the values specified above.

(Stage 1)

Compound [5] can be obtained by reaction of compound [4] with ethylformate in a solvent in the presence of base.

Examples of the base used for the reaction include sodium hydride, tert-butoxide potassium, sodium hydroxide, potassium hydroxide, sodium methoxide, ethoxide sodium, diisopropylamide lithium hexamethyldisilazide lithium and the like.

Preferred examples of the solvent used for the reaction include type solvents ethers, such as 1,4-dioxane, tetrahydrofuran, diethyl ether, 1,2-dimethoxyethane and the like; alcohol solvents such as methanol, ethanol, n-propanol, isopropanol and the like; and polar solvents such as N,N-dimethylformamide, dimethylsulfoxide, acetonitrile and the like.

Compound [4] can be commercially acceptable product or it can be obtained by the conventional method.

(Stage 2)

Compound [6] can be obtained by reaction of a compound [5] with hydrazine in a solvent at a temperature from room temperature to the temperature warms up. This stage is sometimes preferably carried out at a temperature from room temperature to the temperature warms up. To�ome, if necessary, the reaction can be applied in acid.

Preferred examples of the solvent used for the reaction include alcohol solvents such as methanol, ethanol, n-propanol, isopropanol and the like; and polar solvents such as N,N-dimethylformamide, dimethylsulfoxide, acetonitrile and the like.

Examples acid, which is used for the reaction include hydrochloric acid, sulfuric acid, p-toluensulfonate acid, p-toluensulfonate pyridinium and the like.

Compound [7] can be obtained by reaction of compound [6] with iodine in a solvent in the presence of base at a temperature from room temperature to the temperature of heating.

Examples of the base used for the reaction include potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, and the like.

Preferred examples of the solvent used for the reaction include type solvents ethers, such as 1,4-dioxane, tetrahydrofuran and the like; alcohol solvents such as methanol, ethanol, n-propanol, isopropanol and the like; polar solvents such as N,N-dimethylformamide, dimethylsulfoxide, acetonitrile and the like; and a mixture of such solvent with water.

(Stage 4)

Compound [1] can be obtained by the introduction aminosidine �the group (R 9) in compound [7]. For example, when R9represents a tert-butoxycarbonyl group, the compound [1] can be obtained by reaction of compound [7] with di-tert-BUTYLCARBAMATE in a solvent at a temperature from room temperature to a temperature under heating in the presence of base.

Examples of the base used for the reaction include tertiary amines such as triethylamine, 4-dimethylaminopyridine and the like.

Preferred examples of the solvent used for the reaction include type solvents ethers, such as 1,4-dioxane, tetrahydrofuran and the like; ester solvents such as ethyl acetate and the like; hydrocarbon solvents such as toluene, hexane, xylene and the like, and polar solvents such as N,N-dimethylformamide, dimethylsulfoxide, acetonitrile and the like.

A method of producing 3

where each symbol has the values specified above.

(Stage 1)

Compound [9] can be obtained by the introduction aminosidine group (R10in connection [8]. For example, when R10represents a tert-butoxycarbonyl group, compound [9] can be obtained by reaction of compound [8] with di-tert-BUTYLCARBAMATE in a solvent at a temperature from room temperature to the temperature at�revani in the presence of base.

Examples of the base used for the reaction include tertiary amines such as 4-dimethylaminopyridine, triethylamine and the like, with preference given to 4-dimethylaminopyridine.

Preferred examples of the solvent used for the reaction include type solvents ethers, such as 1,4-dioxane, tetrahydrofuran and the like; ester solvents such as ethyl acetate and the like; hydrocarbon solvents such as toluene, hexane, xylene and the like, and polar solvents such as N,N-dimethylformamide, dimethylsulfoxide, acetonitrile and the like.

Connection [8] may be commercially available product or can be obtained by the conventional method.

(Stage 2)

Compound [2] can be obtained by reaction of compound [9] with the borate in a solvent under cooling in the presence of base. The reaction is preferably carried out gradually added dropwise grounds upon cooling and in the presence of borate.

Examples of the borate, which is used for the reaction include triisopropylsilyl, trimethylboron and the like.

Examples of the base used for the reaction include butyllithium, diisopropylamide lithium hexamethyldisilazide lithium and the like.

Preferred examples of the solvent used for the reaction, �fied type solvents ethers, such as 1,4-dioxane, tetrahydrofuran, diethyl ether, 1,2-dimethoxyethane and the like.

Compound [I-b], which is the compound [I] at which R4is a group represented by the formula

which is associated with 5-position or 6-position of the indole ring may also be obtained according to the following method of obtaining 4 or 7.

A method of producing 4

where R11is carboxyterminal group, and other symbols have the meanings given above.

Examples of “carboxyamide group” for R11include alkyl group such as methyl group, ethyl group, tert-butyl group and the like, tert-butyldimethylsilyloxy group, benzyl group, methoxyethoxymethyl group and the like.

(Stage 1)

Compound [10] can be obtained in the same way as in method 1, compounds [1] and the compound [2-1] obtained in the same way as in the method of obtaining 3.

(Stage 2)

Compound [11] can be obtained by removing R11coupling [10] the reaction of removing the protection. The reaction of removing the protection can be performed in conditions suitable for the type R11. For example, when R11represents an alkyl group, compound [11] can be obtained by hydrolysis with�organisations [10] in a solvent in the presence of base at a temperature from room temperature to a temperature under heating and acidification of the resulting solution.

Examples of the base used for the reaction include potassium carbonate, sodium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium hydride, sodium hydride, potassium hydride and the like.

Preferred examples of the solvent used for the reaction include a mixed solvent of water and alcoholic solvents such as methanol, ethanol, n-propanol, isopropanol and the like; and a mixed solvent of such solvent with type solvents ethers, such as 1,4-dioxane, tetrahydrofuran and the like.

(Stage 3)

Compound [I-b] can be obtained by reaction of compound [11] with the amine [12] in a solvent in the presence of a condensation agent at a temperature of from cooling to heating. For smooth reaction, you can apply the activator.

Examples of the condensation agent used for the reaction include N,N'-carbonyldiimidazole, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, hydrochloride 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and the like.

Examples of the activator, which is used for the reaction include hydroxysuccinimide, 1-hydroxy-benzotriazole and the like.

Preferred examples of the solvent used for the reaction include hydrocarbon solvents such as benzene, toluene, hexane, xylene and the p�daubney; halogenated solvents such as dichloro methane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; solvents type of simple ether, such as 1,4-dioxane, diethyl ether, 1,2-dimethoxyethane, tetrahydrofuran and the like; polar solvents such as N,N-dimethylformamide, dimethylsulfoxide, acetonitrile and the like; pyridine; and their mixed solvent.

Amin [12] may be commercially acceptable product, or it can be obtained by the conventional method.

Compound [I-c], which is the compound [I] at which R4is a group represented by the formula

which is associated with 5-position or 6-position of the indole ring may also be obtained by the following method of producing 5 or 6.

A method of producing 5

where R12is aminosidine group; R13represents an alkyl group such as methyl group, ethyl group, tert-butyl group and the like, benzyl group and the like, and other symbols have the meanings given above.

Examples aminosidine group” for R12include 2-(trimethylsilyl)ethoxymethylene group, trityloxy group, tetrahydropyranyloxy group, methoxymethyl group, p-toluensulfonyl �the Rupp and the like, with preference given to 2-(trimethylsilyl)ethoxymethylene the group.

(Stage 1)

Compound [13] can be obtained by the introduction aminosidine group (R12in the compound [10]. For example, when R12represents 2-(trimethylsilyl)ethoxymethylene group, compound [13] can be obtained by reaction of compound [10] with 2-(trimethylsilyl)ethoxymethylene in a solvent under cooling and in the presence of base.

Examples of the base used for the reaction include sodium hydride and the like.

Examples of the solvent used for the reaction include type solvents ethers, such as 1,4-dioxane, diethyl ether, 1,2-dimethoxyethane, tetrahydrofuran and the like; and polar solvents such as N,N-dimethylformamide, dimethylsulfoxide, acetonitrile and the like.

(Stage 2)

Compound [14] can be obtained by removing R11coupling [13]. The reaction can also be conducted in the same manner as in stage 2 of the production method 4.

(Stage 3)

Compound [15] can be obtained by rearrangement of kurzius compound [14] with diphenylphosphorylacetate with obtaining the appropriate isocyanate and the reaction of the obtained isocyanate with the appropriate alcohol (R13OH). Rearrangement of kurzius can also be a reaction of the acid chloride of compound [14] with sodium azide� to obtain the corresponding acid azide, followed by heating. When carrying out the rearrangement of kurzius alcohol is present (R13OH), the isocyanate immediately subjected to reaction with an alcohol to give the compound [15]. For example, when R13represents the benzyl group, compound [15] can be obtained by reaction of compound [14] by adding dropwise diphenylphosphinite in a solvent under heating in the presence of benzyl alcohol and a tertiary amine.

Examples of the tertiary amine used for the reaction include triethylamine and the like.

Preferred examples of the solvent used for the reaction include hydrocarbon solvents such as benzene, toluene, hexane, xylene and the like; and type solvents ethers, such as 1,4-dioxane, diethyl ether, 1,2-dimethoxyethane, tetrahydrofuran and the like.

(Stage 4)

When R7is not a hydrogen atom, the compound [16] can be obtained by the introduction of R7the reaction of compound [15] with an appropriate alkylating agent in a solvent under cooling with ice to room temperature in the presence of base.

Alkylating agent used for the reaction, can be any alkylating agent, if he can enter R7and examples of it include methyliodide, ethyliodide, benzyloxyethanol and the like.

Examples of the base which�OE used for the reaction, include sodium hydride, butyllithium, diisopropylamide lithium hexamethyldisilazide lithium and the like.

Preferred examples of the solvent used for the reaction include hydrocarbon solvents such as benzene, toluene, hexane, xylene and the like; type solvents ethers, such as 1,4-dioxane, diethyl ether, 1,2-dimethoxyethane, tetrahydrofuran and the like, and polar solvents such as N,N-dimethylformamide, dimethylsulfoxide, acetonitrile and the like.

When R7represents a hydrogen atom, the compound [15] can be directly subjected to step 5 without carrying out stage 4.

(Stage 5)

Compound [17] can be obtained by reduction of compound [16] by the conventional method. For example, when R13represents the benzyl group, the compound [17] can be obtained by the conventional method such as catalytic reduction and the like. The catalytic reaction can be performed, for example, in a solvent in the presence of a metal catalyst at a temperature from room temperature to heating under pressure from normal to high and with the use of gaseous hydrogen. As the source of hydrogen can be applied ammonium formate, cyclohexene, DICYCLOHEXYL and the like.

Examples of metal ka�of Aligator, which is used for the reaction include palladium-on-charcoal, palladium hydroxide, palladium black, Raney-Nickel and the like.

Preferred examples of the solvent used for the reaction include alcohol solvents such as methanol, ethanol, n-propanol, isopropanol and the like; solvents type of simple ether, such as 1,4-dioxane, tetrahydrofuran and the like; ester solvents such as ethyl acetate and the like; and their mixed solvents.

(Stage 6)

Compound [19] can be obtained by condensation of compound [17] with the compound [18] according to a commonly used method of amide condensation. For example, compound [18] treated halogenous agent in a solvent at room temperature, while receiving appropriate gelegenheid acid. Then gelegenheid acid is condensed with compound [17] in the presence of a tertiary amine or pyridine at a temperature of from cooling to room temperature to give the compound [19].

Examples halogenides agent, which is used for the reaction include oxaliplatin, thionylchloride, phosphorus oxychloride, phosphorus pentachloride and the like.

Examples of the tertiary amine used for the reaction include triethylamine and the like.

Preferred examples of solvents�of RER, which is used for the reaction include halogenated solvents such as dichloro methane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; type solvents ethers, such as 1,4-dioxane, diethyl ether, 1,2-dimethoxyethane, tetrahydrofuran and the like; and a mixed solvent of such solvent with water.

Compound [18] may be commercially available product, or can be obtained according to the conventional method. When the corresponding gelegenheid acid is commercially available, it can also be used.

In addition, the compound [19] can also be obtained by condensation of compound [17] and compound [18] in the same way as in stage 3 of the production method 4.

(Stage 7)

Compound [I-c] can be obtained by removing R12coupling [19] the reaction of removing the protection. The reaction of removing the protection can be performed using conditions suitable for the type R12. For example, when R12represents 2-(trimethylsilyl)ethoxymethylene group, compound [I-c] can be obtained by reaction of compound [19] in a solvent under heating in the presence of fluoride tetrabutylammonium and Ethylenediamine.

Preferred examples of the solvent used for the reaction include type solvents ethers, such as 1,4-dioxane, tetrahydrofuran and �such WMD, and polar solvents such as N,N-dimethylformamide, dimethylsulfoxide, acetonitrile and the like.

A method of producing 6

where each symbol has the above values.

(Stage 1)

Compound [20] can be obtained by removing R12coupling [16], obtained in stage 4 of the production method 5. The reaction can be conducted in the same way as in stage 7 of the method of obtaining 5.

(Stage 2)

Compound [21] can be obtained by reduction reaction of compound [20]. The reaction can be conducted in the same way as in stage 5 of the method of obtaining 5.

(Stage 3)

Compound [22] can be obtained by condensation of compound [21] and compound [18]. The reaction can be conducted in the same way as in stage 6 of the method of obtaining 5.

Alternatively, the compound [I-c] sometimes directly receive the above reaction without holding stage 4.

(Stage 4)

Compound [I-c] can be obtained from [22] by removing the acetyl group at the pyrazole ring. For example, compound [I-c] can be obtained by hydrolysis of compound [22] in a solvent at from room temperature to heating in the presence of base.

Examples of the base used for the reaction include potassium carbonate, sodium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium hydride, sodium hydride, guide�ID potassium and the like.

Examples of the solvent used for the reaction include aqueous alcohol solvents such as methanol, ethanol, n-propanol, isopropanol and the like; and a mixed solvent of such solvent with type solvents ethers, such as 1,4-dioxane, tetrahydrofuran and the like.

A method of producing 7

(Stage 1)

Compound [24] can be obtained by condensation of compound [14], obtained in stage 2 of the production method 5, with an amine [23]. The reaction can be conducted in the same way as in stage 3 of the production method 4.

(Stage 2)

Compound [25] can be obtained by reaction of compound [23] with an appropriate alkylating agent to introduce the R5. The reaction can be conducted in the same way as in stage 4 of the method of obtaining 5.

(Stage 3)

Compound [I-b] can be obtained by removing R12coupling [25] the reaction of removing the protection. The reaction can be conducted in the same way as in stage 7 of the method of obtaining 5.

EXAMPLES

The present invention is explained in detail below with reference to referential examples, examples and experimental example, which should not be understood as limiting the invention.

Room temperature in the reference examples and examples means the temperature 1-40°C.

Referential example 1

Obtain tert-butyl--iodine-6,6-dimethyl-4,5,6,7-tetrahydroindazole-1-carboxylate

(Stage 1)

Obtaining 3-iodo-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol

In a nitrogen atmosphere to a suspension of sodium hydride (28 g, 697 mmol) in tetrahydrofuran (500 ml) was added dropwise a solution of 3,3-dimethylcyclohexanone (80 g, 634 mmol) in tetrahydrofuran (250 ml) under cooling with ice for approximately 1 hour and the mixture was stirred for 1 hour. Then dropwise over approximately 1 hour was added a solution of ethylformate (99 g, 1.3 mole) in tetrahydrofuran (250 ml) and the mixture was stirred under cooling with ice for 1 hour and at room temperature for 1 hour. To the reaction mixture were added water and ethyl acetate and the organic layer was separated and was extracted with 2 n aqueous sodium hydroxide solution. The aqueous layer was acidified with concentrated hydrochloric acid and was extracted with ethyl acetate. Then the organic layer was washed with saturated brine and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure, while receiving 4,4-dimethyl-2-oxocyclohexanecarboxylate. To a solution of the obtained 4,4-dimethyl-2-oxocyclohexanecarboxylate in methanol (376 ml) was added dropwise a solution of hydrazine monohydrate (31 ml, 640 mmol) in methanol (31 ml) by heating to boiling with reflux for lengthy�and approximately 1 hour and the mixture was stirred for 15 min. The reaction mixture was concentrated under reduced pressure, was added ethyl acetate and water and the organic layer was separated. Then the organic layer was washed with saturated brine and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure, while receiving 6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol. To the solution obtained 6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazole in N,N-dimethylformamide (1.4 l) was added iodine (232 g, 915 mmol) and potassium hydroxide (121 g, 1.8 mole) at room temperature and the mixture was stirred for about 4 hours. Then under cooling with ice added dropwise an aqueous solution (800 ml), sodium bisulfite (80 g). Was added water (2 l) and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. Then to the residue was added hexane (350 ml) and the mixture was stirred at room temperature. Precipitated crystals were collected by filtration, washed with hexane and dried under reduced pressure, while receiving 3-iodo-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol (41 g, yield 23%).

1H-NMR (400 MHz, DMSO-d6) δ: or 0.94 (s, 6H), of 1.47 (t, 2H, J=6,38 Hz), of 2.21 (t, 2H, J=6,38 Hz), 2,33 (s, 2H), 12,69 (s, 1H).

(Stage 2)

On�the doctrine of tert-butyl 3-iodo-6,6-dimethyl-4,5,6,7-tetrahydroindazole-1-carboxylate

To a solution of 3-iodo-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazole (41 g, 147 mmol), triethylamine (22 ml, 155 mmol) and 4-dimethylaminopyridine (824 mg, 7 mmol) in tetrahydrofuran (163 ml) was added dropwise a solution of di-tert-BUTYLCARBAMATE (34 g, 155 mmol) in tetrahydrofuran (41 ml) at room temperature for 40 min and the mixture was stirred for 30 min. the Reaction mixture was then concentrated under reduced pressure. The residue was washed in suspension in hexane (130 ml) at 60°C and cooled with ice. The crystals were collected by filtration, washed with hexane and dried under reduced pressure, while receiving specified in the title compound (53 g, yield 95%).

1H-NMR (400 MHz, DMSO-d6) δ: 0,95 (s, 6H), of 1.46 (t, 2H, J=6,38 Hz) of 1.56 (s, 9H), of 2.23 (t, 2H, J=of 6.26 Hz), 2,63 (s, 2H).

Referential example 2

Obtain 1-tert-butyl-6-methyl 2-brilinta-1,6-dicarboxylate

(Stage 1)

Obtaining methyl-1H-indole-6-carboxylate

In a nitrogen atmosphere to a solution of 1H-indole-6-carboxylic acid (121 g, 752 mmol) in N,N-dimethylformamide (360 ml) was added potassium carbonate (124 g, 900 mmol) and the mixture stirred at room temperature for 1 hour. Then, dropwise, at room temperature for 15 min was added itmean (56 ml, 900 mmol) and the mixture was stirred for 2 hours. Then to the reaction solution d�balali water (1.2 l) and hexane (100 ml) and the mixture stirred at room temperature for 1 hour. Precipitated crystals were collected by filtration, washed successively with water and hexane and dried under reduced pressure, while receiving specified in the title compound (115 g, yield 87%).

1H-NMR (400 MHz, DMSO-d6) δ: 3,85 (3H, C), a 6.53 (1H, d, J=1,61 Hz), 7,60-7,63 (3H, m), 8,07 (1H, s) 11,48 (1H, s).

(Stage 2)

Obtain 1-tert-butyl-6-methylindol-1,6-dicarboxylate

To a solution of methyl 1H-indole-6-carboxylate (124 g, 708 mmol) in tetrahydrofuran (500 ml) was added 4-dimethylaminopyridine (865 mg, 7 mmol). Then, dropwise, at room temperature for approximately 1 hour was added di-tert-BUTYLCARBAMATE (156 g, 715 mmol) in tetrahydrofuran (150 ml) and the mixture was stirred for 1 hour. The reaction mixture was concentrated and the residue was purified by chromatography on silica gel, receiving specified in the title compound (193 g, yield 99%).

1H-NMR (400 MHz, DMSO-d6) δ: of 1.65 (9H, s), 3,89 (3H, C), about 6,82 (1H, DD, J=3,63, 0,86 Hz), 7,74 (1H, d, J=8,06 Hz), the 7.85 (1H, DD, J=8,06, 0,86 Hz), a 7.87 (1H, d, J=3,63 Hz), 8,76 (1H, d, J=0,81 Hz).

(Stage 3)

Obtain 1-tert-butyl-6-methyl-2-brilinta-1,6-dicarboxylate

To a solution of 1-tert-butyl-6-methylindol-1,6-dicarboxylate (107 g, 389 mmol) in tetrahydrofuran (135 ml) was added triisopropylsilyl (135 ml, 584 mmol) and cooled to an internal temperature of -5°C. Then, dropwise, at p�ateenyi 1.5 hours was added a solution of (253 ml, 506 mmol) diisopropylamide lithium in hexane while maintaining the internal temperature of -5°C or below and the mixture was additionally stirred for 1 hour. Then to the reaction solution was added dropwise 10% aqueous citric acid solution (1.2 l) under cooling with ice. The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed with saturated brine, and dried over magnesium sulfate. Magnesium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue in the form of suspension was washed with a mixed solvent of ethyl acetate (133 ml) and hexane (666 ml) and the precipitate was collected by filtration, washed with hexane and dried under reduced pressure, while receiving specified in the title compound (73 g, yield 59%).

1H-NMR (400 MHz, DMSO-d6) δ: 1.62 V (s, 9H), 3,88 (s, 3H), 6,72 (d, 1H, J=0,88 Hz), to 7.68 (t, 1H, J=4,08 Hz), 7,82 (DD, 1H, J=8,16, a 1.54 Hz), of 8.33 (s, 2H), 8,78 (t, 1H, J=0,77 Hz).

Referential example 3

Preparation of (S)-2-(morpholine-4-yl)propionic acid

(Stage 1)

Getting benzyl-(S)-2-(morpholine-4-yl)propionate

In an argon atmosphere to a solution of tosylate benzyl ester of L-alanine (3.4 g, 9.7 mmol) and triethylamine (6.8 ml) in dimethyl sulfoxide (17 ml) was added a solution of 1-bromo-2-(2-bromoethoxy)ethane (1.5 ml, 12 mmol) in dimethylsulfoxide (3 ml) under cooling with ice and the mixture was stirred �ri room temperature for 24 hours. To the reaction solution was added water and ethyl acetate and the organic layer was separated. Then the organic layer was washed with saturated brine and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel, receiving specified in the title compound (1.6 g, yield 64%).

1H-NMR (400 MHz, DMSO-d6) δ: of 1.20 (d, 3H, J=7,25 Hz), 2,44-2,59 (m, 4H), 3,35 (square, 1H, J=7,25 Hz), 3,47-3,59 (m, 4H), 5,16-5,09 (m, 2H), 7,29-7,40 (m, 5H).

(Stage 2)

Preparation of (S)-2-(morpholine-4-yl)propionic acid

In an argon atmosphere to a solution of benzyl-(S)-2-(morpholine-4-yl)propionate (43 g, 172 mmol) in methanol (430 ml) was added 20% palladium hydroxide-on-charcoal (4.3 g) at room temperature and the mixture was stirred for 3 hours in hydrogen atmosphere at normal pressure. The reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure, while receiving specified in the title compound (25.4 g, 93%).

1H-NMR (400 MHz, DMSO-d6) δ: of 1.17 (d, 3H, J=6,98 Hz), 2,47-2,63 (m, 4H), 3,17 (square, 1H, J=6,98 Hz), 3,50-3,63 (m, 4H).

Referential example 4

Preparation of (3-exmortis-4-yl)acetic acid

(Stage 1)

Getting 2-chloro-N-(2-hydroxyethyl)acetamide

In an argon atmosphere to a solution of 2-aminoet�ol (5 g, 82 mmol) and triethylamine (11.4 ml, 82 mmol) in tetrahydrofuran (60 ml) was added dropwise chlorocatechol (6,2 ml, 78 mmol) under cooling with ice over 30 min and the mixture was stirred for 1 hour. The reaction mixture is further stirred at room temperature for 3 hours and dried over magnesium sulfate. Magnesium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel, receiving specified in the title compound (3.2 g, yield 30%).

1H-NMR (400 MHz, DMSO-d6) δ: 3,16 (square, 2H, J=5,87 Hz), 3,42 (square, 2H, J=5,87 Hz), 4,06 (s, 2H), 4,71 (t, 1H, J=5,45 Hz), 8,18 (s, 1H).

(Stage 2)

Getting the morpholine-3-

In an argon atmosphere to a solution of 2-chloro-N-(2-hydroxyethyl)acetamide (3.2 g, 23 mmol) in tetrahydrofuran (64 ml) was added sodium hydride (1.2 g, 30 mmol) under cooling with ice and the mixture was stirred for 1 hour. The mixture is then stirred at room temperature for 1 hour and further at 60°C for 4 hours. After cooling, water was added (540 μl) and the reaction mixture was dried over magnesium sulfate. Magnesium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel, receiving specified in the title compound (232 mg, yield 10%).

1H-�Mr (400 MHz, DMSO-d6) δ: 3,20-3,23 (m, 2H), 3,70-3,73 (m, 2H), 3,96 (s, 2H), of 7.88-8,07 (user.s, 1H).

(Stage 3)

Getting benzyl-(3-exmortis-4-yl)acetate

In an argon atmosphere to a solution of the morpholine-3-she (220 mg, 2.2 mmol) in N,N-dimethylformamide (2.2 ml) was added sodium hydride (105 mg, 2.6 mmol) under cooling with ice and the mixture was stirred for 1 hour. Added benzylbromide (379 μl, 2.4 mmol) and the mixture was stirred for 2 hours. To the reaction solution was added water and ethyl acetate and the organic layer was separated. The aqueous layer was extracted with ethyl acetate twice and the combined organic layers were washed successively with water and saturated brine, and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel, receiving specified in the title compound (321 mg, yield 59%).

1H-NMR (400 MHz, DMSO-d6) δ: 3,40-of 3.43 (m, 2H), 3,83-of 3.85 (m, 2H), 4,08 (s, 2H), is 4.21 (s, 2H), 5,16 (s, 2H), 7,32-7,41 (m, 5H).

(Stage 4)

Preparation of (3-exmortis-4-yl)acetic acid

In an argon atmosphere to a solution of benzyl-(3-exmortis-4-yl)acetate (319 mg, 1.3 mmol) in methanol (5 ml) was added 20% palladium hydroxide-on-carbon (64 mg) at room temperature. Then the mixture was stirred for 2 hours in the atmosphere�'ere of hydrogen at normal pressure. The reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure, while receiving specified in the title compound (206 mg, yield quantitative).

1H-NMR (400 MHz, DMSO-d6) δ: 3,37 is 3.40 (m, 2H), 3,82-3,84 (m, 2H), 4,03 (s, 2H), 4,06 (s, 2H), 12,22-13,57 (user.s, 1H).

Referential example 5

Receiving tert-butyl-6-benzoyloxymethyl-3-iodo-6-methyl-4,5,6,7-tetrahydroindazole-1-carboxylate

(Stage 1)

Getting 7-methyl-1,4-dioxaspiro[4.5]Dean-8-

In a nitrogen atmosphere to a solution of bis(trimethylsilyl)lithium amide (1 M, 100 ml, 100 mmol) in tetrahydrofuran (200 ml) was dropwise added a solution of 1,4-dioxaspiro[4.5]Dean-8-she (15.6 g, 100 mmol) in tetrahydrofuran (50 ml) at -78°C for approximately 30 min and the mixture was stirred for 30 min. Then methyliodide (2.5 ml, 120 mmol) was added dropwise over 5 min and the mixture was stirred at -78°C for 30 min and at room temperature for 2 hours. To the reaction mixture were added saturated aqueous solution of ammonium chloride and the mixture was extracted three times with diethyl simple ether. The combined organic layers were dried over magnesium sulfate. Magnesium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel, receiving specified in the title compound (1.6 g, yield 62%).

1H-NMR (400 MHz, DMSO-d6) δ: of 0.90 (3H, d, J=to 6.62 Hz), of 1.65 (1H, t, J=13,01 Hz), 1,84-2,04 (3H, m), 2,19 (1H, DDD, J=14,50, 5,13, was 3.03 Hz), 2,49-2,69 (2H, m), 3,85-4,06 (4H, m).

(Stage 2)

Getting 7-gidroximetil-7-methyl-1,4-dioxaspiro[4.5]Dean-8-

7-Methyl-1,4-dioxaspiro[4.5]Dean-8-he (10.5 g, 62 mmol) was dissolved in a solution of potassium hydroxide in methanol (10% wt./mass., 60 g). To the solution was added dropwise an aqueous solution of formaldehyde (37%, to 4.6 ml) in methanol (5 ml) under cooling with ice for 20 min and the mixture was stirred for 30 minutes Then to the reaction mixture was added 1 n hydrochloric acid and saturated aqueous solution of ammonium chloride and the mixture was extracted three times with chloroform. The combined organic layers were dried over magnesium sulfate. Magnesium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel, receiving specified in the title compound (6.9 g, yield 56%).

1H-NMR (400 MHz, DMSO-d6) δ: 0.98 in (3H, C), to 1.67 (1H, DD, J=14,00, 1,41 Hz), 1,86-of 1.97 (2H, m), of 2.08 (1H, DD, J=14,00, to 1.61 Hz), 2,33-of 2.48 (2H, m), 3,42-3,50 (2H, m), 3,90-3,95 (4H, m), 4,63 (1H, t, J=5,24 Hz).

(Stage 3)

Preparation of (7-methyl-1,4-dioxaspiro[4.5]DECA-7-yl)methanol

To a solution of 7-gidroximetil-7-methyl-1,4-dioxaspiro[4.5]Dean-8-she (6.9 g, 65 mmol) in methanol (40 ml) there was added�whether p-toluensulfonate (7.4 g, 40 mmol) and the mixture was heated at boiling with reflux for 3 hours. Then to the reaction solution was added methanol (120 ml), cyanoborohydride sodium (2.9 g, 46 mmol) and a solution (100 ml) of zinc chloride (3.1 g, 23 mmol) in methanol and the mixture was heated at boiling with reflux for 2 hours. After cooling, was added 1 n aqueous sodium hydroxide solution (700 ml), the mixture was filtered through celite and the filtrate was extracted three times with ethyl acetate. The combined organic layers were washed successively with water and saturated brine, and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel, receiving specified in the title compound (4.0 g, yield 61%).

1H-NMR (400 MHz, DMSO-d6) δ: to 0.96 (3H, C), 1,18-to 1.87 (8H, m), 3,18 (1H, d, J=8,06 Hz), 3,35 (1H, DD, J=10,88, of 6.45 Hz), 3,51 (1H, DD, J=10,88, 9,07 Hz), 3,93-3,94 (4H, m).

(Stage 4)

Getting 7-benzoyloxymethyl-7-methyl-1,4-dioxaspiro[4.5]Dean

In a nitrogen atmosphere to a solution of (7-methyl-1,4-dioxaspiro[4.5]DECA-7-yl)methanol (4.0 g, 21 mmol) in N,N-dimethylformamide (40 ml) was added sodium hydride (1.1 g, 27 mmol) under cooling with ice and the mixture was stirred for 30 minutes Then to the reaction mixture was added the bromide (3.1 ml, 25 mmol) at room the�erature and the mixture was additionally stirred for 1 hour. To the reaction mixture were added diethyl ether and water and the organic layer was separated. Then the organic layer was washed successively with water and saturated brine, and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel, receiving specified in the title compound (5.7 g, yield 93%).

1H-NMR (400 MHz, DMSO-d6) δ: of 0.95 (3H, C), 1,14-of 1.19 (1H, m), 1,32-1,59 (7H, m), 3,20 (2H, DD, J=28,41, 8.66 roubles Hz), of 3.77 to 3.85 (4H, m), of 4.45 (2H, s), 7,29-to 7.33 (5H, m).

(Stage 5)

Obtaining 3-benzoyloxymethyl-3-methylcyclohexanone

To a solution of 7-benzoyloxymethyl-7-methyl-1,4-dioxaspiro[4.5]Decan (5.3 g, 19 mmol) in a mixed solvent of acetone (42 ml) and water (11 ml) was added p-toluensulfonate pyridinium (4.8 g, 19 mmol) and the mixture was stirred with heating at 80°C for 2 hours. After cooling, to the reaction mixture were added ethyl acetate and water and the organic layer was separated. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed successively with water and saturated brine, and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel, receiving specified in the headers�ke compound (3.9 g, yield 88%).

1H-NMR (400 MHz, DMSO-d6) δ: of 0.88 (3H, C), 1,43-1,49 (1H, m), 1,72-of 1.84 (3H, m), 2,01 (1H, dt, J=13,67, of 1.43 Hz), 2,17 and 2.26 (2H, m), 2,32 (1H, d, J=13,45 Hz), 3,17 (2H, DD, J=10,81, of 8.82 Hz), 4,47 (2H, s), 7,26-7,38 (5H, m).

(Stage 6)

Receiving tert-butyl-6-benzoyloxymethyl-3-iodo-6-methyl-4,5,6,7-tetrahydroindazole-1-carboxylate

In the same way as in referential example 1, indicated in the title compound (3.8 g) was obtained from 3-benzoyloxymethyl-3-methylcyclohexanone (3.9 g).

Reference example 6

Preparation of (2-oxopiperidin-1-yl)acetic acid

(Stage 1)

Getting benzyl-(2-oxopiperidin-1-yl)acetate

In a nitrogen atmosphere to a solution of the piperidine-2-one (9.8 g, 99 mmol) in N,N-dimethylformamide (100 ml) was added sodium hydride (4.4 g, 110 mmol) under cooling with ice and the mixture was stirred for 1 hour. Added benzylbromide (19 ml, 120 mmol) and the mixture was additionally stirred for 2 hours. To the reaction mixture were added ethyl acetate and water and the organic layer was separated, washed successively with water and saturated brine, and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel, receiving specified in the title compound (6.0 g, yield 24%).

1H-NMR (400 MHz, LCA�-d 6) δ: 1,62-of 1.66 (4H, m), 2,11 (2H, t, J=6,45 Hz), 3,10-of 3.12 (2H, m), is 4.21 (2H, s), is 5.18 (2H, s), 7,21-7,40 (5H, m).

(Stage 2)

Preparation of (2-oxopiperidin-1-yl)acetic acid

In a nitrogen atmosphere to a solution of benzyl-(2-oxopiperidin-1-yl)acetate (6.0 g, 24 mmol) in methanol (60 ml) was added 20% palladium hydroxide-on-carbon (400 mg) at room temperature and the mixture was stirred for 4 hours in hydrogen atmosphere at normal pressure. The reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure, while receiving specified in the title compound (4.0 g, yield quantitative).

1H-NMR (400 MHz, DMSO-d6) δ: 1,71-of 1.74 (4H, m), of 2.23 (2H, t, J=6,04 Hz), 3,17-of 3.31 (2H, m), 3,94 (2H, s), is 12.58 (1H, s).

Example 1

Obtaining N-[2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl]-N-methylacetamide

(Stage 1)

Obtain 1-tert-butyl-6-methyl 2-(1-tert-butoxycarbonyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)indole-1,6-dicarboxylate

In an argon atmosphere to a solution of tert-butyl-3-iodo-6,6-dimethyl-4,5,6,7-tetrahydroindazole-1-carboxylate obtained in reference example 1 (49 g, 130 mmol), potassium phosphate (110 g, 520 mmol) and complex (bis(diphenylphosphino)ferrocene)paradigalla-methylene chloride (11 g, 13 mmol) in a mixed solvent of 1,4-dioxane (780 ml) and water (330 ml) was added 1-tert-butyl-6-methyl-2-�arylindole-1,6-dicarboxylate (42 g, 130 mmol) obtained in reference example 2 portions of 2 g when heated at 110°C for 15 min and the mixture was stirred for 5 min. After cooling, to the reaction mixture were added water and ethyl acetate and the organic layer was separated. Then the organic layer was washed successively with water and saturated brine, and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel, receiving specified in the title compound (40 g, yield 58%).

1H-NMR (400 MHz, DMSO-d6) δ: of 1.01 (s, 6H), of 1.40 (s, 9H), of 1.48 (t, 2H, J=6,15 Hz), of 1.57 (s, 9H), is 2.41 (t, 2H, J=5,80 Hz), of 2.72 (s, 2H), 3,90 (s, 3H), 7,06 (s, 1H), to 7.77 (d, 1H, J=8.35 Hz), to 7.89 (DD, 1H, J=8,35, of 1.16 Hz), 8,73 (t, 1H, J=0,70 Hz).

(Stage 2)

Obtaining methyl-2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)indole-6-carboxylate

To a solution of 1-tert-butyl 6-methyl-2-(1-tert-butoxycarbonyl-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)indole-1,6-dicarboxylate (39 g, 75 mmol) in a mixed solvent of methanol (180 ml) and tetrahydrofuran (120 ml) was added dropwise 2 n aqueous sodium hydroxide solution (149 ml, 298 mmol) under cooling with ice for 15 min and the mixture was stirred for 15 min Then was added dropwise 1 n hydrochloric acid to establish a pH of 5. Precipitated crystals sob�Raleigh by filtration, was washed with water and dried under reduced pressure, while receiving specified in the title compound (23 g, yield 97%).

1H-NMR (400 MHz, DMSO-d6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,38 Hz), 2,42 (s, 2H), 2,68 (t, 2H, J=6,15 Hz), 3,85 (s, 3H), to 6.67 (s, 1H), members, 7.59 (s, 2H), 8,07 (s, 1H), 11,71 (s, 1H), 12,66 (s, 1H).

(Stage 3)

Obtaining methyl-2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indole-6-carboxylate

In an argon atmosphere to a solution of methyl 2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)indole-6-carboxylate (23 g, 71 mmol) in N,N-dimethylformamide (230 ml) was added sodium hydride (6.3 g, 157 mmol) in portions approximately 500 mg when the internal temperature of -10°C and the mixture was stirred for 30 min Then 2-(trimethylsilyl)ethoxymethylene (26 g, 157 mmol) was added dropwise during 15 min and the mixture was additionally stirred for 2 hours. To the reaction mixture were added ethyl acetate and water and the organic layer was separated. Then the organic layer was washed successively with water and saturated brine, and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel, receiving specified in the title compound (33 g, yield 80%).

1H-NMR (400 MHz, DMSO-d6)δ: -0,21 (C, 9H), of 0.03 (s, 9H), of 0.68 (t, 2H, J=8,00 Hz), of 0.87 (t, 2H, J=8,12 Hz), of 1.03 (s, 6H), 1,54 (t, 2H, J=of 6.26 Hz), 2,50 (s, 2H), 2,63 (t, 2H, J=of 6.26 Hz), 3,30-of 3.31 (m, 2H) and 3.59 (t, 2H, J=8,00 Hz), a 3.87 (s, 3H), 5,42 (s, 2H), 6,14 (s, 2H), 6,83 (d, 1H, J=0,70 Hz), 7,67-7,72 (m, 2H), 8,22 (s, 1H).

(Stage 4)

Getting 2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indole-6-carboxylic acid

To a solution of methyl 2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indole-6-carboxylate (33 g, 57 mmol) in a mixed solvent of tetrahydrofuran (165 ml) and methanol (165 ml) was added 4 n aqueous sodium hydroxide solution (71 ml, 284 mmol) and the mixture was heated at 60°C for 2 hours. After cooling, the reaction mixture was concentrated, to the residue was added a 10% aqueous solution of citric acid to establish a pH adjusted to 5 and the mixture was extracted with ethyl acetate. Then the organic layer was washed with saturated brine and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure, while receiving specified in the title compound (31 g, yield 97%).

1H-NMR (400 MHz, DMSO-d6) δ: -0,21--0,20 (m, 9H), to -0.05--0,03 (m, 9H), 0,68-0,71 (m, 2H), 0,85-of 0.91 (m, 2H), of 1.03 (s, 6H), 1,54 (t, 2H, J=6,06 Hz), 2,63 (t, 2H, J=5,95 Hz), 3,57-3,61 (m, 2H), 5,42 (s, 2H), 6,13 (d, 2H, J=3,53 Hz), About 6,82 (t, 1H, J=3,42 Hz), 7,65-of 7.70 (m, 2H), 8,20 (s, 1H).

(Stage 5)

Getting benzyl-(2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)carbamate

In an argon atmosphere to a solution of 2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indole-6-carboxylic acid (26 g, 45 mmol), triethylamine (8.2 ml, 59 mmol) and benzyl alcohol (18 ml, 180 mmol) in toluene (260 ml) was added dropwise diphenylphosphoryl (12 ml, 54 mmol) at 115°C for 2 hours. After cooling, to the reaction mixture were added water and the organic layer was separated. Then the organic layer was washed successively with water and saturated brine, and dried over magnesium sulfate. Magnesium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel, and washed with a suspension in hexane (210 ml) with heating at 60°C. the Resulting crystals were collected by filtration, washed with hexane and dried under reduced pressure, while receiving specified in the title compound (28 g, yield 91%).

1H-NMR (400 MHz, DMSO-d6) δ: -0,19 (s, 9H), of 0.03 (s, 9H), is 0.69 (t, 2H, J=Hz 8,16), 0,86 (t, 2H, J=8,05 Hz), of 1.02 (s, 6H), of 1.52 (t, 2H, J=6.18 of Hz), 2,59 (t, 2H, J=6,06 Hz), 3,58 (t, 2H, J=8,05 Hz), 5,17 (s, 2H), 5,38 (s, 2H), 5,96 (s, 2H), 6,61 (s, 1H), 7,10 (DD, 1H, J=8,49, 1.65 Hz), 7,34-of 7.46 (m,6H), 7,86 (s, 1H), of 9.71 (s, 1H).

(Stage 6)

Getting benzyl-N-(2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-methylcarbamate

In an argon atmosphere to a solution of benzyl-(2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)carbamate (3 g, 4.6 mmol) in N,N-dimethylformamide (30 ml) was added sodium hydride (219 mg, 5.5 mmol) under cooling with ice and the mixture was stirred for 10 minutes Then to the reaction mixture were added methyliodide (0.6 ml, 6.9 mmol) and the mixture was additionally stirred for 3 hours. To the reaction mixture were added ethyl acetate and water and the organic layer was separated. Then the organic layer was washed successively with water and saturated brine, and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel, receiving specified in the title compound (2.2 g, yield 69%).

1H-NMR (400 MHz, DMSO-d6) δ: -0,21 (s, 9H), of 0.03 (s, 9H), 0,66 (t, 2H, J=8,01 Hz), 0,86 (t, 2H, J=8,01 Hz), of 1.02 (s, 6H), of 1.53 (t, 2H, J=6,01 Hz), 2.49 USD (s, 2H), 2,60 (t, 2H, J=6,01 Hz), 3,29 (s, 3H), 3,29 (t, 2H, J=8,01 Hz), 3,59 (t, 2H, J=8,01 Hz), 5,09 (s, 2H), 5,39 (s, 2H), 6,00 (s, 2H), 6,70 (s, 1H), 7,03 (DD, 1H, J=to 8.41, 2,00 Hz), 7,26-value of 7, 37 (m, 5H), 7,44-members, 7.59 (m, 2H).

(Stage 7)

Get�of N-(2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-methylamine

A solution of benzyl-N-(2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-methylcarbamate (2.2 g, 3.1 mmol), 10% palladium-on-coal (216 mg) and ammonium formate (989 mg, 16 mmol) in ethanol (30 ml) was heated at boiling with reflux for 2.5 hours. After cooling, the reaction mixture was filtered through snarls and the filtrate concentrated. The residue was purified by chromatography on silica gel, receiving specified in the title compound (1.4 g, yield 79%).

1H-NMR (400 MHz, DMSO-d6) δ: -0,18 (s, 9H), of 0.03 (s, 9H), is 0.69 (t, 2H, J=to 8.41 Hz), 0,86 (t, 2H, J=to 8.41 Hz), 1,01 (s, 6H), of 1.52 (t, 2H, J=6,41 Hz), 2,47 (s, 2H), of 2.57 (t, 2H, J=6,41 Hz), 2,73 (d, 3H, J=5,21 Hz), and 3.31 (t, 2H, J=to 8.41), 3,58 (t, 2H, J=to 8.41 Hz), and 5.36 (s, 2H), 5,50 (square, 1H, J=5,21 Hz), 5,94 (s, 2H), to 6.42-6,55 (m, 3H), 7,25 (d, 1H, J=to 8.41 Hz).

(Stage 8)

Obtaining N-[2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl]-N-methylacetamide

In an argon atmosphere to a solution of N-(2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-methylamine (100 mg, 0.18 mmol) and triethylamine (75 µl, 0,54 mmol) in chloroform (1.5 ml) was added acetyl chloride (19 μl, 0.27 mmol) at room temperature and the mixture was stirred for 2 hours. To the reaction mixture were added water and the mixture was extracted with three R�for ethyl acetate. The combined organic layers were washed successively with water and saturated brine, and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure, obtaining N-(2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-methylacetamide. A solution of the obtained N-(2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-methylacetamide in N,N-dimethylformamide (1.4 ml) was added to the fluoride tetrabutylammonium (1.8 ml, 1.8 mmol), previously concentrated under reduced pressure. Added Ethylenediamine (0.7 ml) and the mixture was stirred under heating at 90°C for 24 hours. After cooling, was added water and ethyl acetate and the organic layer was separated. Then the aqueous layer was extracted with ethyl acetate twice. The combined organic layers were washed successively with water and saturated brine, and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by thin layer chromatography on silica gel, receiving specified in the title compound (26 mg, yield 42%).

Example 2

Obtaining N-[2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl]-N-utilize�amide

(Stage 1)

Obtaining N-(2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-ethylamine

In a nitrogen atmosphere benzyl-N-(2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-ethylcarbamate prepared in the same way as in example 1, step 6, from benzyl-(2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)carbamate obtained in example 1, stage 5. To a solution of the obtained benzyl-N-(2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-ethylcarbamate (979 mg, 1.4 mmol) in methanol (8 ml) was added 20% palladium hydroxide-on-carbon (400 mg). Then the mixture was stirred in hydrogen atmosphere under normal pressure for 1.5 hours. After the reaction, the reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel, receiving specified in the title compound (802 mg, yield 100%).

1H-NMR (400 MHz, DMSO-d6) δ: -0,18 (s, 9H), of 0.03 (s, 9H), of 0.72 (t, 2H, J=8,0 Hz), 0,89 (t, 2H, J=8 Hz), of 1.05 (s, 6H), 1,21-1,24 (m, 3H), of 1.52 and 1.57 (m, 2H), 2,50 (s, 2H), 2,56-of 2.64 (m, 2H), 3,10-3,13 (m, 2H), 3,32-3,36 (m, 2H), 3,61 (t, 2H, J=8,0 Hz), 5,39 (s, 2H), 5,96 (2H), 6,50 (s, 2H), is 6.51-6,54 (m, 1H), 6,61 (user.s, 1H), 7,27 (d, 1H, J=8,0 Hz).

(Stage 2)

Obtaining N-[2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl]-N-ethylacetamide

In the same way as in example 1, step 8, specified in the title compound (24 mg, yield 35%) was obtained from N-(2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-ethylamine (110 mg, 0,19 mmol).

Example 3

Getting benzyl-N-{2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl}-N-methylcarbamate

A solution of benzyl-N-(2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-methylcarbamate (13 g, 19 mmol) obtained in example 1, step 6, N,N-dimethylformamide (102 ml) was added to the fluoride tetrabutylammonium (93 ml, 93 mmol), concentrated previously under reduced pressure, and then was added Ethylenediamine (19 ml). The mixture was stirred under heating at 90°C for 7 hours. After cooling, was added water and ethyl acetate and the organic layer was separated. Then the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed successively with water, 10% aqueous citric acid solution and saturated brine, and dried over sodium sulfate. The sodium sulfate was removed Fi�trevanian and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel, receiving specified in the title compound (7.2 g, yield 91%).

Example 4

Preparation of (S)-N-[2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl]-N-methyl-2-(morpholine-4-yl)propionamide

(Stage 1)

Obtaining N-[2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl]-N-methylamine

In a nitrogen atmosphere to a solution of benzyl-N-{2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl}-N-methylcarbamate obtained in example 3 (7.2 g, 17 mmol), in ethanol (72 ml) was added 10% palladium-on-coal (723 mg) and ammonium formate (2.5 g, 39 mmol) and the mixture was stirred under heating at 65°C for 40 min. After cooling, the reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure. The residue was washed in suspension in water (300 ml). The precipitate was collected by filtration, washed with water and dried under reduced pressure, while receiving specified in the title compound (4.5 g, yield 90%).

1H-NMR (400 MHz, DMSO-d6) δ: of 1.00 (s, 6H), 1,56 (t, 2H, J=6,41 Hz), of 2.38 (s, 2H), 2,61 (t, 2H, J=6,41 Hz), 2,69 (d, 3H, J=4,81 Hz), 5,24-of 5.34 (m, 1H), 6,33-of 6.46 (m, 3H), 7,18 (d, 1H, J=to 8.41 Hz), 10,65 (s, 1H), to 12.28 (s, 1H).

(Stage 2)

Preparation of (S)-N-[2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl]-N-methyl-2-(morpholine-4-yl)propionamide

To a solution of N-{2-(6,6-dimethyl-4,5,6,7-t�trihydro-1H-indazol-3-yl)-1H-indol-6-yl}-N-methylamine (45 mg, Of 0.15 mmol) in pyridine (1 ml) was added (S)-2-(morpholine-4-yl)propionic acid obtained in reference example 3 (110 mg, 0.69 mmol), hydrochloride 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (106 mg, 0,55 mmol) at room temperature and the mixture was stirred for 14 hours. To the reaction mixture were added chloroform and water and the organic layer was separated. The organic layer was dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. Then the residue was dissolved in a mixed solvent of tetrahydrofuran (1 ml) and methanol (1 ml). To the solution was added 2 n aqueous sodium hydroxide solution (0.35 ml) at room temperature and the mixture was stirred for 20 min. To the reaction mixture were added chloroform and water and the organic layer was separated. The organic layer was dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by thin layer chromatography on silica gel, receiving specified in the title compound (52 mg, yield 78%).

Example 5

Obtaining hydrochloride (S)-N-[2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl]-N-methyl-2-(morpholine-4-yl)propionamide

To a solution of (S)-N-[2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl]-N-methyl-2-(morpholine-4-yl)propionamide�, obtained in example 4 (100 mg, 0,23 mmol), in ethyl acetate (1 ml) was added 4 N. hydrochloric acid/ethyl acetate (0.06 ml, 0,24 mmol) at room temperature and the mixture was stirred for 30 min. the Precipitated crystals were collected by filtration, washed with ethyl acetate and dried under reduced pressure, while receiving specified in the title compound (75 mg, 69%).

Example 6

Obtaining N-[2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl]-N-methyl-2-(3-exmortis-4-yl)acetamide

In an argon atmosphere to a solution of N-[2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl]-N-methylamine obtained in example 4, step 1 (40 mg, 0.14 mmol), and (3-exmortis-4-yl)acetic acid obtained in reference example 4 (76 mg, 0.48 mmol), in pyridine (1.3 ml) added hydrochloride 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (91 mg, 0.48 mmol) at room temperature and the mixture was stirred at room temperature for 12 hours. Then the reaction mixture was concentrated under reduced pressure. The residue was dissolved in methanol (1.2 ml) was added 2 n aqueous sodium hydroxide solution (1.0 ml) and the mixture stirred at room temperature for 45 minutes Then to the reaction mixture were added water and ethyl acetate and the organic layer was separated. The aqueous layer was extracted with ethyl acetate twice and are United by� organic layers were washed successively with water and saturated brine, and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel, receiving specified in the title compound (40 mg, yield 67%).

Example 7

Preparation of (2-hydroxy-1-methylethyl)methylamide 2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indole-6-carboxylic acid

(Stage 1)

Preparation of (2-hydroxy-1-methylethyl)amide 2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indole-6-carboxylic acid

To a solution of 2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indole-6-carboxylic acid obtained in example 1, stage 4 (500 mg, 0.88 mmol) in N,N-dimethylformamide (5 ml) was added monohydrate of 1-hydroxybenzotriazole (161 mg, 1.1 mmol), hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (202 mg, 1.1 mmol) and 2-amino-1-propanol (84 mg, 1.1 mmol) at room temperature and the mixture was stirred at room temperature for 7 hours. To the reaction mixture were added water and ethyl acetate and the organic layer was separated. Then the organic layer was washed successively with water and saturated brine, and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced� pressure. The residue was purified by chromatography on silica gel, receiving specified in the title compound (511 mg, yield 93%).

1H-NMR (400 MHz, DMSO-d6) δ: -0,22 (s, 9H), of 0.03 (s, 9H), of 0.68 (t, 2H, J=8,12 Hz), of 0.87 (t, 2H, J=8,12 Hz), of 1.03 (s, 6H), of 1.17 (d, 3H, J=6,72 Hz), 1,54 (t, 2H, J=of 6.26 Hz), 2,50 (s, 2H), 2,62 (t, 2H, J=of 6.26 Hz), 3,29 (t, 2H, J=8,12 Hz), 3,35-3,39 (m, 1H), 3,48-of 3.53 (m, 1H), 3,60 (t, 2H, J=8,12 Hz), 4,01-4,11 (m, 1H), 4,74 (t, 1H, J=5.68 per Hz), 5,41 (s, 2H), 6,11 (s, 2H), 6,76 (s, 1H), EUR 7.57-7.67 per (m, 2H), 8,01 (d, 1H, J=of 7.88 Hz), 8,15 (s, 1H).

(Stage 2)

Obtain [2-(tert-butyldiphenylsilyl)-1-methylethyl]amide 2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indole-6-carboxylic acid

To a solution of (2-hydroxy-1-methylethyl]amide 2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indole-6-carboxylic acid (265 mg, 0,42 mmol) in N,N-dimethylformamide (2.7 ml) was added imidazole (35 mg, 0,51 mmol) and tert-butyldiphenylsilyl (132 μl, 0.51 mmol) under cooling with ice and the mixture was stirred at room temperature for 8 hours. Then to the reaction mixture were added water and ethyl acetate and the organic layer was separated. Then the organic layer was washed successively with water and saturated brine, and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced�th pressure. The residue was purified by chromatography on silica gel, receiving specified in the title compound (341 mg, yield 93%).

1H-NMR (400 MHz, DMSO-d6) δ: -0,24 (s, 9H), of 0.03 (s, 9H), of 0.64 (t, 2H, J=8,12 Hz), of 0.87 (t, 2H, J=8,12 Hz), and 1.00 (s, 9H), of 1.02 (s, 6H), 1.26 in (d, 3H, J=of 6.96 Hz), of 1.53 (t, 2H, J=6,38 Hz), 2,50 (s, 2H), 2,60-2,65 (m, 2H), 3,24-or 3.28 (m, 5H), 3,55-3,65 (m, 3H), 3,70-of 3.77 (m, 1H), 4,23-4,34 (m, 1H), 5,41 (s, 2H), 6,09 (s, 2H), 6,76 (s, 1H), of 7.36-7,47 (m, 6H), 7,58-7,67 (m, 6H), 8,10-8,16 (m, 2H).

(Stage 3)

Obtaining [(2-(tert-butyldiphenylsilyl)-1-methylethyl]methylamide 2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indole-6-carboxylic acid

In an argon atmosphere to a solution of [2-(tert-butyldiphenylsilyl)-1-methylethyl]amide 2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indole-6-carboxylic acid (337 mg, 0,39 mmol) in N,N-dimethylformamide (3.4 ml) was added sodium hydride (19 mg, 0.47 mmol) and methyliodide (36 μl, of 0.58 mmol) under cooling with ice and the mixture was stirred at room temperature for 3 hours. To the reaction mixture were added water and ethyl acetate and the organic layer was separated. Then the organic layer was washed successively with water and saturated brine, and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure�research Institute. The residue was purified by chromatography on silica gel, receiving specified in the title compound (149 mg, yield 44%).

1H-NMR (400 MHz, DMSO-d6) δ: -0,23 (s, 9H), to -0.05 (s, 9H), of 0.59-0,62 (user.m, 2H), 0,86 (DD, 2H, J=10,44, 5,80 Hz), and 0.98 (s, 9H), of 1.02 (s, 6H), of 1.08 (user.s, 3H), 1,54 (t, 2H, J=of 6.26 Hz), 2,50 (s, 2H), 2,61-of 2.64 (user.m, 2H), 2,83 (s, 3H), 3,21-3,29 (m, 2H), 3,38-of 3.46 (m, 0,6 H), 3,54-3,83 (m, 1,4 H), 3,58 (t, 2H, J=8,00 Hz), 4,04-4,17 (m, 0,6 H), 4.72 in-4,90 (user.m, 0,4 H), 5,39-5,41 (user.m, 2H), 5,69-of 5.83 (m, 0,6 H), 5,96-6,09 (m, 1,4 H), was 6.77 (s, 1H), 7,11 (d, 1H, J=9,04 Hz), 7,17-of 7.75 (m, 12H).

(Stage 4)

Preparation of (2-hydroxy-1-methylethyl)methylamide 2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indole-6-carboxylic acid

A solution of [2-(tert-butyldiphenylsilyl)-1-methylethyl]methylamide 2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indole-6-carboxylic acid (145 mg, 0,17 mmol) in N,N-dimethylformamide (1.2 ml) was added to the fluoride tetrabutylammonium (1.7 ml, 1.7 mmol), concentrated at reduced pressure. Added Ethylenediamine (0,29 ml) and the mixture was stirred under heating at 90°C for 14 hours. After cooling, to the mixture was added water and ethyl acetate and the organic layer was separated, washed successively with water, 10% aqueous citric acid solution and saturated brine, and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate con�was interaval under reduced pressure. The residue was purified by chromatography on silica gel, receiving specified in the title compound (57 mg, yield 90%).

Example 8

Obtaining N-[2-(6-gidroximetil-6-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl]-N-methyl-2-(2-oxopiperidin-1-yl)acetamide

(Stage 1)

Obtaining N-(2-{6-benzoyloxymethyl-6-methyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-methylamine

In the same way as in example 1, step 7, specified in the title compound was obtained from tert-butyl-6-benzoyloxymethyl-3-iodo-6-methyl-4,5,6,7-tetrahydroindazole-1-carboxylate obtained in reference example 5 and 1-tert-butyl-6-methyl-2-brilinta-1,6-dicarboxylate obtained in reference example 2.

(Stage 2)

Obtaining N-(2-{6-gidroximetil-6-methyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-methyl-2-(2-oxopiperidin-1-yl)acetamide

To a solution of N-(2-{6-benzoyloxymethyl-6-methyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-methylamine (150 mg, 0,23 mmol) in N,N-dimethylformamide (3 ml) was added (2-oxopiperidin-1-yl)acetic acid, obtained in reference example 6 (43 mg, 0.27 mmol), hydrochloride 1-ethyl-3-(3-dimetilan�propyl)carbodiimide (52 mg, 0,27 mmol) and the monohydrate of 1-hydroxybenzotriazole (37 mg, 0.27 mmol) and the mixture was stirred at room temperature over night. To the reaction mixture were added ethyl acetate and water and the organic layer was separated, washed successively with water and saturated brine, and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel, receiving N-(2-{6-benzoyloxymethyl-6-methyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-methyl-2-(2-oxopiperidin-1-yl)acetamide (158 mg). In a nitrogen atmosphere to a solution of the obtained N-(2-{6-benzoyloxymethyl-6-methyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-methyl-2-(2-oxopiperidin-1-yl)acetamide (158 mg) in a mixed solvent of methanol (0.8 ml) and tetrahydrofuran (0.8 ml) was added 20% palladium hydroxide-on-carbon (150 mg) at room temperature and the mixture was stirred in hydrogen atmosphere at normal pressure for 4 hours. The reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure, while receiving specified in the title compound (120 mg, yield 75%).

1H-NMR (400 MHz, DMSO-d6) δ: -0,21 (9H, s) -0,04 (9H, s), to 0.67 (2H, t, J=of 7.86 Hz), 0,86(2H, t, J=8,06 Hz), of 0.93 (3H, C), 1,44-of 1.73 (6H, m), 2,12-of 2.21 (2H, m), 2,39 (1H, d, J=16,52 Hz), 2,59-to 2.65 (2H, m), 2,59 (1H, d, J=16,52 Hz), up 3.22 (3H, s), 3,27 (2H, s), and 3.31 (2H, t, J=8,06 Hz) and 3.59 (2H, t, J=of 7.86 Hz), 3,81 (2H, s), 4,71 (1H, t, J=5,44 Hz), 5,38 (1H, d, J=11,28 Hz), 5,41 (1H, d, J=11,69 Hz), of 6.02 (1H, d, J=10,48 Hz), 6,07 (1H, d, J=10,88 Hz), 6,74 (1H, s), 7,06 (1H, d, J=7,66 Hz), 7,60 (1H, s), Of 7.64 (1H, d, J=8,06 Hz).

(Stage 3)

Obtaining N-[2-(6-gidroximetil-6-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl]-N-methyl-2-(2-oxopiperidin-1-yl)acetamide

A solution of N-(2-{6-gidroximetil-6-methyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)-N-methyl-2-(2-oxopiperidin-1-yl)acetamide (63 mg, 0.09 mmol) in N,N-dimethylformamide (1.5 ml) was added to the fluoride tetrabutylammonium (0.6 ml, 0.6 mmol), concentrated at reduced pressure. Added Ethylenediamine (0.2 ml) and the mixture was stirred under heating at 80°With during the night. After cooling, was added water and ethyl acetate and the organic layer was separated. Then the organic layer was washed successively with water and saturated brine, and dried over sodium sulfate. The sodium sulfate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by thin layer chromatography on silica gel, receiving specified in the title compound (5.5 mg, yield 16%).

The compounds of examples 9-381 received the same� same way as in the above examples. Structural formulas and data of the spectra of1H-NMR are shown in tables 1-1 - 1-78.

In the tables of compounds in optically active form, indicated (as an optically active form) under No. example.

The spectra of1H-NMR of compounds in solutions of CDCl3or DMSO-D6was measured with the use of tetramethylsilane as an internal standard and all values of δ shown in M. D. Unless specifically stated in the table, the resolving power was measured at 400 MHz.

Symbols in the tables have the following meanings:

s: singlet

d: doublet

t: triplet

q: Quartet

dd: double doublet

ddd: double doublet of doublet

brs: broadened singlet

m: multiplet;

J: constant interaction

Table 1-1
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
11H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-to 1.61 (2H, m) of 1.75 (3H, s), is 2.41 (2H, s), 2,63-2,69 (2H, m), 3,17 (3H, C), 6,57-6,61 (1H, m), of 6.85-6,90 (1H, m), 7,21-of 7.25 (1H, m), 7,52-EUR 7.57 (1H, m), 11,41 (1H, usher.C) 12,54 (1H, usher.C).337 335

21H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), of 1.03 (t, 3H, J=7,00 Hz), 1,58 (t, 2H, J=6,29 Hz), 2,41 (s, 2H), 2,62-2,73 (m, 2H), 3,66 (square, 2H, J=7,00 Hz), 6,60 (s, 1H), at 6.84 (d, 1H, J=8,05 Hz), 7,21 (s, 1H), 7,55 (d, 1H, J=8,05 Hz), 11,38 (s, 1H), of 12.53 (s, 1H).351349
31H-NMR (DMSO-D6) δ: of 1.01 (6H, s, 6H), of 1.57 (2H, t, 2H, J=6,01 Hz), is 2.41 (2H, s, 2H), to 2.65 (2H, t, 2H, J=6,01 Hz), 3,27 (3H, s, 3H), 5,09 (2H, s, 2H), 6,56 (1H, s, 1H), 6,89 (1H, d, 1H, J=8,01 Hz), 7,28-7,34 (6H, m, 6H), 7,47 (1H, d, 1H, J=8,01 Hz), about 11.28 (1H, s, 1H), 12,49 (1H, s, 1H).429427
41H-NMR (DMSO-D6) δ: 0,95-of 1.07 (3H, m), 1,01 (6H, C), a 1.54 to 1.61 (2H, m), 2.21 are-of 2.30 (2H, m), 2,37-to 2.48 (2H, m), is 2.41 (2H, s), 2,62-to 2.73 (2H, m), 3,16-3,24 (1H, m), 3,19 (3H, s), 3,44-of 3.53 (4H, m), 6,57-6,62 (1H, m), 6,86-6,93 (1H, m), 7,26-7,32 (1H, m), 7,51-EUR 7.57 (1H, m), is 11.39 (1H, usher.C) of 12.53 (1H, usher.C).436434

51H-NMR DMSO-D 6) δ: of 1.01 (6H, s) of 1.36 (3H, d, J=5.8 Hz), 1,54-1,62 (2H, m), 2,42 (2H, s), 2,63-of 2.72 (2H, m), 2,96-3,17 (2H, m), 3,20-3,50 (6H, m), 3,65-of 3.99 (4H, m), 6,63-6,69 (1H, m), of 6.96-7,03 (1H, m), 7,34-7,40 (1H, m), 7,61-7,66 (1H, m), 10,29 (1H, usher.C) 11,48 (1H, usher.C) 12,60 (1H, usher.C).436434

Table 1-2
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
61H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,54-to 1.61 (2H, m), 2,42 (2H, s), 2,63-2,71 (2H, m), 3,21 (3H, C), 3,31-3,37 (2H, m), 3,76-3,81 (2H, m), 3,83-of 3.87 (2H, m), 4,00 (2H, s), 6,57-only 6.64 (1H, m), 6,90-6,97 (1H, m), 7,29-to 7.33 (1H, m), 7,55-7,61 (1H, m), 11,48 (1H, usher.C) of 12.55 (1H, usher.C).436434

71H-NMR (DMSO-D6) δ: of 1.01 (6H, C) of 1.04 and 1.10 (3H, m), 1,54-1,60 (2H, m), 2,42 (2H, s), 2,65-2,70 (2H, m), 2,82 (3H, s), 3,20-was 3.54 (2H, m), 3,84-of 4.04 (1H, m), 4,46-4,89 (1H, m), 6,60 (1H, d, J=1.2 Hz), 7,00 (1H, DD, J=8,1, 1,4 Hz), 7,41-the 7.43 (1H, m), 7,51 (1H, d, J=8,1 Hz), 11,38 (1H, usher.C) 12,52 (1H, usher.C).381 379
81H-NMR (DMSO-D6) δ: 0,92 (3H, s), of 1.53 to 1.68 (6H, m), 2,17 (2H, s) to 2.29 (1H, d, J=16,12 Hz), of 2.54 (1H, d, J=16,12 Hz), 2,59-2,77 (2H, m), 3,19 (3H, s), 3,20-of 3.25 (2H, m), 3,26 (2H, s), of 3.77 (2H, s), 4,62 (1H, s), 6,60 (1H, C) at 6.92 (1H, d, J=7,66 Hz), 7,31 (1H, s), 7,56 (1H, d, J=7,66 Hz), 11,38 (1H, s) 12,50 (1H, s).450448

91H-NMR (DMSO-D6) δ: of 1.02 (s, 6H), 1,59 (t, 2H, J=6,29 Hz), 2,43 (s, 2H), 2,66-of 2.75 (m, 2H), 6,66 (s, 1H), was 7.08 (t, 1H, J=7,39 Hz), 7,34 (t, 2H, J=7,94 Hz), 7,61 (s, 2H), 7,81 (d, 2H, J=7,50 Hz), 8,02 (s, 1H), 10,15 (C, 1H), range of 11.64 (s, 1H), was 12.61 (s, 1H).385383
101H-NMR (DMSO-D6) δ: 0,99 (s, 6H), 1.55 V (t, 2H, J=6,29 Hz), is 2.40 (s, 2H), 2,58-of 2.67 (m, 2H), 3,39 (s, 3H), of 6.49 (s, 1H), about 6,82 (d, 1H, J=7,94 Hz), 7,07-to 7.18 (m, 3H), 7,20-7,29 (m, 3H), 7,43 (s, 1H), at 11.37 (s, 1H), 12,54 (C, 1H).399397

Table 1-3
No. etc.Structural formula NMRMS (M+H)MS (M-N)
111H-NMR (DMSO-D6) δ: of 0.92 (9H, s), 1,01 (6H, s), 1.56 to to 1.61 (2H, m), 2,42 (2H, s), 2,65-2,71 (2H, m), 3,12 (2H, d, J=6.3 Hz), 6,61 (1H, s), 7,47-7,54 (2H, m), 7,92 (1H, s), 8,17 (1H, t, J=6.3 Hz), 11,51 (1H, usher.C) 12,57 (1H, usher.C).379377

121H-NMR (DMSO-D6, 300 MHz) δ: 0,89 (3H, s), of 0.91 (3H, C), 1,01 (6H, s), 1,55-to 1.61 (2H, m), 1,81-of 1.92 (1H, m), 2,42 (2H, s), 2,64-2,71 (2H, m), 3,06-of 3.12 (2H, m), 6,61 (1H, s), 7,45-7,54 (2H, m), 7,90-of 7.93 (1H, m), 8,26-8,32 (1H, m), 11,51 (1H, usher.C) 12,56 (1H, usher.C).365363
131H-NMR (DMSO-D6) δ: of 0.92 (9H, s), 1,01 (6H, s), of 1.09 (3H, d, J=6,8 Hz), 1,53-1,62 (2H, m), 2,42 (2H, s), 2,63-2,77 (2H, m), 3,96-4,06 (1H, m), 6,61 (1H, s), 7,43-EUR 7.57 (2H, m), 7,72-7,80 (1H, m) to 7.89 (1H, usher.C) 11,47 (1H, usher.C) 12,56 (1H, usher.C).393391
141H-NMR (DMSO-D6) δ: of 1.01 (6H, s, A 1.54 to 1.61 (2H, m), of 2.21 (3H, s), 2,29-of 2.38 (4H, m), 2,42 (2H, s), 2,64-2,71 (2H, m), 3,44-3,61 (4H, m), 6,59-6,62 (1H, m), 6,97-7,01 (1H, m), of 7.42-of 7.46 (1H, m), 7,51-to 7.55 (1H, m), of 11.45 (1H, usher.C) 12,57 (1H, usher.C).392390

151H-NMR (DMSO-D6) δ: 0,67-1,17 (9H, m), 1,01 (6H, s), 1,54-1,62 (2H, m), 2,42 (2H, s), 2,64-to 2.73 (2H, m), 3,03 (3H, s), 3,36 (2H, s), 6,60 (1H, s), of 6.96-was 7.08 (1H, m), 7,41-of 7.48 (1H, m), 7,49-7,56 (1H, m), 11,38 (1H, usher.C) of 12.55 (1H, usher.C).393391

Table 1-4
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
161H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,30-of 1.43 (2H, m), 1,53-to 1.61 (2H, m), 1,69-to 1.82 (2H, m), 2,42 (2H, s), 2,62-to 2.73 (2H, m), 3,13-up 3.22 (2H, m), 3,64-4,01 (3H, m), 4,78 (1H, d, J=4,2 Hz), 6,59-6,63 (1H, m), of 6.96-7,01 (1H, m), Of 7.42 was 7.45 (1H, m), 7,50-7,55 (1H, m) 11,44 (1H, usher.C) 12,56 (1H, usher.C).393391

171H-NMR (DMSO-D6, 300 MHz) δ: 0,72-of 0.95 (6H, m), 1,01 (6H, s), 1,54-1,62 (2H, m), 1.93 and-of 2.06 (1H, m), 2,42 (2H, s), 2,64-of 2.72 (2H, m) to 2.94 (3H, s), 3,17-3,30 (2H, m), 6,60 (1H, s), 6,94-of 6.99 (1H, m), value of 7, 37-the 7.43 (1H, m), 7,50-7,54 (1H, m), 11,41 (1H, usher.C) of 12.55 (1H, usher.C).379377
181H-NMR (DMSO-D6, 300 MHz) δ: 0,75 is 0.81 (6H, m), 0,95-1,04 (4H, m), 1,01 (6H, s), 1,13-of 1.27 (2H, m), 1,55-to 1.61 (2H, m), 2,39-2,43 (2H, m), 2,65-to 2.73 (2H, m), 2,79-2,90 (4H, m), 6,59-6,62 (1H, m), to 6.88-7,00 (1H, m), value of 7, 37-7,40 (1H, m), 7,50-7,54 (1H, m), 11,36 (1H, usher.C) 12,54 (1H, usher.C).407405
191H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-to 1.61 (2H, m), 2,42 (2H, s), 2,64-of 2.72 (2H, m), 3.46 in is 3.57 (4H, m), 3,58-to 3.67 (4H, m), 6,60-6,63 (1H, m), 6,99-to 7.04 (1H, m), 7,45-of 7.48 (1H, m), 7,51-7,56 (1H, m), 11,47 (1H, usher.C) 12,57 (1H, usher.C).379377

201H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.15 (3H, d, J=6,7 Hz), 1,55-was 1.62 (2H, m), 2,42 (2H, s), 2,64-to 2.73 (2H, m), 3,33-3,39 (1H, m), 3.45 points-of 3.53 (1H, m), 3,98 of 4.09 (1H, m), 4,71(1H, user.C), 6,61 (1H, usher.C) of 7.46-7,54 (2H, m), of 7.88-of 7.95 (2H, m), of 11.53 (1H, usher.C) is 12.58 (1H, usher.C).367365

Table 1-5
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
211H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.15 (3H, d, J=6,7 Hz), 1,55-was 1.62 (2H, m), 2,42 (2H, s), 2,64-of 2.72 (2H, m), 3,26-and 3.31 (1H, m), or 3.28 (3H, s), 3,40-of 3.46 (1H, m), 4,18-to 4.26 (1H, m), 6,59-of 6.65 (1H, m), 7,45-to 7.55 (2H, m), 7,90-7,94 (1H, m), with 8.05 (1H, d, J=8,1 Hz), of 11.53 (1H, usher.C) is 12.58 (1H, usher.C).381379

221H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,06-to 1.14 (3H, m), 1,54-to 1.61 (2H, m), 2,42 (2H, s), 2,64-of 2.72 (2H, m), of 2.81 (3H, s), is 3.08-to 3.56 (5H, m), 3,95-to 4.26 (1H, m), 6,57-only 6.64 (1H, m), 6,94-of 6.99 (1H, m), 7,40-the 7.43 (1H, m), 7,49-7,54 (1H, m), 11,41 (1H, usher.C) 12,56 (1H, usher.C).395393
23 1H-NMR (DMSO-D6) δ: of 0.91 (3H, d, J=7,0 Hz), of 0.93 (3H, d, J=7,0 Hz), of 1.01 (6H, s), 1,55-to 1.61 (2H, m), 1,90-2,00 (1H, m), 2,42 (2H, s), 2,65-of 2.72 (2H, m), 3,53 (2H, t, J=5,6 Hz), 3,80-3,88 (1H, m), 4,56 (1H, t, J=5,7 Hz), 6,60-6,63 (1H, m), of 7.48-7,54 (2H, m), 7,74-7,79 (1H, m), 7,90-7,94 (1H, m), to 11.52 (1H, usher.C) is 12.58 (1H, usher.C).395393

241H-NMR (DMSO-D6) δ: of 0.91 (3H, d, J=5.8 Hz), of 0.93 (3H, d, J=5.8 Hz), 1,01 (6H, s), 1,54-1,62 (2H, m), 1.85 to 1,95 (1H, m), 2,42 (2H, s), 2,64-to 2.73 (2H, m), 3,26 (3H, s), 3,42-3,51 (2H, m), 3,97-of 4.04 (1H, m), 6,59-of 6.65 (1H, m), of 7.48-to 7.55 (2H, m), of 7.88-7,98 (2H, m), 11,51 (1H, usher.C) 12,57 (1H, usher.C).409407
251H-NMR (DMSO-D6) δ: of 0.68 and 1.05 (6H, m), 1,01 (6H, s), 1,55-was 1.62 (2H, m), 1,72-of 1.97 (1H, m), 2,42 (2H, s), 2,64-2,71 (2H, m), 2,79-2,87 (3H, m), 3,45-3,71 (3H, m), 4,66-is 4.85 (1H, m), 6,56-6,61 (1H, m), 6,95-7,07 (1H, m), 7,39-7,55 (2H, m), 11,36-11,42 (1H, m), 12,52-12,57 (1H, m).409407

Table 1-6
No. etc.Structural formulaNMRMS (M+�) MS (M-N)
261H-NMR (DMSO-D6) δ: of 0.69 and 1.05 (6H, m), and 1.00 (6H, s), 1,53-to 1.61 (2H, m), 1,76-of 1.98 (1H, m), is 2.41 (2H, s), 2,63-2,71 (2H, m), of 2,75 2,84 (3H, m), 3,25-of 3.31 (3H, m), 3,42-3,65 (3H, m), 6,55-6,62 (1H, m), 6,91-6,98 (1H, m), Value of 7, 37-of 7.42 (1H, m), of 7.46-7,54 (1H, m), at 11.37-11,44 (1H, m), 12,54 (1H, usher.C).423421
271H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,58 (2H, t, J=6,40 Hz), is 2.41 (2H, s), 2,63-2,69 (2H, m), of 6.52 (1H, s), 7,28 (1H, d, J=at 8.60 Hz), 7,44 (1H, d, J=at 8.60 Hz), 7,49-7,63 (3H, m), 7,95-with 8.05 (3H, m), 10,14 (1H, s), 11,24 (1H, C), Of 12.46 (1H, s).385383
281H-NMR (DMSO-D6) δ: 1,00 (6H, s), of 1.07 and 1.13 (3H, m), of 1.53 to 1.60 (2H, m), 2,28-of 2.35 (2H, m), is 2.40 (2H, s), 2,62-2,69 (2H, m), of 6.46-6,50 (1H, m), 7,03-was 7.08 (1H, m), 7,35-7,39 (1H, m), 7.87 ft-7,91 (1H, m), 9,72 (1H, usher.C) to 11.11 (1H, usher.C) 12,41 (1H, usher.C).337335

291H-NMR (DMSO-D6) δ: 1,00 (6H, s), of 1.52 of-1.59 (2H, m), is 2.40 (2H, s), 2,60-2,69 (2H,m), 5,69 (2H, usher.C), 6,41-of 6.45 (1H, m), 6,80-6,86 (1H, m), 7,29-7,34 (1H, m), 7,65-to 7.68 (1H, m) to 8.36 (1H, usher.C) 11,00 (1H, usher.C) 12,40 (1H, usher.C).324322
301H-NMR (DMSO-D6) δ: of 0.99 (6H, s), of 1.55 (2H, t, J=6,06 Hz), 2,39 (2H, s), 2,58-of 2.66 (2H, m), 3,40 (3H, s), of 6.49 (1H, s), is 6.81 (1H, d, J=at 8.60 Hz), 7,07 (1H, s), 7,11-7,22 (3H, m), 7.23 percent-7,30 (2H, m), 7,38 (1H, d, J=to 8.38 Hz), 11,22 (1H, s) 12,48 (1H, s).399397
311H-NMR (DMSO-D6) δ: of 0.99 (6H, s), 1,53-1,58 (2H, m), 2,39 (2H, s), 2,59-to 2.65 (2H, m), 3.43 points (3H, C), 6,50 (1H, s), 6,84-to 6.88 (1H, m), 7,09-7,12 (1H, m), of 7.36-of 7.42 (2H, m), 7,50-members, 7.59 (2H, m), 7,60-7,65 (1H, m), of 11.25 (1H, usher.C) 12,49 (1H, usher.C).467465

Table 1-7
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
321H-NMR (DMSO-D6, 300 MHz) δ: of 0.91 (3H, t, J=7.5 Hz), 1,01 (6H, C), a 1.54 to 1.61 (2H,m), 1,95-of 2.05 (2H, m), is 2.41 (2H, s), 2,62-2,71 (2H, m), 3,18 (3H, C), 6,57-6,61 (1H, m), 6,84-6,89 (1H, m), 7,21-of 7.24 (1H, m), 7,51-EUR 7.57 (1H, m), is 11.39 (1H, usher.C) of 12.53 (1H, usher.C).351349
331H-NMR (DMSO-D6, 300 MHz) δ: of 1.01 (6H, s), 1,25-of 1.36 (2H, m), 1.41 to 1,71 (8H, m), is 2.41 (2H, s), 2,52-2,60 (1H, m), 2,64-2,70 (2H, m), 3,18 (3H, C), 6,57-6,62 (1H, m), 6,83-6,89 (1H, m), 7,22-7,26 (1H, m), 7,51-EUR 7.57 (1H, m), 11,38 (1H, usher.C) 12,54 (1H, usher.C).391389

341H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.03 (3H, d, J=6,8 Hz), 1,55-to 1.61 (2H, m), is 2.41 (2H, s), 2,64-2,70 (2H, m), 3,20 (3H, s), 4,00-is 4.15 (2H, m), 6,58-only 6.64 (1H, m), 6,86-6,91 (1H, m), 7,22-7,30 (1H, m), 7,52-members, 7.59 (1H, m), 11,41 (1H, usher.C) of 12.53 (1H, usher.C).367365
351H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-to 1.61 (2H, m), 2,42 (2H, s), 2,63-2,71 (2H, m), 3,21 (3H, C), 3,66-to 3.76 (2H, m), 4,48 (1H, t, J=5,7 Hz), to 6.57-6,63 (1H, m), 6,84-6,90 (1H, m), 7,21-7,27 (1H, m), 7,50-7,58 (1H, m), 11,42 (1H, usher.C) 12,54 (1H, usher.C).353351
36 1H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-to 1.61 (2H, m), is 2.41 (2H, s), 2,63-of 2.72 (2H, m), 3,14-of 3.24 (6H, m), 3,73 (2H, s), 6,57-6,63 (1H, m), of 6.85-at 6.92 (1H, m), 7.23 percent-7,27 (1H, m), 7,52-7,58 (1H, m), 11,42 (1H, usher.C) 12,54 (1H, usher.C).367365

Table 1-8
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
371H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.20 (6H, user.C) a 1.54 to 1.61 (2H, m), is 2.41 (2H, s), 2,63-2,71 (2H, m), 3,30 (3H, s), of 4.88 (1H, usher.C), 6,54-6,62 (1H, m), about 6,82-6,90 (1H, m), 7,21-7,28 (1H, m), of 7.46-7,51 (1H, m), made 11.32 (1H, usher.C) for 12.51 (1H, usher.C).381379
381H-NMR (DMSO-D6) δ: of 0.74 (3H, t, J=7,4 Hz), 1,01 (6H, s), of 1.40-1.50 (2H, m), 1,55-to 1.61 (2H, m), 1,95-2,02 (2H, m), 2,42 (2H, s), 2,64-2,69 (2H, m), 3,18 (3H, C), 6,57-6,61 (1H, m), about 6,82-to 6.88 (1H, m), 7,20-7.23 percent (1H, m), 7,52-EUR 7.57 (1H, m) 11,40 (1H, usher.C) 12,54 (1H, usher.C).365363
39 1H-NMR (DMSO-D6) δ: of 0.90 (3H, C), of 0.92 (3H, C), 1,01 (6H, s), 1,55-to 1.61 (2H, m), 2,42 (2H, s), 2,45-2,53 (1H, m), 2,64-2,70 (2H, m), 3,16 (3H, C), 6,58-6,62 (1H, m), of 6.85-6,90 (1H, m), 7,21-7,26 (1H, m), 7,53-7,58 (1H, m)That is 11.39 (1H, usher.C) 12,54 (1H, usher.C).365363

401H-NMR (DMSO-D6) δ: of 0.75 (3H, C), and 0.77 (3H, C), 1,01 (6H, s), 1,55-to 1.61 (2H, m), 1,89-of 1.93 (2H, m), 1,94-2,02 (1H, m), 2,42 (2H, s), 2,64-2,70 (2H, m), 3,18 (3H, C), 6,57-6,61 (1H, m), 6,81-6,86 (1H, m), 7,18-7,22 (1H, m), 7,52-7,58 (1H, m) 11,40 (1H, usher.C) 12,54 (1H, usher.C).379377
411H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.08 (3H, d, J=6,4 Hz), 1,54-to 1.61 (2H, m), 2,42 (2H, s), 2,64-2,70 (2H, m), of 3.04 (3H, s), 3,21 (3H, s), with 3.79 (1H, square, J=6.3 Hz), to 6.58-6,62 (1H, m), 6,86-6,91 (1H, m), 7.24 to 7,28 (1H, m), 7,54 and 7.60 (1H, m) 11,40 (1H, usher.C), 12,53-of 12.55 (1H, usher.m).381379

Table 1-9
No. etc.Structural formulaNMRMS (M-N)
421H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,12-of 1.49 (6H, m) of 1.53 to 1.63 (2H, m), is 2.41 (2H, s), 2,63-2,69 (2H, m), 2,93-3,58 (6H, m), 6,54-to 6.58 (1H, m), 6,80-6,86 (1H, m), 7,18-of 7.25 (1H, m), 7,44-7,49 (1H, m), of 11.29 (1H, usher.C) for 12.51 (1H, usher.C).395393
431H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,54-to 1.61 (2H, m), is 2.41 (2H, s), 2,64-of 2.72 (2H, m), 3,18-3,27 (1H, m), 3,20 (3H, s), 3,40-3,48 (1H, m), 3,97-of 4.04 (1H, m), 4,50-4,56 (1H, m), of 4.77 (1H, d, J=6,6 Hz), 6,56-only 6.64 (1H, m), 6,87-6,93 (1H, m), 7,26-7,31 (1H, m), 7,51-EUR 7.57 (1H, m), 11,42 (1H, usher.C) of 12.53 (1H, usher.C).383381

441H-NMR (DMSO-D6) δ: to be 0.97 and 1.05 (3H, m), 1,01 (6H, s), 1,55-1,60 (2H, m), 2,42 (2H, s), 2,64-2,70 (2H, m), 3,18 (3H, s), 3,29-3,37 (2H, m), of 3.75 (2H, s), 6,58-6,61 (1H, m), of 6.85-6,91 (1H, m), 7,22-7,27 (1H, m), 7,52-to 7.55 (1H, m), of 11.43 (1H, usher.C) 12,54 (1H, usher.C).381379
451H-NMR (DMSO-D6) δ: of 1.01 (6H, C), 1,55-to 1.61 (2H, m), 2,42 (2H, s), 2,64-2,69 (2H, m), 3,23 (3H, s) to 4.41 (2H, s), 6,60-6,63 (1H, m), 6,71-6,78 (2H, m), 6,87-6,93 (1H, m), 6,99-to 7.04 (1H, m), 7,20-7,27 (2H, m), of 7.36-7,40 (1H, m), 7,56-7,61 (1H, m), 11,47 (1H, user.C) of 12.55 (1H, usher.C).429427
461H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.03 (3H, d, J=6,9 Hz), 1.56 to to 1.61 (2H, m), is 2.41 (2H, s), 2,64-2,71 (2H, m), 3,20 (3H, C), 4,01-4,10 (1H, m), 4,73 (1H, d, J=7,3 Hz), to 6.57-6,62 (1H, m), of 6.85-6,91 (1H, m), 7.23 percent-7,28 (1H, m), 7,53-7,58 (1H, m), of 11.43 (1H, usher.C) 12,54 (1H, usher.C).367365

1H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-to 1.61 (2H, m), is 2.41 (2H, s), 2,63-2,71 (2H, m), 3,10 (3H, C), 3,21 (3H, C), 3,35-of 3.43 (1H, m), 3,45-was 3.54 (1H, m), 3.75 to-3,81 (1H, m), 4,68-4,74 (1H, m), 6,58-only 6.64 (1H, m), 6,87-6,93 (1H, m), 7,25-7,32 (1H, m), 7,54-7,63 (1H, m), of 11.43 (1H, usher.C) of 12.55 (1H, usher.C).
Table 1-10
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
471H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,54-1,62 (2H, m), 2,39-of 2.44 (2H, m), 2,64-2,70 (2H, m), is 3.08 (6H, s), up 3.22 (3H, s), 3,30-to 3.38 (1H, m), 3.43 points-3,52 (1H, m), 3,86-3,94 (1H, m), 6,58-to 6.66 (1H, m), 6,87-6,98 (1H, m), 7,25-7,34 (1H, m), 7,53-7,63 (1H, m), 11,46 (1H, usher.C) of 12.55 (1H, usher.C).411409
48397395

491H-NMR (DMSO-D6) δ: 0,66 (3H, t, J=7,4 Hz), 1,01 (6H, s), 1,26-of 1.38 (1H, m), 1.41 to of 1.54 (1H, m), 1,55-to 1.61 (2H, m), 2,42 (2H, s), 2,63-2,70 (2H, m), 3,21 (3H, s), 3,82-are 3.90 (1H, m), 4,67 (1H, d, J=7,7 Hz), to 6.58-6,62 (1H, m), 6,84-6,90 (1H, m), 7,21-7,30 (1H, m), 7,51-7,61 (1H, m), of 11.43 (1H, usher.C) of 12.55 (1H, usher.C).381379
501H-NMR (DMSO-D6) δ: 0,61-was 0.77 (3H, m), 1,01 (6H, s), 1,39-of 1.65 (4H, m), 2,42 (2H, s), 2,63-2,70 (2H, m), 3,09 (3H, s), up 3.22 (3H, s), 3,58-to 3.67 (1H, m), 6,57-to 6.67 (1H, m), about 6,82-6,94 (1H, m), 7,21-7,31 (1H, m), 7,53-7,63 (1H, m), 11,42 (1H, usher.C) of 12.55 (1H, usher.C).395393
511H-NMR (DMSO-D6) δ: 1,00 (6H, s), 1,53-to 1.61 (2H, m), is 2.41 (2H, s), 2,63-2,69 (2H, m), 3,17 (3H, C), 4,17 (2H, d, J=6,0 Hz), 6,13 (1H, t, J=6.1 Hz), 6,55-6,59 (1H, m), of 6.85-6,90 (1H, m), made 7.16 interest-7.23 percent (3H, m), 7,25-7,31 (3H, m), 7,50-,55 (1H, m) to 11.35 (1H, usher.C) for 12.51 (1H, usher.C).428426

Table 1-11
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
521H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,52-to 1.69 (3H, m), 1,70-1,80 (1H, m), 1,84-of 1.96 (2H, m), is 2.41 (2H, s), 2,62-2,71 (2H, m), 3,19 (3H, C), 3,59-3,66 (1H, m), of 3.77 to 3.85 (1H, m), 4,15-to 4.23 (1H, m), 6,56-6,63 (1H, m), 6,84-6,93 (1H, m), 7,22-7,29 (1H, m), 7,51-members, 7.59 (1H, m), 11,42 (1H, usher.C) 12,54 (1H, usher.C).393391
531H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,53-to 1.61 (2H, m), is 2.41 (2H, s), 2,62-to 2.73 (2H, m), of 3.07 (3H, C), 3,13-3,26 (1H, m), 3,21 (3H, C), 3,38-of 3.45 (1H, m), 4,08-4,16 (1H, m), to 4.98 (1H, d, J=7,3 Hz), to 6.57-6,63 (1H, m), Of 6.85-at 6.92 (1H, m), 7,25-7,31 (1H, m), 7,52-members, 7.59 (1H, m) 11,44 (1H, usher.C) of 12.53 (1H, usher.C).397395

541H-I�R (DMSO-D 6) δ: of 1.01 (6H, s), 1,54-to 1.61 (2H, m), is 2.41 (2H, s), 2,62-2,69 (2H, m), 3,14 (3H, C), 5,47 (2H, usher.C), 6,54-to 6.58 (1H, m), 6,83-to 6.88 (1H, m), 7,21-of 7.25 (1H, m), of 7.48-7,54 (1H, m), made 11.32 (1H, usher.C) for 12.51 (1H, usher.C).338336
551H-NMR (DMSO-D6) δ: 0.79 in (3H, t, J=7.5 Hz), 1,01 (6H, s), 1,37-of 1.46 (2H, m), 1,55-to 1.61 (2H, m), is 2.41 (2H, s), 2,64-2,69 (2H, m), 3,19 (3H, C), 3,22-3,27 (2H, m), 3,76 (2H, s), 6,58-6,61 (1H, m), of 6.85-6,90 (1H, m), 7.23 percent-7,26 (1H, m), 7,51-7,56 (1H, m), 11,41 (1H, usher.C) 12,54 (1H, usher.C).395393
561H-NMR (DMSO-D6) δ: 0.94 in (3H, C), is 0.96 (3H, C), 1,01 (6H, s), 1,55-to 1.61 (2H, m), is 2.41 (2H, s), 2,64-2,71 (2H, m), 3,18 (3H, C), 3,38-3,47 (1H, m), of 3.75 (2H, s), 6,57-6,63 (1H, m), of 6.85-6,91 (1H, m), 7.23 percent-7,27 (1H, m), 7,51-EUR 7.57 (1H, m), 11,41 (1H, usher.C) of 12.53 (1H, usher.C).395393

Table 1-12
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
57 1H-NMR (DMSO-D6) δ: 0.98 in (6H, s), 1,51-of 1.57 (2H, m), 2,39 (2H, s), 2,58-2,63 (2H, m), 3.43 points (3H, s), of 6.46-is 6.51 (1H, m), about 6,82-to 6.88 (1H, m), 7,20-7.23 percent (1H, m), to 7.33-7,39 (1H, m), of 7.48-7,54 (2H, m), 7,63-to 7.68 (1H, m), To 7.77-of 7.82 (2H, m), 11,38 (1H, usher.C) for 12.51 (1H, usher.C).427425
581H-NMR (DMSO-D6) δ: 0,86 (3H, d, J=6,9 Hz), 1,01 (6H, s), 1,55-to 1.61 (2H, m), is 2.41 (2H, s), 2,62-2,73 (3H, m), 3,04-of 3.09 (1H, m), 3,11 (3H, C), 3,18 (3H, usher.C), 3,45-3,50 (1H, m), 6,58-6,62 (1H, m), 6,83-6,89 (1H, m), 7.23 percent-7,27 (1H, m), 7,52-7,58 (1H, m) 11,40 (1H, usher.C) of 12.53 (1H, usher.C).395393

591H-NMR (DMSO-D6) δ: 1,00 (6H, s), 1,54-1,59 (2H, m), 2,22 (3H, s), is 2.40 (2H, s), 2,62-of 2.68 (2H, m) to 3.38 (3H, s), of 6.02 (1H, s), of 6.52-6,56 (1H, m), 6,81-6,86 (1H, m), 7,15-to 7.18 (1H, m), 7,41 was 7.45 (1H, m) to 11.35 (1H, usher.C) 12,52 (1H, usher.C).404402
601H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,22-of 1.38 (1H, m), 1,39-of 1.48 (2H, m), 1,55-1,71 (4H, m), 2,42 (2H, s), 2,64-2,70 (2H, m), 2,92-of 3.00 (2H, m), 3,17 (3H, C), 3,69-of 3.77 (2H, m), 6,59-6,62 (1H, m), 6,86-6,91 (1H, m), 7.23 percent-7,26 (1H, m), 7,54-members, 7.59 (1H, m), 11,38 (1H, usher.C) 12,54 (1H, usher.C). 407405
611H-NMR (DMSO-D6) δ: of 0.87 (3H, d, J=6,9 Hz), 1,01 (6H, s), 1,55-1,60 (2H, m), is 2.41 (2H, s), 2,52-of 2.58 (1H, m), 2,64-2,70 (2H, m), 3,12-3,19 (1H, m), 3,18 (3H, C), 3,49-to 3.56 (1H, m), 4,51 (1H, t, J=5.4 Hz), to 6.58-6,62 (1H, m), 6,86-6,90 (1H, m), 7,25-7,28 (1H, m), 7,53-7,56 (1H, m), at 11.37 (1H, usher.C) 12,52 (1H, usher.C).381379

Table 1-13
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
621H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,54-to 1.61 (2H, m), 2.21 are-of 2.27 (2H, m), is 2.41 (2H, s), 2,63-2,70 (2H, m), of 3.12 (3H, s), 3,18 (3H, s), 3,44-3,50 (2H, m), 6,57-6,63 (1H, m), 6,83-6,90 (1H, m), 7,20-7,26 (1H, m), 7,51-EUR 7.57 (1H, m), 11,42 (1H, usher.C) 12,54 (1H, usher.C).381379
631H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-to 1.61 (2H, m), 2,15-of 2.23 (2H, m), is 2.41 (2H, s), 2,62-of 2.72 (2H, m), 3,18 (3H, s), 3,50-3,59 (2H, m), 4,39 (1H, t, J=5.1 Hz), to 6.57-6,63 (1H, m), 6,84-6,91 (1H, m), 7,217,27 (1H, m), 7,51-members, 7.59 (1H, m), 11,42 (1H, usher.C) 12,54 (1H, usher.C).367365

641H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,34-of 1.46 (1H, m), 1,51-1,62 (5H, m), 1,92 (3H, C), 2,15-of 2.23 (1H, m), 2,42 (2H, s), 2,44-2,53 (1H, m), 2,63 is 2.76 (3H, m), 3,17 (3H, C), 3,65-3,73 (1H, m), is 4.21 stable at 4.29 (1H, m), 6,57-only 6.64 (1H, m), 6,86-6,94 (1H, m), 7.23 percent-7,28 (1H, m), 7,54-members, 7.59 (1H, m) 11,40 (1H, usher.C) 12,54 (1H, usher.C).448446
651H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,40-of 1.54 (4H, m), 1.56 to to 1.68 (4H, m), from 2.00 (3H, s), 2,09-2,19 (1H, m), 2,42 (2H, s), 2,61-of 2.72 (4H, m), 3,16 (3H, C), 6,57-only 6.64 (1H, m), 6,84-6,91 (1H, m), 7,20-7,27 (1H, m), 7,52-7,58 (1H, m), 11,38 (1H, usher.C) 12,54 (1H, usher.C).420418

661H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,54-to 1.61 (2H, m), 1,69-to 1.79 (1H, m), 1,96-of 2.06 (1H, m), 2,42 (2H, s), 2,63-to 2.74 (2H, m), 2,85-to 2.94 (1H, m), 3,20 (3H, s), 3,47-was 3.54 (1H, m), 3,55-3,65 (2H, m), 3,66-3,73 (1H, m), 6,57-6,63 (1H, m), of 6.85-at 6.92 (1H, m), 7,21-7,27 (1H, m), 7,54-members, 7.59 (1H, m), 11,42 (1H, usher.C) 12,54 (1H, usher.C).393 391

Table 1-14
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
671H-NMR (DMSO-D6) δ: of 0.64 (3H, d, J=6,9 Hz) to 0.72 (3H, d, J=6,9 Hz), 1,01 (6H, s), 1,55-to 1.61 (2H, m), 1,70-1,80 (1H, m), 2,42 (2H, s), 2,63-2,71 (2H, m), up 3.22 (3H, s), 3,63-3,70 (1H, m), 4,59 (1H, d, J=8,1 Hz), 6,57-6,62 (1H, m), 6,83-6,89 (1H, m), 7,22-7,27 (1H, m), 7,52-EUR 7.57 (1H, m), at 11.37 (1H, usher.C) for 12.51 (1H, usher.C).395393

681H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1.56 to to 1.61 (2H, m), 2,42 (2H, s), 2,64-2,71 (2H, m), 3,20 (3H, C) to 5.05 (1H, d, J=7,3 Hz), 5,49 (1H, d, J=7,3 Hz), to 6.58-6,63 (1H, m), 6.67 cm to 6.75 (1H, m), 6,98-7,03 (2H, m), 7,11-7,17 (1H, m), 7,18-7.23 percent (3H, m), 7,47-7,54 (1H, m), of 11.43 (1H, usher.C) 12,54 (1H, usher.C).429427
691H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.08 (6H, s), 1.56 to to 1.60 (2H, m), 2,18 (2H, s), is 2.41 (2H, s), 2,65-2,69 (2H, m), 3,20 (3H,s), 4,94 (1H, s), 6,59-6,61 (1H, m), 6,83-6,87 (1H, m), 7,21-7.23 percent (1H, m), 7,53-EUR 7.57 (1H, m), 11,42 (1H, usher.C) 12,54 (1H, usher.C).395393
701H-NMR (DMSO-D6) δ: of 0.91 (3H, t, J=7.5 Hz), 1,01 (6H, s), 1.56 to to 1.61 (2H, m), 1,97-2,05 (2H, m), 2,43 (2H, s), 2,66-2,71 (2H, m), 3,18 (3H, s), 6,63-to 6.66 (1H, m), of 6.85-6,90 (1H, m), 7,24-7,27 (1H, m), 7,52-7,58 (1H, m), 11,41 (1H, usher.C).351349, 385

711H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,26-of 1.36 (1H, m), 1,54-1,60 (2H, m), 1,62-of 1.76 (2H, m), 1,87-of 1.97 (1H, m), 2,05-to 2.13 (1H, m), 2,28-a 2.36 (1H, m), is 2.41 (2H, s), 2,63-2,71 (2H, m), 3,18 (3H, C), 3,47-of 3.53 (1H, m), 3,55-3,61 (1H, m), 4,05-4,13 (1H, m), 6,57-6,62 (1H, m), 6,83-to 6.88 (1H, m), 7,20-7,26 (1H, m), 7,52-7,56 (1H, m), 11,41 (1H, usher.C) of 12.53 (1H, usher.C).407405

Table 1-15
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
721H-NMR (DMSO-D6) δ: of 0.63 to 0.76 (2H, m), from 0.92 to 1.06 (1H, m), 1,01 (6H, s), 1,09-to 1.21 (2H, m), 1,49-1,62 (7H, m), 1,64-of 1.75 (1H, m), 1,87-of 1.93 (2H, m), is 2.41 (2H, s), 2,63-2,70 (2H, m), 3,18 (3H, C), 6,56-6,62 (1H, m), 6,78-of 6.85 (1H, m), 7,17-7,21 (1H, m), 7,51-EUR 7.57 (1H, m), is 11.39 (1H, usher.C) of 12.53 (1H, usher.C).419417

731H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,54-1,62 (2H, m), 2,42 (2H, s), 2,63-to 2.73 (2H, m), 3,23 (3H, s), 4,48 (2H, s), 5,97-6,03 (2H, m), 6,60-to 6.67 (1H, m), 7,01-7,07 (1H, m), 7,38-of 7.42 (1H, m), 7,44-7,50 (2H, m), 7,58-7,63 (1H, m), 11,56 (1H, usher.C) 12,57 (1H, usher.C).430428
741H-NMR (DMSO-D6) δ: 0,62 was 1.06 (2H, m), 1,01 (6H, s), 1,28-of 1.49 (2H, m), 1,55-of 1.93 (6H, m), 2,10-to 2.29 (1H, m), is 2.41 (2H, s), 2,64-2,71 (2H, m), 3,12-of 3.18 (6H, m), 3,19-3,24 (1H, m), 6,58-6,63 (1H, m), of 6.85-6,89 (1H, m), 7,21-7,27 (1H, m), 7,52-7,58 (1H, m), 11,36 (1H, usher.C) of 12.53 (1H, usher.C).435433
751H-NMR (DMSO-D6) δ: of 0.95 (6H, C) of 1.01 (6H, s), 1,55-to 1.61 (2H, m), 2,42 (2H, s), 2,64-2,70 (2H, m), 3,11 (2H, s), 3,13 (3H, C), 4,36 (2H, s), 6,59-6,63 (1H, m), 6,84-to 6.88 (1H, m), 7,25-7,31 (4H, m), 7,32-of 7.7 (2H, m), 7,49-7,53 (1H, m), 11,41 (1H, usher.C) of 12.53 (1H, usher.C).485483

761H-NMR (DMSO-D6) δ: of 0.85 (6H, C) of 1.01 (6H, s), 1,54-1,62 (2H, m), is 2.41 (2H, s), 2,61-of 2.75 (2H, m), 3,13 (3H, s), 3,23 (2H, d, J=5,6 Hz), 4,48-4,56 (1H, m), 6,55-only 6.64 (1H, m), of 6.85-to 6.95 (1H, m), 7,24-7,32 (1H, m), Of 7.48-7,56 (1H, m), at 11.37 (1H, usher.C) of 12.53 (1H, usher.C).395393

Table 1-16
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
771H-NMR (DMSO-D6) δ: 0,62-0,86 (2H, m), of 0.94 and 1.13 (3H, m), 1,01 (6H, s), 1,26-of 1.33 (1H, m), 1,44-of 1.64 (6H, m), 1,66-of 1.74 (1H, m), is 2.41 (2H, s), 2,64-2,70 (2H, m), 3,21 (3H, s), 3,62-to 3.67 (1H, m), 4,65 (1H, d, J=7,7 Hz), 6,58-6,63 (1H, m), 6,83-to 6.88 (1H, m), 7,22-7,27 (1H, m), 7,52-EUR 7.57 (1H, m), 11,41 (1H, usher.C) of 12.53 (1H, usher.C).435433

78 1H-NMR (DMSO-D6) δ: 0,61-0,86 (2H, m), from 0.92 to 1.15 (3H, m), 1,01 (6H, s), 1,26-of 1.33 (1H, m), 1,44-of 1.63 (6H, m), 1,67-of 1.74 (1H, m), 2,42 (2H, s), 2,64-2,70 (2H, m), 3,21 (3H, s), 3,62-to 3.67 (1H, m), 4,65 (1H, d, J=7,7 Hz), 6,57-6,62 (1H, m), 6,83-to 6.88 (1H, m), 7,21-7,26 (1H, m), 7,53-EUR 7.57 (1H, m), 11,42 (1H, usher.C) 12,54 (1H, usher.C).435433
791H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,24-of 1.33 (2H, m), 1,36-of 1.47 (4H, m), 1,55-to 1.61 (2H, m), 2,17-of 2.35 (4H, m), is 2.41 (2H, s), 2,63-2,71 (2H, m), 2,78-2,87 (2H, m), 3,17 (3H, C), 6,57-6,61 (1H, m), 6,83-6,89 (1H, m), 7,21-7,27 (1H, m), 7,50-7,56 (1H, m) 11,40 (1H, usher.C) of 12.53 (1H, usher.C).420418

801H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,54-to 1.61 (2H, m), 2,27-is 2.37 (4H, m), is 2.41 (2H, s), 2,63-2,71 (2H, m), 2,86 (2H, s), 3,18 (3H, s), 3.46 in-of 3.53 (4H, m), 6,57-only 6.64 (1H, m), of 6.85-at 6.92 (1H, m), 7.24 to 7,31 (1H, m), 7,51-EUR 7.57 (1H, m) 11,41 (1H, usher.C) of 12.53 (1H, usher.C).422420
811H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,27-of 1.39 (2H, m), 1,55-to 1.61 (2H, m), 1,68-to 1.77 (2H, m), 2,00-2,10 (2H, m), is 2.41 (2H, s), 2,52 at 2.59 (2H, m), 2,64-2,71 (2H, m), 2,84 (2H, s), 3,01-3,09 1H, m), 3,17 (6H, s), 6,56-6,62 (1H, m), about 6,82-6,90 (1H, m), 7,22-7,28 (1H, m), 7,49-EUR 7.57 (1H, m), 11,41 (1H, usher.C) of 12.53 (1H, usher.C).450448

Table 1-17
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
821H-NMR (DMSO-D6) δ: 0,62-0,74 (2H, m), 1,01 (6H, s), 1,37-of 1.50 (2H, m), 1.56 to to 1.61 (2H, m), 1,63-1,70 (2H, m), 1,86-to 1.94 (2H, m), 2,10-of 2.20 (1H, m), is 2.41 (2H, s), 2,64-2,70 (2H, m), 2,95-3,05 (1H, m), 3,12-3,19 (6H, m), 6,58-only 6.64 (1H, m), of 6.85-6,91 (1H, m), 7,21-7,27 (1H, m), 7,53-7,58 (1H, m), 11,36 (1H, usher.C) of 12.53 (1H, usher.C).435433
831H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-to 1.61 (2H, m), 1.85 to of 1.93 (2H, m), 2,14-of 2.21 (2H, m), is 2.41 (2H, s), 2,64-2,70 (2H, m), 3,19 (3H, s), 3,29-3,37 (1H, m), 3,71 (2H, s), 6,59-only 6.64 (1H, m), 6,90-of 6.96 (1H, m), 7,28-to 7.33 (1H, m), 7,55-to 7.60 (1H, m), 11,46 (1H, usher.C) 12,54 (1H, usher.C).420418

84 1H-NMR (DMSO-D6) δ: 0,97-of 1.09 (2H, m), 1,01 (6H, s), 1,23-of 1.34 (2H, m), 1,49-1,62 (4H, m), 1,74-to 1.86 (2H, m), of 2.16 and 2.26 (1H, m), is 2.41 (2H, s), 2,63-2,71 (2H, m), 3,15 (3H, s), 3,59-to 3.67 (1H, m), 4,19-to 4.26 (1H, m), 6,56-6,63 (1H, m), about 6,82-6,89 (1H, m), of 7.19-7,26 (1H, m), 7,51-EUR 7.57 (1H, m), 11,36 (1H, usher.C) of 12.53 (1H, usher.C).421419
851H-NMR (DMSO-D6) δ: 0,94-1,06 (8H, m), 1,28-of 1.37 (2H, m), 1,55-1,60 (2H, m), 1,61-to 1.79 (4H, m), 2,20-to 2.29 (1H, m), is 2.41 (2H, s), 2,62-2,71 (2H, m), 3,15 (6H, s), 3,19-3,24 (1H, m), 6,57-only 6.64 (1H, m), 6,83-6,89 (1H, m), 7,20-7,27 (1H, m), 7,52-7,58 (1H, m), 11,36 (1H, usher.C) of 12.53 (1H, usher.C).435433

861H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,54-to 1.61 (2H, m), is 2.41 (2H, s), 2,63-2,71 (2H, m), 3,23 (3H, C), a 4.53 (2H, s), 6,59-to 6.66 (1H, m), 7,01-was 7.08 (1H, m), 7,17-7,22 (1H, m), 7,25-7,31 (1H, m), value of 7, 37-7,44 (1H, m), EUR 7.57-7,63 (1H, m), 8,12-8,17 (2H, m), 11,49 (1H, usher.C) of 12.55 (1H, usher.C).430428

Table 1-18
No. etc.Structural formulaNMR MS (M+H)MS (M-N)
871H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,53-to 1.61 (2H, m), 1,65-of 1.83 (2H, m), is 2.41 (2H, s), 2,61-of 2.72 (2H, m), 3,19 (3H, C), 3,48-of 3.66 (4H, m), 3,73-3,84 (2H, m), 3,99-4,07 (1H, m), 6,54-to 6.66 (1H, m), 6,84-6,94 (1H, m), 7,21-to 7.33 (1H, m), 7,50-7,58 (1H, m), of 11.43 (1H, usher.C) of 12.55 (1H, usher.C)423421

881H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,22-1,33 (2H, m), 1,54-to 1.61 (2H, m), 1,65-of 1.74 (2H, m), is 2.41 (2H, s), 2,62-2,71 (2H, m), 3,19 (3H, C), 3,21-3,27 (2H, m), 3,35-3,44 (1H, m), 3,66-3,74 (2H, m), 3,82 (2H, s), 6,57-only 6.64 (1H, m), 6,86-6,93 (1H, m), 7.24 to 7,30 (1H, m), 7,51-EUR 7.57 (1H, m), of 11.43 (1H, usher.C) 12,54 (1H, usher.C).437435
891H-NMR (DMSO-D6) δ: of 1.01 (6H, C), a 1.54 to 1.63 (2H, m), 2,42 (2H, s), 2,64-to 2.73 (2H, m), 3,23 (3H, C), 4,59 (2H, s), 6,60-to 6.67 (1H, m), about 6,82 (1H, s), 7,01-7,07 (1H, m) to 7.04 (1H, s), of 7.36-of 7.42 (1H, m), of 7.48 (1H, s), EUR 7.57-7,65 (1H, m), of 11.53 (1H, usher.C) 12,56 (1H, usher.C).403401

90 1H-NMR (DMSO-D6) δ: 0,90-of 1.04 (1H, m), 1,01 (6H, s), 1,22-1,47 (3H, m), 1,48-to 1.61 (3H, m), 1,63 is 1.71 (1H, m), 2,00-2,07 (1H, m), of 2.18 and 2.26 (1H, m), 2,42 (2H, s), 2,63-2,71 (2H, m), 3,18 (3H, C), 3,22-3,30 (1H, m), 3,59-to 3.67 (1H, m), and 3.72 and 3.78 (1H, m), 6,56-6,63 (1H, m), of 6.79-6,87 (1H, m), 7,18-of 7.25 (1H, m), 7,51-EUR 7.57 (1H, m) 11,40 (1H, usher.C) 12,54 (1H, usher.C).421419
911H-NMR (DMSO-D6) δ: to 0.89 (9H, s), 1,01 (6H, s), 1,55-to 1.61 (2H, m), 1,98 (2H, s), is 2.41 (2H, s), 2,64-2,71 (2H, m), 3,17 (3H, s), 6,55-of 6.63 (1H, m), was 6.77-of 6.85 (1H, m), made 7.16 interest-7.23 percent (1H, m), 7,51-EUR 7.57 (1H, m), 11,38 (1H, usher.C) of 12.53 (1H, usher.C).393391

Table 1-19
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
921H-NMR (DMSO-D6) δ: from 0.87 to 0.98 (2H, m), 1,01 (6H, s), 1,35-of 1.46 (4H, m), 1,55-to 1.61 (2H, m), 1,61-1,70 (2H, m), 2.00 in of 2.06 (2H, m), 2,08-2,17 (1H, m), is 2.41 (2H, s), 2,64-2,71 (2H, m), 3,18 (3H, C), 6,56-6,62 (1H, m), 6,80-6,87 (1H, m), 7,18-7,24 (1H, m), 7,51-EUR 7.57 (1H, m), at 11.37 (1H, usher.C) of 12.53 (1H, usher.C).405 403
931H-NMR (DMSO-D6) δ: 0,63-0,75 (2H, m), 1,01 (6H, s), 1,03-to 1.14 (4H, m), 1,30-to 1.38 (2H, m), 1.41 to of 1.49 (2H, m), 1,50-1,60 (5H, m), 1,98-of 2.05 (2H, m), is 2.41 (2H, s), 2,64-2,71 (2H, m), 3,17 (3H, C), 6,57-only 6.64 (1H, m), About 6,82-to 6.88 (1H, m), 7,20-of 7.25 (1H, m), 7,52-EUR 7.57 (1H, m), is 11.39 (1H, usher.C) 12,54 (1H, usher.C).433431

941H-NMR (DMSO-D6) δ: from 0.92 to 0.99 (2H, m), 1,01 (6H, s), 1,46-of 1.53 (2H, m), 1.56 to to 1.61 (2H, m), 1,89-of 1.98 (3H, m), is 2.41 (2H, s), 2,64-2,70 (2H, m), 3,16-3,26 (2H, m), 3,18 (3H, C), 3,69-of 3.75 (2H, m), 6,56-6,63 (1H, m), 6,81-6,87 (1H, m), 7,18-7,24 (1H, m), 7,52-7,58 (1H, m) 11,40 (1H, usher.C) 12,54 (1H, usher.C).421419
95
stereoisomer D. 96
1H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,06-of 1.18 (1H, m), 1,31-of 1.49 (2H, m), 1.56 to to 1.61 (2H, m), 1,65-to 1.77 (2H, m), 2,42 (2H, s), 2,64-of 2.72 (2H, m), 2,90-2,96 (1H, m), 3,05-3,13 (1H, m), 3,21 (3H, C), 3,36-of 3.42 (1H, m), 3,62-of 3.69 (1H, m), 3.75 to-3,81 (1H, m), 4,75 (1H, d, J=7,7 Hz), to 6.57-only 6.64 (1H, m), of 6.85-6,91 (1H, m), 7,22-7,27 (1H, m), 7,53-7,58 (1H, m), of 11.43 (1H, usher.C) of 12.53 (1H, usher.C).437435

96

stereoisomer Ave 95
1H-NMR (DMSO-D6) δ: 0,93-1,11 (2H, m), 1,01 (6H, s), 1,28-of 1.85 (5H, m), 2,42 (2H, s), 2,64-2,70 (2H, m), 2,97-3,16 (2H, m), 3,21 (3H, C), 3,57-of 3.78 (2H, m), 4,45-4,49 (1H, m), 4,96 (1H, d, J=8,1 Hz), to 6.58-6,61 (1H, m), 6,84-6,89 (1H, m), 7.23 percent-7,27 (1H, m), 7,52-EUR 7.57 (1H, m), 11,42 (1H, usher.C) of 12.53 (1H, usher.C).437435

Table 1-20
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
971H-NMR (DMSO-D6) δ: 0,48-0,60 (1H, m), 0,72-0,84 (1H, m), of 0.91 (3H, d, J=6,7 Hz), of 1.01 (6H, s), 1,06-of 1.18 (2H, m), 1,35-1,45 (1H, m), 1,51-of 1.70 (8H, m), of 2.05 to 2.14 (1H, m), 2,42 (2H, s), 2,64-2,71 (2H, m), 3,18 (3H, C), 6,58-6,63 (1H, m), 6,80-6,86 (1H, m), of 7.19-7,24 (1H, m), 7,53-7,58 (1H, m), at 11.37 (1H, usher.C) of 12.53 (1H, usher.C).433431

981H-NMR (DMSO-D6) δ: 0,77-0,89 (1H, m), of 0.92 (3H, d, J=6,7 Hz), of 1.01 (6H, s), 1,05-to 1.14 (1H, m), 1,45-of 1.54 (2H, m), 1.56 to to 1.69 (3H m), 2,09-2,17 (1H, m), 2,42 (3H, s), 2,65-2,70 (2H, m), 3,14-of 3.25 (2H, m), 3,19 (3H, C), 3,72-3,81 (2H, m), 6,57-6,62 (1H, m), 6,81-6,86 (1H, m), 7,20-of 7.24 (1H, m), 7,54-members, 7.59 (1H, m), 11,38 (1H, usher.C) 12,54 (1H, usher.C).435433
99
stereoisomer D. 100
1H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,08-of 1.65 (10H, m), 1,76-of 1.84 (1H, m), 2,42 (2H, s), 2,65-2,71 (2H, m), 2,84 (3H, C), 3,15 (3H, C), 3,36 is 3.40 (1H, m), 6,58-only 6.64 (1H, m), 6,84-6,89 (1H, m), 7,21-7,27 (1H, m), 7,53-members, 7.59 (1H, m), 11,38 (1H, usher.C) of 12.53 (1H, usher.C).435433

100
stereoisomer D. 99
1H-NMR (DMSO-D6) δ: 0.80 to of 1.08 (2H, m), 1,01 (6H, s), 1,16-to 1.34 (2H, m), 1,51-of 1.66 (4H, m), 1,81-of 1.96 (2H, m), 2,20-of 2.30 (1H, m), 2,42 (2H, s), 2,65-2,77 (3H, m), of 3.12 (3H, s), 3,16 (3H, s), 6,59-of 6.65 (1H, m), of 6.85-at 6.92 (1H, m), 7.23 percent-7,29 (1H, m), 7,54-members, 7.59 (1H, m), 11,38 (1H, usher.C) 12,54 (1H, usher.C).435433
1011H-NMR (DMSO-D6) δ: 0,66-0,78 (2H, m), 1,01 (6H, s), 1,36-of 1.48 (2H, m), 1,55-1,65 (4H, m), 1,68-of 1.76 (2H, m), 2,06-of 2.15 (1H, m), 2,42 (2H, s), 2,64-of 2.72 (2H, m), 3,15 (3H, s), 3,20-3,29 (1H, m), 4,36 (1H, d, J=4,6 Hz), 6,59-of 6.65 (1H, m), 6,83-6,90 (1H, m), 7,21-7,28 (1H, m), 7,53-7,61 (1H, m), To 11.35 (1H, usher.C) 12,52 (1H, usher.C).421419

Table 1-21
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
1021H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,15-of 1.45 (6H, m), 1,49-1,62 (4H, m), 1,67 is 1.78 (2H, m), is 2.41 (2H, s), 2,62-2,71 (2H, m), 3,23 (3H, C), 4,57-a 4.64 (1H, m), of 6.52-to 6.57 (1H, m), 6,83-6,89 (1H, m), 7,22-7,27 (1H, m), Of 7.42-of 7.48 (1H, m), 11,26 (1H, usher.C) 12,49 (1H, usher.C).421419
1031H-NMR (DMSO-D6) δ: 0,94 was 1.06 (1H, m), 1,01 (6H, s), 1,37-of 1.44 (2H, m), 1,55-to 1.61 (2H, m), 1,64 is 1.71 (1H, m), 1,86-of 1.96 (3H, m), is 2.41 (2H, s), 2,63-2,71 (2H, m), 2,80-2,87 (1H, m), 3,13-3,21 (1H, m), 3,18 (3H, C), 3,61-3,68 (2H, m), 6,58-6,62 (1H, m), about 6,82-6,87 (1H, m), 7,18-7.23 percent (1H, m), 7,52-EUR 7.57 (1H, m), is 11.39 (1H, usher.C) of 12.53 (1H, usher.C).421419

1041H-NMR DMSO-D 6) δ: of 1.01 (6H, s), of 1.02 (3H, d, J=7,0 Hz), 1,54-1,62 (2H, m), 2.21 are-to 2.29 (2H, m), 2,38-2.49 USD (2H, m), 2,42 (2H, s), 2,64-2,70 (2H, m), 3,15-3,24 (1H, m), 3,19 (3H, C), 3,45-3,51 (4H, m), 6,56-6,62 (1H, m), Of 6.85-6,93 (1H, m), 7,26-to 7.33 (1H, m), 7,51-EUR 7.57 (1H, m), is 11.39 (1H, usher.C) 12,54 (1H, usher.C).436434
1051H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-to 1.61 (2H, m), 1,64-of 1.73 (4H, m), 2,14-of 2.20 (2H, m), 2,42 (2H, s), 2,64-to 2.73 (2H, m), 3,17-3,26 (2H, m), 3,19 (3H, C), of 3.77 (2H, s), 6,58-only 6.64 (1H, m), 6,89-of 6.96 (1H, m), 7,27-to 7.33 (1H, m), 7,54-7,61 (1H, m), of 11.45 (1H, usher.C) 12,54 (1H, usher.C).434432

1061H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.02 (3H, C), of 1.40 (3H, C), 1,55-to 1.61 (2H, m), is 2.41 (2H, s), 2,59-2,71 (3H, m), 2,78-2,86 (1H, m), 3,14-3,19 (1H, m), 3,24 (3H, s), 6,59-only 6.64 (1H, m), to 6.88-6,93 (1H, m), 7,25-7,29 (1H, m), 7,56-7,61 (1H, m), is 11.39 (1H, usher.C) 12,52 (1H, usher.C).435433

Table 1-22
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
1071H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,22-of 1.39 (2H, m), 1,54-of 1.66 (4H, m), 1,95-of 2.06 (2H, m), 2,42 (2H, s), 2,53-2,61 (2H, m), 2,64-2,70 (2H, m), 2,82 (2H, s), 3,17 (3H, s), 3,29-3,37 (1H, m), 4,46 (1H, d, J=3,9 Hz), 6,57-6,61 (1H, m), 6,83-to 6.88 (1H, m), 7,22-7,26 (1H, m), 7,50-7,56 (1H, m) 11,40 (1H, usher.C) of 12.53 (1H, usher.C).436434

1081H-NMR (DMSO-D6) δ: of 1.00 (3H, d, J=7,7 Hz), of 1.01 (6H, s), 1,20-1,32 (2H, m), 1,52-to 1.67 (4H, m), 2,01-2,10 (1H, m), 2,19-to 2.29 (1H, m), 2,35-2,47 (1H, m), 2,42 (2H, s), 2,57-of 2.64 (1H, m), 2,65-2,70 (2H, m), 3,17 (3H, C), 3,18-of 3.25 (1H, m), 3,27-3,37 (1H, m), of 4.45 (1H, d, J=3,9 Hz), 6,56-6,61 (1H, m), 6,83-6,90 (1H, m), 7.23 percent-7,29 (1H, m), 7,50-EUR 7.57 (1H, m), is 11.39 (1H, usher.C) of 12.53 (1H, usher.C).450448
1091H-NMR (DMSO-D6) δ: 0,85-0,97 (1H, m), 1,01 (6H, s), 1,23-of 1.39 (2H, m), 1,45-of 1.53 (1H, m), 1.55 V-to 1.63 (2H, m), 1,67-of 1.76 (2H, m), 1,79-of 1.89 (1H, m), 2,42 (2H, s), 2,64-2,70 (2H, m), 2,71-2,78 (1H, m), 2,80-of 2.91 (2H, m), 3,17 (3H, C), or 3.28-of 3.43 (1H, m), 4,48 (1H, d, J=4,9 Hz), to 6.57-6,62 (1H, m), 6,83-6,90 (1H, m), 7,21-7,27 (1H, m), 7,50-7,58 (1H, m) 11,40 (1H, usher.C) of 12.53 (1H, usher.C).436434

1101H-NMR (DMSO-D6) δ: 0,89-0,99 (1H, m), 1,01 (6H, s), 1,26-of 1.39 (1H, m), 1,44-of 1.53 (1H, m), 1,55-was 1.62 (2H, m), 1,67 is 1.78 (2H, m), 1,80-1,90 (1H, m), 2,42 (2H, s), 2,63-2,70 (2H, m), 2,71-2,78 (1H, m), 2,80-of 2.93 (2H, m), 3,17 (3H, C), 3,33-3,44 (1H, m), 4,48 (1H, d, J=4,6 Hz), to 6.57-6,62 (1H, m), about 6,82-6,90 (1H, m), 7,21-7,27 (1H, m), 7,49-7,58 (1H, m) 11,40 (1H, usher.C) of 12.53 (1H, usher.C).436434
1111H-NMR (DMSO-D6) δ: 0,90-of 1.09 (2H, m), 1,01 (6H, s), 1,20-of 1.36 (2H, m), 1,40-1,62 (4H, m), 1,69 and 2.26 (4H, m), is 2.41 (2H, s), 2,57-2,79 (4H, m), 3,18 (3H, C), 3,21-to 3.41 (1H, m), to 4.41-4,50 (1H, m), 6,55-of 6.63 (1H, m), 6,83-6,91 (1H, m), 7,22-7,31 (1H, m), 7,51-EUR 7.57 (1H, m), 11,38 (1H, usher.C) of 12.53 (1H, usher.C).450448

Table 1-23
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
1121H-NMR (DMSO-D6) δ: 0,90-of 1.09 (3H, m), 1,01 (6H, s), 1,19-of 2.27 (10H, m), 2,42 (2H, s), 2,57-2,80 (3H, m), 3,18 (3H, C), 3,22-to 3.41 (1H, m), 4,40-4,51 (1H, m, 6,54-6,63 (1H, m), 6,83-6,91 (1H, m), 7.23 percent-7,32 (1H, m), 7,51-EUR 7.57 (1H, m), 11,38 (1H, usher.C) of 12.53 (1H, usher.C).450448
1131H-NMR (DMSO-D6) δ: 0,96-1,04 (9H, m), 1,23-of 1.36 (2H, m), 1,54-1,62 (2H, m), 1,67 is 1.78 (2H, m), 2,04-2,12 (1H, m), 2,22-of 2.30 (1H, m), is 2.37 to 2.45 (1H, m), 2,42 (2H, s), 2,58-of 2.75 (3H, m), 3,00-is 3.08 (1H, m), 3,17 (3H, C), 3,18 (3H, C), 3,19-of 3.25 (1H, m), 6,57-6,61 (1H, m), 6,84-6,90 (1H, m), 7,25-7,30 (1H, m), 7,50-7,56 (1H, m) 11,40 (1H, usher.C) of 12.53 (1H, usher.C).464462

1141H-NMR (DMSO-D6) δ: 0,89 was 1.06 (1H, m), 1,01 (6H, s), 1,23-of 1.39 (1H, m), 1,49-1,62 (3H, m), 1,79-of 1.88 (2H, m), 1,90-2,00 (1H, m), 2,42 (2H, s), 2,47-by 2.55 (1H, m), 2,63-2,69 (2H, m), of 2,75 2,82 (1H, m), 2,85-to 2.94 (2H, m), 3,05-3,14 (1H, m), 3,15-of 3.21 (6H, m), 6,56-6,62 (1H, m), 6,83-6,90 (1H, m), 7,21-7,27 (1H, m), 7,50-7,58 (1H, m), 11,41 (1H, usher.C) of 12.53 (1H, usher.C).450448
1151H-NMR (DMSO-D6) δ: 0,90-0,99 (1H, m), 1,01 (6H, s), 1,23-of 1.40 (1H, m), 1,48-1,62 (3H, m), 1,78-of 1.88 (2H, m), 1,90-2,00 (1H, m), 2,42 (2H, s), 2,48 is 2.55 (1H, m), 2,63-2,70 (2H, m), of 2,75 2,82 (1H, m), 2,84-to 2.94 (2H, m), 3,04-3,14 (1H, m), 3,15-of 3.21 (6H, m), 6,56-6,62 (1H, m), 6,83-6,90 (1H, m), 7,21-7,28(1H, m), 7,49-7,58 (1H, m), 11,41 (1H, usher.C) of 12.53 (1H, usher.C).450448

1161H-NMR (DMSO-D6) δ: 0,90-1,11 (10H, m), 1,20-of 1.65 (4H, m), 1,80-2,34 (4H, m), 2,42 (2H, s), 2,47-2,59 (1H, m), 2,63-of 2.75 (2H, m), 2,83-3,05 (1H, m), 3,06-3,30 (7H, m), 6,56-6,63 (1H, m), 6,84-6,91 (1H, m), 7.24 to 7,31 (1H, m), 7,51-7,58 (1H, m) 11,40 (1H, usher.C) of 12.53 (1H, usher.C).464462

Table 1-24
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
1171H-NMR (DMSO-D6) δ: 0,90-1,08 (10H, m), 1,19-of 1.64 (4H, m), 1,80-of 2.05 (3H, m), 2,11-of 2.35 (1H, m), 2,42 (2H, s), 2,48-of 2.57 (1H, m), 2,63-of 2.75 (2H, m), 2,83-3,30 (8H, m), 6,57-6,62 (1H, m), of 6.85-6,94 (1H, m), 7.24 to 7,31 (1H, m), 7,51-7,58 (1H, m) 11,40 (1H, usher.C) of 12.53 (1H, usher.C).464462

118 1H-NMR (DMSO-D6) δ: 0,92-1,09 (12H, m), 1,55-1,60 (2H, m), 1,61-is 2.37 (2H, m), is 2.41 (2H, s), 2,56-is 2.88 (6H, m), 3,18 (3H, s), 3,44-3,84 (2H, m), 6,55-of 6.63 (1H, m), 6,83-6,91 (1H, m), 7,22-7,30 (1H, m), 7,50-7,56 (1H, m), 11,41 (1H, usher.C) 12,54 (1H, usher.C).450448
1191H-NMR (DMSO-D6) δ: to 0.96 (6H, d, J=6.3 Hz), 1,01 (6H, s), 1.56 to to 1.60 (2H, m), 1,62-to 1.69 (2H, m), 2,42 (2H, s), 2,57-2,63 (2H, m), 2,65-2,71 (2H, m), 2,84 (2H, s), 3,18 (3H, s), 3,44-3,55 (2H, m), 6,57-6,63 (1H, m), 6,84-6,90 (1H, m), 7.23 percent-7,28 (1H, m), 7,50-EUR 7.57 (1H, m), 11,42 (1H, usher.C) 12,54 (1H, usher.C).450448
1201H-NMR (DMSO-D6) δ: 0,90-1,12 (15H, m), 1,54-1,62 (2H, m), 1,76-2,03 (2H, m), 2,28-2,56 (4H, m), 2,64-2,70 (2H, m), 3,15-3,24 (4H, m), 3,40-3,84 (2H, m), 6,57-6,63 (1H, m), 6,84-6,91 (1H, m), 7,25-7,30 (1H, m), 7,51-7,58 (1H, m), 11,42 (1H, usher.C) 12,54 (1H, usher.C).464462

1211H-NMR (DMSO-D6) δ: from 0.92 to 1.13 (15H, m), 1,55-to 1.61 (2H, m), 1,76-2,02 (2H, m), 2,29-2,56 (4H, m), 2,63-2,70 (2H, m), 3,16-3,24 (4H, m), 3,38-3,51 (2H, m), 6,57-6,62 (1H, m), 6,84-6,90 (1H, m), 7,25-7,30 (1H, m), 7,52-7,56 (1H, m), 11,42 (1H, usher.C) 12,54 (1H, usher.C). 464462

Table 1-25
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
1221H-NMR (DMSO-D6) δ: 0,97-of 1.04 (9H, m), 1,26-of 1.34 (2H, m), 1,35-of 1.43 (4H, m), 1,53-1,62 (2H, m), 2,18-of 2.27 (2H, m), is 2.37 to 2.45 (2H, m), 2,42 (2H, s), 2,64-2,70 (2H, m), 3,18 (3H, C), 3,19-3,23 (1H, m), 6,57-6,62 (1H, m), 6,84-6,91 (1H, m), 7.24 to 7,30 (1H, m), 7,50-7,56 (1H, m), at 11.37 (1H, usher.C) of 12.53 (1H, usher.C).434432

1231H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,26-of 1.38 (2H, m), 1,53-of 1.65 (3H, m), 1,76-to 1.86 (1H, m), 2,42 (2H, s), 2,63-of 2.72 (2H, m), 3,03-3,14 (1H, m), 3,19 (3H, C), 3,21-3,30 (2H, m), 3,50 is 3.57 (1H, m), 3,60-to 3.67 (1H, m), 3,77-3,88 (2H, m), 6,57-of 6.65 (1H, m), of 6.85-6,93 (1H, m), 7.23 percent-7,30 (1H, m), 7,51-EUR 7.57 (1H, m), 11,42 (1H, usher.C) 12,54 (1H, usher.C).437435
1241H-NMR (DMSO-D6) δ: 0,78-of 0.91 (1H, m), and 1.0 (6H, C), 1,05-is 1.51 (6H, m), 1,52-to 1.69 (4H, m), 1,76-of 1.83 (1H, m), 2,14 and 2.26 (1H, m), 2,42 (2H, s), 2,64-2,71 (2H, m), 3,15 (3H, s), 6,59-6,63 (1H, m), 6,83-6,89 (1H, m), 7,22-7,26 (1H, m), 7,53-7,58 (1H, m), Of 11.34 (1H, usher.C) 12,19 (1H, usher.C).405403

1251H-NMR (DMSO-D6) δ: 0,89-0,97 (3H, m), 1,01 (6H, s), 1.56 to to 1.61 (2H, m), 2,06-2,31 (2H, m), is 2.41 (2H, s), 2,65-2,70 (2H, m), 2,72-to 2.94 (3H, m), 3,16-of 3.25 (3H, m), 3,78-3,84 (2H, m), 6,59-only 6.64 (1H, m), 6,89-6,98 (1H, m), 7,28-7,34 (1H, m), 7,54-7,61 (1H, m), 11,42 (1H, usher.C) for 12.51 (1H, usher.C).422420
1261H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-to 1.61 (2H, m), of 1.80 (1H, usher.C), 2,13-to 2.18 (3H, m), is 2.41 (2H, s), 2,64-2,70 (2H, m), 2,92-of 2.97 (2H, m), 3,21 (3H, C), 6,58-6,63 (1H, m), 6,84-6,89 (1H, m), 7,22-7,26 (1H, m), 7,53-7,58 (1H, m), at 11.37 (1H, usher.C) for 12.51 (1H, usher.C).366364

Table 1-26
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
127 1H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,46-to 1.69 (8H, m), 2,34-of 2.45 (2H, m), 2,42 (2H, s), 2,64-of 2.72 (2H, m), 3,18 (3H, s), 3,29-3,36 (2H, m), 3,82 (2H, s), 6,58-of 6.65 (1H, m), 6,90-of 6.96 (1H, m), 7,27-7,35 (1H, m), 7,54-to 7.60 (1H, m) 11,44 (1H, usher.C) 12,54 (1H, usher.C).448446
1281H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-to 1.61 (2H, m), 1,81-2,02 (3H, m), 2,08-to 2.18 (1H, m), is 2.41 (2H, s), 2,64-2,70 (2H, m), 3,21 (3H, s), 4,00-of 4.04 (1H, m), 6,59-6,63 (1H, m), to 6.88-6,93 (1H, m), 7,27-7,30 (1H, m), 7,55-members, 7.59 (1H, m), 7,63 (1H, usher.C) of 11.45 (1H, usher.C) of 12.55 (1H, usher.C).406404

1291H-NMR (DMSO-D6) δ: 0,84-0,92 (3H, m), 1,01 (6H, C), a 1.54 to 1.61 (2H, m), 1,72-of 1.85 (2H, m), 2,42 (2H, s), 2,64-2,71 (2H, m), 3,01-3,52 (5H, m), 3,32 (3H, C), 3,72-3,98 (5H, m), 6,63-to 6.67 (1H, m), 6,95-7,01 (1H, m), To 7.33-value of 7, 37 (1H, m), 7,61-7,65 (1H, m), of 10.25 (1H, usher.C) 11,49 (1H, usher.C).450448
1301H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.08 (3H, d, J=6,6 Hz), 1,55-to 1.61 (2H, m), 2,42 (2H, s), 2,64-2,71 (2H, m), 3,20 (3H, s), 3,47-3,55 (2H, m), 3,56-3,61 (1H, m), 3,76-3,81 (1H, m), 3,98 (1H, d, J=16.5 Hz), 4,03 (1H, d, J=16,8 Hz), 4,08-4,15 (1H, m), 6,59-only 6.64 (1H, m), 6,93-of 6.99 (1H, m), 7,31-of 7.36 (1H, m), 7,55-7,61 (1H, m), 11,46 (1H, usher.C) 12,54 (1H, usher.C).450448

1311H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,32-1,63 (10H, m), 2,42 (2H, s), 2,62-to 2.73 (2H, m), 3,13-3,19 (1H, m), 3,20 (3H, s), 3,37-3,44 (1H, m), 3,64-3,70 (1H, m), 4,04-of 4.12 (1H, m) to 4.92 (1H, d, J=7,4 Hz), 6,56-only 6.64 (1H, m), 6,84-6,94 (1H, m), 7.23 percent-7,31 (1H, m), 7,50-members, 7.59 (1H, m), 11,46 (1H, usher.C) 12,54 (1H, usher.C).451449

Table 1-27
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
1321H-NMR (DMSO-D6) δ: of 0.94-0.98 (6H, m), 1,01 (6H, C), a 1.54 to 1.61 (2H, m), is 2.41 (2H, s), 2,63-2,71 (2H, m), 3,14-3,19 (1H, m), 3,20 (3H, C), 3,34-3,40 (1H, m), 3,41-3,47 (1H, m), 4,03-4,11 (1H, m), 4,90 (1H, d, J=6,6 Hz), 6,56-6,63 (1H, m), of 6.85-at 6.92 (1H, m), 7.24 to 7,31 (1H, m), 7,51-EUR 7.57 (1H, m), of 11.45 (1H, usher.C) of 12.53 (1H, usher.C).425423

1331H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.06 (3H, d, J=7,0 Hz), 1,39-of 1.73 (6H, m), 1,85-2,05 (2H, m), is 2.41 (2H, s), 2,61-to 2.73 (2H, m), 2,88-2,96 (1H, m), 3,16 (3H, C), 3,19-3,27 (1H, m), 4,82-is 4.93 (1H, m), a 6.53-6,62 (1H, m), 6,86-to 6.95 (1H, m), 7.23 percent-7,34 (1H, m), 7,47-7,54 (1H, m), at 11.37 (1H, usher.C) of 12.53 (1H, usher.C).448446
1341H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.09 (3H, d, J=7,1 Hz), 1,55-to 1.61 (2H, m), 1,76-of 1.97 (2H, m), 2,04-2,11 (2H, m), is 2.41 (2H, s), 2,64-2,71 (2H, m), 3,17 (3H, C), 3,21-or 3.28 (1H, m), 3,49-to 3.56 (1H, m), 4,58-of 4.66 (1H, m), 6,56-6,63 (1H, m), to 6.88-6,94 (1H, m), 7,25-7,31 (1H, m), 7,51-EUR 7.57 (1H, m), is 11.39 (1H, usher.C) of 12.53 (1H, usher.C).434432

1351H-NMR (DMSO-D6) δ: 0,99-1,04 (9H, m), 1,55-1,60 (2H, m), 2.21 are-to 2.29 (2H, m), of 2.38 to 2.48 (2H, m), is 2.41 (2H, s), 2,63-2,69 (2H, m), 3,16-3,23 (1H, m), 3,19 (3H, s), 3.45 points-of 3.50 (4H, m), 6,58-6,60 (1H, m), 6,86-6,90 (1H, m), 7,27-7,30 (1H, m), 7,52-7,56 (1H, m), is 11.39 (1H, usher.C) of 12.53 (1H, usher.C).436434
1361H-�Mr (DMSO-D 6) δ: 0,99-of 1.07 (3H, m), 1,01 (6H, s), 1,39-of 1.50 (1H, m), 1,55-to 1.61 (2H, m), 2,08-of 2.24 (3H, m), 2,40-of 2.44 (2H, m), 2,65-2,71 (2H, m), 3,19 (3H, s), 3,40 (1H, d, J=16.9 and Hz), 3,68-3,76 (1H, m), 3,94 (1H, d, J=16.9 and Hz), 6,59-6,63 (1H, m), at 6.92-6,98 (1H, m), 7,30-7,35 (1H, m), 7,56-7,61 (1H, m), 11,41 (1H, usher.C) for 12.51 (1H, usher.C).434432

Table 1-28
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
1371H-NMR (DMSO-D6) δ: 0,96-1,08 (3H, m), 1,01 (6H, s), 1,46-of 1.65 (4H, m), 1,71-1,90 (2H, m), 2,14-2,19 (2H, m), is 2.41 (2H, s), 2,64-2,71 (2H, m), 3,19 (3H, s), 3,42-3,52 (2H, m), 4,04-4,11 (1H, m), 6,58-6,62 (1H, m), 6,91-6,97 (1H, m), 7,30-7,34 (1H, m), 7,54-members, 7.59 (1H, m) 11,40 (1H, usher.C) for 12.51 (1H, usher.C).448446
1381H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-to 1.61 (2H, m), 2,18-of 2.25 (2H, m), 2,42 (2H, s), 2,65-2,71 (2H, m), 3,09-3,14 (2H, m), 3,20 (3H, s), 3,29-to 3.34 (2H, m), 3,51 (2H, s), 6,58-only 6.64 (1H, m), to 6.88-6,94 (1H, m), 7,26-7,31 (1H, m), 7,55-to 7.60 (1H, m), of 11.43 (1H, usher.C) for 12.51 (1H, usher.C).456454

1391H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-to 1.79 (4H, m), 1,84-of 1.95 (2H, m), is 2.41 (2H, s), 2,64-2,70 (2H, m), 3,19 (3H, C), 3,59-3,66 (1H, m), 3,78-of 3.85 (1H, m), 4,16-to 4.23 (1H, m), 6,57-of 6.65 (1H, m), of 6.85-at 6.92 (1H, m), 7.23 percent-7,31 (1H, m), 7,52-7,58 (1H, m), 11,41 (1H, usher.C) of 12.53 (1H, usher.C).393391
1401H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,54 is 1.78 (4H, m), 1,84-of 1.95 (2H, m), is 2.41 (2H, s), 2,62-of 2.72 (2H, m), 3,18 (3H, C), 3,58-3,66 (1H, m), 3,78-of 3.85 (1H, m), 4,16-4,22 (1H, m), 6,56-only 6.64 (1H, m), 6,84-6,93 (1H, m), 7,21-7,29 (1H, m), 7,52-members, 7.59 (1H, m), 11,41 (1H, usher.C) of 12.53 (1H, usher.C).393391

1411H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-of 1.64 (6H, m), 2,05-2,11 (2H, m), 2,19 and 2.26 (2H, m), 2,42 (2H, s), 2,63-2,69 (2H, m), 3,10-3,15 (2H, m), 3,18 (3H, C), 3,34-3,40 (2H, m), 6,57-6,61 (1H, m), 6,83-to 6.88 (1H, m), Between 7.20-7.23 percent (1H, m), 7,52-7,56 (1H, m), 11,42 (1H, usher.C) of 12.53 (1H, usher.C).448446

Table 1-29
No. etc. Structural formulaNMRMS (M+H)MS (M-N)
1421H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1.55 V-to 1.63 (3H, m), 2,04-to 2.14 (4H, m), is 2.41 (2H, s), 2,44-a 2.53 (4H, m), 2,64-2,70 (2H, m), 3,21 (3H, C), 3,79-a 3.87 (1H, m), 6,57-6,62 (1H, m), 6,86-at 6.92 (1H, m), 7.23 percent-7,28 (1H, m), 7,53-7,58 (1H, m), at 11.37 (1H, usher.C) for 12.51 (1H, usher.C).434432

1431H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,46-of 1.54 (1H, m), 1,55-to 1.61 (2H, m), 1.91 a-2,19 (4H, m), 2,24-2,31 (1H, m), is 2.41 (2H, s), 2,64-2,70 (2H, m), 3,19 (3H, C), 3,78-3,86 (1H, m), 6,58-6,63 (1H, m), 6,86-6,91 (1H, m), 7,22-7,28 (1H, m), 7,35 (1H, usher.C), 7,53-7,58 (1H, m), 11,41 (1H, usher.C) of 12.53 (1H, usher.C).420418
1441H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-to 1.61 (2H, m), 1,77-to 1.86 (2H, m), 2,07-to 2.13 (2H, m), 2,18-of 2.23 (2H, m), is 2.41 (2H, s), 2,64-2,70 (2H, m), 3,15-3,21 (2H, m), 3,18 (3H, s), 3,29-a 3.35 (2H, m), 6,57-6,62 (1H, m), 6,84-6,89 (1H, m), 7,20-of 7.25 (1H, m), 7,52-EUR 7.57 (1H, m), 11,38 (1H, usher.C) for 12.51 (1H, usher.C).434432

1451H-NMR (DMSO-D6) δ: of 0.59 (3H, d, J=6,0 Hz), 1,01 (6H, s), 1,51-1,62 (2H, m), 2,31-2.49 USD (2H, m), is 2.41 (2H, s), 2,56-to 2.74 (3H, m), 2,82-2,95 (2H, m), 3,14-3,23 (1H, m), 3,18 (3H, C), 3,33-to 3.41 (1H, m), 3.43 points-3,50 (1H, m), 3,55-3,63 (1H, m), 6,55-only 6.64 (1H, m), about 6,82-at 6.92 (1H, m), 7,22-7,30 (1H, m), 7,49-7,58 (1H, m), is 11.39 (1H, usher.C) of 12.53 (1H, usher.C).436434
1461H-NMR (DMSO-D6) δ:
-From 0.12 to 1.17 (6H, m), 1,01 (6H, s), 1,54-1,62 (2H, m), 2,19-of 2.48 (2H, m), is 2.41 (2H, s), 2,60-of 2.92 (4H, m), 3,12-of 3.80 (4H, m), 3,17 (3H, C), 6,50-6,62 (1H, m), 6,84-of 6.99 (1H, m), 7,26-of 7.42 (1H, m), of 7.48-7,58 (1H, m), at 11.37-11,44 (1H, m), of 12.53 (1H, usher.C).
450448

Table 1-30
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
1471H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,10 (3H, d, J=7,0 Hz), 1,53-1,62 (2H, m), 2,42 (2H, s), 2,62 is 2.76 (2H, m), 3,11-up 3.22 (1H, m), 3,18 (3H, s), 3,39-3,47 (1H, m), 3,64-3,73 (1H, m), 3.75 to of 3.92 (3H, m), 4,91-5,00 (1H, m), 6,55-6,6 (1H, m), 6,91-6,97 (1H, m), 7,28-to 7.33 (1H, m), 7,50-7,56 (1H, m), of 11.43 (1H, usher.C) of 12.53 (1H, usher.C).450448
1481H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,47-of 1.76 (6H, m), 1,96-2,04 (1H, m), 2,12 (3H, C), is 2.41 (2H, s), 2,63-2,69 (2H, m), 2,83-of 2.91 (2H, m), 3,19 (3H, C), 6,58-6,62 (1H, m), 6,81-6,86 (1H, m), of 7.19-7.23 percent (1H, m), 7,52-EUR 7.57 (1H, m), at 11.37 (1H, usher.C) of 12.53 (1H, usher.C).406404

1491H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,47-of 1.76 (6H, m), 1,96-2,05 (1H, m), 2,12 (3H, C), is 2.41 (2H, s), 2,63-2,70 (2H, m), 2,84-of 2.92 (2H, m), 3,19 (3H, C), 6,57-6,63 (1H, m), 6,80-6,87 (1H, m), 7,18-7,24 (1H, m), 7,52-7,58 (1H, m), at 11.37 (1H, usher.C) of 12.53 (1H, usher.C).406404
1501H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,54-to 1.61 (2H, m), 1,79-to 1.94 (2H, m), 2,03-2,12 (1H, m), 2,19-to 2.29 (1H, m), 2,42 (2H, s), of 2.57 (3H, s), 2,64-2,71 (2H, m), 3,24 (3H, C), 4,04-4,08 (1H, m), 6,60-6,63 (1H, m), at 6.92-6,97 (1H, m), 7,29-7,32 (1H, m), EUR 7.57-7.62 mm (1H, m) 11,44 (1H, usher.C) 12,54 (1H, usher.C).420418
151img src="https://img.russianpatents.com/1211/12116712-s.jpg" height="49" width="51" /> 1H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-to 1.61 (2H, m), 1,80-of 1.93 (2H, m), 2,03-2,12 (1H, m), 2,19-to 2.29 (1H, m), 2,42 (2H, s), of 2.57 (3H, s), 2,64-2,71 (2H, m), 3,24 (3H, C), 4,03-4,08 (1H, m), 6,60-6,63 (1H, m), 6,91-6,97 (1H, m), 7,29-7,32 (1H, m), EUR 7.57-7,61 (1H, m) 11,44 (1H, usher.C) 12,54 (1H, usher.C).420418

Table 1-31
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
152
stereoisomer Ave 153
1H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,15-1,25 (6H, m), 1,55-1,60 (2H, m), is 2.41 (2H, s), 2,64-2,71 (2H, m), 2,88-2,99 (1H, m), 3,12-3,21 (1H, m), 3,16 (3H, C), 3,36-of 3.42 (1H, m), 3,82-3,88 (1H, m), 3,93-4,00 (1H, m), 4,47-4,55 (1H, m), 6,56-6,60 (1H, m), 6,90-to 6.95 (1H, m), 7,28-7,31 (1H, m), 7,50-7,55 (1H, m), is 11.39 (1H, usher.C) of 12.53 (1H, usher.C).464462
153
stereoisomer D. 152
1H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,15-of 1.26 (6H, m), 1,55-to 1.61 (2H, m), is 2.41 (2H, s), 2,63-2,71 (2H, m), 3,19 (3H, C), 3,64-3,73 (2H, m), 3,79-3,89 (2H, m), 3,93-4,01 (1H, m), 4,90-to 4.98 (1H, m), 6,56-6,60 (1H, m), 6,91-6,97 (1H, m), 7,28-7,32 (1H, m), 7,50-7,55 (1H, m), or 11.4 (1H, user.C) of 12.53 (1H, usher.C).464462

1541H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-to 1.61 (2H, m), 2,42 (2H, s), 2,65-2,70 (2H, m), 3,21 (3H, C), 3,54-of 3.60 (2H, m), of 3.69 (2H, s), 4,21-4,28 (2H, m), 6,60-6,63 (1H, m), 6,91-to 6.95 (1H, m), 7,29-7,31 (1H, m), EUR 7.57-7,61 (1H, m), 11,47 (1H, usher.C) 12,54 (1H, usher.C).422420
1551H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-to 1.61 (2H, m), 2,39-of 2.46 (2H, m), is 2.41 (2H, s), 2,64-2,71 (2H, m), 2,89-2,96 (2H, m), 3,00-of 3.04 (2H, m), 3,16 (3H, C), 3,21 (6H, s), 3,70 is 3.76 (2H, m), 6,57-6,62 (1H, m), 6,83-6,89 (1H, m), 7,20-7,26 (1H, m), 7,51-7,56 (1H, m) 11,40 (1H, usher.C) of 12.53 (1H, usher.C).466464
1561H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,53-1,62 (2H, m), 2,42 (2H, s), 2,63-of 2.72 (2H, m), up 3.22 (3H, s), 4,43 (2H, s), 6,12-of 6.20 (1H, m), 6,28-6.35 mm (1H, m), 6,60-to 6.67 (1H, m), of 6.99-7,05 (1H, m), 7,35-of 7.46 (2H, m), 7,51-EUR 7.57 (1H, m) members, 7.59-7,65 (1H, m), 11,50 (1H, usher.C) of 12.55 (1H, usher.C).430428

Table 1-32
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
1571H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-to 1.61 (2H, m), 2,42 (2H, s), 2,65-2,71 (2H, m), 3,23 (3H, C), 4,71 (2H, s), 6.18 of-6,22 (1H, m), 6,62-to 6.66 (1H, m), 6,98-7,03 (1H, m), 7,34-7,41 (2H, m), RUB 7.59-of 7.64 (2H, m), 11,48 (1H, usher.C) of 12.55 (1H, usher.C).403401
1581H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,19-of 1.29 (1H, m), 1,32-1,69 (9H, m), 2,42 (2H, s), 2,62-to 2.74 (2H, m), 3,20 (3H, s), 3,29-to 3.38 (1H, m), 3,45-3,52 (1H, m), 3,74-3,84 (1H, m), 3,89-to 3.96 (1H, m), 4,63 (1H, usher.C), 6,60-only 6.64 (1H, m), 6,87-6,93 (1H, m), 7,27-7,31 (1H, m), 7,54-members, 7.59 (1H, m), 11,42 (1H, usher.C) 12,54 (1H, usher.C).451449

1591H-NMR (DMSO-D6) δ: of 0.85 (3H, d, J=6,0 Hz), of 0.97 (3H, d, J=6,2 Hz), 1,01 (6H, C), a 1.54 to 1.61 (2H, m), is 2.41 (2H, s), 2,63-2,71 (2H, m), 3,20 (3H, s), 3,30-to 3.38 (1H, m), 3,40-was 3.54 (2H, m), 3,95-4,00 (1H, m), 4,63 (1H, usher.C), 6,58-only 6.64 (1H, m), 6,87-at 6.92 (1H, m), 7,26-7,32 (1H, m), 7,54-members, 7.59 (1H, m), 11,41 (1H, usher.C) of 12.53 (1H, ush�R. C). 425423
1601H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,54-to 1.61 (2H, m), 1,68 is 1.78 (1H, m), 1,92-2,02 (1H, m), 2,08-of 2.27 (2H, m), 2,42 (2H, s), 2,64-of 2.72 (2H, m), 3,20 (3H, C), 3,24-3,30 (1H, m), 3,45-3,51 (1H, m), 3,57-to 3.67 (2H, m), 3,90-at 3.97 (1H, m), 4.72 in-of 4.77 (1H, m), 6,59-6,63 (1H, m), 6,91-of 6.96 (1H, m), 7,29-7,34 (1H, m), 7,56-7,61 (1H, m), 11,47 (1H, usher.C) 12,54 (1H, usher.C).450448

1611H-NMR (DMSO-D6) δ: from 0.92 to 1.38 (6H, m), 1,01 (6H, s), 1.56 to to 1.61 (2H, m), 2,23-2,60 (4H, m), is 2.41 (2H, s), 2,63-2,70 (2H, m), 3,23-3,83 (7H, m), a 6.53-6,59 (1H, m), 6,69-6,89 (1H, m), 7,10-7,39 (1H, m), 7,43-of 7.48 (1H, m), Of 11.34 (1H, usher.C) 12,49 (1H, usher.C).450448

Table 1-33
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
1621H-NMR (DMSO-D6) δ: 0,98-1,05 (3H, m) of 1.01 (6H, C), 1,44-of 1.54 (1H, m), 1.56 to to 1.61 (2H, m), 2,10-2,19 (1H, m), 2.26 and-2,34 (1H, m), 2,42 (2H, s), 2,64-2,71 (2H, m), 3,19 (3H, s), 3,26-to 3.34 (2H, m), 3,65 is 3.76 (2H, m), 6,60-6,63 (1H, m), 6,90-to 6.95 (1H, m), 7,28-7,32 (1H, m), 7,56-to 7.60 (1H, m), 11,46 (1H, usher.C) 12,54 (1H, usher.C).434432

1631H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.07 (6H, s), 1,55-to 1.61 (2H, m), 2,03 (2H, s), 2,42 (2H, s), 2,64-2,70 (2H, m), 3,09 (2H, s), 3,19 (3H, s), 3,70 (2H, s), 6,59-6,63 (1H, m), 6,89-to 6.95 (1H, m), 7,27-7,31 (1H, m), To 7.55 and 7.60 (1H, m), 11,46 (1H, usher.C) 12,54 (1H, usher.C).448446
1641H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,54-to 1.61 (2H, m), 1,99-2,07 (1H, m), 2,38-2,48 (1H, m), 2,42 (2H, s), 2,64-of 2.72 (2H, m), 3,12-up 3.22 (1H, m), 3,19 (3H, C), 3,56-3,65 (2H, m), 3,81-3,88 (1H, m), 4,23-4,30 (1H, m), 5,11 (1H, d, J=4.4 Hz), to 6.58-6,63 (1H, m), 6,90-of 6.96 (1H, m), 7,27-7,32 (1H, m), 7,55-7,61 (1H, m), 11,46 (1H, usher.C) 12,54 (1H, usher.C).436434

1651H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-1,60 (2H, m), 1,68-of 2.00 (7H, m), is 2.41 (2H, s), 2,63-2,70 (2H, m), 3,14-of 3.25 (3H, m), 3,32-3,52 (2H, m), 4,22-to 4.28 (1H, m), 6,57-6,63 (1H, m), at 6.92-of 6.99 (1H, m), 7,30-value of 7, 37 (1H, m), 7,52-7,61 (1H, m), is 11.39-11,44 (1H, m), 12,50-12,56 (1H, m)434432
1661H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,54-to 1.61 (2H, m), 1,62-of 2.01 (7H, m), is 2.41 (2H, s), 2,61-to 2.73 (2H, m), 3,12-of 3.25 (3H, m), 3,36-3,55 (2H, m), 4,22-4,30 (1H, m), 6,57-to 6.66 (1H, m), at 6.92-7,00 (1H, m), 7,31-the 7.43 (1H, m), 7,51-a 7.62 (1H, m), is 11.39 (1H, usher.C) of 12.53 (1H, usher.C).434432

Table 1-34
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
1671H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,24 (3H, d, J=6,8 Hz), 1,55-to 1.61 (2H, m), 2,42 (2H, s), 2,64-2,70 (2H, m), 3,17-3,24 (1H, m), 3,20 (3H, s), 3.46 in-was 3.54 (1H, m), 3,65-and 3.72 (1H, m), 3,73-of 3.80 (1H, m), 3,82-of 3.91 (2H, m), Of 4.09 (1H, square, J=6,9 Hz), 6,59-6,63 (1H, m), 6,90-of 6.96 (1H, m), 7,29-7,32 (1H, m), 7,55-to 7.60 (1H, m), 11,47 (1H, usher.C) 12,54 (1H, usher.C).450448
1681H-NMR (DMSO-D 6) δ: of 1.01 (6H, s), of 1.08 (3H, d, J=6,6 Hz), 1,55-1,60 (2H, m), is 2.41 (2H, s), 2,64-2,70 (2H, m), of 3.04 (3H, s), 3,21 (3H, s), with 3.79 (1H, square, J=6.3 Hz), to 6.58-only 6.64 (1H, m), 6,87-6,91 (1H, m), 7,21-7,29 (1H, m), 7,54-members, 7.59 (1H, m), is 11.39 (1H, usher.C) of 12.53 (1H, usher.C).381379

1691H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.08 (3H, d, J=6,4 Hz), 1,55-to 1.61 (2H, m), is 2.41 (2H, s), 2,64-2,71 (2H, m), of 3.04 (3H, s), 3,21 (3H, s), with 3.79 (1H, square, J=6,2 Hz), 6,59-6,63 (1H, m), 6,86-6,91 (1H, m), 7.23 percent-7,29 (1H, m), 7,54-members, 7.59 (1H, m) to 11.35 (1H, usher.C) for 12.51 (1H, usher.C).381379
1701H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-of 1.66 (3H, m), 1,82-of 1.91 (1H, m), 2,03-2,11 (1H, m), 2,36-of 2.44 (1H, m), is 2.41 (2H, s), 2,65-2,71 (2H, m), 3,14-3,23 (1H, m), 3,19 (3H, C), 3,25-a 3.35 (1H, m), 3,60-3,68 (1H, m), 3,86-of 3.95 (2H, m), 4,87 (1H, d, J=4.0 Hz), 6,59-only 6.64 (1H, m), 6,89-to 6.95 (1H, m), 7,28-7,34 (1H, m), 7,53-to 7.60 (1H, m) 11,40 (1H, usher.C) for 12.51 (1H, usher.C).450448

1711H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.08 (3H, d, J=6.3 Hz), 1,54-1,62 (2H, m), 2,42 (2H, s), 2,62-of 2.75 (2H, m), 3,20 (3H, s), 3,47-to 3.6 (3H, m), 3.75 to 3,82 (1H, m), 3,98 (1H, d, J=16.5 Hz), 4,03 (1H, d, J=16.5 Hz), 4,08-4,16 (1H, m), 6,58-of 6.65 (1H, m), 6,93-7,01 (1H, m), 7,30-value of 7, 37 (1H, m), 7,55-the 7.62 (1H, m), 11,47 (1H, usher.C) 12,54 (1H, usher.C).450448

Table 1-35
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
1721H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.08 (3H, d, J=6.3 Hz), 1,54-1,62 (2H, m), 2,42 (2H, s), 2,63-2,71 (2H, m), 3,20 (3H, s), 3,47-3,62 (3H, m), 3.75 to 3,82 (1H, m), 3,98 (1H, d, J=16.5 Hz), 4,03 (1H, d, J=16.5 Hz), 4,08-4,16 (1H, m), 6,57-of 6.65 (1H, m), at 6.92-7,01 (1H, m), 7,30-of 7.36 (1H, m), 7,55-the 7.62 (1H, m), 11,47 (1H, usher.C) 12,54 (1H, usher.C).450448

1731H-NMR (DMSO-D6) δ: of 0.78 (3H, d, J=6,4 Hz), of 0.90 (3H, d, J=6,4 Hz), 1,01 (6H, s), 1,55-to 1.61 (2H, m), 1,99-of 2.09 (1H, m), 2,30-of 2.38 (2H, m), is 2.41 (2H, s), 2,51-2,56 (2H, m), 2,63-2,71 (2H, m), 2,82-is 2.88 (1H, m), 3,23 (3H, C), 3,41-of 3.50 (4H, m), 6,57-6,61 (1H, m), about 6,82-to 6.88 (1H, m), 7.23 percent-7,27 (1H, m), 7,51-7,56 (1H, m), 11,36 (1H, usher.C) for 12.51 (1H, usher.C).464 462
1741H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.05 (6H, s), 1.55 V-to 1.63 (4H, m), 1,69-of 1.76 (2H, m), is 2.41 (2H, s), 2,64-2,70 (2H, m), 3,19 (3H, C), 3,22-3,27 (2H, m), 3,71 (2H, s), 6,58-6,63 (1H, m), to 6.88-6,94 (1H, m), 7,28-7,32 (1H, m), 7,54-members, 7.59 (1H, m), 11,41 (1H, usher.C) for 12.51 (1H, usher.C).462460

1751H-NMR (DMSO-D6) δ: to 0.96 (6H, C) of 1.01 (6H, s), 1,48-of 1.54 (2H, m), 1,55-to 1.61 (2H, m) of 2.16-2.22 (2H, m), is 2.41 (2H, s), 2,64-2,71 (2H, m), 2,98 (2H, s), 3,19 (3H, C), of 3.75 (2H, s), 6,58-6,63 (1H, m), to 6.88-to 6.95 (1H, m), 7,27-7,32 (1H, m), 7,53-members, 7.59 (1H, m), 11,41 (1H, usher.C) for 12.51 (1H, usher.C).462460
1761H-NMR (DMSO-D6) δ: 0,68-1,94 (11H, m), 1,01 (6H, s), is 2.41 (2H, s), 2,64-2,71 (2H, m), 2,88-3,29 (9H, m), 6,56-6,63 (1H, m), 6,78-6,86 (1H, m), made 7.16 interest-7.23 percent (1H, m), 7,50-EUR 7.57 (1H, m) to 11.35 (1H, usher.C) 12,50 (1H, usher.C).449447

Table 1-36
No. etc.Structural formula NMRMS (M+H)MS (M-N)
1771H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-was 1.62 (2H, m), 1,69-to 1.79 (1H, m), 1,92-2,03 (1H, m), 2,08-of 2.28 (2H, m), 2,42 (2H, s), 2,64-to 2.74 (2H, m), 3,20 (3H, C), 3,24-of 3.33 (1H, m), 3,45-3,52 (1H, m), 3,57-to 3.67 (2H, m), 3,89-3,98 (1H, m), 4,70-of 4.75 (1H, m), 6,59-6,63 (1H, m), 6,91-6,97 (1H, m), 7,30-7,34 (1H, m), 7,55-7,61 (1H, m), of 11.43 (1H, usher.C) for 12.51 (1H, usher.C).450448
1781H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1.56 to to 1.61 (2H, m), 2,42 (2H, s), 2,64-2,71 (2H, m), 2,82-2,89 (3H, m), 3,17-up 3.22 (3H, m), of 3.75 (2H, s), 5,00-of 5.06 (2H, m), 6,57-6,62 (1H, m), 6,70-6,94 (1H, m), 7.23 percent-of 7.42 (6H, m), Of 7.48-members, 7.59 (1H, m), 11,41 (1H, usher.C) for 12.51 (1H, usher.C).500498

1791H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.15 (9H, s), 1,55-1,60 (2H, m), is 2.41 (2H, s), 2,65-2,70 (2H, m), 3,01 (3H, C), 3,19 (3H, C), of 3.77 (2H, s), 6,58-only 6.64 (1H, m), 6,89-to 6.95 (1H, m), 7,29-7,34 (1H, m), 7,54-to 7.60 (1H, m), 11,41 (1H, usher.C) 12,50 (1H, usher.C).450448
180 1H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-1,60 (2H, m), is 2.41 (2H, s), 2,65-2,70 (2H, m), 2,73-2,90 (3H, m), 3,18-3,27 (6H, m), of 3.77-4,07 (4H, m), 6,59-only 6.64 (1H, m), 6,91-6,97 (1H, m), 7,30-7,35 (1H, m), 7,55-to 7.60 (1H, m), 11,42 (1H, usher.C) for 12.51 (1H, usher.C).438436
1811H-NMR (DMSO-D6) δ: of 1.01 (6H, s) to 1.14 (3H, d, J=6,4 Hz), 1,55-to 1.61 (2H, m), 2,42 (2H, s), 2,65-2,70 (2H, m), 3,14-3,26 (2H, m), 3,20 (3H, s), 3,71-3,94 (3H, m), was 4.02 (2H, s), 6,60-6,61 (1H, m), 6,89-to 6.95 (1H, m), 7,29-7,32 (1H, m), 7,55-to 7.60 (1H, m), of 11.43 (1H, usher.C) for 12.51 (1H, usher.C).478476

Table 1-37
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
1821H-NMR (DMSO-D6) δ: of 1.01 (6H, s) to 1.14 (3H, d, J=6.3 Hz), 1,55-to 1.61 (2H, m), 2,38-of 2.44 (2H, m), 2,64-2,71 (2H, m), 3,15-3,26 (2H, m), 3,20 (3H, s), 3,71-of 3.78 (1H, m), 3,80-of 3.95 (2H, m), was 4.02 (2H, s), 6,60-6,63 (1H, m), 6,91-to 6.95 (1H, m), 7,29-7,32 (1H, m), 7,56-to 7.60 (1H, m), 11,48 (1H, usher.C) of 12.55 (1H, usher.C).450448
1831H-NMR (DMSO-D6) δ: of 1.00 (6H, C) of 1.01 (6H, s), 1.56 to to 1.61 (2H, m), 1,73-to 1.79 (2H, m), 2,42 (2H, s), 2,65-2,71 (2H, m), 3,19 (3H, s), 3,26-3,30 (2H, m), of 3.69 (2H, s), 6,59-of 6.65 (1H, m), 6,90-of 6.96 (1H, m), 7,27-7,34 (1H, m), 7,56-7,61 (1H, m), 11,47 (1H, usher.C) of 12.55 (1H, usher.C).448446

1841H-NMR (DMSO-D6) δ: of 1.01 (6H, s), to 1.22 (6H, s), 1,53-1,62 (2H, m), 2,42 (2H, s), 2,65-2,70 (2H, m), 3,17-3,24 (2H, m), 3,20 (3H, s), 3,83 (2H, s), 3,97 (2H, s), 6,59-of 6.65 (1H, m), 6,91-of 6.96 (1H, m), 7,28-of 7.36 (1H, m), 7,55-7,61 (1H, m), of 11.45 (1H, usher.C) of 12.55 (1H, usher.C).464462
1851H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,53-1,62 (2H, m), 2,42 (2H, s), 2,62-to 2.79 (4H, m), 3,15-of 3.43 (2H, m), 3,19 (3H, C), only 3.57 (2H, s), 6,29 (1H, usher.C), 6,59-only 6.64 (1H, m), 6,89-6,94 (1H, m), 7,26-7,32 (1H, m), 7,55-7,61 (1H, m), of 11.43 (1H, usher.C) of 12.46 (1H, usher.C).421419
1861H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,54-to 1.61 (2H, m), is 2.41 (2H, s), 2,61 (3H, s), 2,65-2,71 (2H, m), 3,14-3,26 (2H, m), 3,18 (3H, C), or 3.28-3,36 (2H, m, 3,59 (2H, s), 6,58-to 6.66 (1H, m), 6,87-of 6.96 (1H, m), 7,25-to 7.33 (1H, m), 7,54-7,61 (1H, m) 11,44 (1H, usher.C) 12,54 (1H, usher.C).435433

Table 1-38
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
1871H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,28-of 1.36 (2H, m), 1,39-of 1.50 (4H, m), 1,53-1,62 (4H, m), 2,35-of 2.44 (2H, m), 2,42 (2H, s), 2,64-2,70 (2H, m), 3,18 (3H, C), 3,41-3,47 (2H, m), of 3.75 (2H, s), 6,58-6,63 (1H, m), 6,90-of 6.96 (1H, m), 7,28-to 7.33 (1H, m), 7,53-7,61 (1H, m) 11,44 (1H, usher.C) of 12.53 (1H, usher.C).462460
1881H-NMR (DMSO-D6) δ: 0,96-1,05 (3H, m), 1,01 (6H, C), a 1.54 to 1.61 (2H, m), 1,76-of 1.88 (1H, m), 2,27-to 2.40 (2H, m), 2,42 (2H, s), 2,64-2,71 (2H, m), 2,92-2,98 (1H, m), 3,19 (3H, s), 3,42-3,49 (1H, m), 3,63-to 3.76 (2H, m), 6,59-6,63 (1H, m), 6,90-of 6.96 (1H, m), 7,27-7,32 (1H, m), 7,55-7,61 (1H, m), 11,46 (1H, usher.C) 12,54 (1H, usher.C).434432

189 1H-NMR (DMSO-D6) δ: 0.98 in (6H, C) of 1.01 (6H, s), 1,49-of 1.55 (2H, m), 1.56 to the 1.62 (2H, m), 1,98 (2H, s), is 2.41 (2H, s), 2,63-of 2.72 (2H, m), 3,19 (3H, s), 3,23-of 3.31 (2H, m), 3,76 (2H, s), 6,58-only 6.64 (1H, m), 6,90-of 6.96 (1H, m), 7,28-7,34 (1H, m), 7,55-7,61 (1H, m), 11,46 (1H, usher.C) 12,54 (1H, usher.C).462460
1901H-NMR (DMSO-D6) δ: 0,81-of 0.91 (3H, m), and 1.00 (6H, s), 1,55-to 1.61 (2H, m), 1,69-of 1.85 (2H, m), is 2.41 (2H, s), 2,63-2,70 (2H, m), 3,00-3,58 (5H, m), 3,32 (3H, s), 3,68-of 3.99 (4H, m), 6,62-to 6.67 (1H, m), 6,93-7,00 (1H, m), 7,31-of 7.36 (1H, m), RUB 7.59-7,65 (1H, m), of 10.09 (1H, usher.C) 11,47 (1H, usher.C) 12,57 (1H, usher.C).450448

1911H-NMR (DMSO-D6) δ: is 0.84 (3H, DD, J=77,7, to 38.8 Hz), 1,01 (6H, s), 1,54-1,62 (2H, m), 1,69-of 1.85 (2H, m), 2,42 (2H, s), 2,64-2,71 (2H, m), 2,99-3,55 (5H, m), of 3.33 (3H, s), 3,70-4,01 (4H, m), 6,61-to 6.67 (1H, m), at 6.92-7,01 (1H, m), 7,31-7,38 (1H, m), RUB 7.59-7,66 (1H, m), 10,14 (1H, usher.C) 11,48 (1H, usher.C) is 12.58 (1H, usher.C).450448

Table 1-39
No. etc.Structural formula NMRMS (M+H)MS (M-N)
1921H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-to 1.61 (2H, m), 1,82-of 1.97 (3H, m), is 2.41 (2H, s), 2,65-2,70 (2H, m), 2,70-2,95 (3H, m), 3,17-of 3.25 (3H, m), 3,76-3,84 (2H, m), 6,59-6,63 (1H, m), 6,89-6,98 (1H, m), 7,28-7,34 (1H, m), 7,55-7,61 (1H, m), of 11.45 (1H, usher.C) of 12.53 (1H, usher.C).408406

1931H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,10-of 1.19 (6H, m), 1,55-to 1.61 (2H, m), 2,23-of 2.45 (4H, m), 2,65-2,70 (2H, m), 2,73-of 2.99 (3H, m), 3,18-3,24 (3H, m), 3,81-3,94 (2H, m), 4,77-4,82 (1H, m), 6,59-only 6.64 (1H, m), 6,91-6,98 (1H, m), 7,30-7,35 (1H, m), 7,55-to 7.60 (1H, m), 11,41 (1H, usher.C) for 12.51 (1H, usher.C).466464
1941H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,15-1,62 (8H, m), 1,78-to 1.87 (2H, m), 2,14-of 2.64 (1H, m), is 2.41 (2H, s), 2,65-2,70 (2H, m), 2,72-of 3.00 (3H, m), 3,16-of 3.25 (6H, m), 3,34-to 3.38 (1H, m), 3,73-a 3.87 (2H, m), 6,59-only 6.64 (1H, m), 6,90-6,98 (1H, m), 7,28-7,35 (1H, m), 7,54-of 7.62 (1H, m), 11,34-11,49 (1H, m), 12,50 (1H, usher.C).506504

1H-NMR (DMSO-D6) δ: 0,95-of 1.08 (9H, m), 1,01 (6H, s), 1.26 in (3H, C) of 1.54 to 1.60 (2H, m), is 2.41 (2H, s), by 2.55 (1H, s), 2,63-of 2.72 (2H, m), of 2.66 (1H, s), 3,18 (3H, C), 4,60-to 4.76 (1H, m), 6,54-6,62 (1H, m), about 6,82-at 6.92 (1H, m), 7,21-7,31 (1H, m), 7,50-7,55 (1H, m), is 11.39 (1H, usher.C) 12,50 (1H, usher.C).480478
1961H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,50-to 1.61 (3H, m), 1,94-2,07 (1H, m), 2,12-of 2.27 (2H, m), 2,42 (2H, s), 2,65-2,71 (2H, m), 3,19 (3H, s), 3,20 (3H, C), 3,25-a 3.35 (2H, m), 3,54-of 3.60 (1H, m), 3,74-3,82 (1H, m), 3,89-at 3.97 (1H, m), 6,60-only 6.64 (1H, m), 6,89-6,94 (1H, m), 7,29-to 7.33 (1H, m), 7,56-7,61 (1H, m), of 11.43 (1H, usher.C) 12,52 (1H, usher.C).464462

Table 1-40
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
1971H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,52-to 1.61 (3H, m), 1,96-of 2.06 (1H, m), 2,12 and 2.26 (2H, m), 2,42 (2H, s), 2,64-of 2.72 (2H, m), 3,20 (3H, s), 3,20 (3H, C), 3,25-3,37 (2H, m), 3,57 (1H, d, J=16.5 Hz), 3,74-3,82 (1H, m), 3,93 (1H, d, J=16.5 Hz), 6,59-only 6.64 (1H, m), 6,8-6,94 (1H, m), 7,27-to 7.33 (1H, m), 7,56-7,61 (1H, m), of 11.43 (1H, usher.C) for 12.51 (1H, usher.C).464462
1981H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,55-to 1.61 (2H, m), is 2.41 (2H, s), 2,63-of 2.72 (2H, m), 2,76-2,85 (3H, m), 3,20 (3H, s), 3,50-3,59 (3H, m), 3,71 (2H, s), 6,58-of 6.65 (1H, m), 6,86-to 6.95 (1H, m), from 7.24 to 7.33 (1H, m), 7,54-7,61 (1H, m) 11,44 (1H, usher.C) of 12.53 (1H, usher.C).424422

1991H-NMR (DMSO-D6) δ: 0,88-0,98 (6H, m), 1,01 (6H, s), 1,55-to 1.61 (2H, m), is 2.41 (2H, s), 2,65-2,70 (2H, m), 2,71-3,01 (4H, m), 3,16-of 3.25 (3H, m), 3.75 to 3.89 points (2H, m), 6,59-of 6.65 (1H, m), 6,90-of 6.99 (1H, m), 7,29-7,35 (1H, m), 7,55-7,61 (1H, m), of 11.45 (1H, usher.C) of 12.53 (1H, usher.C).436434
2001H-NMR (DMSO-D6) δ: 0,62-0,73 (4H, m), 1,01 (6H, s), 1,54-1,62 (2H, m), 1,87-of 1.95 (1H, m), is 2.41 (2H, s), 2,65-2,71 (2H, m), 2,73-3,13 (3H, m), 3,16-3,26 (3H, m), 3,79-of 4.04 (2H, m), 6,57-only 6.64 (1H, m), to 6.88-7,00 (1H, m), 7,26-of 7.36 (1H, m), 7,53-7,61 (1H, m) 11,44 (1H, usher.C) of 12.53 (1H, usher.C).434432

2011H-NMR (DMSO-D6) δ: up 7.17 (3H, s), of 7.42 (6H, s), 7,56 (3H, s), 7,95-8,02 (2H, m), 8,25-of 8.33 (1H, m), 8,55-8,64 (1H, m), of 8.82 (2H, s), 9,05-9,12 (2H, m), 9,24-9,29 (1H, m), 9,61 (3H, C), for 9.88 and 9.95 (1H, m), 10,16-10,23 (1H, m), 12,99-13,04 (1H, m), 13,25-of 13.32 (1H, m), 13,62-13,68 (1H, m), 13,95-13,99 (1H, m), 17,79 (1H, usher.C) of 18.94 (1H, usher.C).421419

Table 1-41
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2021H-NMR (DMSO-D6) δ: 0,82-of 1.04 (9H, m), 1,40-of 1.46 (2H, m), 1,62 (2H, s), of 2.27 (2H, s), 2,49-of 2.67 (6H, m), 3,00-of 3.07 (3H, m), 4,31-of 4.83 (1H, m), 6,41-6,47 (1H, m), 6,70-was 6.77 (1H, m), between 7.09-7.13 (1H, m), 7,34-the 7.43 (1H, m), 11,20-11,31 (1H, m), 12,35-12,41 (1H, m).422420

2031H-NMR (DMSO-D6) δ: 0,72 (t, 2H, J=7,4 Hz), of 0.91 (t, 1H, J=6,8 Hz), 1,01 (s, 6H), was 1.04 (d, 2H, J=7,1 Hz), of 1.15 (d, 1H, J=6,8 Hz), 1,58 (t, 3H, J=6.3 Hz), 1,97-2,12 (m, 2H), 2,41 (s, 2H), 2,67 (s, 3H), 2,78 (�, 2H), 3,15-3,20 (m, 3H), 4,48-of 4.54 (m, 0,3 H), 4,96-5,03 (m, 0,7 H), 6,55-6,62 (m, 1H), 6,84-at 6.92 (m, 1H), 7,20-7,30 (m, 1H), 7,47-EUR 7.57 (m, 1H), 11,28-11,46 (m, 1H), 12,52 (user.s, 1H).436434
2041H-NMR (DMSO-D6) δ: 0,27-of 1.26 (10H, m), 1,01 (6H, s), 1,55-to 1.61 (2H, m), is 2.41 (2H, s), 2,61-of 2.91 (5H, m), 3,14-3,21 (3H, m), 4,61-5,04 (1H, m), 6,55-6,61 (1H, m), 6,87-to 6.95 (1H, m), 7,22-7,32 (1H, m), 7,47-members, 7.59 (1H, m), Made 11.32-11,47 (1H, m), 12,49-of 12.55 (1H, m).450448

2051H-NMR (DMSO-D6) δ:
-0,21-1,75 (10H, m), 1,01 (6H, s), is 2.41 (2H, s), 2,63-of 3.04 (5H, m), 3,13-3,23 (3H, m), 4,85-5,04 (1H, m), 6,54-6,60 (1H, m), of 6.85-at 6.92 (1H, m), 7,21-7,31 (1H, m), 7,47-7,56 (1H, m), 11,31-11,41 (1H, m), 12,48-of 12.55 (1H, m).
448446
2061H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), of 1.06 (t, 3H, J=7,25 Hz), 1,58 (t, 2H, J=6,45 Hz), 2,42 (s, 2H), 2,63-of 2.72 (m, 2H), 3,61-3,74 (m, 4H), of 4.45 (t, 1H, J=5,64 Hz), 6,61 (s, 1H), 6,83 (d, 1H, J=of 7.86 Hz), 7,21 (s, 1H), 7,55 (d, 1H, J=of 7.86 Hz), 11,41 (s, 1H), of 12.55 (s, 1H).367365

Table 1-42
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2071H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), was 1.04 (t, 3H, J=7,05 Hz), 1,58 (t, 2H, J=6,45 Hz), 2,42 (s, 2H), 2,67 (s, 2H), 3,17 (s, 3H), 3,62-and 3.72 (m, 4H), 6,60 (s, 1H), at 6.84 (d, 1H, J=is 8.46 Hz), 7,21 (s, 1H), 7,55 (d, 1H, J=is 8.46 Hz), 11,41 (s, 1H), 12,54 (s, 1H).381379

2081H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), of 1.57 (t, 2H, J=6,45 Hz), is 2.40 (s, 2H), 2,65-2,67 (user.m, 2H), of 4.09 (t, 2H, J=7,96 Hz), 4,43 (t, 2H, J=7,96 Hz), a 6.53 (s, 1H), made 7.16 interest (d, 1H, J=8,87 Hz), 7,49 (d, 1H, J=8,87 Hz), 7,61 (s, 1H), 11,24 (s, 1H), 12,47 (s, 1H).351349
2091H-NMR (DMSO-D6) δ: to 0.89 (t, 3H, J=of 7.42 Hz), 1,01 (s, 6H), 1,58 (t, 2H, J=6,25 Hz), of 1.97 (square, 2H, J=of 7.42 Hz), 2,41 (s, 2H), 2,63-2,71 (m, 2H), 3,44-3,52 (m, 2H), 3,69 (t, 2H, J=6,36 Hz), 4,63 (t, 1H, J=5,64 Hz), 6,59 (s, 1H), 6,86 (d, 1H, J=is 8.46 Hz), 7,24 (s, 1H), 7,53 (d, 1H, J=is 8.46 Hz), at 11.37 (s, 1H), 12,52 (s, 1H).3812101H-NMR (DMSO-D6) δ: of 1.00 (s, 6H), of 1.57 (t, 2H, J=6,25 Hz), 2,08 (TT, 2H, J=7,05, 7,05 Hz), is 2.40 (s, 2H), 2,46-2,51 (m, 2H), 2,59-of 2.72 (m, 2H), 3,86 (t, 2H, J=7,05 Hz), of 6.52 (s, 1H), 7,20 (d, 1H, J=is 8.46 Hz), of 7.46 (d, 1H, J=is 8.46 Hz), 7,69 (s, 1H), 11,21 (s, 1H), 12,47 (s, 1H).349347

2111H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,25 Hz), 1,80-of 1.93 (m, 4H), 2,39 (t, 2H, J=6,25 Hz), 2,41 (s, 2H), 2,62-2,71 (m, 2H), 3,56-3,65 (m, 2H), 6,55 (s, 1H), is 6.81 (d, 1H, J=is 8.46 Hz), of 7.19 (s, 1H), of 7.46 (d, 1H, J=is 8.46 Hz), 11,30 (s, 1H), 12,50 (s, 1H).363361

Table 1-43
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2121H-NMR (DMSO-D6) δ: to 0.89 (t, 3H, J=of 7.42 Hz), 1,01 (s, 6H), 1,58 (t, 2H, J=6,25 Hz), of 1.97 (square, 2H, J=of 7.42 Hz), 2,41 (s, 2H), 2,62-of 2.72 (m, 2H), 3,21 (s, 3H), 3,39 (t, 2H, J=6,04 Hz), 3,39 (s, 2H), 3,79 (t, 2H, J=6,04 Hz), 6,60 (s, 1H), at 6.84 (d, 1H, J=compared to 8.26 Hz), 7,24 (s, 1H), 7,54 (d, 1H, J=compared to 8.26 Hz), 11,38 (s, 1H), of 12.53 (s, 1H).395393

2131H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6.18 of Hz), 2,41 (s, 2H), 2,63-2,70 (m, 2H), 3,17 (s, 3H), 3,48 (square, 2H, J=6,03 Hz), to 3.64-3,74 (m, 4H), 4,67 (t, 1H, J=to 5.62 Hz), 6,60 (s, 1H), to 6.88 (d, 1H, J=Hz 8,16), 7,27 (s, 1H), 7,53 (d, 1H, J=Hz 8,16), 11,41 (s, 1H), of 12.53 (s, 1H).397395
2141H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,03 Hz), 1,72 (s, 3H), 2,41 (s, 2H), of 2.66 (t, 2H, J=6,03 Hz), 3,47 (TD, 2H, J=6,40, 6,00 Hz), 3,68 (t, 2H, J=6,61 Hz) a 4.64 (t, 1H, J=5.68 per Hz), 6,59 (s, 1H), to 6.88 (d, 1H, J=8,23 Hz), 7,25 (s, 1H), 7,53 (d, 1H, J=8,23 Hz), is 11.39 (s, 1H), of 12.53 (s, 1H).367365

2151H-NMR (DMSO-D6) δ: 0,75-0,90 (m, 2H), 0.98 to 1.14 in (m, 1H), 1,01 (s, 6H), 1,29-of 1.42 (m, 2H), 1,42-of 1.50 (m, 1H), 1,51-of 1.65 (m, 6H), 2,07-2,17 (m, 1H), 2,11 (s, 6H), to 2.29 (t, 2H, J=7,05 Hz), 2,42 (s, 2H), 2,64-of 2.72 (m, 2H), 3,61 is 3.76 (m, 2H), 6,60 (s, 1H), at 6.84 (d, 1H, J=compared to 8.26 Hz), 7,24 (s, 1H), 7,55 (d, 1H, J=compared to 8.26 Hz), 11,36 (s, 1H), 12,54 (s, 1H). 462460
2161H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,38-of 1.48 (m, 2H), 1,54-of 1.73 (m, 4H), 2,12 (s, 6H), 2,29-2,31 (m, 1H), 2,35-of 2.44 (m, 3H), 2,42 (s, 2H), 2,63-to 2.74 (m, 2H), equal to 2.94 (t, 2H, J=of 11.08 Hz), to 3.64 and 3.78 (m, 4H), 6,61 (s, 1H), 6,86 (d, 1H, J=8,06 Hz), 7,26 (s, 1H), 7,56 (d, 1H, J=8,06 Hz), at 11.37 (s, 1H), 12,54 (s, 1H).464462

Table 1-44
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2171H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,25 Hz), 1,66-1,78 (m, 1H), 1,95-of 2.06 (m, 1H), 2,15 (s, 6H), 2,29-of 2.38 (m, 2H), 2,41 (s, 2H), 2,63-of 2.72 (m, 2H), 2,79-2,86 (m, 1H), 3,45-3,52 (m, 1H), 3,53-to 3.64 (m, 2H), 3,65-and 3.72 (m, 1H), 3,71-3,82 (user.m, 1H), 6,61 (s, 1H), of 6.87 (d, 1H, J=compared to 8.26 Hz), 7,26 (s, 1H), 7,56 (d, 1H, J=compared to 8.26 Hz), 11,40 (s, 1H), 12,54 (s, 1H).450448
2181H-NMR (DMSO-D6) δ: 0,75-of 0.91 (m, 1H), 0,86 (t, 3H, J=7,15 Hz), 1,01 (s, 6H), 1,02-of 1.13 (m, 1H), 1,20-1,50 (m, 4H, 1,51-of 1.65 (m, 8H), 2,07 (s, 6H), 2,09-2,17 (m, 1H), measuring 2.20 (t, 2H, J=7,15 Hz), 2,42 (s, 2H), 2,62-2,73 (m, 2H), 3,53-3,66 (m, 2H), 6,61 (s, 1H), 6,83 (d, 1H, J=of 7.86 Hz), 7,22 (s, 1H), 7,56 (d, 1H, J=of 7.86 Hz), To 11.35 (s, 1H), 12,54 (s, 1H).476474

2191H-NMR (DMSO-D6) δ: of 0.62 to 0.76 (m, 2H), 1,01 (s, 7H), 1,08-1,22 (m, 2H), 1,48-1,62 (m, 7H), 1,62-of 1.74 (m, 1H), of 1.84 (d, 2H, J=6.85 Hz), 2,12 (s, 6H), of 2.30 (t, 2H, J=7,05 Hz), 2,42 (s, 2H), 2,63-2,73 (m, 2H), 3,67-of 3.78 (m, 2H), 6,59 (s, 1H), is 6.81 (d, 1H, J=8,06 Hz), 7,21 (s, 1H), 7,53 (d, 1H, J=8,06 Hz), 11,38 (s, 1H), of 12.53 (s, 1H).476474
2201H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,53-to 1.79 (m, 4H), 1,81-of 1.93 (m, 2H), 2,13 (s, 6H), of 2.30 (t, 2H, J=7,05 Hz), 2,42 (s, 2H), of 2.66 (t, 2H, J=6,04 Hz), 3,62 (TD, 1H, J=7,45, 4,30 Hz), 3,65-of 3.77 (m, 2H), 3,81 (square, 1H, J=7,25 Hz), 4,11 (DD, 1H, J=7,25, 5,64 Hz), 6,60 (s, 1H), 6,86 (d, 1H, J=compared to 8.26 Hz), 7,26 (s, 1H), 7,54 (d, 1H, J=compared to 8.26 Hz), 11,41 (s, 1H), 12,54 (s, 1H).450448

Table 1-45
No. etc.Structural formulaNMRMS (M+H) MS (M-N)
2211H-NMR (DMSO-D6) δ: 0,89-of 1.07 (2H, m), 1,01 (6H, s), of 1.48 (2H, d, J=12,89 Hz), 1,57 of-1.59 (2H, m), 1,89-of 1.92 (3H, m), of 2.15 (6H, s), 2,34 (2H, s), 2,42 (2H, s), 2,67 (2H, s), 3,14-3,39 (2H, m), 3,73 (4H, d, J=10,07 Hz), 3,92-4,07 (0H, m), 6,61 (1H, s), 6,83 (1H, d, J=7,66 Hz), 7.23 percent (1H, s), 7,55 (1H, d, J=7,66 Hz), 11,38 (1H, s), of 12.53 (1H, s).478476
2221H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,58 (2H, t, J=6,25 Hz), 2,14 (6H, s), is 2.30 (2H, t, J=6.85 Hz), 2,42 (2H, s), 2,67 (2H, t, J=5,84 Hz), 3,17 (3H, C), to 3.67 (2H, s), and 3.72 (2H, t, J=of 6.65 Hz), 6,60 (1H, s) 6,86 (1H, d, J=is 8.46 Hz), 7,26 (1H, s), 7,54 (1H, d, J=is 8.46 Hz), 11,42 (1H, s), 12,54 (1H, s).424422

2231H-NMR (DMSO-D6) δ: 1,00 (6H, s), 1.41 to of 1.44 (2H, m), 1,54-to 1.69 (6H, m), 2,07 (6H, s), of 2.20 (2H, t, J=7,07 Hz), a 2.36-2,43 (2H, m), 2,52-2,70 (3H, m) to 2.94 (2H, t, J=of 11.02 Hz), 3,62 (2H, t, J=7,30 Hz), and 3.72 (2H, DD, J=11,36, 2,78 Hz), 6,61 (1H, s), of 6.85 (1H, d, J=8,12 Hz), 7.23 percent (1H, s), 7,56 (1H, d, J=8,12 Hz) to 11.35 (1H, s), 12,54 (1H, s).478476
224 1H-NMR (DMSO-D6) δ: 1,00 (6H, s), 1.56 to of 1.75 (6H, m), 1,83-of 1.92 (2H, m), 2,10 (6H, s), 2,24 (2H, t, J=of 6.96 Hz), is 2.41 (2H, s), of 2.66 (2H, s), 3,56-3,70 (3H, m), 3,81 (1H, square, J=of 7.19 Hz), of 4.12 (1H, DD, J=7,54, of 5.68 Hz), 6,60 (1H, C) of 6.85 (1H, d, J=8.35 Hz), 7.23 percent (1H, s), 7,55 (1H, d, J=8.35 Hz), 11,40 (1H, s), of 12.53 (1H, s).464462

Table 1-46
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2251H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1.56 to of 1.64 (4H, m), 1,71-of 1.75 (1H, m), 1,98-2,03 (1H, m), of 2.08 (6H, s), 2,22 (2H, t, J=7,05 Hz), is 2.41 (2H, s), 2,54-2,69 (3H, m), 2,79-2,87 (1H, m), 3.46 in-and 3.72 (6H, m), 6,62 (1H, s), Of 6.85 (1H, d, J=8,06 Hz), 7.23 percent (1H, s), EUR 7.57 (1H, d, J=8,06 Hz), at 11.37 (1H, s), of 12.53 (1H, s).464462
2261H-NMR (DMSO-D6) δ: 0,94-of 1.03 (2H, m), 1,01 (6H, s), of 1.48 (2H, d, J=11,69 Hz), 1.56 to of 1.64 (4H, m), 1,91-of 1.92 (1H, m), 1,91 (2H, s), 2,10 (6H, s), of 2.23 (2H, t, J=7,05 Hz), 2,42 (2H, s), 2,65-2,69 (2H, m), 3,20-3,26 (2H, m), 3,63-to 3.74 (4H, m), 6,61 (1H, s), is 6.81 (1H, d, J=is 8.46 Hz), 7,20 (1H, s), 7,56 (1H, d, J=is 8.46 Hz), at 11.37 (1H, s), of 12.53 (1H, s). 492490

2271H-NMR (DMSO-D6) δ: 1,00 (6H, s), of 1.57 (2H, t, J=6,29 Hz), to 1.87 (1H, DD, J=12,24, 9,15 Hz), a 2.36-2,47 (1H, m), is 2.40 (2H, s), 2,65-of 2.67 (2H, m), 3,74-of 3.78 (2H, m), 4,25-4,34 (1H, m), of 5.68 (1H, d, J=5,73 Hz), a 6.53 (1H, s), 7.23 percent (1H, d, J=to 8.38 Hz), of 7.48 (1H, d, J=to 8.38 Hz), 7,74 (1H, s), 11,22 (1H, s), of 12.46 (1H, s).365363
2281H-NMR (DMSO-D6) δ: 1,00 (6H, s), of 1.57 (2H, t, J=6,29 Hz), 2,02-of 2.21 (2H, m), is 2.40 (2H, s), 2,62-2,73 (3H, m), 3,63-of 3.75 (2H, m), 3,76-3,88 (2H, m), of 4.77 (1H, t, J=5,18 Hz), of 6.52 (1H, s), 7,21 (1H, d, J=to 8.38 Hz), 7,45 (1H, d, J=to 8.38 Hz), of 7.70 (1H, s), 11,21 (1H, s), of 12.46 (1H, s).379377

Table 1-47
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2291H-NMR (DMSO-D6) δ: 1,00 (6H, s), of 1.17 (3H, d, J=of 7.19 Hz), of 1.57 (2H, t, J=6,38 Hz), 1,65-1,75 (1H, m), 2.9 to a high of 2.35 (1H, m), is 2.40 (2H, s), 2,57-2,70 (3H, m), of 3.77-3,82 (2H, m), of 6.52 (1H, s), 7,21 (1H, d, J=8.35 Hz), of 7.46 (1H, d, J=8.35 Hz), of 7.70 (1H, s), 11,21 (1H, s), of 12.46 (1H, s).363361
2301H-NMR (DMSO-D6) δ: 1,00 (6H, s), of 1.06 (3H, s), of 1.57 (2H, t, J=6,29 Hz), 1,78-of 1.85 (1H, m), 2,30-a 2.36 (1H, m), is 2.40 (2H, s), of 2.66 (2H, s), 3,27-3,30 (1H, m), 3,58 (1H, DD, J=10,26, of 5.40 Hz), of 3.78 (2H, t, J=7,17 Hz), 4,91 (1H, t, J=5,40 Hz), of 6.52 (1H, s), 7.23 percent (1H, d, J=to 8.38 Hz), of 7.46 (1H, d, J=to 8.38 Hz), 7,71 (1H, s), 11,21 (1H, s), of 12.46 (1H, s).393391

2311H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,24-of 1.40 (2H, m), 1,48-to 1.67 (8H, m), is 2.41 (2H, s), 2.49 USD is 2.55 (1H, m), 2,66-2,69 (2H, m), 3,44-3,51 (2H, m), 3,66-and 3.72 (2H, m), 4,59 (1H, t, J=5,64 Hz), 6,60 (1H, s) 6,86 (1H, d, J=8,06 Hz), 7,25 (1H, s), 7,53 (1H, d, J=8,06 Hz), 11,31 (1H, s) 12,50 (1H, s).421419
2321H-NMR (DMSO-D6) δ: from 0.92 to 1.01 (2H, m), 1,01 (6H, s), 1,47-of 1.50 (2H, m), 1,55-1,60 (2H, m), 1,88-of 1.95 (1H, m), of 1.92 (2H, s), 2,42 (2H, s), 2,66-of 2.68 (2H, m), 3,19-3,26 (2H, m), 3,44-3,51 (2H, m), 3,68-to 3.74 (4H, m), 4,62 (1H, t, J=5,44 Hz), 6,60 (1H, s), at 6.84 (1H, d, J=is 8.46 Hz), 7,22 (1H, s), 7,54 (1H, d, J=is 8.46 Hz), 11,38 (1H, s), of 12.53 (1H, s). 451449

2331H-NMR (DMSO-D6) δ: 0,61-of 0.72 (2H, m), 1,01 (6H, s), 1,37-of 1.49 (2H, m), 1,55-1,70 (4H, m), 1,84-of 1.93 (2H, m), 2,02-for 2.14 (1H, m), is 2.41 (2H, s), 2,64-to 2.73 (2H, m), 2,95-of 3.04 (1H, m), 3,13 (3H, C), 3,41-3,49 (2H, m), 3,63-3,70 (2H, m), 4,58 (1H, t, J=5,24 Hz), 6,60 (1H, s) 6,86 (1H, d, J=8,06 Hz), 7,25 (1H, s), 7,54 (1H, d, J=8,06 Hz), made 11.32 (1H, s), for 12.51 (1H, s).465463

Table 1-48
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2341H-NMR (DMSO-D6) δ: 0,64-was 0.77 (2H, m), 1,01 (6H, s), of 1.35 to 1.47 (2H, m), 1,54-of 1.65 (4H, m), 1,67-to 1.77 (2H, m), 1,98-2,10 (1H, m), 2,42 (2H, s), 2,63-of 2.75 (2H, m), 2,68 (2H, s), 3,17-3,29 (1H, m), 3,41-3,50 (2H, m), 3,61-3,73 (0H, m), 4,31 (1H, d, J=4,84 Hz), 4,57 (1H, t, J=5,44 Hz), 6,60 (1H, s), of 6.85 (1H, d, J=8,06 Hz), 7,25 (1H, s), 7,54 (1H, d, J=8,06 Hz), made 11.32 (1H, s) 12,50 (1H, s).451449

1H-NMR (DMSO-D6) δ: 0,63-0,75 (2H, m), 0,94-of 1.07 (1H, m), 1,01 (6H, s), from 1.07 to 1.21 (2H, m), 1,50-to 1.63 (7H, m), 1,64-of 1.77 (1H, m) to 1.86 (2H, d, J=6.85 Hz), 2,42 (2H, s), 2,64-2,71 (2H, m), 3.46 in-3,50 (2H, m), 3,67-3,71 (2H, m), 4,58 (1H, t, J=5,44 Hz), 6,59 (1H, s), about 6,82 (1H, d, J=8,06 Hz), 7,21 (1H, s), 7,53 (1H, d, J=8,06 Hz), 11,33 (1H, s) 12,50 (1H, s).449447
2361H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,42-1,45 (2H, m), 1,57-of 1.70 (4H, m), 2,37-to 2.46 (1H, m), 2,42 (2H, s), 2,66-2,69 (2H, m), 2,92-2,98 (2H, m), 3,45-3,49 (2H, m), 3,67-to 3.74 (4H, m), 4,59 (1H, t, J=5,64 Hz), 6,60 (1H, s), To 6.88 (1H, d, J=8,06 Hz), 7,27 (1H, s), 7,54 (1H, d, J=8,06 Hz), made 11.32 (1H, s) 12,50 (1H, s).437435

2371H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1.56 to of 1.75 (4H, m), 1,82-to 1.94 (2H, m), is 2.41 (2H, s), 2,62-of 2.72 (2H, m), 3,42-3,55 (2H, m), 3,57-3,74 (3H, m), 3,81 (1H, square, J=7,12 Hz), 4,14 (1H, DD, J=7,25, 5,64 Hz), 4,63 (1H, t, J=5,64 Hz), 6,59 (1H, s), to 6.88 (1H, d, J=8,06 Hz), 7,27 (1H, s), 7,53 (1H, d, J=8,06 Hz), 11,36 (1H, s) 12,50 (1H, s).423421

Table 1-49
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2381H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,54-1,62 (2H, m), 1,68-to 1.77 (1H, m), 1,97-of 2.06 (1H, m), 2,42 (2H, s), 2,61-2,71 (2H, m), 2,80-is 2.88 (1H, m), 3,45-to 3.76 (8H, m), USD 4.61 (1H, t, J=5,44 Hz), 6,60 (1H, s), to 6.88 (1H, d, J=8,06 Hz), 7,26 (1H, s), 7,55 (1H, d, J=8,06 Hz) to 11.35 (1H, s) 12,50 (1H, s).423421

2391H-NMR (DMSO-D6) δ: 0,75-0,90 (2H, m), 0,98-of 1.12 (1H, m), 1,01 (6H, s), 1,31-of 1.47 (3H, m), of 1.52 to 1.63 (6H, m), 2,08-2,19 (1H, m), is 2.41 (2H, s), 2,63-2,71 (2H, m), 3,41-of 3.50 (3H, m), 3,62-3,73 (2H, m), 4,60 (1H, t, J=to 5.62 Hz), 6,60 (1H, s), of 6.85 (1H, d, J=8,16 Hz), 7,24 (1H, s), 7,54 (1H, d, J=Hz 8,16), of 11.34 (1H, s), 12,52 (1H, s).435433
2401H-NMR (DMSO-D6) δ: 0,92-1,02 (2H, m), 1,01 (6H, s), 1,27-of 1.38 (2H, m), 1,54-to 1.79 (6H, m), 2,11-of 2.23 (1H, m), is 2.41 (2H, s), 2,65-2,71 (2H, m), 3,18-3,23 (1H, m), 3.43 points-3,48 (2H, m), 3,64-to 3.67 (2H, m), 4,60 (1H, t, J=to 5.62 Hz), 6,60 (1H, s) 6,86 (1H, d, J=8,16 Hz), 7,25 (1H, s), 7,54 (1H, d, J=8,16 Hz), 8,31 (0H,), of 11.34 (1H, s), 12,52 (1H, s). 465463

2411H-NMR (DMSO-D6) δ: 0,43-0,62 (1H, m), to 0.67 and 0.90 (1H, m), of 0.90 (3H, d, J=to 6.62 Hz), 1,01 (6H, s), 1,05-1,19 (2H, m), 1,35-of 1.44 (1H, m), of 1.50 to 1.68 (6H, m), 1,94-2,07 (1H, m), is 2.41 (2H, s), 2,63-2,71 (2H, m), 3.43 points-of 3.53 (2H, m), 3,56-3,81 (2H, m), USD 4.61 (1H, t, J=5,51 Hz), 6,59 (1H, s), about 6,82 (1H, d, J=7,94 Hz), 7.23 percent (1H, s), 7,54 (1H, d, J=7,94 Hz), of 11.34 (1H, s), 12,52 (1H, s).463461

Table 1-50
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2421H-NMR (DMSO-D6) δ: 0,74-of 1.20 (2H, m), of 0.91 (3H, d, J=to 6.62 Hz), 1,01 (6H, s), 1,42 is 1.71 (5H, m), 1,99-2,10 (1H, m), is 2.41 (2H, s), 2,64-2,71 (2H, m), 3,16-3,23 (2H, m), 3.43 points-3,84 (6H, m), 4,62 (1H, t, J=5,40 Hz), 6,60 (1H, (C), at 6.84 (1H, d, J=7,94 Hz), 7,24 (1H, s), 7,55 (1H, d, J=7,94 Hz) to 11.35 (1H, s), 12,52 (1H, s).465463

243 1H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.35 (3H, C) of 1.54 to 1.60 (2H, m), 2,01-2,07 (1H, m), 2,28-of 2.35 (1H, m), is 2.41 (2H, s), 2,62-2,70 (2H, m), of 3.25 (3H, s), 3,72-3,86 (2H, m), 6,54 (1H, s), 7,22 (1H, d, J=to 8.38 Hz), 7,49 (1H, d, J=to 8.38 Hz), 7,74 (1H, s), of 11.25 (1H, s), 12,47 (1H, s).393391
2441H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.30 (3H, C), of 1.57 (2H, t, J=6,40 Hz), is 2.09 (2H, t, J=6,84 Hz), is 2.41 (2H, s), 2,62-2,70 (2H, m), 3,67-of 3.85 (2H, m), the 5.45 (1H, C), a 6.53 (1H, s), 7.23 percent (1H, d, J=to 8.38 Hz), of 7.48 (1H, d, J=to 8.38 Hz), 7,74 (1H, s), 11,24 (1H, s), of 12.46 (1H, s).379377

245
stereoisomer Ave 246
1H-NMR (DMSO-D6) δ: of 1.01 (6H, C) of 1.04-of 1.20 (1H, m), 1,30-is 1.51 (1H, m), 1,58 (2H, t, J=6,45 Hz), 1,64-of 1.74 (2H, m), 2,42 (2H, s), 2,50-of 2.57 (1H, m), 2,64-2,70 (2H, m), 2,90-2,96 (1H, m), 3,03-3,14 (1H, m), 3,36 is 3.59 (3H, m), 3,62-with 3.79 (4H, m), 4,66-4,71 (2H, m), 6,60 (1H, s), 6,87 (1H, d, J=8,06 Hz), 7,27 (1H, s), 7,54 (1H, d, J=8,06 Hz), 11,42 (1H, s), of 12.53 (1H, s).467465

Table 1-51
No. etc.Structural formula NMRMS (M+H)MS (M-N)
246
stereoisomer Ave 245
1H-NMR (DMSO-D6) δ: 0,98-of 1.16 (2H, m), and 1.00 (6H, s), 1,28-of 1.53 (2H, m), of 1.57 (2H, t, J=6,25 Hz), 1,73-of 1.83 (1H, m), is 2.41 (2H, s), 2,63-2,70 (2H, m), 2,95-of 3.00 (1H, m), 3,07-3,14 (1H, m), 3,44-of 3.78 (7H, m), of 4.66 (1H, t, J=5,44 Hz), 4,91 (1H, d, J=8,06 Hz), 6,60 (1H, s), 6,87 (1H, d, J=8,06 Hz), 7,27 (1H, s), 7,53 (1H, d, J=8,06 Hz) 11,40 (1H, s), 12,52 (1H, s).467465

2471H-NMR (DMSO-D6) δ: of 0.76 (6H, d, J=6.85 Hz), 1,01 (6H, s), 1,58 (2H, t, J=6,25 Hz), to 1.87 (2H, d, J=6.85 Hz), 1,95-of 1.99 (1H, m), is 2.41 (2H, s), 2,63-2,70 (2H, m), 3,45-3,51 (2H, m), 3,67-and 3.72 (2H, m), of 4.54-to 4.68 (1H, m), 6,60 (1H, s), 6,83 (1H, d, J=is 8.46 Hz), 7,22 (1H, s), 7,53 (1H, d, J=is 8.46 Hz), 11,36 (1H, s), 12,52 (1H, s).409407
2481H-NMR (DMSO-D6) δ: 0,94-1,08 (1H, m), 1,01 (6H, s) to 1.21 and 1.33 (3H, m), 1,49-of 1.61 (4H, m), 1,73-of 1.85 (2H, m), 2,09-to 2.18 (1H, m), is 2.41 (2H, s), 2,64-2,71 (2H, m), of 3.46 (2H, t, J=of 6.65 Hz), 3,56-3,73 (3H, m), 6,61 (1H, s), 6,86 (1H, DD, J=is 8.46, of 1.81 Hz), 7,25 (1H, s), 7,54 (1H, d, J=is 8.46 Hz), made 11.32 (1H, s), 12,52 (1H, s).451 449

2491H-NMR (DMSO-D6) δ: from 0.92 to 1.01 (2H, m), 1,01 (6H, s), 1,47-of 1.50 (2H, m), 1,55-1,60 (2H, m), 1,88-of 1.95 (1H, m), of 1.92 (2H, s), 2,42 (2H, s), 2,66-of 2.68 (2H, m), 3,19-3,26 (2H, m), 3,44-3,51 (2H, m), 3,68-to 3.74 (4H, m), 4,62 (1H, t, J=5,44 Hz), 6,60 (1H, s), at 6.84 (1H, d, J=is 8.46 Hz), 7,22 (1H, s), 7,54 (1H, d, J=is 8.46 Hz), 11,38 (1H, s), of 12.53 (1H, s).451449

Table 1-52
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2501H-NMR (DMSO-D6) δ: 1,00 (6H, s), from 1.07 to 1.32 (5H, m), 1,49-of 1.95 (9H, m), of 2.05 to 2.14 (1H, m), is 2.40 (2H, s), 2,50-of 2.58 (1H, m), 2,65 (2H, s), 3,66-3,86 (2H, m), of 6.52 (1H, s), 7,18 (1H, d, J=8,12 Hz), 7,45 (1H, d, J=8,12 Hz), To 7.68 (1H, s), 11,19 (1H, s), of 12.46 (1H, s).431429

2511H-NMR (DMSO-D6) δ: 0.80 to 1,78 (14H, m), and 1.00 (6H, s), 1,99-2,7 (1H, m), is 2.40 (2H, s), 2,59-2,70 (2H, m), 3.46 in-to 3.82 (4H, m), 4,79 (1H, s), of 6.52 (1H, s), 7,20 (1H, d, J=8.35 Hz), 7,45 (1H, d, J=8.35 Hz), of 7.70 (1H, s), 11,19 (1H, s), of 12.46 (1H, s).461459
2521H-NMR (DMSO-D6) δ: of 1.01 (6H, C) of 1.01 (3H, d, J=6,72 Hz), 1,58 (2H, t, J=6,25 Hz), 2,18-of 2.30 (2H, m), 2,39-of 2.48 (2H, m), is 2.41 (2H, s), 2,62-2,71 (2H, m), 3,13 (1H, square, J=6,72 Hz), 3.46 in-3,52 (6H, m), 3,59-of 3.78 (2H, m), USD 4.61 (1H, t, J=5,44 Hz), 6,59 (1H, s), 6,89 (1H, s), 7,29 (1H, s), 7,52 (1H, d, J=8,06 Hz), 11,33 (1H, s) 12,50 (1H, s).466464

2531H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,58 (2H, t, J=6,06 Hz), to 1.67 (4H, s), 2,12-of 2.21 (2H, m), 2,42 (2H, s), 2,63-to 2.73 (2H, m), 3,17-of 3.25 (2H, m), 3,44-3,52 (2H, m), of 3.69 (2H, t, J=is 6.51 Hz), 3,73 (2H, C), a 4.65 (1H, t, J=5,73 Hz), 6,60 (1H, s), at 6.92 (1H, d, J=7,94 Hz), 7,31 (1H, s), 7,55 (1H, d, J=7,94 Hz), of 11.43 (1H, s), of 12.53 (1H, s).464462
2541H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,58 (2H, t, J=6,25 Hz), 2,27-of 2.35 (3H, m), is 2.41 (2H, s), 2,67 (3H, t, J=6,25 Hz), 2,83 (2H, s), or 3.28 (2H, s), 3,44-3,52 (4H, m), 3,68 (2H, t, J=6,45 Hz), USD 4.61 (1H, t, J=5,64 Hz), 6,60 (1H, s), to 6.88 (1H, d, J=8,06 Hz), 7,29 (1H, s), 7,53 (1H, d, J=8,06 Hz), of 1.33 (1H, C) of 12.43 (1H, s).452450

Table 1-53
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2551H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.02 (3H, d, J=6,45 Hz), 1,58 (2H, t, J=6,25 Hz), 2,22-2,31 (2H, m), 2,39-of 2.48 (4H, m), 2,64-2,71 (2H, m), 3,13 (1H, square, J=6,45 Hz), 3,42-to 3.56 (6H, m), 3,60-with 3.79 (2H, m), 4,62 (1H, t, J=5,44 Hz), 6,60 (1H, s), to 6.88 (1H, d, J=is 8.46 Hz), 7,31 (1H, s), 7,53 (1H, d, J=is 8.46 Hz), made 11.32 (1H, s) 12,50 (1H, s).466464
2561H-NMR (DMSO-D6) δ: of 1.01 (6H, C) of 1.43 to 1.68 (8H, m), 2,31-of 2.45 (4H, m), 2,64-of 2.72 (2H, m), and 3.31 (2H, s), 3.43 points-3,51 (2H, m), 3,68 (2H, t, J=is 6.51 Hz), of 3.78 (2H, s) a 4.64 (1H, t, J=5,40 Hz), 6,61 (1H, s), at 6.92 (1H, d, J=7,72 Hz), 7,32 (1H, s), 7,56 (1H, d, J=7,72 Hz), 11,42 (1H, s), 12,52 (1H, s).478476

2571H-NMR (DMSO-D 6) δ: of 1.01 (6H, C) of 1.01 (3H, d, J=7,06 Hz), 1,43-of 1.54 (2H, m), 1,58 (1H, t, J=6,29 Hz), 2,10-2,19 (1H, m), 2,24-of 2.35 (1H, m), 2,42 (2H, s), 2,64-2,70 (2H, m), 3,23-3,30 (2H, m), 3,44-3,51 (2H, m), 3,64-3,73 (4H, m), of 4.66 (1H, t, J=to 5.62 Hz), 6,61 (1H, s), at 6.92 (1H, d, J=to 8.38 Hz), 7,32 (1H, s), EUR 7.57 (1H, d, J=to 8.38 Hz), of 11.45 (1H, s), of 12.53 (1H, s).464462
2581H-NMR (DMSO-D6) δ: 0,96-1,07 (13H, m), 1,22-1,32 (2H, m), 1,49-of 1.61 (4H, m), 1,74-to 1.87 (2H, m), 2,06-2,19 (1H, m), is 2.41 (2H, s), 2,64-2,71 (2H, m), 3,58-3,68 (3H, m), is 4.21 (1H, s), 6,60 (1H, s), about 6,82 (1H, d, J=at 8.60 Hz), 7,20 (1H, s), 7,55 (1H, d, J=at 8.60 Hz), 11,33 (1H, s), 12,52 (1H, s).435433

Table 1-54
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2591H-NMR (DMSO-D6) δ: 0,95-of 1.07 (8H, m), 1,23-1,32 (2H, m), 1,48-1,62 (4H, m), 1,72-to 1.87 (2H, m), 2,09-of 2.20 (1H, m), is 2.41 (2H, s), 2,62-of 2.72 (2H, m), 3,21 (3H, C), 3,38 (2H, t, J=6.18 of Hz) and 3.59-3,65 (1H, m), 3,71-3,82 (2H, m), Is 4.21 (1H, d, J=2,87 Hz), 6,61 (1H, s), at 6.84 (1H, d, J=to 8.38 Hz), 7,25 (1H, s), 7,54 (1H, d, J=to 8.38 Hz), of 11.34 (1H, s), of 12.53 (1H, s).465 463
2601H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.05 (3H, t, J=7,25 Hz), 1,24 (3H, d, J=6.85 Hz), 1,58 (2H, t, J=6,45 Hz), 2,42 (2H, s), 2,64-2,71 (2H, m), 3,16-3,23 (1H, m), 3,44-of 3.53 (1H, m), 3,63-3,84 (5H, m), 3,84-3,92 (1H, m), 4,08 (1H, square, J=6.85 Hz), 6,61 (1H, s), to 6.88 (1H, d, J=7,66 Hz), 7,28 (1H, s), 7,58 (1H, d, J=8,06 Hz) 11,41 (1H, s), for 12.51 (1H, s).464462

2611H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,02-1,09 (6H, m), 1,58 (2H, t, J=6,25 Hz), is 2.41 (2H, s), 2,64-of 2.72 (2H, m), 3,42-3,73 (5H, m), of 3.78 (1H, DD, J=11,48, of 3.43 Hz), of 4.00 (2H, DD, J=18,54, 16,52 Hz), 4,08 (1H, d, J=16,52 Hz), 6,62 (1H, C) at 6.92 (1H, d, J=is 8.46 Hz), 7,31 (1H, s), members, 7.59 (1H, d, J=is 8.46 Hz), 11,40 (1H, s), for 12.51 (1H, s).464462
2621H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.07 (3H, d, J=6,45 Hz), 1,58 (2H, t, J=6,45 Hz), is 2.41 (2H, s), 2,65-2,71 (2H, m), up 3.22 (3H, s) to 3.41 (2H, t, J=6,04 Hz), 3,44-of 3.53 (2H, m), 3,57 (1H, DD, J=11,48, 3,83 Hz), 3.75 to 3,84 (3H, m), Of 4.00 (2H, DD, J=18,33, 16,52 Hz), 4,10 (1H, d, J=16,52 Hz), 6,62 (1H, s), 6,93 (1H, d, J=8,06 Hz), 7,34 (1H, s), 7,58 (1H, d, J=8,06 Hz) 11,41 (1H, s), for 12.51 (1H, s).494492

Table 1-55
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2631H-NMR (DMSO-D6) δ: 0,75-of 0.88 (1H, m), of 0.91 (3H, d, J=6.85 Hz), 0,96-1,18 (11H, m), 1,45-of 1.54 (2H, m), 1,58 (2H, t, J=6,45 Hz), 1,60 is 1.71 (1H, m), 1,98-of 2.09 (1H, m), is 2.41 (2H, s), 2,68 (2H, t, J=6,45 Hz), 3,20 (2H, t, J=11,69 Hz), 3,58-3,83 (3H, m), 6,61 (1H, s), 6,80 (1H, d, J=is 8.46 Hz), 7,20 (1H, s), EUR 7.57 (1H, d, J=is 8.46 Hz), 11,30 (1H, s), 12,49 (1H, s).449447
2641H-NMR (DMSO-D6) δ: use 0.75 to 0.89 (1H, m), 0,89 (3H, t, J=8.66 roubles Hz), 0,97-1,19 (2H, m), 1,01 (6H, s), 1,45-1,55 (2H, m), 1,57-of 1.70 (1H, m), 1,58 (2H, t, J=6,25 Hz), 2.00 in of 2.12 (1H, m), is 2.41 (2H, s), 2,62-of 2.72 (2H, m), 3,15-3,24 (5H, m), 3,36-3,47 (2H, m), 3,61-4,01 (3H, m), 6,61 (1H, s), about 6,82 (1H, d, J=8,06 Hz), 7,25 (1H, s), 7,55 (1H, d, J=8,06 Hz), made 11.32 (1H, s) 12,50 (1H, s).479477

2651H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,24 (3H, d, J=6,84 Hz), 1,58 (2H, t, J=6,29 Hz), 2,42 (2H, s), 2,63-to 2.74 (2H, m), 3,1-of 3.25 (4H, m), 3,39 (2H, t, J=5,95 Hz), 3.43 points-of 3.53 (1H, m), 3,62-3,94 (6H, m), 4,08 (1H, square, J=6,76 Hz), 6,61 (1H, C), 6,90 (1H, d, J=to 8.38 Hz), 7,31 (1H, s), EUR 7.57 (1H, d, J=to 8.38 Hz), 11,47 (1H, s), 12,54 (1H, s).494492
2661H-NMR (DMSO-D6) δ: 0,93-of 1.04 (5H, m), 1,01 (6H, s), 1,27-of 1.36 (2H, m), 1,55-to 1.79 (4H, m), 1,58 (2H, t, J=6,38 Hz), 2,11-of 2.21 (1H, m), is 2.41 (2H, s), 2,63-of 2.72 (2H, m), 3,15 (3H, C), 3,18-3,23 (1H, m), 3,63 (2H, square, J=of 6.96 Hz), 6,60 (1H, s), about 6,82 (1H, d, J=8,12 Hz), 7,20 (1H, s), 7,55 (1H, d, J=8,12 Hz) to 11.35 (1H, s), of 12.53 (1H, s).449447

Table 1-56
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2671H-NMR (DMSO-D6) δ: from 0.92 to 1.05 (2H, m), 1,01 (6H, s), 1,27-of 1.36 (2H, m), 1,51-of 1.81 (4H, m), 1,58 (2H, t, J=of 6.26 Hz), 2,13-of 2.23 (1H, m), is 2.41 (2H, s), 2,63-of 2.72 (2H, m), 3,15 (3H, C), 3,18-3,23 (1H, m), 3,20 (3H, s), 3,38 (2H, t, J=6,15 Hz), of 3.69-3,82 (2H, m), 6,60 (1H, s), at 6.84 (1H, d, J=8.35 Hz), 7,24 (1H, s), 7,54 (1H, d, J=8.35 Hz), 11,36 (1H, s), of 12.53 (1H, s).479477
268 1H-NMR (DMSO-D6) δ: 0,92-of 1.09 (2H, m), 1,01 (6H, s), was 1.04 (3H, t, J=7,05 Hz), of 1.48 (2H, d, J=12,89 Hz), 1,58 (2H, t, J=6,45 Hz), of 1.92 (3H, s), 2,42 (2H, s), 2,67 (2H, t, J=6,45 Hz), 3,18-3,27 (2H, m) to 3.67 (2H, square, J=7,05 Hz), 3,68-to 3.76 (2H, m), 6,60 (1H, s), of 6.79 (1H, d, J=8,06 Hz), 7,18 (1H, s), 7,55 (1H, d, J=8,06 Hz), of 11.34 (1H, s), for 12.51 (1H, s).435433

2691H-NMR (DMSO-D6) δ: from 0.92 to 1.05 (2H, m), 1,01 (6H, s), 1,44-of 1.52 (2H, m), 1,58 (2H, t, J=6,25 Hz), of 1.92 (3H, s), 2,42 (2H, s), 2,63-2,71 (2H, m), 3,18-3,27 (2H, m), 3,21 (3H, s), 3,40 (2H, t, J=6,04 Hz), 3,68-to 3.76 (2H, m), 3,76-3,84 (2H, m), 6,60 (1H, s), is 6.81 (1H, d, J=is 8.46 Hz), 7,22 (1H, s), 7,54 (1H, d, J=is 8.46 Hz), to 11.35 (1H, s) 12,50 (1H, s).465463
2701H-NMR (DMSO-D6) δ: of 1.01 (6H, s), was 1.04 (3H, t, J=6,98 Hz), 1,45-of 1.54 (2H, m), 1,54-of 1.65 (6H, m), 2,34-2,41 (2H, m), 2,42 (2H, s), 2,63-2,71 (2H, m), or 3.28-to 3.34 (2H, m), 3,66 (2H, square, J=6,98 Hz), of 3.77 (2H, s), 6,61 (1H, s), 6,87 (1H, d, J=is 8.46 Hz), 7,27 (1H, s), 7,56 (1H, d, J=is 8.46 Hz), is 11.39 (1H, s), for 12.51 (1H, s).462460

Table 1-57
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2711H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.05 (3H, t, J=7,05 Hz), of 1.07 (3H, d, J=6,04 Hz), 1,58 (2H, t, J=6,04 Hz), 2,42 (2H, s), 2,67 (2H, t, J=6,04 Hz), of 3.46 (1H, d, J=16,52 Hz), 3,47-was 3.54 (1H, m), 3,54-3,61 (1H, m), 3,61-3,73 (2H, m), 3.75 to 3,82 (1H, m), 3,95-4,05 (2H, m), 4,08 (1H, d, J=16,52 Hz), 6,61 (1H, s), 6,91 (1H, d, J=8,06 Hz), 7,30 (1H, s), 7,58 (1H, d, J=8,06 Hz) 11,40 (1H, s), for 12.51 (1H, s).464462
2721H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.07 (3H, d, J=6,04 Hz), 1,58 (2H, t, J=6,25 Hz), 2,42 (2H, s), 2,63-2,71 (2H, m), up 3.22 (3H, s) to 3.41 (2H, t, J=6,04 Hz), 3.43 points-of 3.53 (2H, m), 3,54-of 3.60 (1H, m), 3,73-3,85 (3H, m), 3,94-of 4.05 (2H, m), 4,10 (1H, d, J=16,52 Hz), 6,61 (1H, s), 6,93 (1H, d, J=is 8.46 Hz), 7,34 (1H, s), 7,58 (1H, d, J=is 8.46 Hz), 11,42 (1H, s), for 12.51 (1H, s).494492

2731H-NMR (DMSO-D6) δ: 0,66 is 0.81 (1H, m), 0,94-1,09 (2H, m), 1,01 (6H, s), was 1.04 (3H, t, J=7,12 Hz), to 1.21-to 1.38 (2H, m), 1,53-of 1.95 (8H, m), 2,42 (2H, s), 2,61-to 2.73 (2H, m), 2,86-of 2.97 (1H, m), 3,09 (1H, s), 3,17 (2H, s), 3,66 (2H, �V., J=7,12 Hz), 6,61 (1H, s), 6,78 (1H, d, J=8,06 Hz), 7,17 (1H, s), 7,54 (1H, d, J=is 8.46 Hz), made 11.32 (1H, s), for 12.51 (1H, s).463461
2741H-NMR (DMSO-D6) δ: 0,67-0,81 (1H, m), 0,92-of 1.09 (2H, m), 1,01 (6H, s), 1,21-to 1.38 (2H, m), 1,52-to 1.94 (8H, m), is 2.41 (2H, s), 2,64-of 2.72 (2H, m), 2,86-2,96 (1H, m), 3,09 (1H, s), 3,17 (2H, s), 3,21 (3H, s), 3,40 (2H, t, J=6,04 Hz), 3.75 to 3,83 (2H, m), 6,59 (1H, s), 6,80 (1H, d, J=7,66 Hz), 7,21 (1H, s), 7,53 (1H, d, J=7,66 Hz) to 11.35 (1H, s) 12,50 (1H, s).493491

Table 1-58
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2751H-NMR (DMSO-D6) δ: of 1.01 (6H, C) of 1.01 (3H, d, J=6,72 Hz), of 1.06 (3H, t, J=7,05 Hz), 1,58 (2H, t, J=6,25 Hz), 2,21-2,31 (2H, m), 2,39-2.49 USD (2H, m), is 2.41 (2H, s), 2,63-2,70 (2H, m), of 3.12 (1H, square, J=6,72 Hz), 3,48 (4H, t, J=4,43 Hz), 3,60-and 3.72 (2H, m), 6,59 (1H, s), at 6.84 (1H, d, J=8,87 Hz), 7,25 (1H, s), 7,54 (1H, d, J=8,87 Hz), 11,33 (1H, s) 12,50 (1H, s).450448
276 1H-NMR (DMSO-D6) δ: of 1.01 (6H, C) of 1.01 (3H, d, J=6.85 Hz), 1,58 (2H, t, J=6,45 Hz), 2,21-2,31 (2H, m), 2,39-of 2.48 (2H, m), is 2.41 (2H, s), 2,63-2,71 (2H, m), 3,14 (1H, square, J=6.85 Hz), 3,23 (3H, C), 3,38-of 3.46 (2H, m), 3,48 (4H, t, J=4,43 Hz), 3,65-3,94 (2H, m), 6,59 (1H, s) 6,86 (1H, usher.C), 7,30 (1H, s), 7,53 (1H, d, J=8,06 Hz), of 11.34 (1H, s) 12,50 (1H, s).480478

2771H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.05 (3H, t, J=7,25 Hz), 1,22 (6H, s), 1,58 (2H, t, J=6,25 Hz), 2,42 (2H, s), 2,65-2,71 (2H, m), 3,21 (2H, s), 3,68 (2H, square, J=7,25 Hz), of 3.78 (2H, s), 3,97 (2H, s), 6,62 (1H, s), 6,89 (1H, d, J=is 8.46 Hz), 7,29 (1H, s), members, 7.59 (1H, d, J=is 8.46 Hz), 11,41 (1H, s), for 12.51 (1H, s).478476
2781H-NMR (DMSO-D6) δ: of 1.01 (6H, s), to 1.22 (6H, s), 1,58 (2H, t, J=6,45 Hz), 2,42 (2H, s), 2,68 (2H, t, J=6,45 Hz), 3,20 (2H, s), up 3.22 (3H, s), 3,40 (2H, t, J=5,84 Hz), with 3.79 (2H, s), 3,81 (2H, t, J=5,84 Hz), 3,97 (2H, s), 6,62 (1H, C), 6,90 (1H, d, J=is 8.46 Hz), to 7.33 (1H, s), 7,58 (1H, d, J=is 8.46 Hz), 11,42 (1H, s), for 12.51 (1H, s).508506

2791NAMR (DMSO-D 6) δ: of 1.01 (6H, s), of 1.05 (3H, t, J=7,17 Hz), of 1.13 (3H, d, J=5,95 Hz), 1,58 (2H, t, J=6,06 Hz), is 2.41 (2H, s), 2,65-2,71 (2H, m), 3,15-3,25 (2H, m), 3,63-3,73 (3H, m), 3,80-3,90 (2H, m), was 4.02 (2H, s), 6,62 (1H, C), 6,89 (1H, d, J=to 8.38 Hz), 7,28 (1H, s), members, 7.59 (1H, d, J=to 8.38 Hz), of 11.45 (1H, s), 12,54 (1H, s).464462

Table 1-59
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2801H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.13 (3H, d, J=6,03 Hz), 1,58 (2H, t, J=6,38 Hz), 2,42 (2H, s), 2,64-of 2.72 (2H, m), 3,14-of 3.25 (5H, m), 3,39 (2H, t, J=6,03 Hz), 3,70 (1H, d, J=16,70 Hz), 3,78-of 3.91 (4H, m), was 4.02 (2H, s), 6,62 (1H, C), 6,90 (1H, d, J=8,12 Hz), 7,32 (1H, s), 7,58 (1H, d, J=8,12 Hz), 11,47 (1H, s), 12,54 (1H, s).494492

2811H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,44-of 1.66 (8H, m), 2,34-of 2.46 (4H, m), 2,64-of 2.72 (2H, m), 3,21 (3H, s), or 3.28-a 3.35 (2H, m), 3,39 (2H, t, J=6,03 Hz), 3.75 to 3,82 (4H, m), 6,61 (1H, C), 6,90 (1H, d, J=8,12 Hz), 7,31 (1H, s), 7,56 (1H, d, J=8,12 Hz), 11,44 (1H, s), 12,54 (1H, s).492 490
2821H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.05 (3H, t, J=of 7.19 Hz), of 1.13 (3H, d, J=of 6.26 Hz), 1,58 (2H, t, J=6,38 Hz), 2,42 (2H, s), 2,64-of 2.72 (2H, m), 3,14-3,26 (2H, m), 3,62-3,74 (3H, m), 3,79-3,90 (2H, m), was 4.02 (2H, s), 6,62 (1H, C), 6,89 (1H, d, J=8.35 Hz), 7,28 (1H, s), members, 7.59 (1H, d, J=8.35 Hz), 11,46 (1H, s), 12,54 (1H, s).464462

2831H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.13 (3H, d, J=of 6.26 Hz), 1,58 (2H, t, J=of 6.26 Hz), 2,42 (2H, s), 2,64-2,71 (2H, m), 3,14-3,26 (5H, m), 3,39 (2H, t, J=5,91 Hz), 3,70 (1H, d, J=16,46 Hz), of 3.77-of 3.91 (4H, m), was 4.02 (2H, s), 6,62 (1H, C), 6,90 (1H, d, J=8.35 Hz), 7,32 (1H, s), 7,58 (1H, d, J=8.35 Hz), 11,47 (1H, s), of 12.55 (1H, s).494492

Table 1-60
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2841H-NMR (DMSO-D6) δ: of 1.00 (6H, C) of 1.01 (6H, s), was 1.04 (3H, t, J=to 7.28 Hz), 1,58 (2H, t, J=6.18 of Hz), 1,5 (2H, t, J=6,73 Hz), 2,42 (2H, s), 2,64-2,71 (2H, m), 3,24-of 3.32 (2H, m) to 3.64 (2H, s), to 3.67 (2H, square, J=to 7.28 Hz), 6,62 (1H, s), 6,89 (1H, d, J=8,16 Hz), 7,27 (1H, s), members, 7.59 (1H, d, J=Hz 8,16), of 11.45 (1H, s), 12,54 (1H, s).462460

2851H-NMR (DMSO-D6) δ: of 1.00 (6H, C) of 1.01 (6H, s), 1,58 (2H, t, J=6,45 Hz), of 1.76 (2H, t, J=6.85 Hz), 2,42 (2H, s), 2,64-2,71 (2H, m), up 3.22 (3H, s), 3,24-of 3.31 (2H, m), 3,39 (2H, t, J=5,84 Hz), 3,65 (2H, s), 3,80 (2H, t, J=6,04 Hz), 6,62 (1H, C), 6,90 (1H, d, J=7,66 Hz), 7,31 (1H, s), 7,58 (1H, d, J=is 8.46 Hz), 11,42 (1H, s), for 12.51 (1H, s).492490
2861H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,58 (2H, t, J=of 6.26 Hz), 2,42 (2H, s), 2,62-of 2.72 (2H, m), up 3.22 (3H, s), 3,29-3,36 (2H, m), 3,40 (2H, t, J=5,91 Hz), 3.75 to of 3.85 (6H, m) 4,00 (2H, s), 6,62 (1H, s), 6,91 (1H, d, J=8.35 Hz), 7,32 (1H, s), 7,58 (1H, d, J=8.35 Hz), 11,47 (1H, s), of 12.55 (1H, s).480478

2871H-NMR (DMSO-D6) δ: of 1.01 (6H, s), 1,58 (2H, t, J=of 6.26 Hz), 1,63-1,72 (4H, m), 2,13-of 2.20 (2H, m), is 2.41 (2H, s), 2,64-of 2.72 (2H, m), 3,21 (5H, s), 3,39 (2H, t, J=5,91 Hz), 3,73 (2H, s), 3,80 (2H, t, J=5,91 Hz), 6,61 (1H, �), 6,90 (1H, d, J=8.35 Hz), 7,31 (1H, s), EUR 7.57 (1H, d, J=8.35 Hz), of 11.45 (1H, s), 12,54 (1H, s).478476

Table 1-61
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2881H-NMR (DMSO-D6) δ: of 1.01 (6H, s), of 1.05 (3H, t, J=of 7.19 Hz), 1,58 (2H, t, J=of 6.26 Hz), 2,42 (2H, s), 2,63-of 2.72 (2H, m), or 3.28-3,36 (2H, m), 3,68 (2H, square, J=7,11 Hz), 3.75 to 3,82 (4H, m), 4,00 (2H, s), 6,62 (1H, C), 6,90 (1H, d, J=8,12 Hz), 7,28 (1H, s), members, 7.59 (1H, d, J=8,12 Hz), of 11.45 (1H, s), 12,54 (1H, s).450448

2891H-NMR (DMSO-D6) δ: of 1.01 (6H, s), was 1.04 (3H, t, J=of 7.19 Hz), 1,58 (2H, t, J=of 6.26 Hz), 1,64 is 1.71 (4H, m), 2,12-of 2.20 (2H, m), is 2.41 (2H, s), 2,64-2,71 (2H, m), 3,18-of 3.25 (2H, m), 3,66 (2H, square, J=of 7.19 Hz), and 3.72 (2H, s), 6,61 (1H, C), to 6.88 (1H, d, J=8.35 Hz), 7,27 (1H, s), EUR 7.57 (1H, d, J=8.35 Hz), 11,44 (1H, s), 12,54 (1H, s).448446
290 1H-NMR (DMSO-D6) δ: of 1.01 (6H, s), was 1.04 (3H, t, J=6,25 Hz), of 1.08 (6H, s), 1,58 (2H, t, J=6,45 Hz), 2,13 (2H, s), is 2.41 (2H, s), 2,62-2,71 (2H, m), of 3.69 (2H, square, J=6,25 Hz), 4,97 (1H, s), 6,60 (1H, s), is 6.81 (1H, d, J=8,06 Hz), of 7.19 (1H, s), 7,56 (1H, d, J=8,06 Hz), is 11.39 (1H, s), 12,54 (1H, s).409407

2911H-NMR (DMSO-D6) δ: 0,97-1,10 (3H, m), 1,01 (6H, s), 1,58 (2H, t, J=6,29 Hz), 1,95 (2H, s), is 2.41 (2H, s), 2,64-2,70 (2H, m), 2,71 (2H, s), of 2.92 (2H, s), 3,62-of 3.80 (4H, m), 6,59-only 6.64 (1H, m), of 6.85-6,93 (1H, m), 7.24 to 7,31 (1H, m), 7,55-the 7.62 (1H, m), 11,42 (1H, s), 12,54 (1H, s).422420
2921H-NMR (DMSO-D6) δ: 0.87 to 1,09 (6H, m), 1,01 (6H, s), 1,58 (2H, t, J=6,40 Hz), 2,04-2,31 (2H, m), 2,42 (2H, s), 2,64-2,71 (2H, m), 2,73 (1H, s), of 2.92 (2H, s), 3,61-of 3.80 (4H, m), 6,59-6,63 (1H, m), of 6.85-6,93 (1H, m), 7.24 to 7,30 (1H, m), 7,54-of 7.62 (1H, m), of 11.43 (1H, s), of 12.53 (1H, s).436434

Table 1-62
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2931H-NMR (DMSO-D6) δ: of 1.02 (s, 6H), 1,59 (t, 2H, J=6,28 Hz), 2,42 (s, 2H), 2,69 (s, 2H), 6,70 (s, 1H), 7,07 (DD, 1H, J=11,59, 4,11 Hz), 7,32-of 7.36 (m, 2H), of 7.46 (d, 1H, J=8,69 Hz), 7,71 (d, 1H, J=8,21 Hz), 7,81 (DD, 2H, J=of 8.57, 1,09 Hz), 8,21 (s, 1H), of 10.09 (s, 1H), at 11.57 (s, 1H), 12,56 (s, 1H).385383
2941H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=USD 6.16 Hz), 2,42 (s, 2H), 2,68 (t, 2H, J=6,04 Hz), 2,79 (d, 3H, J=4,35 Hz), 6,63 (d, 1H, J=1,21 Hz), 7,38 (d, 1H, J=to 8.45 Hz), EUR 7.57 (DD, 1H, J=8,45, 1,69 Hz), 8,04 (s, 1H), 8,22 (d, 1H, J=4,59 Hz), 11,46 (s, 1H), of 12.53 (s, 1H).323321
2951H-NMR (DMSO-D6) δ: 0,99 (s, 6H), 1.55 V (t, 2H, J=6,40 Hz), 2,39 (s, 2H), 2,62 (s, 2H), 3,39 (s, 3H), 6,47 (s, 1H), 6,97 (d, 1H, J=to 8.45 Hz), 7,08-7,25 (m, 6H), 7,49 (s, 1H), of 11.34 (s, 1H), 12,49 (s, 1H).399397

2961H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,40 Hz), 2,41 (s, 2H), 2,67 (s, 2H), 2,99 (s, 6H), 6,62 (s, 1H), 7,11 (d, 1H, J=8,21 Hz), 7,40 (d, 1H, J=821 Hz), 7,58 (s, 1H), 11,42 (s, 1H), of 12.53 (s, 1H).337335
2971H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,28 Hz), 2,42 (s, 2H), 2,68 (t, 2H, J=5,92 Hz), 6,62 (s, 1H), to 7.04 (s, 1H), value of 7, 37 (d, 1H, J=to 8.45 Hz), a 7.62 (d, 1H, J=to 8.45 Hz), 7,78 (s, 1H), 8,10 (s, 1H), 11,47 (s, 1H), Of 12.53 (s, 1H).309307

Table 1-63
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
2981H-NMR (DMSO-D6) δ: of 1.02 (d, 6H, J=8,58 Hz), 1,58 (t, 2H, J=of 6.26 Hz), 2,41 (s, 2H), 2,66 (d, 2H, J=5,10 Hz), only 3.57 (t, 8H, J=15,07 Hz), 6,63 (s, 1H), 7,12 (d, 1H, J=8,58 Hz), 7,41 (d, 1H, J=8,58 Hz), members, 7.59 (s, 1H), 11,47 (C, 1H), 12,54 (s, 1H).379377

2991H-NMR (DMSO-D6) δ: 0,92 (s, 9H), 1,01 (s, 6H), of 1.09 (d, 3H, J=6,84 Hz), 1,58 (t, 2H, J=5,95 Hz), 2,42 (s, 2H), 2,67 (s, 2H), 4,01 (�d, 1H, J=9,37, to 6.95 Hz), only 6.64 (s, 1H), 7,38 (d, 1H, J=at 8.60 Hz), EUR 7.57 (DD, 1H, J=at 8.60, a 1.54 Hz), 7,73 (d, 1H, J=9,26 Hz), with 8.05 (s, 1H), 11,44 (s, 1H), of 12.53 (s, 1H).393391
3001H-NMR (DMSO-D6) δ: 0,76 (s, 4H), 1,01 (s, 11H), 1,19 (d, 3H, J=18,84 Hz), 1,58 (t, 2H, J=6,03 Hz), 2,41 (s, 2H), 2,68 (s, 2H), 2,82 (s, 3H), 6,62 (s, 1H), to 7.04 (s, 1H), of 7.42-7,49 (m, 2H), 11,40 (s, 1H), 12,52 (s, 1H).407405
3011H-NMR (DMSO-D6) δ: 0,99 (d, 6H, J=13,67 Hz), of 1.40 (s, 2H), 1,58 (t, 2H, J=6.18 of Hz), 1,69 (s, 1H), 1,88 (s, 1H), 2,41-2,51 (m, 3H), 2,66-of 3.07 (m, 4H), 3,48 (d, 1H, J=9,92 Hz), 3,84 (s, 1H), of 4.88 (s, 1H), 6,61 (s, 1H), Was 7.08 (d, 1H, J=to 8.38 Hz), 7,39 (d, 1H, J=to 8.38 Hz), 7,55 (s, 1H), 11,44 (s, 1H), 12,54 (s, 1H).393391

Table 1-64
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
3021H-NMR (DMSO-D6) δ: of 1.02 (d, 6H, J=11,69 Hz), 1,3 (d, 2H, J=9,04 Hz), 1,58 (t, 2H, J=6,06 Hz), of 1.74 (s, 2H), 2,41 (s, 2H), 2,67 (t, 2H, J=5,84 Hz), 3,17 (DD, 2H, J=16,32, 6,40 Hz), 3,70-3,84 (m, 3H), of 4.77 (d, 1H, J=3,97 Hz), 6,62 (s, 1H), was 7.08 (DD, 1H, J=to 8.38, To 1.32 Hz), 7,39 (d, 1H, J=to 8.38 Hz), 7,54 (s, 1H), of 11.45 (s, 1H), 12,54 (s, 1H).393391
3031H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (s, 2H), 2,42 (s, 2H), 2,68 (s, 2H), 3,30-3,35 (m, 2H), 3,52 (square, 2H, J=6,03 Hz), 4,71 (t, 1H, J=5,51 Hz), 6,63 (s, 1H), 7,38 (d, 1H, J=to 8.38 Hz), members, 7.59 (d, 1H, J=to 8.38 Hz), 8,07 (s, 1H), 8,22 (s, 1H), 11,48 (s, 1H), 12,54 (s, 1H).353351

3041H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6.18 of Hz), 2,41 (s, 2H), 2,67 (s, 2H), of 3.00 (s, 3H), 3,17 (DD, 1H, J=of 5.29, of 1.76 Hz), 3,40-3,50 (m, 3H), 4,76 (t, 1H, J=5,40 Hz), 6,60 (s, 1H), 7,10 (d, 1H, J=to 8.38 Hz), 7,38 (d, 1H, J=to 8.38 Hz), EUR 7.57 (s, 1H), 11,42 (s, 1H), of 12.53 (s, 1H).367365
3051H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,25 Hz), 2,42 (s, 2H), 2,69 (s, 2H), 3,66 (s, 3H), 4,01 (d, 2H, J=5,64 Hz), 6,66 (s, 1H), 7,41 (d, 1H, J=is 8.46 Hz), 7,61 (d, 1H, J=is 8.46 Hz), 8,10 (s, 1H), 8,75 (t, 1H, J=5,64 Hz), 11,54 (s, 1H), 12,56 (s, 1H). 381379
3061H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,45 Hz), 2,42 (s, 2H), 2,69 (t, 2H, J=6,04 Hz), 3,92 (d, 2H, J=5,64 Hz), to 6.67 (d, 1H, J=1,21 Hz), 7,41 (d, 1H, J=is 8.46 Hz), a 7.62 (DD, 1H, J=is 8.46, to 1.61 Hz), 8,10 (s, 1H), 8,63 (t, 1H, J=5,84 Hz), 11,50 (s, 1H), 12,54 (s, 2H).367365

Table 1-65
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
3071H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,10 (d, 6H, J=6.18 of Hz), 1,58 (t, 2H, J=6,29 Hz), 2,42 (s, 2H), 2,68 (s, 2H), 3,39 (square, 2H, J=6,03 Hz), 3,49 (t, 2H, J=6,29 Hz), 3,55-3,61 (m, 1H), 6,63 (s, 1H), 7,38 (d, 1H, J=to 8.38 Hz), Members, 7.59 (d, 1H, J=to 8.38 Hz), 8,06 (s, 1H), 8,27 (s, 1H), 11,48 (s, 1H), of 12.55 (s, 1H).395393
3081H-NMR (DMSO-D6) δ: of 0.87 (t, 3H, J=7,39 Hz), of 1.02 (s, 6H), 1,51-1,58 (m, 4H), 2,43 (s, 2H), 2,69 (s, 2H), 3,33-of 3.53 (m, 6H), only 6.64 (s, 1H), 7,39 (d, 1H, J=to 8.38 Hz), 7,60 (d, 1H, J=to 8.38 Hz), 8,07 (s, 1H),8,30, 1H), 11,50 (s, 1H), of 12.55 (s, 1H).395393

3091H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,29 Hz), 2,42 (s, 2H), 2,68 (s, 2H), to 3.64 (q, 2H, J=5,88 Hz), 4,12 (t, 2H, J=6,06 Hz), only 6.64 (s, 1H), 6,91-of 6.99 (m, 3H), 7,27-7,32 (m, 2H), 7,39 (d, 1H, J=at 8.60 Hz), A 7.62 (d, 1H, J=of 8.82 Hz), 8,10 (s, 1H), and 8.50 (t, 1H, J=5,07 Hz), 11,50 (s, 1H), of 12.55 (s, 1H).429427
3101H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,29 Hz), 2,42 (s, 2H), 2,68 (t, 2H, J=6,06 Hz), or 3.28 (s, 3H), 3.43 points-3,48 (m, 4H), 6,63 (d, 1H, J=1,32 Hz), 7,38 (d, 1H, J=at 8.60 Hz), members, 7.59 (DD, 1H, J=at 8.60, a 1.54 Hz), 8,07 (s, 1H), 8,30 (t, 1H, J=4,96 Hz), 11,49 (s, 1H), 12,54 (s, 1H).367365
3111H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6.18 of Hz), 2,41 (s, 2H), 2,68 (s, 2H), 3,03 (s, 3H), of 3.69 (s, 3H), 4,22 (s, 2H), only 6.64 (s, 1H), 7,13 (s, 1H), 7,45-7,54 (m, 2H), 11,48 (s, 1H), of 12.55 (s, 1H).395393

312 1H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,38 Hz), 2,41 (s, 2H), 2,68 (t, 2H, J=6,15 Hz), 3,02 (s, 3H), 4,03-to 4.14 (m, 2H), only 6.64 (s, 1H), 7,03-7,13 (m, 1H), 7,43-7,58 (m, 2H), 11,46 (s, 1H), 12,65 (s, 2H).381379
3131H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,29 Hz), 2,41 (s, 2H), 2,67 (s, 2H), 2,99 (C, 3H), 3,26 (user.s, 3H), 3,48 (user.s, 4H), 6,61 (s, 1H), to 7.09 (d, 1H, J=7,94 Hz), 7,39 (d, 1H, J=8,16 Hz), 7,55 (s, 1H), of 11.43 (s, 1H), of 12.53 (s, 1H).381379

Table 1-66
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
3141H-NMR (DMSO-D6) δ: of 1.00 (s, 6H), of 1.57 (t, 2H, J=6,29 Hz), 2,41 (s, 2H), 2,66 (user.s, 2H), 2,90 (s, 3H), a 4.65 (s, 2H), 6,62 (s, 1H), 7,15-of 7.42 (m, 7H), 7,63 (s, 1H), of 11.45 (s, 1H), of 12.53 (s, 1H).413411

315 1H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,29 Hz), 2,42 (s, 2H), 2,68 (user.s, 2H), 4,49 (d, 2H, J=5,95 Hz), only 6.64 (s, 1H), 7,21-7,45 (m, 6H), of 7.64 (d, 1H, J=to 8.38 Hz), 8,13 (s, 1H), 8,86 (t, 1H, J=5,73 Hz), 11,50 (s, 1H), of 12.55 (s, 1H).399397
3161H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,25 Hz), 2,42 (s, 2H), 2,68 (user.s, 2H), 4,76 (d, 2H, J=6,04 Hz), 6,66 (s, 1H), of 7.42 (d, 1H, J=8,87 Hz), 7,63-7,72 (m, 3H), 8,14 (s, 1H), 9,21 (t, 1H, J=5,64 Hz), for 11.55 (s, 1H), 12,56 (s, 1H).406404
3171H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,25 Hz), 2,42 (s, 2H), 2,69 (t, 2H, J=6,25 Hz), 4,74 (d, 2H, J=5,64 Hz), 6,66 (s, 1H), of 7.36-7,44 (m, 1H), 7,65 (d, 1H, J=7,25 Hz), 8,14 (s, 1H), 8,58 (t, 1H, J=3,02 Hz), 8,95 (s, 1H), to 11.52 (s, 1H), of 12.55 (s, 1H).391389

3181H-NMR (DMSO-D6) δ: of 1.02 (s, 6H), 1,59 (t, 2H, J=6,25 Hz), 2,42 (s, 2H), 2,68 (user.s, 2H), 4,32 (d, 2H, J=5,64 Hz), 6,50 (t, 1H, J=1,41 Hz), only 6.64 (s, 1H), 7,39 (d, 1H, J=is 8.46 Hz), members, 7.59-7,63 (m, 3H), 8,09 (s, 1H), 8.66 roubles (t, 1H, J=5,84 Hz), 11,50 (s, 1H), 12,56 (s, 1H). 389387
3191H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,25 Hz), 2,41 (s, 2H), 2,68 (t, 2H, J=6,25 Hz), 3,60 (s, 3H), of 4.45 (d, 2H, J=5,24 Hz), of 5.89 (DD, 1H, J=3,43, 2,62 Hz), 5,97 (DD, 1H, J=3,43, of 1.81 Hz), only 6.64 (DD, 2H, J=5,04, 3,02 Hz), 7,38 (d, 1H, J=is 8.46 Hz), a 7.62 (DD, 1H, J=is 8.46, to 1.61 Hz), 8,10 (d, 1H, J=1,21 Hz), 8,55 (t, 1H, J=5,44 Hz), 11,51 (s, 1H).402400

Table 1-67
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
3201H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), of 1.33 (s, 6H), 1,58 (t, 2H, J=6,25 Hz), 2,41 (s, 2H), 2,67 (s, 2H), 3,51 (s, 2H), 4,97-5,10 (m, 1H), 6,63 (s, 1H), of 7.36-value of 7, 37 (m, 2H), 7,53 (d, 1H, J=is 8.46 Hz), 8,01 (s, 1H), 11,47 (s, 1H)That 12,54 (s, 1H).381379
3211H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,25 Hz), 2,42 (s, 2H), 2,68 (t, 2H, J=5,64 Hz), 3,26 (s, 3H), 3,56 (s, 3H), 6,66 (s, 1H), 7,34-the 7.43 (m, 2H), a 7.85 (s, 1H), 11,50 (s, 1H), 12,5 (C, 1H).353351
3221H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,25 Hz), 2,44-2,48 (m, 8H), 2,68 (s, 2H), 3,40 (square, 2H, J=6,58 Hz), 3,58 (t, 4H, J=4,43 Hz), 6,63 (s, 1H), 7,38 (d, 1H, J=is 8.46 Hz), EUR 7.57 (d, 1H, J=9,27 Hz), with 8.05 (s, 1H), By 8.20 (t, 1H, J=5,44 Hz), 11,49 (s, 1H), of 12.55 (s, 1H).422420

3231H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,25 Hz), of 2.25 (s, 6H), 2,42 (s, 2H), 2,68 (s, 2H), 3,38 (q, 4H, J=6,45 Hz), only 6.64 (s, 1H), 7,38 (d, 1H, J=8,06 Hz), 7,58 (d, 1H, J=8,06 Hz), with 8.05 (s, 1H), 8,20 (s, 1H), 11,49 (s, 1H), of 12.55 (s, 1H).380378
3241H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,59 (t, 2H, J=6,25 Hz), 2,42 (s, 2H), 2,69 (t, 2H, J=5,84 Hz), 6,69 (s, 1H), 7,45 (d, 1H, J=8.66 roubles Hz), of 7.75 (DD, 1H, J=8.66 roubles, of 1.41 Hz), 8,29 (s, 1H), to 11.69 (s, 1H), 12,02 (user.s, 1H), 12,24 (user.s, 1H), 12,60 (s, 1H).409407
3251H-NMR (DMSO-D6) δ: of 1.02 (6H), As 1.59 (t, 2H, J=6,04 Hz), 2,42 (s, 2H), 2,70 (s, 2H), 4,10 (s, 3H), 6,70 (s, 1H), 7,47 (d, 1H, J=8,87 Hz), 7,83 (d, 1H, J=8,87 Hz), to 8.38 (s, 1H), 11,70 (s, 1H), of 12.55-12,60 (m, 2H).423421

3261H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), of 1.47 (s, 6H), 1,59 (t, 2H, J=6,25 Hz), 2,42 (s, 2H), 2,68 (t, 2H, J=5,84 Hz), of 6.65 (s, 1H), 7,39 (d, 1H, J=8.66 roubles Hz), members, 7.59 (DD, 1H, J=8.66 roubles, of 1.81 Hz), 8,09 (s, 1H), 8,24 (s, 1H), 11,47 (C, 1H).395393

Table 1-68
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
3271H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), of 1.36 (s, 9H), of 1.44 (s, 6H), 1,59 (t, 2H, J=6,25 Hz), 2,42 (s, 2H), 2,68 (d, 2H, J=6,04 Hz), only 6.64 (s, 1H), 7,38 (d, 1H, J=is 8.46 Hz), 7,56 (d, 1H, J=is 8.46 Hz), with 8.05 (s, 1H), 8,24 (s, 1H), 11,49 (s, 1H), of 12.55 (s, 1H).451449
3281H-NMR (LCA�-D 6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,25 Hz), 2,42 (s, 2H), 2,67 (s, 2H), 3,54 (t, 4H, J=5,84 Hz), 3,98 (DD, 1H, J=13,70, 6,04 Hz), a 4.65 (t, 2H, J=5,84 Hz), only 6.64 (s, 1H), 7,38 (d, 1H, J=8,06 Hz), 7,60 (d, 1H, J=9,27 Hz), 7,72 (d, 1H, J=8,06 Hz), 8,09 (s, 1H), 11,49 (s, 1H), of 12.55 (s, 1H).383381

3291H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,45 Hz), 2,41 (s, 2H), 2,67 (s, 2H), to 3.64 (s, 3H), 4,47 (d, 2H, J=5,64 Hz), 6,63 (s, 1H), 6,83 (s, 1H), 7,38 (d, 1H, J=is 8.46 Hz), 7,54 (s, 1H), 7,61 (d, 1H, J=is 8.46 Hz), 8,09 (s, 1H), 8,63 (s, 1H), 11,50 (s, 1H), of 12.55 (s, 1H).403401
3301H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), is 1.11 (t, 6H, J=of 6.65 Hz), 1,58 (t, 2H, J=6,45 Hz), 2,41 (s, 2H), 2,63-of 2.72 (m, 2H), 3,25-3,46 (user.m, 4H), 6,61 (s, 1H), to 7.04 (d, 1H, J=8,06 Hz), 7,39 (d, 1H, J=8,06 Hz), 7,50 (s, 1H), 11,42 (s, 1H), 12,54 (s, 1H).365363
3311H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), is 1.11 (t, 3H, J=of 6.65 Hz), 1,58 (t, 2H, J=6,25 Hz), 2,41 (s, 2H), 2,68 (t, 2H, J=6,25 Hz), 2,95 (s, 3H), 3,34-3,36 (m, 2H), 6,63 (d, 1H, J=1,21 Hz), was 7.08 (DD, 1H, J=is 8.46, 1,21 Hz), 7,40 (d, 1H, J=is 8.46 Hz), 7,54 (s, 1H), 11,40 (s, 1H).351 349

3321H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,45 Hz), 1,84 (d, 4H, J=16,92 Hz), 2,41 (s, 2H), 2,66-of 2.68 (m, 2H), 3,48 (t, 4H, J=of 6.65 Hz), 6,62 (s, 1H), 7,24 (d, 1H, J=is 8.46 Hz), 7,38 (d, 1H, J=is 8.46 Hz), 7,71 (s, 1H), 11,44 (s, 1H), 12,54 (s, 1H).363361

Table 1-69
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
3331H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,52-1,62 (m, 8H), 2,41 (s, 2H), 2,63-2,71 (m, 2H), 3,48 (s, 4H), 6,61 (s, 1H), 7,07 (d, 1H, J=7,66 Hz), 7,39 (d, 1H, J=7,66 Hz), 7,53 (s, 1H), 11,44 (s, 1H), 12,54 (s, 1H).377375
3341H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,25 Hz), 2,42 (s, 2H), 2,62-of 2.72 (m, 4H), of 3.75 (user.s, 2H), 4,52 (user.s, 2H), of 6.65 (s, 1H), 7,15 (d, 1H, J=is 8.46 Hz), the 7.43 (d, 1H, J=is 8.46 Hz), 7,49 (s, 1H), 7.62 mm (s, 1H), 11,48 (s, 1H), of 12.55 (�, 1H).415413

3351H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,25 Hz), 2,41 (s, 2H), 2,63-of 2.72 (m, 2H), 3,34-3,40 (m, 2H), 3,58 (d, 1H, J=5,44 Hz), 3,61 (d, 1H, J=5,44 Hz), 3,98 (user.s, 1H), of 4.09 (user.s, 1H), to 4.92 (user.s, 2H), 6,63 (s, 1H), 7,22 (d, 1H, J=8,06 Hz), 7,39 (d, 1H, J=8,06 Hz), 7,69 (s, 1H), 11,46 (s, 1H), 12,54 (s, 1H).395393
3361H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,40 (d, 9H, J=6,45 Hz), 1,58 (t, 2H, J=6,25 Hz), 2,42 (s, 2H), 2,63-2,71 (m, 2H), 3,38 (user.s, 4H), 3,50 (user.s, 4H), 6,62 (s, 1H), 7,12 (d, 1H, J=compared to 8.26 Hz), 7,41 (d, 1H, J=compared to 8.26 Hz), members, 7.59 (s, 1H), 11,47 (s, 1H), of 12.55 (s, 1H).478476
3371H-NMR (DMSO-D6) δ: 0,96-of 1.09 (m, 9H), 1,58 (t, 2H, J=6,25 Hz), 2.26 and-of 2.50 (m, 6H), 2,41 (s, 2H), 2,61-of 2.75 (m, 2H), 3,40-3,66 (m, 4H), 6,63 (s, 1H), 7,10 (d, 1H, J=is 8.46 Hz), 7,40 (d, 1H, J=is 8.46 Hz), 7,56 (s, 1H), 11,46 (C, 1H), of 12.55 (s, 1H).406404

338 1H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,45 Hz), 2,41 (s, 2H), 2,63-2,71 (m, 2H), 3,24 (s, 3H), 3,37 (s, 3H), 3.43 points-3,52 (m, 2H), 3,57-3,71 (m, 2H), 3,84-3,94 (m, 1H), 3,95-4,05 (m, 1H), only 6.64 (s, 1H), 7,24 (d, 1H, J=compared to 8.26 Hz), 7,40 (d, 1H, J=compared to 8.26 Hz), 7,71 (s, 1H), 11,46 (s, 1H), 12,54 (s, 1H).423421

Table 1-70
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
3391H-NMR (DMSO-D6) δ: 0,99 (s, 6H), 1,54 (d, 2H, J=5,51 Hz), 2,39 (s, 2H), 2,61 (s, 2H), 3,38 (s, 3H), 6,45 (s, 1H), 6,86 (d, 1H, J=7,94 Hz), 7,18-7.23 percent (m, 7H), about 11.28 (s, 1H), 12,50 (s, 1H).399397
3401H-NMR (DMSO-D6) δ: to 0.89 (t, 3H, J=7,54 Hz), 1,01 (s, 6H), 1,59 (d, 2H, J=6,40 Hz), of 1.99 (square, 2H, J=7,66 Hz), 2,41 (s, 2H), 2,67 (s, 1H), 3,17 (s, 4H), to 6.58 (s, 1H), 6,94 (d, 1H, J=9,04 Hz), 7,41 (s, 2H), is 11.39 (s, 1H), 12,54 (s, 1H).351349

3411H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1.41 to of 1.66 (m, 6H), 2,41 (s, 3H), 2,67 (s, 2H), equal to 2.94 (t, 2H, J=11 and 68 Hz), 3,16 (s, 3H), and 3.72 (d, 2H, J=9,42 Hz), 6,60 (s, 1H), of 6.96 (d, 1H, J=9,42 Hz), 7,41 was 7.45 (m, 2H), of 11.45 (s, 1H), Of 12.55 (s, 1H).407405
3421H-NMR (DMSO-D6) δ: of 0.75 (d, 6H, J=6,40 Hz), 1,01 (s, 6H), 1,58 (t, 2H, J=6,29 Hz), 1,91-of 1.97 (m, 3H), 2,42 (s, 2H), 2,66 (d, 2H, J=5,95 Hz), 3,18 (s, 3H), to 6.58 (s, 1H), 6,90 (d, 1H, J=to 8.38 Hz), 7,38-7,41 (m, 2H), 11,41 (s, 1H), 12,54 (s, 1H).379377

Table 1 to 71
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
3431H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,29 Hz), 2,41 (s, 2H), 2,67 (s, 2H), 3,20 (t, 4H, J=14,00 Hz), of 3.69 (s, 2H), to 6.58 (s, 1H), 6,95 (d, 1H, J=7,94 Hz), 7,41-the 7.43 (m, 2H), of 11.43 (s, 1H), 12,54 (s, 1H).353351

344 1H-NMR (DMSO-D6) δ: of 1.01 (s, 6H), 1,58 (t, 2H, J=6,29 Hz), 2,41 (s, 2H), 2,67 (d, 2H, J=4,85 Hz), 6,55 (s, 1H), 7,35 (d, 2H, J=5,51 Hz), 7,50-7,58 (m, 3H), 7,95-7,98 (m, 3H), 10,07 (s, 1H), 11,20 (s, 1H), 12,49 (s, 1H).385383
3451H-NMR (DMSO-D6) δ: of 1.00 (s, 6H), 1,10 (t, 3H, J=7,50 Hz), of 1.57 (t, 2H, J=6,29 Hz), 2,30 (square, 2H, J=EUR 7.57 Hz), is 2.40 (s, 2H), 2,67 (d, 2H, J=of 5.29 Hz), of 6.49 (s, 1H), made 7.16 interest-7,26 (m, 2H), 7,81 (s, 1H), 9,61 (s, 1H), to 11.11 (s, 1H), 12,47 (s, 1H).337335
3461H-NMR (DMSO-D6) δ: of 0.92 (3H, C), 0,96-1,06 (2H, m), 1,21-of 1.39 (2H, m), 1,50-1,80 (6H, m), 2.21 are-2,33 (1H, m) to 2.29 (1H, d, J=16,52 Hz), 2,55 (1H, d, J=16,52 Hz), 2,57-to 2.73 (2H, m), 3,16 (6H, s), 3,18-3,24 (1H, m), 3,26 (2H, d, J=5,24 Hz), 4,62 (1H, t, J=5,24 Hz), 6,59 (1H, s) 6,86 (1H, d, J=7,66 Hz), 7.23 percent (1H, s), 7,54 (1H, d, J=7,66 Hz), made 11.32 (1H, s) 12,50 (1H, s).451449

3471H-NMR (DMSO-D6) δ: 0.98 in (3H, C), 1,53-of 1.75 (6H, m), 2,11-of 2.21 (2H, m), 2,35 (1H, d, J=16,12 Hz), 2,56 (1H, d, J=15,72 Hz), 2,61-2,70 (2H, m), 3,15-3,26 (7H, m), or 3.28 (3H, s), of 3.77 (2H, s), 6,60 1H, C) at 6.92 (1H, d, J=7,66 Hz), 7,29 (1H, s), 7,56 (1H, d, J=7,66 Hz), of 11.45 (1H, s), of 12.55 (1H, s).464462

Table 1-72
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
3481H-NMR (DMSO-D6) δ: of 0.95 was 1.06 (2H, m), and 0.98 (3H, C), 1,28-of 1.36 (2H, m), 1,54-to 1.79 (6H, m), 2,20-to 2.29 (1H, m), 2,35 (1H, d, J=16,12 Hz), 2,56 (1H, d, J=16,12 Hz), 2,62-2,70 (2H, m), 3,15 (6H, s), 3,19 (2H, s), 3,19-3,24 (1H, m), or 3.28 (3H, s), 6,60 (1H, s) 6,86 (1H, d, J=8,06 Hz), 7.23 percent (1H, s), 7,55 (1H, d, J=8,06 Hz), 11,36 (1H, s), 12,54 (1H, s).465463

3491H-NMR (DMSO-D6) δ: of 0.92 (3H, C), 1,21-of 1.39 (2H, m), 1,46 is 1.72 (8H, m) to 2.29 (1H, d, J=15,88 Hz), 2,43-of 2.75 (4H, m), 3,18 (3H, s), 3,23-3,29 (2H, m), 4,65 (1H, t, J=4,96 Hz), to 6.58 (1H, s) 6,86 (1H, d, J=to 8.38 Hz), 7.23 percent (1H, C), 7,54 (1H, d, J=to 8.38 Hz), 11,36 (1H, s), 12,52 (1H, s).407405
350 1H-NMR (DMSO-D6) δ: 1,68-of 1.81 (m, 4H), 2,56-of 2.68 (m, 4H), 3,39 (s, 3H), of 6.46 (s, 1H), is 6.81 (d, 1H, J=8.35 Hz), 7,07 (s, 1H), 7,12-7.23 percent (m, 3H), 7,28 (d, 2H, J=6,72 Hz), value of 7, 37 (d, 1H, J=8.35 Hz), at 11.23 (s, 1H), 12,52 (s, 1H).371369
3511H-NMR (DMSO-D6) δ: of 0.91 (t, 3H, J=of 7.42 Hz), 1,73-of 1.83 (m, 4H), 2,01 (square, 2H, J=of 7.42 Hz), 2,58-2,71 (m, 4H), 3,18 (s, 3H), 6,56 (s, 1H), 6,86 (d, 1H, J=8,12 Hz), 7,22 (s, 1H), 7,54 (d, 1H, J=8,12 Hz) 11,40 (s, 1H), 12,57 (s, 1H).323321

3521H-NMR (DMSO-D6) δ: 1,71-of 1.84 (m, 4H), 2,56-to 2.74 (m, 4H), 3,18 (s, 3H), 3,19 (s, 3H), 3,73 (s, 2H), to 6.57 (s, 1H), to 6.88 (d, 1H, J=8,00 Hz), 7,24 (s, 1H), 7,54 (d, 1H, J=8,00 Hz), of 11.43 (s, 1H), is 12.58 (s, 1H).339337

Table 1-73
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
353 1H-NMR (DMSO-D6) δ: of 1.08 (d, 3H, J=6,45 Hz), 1,34-1,49 (m, 1H), 1,82-of 1.97 (m, 2H), 2,15-of 2.27 (m, 1H), 2,58-2,69 (m, 1H), 2,70-2,82 (m, 2H), 3,18 (s, 3H), 3,19 (s, 3H), 3,73 (s, 2H), to 6.57 (s, 1H), to 6.88 (d, 1H, J=compared to 8.26 Hz), 7,24 (s, 1H), 7,54 (d, 1H, J=compared to 8.26 Hz), 11,42 (s, 1H), of 12.55 (s, 1H).353351

3541H-NMR (DMSO-D6) δ: of 0.91 (t, 3H, J=of 7.42 Hz), of 1.08 (d, 3H, J=6.85 Hz), of 1.33-1,49 (m, 1H), 1,83-of 1.95 (m, 2H), 2,01 (square, 2H, J=of 7.42 Hz), 2,15-of 2.27 (m, 1H), 2,57-2,69 (m, 1H), 2,69-2,82 (m, 2H), 3,17 (s, 3H), 6,56 (s, 1H), 6,86 (d, 1H, J=compared to 8.26 Hz), 7,22 (s, 1H), 7,54 (d, 1H, J=compared to 8.26 Hz), 11,38 (s, 1H), 12,54 (s, 1H).337335
3551H-NMR (DMSO-D6) δ: of 0.91 (t, 3H, J=7.38 per Hz), of 1.08 (d, 3H, J=6,49 Hz), 1,34-1,49 (m, 1H), 1,83-of 1.95 (m, 2H), 2,01 (square, 2H, J=7.38 per Hz), 2,15-of 2.27 (m, 1H), 2,56-2,69 (m, 1H), 2,70-2,83 (m, 2H), 3,18 (s, 3H), to 6.57 (s, 1H), 6,86 (d, 1H, J=8,12 Hz), 7,22 (s, 1H), 7,54 (d, 1H, J=8,12 Hz) 11,40 (s, 1H), of 12.55 (s, 1H).337335

3561H-NMR (DMSO-D6) δ: of 1.08 (d, 3H, J=6,62 Hz), 1,34-of 1.50 (m, 1H), 1,83-of 1.98 (m, 2H), 2,15-of 2.27 (m, 1H), 2,58-2,69 (m, 1H, 2,70-2,84 (m, 2H), 3,18 (s, 3H), 3,19 (s, 3H), 3,73 (s, 2H), to 6.57 (s, 1H), to 6.88 (d, 1H, J=7,83 Hz), 7,24 (s, 1H), 7,54 (d, 1H, J=7,83 Hz), 11,42 (s, 1H), 12,54 (s, 1H).353351
3571H-NMR (DMSO-D6) δ: of 1.06 (d, 3H, J=6,49 Hz), 1,31-of 1.47 (m, 1H), 1,80-1,94 (m, 2H), 2,13-of 2.25 (m, 1H), 2,53-of 2.64 (m, 1H), 2,65-2,78 (m, 2H), 3,39 (s, 3H), of 6.46 (s, 1H), is 6.81 (d, 1H, J=8,23 Hz), 7,07 (s, 1H), 7,15-of 7.19 (m, 3H), 7,28 (d, 2H, J=6,72 Hz), value of 7, 37 (d, 1H, J=8,23 Hz), at 11.23 (s, 1H), 12,50 (s, 1H).385383

Table 1-74
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
3581H-NMR (DMSO-D6) δ: of 1.06 (d, 3H, J=6,49 Hz), 1,31-of 1.47 (m, 1H), 1,79-1,94 (m, 2H), 2,11-of 2.25 (m, 1H), 2,55-of 2.64 (m, 1H), 2,65-2,78 (m, 2H), 3,39 (s, 3H), of 6.46 (s, 1H), is 6.81 (d, 1H, J=8,23 Hz), 7,07 (s, 1H), 7,12-7.23 percent (m, 3H), 7,28 (d, 2H, J=6,49 Hz), value of 7, 37 (d, 1H, J=8,23 Hz), at 11.23 (s, 1H), 12,50 (s, 1H).385383
359 1H-NMR (DMSO-D6) δ: of 0.95 (d, 6H, J=5,95 Hz), 1,72-of 1.84 (m, 4H), 2,59-2,73 (m, 4H), 3,18 (s, 3H), 3,39-3,48 (m, 1H), of 3.75 (s, 2H), to 6.57 (s, 1H), to 6.88 (d, 1H, J=8,16 Hz), 7,25 (s, 1H), 7,54 (d, 1H, J=Hz 8,16), 11,41 (s, 1H), 12,56 (s, 1H).367365
3601H-NMR (DMSO-D6) δ: of 1.75 (s, 3H), 1,76-to 1.82 (m, 4H), 2,57-of 2.72 (m, 4H), 3,17 (s, 3H), 6,56 (s, 1H), to 6.88 (d, 1H, J=8,12 Hz), 7.23 percent (s, 1H), 7,54 (d, 1H, J=8,12 Hz) 11,40 (s, 1H), 12,57 (s, 1H).309307

3611H-NMR (DMSO-D6) δ: of 0.76 (d, 6H, J=6,49 Hz), 1,72-of 1.84 (m, 4H), 1.91 a (d, 2H, J=6,72 Hz), 1,92-2,04 (m, 1H), 2,57-2,73 (m, 4H), 3,18 (s, 3H), 6,56 (s, 1H), 6,83 (d, 1H, J=8,23 Hz), of 7.19 (s, 1H), 7,54 (d, 1H, J=8,23 Hz), Is 11.39 (s, 1H), 12,57 (s, 1H).351349
3621H-NMR (DMSO-D6) δ: 1,74-to 1.82 (m, 4H), 2,58-of 2.72 (m, 4H), 3,23 (s, 3H), 4,42 (s, 2H), 6,59 (s, 1H), 6.75 in (d, 2H, J=of 7.88 Hz), 6,90 (t, 1H, J=7,30 Hz), 7,02 (d, 1H, J=7,65 Hz), 7.23 percent (t, 2H, J=of 7.88 Hz), 7,38 (s, 1H), Members, 7.59 (d, 1H, J=8.35 Hz), 11,47 (s, 1H), is 12.58 (s, 1H).401399

Table 1-75
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
3631H-NMR (DMSO-D6) δ: 1,01 (s, 3H), was 1.04 (s, 3H), 2,48 (DD, 2H, J=53,80, 15,92 Hz), 2,72-of 3.04 (m, 2H), 3,51 (t, 1H, J=5,04 Hz), USD 4.61 (DD, 2H, J=85,63, to 11.89 Hz), 5,09 (s, 2H), 6,59 (s, 1H), 6,89 (d, 1H, J=compared to 8.26 Hz), 7,22-7,39 (m, 11H), Of 7.48 (d, 1H, J=compared to 8.26 Hz), of 11.29 (s, 1H), 12,52 (s, 1H).535533
3641H-NMR (DMSO-D6) δ: of 0.91 (t, 3H, J=7,29 Hz), of 1.03 (d, 6H, J=15,72 Hz), 2,01 (square, 2H, J=7,29 Hz), 2.49 USD (DD, 23H, J=54,60, 15,92 Hz), 2,74-3,03 (m, 2H), 3,18 (s, 3H), 3,51 (t, 1H, J=5,04 Hz), USD 4.61 (DD, 2H, J=86,84, to 11.89 Hz), of 6.65 (s, 1H), to 6.88 (d, 1H, J=compared to 8.26 Hz), 7,20-7,39 (m, 6H), 7,56 (d, 1H, J=compared to 8.26 Hz), 11,38 (s, 1H), is 12.58 (user.s, 1H).457455

3651H-NMR (DMSO-D6) δ: of 0.91 (3H, t, J=of 7.42 Hz), 1,76-1,90 (2H, m), 2,01 (2H, square, J=of 7.42 Hz), 2,51-2,77 (4H, m), 2,93 (2H, DD, J=was 15.19, 4,29 Hz), 3,18 (3H, C), 4,01 is 4.03 (1H, m), 4,84 (1H, d, J=3,94 Hz), 6,55 (1H with), 6,87 (1H, d, J=8,12 Hz), 7.23 percent (1H, s), 7,56 (1H, d, J=8,12 Hz), is 11.39 (1H, s), 12,57 (1H, s).339337
3661H-NMR (DMSO-D6) δ: 1,74-1,90 (2H, m), 2,53-2,76 (5H, m), 2,90-to 2.94 (1H, m), 3,17 (3H, C), 3,18 (3H, C), 3,73 (2H, s), 3,96-of 4.05 (1H, m), a 4.83 (1H, d, J=3,71 Hz), 6,55 (1H, s), 6,89 (1H, d, J=of 7.88 Hz), 7,24 (1H, s), 7,55 (1H, d, J=8,12 Hz), 11,42 (1H, s), is 12.58 (1H, s).355353
3671H-NMR (DMSO-D6) δ: 1,69-1,89 (2H, m), 2,45-to 2.74 (5H, m), 2,86-2,90 (1H, m), 3,39 (3H, s), 3,93-was 4.02 (1H, m), to 4.81 (1H, s), 6,44 (1H, s), is 6.81 (1H, d, J=8,12 Hz), 7,07 (1H, s), 7,15-to 7.18 (3H, m), 7,28 (2H, d, J=6,49 Hz), 7,38 (1H, d, J=8,12 Hz), 11,22 (1H, s), 12,52 (1H, s).387385

Table 1-76
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
3681H-NMR (DMSO-D6) δ: of 0.90 (3H, t, J=of 7.42 Hz), 1,82-of 2.05 (2H, m), from 2.00 (4H, square, J=of 7.42 Hz), 2,56-of 2.75 (3H,m), 2,98-2,99 (1H, m), 3,17 (3H, C), of 3.33 (3H, s), and 3.72 (1H, d, J=5,57 Hz), 6,59 (1H, s), 6,87 (1H, d, J=8,58 Hz), 7,22 (1H, s), 7,55 (1H, d, J=8,58 Hz), is 11.39 (1H, s) 12,60 (1H, s).353351
3691H-NMR (DMSO-D6) δ: 1.85 to 1.98 m (2H, m), 2,61-of 2.72 (3H, m), 2,96-of 3.00 (1H, m), 3,17 (3H, C), 3,18 (3H, C), of 3.33 (2H, s), 3,69-of 3.75 (1H, m), 3,73 (3H, s), 6,60 (1H, s), 6,89 (1H, d, J=8,12 Hz), 7,25 (1H, s), 7,55 (1H, d, J=8,12 Hz), of 11.43 (1H, s), was 12.61 (1H, s).369367

3701H-NMR (DMSO-D6) δ: 1,85-of 1.93 (2H, m), 2,61-to 2.65 (3H, m), 2,91-2,95 (1H, m), and 3.31 (3H, s), 3,39 (3H, s), of 3.69 (1H, d, J=5,80 Hz), of 6.49 (1H, s), is 6.81 (1H, d, J=8,58 Hz), 7,07 (1H, s), 7,15-to 7.18 (3H, m), 7,27-7,28 (2H, m), 7,38 (1H, d, J=8,58 Hz), 11,22 (1H, s), of 12.55 (1H, s).401399
3711H-NMR (DMSO-D6) δ: of 0.90 (4H, t, J=7,30 Hz), 1,10 (3H, d, J=6,03 Hz), of 1.12 (3H, d, J=6,03 Hz), 1,73-of 1.96 (2H, m), 2,01 (2H, square, J=7,30 Hz), 2,53-2,71 (4H, m), 2,94-2,98 (1H, m), 3,17 (3H, s), 3,80 (1H, Sept., J=6,03 Hz), 3,84-3,94 (1H, m), to 6.57 (1H, s) 6,86 (1H, d, J=of 7.88 Hz), 7,22 (1H, s), 7,54 (1H, d, J=of 7.88 Hz), at 11.37 (1H, s), is 12.58 (1H, s).381 379

3721H-NMR (DMSO-D6) δ: of 0.91 (3H, t, J=7,39 Hz), and 0.98 (3H, C), 1,01 (3H, s), a 2.01 (2H, square, J=7,39 Hz), 2,39 (1H, d, J=16,10 Hz), 2,51 (9H, d, J=16,10 Hz), 2,70 (1H, DD, J=16,54, 5,07 Hz), of 2.92 (1H, DD, J=16,54, to 4.41 Hz), 3,18 (3H, C), Of 3.25 (1H, DD, J=5,07, to 4.41 Hz), 3,34 (4H, s), of 6.65 (1H, s), to 6.88 (1H, d, J=8,16 Hz), 7,24 (1H, s), 7,56 (1H, d, J=Hz 8,16), 11,38 (1H, s), of 12.55 (1H, s).381379

Table 1-77
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
3731H-NMR (DMSO-D6) δ: of 0.91 (3H, t, J=7,45 Hz), of 0.96 (6H, s), a 2.01 (2H, square, J=7,45 Hz), is 2.37 (1H, d, J=16,12 Hz), 2,53-2,61 (1H, m), of 2.57 (1H, d, J=16,12 Hz), 2,83-of 2.92 (1H, m), 3,18 (3H, C), 3,58-3,61 (1H, m), 4,70 (1H, d, J=4,84 Hz), 6,55 (1H, s) 6,86 (1H, d, J=is 8.46 Hz), 7.23 percent (1H, s), 7,55 (1H, d, J=is 8.46 Hz), to 11.35 (1H, s) 12,50 (1H, s).367365

1H-NMR (DMSO-D6) δ: 1,00 (6H, s), of 1.57 (2H, t, J=6,25 Hz), 2,04 (3H, s), is 2.40 (2H, s), 2,60-of 2.68 (2H, m), 6,48 (1H, C) to 7.04 (1H, DD, J=is 8.46, to 1.61 Hz), value of 7, 37 (1H, d, J=is 8.46 Hz), a 7.87 (1H, s), 9,78 (1H, s), 11,12 (1H, s), 12,42 (1H, s).
374 323321
3751H-NMR (DMSO-D6) δ: of 1.01 (6H, s) to 1.21 (3H, d, J=6.85 Hz), of 1.57 (2H, t, J=6,25 Hz), is 2.40 (2H, s), 2,49-of 2.69 (6H, m), up 3.22 (1H, square, J=6.85 Hz), 3,58-to 3.67 (4H, m), of 6.49 (1H, s), was 7.08 (1H, d, J=is 8.46 Hz), 7,39 (1H, d, J=is 8.46 Hz), to 7.89 (1H, s), 9,65 (1H, s), is 11.17 (1H, s), 12,44 (1H, s).422420

Table 1-78
No. etc.Structural formulaNMRMS (M+H)MS (M-N)
3761H-NMR (DMSO-D6) δ: 0.98 m (d, 3H, J=6,45 Hz), 1,01 (s, 6H), 1,58 (t, 2H, J=6,25 Hz), 2,23-to 2.29 (m, 1H), 2,41 (s, 2H), 2,49-2,56 (m, 1H), 2,66-2,69 (m, 2H), 3,17 (square, 1H, J=6,72 Hz), up 3.22 (s, 3H), 4,39-to 4.41 (m, 1H), 6,62 (s, 1H), of 6.87 (d, 1H, J=compared to 8.26 Hz), 7,26 (s, 1H), EUR 7.57 (d, 1H, J=compared to 8.26 Hz), 11,38 (s, 1H), 12,54 (s, 1H).410408
377 1H-NMR (DMSO-D6) δ: or = 0.97 (d, 3H, J=6,69 Hz), 1,01 (s, 6H), 1,58 (t, 2H, J=6,29 Hz), 2,41 (s, 2H), 2,63-of 2.72 (m, 2H), 3,19 (s, 3H), 3,37 (square, 1H, J=6,69 Hz), 6,61 (s, 1H), 6,91 (d, 1H, J=8,16 Hz), 7,28 (s, 1H), 7,56 (d, 1H, J=Hz 8,16), 11,42 (s, 1H), of 12.55 (s, 1H).366364

3781H-NMR (DMSO-D6) δ: of 1.01 (6H, C) of 1.01 (3H, d, J=5,64 Hz), 1,58 (2H, t, J=6,25 Hz), is 2.41 (2H, s), 2,56-of 2.72 (3H, m), 3,18 (3H, s), 3,20-3,48 (5H, m), 3,62-3,73 (1H, m), of 4.44-of 4.54 (1H, m), 6,28-6.35 mm (1H, m), 6,59 (1H, s), To 6.88 (1H, d, J=is 8.46 Hz), 7,27 (1H, s), 7,54 (1H, d, J=is 8.46 Hz), is 11.39 (1H, s), of 12.53 (1H, s).452450
3791H-NMR (DMSO-D6) δ: of 1.01 (6H, s), was 1.04 (3H, d, J=6.85 Hz), 1,58 (2H, t, J=6,25 Hz), is 2.41 (2H, s), 2,58 (1H, square, J=6.18 of Hz), 2,68 (2H, t, J=5,84 Hz), 3,05-3,52 (10H, m), 6,61 (1H, C), 6,90 (1H, d, J=is 8.46 Hz), 7,30 (1H, s), 7,55 (1H, d, J=is 8.46 Hz), at 11.37 (1H, s), 12,52 (1H, s).468466

3801H-NMR (DMSO-D6) δ: of 1.01 (6H, s) of 1.26 (3H, d, J=6,72 Hz), 1,58 (2H, t, J=6,15 Hz), 2,43(2H, C), 2,68 (2H, t, J=of 6.26 Hz), 3,05 (2H, s), or 3.28 (3H, s), 3,73 (2H, t, J=5,10 Hz), a 3.87 (1H, d, J=5,80 Hz), 4,06 (2H, s), to 6.67 (1H, d, J=1,39 Hz), 7,01 (1H, DD, J=8,35, to 1.86 Hz), 7,39 (1H, C), a 7.62 (1H, d, J=8,12 Hz), 8,93 (1H, s), 9,20 (1H, s), an 11.58 (1H, s).468466
3811H-NMR (DMSO-D6) δ: 1,00 (6H, s) of 1.36 (3H, d, J=5.8 Hz), 1.56 to to 1.60 (2H, m), 2,42 (2H, s), 2,66-2,69 (2H, m), 2,96-3,20 (2H, m), 3,23-of 3.46 (6H, m), 3,69-of 3.87 (4H, m), 6,60-to 6.66 (1H, m), 6,87-7,01 (1H, m), 7,27-value of 7, 37 (1H, m), 7,51-of 7.64 (1H, m), 10,44 (1H, usher.C) 11,54 (1H, usher.C) 12,60 (1H, usher.C).436434

Experimental example: inhibiting ITK activity

(1) preparation of enzyme hITK

Enzyme hITK received a strong expression of FLAG-tagged full-hITK in Sf9 cells and the purification of his column with anti-FLAG-antibody.

(2) Obtaining biotinylating GST-SLP76

Biotinylating GST-SLP76 received a strong expression of GST-tagged SLP76 (aa95-175) in Escherichia coli, cleaning it on a column of glutathioneperoxidase and bioterrorism product.

(3) obtaining the solution

(i) Buffer for cultivation: 20 mmol/l 3-(N-morpholino)propanesulfonic acid (pH 7.0) (DOJINDO LABORATORIES), 10 mmol/l magnesium chloride (Sigma-Aldrich Corporation), 1 mmol/l of dithiothreitol (Nacalai Tesque, Inc.), A 0.1% gelatin (Sigma-Aldrich Corporation),

(ii) substrate solution: 0.2 mg/ml biotinylated�about GST-SLP76, 100 μmol/l ATP (Sigma-Aldrich Corporation), obtained using the buffer for dilution,

(iii) a solution of the test compounds: test compound, 50% dimethylsulfoxide (DMSO) obtained using the buffer for dilution,

(iv) enzyme solution: 50 ng/ml of the enzyme hITK obtained using buffer for cultivation,

(v) reference solution: the solution after removal of the test compounds from a mixture of the above solutions (i), (ii) and (iii),

(vi) blank solution: the solution after removal of ATP from the mixture of the above solutions (i), (ii) and (iii),

(vii) a buffer for detection: 0.1 μg/ml antiphosphotyrosine (PT66)-cryptate (Cisbio), 2.5 ág/ml strategicinitiatives XL665 (Cisbio), 50 mmol/l 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (pH 7,4) (Nacalai Tesque, Inc.), 30 mmol/l EDTA (NipponGene), and 0.1% Triton X (Sigma-Aldrich Corporation), 200 mmol/l of potassium fluoride (Wako Pure Chemical Industries, Ltd.), 0.05% bovine serum albumin (Sigma-Aldrich Corporation).

(4) Measurement of inhibiting ITK activity

Of the substrate solution (25 μl/well), the solution of the test compound (5 μl/well) and the enzyme solution (20 μl/well) was added to a 96 well plate with white half of the area (plate, Corning Incorporated 3642) to start the kinase reaction. The tablet was kept in static conditions at room temperature for 10 min. Then the tablet was added a buffer for detection (50 µl/well). After 2 hour after addition of the buffer �La detection measured the fluorescence intensity at 620 nm (excited at 337 nm) and fluorescence intensity at 665 nm (excited at 620 nm) microplate reader for reading fluorescence.

The ratio (fluorescence intensity at 665 nm/fluorescence intensity at 620 nm ×10000) of each test compound was calculated from the measured fluorescence intensity. At the same time a measurement was performed using a solution for the blank solution and the control solution and the percent control values of each of the test compounds was calculated by the following formula.

% of control = (the ratio of the test compounds against the blank solution)/(the ratio of control - against blank solution)×100

The degree of inhibition of ITK (%) = 100-(% control)

The value of IC50was calculated from the concentrations of the test compounds at 2 points, between which is a 50% degree of inhibition of ITK. The results are shown in table 2 in units of nm. A numeric value in % in the table shows the degree of inhibition of ITK (%) at the concentration indicated in parentheses.

Table 2-1
No. exampleIC50ITK(nm)
17
25
339
42
53
62
739
83
9334
1045
1136
1233
1399
1440
159
1625
175
1845
1923
2047
2130
2240

2318
2425
25 26
2685
27327
28201
2985
3010
3134
324
3311
345
355
36<3
378
385
394
406
414
4222
436
44<3
45<3
46 5
478
486

493
504
5126
52<3
538
5418

Table 2-2
No. exampleIC50ITK(nm)
55<3
56<3
5717
586
597
605
616
624
63
646
6555
663
674
687
694
703
71<3

729
73<3
744
7534
764
776
787
7913
803
818
827
83<3
84<3
854
86<3
87<3
883
89<3
904
9113
9210
9348
944
953
963
9720

983
9926
1005
10113
102117
1033
4
1052
1067
10710
10815

Table 2-3
No. exampleIC50ITK(nm)
1096
1107
1119
1127
1139
1145
1154
1169
1176
1183
1193
1205

121 5
12220
1232
12412
1251
1268
1271
1282
1295
1302
13125
13213
13310
1348
1356
1362
1372
1383
1392
1402
14110
1425
1433
1449
1453
14611

1478
14819
14910
1502
1513
15214
1535
1542
1559
156<1
1571
1585
1597
1601
16122
1

Table 2-4
No. exampleIC50ITK(nm)
1631
1643
1655
1661
1671
1683
1693

170<1
1711
1722
17313
1742
1752
1767
1772
1784
1791
180<1
1811
1822
1831
1841
1852
1861
1872
1881
1891
1904
1917
1922
1932
1942
19520

1964
1972
1981
19 2
2001
20110
20214
20312
20449.2 percent (30 nm)
20527
2065
2074
20829
2094
21036
21133
2125
213<3
214<3
215<3
2168

Table 2-5
No. exampleIC50ITK(nm)
217<3
218<3

2194
220<3
2213
222<3
2235
2241
2252
2262
22734
22840
22938
23025
2312
2323
23310
23416
2358
2366
2372
2382
2395
2403
24123
2423
24324
24423

24510
2467
2474
2482
2497
250139
25134
25211
2532
2545
2553
2561
2571
2584
2593
260<1
2611
2623
2637
26410
2652
2667
2675
2685
2696
2702

Table 2-6
No. exampleIC50ITK(nm)
2713
2723
27311
274 9
2752
2764
2771
2781
279<1
2802
2811
2822
2832
2841
2852
2862
2871
2881
289<1
2908
2911
2922
293263

294 51
295138
29658
29748
29844
29974
300221
30137
30239
30333
30427
30513
30627
30761
30849
309102
31047
31132
31227
31347
314143
315 60
31647
31721
31845
31946

32049
32148
32241
32334
324140

Table 2-7
No. exampleIC50ITK(nm)
325246
32642
327132
32826
32913
33080
33160
332 46
333106
33431
33526
33678
33749
33833
339842
340129
341333
342245

343135
344278
34588
3465
3474
3488
3492
35062
35124
352 37
35316
35416
3559
3569
35729
35838
35921
36067
36120
36212
363485
36445
36545
36682
36775
368131

369207
370204
371112
372 11
3738
374130
375110

Table 2-8
No. exampleIC50ITK(nm)
3762
3776
3782
3794
3802
3812

The test compounds of examples 380 and 381, the concentration of ATP in solution of the substrate was 6 μmol/L.

From the above results it is clear that the compound of the present invention has an inhibiting ITK activity.

Example of preparation 1 (preparation of capsules)

1) connection example 130 mg
2) microcrystalline cellulose10 mg
3) lactose 19 mg
4) magnesium stearate1 mg

1), 2), 3) and 4) are mixed and the gelatin capsule filled with a mixture.

Example of preparation 2 (a pill)

1) connection example 110 g
2) lactose50 g
3) corn starch15 g
4) calcium salt carmellose44 g
4) magnesium stearate1 g

All specified quantity of 1), 2) and 3) and 30 g of 4) are mixed with water, the mixture is dried in vacuo and sieved. The sifted powder is mixed with 14 g of 4) and 1 g of 5) and the mixture was tableted teletrauma dishwasher. Thus get a 1000 tablets, each tablet contains 10 mg of the compound of example 1.

Industrial applicability

Therefore, the indole derivative of the present invention may be a pharmaceutical agent effective for the treatment or prevention of inflammatory diseases, allergic diseases, autoimmune diseases, transplant rejection and other similar diseases.

This application is based on claims� patent No. 2009-268040, which is registered in Japan, and the contents of which are fully included in the given context.

1. The compound represented by the following formula [I] or its pharmaceutically acceptable salt,

where
R1is a
(1) a hydrogen atom,
(2) a hydroxy-group or
(3) C1-6alkoxygroup, optionally substituted C6-10aryl group(s);
R2and R3are the same or different and each represents a
(1) a hydrogen atom or
(2) C1-6alkyl group, optionally substituted with 1-3 substituents selected from
(a) hydroxyl groups and
(b) C1-6alkoxygroup; and
R4is a group represented

which is associated with 5-position or 6-position of the indole ring,
in which
R5is a
(1) a hydrogen atom or
(2) C1-6alkyl group and
R6is a
(1) a hydrogen atom,
(2) C1-6alkyl group, optionally substituted with 1-3 substituents selected from
(a) hydroxyl groups,
(b) C1-6alkoxygroup,
(c) carboxypropyl,
(d) C1-6alkoxycarbonyl group,
(e) C6-10aryl group,
(f) C6-10aryloxy groups,
(g) amino group optionally mono - or disubstituted C1-6alkyl group(s)
(h) a 5-or 6-membered unsaturated heterocyclic group, optionally substituted C1-6alkyl group(s) and
(i) 5 - or 6-membered saturated heterocyclic group,
(3) C1-6alkoxygroup,
(4) C6-10aryl group, or
(5) a 5 - or 6-membered unsaturated heterocyclic group, optionally substituted with 1-3 substituents selected from
(a) hydroxyl groups and
(b) C1-6alkoxygroup, or
R5and R6together with the nitrogen atom to which they are linked, form a 5 - or 6-membered cyclic amine (specified cyclic amine optionally condensed with 5 - or 6-membered unsaturated heterocycle), optionally substituted with 1-3 substituents selected from
(a) hydroxyl groups,
(b) C1-6alkyl group,
(c) C1-6alkoxygroup and
(d) C1-6alkoxycarbonyl group;
R7is a
(1) a hydrogen atom or
(2) C1-6alkyl group, optionally substituted with 1-3 substituents selected from
(a) hydroxyl groups,
(b) C1-6alkoxygroup and
(c) amino, optionally mono - or disubstituted C1-6alkyl group(s) and
R8is a
(1) C1-6alkyl group, optionally substituted with 1-3 substituents selected from
(a) hydroxyl groups,
(b) C1-6alkoxygroup, optionally substituted C6-10aryl group(s)
(c) C3-6cycloalkyl group, neo�Astelin substituted C 1-6alkoxygroup(AMI),
(d) C6-10aryl group,
(e) a 5 - or 6-membered unsaturated heterocyclic group optionally substituted by oxopropoxy(AMI),
(f) 5-8-membered saturated heterocyclic group, optionally substituted with 1-3 substituents selected from
(i) hydroxyl groups,
(ii) C1-6alkyl group, optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup,
(iii) C1-6alkoxygroup and
(iv) the carbonyl group,
(g) C3-6cycloalkylcarbonyl,
(h) C6-10aryloxy groups,
(i) 5 - or 6-membered unsaturated geterotsiklicheskikh,
(j) a 5 - or 6-membered saturated geterotsiklicheskie and
(k) an amino group optionally mono - or disubstituted by substituents selected from
(i) C1-6alkyl group, optionally substituted with 1-3 substituents chosen from hydroxyl groups, carboxypropyl and carboxy-(C1-6alkoxygroup,
(ii) C1-6alkylcarboxylic group, optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup,
(iii) C1-6alkoxycarbonyl group, an optionally substituted C6-10aryl group(s) and
(iv) C3-6cycloalkylcarbonyl group, an optionally substituted C1-6alkoxygroup(AMI),
(2) C1-6alkoxygroup, optionally substituted C 6-10aryl group(s)
(3) C3-6cycloalkyl group, optionally substituted with 1-3 substituents selected from
(a) hydroxyl groups and
(b) C1-6alkoxygroup,
(4) C6-10aryl group, an optionally substituted C1-6alkyl group(s) optionally substituted by 1 to 3 halogen atoms,
(5) an amino group optionally mono - or disubstituted C1-6alkyl group(s) optionally substituted C6-10aryl group(s)
(6) a 5 - or 6-membered unsaturated heterocyclic group, an optionally substituted C1-6alkyl group(s)
(7) a 5 - or 6-membered saturated heterocyclic group, optionally substituted with 1-3 substituents selected from
(a) C1-6alkyl group,
(b) C1-6alkylcarboxylic groups and
(c) the carbonyl group,
(8) C3-6cycloalkylation or
(9) C6-10arylcarbamoyl group, or
R7and R8together with the nitrogen atom and the carbon atom to which they are linked, form a 5 - or 6-membered cyclic amine substituted by exography and optionally additionally substituted by 1-3 substituents selected from
(a) hydroxyl groups,
(b) C1-6alkyl group, optionally substituted hydroxy-group(s)
(c) C1-6alkoxygroup and
(d) C3-6cycloalkyl group.

2. The connection represented by the following� formula [I-a], or its pharmaceutically acceptable salt

where
R1is a
(1) a hydrogen atom,
(2) a hydroxy-group or
(3) C1-6alkoxygroup, optionally substituted C6-10aryl group(s);
R2and R3are the same or different and each represents a
(1) a hydrogen atom or
(2) C1-6alkyl group, optionally substituted with 1-3 substituents selected from
(a) hydroxyl groups and
(b) C1-6alkoxygroup;
R7'represents C1-6alkyl group, optionally substituted with 1-3 substituents selected from
(a) hydroxyl groups,
(b) C1-6alkoxygroup and
(c) amino, optionally mono - or disubstituted C1-6alkyl group(s) and
R8is a
(1) C1-6alkyl group, optionally substituted with 1-3 substituents selected from
(a) hydroxyl groups,
(b) C1-6alkoxygroup, optionally substituted C6-10aryl group(s)
(c) C3-6cycloalkyl group, an optionally substituted C1-6alkoxygroup(AMI),
(d) C6-10aryl group,
(e) a 5 - or 6-membered unsaturated heterocyclic group optionally substituted by oxopropoxy(AMI),
(f) 5-8-membered saturated heterocyclic group, optionally substituted with 1-3 substituents, you�from early
(i) hydroxyl groups,
(ii) C1-6alkyl group, optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup,
(iii) C1-6alkoxygroup and
(iv) the carbonyl group,
(g) C3-6cycloalkylcarbonyl,
(h) C6-10aryloxy groups,
(i) 5 - or 6-membered unsaturated geterotsiklicheskikh,
(j) a 5 - or 6-membered saturated geterotsiklicheskie and
(k) an amino group optionally mono - or disubstituted by substituents selected from
(i) C1-6alkyl group, optionally substituted with 1-3 substituents chosen from hydroxyl groups, carboxypropyl and carboxy-(C1-6alkoxygroup,
(ii) C1-6alkylcarboxylic group, optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup,
(iii) C1-6alkoxycarbonyl group, an optionally substituted C6-10aryl group(s) and
(iv) C3-6cycloalkylcarbonyl group, an optionally substituted C1-6alkoxygroup (AMI),
(2) C1-6alkoxygroup, optionally substituted C6-10aryl group(s)
(3) C3-6cycloalkyl group, optionally substituted with 1-3 substituents selected from
(a) hydroxyl groups and
(b) C1-6-alkoxygroup,
(4) C6-10aryl group, an optionally substituted C1-6alkyl group(s), optional�tive substituted by 1-3 halogen atoms,
(5) an amino group optionally mono - or disubstituted C1-6alkyl group(s) optionally substituted C6-10aryl group(s)
(6) a 5 - or 6-membered unsaturated heterocyclic group, an optionally substituted C1-6alkyl group(s)
(7) a 5 - or 6-membered saturated heterocyclic group, optionally substituted with 1-3 substituents selected from
(a) C1-6alkyl group,
(b) C1-6alkylcarboxylic groups and
(c) the carbonyl group,
(8) C3-6cycloalkylation or
(9) C6-10arylcarbamoyl group, or
R7'and R8together with the nitrogen atom and the carbon atom to which they are linked, form a 5 - or 6-membered cyclic amine substituted by exography and optionally additionally substituted by 1-3 substituents selected from
(a) hydroxyl groups,
(b) C1-6alkyl group, optionally substituted hydroxy-group(s)
(c) C1-6alkoxygroup and
(d) C3-6cycloalkyl group.

3. The compound according to claim 2, in which
R1represents a hydrogen atom and
R2and R3are the same or different and each represents C1-6alkyl group,
or its pharmaceutically acceptable salt.

4. The compound according to claim 3, in which
R7'represents C1-6alkyl group and
R8is with�fight C 1-6alkyl group, substituted with 1-3 substituents selected from
(a) hydroxyl groups,
(b) C1-6alkoxygroup, optionally substituted C6-10aryl group(s)
(c) C3-6cycloalkyl group, an optionally substituted C1-6alkoxygroup(AMI),
(d) C6-10aryl group,
(e) a 5 - or 6-membered unsaturated heterocyclic group optionally substituted by oxopropoxy(AMI),
(f) 5-8-membered saturated heterocyclic group, optionally substituted with 1-3 substituents selected from
(i) hydroxyl groups,
(ii) C1-6alkyl group, optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup,
(iii) C1-6alkoxygroup and
(iv) the carbonyl group,
(g) C3-6cycloalkylcarbonyl,
(h) C6-10aryloxy groups,
(i) 5 - or 6-membered unsaturated geterotsiklicheskikh,
(j) a 5 - or 6-membered saturated geterotsiklicheskie and
(k) an amino group optionally mono - or disubstituted by substituents selected from
(i) C1-6alkyl group, optionally substituted with 1-3 substituents chosen from hydroxyl groups, carboxypropyl and carboxy-(C1-6alkoxygroup,
(ii) C1-6alkylcarboxylic group, optionally substituted with 1-3 substituents chosen from hydroxyl groups and C1-6alkoxygroup,
(iii) C1-6alcox�carbonyl group, optionally substituted C6-10aryl group(s) and
(iv) C3-6cycloalkylcarbonyl group, an optionally substituted C1-6alkoxygroup(AMI),
or its pharmaceutically acceptable salt.

5. Compound selected from compounds of the following formulas:











or its pharmaceutically acceptable salts.

6. The compound of the following formula

or its pharmaceutically acceptable salt.

7. The compound of the following formula

or its pharmaceutically acceptable salt.

8. The compound of the following formula

or its pharmaceutically acceptable salt.

9. The compound of the following formula

or its pharmaceutically acceptable salt.

10. The compound of the following formula

or its pharmaceutically acceptable salt.

11. The compound of the following formula

or its pharmaceutically acceptable price�acceptable salt.

12. Pharmaceutical composition intended for inhibiting inducible T-cell kinase (ITK), containing the compound according to any one of claims. 1-11 or its pharmaceutically acceptable salt and pharmaceutically acceptable carrier.

13. The ITK inhibitor containing the compound according to any one of claims. 1-11 or its pharmaceutically acceptable salt.

14. Agent for the treatment or prevention of inflammatory diseases containing a compound according to any one of claims. 1-11 or its pharmaceutically acceptable salt.

15. A compound according to claim 14, where the inflammatory disease is rheumatoid arthritis.

16. Agent for the treatment or prevention of allergic diseases containing a compound according to any one of claims. 1-11 or its pharmaceutically acceptable salt.

17. Agent for the treatment or prevention of autoimmune diseases containing a compound according to any one of claims. 1-11 or its pharmaceutically acceptable salt.

18. A compound according to claim 17, where the autoimmune disease is rheumatoid arthritis.

19. Inhibitor of rejection in the transplantation comprising compound according to any one of claims. 1-11 or its pharmaceutically acceptable salt.

20. Method of inhibiting ITK in a mammal, containing the introduction of a pharmaceutically effective amount of a compound according to any one of claims. 1-11 or its pharmaceutically acceptable salt to a mammal.

2. Method of treating or preventing inflammatory disease in a mammal, comprising administering pharmaceutically effective amount of a compound according to any one of claims. 1-11 or its pharmaceutically acceptable salt to a mammal.

22. A method according to claim 21, in which the inflammatory disease is rheumatoid arthritis.

23. Method of treating or preventing an allergic disease in a mammal, comprising administering pharmaceutically effective amount of a compound according to any one of claims. 1-11 or its pharmaceutically acceptable salt to a mammal.

24. Method of treating or preventing autoimmune disease in a mammal, comprising administering pharmaceutically effective amount of a compound according to any one of claims. 1-11 or its pharmaceutically acceptable salt to a mammal.

25. A method according to claim 24, where the autoimmune disease is rheumatoid arthritis.

26. A method of suppressing rejection during transplantation in a mammal, comprising administering pharmaceutically effective amount of a compound according to any one of claims. 1-11 or its pharmaceutically acceptable salt to a mammal.

27. Use of a compound according to any one of claims. 1-11 or its pharmaceutically acceptable salt to obtain funds for the treatment or prevention of inflammatory diseases.

28. The use according to claim 27, in which� inflammatory disease is rheumatoid arthritis.

29. Use of a compound according to any one of claims. 1-11 or its pharmaceutically acceptable salt to obtain funds for the treatment or prevention of allergic diseases.

30. Use of a compound according to any one of claims. 1-11 or its pharmaceutically acceptable salt to obtain funds for the treatment or prevention of autoimmune diseases.

31. The use according to claim 30, in which the autoimmune disease is rheumatoid arthritis.

32. Use of a compound according to any one of claims. 1-11 or its pharmaceutically acceptable salt to obtain an inhibitor of rejection during transplantation.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to field of organic chemistry, namely to method of obtaining 7-R-pyrido[1,2-a]benzimidazoles of general formula, , where a) R=CF3, R'=H; b) R=CN, R'=H; c) R=COOH, R'=H; d) R=COOCH3, R'=H; e) R=COOC2H5, R'=H; f) R=COOPh, R'=H; g) R=CF3, R'=CH3; h) R=CN, R'=CH3, which consists in the fact that reduction of N-(2-nitro-4-R-phenyl)-3,5-R'-pyridinium chlorides is carried out in mixture of alcohol and 4% hydrochloric acid, taken in ratio 1:1, by means of electric current in electrolyser without diaphragm in galvanostatic mode at temperature 40°C on lead cathode, with passing charge in 4 F for 0.5 h, current power 0.4 A through electrolytic cell, with application of platinum anode, target products are extracted by filtration of precipitated sediment after processing reaction mixture with ammonium hydroxide.

EFFECT: method of obtaining derivatives of pyrido[1,2-a]benzimidazoles, which can be applied as semi-products for synthesis of biologically active substances, demonstrating antioxidant activity, which finds application in field of optoelectronics, for example non-linear optics, has been elaborated.

8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of structural formula

,

having Aβ42 secretion inhibiting activity. In formula I , hetaryl I is a five- or six-member heteroaryl group containing 1-3 heteroatoms selected from O, S or N, hetaryl II is a five- or six-member heteroaryl group containing 1-3 heteroatoms as defined above for hetaryl I, or is a bicyclic ring system containing 1-4 heteroatoms selected from S, O or N, where at least one ring is aromatic by nature, R1 is C1-7-alkyl, C1-7-alkoxy, C1-7-alkyl substituted with a halogen, or a halogen; R2 is a halogen, C1-7-alkyl, C1-7-alkoxy, hydroxy, C1-7-alkyl substituted with a halogen, C1-7-alkyl substituted with a hydroxy, or benzo[1,3]dioxolyl or is -(CHR)p-phenyl, optionally substituted with a halogen, C1-7-alkyl, C1-7-alkoxy, S(O)2-C1-7-alkyl, cyano, nitro, C1-7-alkoxy substituted with a halogen, dimethylamino, -(CH2)p-NHC(O)O-C1-7-alkyl or C1-7-alkyl, substituted with a halogen. The values of radicals R, R3, R4,p, n, m, o are given in the claim.

EFFECT: invention relates to a method of producing said compounds, a medicinal agent containing said compounds and a method of treating Alzheimer's disease, cerebral amyloid angiopathy, Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D), vascular dementia, dementia pugilistica or Down syndrome, associated with β amyloid activity.

21 cl, 283 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compounds, which possess an inhibiting activity with respect to anti-apoptotic Bcl-2 proteins. The invention also relates to a pharmaceutical composition, containing the said compounds, and to a method of treating urinary bladder cancer, brain cancer, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukaemia, colorectal cancer, oesophageal cancer, hepatocellular cancer, lymphoblast leukosis, follicular lymphoma, lymphoid malignant diseases of a T-cell or B-cell origin, melanoma, myelogenous leukaemia, myeloma, oral cavity cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small-cell lung cancer or spleen cancer.

EFFECT: obtaining the compounds, possessing the inhibiting activity with respect to anti-apoptotic Bcl-2 proteins.

4 cl, 5 tbl, 405 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel N-containing heteroaryl derivatives of formula I or II or their pharmaceutically acceptable salts, which possess properties of JAK kinase, in particular JAK3, and can be applied for treating such diseases as asthma and chronic obstructive pulmonary disease (COPD). In formulae A represents carbon and B represents nitrogen or A represents nitrogen and B represents carbon; W represents CH or N; R1 and R2, independently represent hydrogen, C1-4alkyl, halogenC1-4alkyl, -CN; R3 represents C1-4alkyl, R9-C1-4alkyl, Cy1, where Cy1 is optionally substituted with one or several substituents R10; R4 represents hydrogen, C1-4alkyl, R12R7N-C0alkyl, where one of R7 and R12 represents hydrogen, and the other represents C1-4alkyl or group R13, which is selected from C1-5alkyl, Cy2-C0alkyl; R5 represents hydrogen; R6 represents hydrogen, C1-4alkyl, C1-4alkoxyC1-4alkyl, hydroxyC1-4alkyl, R12R7N-C1-4alkyl, R16CO-C0alkyl, Cy1; R7 represents hydrogen or C1-4alkyl; R9 represents halogen, -CN, -CONR7R12, -COR13, CO2R12, -OR12, -SO2R13, -SO2NR7R12, -NR7R12, -NR7COR12; R10 represents C1-4alkyl or R9-C0-4alkyl; R11 represents C1-4alkyl, halogen, -CN, -NR7R14; R12 represents hydrogen or R13; R13 represents C1-5alkyl, hydroxyC1-4alkyl, cyanoC1-4alkyl, Cy2-C0alkyl or R14R7N-C1-4alkyl; where Cy2 is optionally substituted with one or several constituents R11; R14 represents hydrogen or C1-4alkyl; R16 represents C1-4alkyl, halogenC1-4alkyl, C1-4alkoxyC1-4alkyl, hydroxyC1-4alkyl or cyanoC1-4alkyl; Cy1 represents monocyclic carbocyclic unsaturated or saturated ring, selected from C3-C6cycloalkyl, phenyl, or saturated monocyclic 4-6-membered heterocyclic ring, containing from 1 to 2 heteroatoms, selected from N and S, or partially unsaturated 10-membered bicyclic heterocyclic ring, containing oxygen atom as heteroatom, which can be substituted with group R11, where said ring is bound with the remaining part of molecule via any available C atom, and where one or several ring C or S atoms are optionally oxidised with formation of CO or SO2; and Cy2 represents monocyclic carbocyclic unsaturated ring, selected from C3-C6cycloalkyl, or aromatic monocyclic 4-6-membered heterocyclic ring, containing from 1 to 2 heteroatoms, selected from N and S, or unsaturated 10-membered bicyclic heterocyclic ring, containing oxygen atom as heteroatom, which can be substituted with group R11, where said ring is bound with the remaining part of molecule via any available atom C or N.

EFFECT: obtaining novel heteroaryl derivatives.

27 cl, 41 ex

Ethinyl derivatives // 2553461

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to ethinyl derivatives of formula I, where X represents N or C-R1; Y represents N or C-R2; Z represents CH or N; R4 represents 6-membered ring, containing 0, 1 or 2 nitrogen atoms, possibly substituted with 1-2 groups, selected from halogen, lower alkyl, lower alkoxy or NRR'; R1 represents hydrogen, lower alkyl, lower hydroxyalkyl, lower cycloalkyl or represents 5-6-membered heterocycloalkyl, containing 1-2 heteroatoms, selected from O and N; R2 represents hydrogen, CN; R and R' independently on each other represent hydrogen; or their pharmaceutically acceptable salts or acid-addition salts. Invention also relates to pharmaceutical composition, possessing activity of positive allosteric modulator of mGluR5 receptor, including effective quantity of at least one invention compound, and to application of invention compounds for manufacturing medication for treatment or prevention of diseases, associated with positive allosteric modulators of mGluR5 receptor.

EFFECT: obtained are novel compounds, which can be applied as positive allosteric modulator of mGluR5 receptor.

14 cl, 51 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of formula (I), their pharmaceutically acceptable salts, tautomers or stereoisomers. In formula R1 represents benzimidazolyl optionally substituted by C1-4alkyl, C1-4alkoxyC1-4alkyl, hydroxyC1-4alkyl, dimethylaminoC1-4alkyl or oxo group; benzioxazolyl optionally substituted by C1-4alkyl or amino group; benzotriazolyl optionally substituted by C1-4alkyl; dihydrobenzisothiazol-1,1-dionyl; pyrimidyl; dihydroisoquinolinonyl optionally substituted by oxo group; imidazopyridyl; indazolyl optionally substituted by C1-4alkyl, hydroxyC1-4alkyl, C1-4alkoxyC1-4alkyl, tetrahydropyranylamino, piperidinylamino, halogen, trifluoromethyl or amino group; indolinyl optionally substituted by C1-4alkyl, hydroxyC1-4alkyl, carboxylate or oxo group; isoindolinyl optionally substituted by C1-4alkyl, aminoC1-4alkyl, hydroxyC1-4alkyl, C1-4alkoxyC1-4alkyl or oxo group; phenyl optionally substituted by C1-4alkyl, C1-4alkoxy, halogen, cyano, trifluoromethyl, carbamoyl, methylcarbamoyl, piperidinylcarbamoyl, methylpiperidinylcarbamoyl, aminoC1-4alkyl, carboxyl, amino, dialkylamino, imidazolyl, pyrrolidin-2-one, triazolyl, morpholinyl, C1-4alkylcarbonylamino, C1-4alkoxyC1-4alkoxy or hydroxyC1-4alkyl; pyrazolopyridyl optionally substituted by C1-4alkyl; pyridyl optionally substituted by C1-4alkyl, C1-4alkoxy, halogen, cyano, hydroxy, amino, morpholinyl, carbamoyl, monoC1-4alkylamino, diC1-4alkylamino, aminoC1-4alkoxy, aminoC1-4alkylamino, hydroxypiperidinyl, hydroxyC1-4alkyl, hydroxyC1-4alkoxy, pyrrolidinylC1-4alkylamino, pyrrolidinylC1-4alkoxy; pyrrolopyridinyl optionally substituted by oxo group; quinolinyl optionally substituted by amino or hydroxy group; or triazolopyridyl substituted by C1-4alkyl. The other radical values are presented in the patent claim. The invention also refers to individual compounds, to a pharmaceutical composition, possessing kinase inhibitory activity and containing an effective amount of the compound of the invention, to a method for kinase inhibition in a cell, to a method of treating or preventing inflammatory conditions, immunological conditions, allergic conditions, rheumatic conditions, cancer, and neuroinflammatory diseases.

EFFECT: there are prepared new compounds possessing Syk, FLT3, JAK1, JAK2 inhibitory activity.

21 cl, 1 tbl, 133 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of organic chemistry, namely to novel heterocyclic compounds of formula (1) and/or to their pharmaceutically acceptable salts, where A1 represents CH; A4and A5 independently represent CR2 or N; A2 and A3 together with ring B represent 5-membered heteroaryl or heterocycle, with said 5-membered heteroaryl or heterocycle being selected from where t represents 1 or 2; and R3 is independently selected from H, C1-C6 alkyl, C6-aryl, C3-C6-membered cycloalkyl, C(O)NRcRd, -ORb, heteroaryl, representing pyridine, and heterocycle, representing piperidine and tetrahydropyran; and each of said alkyl, aryl, cycloalkyl, heteroaryl and heterocycle can be substituted with one group, independently selected from C1-C6 alkyl, possibly substituted with one substituent, selected from -CONMe2, C3-membered cycloalkyl, -CN, -OMe, -pyridine, tetrahydropyran, -CO-morpholine, -CO-pyrrolidine, (3-methyl)oxetane; -OH; -C(O)Ra; -CN; -C(O)NRcRd; -NRcRd; -ORb; -S(O)nRe; halogen, and substituted with one group -COMe heterocycle, representing piperidine, on condition that when A4 represents CR2, A2 and A3 together with ring B are selected from structure (3), (5) or (6); represents single bond or double bond; R1 represents heteroaryl, representing 6-membered or 9-10-membered aromatic mono- or bicyclic ring, containing 1-3 heteroatoms, selected from nitrogen, oxygen and sulphur; possibly substituted with one or two groups, independently selected from C1alkyl, C2alkinyl, -NRcRd, -NRcS(O)nRe, -ORb, halogen, halogenalkyl; R2 is independently selected from H; each Ra, Rb, Rc, Rd, and Re is independently selected from H; C1-C4alkyl, possibly substituted with one substituent, selected from -OH, -OMe, -CN, -NH2, -NMe2, C3-cycloalkyl; C2-C3alkenyl; C3alkinyl; C6aryl, possibly substituted with one or more substituents, selected from fluorine or methyl group; C3-membered cycloalkyl, possibly substituted with one substituent, selected from -OH and -CN; halogenalkyl; heteroaryl, representing pyridine; and substituted with one methyl group heterocycle, representing piperidine, or Rc and Rd together with atom (atoms) which they are bound to form 5-6-membered heterocyclic ring, representing pyrrolidine or morpholine; and in each case n is independently equal 2. Invention also relates to particular compounds, pharmaceutical composition, based on claimed compounds; method of inhibiting PI3K and/or mTOR activity and to application of claimed compounds.

EFFECT: novel compounds, useful for inhibiting PI3K and/or mTOR activity have been obtained.

15 cl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the field of organic chemistry, namely to a compound of formula (I), or its tautomer, or a pharmaceutically acceptable salt, where each of Z1 and Z2: N and CR, where at least, one of Z1 and Z2 represents CR, and each R: H, C1-C4 alkyl and -N(R3)(R3); W: -O-, -N(C1-C4) alkyl and -C(R6)(R6) -, and each R6: H and C1-C4 alkyl, or two R6, bound with the same carbon atom, are taken together with the formation of =O, R1: a phenyl and heterocycle, which represents a saturated or unsaturated 5-6-member monocyclic ring, containing 1-3 heteroatoms, selected from atoms N, S and O, or a 8-12-member bicyclic ring, each cycle of which is selected from a saturated, unsaturated and aromatic cycle, containing 1-2 nitrogen atoms, where R1 is optionally substituted with one or more substituents, independently selected from halogen, C1-C4 alkyl, =O, fluorosubstituted C1-C2 alkyl, -O-R3, -(C1-C4 alkyl)-N(R3)(R3), -N(R3)(R3) and -C(O)-N(R3)(R3), R2: a phenyl and heterocycle, which represents an unsaturated 5-6-member monocyclic ring, containing 1-2 heteroatoms, selected from atoms N and O, or represents dihydrobenzofuranyl, where R2 is optionally substituted with 1-2 substituents, independently selected from a halogen, -C≡N, C1-C4 alkyl, C1-C2 fluorosubstituted alkyl, -O-R3, -(C1-C4 alkyl)-N(R3)(R3) and -N(R3)(R3); each R3: -C1-C4 alkyl; or two R3 are taken together with a nitrogen atom, which they are bound with, with the formation of a 4-8-member unsaturated heterocycle, optionally containing one additional heteroatom, selected from N and O, where in case when R3 represents an alkyl, the said alkyl is optionally substituted with two -OH groups, and when two R3 are taken together with a nitrogen atom, which they are bound with, with the formation of a 4-8-member saturated heterocycle, the said saturated heterocycle is optionally substituted with fluorine by any carbon atom; and is substituted with hydrogen by any capable of substitution nitrogen atom; p equals 1, 2 or 3; X2 is selected from -C(=O)-♣, -C(=O)-O-♣, -C(=O)-NH-♣, -S(=O)2-NH-♣ and -C(=O)-NH-CR4R5-♣, where: ♣ represents a site, by which X2 is bound with R1; and each R4 and R5 represents hydrogen. The invention also relates to compounds of formulas (IV), (V), (VI), particular the compounds, a pharmaceutical composition based on the compound of formulas (I), (IV)-(VI) and to a method of treatment, based on the application of the said compounds.

EFFECT: novel heterocyclic compounds, possessing sirtuin-modelling activity are obtained.

26 cl, 2 tbl, 40 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 5,6-dihydropyrrolo[2,1-a]isoquinoline derivatives 1-4 having the general structural formula: , where 1 - R=CH3, 2 - R=CH2CH3, 3 - R=CH2CF3, 4 - R=CH(CH3)2, characterised by that 6,7-diethoxy-3,4-dihydro-1-(3,4-diethoxybenzoyl)isoquinoline is mixed with methyl propiolate and methane, or ethanol, or 2,2,2-trifluoroethanol, or isopropanol and stirred at temperature of +50°C, the precipitate obtained at the end of the reaction and after removing reagents, is crystallised in ether.

EFFECT: method of producing derivatives which can be used as intermediate compounds when producing biologically active compounds.

4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to dihydroazol compounds of formula (I) wherein R1 means a C1-C6alkyl or C1-C6haloalkyl; X means a phenyl, which can be unsubstituted or substituted by one or more halogens, C1-C12alkyls, C3-C10cycloalkyls, C1-C12haloalkyls, C2-C12alkenyls, C2-C12haloalkenyls, C1-C12alkinyls or C1-C12haloalkynyls; A1 means hydrogen, and A2 means CR7R8; G means G-1 or G-2; B1, B2, B3, B4 and B5 independently mean N or C-R9; Y means Y-1, Y-2, Y-3, Y-4, Y-5, Y-6, Y-7, Y-8 or Y-9 (as it is presented in the patent claim); R2, R3 independently mean hydrogen, C1-C12alkyl, C1-C12haloalkyl, thio-C1-C12alkyl, C1-C12alkylthio-C1-C12alkyl, hydroxy-C1-C12alkyl, C1-C12alkoxy-C1-C12alkyl, C2-C12alkenyl, C2-C12haloalkenyl, C2-C12alkynyl, C2-C12haloalkynyl, C3-C10cycloalkyl; R4 independently means hydrogen, C1-C12alkyl, C1-C12haloalkyl, thio-C1-C12alkyl, C1-C12alkylthio-C1-C12alkyl, hydroxy-C1-C12alkyl, C1-C12alkoxy-C1-C12alkyl, C2-C12alkenyl, C2-C12haloalkenyl, C2-C12alkynyl, C2-C12haloalkynyl or C3-C10cycloalkyl; R7 and R8 independently mean hydrogen, C1-C12alkyl or C1-C12haloalkyl; R9 means hydrogen, halogen, C1-C12alkyl, C1-C12haloalkyl, C1-C12alkenyl, C2-C12haloalkenyl, C2-C12alkynyl or C2-C12haloalkynyl; each R10, R11, R12 and R13 independently means hydrogen, C1-C12alkyl or C1-C12haloalkyl; or R10 together with R11 form =O, =S or =NR2; or R12 together with R13 form =O, =S or =NR2; n=1. The invention also refers to compositions for treating or preventing endoparasitic infections or ectoparasitic invasions in animals and for protecting crops, plants, planting stock or timber against pests, to a method of treating or preventing endoparasitic infections or ectoparasitic invasions in animals, to a method for protecting crops and growing plants against pest attacks or invasions, to a method for preventing or controlling a pest invasion on site, and to using the compounds of formula (I).

EFFECT: compounds of formula (I) applicable for preventing or treating endoparasitic infections or ectoparasitic invasions in animals, and also as pesticides

30 cl, 2 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of structural formula

,

having Aβ42 secretion inhibiting activity. In formula I , hetaryl I is a five- or six-member heteroaryl group containing 1-3 heteroatoms selected from O, S or N, hetaryl II is a five- or six-member heteroaryl group containing 1-3 heteroatoms as defined above for hetaryl I, or is a bicyclic ring system containing 1-4 heteroatoms selected from S, O or N, where at least one ring is aromatic by nature, R1 is C1-7-alkyl, C1-7-alkoxy, C1-7-alkyl substituted with a halogen, or a halogen; R2 is a halogen, C1-7-alkyl, C1-7-alkoxy, hydroxy, C1-7-alkyl substituted with a halogen, C1-7-alkyl substituted with a hydroxy, or benzo[1,3]dioxolyl or is -(CHR)p-phenyl, optionally substituted with a halogen, C1-7-alkyl, C1-7-alkoxy, S(O)2-C1-7-alkyl, cyano, nitro, C1-7-alkoxy substituted with a halogen, dimethylamino, -(CH2)p-NHC(O)O-C1-7-alkyl or C1-7-alkyl, substituted with a halogen. The values of radicals R, R3, R4,p, n, m, o are given in the claim.

EFFECT: invention relates to a method of producing said compounds, a medicinal agent containing said compounds and a method of treating Alzheimer's disease, cerebral amyloid angiopathy, Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D), vascular dementia, dementia pugilistica or Down syndrome, associated with β amyloid activity.

21 cl, 283 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula:

I

where (a) X is N or CR8; (b) R1 is H, F, Cl, Br; (c) R2 is H; (d) R3 is H, F, Cl, Br; (e) R4 is H, F, Cl, Br, I, CN, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C2-C6alkenyl, substituted or unsubstituted C6-aryl, SR9, where each of said R4, which is substituted, contains one or more substitutes selected from F, Cl, Br; (f) R5 is H, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C2-C6alkenyl, C(=X1)R9, C(=X1)OR9, C1-C6alkylC6-aryl (where the aryl can be substituted or unsubstituted), R9X2C(=X1)R9, R9X2R9, C(=O)(C1-C6alkyl)S(O)n(C1-C6alkyl), C(=O)(C1-C6alkyl)C(=O)O(C1-C6alkyl), (C2-C6alkenyl)C(=O)O(C1-C6alkyl), SR9, R9S(O)nR9; where each of said R5, which is substituted, contains one substitute selected from F, Cl, Br, C3-C10cycloalkyl, OR9, optionally, R5 and R7 can be bonded to form a C3 cyclic system; (g) R6 is O, S, NR9; (h) R7 is substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C2-C6alkenyl, substituted or unsubstituted C1-C6alkoxy, substituted or unsubstituted C3-C10cycloalkyl, substituted or unsubstituted C6-aryl, substituted or unsubstituted C1-C20heterocyclyl, selected from thiazole, oxazole, isothiazole, thiophene, pyrroidine, furan, tetrahydrothiophene, pyridazine, piperdine, pyrazole, OR9, OR9S(O)nR9, C(=X1)R9, R9C(=X1)OR9, N(R9)2, N(R9)(R9S(O)nR9), SR9, R9S(O)nR9, C1-C6alkylC1-C20heterocyclyl (where the heterocyclyl is selected from triazole and pyrazole), C1-C6alkylS(=N-CN)(C1-C6alkyl), C1-C6alkylS(O)(=N-CN)(C1-C6alkyl), C1-C6alkylNH(C(=O)OC1-C6alkyl), C1-C6 alkylC(=O)OC1-C6alkyl, C1-C6alkyl(C6-aryl)NH(C(=O)OC1-C6alkyl), C1-C6alkyl(S-C1-C6alkyl)NH(C(=O)OC1-C6alkyl), C1-C6alkyl(S-C1-C6alkyl-C6-aryl)NH(C(=O)OC1-C6alkyl), C1-C6 alkyl(NHC(=O)OC1-C6alkylC6-aryl)NH(C(=O)OC1-C6alkyl), C1-C6alkyl(OC1-C6alkylC6-C20aryl)NH(C(=O)OC1-C6alkyl), C1-C6alkylNH(C1-C6alkyl)(C(=O)OC1-C6alkyl), C1-C6alkylNH(C1-C6alkyl), C1-C6alkylN(C1-C6 alkyl)(S(O)nC1-C6alkyl), C1-C6alkylN(C1-C6alkyl)(S(O)nC1-C6alkenylC6-aryl), C1-C6alkylN(C1-C6alkyl)(C(=O)C1-C20heterocyclyl) (where the heterocyclyl is selected from pyrazole or thiophene), C1-C6alkylN(C1-C6alkyl)(C(=O)OC1-C6alkylC6-aryl), NH(C1-C6alkylS(O)nC1-C6alkyl), where each of said R7, which is substituted, contains one or more substitutes selected from F, Cl, Br, C1-C6 alkyl, C3-C10 cycloalkyl, C(=X1)R9, C(=X1)OR9, =X2, S(=X2)nR9; (i) R8 is H, F, Cl, Br, I, CN, unsubstituted C1-C6alkoxy, C(=X)OR9, S(O)nR9; (j) R9 (each independently) is H, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C2-C6alkenyl, substituted or unsubstituted C1-C6alkoxy, substituted or unsubstituted C2-C6alkenyloxy, substituted or unsubstituted C3-C10cycloalkyl, substituted or unsubstituted C6-aryl, where each of said R9, which is substituted, contains one or more substitutes selected from F, Cl, Br, C1-C6alkyl, OC1-C6 alkyl, C6-aryl; (k) n equals 0, 1 or 2; (l) X1 is (each independently) O; (m) X2 is (each independently) O. The invention also relates to versions of the compound of formula (I). Compounds of formula (I) are intended for pest control and seed treatment.

EFFECT: thiazole derivatives for pest control.

12 cl, 2 tbl, 83 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula , wherein Y and Z are independently specified in a group of a) or b) so that one of Y or Z is specified in the group a), and another one - in the group b); the group a) represents i) substituted C6-10aryl; ii) C3-8cycloalkyl; iii) trifluoromethyl or iv) heteroaryl specified in a group consisting of thienyl, furanyl, thiazolyl, isothiazolyl, oxazolyl, pyrrolyl, pyridinyl, isoxazolyl, imidazolyl, furasan-3-yl, benzothienyl, thieno[3,2-b]thiophen-2-yl, pyrazolyl, triazolyl, tetrazolyl and [1,2,3]thiadiazolyl; the group b) represents i) C6-10aryl; ii) heteroaryl specified in a group consisting of thiazolyl, pyridinyl, indolyl, pyrrolyl, benzoxazolyl, benzothiazolyl, benzothienyl, benzofuranyl, imidazo[1,2-a]pyridin-2-yl, furo[2,3-b]pyridinyl, pyrrolo[2,3-b]pyridinyl, pyrrolo[3,2-b]pyridinyl, thieno[2,3-b]pyridinyl, quinolinyl, quinazolinyl, thienyl and benzimidazolyl; iii) benzofused heterocyclyl attached through a carbon atom, and when a heterocyclyl component contains a nitrogen atom, the carbon atom is optionally substituted by one substitute specified in a group consisting of C3-7cycloalkylcarbonyl; C3-7cycloalkylsulphonyl; phenyl; phenylcarbonyl; pyrrolylcarbonyl; phenylsulphonyl; phenyl(C1-4)alkyl; C1-6alkylcarbonyl; C1-6alkylsulphonyl; pyrimidinyl and pyridinyl; C3-7cycloalkylcarbonyl, phenyl, phenylcarbonyl, phenyl(C1-4)alkyl and phenylsulphonyl are optionally substituted by trifluoromethyl, or by one or two fluor-substitutes; iv) phenoxatiynyl; vi) fluoren-9-on-2-yl; vii) 9,9-dimethyl-9H-fluorenyl; viii) 1-chlornaphtho[2,1-b]thiophen-2-yl; ix) xanthen-9-on-3-yl; x) 9-methyl-9H-carbazol-3-yl; xi) 6,7,8,9-tetrahydro-5H-carbazol-3-yl; xiii) 3-methyl-2-phenyl-4-oxochromen-8-yl; or xiv) 1,3-dihydrobenzimidazol-2-on-5-yl optionally substituted by 1-phenyl, 1-(2,2,2-trifluoroethyl), 1-(3,3,3-trifluoropropyl) or 1-(4,4-difluorocyclohexyl); 1-phenyl is optionally substituted by one or more fluor-substitutes or trifluoromethyl; or xv) 4-(3-chlorophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8-yl; R1 represents C6-10aryl, C1-3alkyl, benzyloxymethyl, hydroxy(C1-3)alkyl, aminocarbonyl, carboxy, trifluoromethyl, spirofused cyclopropyl, 3-oxo or aryl(C1-3)alkyl; or when s is equal to 2 and R1 represents C1-3alkyl, the substitutes C1-3akyl is taken with a piperazine ring to form 3,8-diazabicyclo[3.2.1]octanyl or 2,5-diazabicyclo[2.2.2]octanyl ring system, and its pharmaceutical compositions.

EFFECT: preparing the new pharmaceutical compositions.

20 cl, 7 tbl, 72 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of obtaining 5-(het)aryl-4-(2-thienyl)-2-(thio)morpholylpyrimidine, represented by the general formula : where X=O or S, Ar=3-nitrophenyl or 2-thienyl. The described method consists in the fact that at the first stage 5-brom-4-(2-thienyl)-2-(thio)morpholylpyrimidine is obtained by interaction with the excess of 2-thienyllithium in the absolute ether at first at a temperature from -20 to -25°C for not less than 1 hour, and then at room temperature for not less than 18 hours, a solution of a mixture of potassium hexacyonoferrate (III) and potassium hydroxide in water are added with further mixing for 4 hours at room temperature, the ether phase is separated and distilled and the obtained remaining part is subjected to chromatographic separation on silica gel with the ratio in the eluent ethylacetate-hexane, 1:3, with (het)arylboric acid and tetrakis(triphenyphosphine)palladium(0) in tetrahydrofurane, a water solution of potassium carbonate is added and the obtained mixture is irradiated by microwave radiation at 155°C for 20 minutes, the solvent is distilled under a reduced pressure, the obtained residual is subjected to chromatographic separation on silica gel with the ratio in the eluent ethylacetate - hexane, 1:2 with obtaining the target product.

EFFECT: claimed is the highly-efficient two-stage method of obtaining 5-(het)aryl-4-(2-thienyl)-2-(thio)morpholylpyrimidines, which can have a wide spectrum of biological activity.

4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to fluorinated aminotriazole derivatives of formula

,

wherein A represents a group specified in furanyl, oxazolyl and thiazolyl, wherein two attachment points of the above group are found in 1,3-position; R1 represents phenyl, which is unsubstituted, mono- or disubstituted, wherein the substitutes are independently specified in a group consisting of halogen, methyl, methoxy group, trifluoromethyl, trifluormethoxy group and dimethylamino group; and R2 represents hydrogen, methyl, ethyl or cyclopropyl. Besides, the invention refers to a pharmaceutical composition containing the compound of formula (I), and to using the compound of formula (I) for preparing a therapeutic agent.

EFFECT: compounds of formula (I) possessing the agonist activity in relation to ALX receptor.

26 cl, 2 tbl, 36 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to specific compounds or to their therapeutically acceptable salt presented in the patent claim and representing sulphonyl benzamide derivatives. The invention also refers to a pharmaceutical composition inhibiting the activity of anti-apoptotic proteins of the family Bcl-2, containing an excipient and an effective amount of a specific sulphonyl benzamide derivative.

EFFECT: sulphonyl benzamide derivatives inhibiting the activity of anti-apoptotic Bcl-2 proteins.

2 cl, 3 tbl, 558 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula or its therapeutically acceptable salts, wherein A1 represents furyl, imidazolyl, isothiazolyl, isoxazolyl, pyrazolyl, pyrrolyl, thiazolyl, thiadiazolyl, thienyl, triazolyl, piperidinyl, morpholinyl, dihydro-1,3,4-thiadiazol-2-yl, benzothien-2-yl, banzothiazol-2-yl, tetrahydrothien-3-yl, [1,2,4]triazolo[1,5-a]pyrimidin-2-yl or imidazo[2,1-b][1,3]-thiazol-5-yl; wherein A1 is unsubstituted or substituted by one, or two, or three, or four, or five substitutes independently specified in R1, OR1, C(O)OR1, NHR1, N(R1)2, C(N)C(O)R1, C(O)NHR1, NHC(O)R1, NR1C(O)R1, (O), NO2, F, Cl, Br and CF3; R1 represents R2, R3, R4 or R5; R2 represents phenyl; R3 represents pyrazolyl or isoxazolyl; R4 represents piperidinyl; R5 represents C1-C10alkyl or C2-C10alkenyl each of which is not specified or specified by substitutes specified in R7, SR7, N(R7)2, NHC(O)R7, F and Cl; R7 represents R8, R9, R10 or R11; R8 represents phenyl; R9 represents oxadiazolyl; R10 represents morpholinyl, pyrrolidinyl or tetrahydropyranyl; R11 represents C1-C10alkyl; Z1 represents phenylene; Z2 represents piperidine unsubstituted or substituted by OCH3, or piperazine; both Z1A and Z2A are absent; L1 represents C1-C10alkyl or C2-C10alkenyl each of which is unsubstituted or substituted by R37B; R37B represents phenyl; Z3 represents R38 or R40; R38 represents phenyl; R40 represents cyclohexyl or cyclohexenyl; wherein phenylene presented by Z1 is unsubstituted or substituted by the group OR41; R41 represents R42 or R43; R42 represents phenyl, which is uncondensed or condensed with pyrrolyl, imidazolyl or pyrazole; R43 represents pyridinyl, which is uncondensed or condensed with pyrrolyl; wherein each cyclic fragment presented by R2, R3, R4, R8, R9, R10, R38, R40, R42 and R43 is independently unsubstituted or substituted by one or more substitutes independently specified in R57, OR57, C(O)OR57, F, Cl CF3 and Br; R57 represents R58 or R61; R58 represents phenyl; R61 represents C1-C10alkyl; and wherein phenyl presented by the group R58 is unsubstituted or substituted by one or more substitutes independently specified in F and Cl.

EFFECT: invention refers to a pharmaceutical composition containing the above compounds, and to a method of treating diseases involving the expression of anti-apoptotic Bcl-2 proteins.

7 cl, 2 tbl, 48 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of structural formula

possessing inhibitory activity on BTK, TEC, BMX, ITK, ErbB1, ErbB4 and/or JAK3 kinases. In formula (I-b), ring A and ring B represents phenyl; Ry represents -CN, -CF3, C1-4 aliphatic group, C1-4 halogenaliphatic group, -OR, -C(O)R or -C(O)N(R)2; each group R independently represents hydrogen or a group specified in C1-6 aliphatic group optionally containing a substitute presented by halogen, -(CH2)0-4R°, -(CH2)0-4OR°, -(CH2)0-4N(R°)2, -(CH2)0-4N(R°)C(O)OR°, -(CH2)0-4C(O)R°, -(CH2)0-4S(O)2R°, or 5-6-merous substituted or aryl ring containing 1-2 heteroatoms independently specified in nitrogen or oxygen optionally substituted by group =O, -(CH2)0-4R°, -(CH2)0-4N(R°)2 or -(CH2)0-4OR°; phenyl; 5-6-merous heterocyclic ring containing 1-2 heteroatoms independently specified in nitrogen, oxygen or sulphur optionally substituted by group -(CH2)0-4R°, -(CH2)0-4OR° or =O; or 6-merous monocyclic heteroaryl ring containing 1 nitrogen atom; W1 and W2 represent -NR2-; R2 represents hydrogen, C1-6aliphatic group or -C(O)R; m and p are independently equal to 0, 1, 2, 3 or 4; Rx is independently specified in -R, -OR, -O(CH2)qOR or halogen, wherein q=2; Rv is independently specified in -R or halogen; R1 and R° radical values are presented in the patent claim. The invention also refers to a pharmaceutical composition containing the above compounds.

EFFECT: preparing the compounds possessing the inhibitory activity on BTK, TEC, BMX, ITK, ErbB1, ErbB4 and/or JAK3 kinases.

17 cl, 25 dwg, 20 tbl, 286 ex

FIELD: chemistry.

SUBSTANCE: group of inventions relates to an imine derivative, represented by formula , where "Ar" stands for pyridine, containing a chlorine atom on a ring or thiazole, which can contain the chlorine atom on a ring; "X" stands for a sulphur atom or CH2; when "Y" represents COR1, "R1" stands for a hydrogen atom or a C1-C5alkyl group, halogenated methyl group, except trifluoromethyl group, halogenated C2-C5alkyl group, C2-C5alkenyl group, halogenated C2-C5alkenyl group, C3-C5alkinyl group, non-substituted or substituted with an atom of chlorine, fluorine, methyl group or acetamide phenyl group, non-substituted (C6) aryl(C1-C3)alkyl group, (C1-C4)alkoxy (C1-C5)alkyl group, C1-C3alkoxycarbonyl group, (C1-C3) alkylsulphonyl (C1-C3)alkyl group, (C1-C3)alkylthio (C1-C3)alkyl group, non-substituted or substituted with a methyl group or a fluorine atom C3-C7cycloalkyl group, cyano(C1-C3) alkyl group, non-substituted phenoxy(C1-C3) alkyl group, non-substituted pyridylmethyl group, non-substituted imidazolylmethyl group, furanyl group, morpholine group, adamantly group, isothiocyanate group or a heterocyclic ring selected from quinoline, indole, pyridine, pyrazine, pyridazine or tetrahydrofurane, substituted with one, two or five substituents, selected from chlorine, bromine, trifluoromethane or fluorine, and a non-substituted heterocyclic ring, selected from quinoline, indole, pyridine, pyrazine, pyridazine or tetrahydrofurane, when "Y" represents CONR3R4 "R3" and "R4" stands for a hydrogen atom or C1-C5alkyl group, C1-C3alkoxygroup, non-substituted phenyl group, (C1-C3)alkoxy(C1-C3)alkyl group, C1-C3alkoxycarbonylmethyl group, non-substituted C3-C7cycloalkyl group, non-substituted benzenesulphonyl group; except the cases, when "R3" and "R4" simultaneously stand for hydrogen; when "Y" represents CONHCOR5, "R5" stands for a halogenated C1-C5alkyl group, non-substituted phenyl group; when "Y" represents CO2R9, "R9" stands for C1-C7alkyl group, halogenated C1-C5alkyl group, C2-C5alkenyl group, halogenated C2-C5alkenyl group, C3-C5alkinyl group, non-substituted or substituted with chlorine, fluorine or a nitro group naphthyl or a phenyl group, non-substituted (C6)aryl(C1-C3)alkyl group, (C1-C3)alkoxy (C1-C3) alkyl group, (C1-C3)alkylthio (C1-C3)alkyl group, tri(C1-C3alkyl)silyl(C1-C3)alkyl group, non-substituted C3-C7cycloalkyl group, 3-6-membered non-substituted heterocycloalkyl group, containing an oxygen atom as the heteroatom, non-substituted or substituted with methoxygroup phenylmethyl group, non-substituted furanylmethyl group, non-substituted thienylmethyl group, non-substituted pyridylmethyl group, succinimide group. The group of inventions also relates to methods of obtaining imine derivative of formula (1) (versions). The compound by the invention can be obtained from compounds, selected from the group, consisting of compounds, represented by formulas ACO-B (5), ACOOCOA (6), ACOOH (7), D-N=C=O (8) or HCO2Et(10) in the interaction with the compound of formula .

EFFECT: imine derivative, used as an insecticide, possessing the prolonged effect and wide spectrum of action.

5 cl, 22 tbl, 1 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I) and (II), which possess the blocking activity on voltage-sensitive sodium channels, such as TTX-S channels, and their pharmaceutically salts. In general formula (I) and (II), R1 represents -CF3, -CHF2, -OCF3, -OCHF2, -OCH2CHF2/ -OCH2CF3, -OCF2CHF2; -OCF2CF3, -OCH2CH2CF3, -OCH(CH3)CF3, -OCH2C(CH3)F2, -OCH2CF2CHF2, -OCH2CF2CF3, OCH2CH2OCH2CF3, -NHCH2CF3, -SCF3, -SCH2CF3, -CH2CF3 -CH2CH2CF3, -CH2OCH2CF3 and -OCH2CH2OCF3; R2 is specified in (1) hydrogen, (2) halogen (3) -On-C1-6 alkyl, (4) -On-C3-6 cycloalkyl, (5) -On-phenyl, (6) -On-heterocyclic group, (7) -NR7 (C=O)R8; wherein n is equal to 0 or 1, p is equal to 1, 2; R3 and R4 represents hydrogen or C1-6 alkyl, X represents carbon atom; Y represents hydrogen or C1-6 alkyl; Ar represents 4-pyridyl, 4-pyrimidyl or 6-pyrimidyl, which is substituted in the 2nd position by a substitute, which is independently specified in (1) -(C=O)-NR7R8, (2) -NR7(C=O)R8; R9 is specified in: (1) hydrogen, (2) halogen, (3) -On-C1-6 alkyl, wherein alkyl is unsubstituted or substituted by hydroxyl; q is equal to 1, 2 or 3; R10 independently represents hydrogen, C1-6 alkyl, C2-6alkenyl, C3-7 cycloalkyl or phenyl, which is unsubstituted or substituted by one or substitutes independently specified in hydroxyl, -On-C1-6 alkyl and -C3-7 cycloalkyl.

EFFECT: preparing the compounds possessing the blocking activity on voltage-sensitive sodium channels.

7 cl, 2 tbl, 1281 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of structural formula

,

having Aβ42 secretion inhibiting activity. In formula I , hetaryl I is a five- or six-member heteroaryl group containing 1-3 heteroatoms selected from O, S or N, hetaryl II is a five- or six-member heteroaryl group containing 1-3 heteroatoms as defined above for hetaryl I, or is a bicyclic ring system containing 1-4 heteroatoms selected from S, O or N, where at least one ring is aromatic by nature, R1 is C1-7-alkyl, C1-7-alkoxy, C1-7-alkyl substituted with a halogen, or a halogen; R2 is a halogen, C1-7-alkyl, C1-7-alkoxy, hydroxy, C1-7-alkyl substituted with a halogen, C1-7-alkyl substituted with a hydroxy, or benzo[1,3]dioxolyl or is -(CHR)p-phenyl, optionally substituted with a halogen, C1-7-alkyl, C1-7-alkoxy, S(O)2-C1-7-alkyl, cyano, nitro, C1-7-alkoxy substituted with a halogen, dimethylamino, -(CH2)p-NHC(O)O-C1-7-alkyl or C1-7-alkyl, substituted with a halogen. The values of radicals R, R3, R4,p, n, m, o are given in the claim.

EFFECT: invention relates to a method of producing said compounds, a medicinal agent containing said compounds and a method of treating Alzheimer's disease, cerebral amyloid angiopathy, Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D), vascular dementia, dementia pugilistica or Down syndrome, associated with β amyloid activity.

21 cl, 283 ex

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