MXPA06005305A - Process for producing thiazole derivative - Google Patents

Abstract

A process for producing the compound of the formula (5) according to the following reaction scheme.

Description

PROCEDURE FOR PRODUCING A TIAZOL DERIVATIVE FIELD OF THE INVENTION The present invention relates to a process for producing intermediates of a useful compound having an inhibitory action on an activated coagulation factor X, and which is therefore useful as a preventive / therapeutic drug for thrombus-related diseases.

BACKGROUND OF THE INVENTION It is known that compounds having a heterocyclic group and a diamine structure are useful as preventive / therapeutic drugs for a variety of thrombus-related diseases, because they exhibit an excellent inhibitory action against an activated coagulation factor (FXa). patent 1 to 6, and others). To introduce a heterocyclic group in any of the mentioned compounds, the compound of the formula (5); that is, 5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cjpyridine-2-carboxylic acid (hereinafter referred to as compound (5)): It is an important intermediary. In a process that has hitherto been known to produce the compound (5), a piperidone derivative is treated with phosphorus sulphide to thereby form a thiazole ring, and then, a methyl group is introduced to the 5-position using aluminum hydride lithium, and position 2 is converted to a lithium salt of the carboxylic acid (see, for example, Patent Document 7). In another known method, a mercapto group that has been introduced into a protected aminopyridine is subjected to a ring-forming reaction, followed by chemical reduction of the pyridine ring to thereby form a lithium salt of the carboxylic acid (see, for example, Patent Document 1). Even in another known process, a protected piperidone is first transformed into 2-amino-4,5,6,7-tetrahydrothiazole [5,4-cJpyridine (hereinafter referred to as compound (2)) in the presence of a secondary amine using powder of sulfur and cyanamide, then brominated with copper (II) bromide and alkyl nitrite, after which a methyl group is introduced to the 5-position using formaldehyde and triaceto-sodium borohydride, and 2-bromo-5-methyl The resulting 4,5,5,6,7-tetrahydrothiazole [5,4-c] pyridine (hereinafter referred to as compound (3)) is converted to a lithium salt of the carboxylic acid (see, for example, Patent Document 1). ).

However, any of the above methods encompasses reactions that are difficult to manipulate when carried out on an industrial scale, and includes a considerable number of steps, since protection / deprotection steps are needed. Furthermore, since chromatography is used to purify, the overall production time is extended, which represents a disadvantage in the industry. Also, a compound (5) isolated as a lithium salt is extremely hygroscopic, and therefore handling is difficult. In addition, since the compound (5) lacks stability, problems related to storage arise. Meanwhile, it has been known that compound (2) is obtained by reacting 1-methyl-4-piperidone (hereinafter referred to as compound (1)) with bromine (see for example, Patent Document 8). However, the use of bromine represents industrial disadvantages, since it is difficult to handle and leaves a great burden on the environment; In addition, during the procedure, a brominated compound has to be isolated as an intermediate, which means that the procedure requires two steps. Another method that has been known to prepare a compound (3) includes bromination of the compound (2) with copper (II) bromide (see, for example, Patent Document 9). However, this method requires copper (II) bromide in an amount equal to or greater than compound (2), which makes it difficult to separate the by-product from copper salts after the reaction, and chromatography is necessary to purify the product. compound (3). Consequently, the method is inconvenient in the industry. [Patent Document 1] International Publication WO 01/74774 [Patent Document 2J International Publication WO 03/000680 [Patent Document 3] International Publication WO 03/016302 [Patent Document 4] International Publication WO 2004/058715 [Patent Document 5] International Publication WO 2004/058728 [Patent Document 6J International Publication WO 03/000657 [Patent Document 7J International Publication WO 01/62763 [Patent Document 8] Patent of the Netherlands No. 6610324 [Patent Document 9J International Publication WO 92/07849 BRIEF DESCRIPTION OF THE INVENTION Problems to be solved by the invention The object of the present invention is to provide a process for industrially producing, through the use of inexpensive starting materials, intermediates of a useful compound, the present an inhibiting effect of activated factor X of blood coagulation. The procedure allows the efficient production of intermediaries with a reduced number of production steps.

Means for solving the problems In order to solve the aforementioned problems, the inventors of the present invention have studied exhaustively and have discovered that (a) a compound (5) can be produced efficiently by subjecting a compound (3) to cyanate treatment for thus giving 2-cyano-5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cJpyridine (compound (4)) and then hydrolyzing the compound (4); (b) -the compound (5) can be produced by subjecting a compound (2) to reduction and thus giving 4,5,6,7-tetrahydrothiazole [5,4-cJpyridine (compound 6) to then subjecting the compound (6). ) to trihalogenoacetylation and then to hydrolysis; and (c) the compound (2) can conveniently be produced from a compound (1) with a single step by the use of a catalytic amount of a secondary amine, the compound (3) can be produced from the compound (2) without copper (II) bromide, and each of the compounds (2) to (6) can be isolated by treatment with an acid compound, such as a stable salt with the acid compound; and that, through the use of any of these steps in combination, the compound (5) can be produced on an industrial scale with a small number of production steps. The present invention is carried out based on the findings. Accordingly, the present invention provides a process for producing a compound represented by the formula (5) or its salt: wherein the process is characterized by comprising the reaction of a compound represented by the formula (3) or its salt: with a metal cyanide, in order to obtain a compound represented by the formula (4) or its salt: and hydrolyzing the obtained compound or its salt.

The present invention also provides a process for producing a compound represented by the formula (4) or its salt: wherein the process is characterized by comprising the reaction of a compound represented by the formula (3) or its salt: with a metal cyanide. The present invention also provides a process for producing a compound represented by the formula (5) or its salt: wherein the process is characterized by comprising the hydrolyzation of a compound represented by the formula (4) or its salt.

The present invention also provides a process for producing a compound represented by the formula (5) or its salt: wherein the process is characterized by comprising the reaction of a compound represented by the formula (2) or its salt: with an alkali metal nitrite in the presence of a reducing agent in an aqueous solution of an acidic compound, to then obtain a compound represented by the formula (6) or its salt: and reacting the obtained compound or its salt with trihalogenoacetyl halide in the presence of a base, followed by hydrolysis. The present invention also provides a process for producing a compound represented by the formula (6) or its salt: (6) wherein the process is characterized by comprising the reaction of a compound represented by the formula (2) or its salt: with an alkali metal nitrite in the presence of a reducing agent in an aqueous solution of an acidic compound. The present invention also provides a process for producing a compound represented by the formula (5) or its salt: wherein the process is characterized by comprising the reaction of a compound represented by the formula (6) or its salt: with trihalogenoacetyl halide in the presence of a base, followed by hydrolysis. The present invention also provides a process for producing a compound represented by the formula (5) or its salt: wherein the process is characterized by comprising the reaction of a compound represented by formula (1) or its salt: with sulfur powder and cyanamide in the presence of a secondary amine, to then obtain a compound represented by the formula (2) or its salt: and reacting the obtained compound or its salt, hydrobromic acid and alkali metal nitrite, to then obtain a compound represented by the formula (3) or its salt: and reacting the obtained compound or its salt with alkyl lithium and carbon dioxide. The present invention also provides a process for producing a compound represented by the formula (2) or its salt: wherein the process is characterized by comprising the reaction of a compound represented by formula (1) or its salt: with sulfur powder and cyanamide in the presence of a secondary amine. The present invention also provides a process for producing a compound represented by the formula (3) or its salt: wherein the process is characterized by comprising the reaction of a compound represented by the formula (2) or its salt: with hydrobromic acid and an alkali metal nitrite. The present invention also provides a salt formed between an acidic compound and a compound represented by the formula (4).

The present invention also provides a salt formed between an acidic compound and a compound represented by the formula (5).

The present invention also provides a salt formed between an acidic compound and a compound represented by the formula (6).

The present invention also provides a salt formed between an acidic compound and a compound represented by the formula (2).

The present invention also provides a salt formed between an acidic compound and a compound represented by the formula (3). or > The present invention also provides a process for producing a compound represented by formula (8) or its salt: (wherein each of R1 and R2 represents a hydrogen, hydroxyl, alkyl or alkoxy atom; Q1 represents C1-C8 alkylene, C2-C8 alkenylene, or - (CH2) m -CH2-A-CH2- (CH2 ) n- (where each of m and n represents 0 or an integer from 1 to 3 and A represents an oxygen atom, a nitrogen atom, a sulfur atom, -SO-, -S02-, -NH-, - O-NH-, -NH-NH-, -S-NH-, -SO-NH-, or S02-NH-), each of R3 and R4, which is a substituent bonded to a carbon atom, an atom of nitrogen, or a sulfur atom forming the ring containing Q1, represents a hydrogen atom, hydroxyl, alkyl, alkenyl, alkynyl, a halogen atom, halogenalkyl, cyano, cyanoalkyl, amino, aminoalkyl, N-alkylaminoalkyl, N , N-dialkylaminoalkyl, acyl, acylalkyl, acylamino which may have a substituent, alkoxyimino, hydroxyimino, acylaminoalkyl, alkoxy, alkoxyalkyl, hydroxyalkyl, carboxyl, carboxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkoxycarbonylalkyl no, carboxyalkylamino, alkoxycarbonylamino, alkoxycarbonylaminoalkyl, carbamoyl, N-alkylcarbamoyl whose alkyl may or may not be substituted, N, N-dialkylcarbamoyl whose alkyl may or may not be substituted, N-alkenylcarbamoyl, N-alkenylcarbamoylalkyl, N-alkenyl-N- alkylcarbamoyl, N-alkenyl-N-alkylcarbamoylalkyl, N-alkoxycarbamoyl, N-alkyl-N-alkoxycarbamoyl, N-alkoxycarbamoylalkyl, N-alkyl-N-alkoxycarbamoylalkyl, carbazoyl which can be substituted by 1 to 3 alkyl, alkylsulfonyl, alkylsulfonylalkyl, heterocyclic carbonyl groups of 3 to 6 elements which may have a substituent, carbamoylalkyl, N-alkylcarbamoylalkyl whose alkyl may or may not be substituted, N, N-dialkylcarbamoylalkyl alkyl may or may not be substituted, carbamoyloxyalkyl, N-alkylcarbamoyloxyalkyl, N, N-dialkylcarbamoyloxyalkyl, carbonylalkyl heterocyclic of 3 to 6 elements which may have a substituent, heterocyclic carbonyloxyalkyl of 3 to 6 elements which may have a substituent, aryl, aralkyl, 3-6 membered heterocyclic group which may have a substituent, 3-6 membered heterocyclic alkyl which may have a substituent, alkylsulfonylamino, arylsulfonylamino, alkylsulfonylaminoalkyl, arylsulfonylaminoalkyl, alkylsulfonylaminocarbonyl, arylsulfonylaminocarbonyl, alkylsulfonylaminocarbonylalkyl, arylsulfonylaminocarbonylalkyl, oxo, carbamo yloxy, aralkyloxy, carboxyalkyloxy, alcoxicarbonilalquiloxi, acyloxy, acyloxyalkyl, ariisulfonilo, alcoxicarbonilalquilsulfonilo, carboxialquilsulfonilo, alcoxicarbonilacilo, alcoxialquiloxicarbonilo, hydroxyacyl, alkoxyacyl, halogenoacilo, carboxyacyl, aminoacyl, acyloxyacyl, aciloxialquilsulfonilo, hydroxyalkylsulfonyl, alcoxialquilsulfonilo, sulfonyl heterocyclic 3 to 6-membered can have a substituent, heterocyclic oxy of 3 to 6 elements which may have a substituent, N-alkylaminoacyl, N, N-dialkylaminoacyl, N, N-dialkylcarbamoylacyl whose alkyl may or may not be substituted, N, N-dialkylcarbamoylallylsulfonyl whose alkyl may or may not be substituted can be substituted, alkylsulfonylacyl, N-arylcarbamoyl, carbamoyl N-heterocyclic of 3 to 6 elements, N-alkyl-N-arylcarbamoyl, carbamoyl N-alkyl-N-heterocyclic of 3 to 6 elements, N-arylcarbamoylalkyl, carbamoylalkyl N-heterocyclic from 3 to 6 elements, N-alkyl-N-arylcarbamoylalkyl, carbamoi N-alkyl-N-heterocyclic alkyl of 3 to 6 elements, aminocarbothioyl, N-alkylaminocarbothioyl, N, N-dialkylaminocarbothioyl, alkoxyalkyl (thiocarbonyl), alkylthioalkyl, or N-acyl-N-alkylaminoalkyl; when R3 and R4 are linked to form a group, the group represents C1-C5 alkylene, C2-C5 alkenylene, C1-C5 alkylenedioxy, or carbonyldioxy; Q2 represents aryl which may have a substituent, arylalkenyl which may have a substituent, arylalkynyl which may have a substituent, heteroaryl which may have a substituent, heteroarylalkenyl which may have a substituent, a saturated or unsaturated, bicyclic or tricyclic condensed hydrocarbon group, which may have a substituent, or a saturated or unsaturated, bicyclic or tricyclic condensed heterocyclic group, which may have a substituent; T1 represents carbonyl, sulfonyl, -C (= 0) -C (= 0) -N (R ') -, -C (= S) -C (= 0) -N (R') -, -C (= 0) -C (= S) -N (R ') -, -C (= S) -C (= S) -N (R') - (wherein R 'represents a hydrogen atom, hydroxyl, alkyl, or alkoxy), -C (= 0) -A1- N (R ") - (wherein A1 represents a C1-C5 alkylene which may have a substituent and R" represents a hydrogen, hydroxyl, alkyl, or alkoxy atom ), -C (= 0) -NH-, -C (= S) -NH-, -C (= 0) -NH-NH-, -C (= 0) -A2-C (= 0) - ( wherein A2 represents a single bond or C1-C5 alkylene), -C (= 0) -A3-C (= 0) -NH- (wherein A3 represents C1-C5 alkylene), -C (= 0) -C (= NORa) -N (Rb) -, -C (= S) -C (= NORa) -N (Rb) - (where Ra represents a hydrogen atom, alkyl, or alkanoyl and Rb represents an atom of hydrogen, hydroxyl, alkyl, or alkoxy), -C (= 0) -N = N-, -C (= S) -N = N-, -C (= NORc) -C (= 0) -N ( Rd) - (wherein Rc represents a hydrogen, alkyl, alkanoyl, aryl, or aralkyl atom and Rd represents a hydrogen, hydroxyl, alkyl, or alkoxy atom), -C (= NN (Re) (Rf)) - C (= 0) -N (R9) - (where, each one of Re and R represents a hydrogen atom, alkyl, alkanoyl, or alkyl (thiocarbonyl) and R9 represents a hydrogen, hydroxyl, alkyl, or alkoxy), -C (= 0) -NH-C (= 0) - , -C (= S) -NH-C (= 0) -, -C (= 0) -NH-C (= S) -, -C (= S) -NHC (= S) -, -C ( = 0) -NH-S02-, -S02-NH-, -C (= NCN) -NH-C (= 0) -, -C (= S) -C (= 0) -, or thiocarbonyl), in wherein the process is characterized by comprising the reaction of a compound which is represented by the formula (5) and which is produced through any of the above processes, or its salt: < * > with diamines represented by the formula (7) or its salt (where R1, R2, R3, R4, T1, Q, and Q2 have the same meanings as already described). The present invention also provides a process for producing a compound represented by formula (8) or its salt: (wherein R1, R2, R3, R4, T1, Q1, and Q2 have the same meanings as already described), wherein the process is characterized by comprising the reaction of a compound that is represented by the formula (5) and which occurs through any of the above procedures, or its salt: with diamines represented by the formula (9) or its salt: N- Rk (wherein Rk is a protecting group of the amino group and R1, R2, R3, R4, and Q1 have the same meanings as already described) to then obtain a compound represented by the formula (10): (wherein R1, R2, R3, R4, Q1, and R? have the same meanings as already described), and remove Rk of the obtained compound or its salt, so as to produce a compound represented by the formula (11) or its Salt: (wherein R1, R2, R3, R4, and Q1 have the same meanings as already described), and reacting the obtained compound or its salt with a compound represented by the formula (12) or its salt: HO- T1- Q2 (1 2) (where T1 and Q2 have the same meanings that were already described). The present invention also provides a process for producing a compound represented by the formula (8 '): (wherein R1, R3, R4,, Q1, and Q2 have the same meanings as already described), wherein the process is characterized by comprising the reaction of a compound that is represented by the formula (5) and that is produced through any of the above procedures, or your salt: with diamines represented by the formula (13) or its salt: R1 R * \ Q K • R "zl - (1 3) HN N3 (wherein R1, R3, R4, and Q1 have the same meanings as already described) so as to obtain a compound represented by the formula (14) or its salt: < i) (wherein R1, R3, R4, and Q1 have the same meanings as already described), and reducing the obtained compound or its salt, to then produce a compound represented by the formula (11 ') or its salt: (wherein R1, R3, R4, and Q1 have the same meanings as already described), and reacting the obtained compound or its salt with a compound represented by the formula (12) or its salt: HO-T1- Q2 (1 2) (where T1 and Q2 have the same meanings that were already described).

Effects of the invention The methods of the present invention allow the production of a compound (5) in a manner convenient in the industry.

With the use of the methods of the present invention a compound can be produced which has an excellent Fxa inhibitory effect, and therefore useful as a preventive / therapeutic drug for thrombotic diseases, conveniently in the industry.

PREFERRED MODALITY OF THE INVENTION The processes for producing the compound (5) according to the present invention are represented by the following reaction scheme and will be described below.

: H.H ) Step (A): 1-Methyl-4-piperidone (1), or its salt, is reacted in the presence of a secondary amine, with a sulfur powder and a cyanamide, to then produce a compound (2) or its salt . The compound (1) can be prepared through, for example, methylation of 4-piperidone using a conventional method. The cyanamide of preference is used in an amount of 1 to 2 equivalents, more preferably 1 equivalent on the basis of 1 mole of the compound (1). The sulfur powder is preferably used in an amount of 1 to 2 equivalents, more preferably 1 equivalent on the basis of 1 mole of the compound (1). No particular limitation is imposed on the secondary amine. Examples of the secondary amine include diethylamine, diisopropylamine, pyrrolidine, piperidine and morpholine, with pyrrolidine being preferred among them. The amount of secondary amine added may be a catalytic amount, preferably from 0.01 to 1.2 equivalents, more preferably from 0.1 to 0.5 equivalents, even more preferably 0.1 equivalents based on 1 mole of the compound (1). No particular limitation is imposed on the reaction solvent, as long as the solvent is inert with respect to the reaction. Examples of the solvent that can be employed include alcohol solvents, such as methanol, ethanol, and 2-propanol; ether solvents, such as diethyl ether, tetrahydrofuran, and 1,4-dioxane; acetonitrile; and acetic ester acetic acid solvents, such as ethyl acetate and isopropyl acetate. Among these solvents, alcohol solvents are preferred, 2-propanol being more preferred among them. The reaction temperature, which differs depending on the solvent that is employed, is typically within the range from 0 ° C to the boiling point of the solvent, preferably a scale of 45 ° C to the boiling point of the solvent. The reaction is carried out for about 1 to 24 hours, preferably about 2 to 5 hours until complete completion.

The reaction mixture can be directly subjected to filtration to isolate the compound (2) as crystals. Alternatively, when the compound (2) is to be isolated in the form of a salt, an acidic compound is added to the reaction mixture. The "acid compound" refers to a compound which, by itself, is acid, or which, when dissolved in water, is acidic. Examples of the acidic compound that can be used include organic carboxylic acids, such as oxalic acid, acetic acid, benzoic acid, p-nitrobenzoic acid, malic acid, tartaric acid, succinic acid, maleic acid, and fumaric acid; organic sulfonic acids, such as p-toluenesulfonic acid, and methanesulfonic acid; and inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, and phosphoric acid. Among these acidic compounds, hydrobromic acid is preferred. Step (B): The compound (2), or its salt, is reacted in the presence of hydrobromic acid with an alkali metal nitrite to then give a compound (3) or its salt. Examples of the alkali metal nitrite that may be employed include sodium nitrite, potassium nitrite and lithium nitrite, with sodium nitrite being preferred. The alkali metal nitrite is preferably used in an amount of 1 to 3 equivalents, more preferably 1.5 equivalents based on 1 mole of the compound (2). The reaction is carried out at a temperature falling within the range of -20 to 100 ° C, preferably -5 to 15 ° C for about 1 to 36 hours, preferably 3 to 24 hours until completion total. Compound (2) can be isolated through the addition of an aqueous solution of an alkali metal hydroxide (eg, sodium hydroxide, potassium hydroxide, or lithium hydroxide) or an alkaline earth metal hydroxide (eg, hydroxide) of calcium or barium hydroxide), preferably aqueous sodium hydroxide, to alkaline the mixture (approximately pH 12 to 13); extraction of the mixture by the use of a suitable solvent; and evaporation under reduced pressure. No particular limitation is imposed on the solvent used for the extraction. Examples of extraction solvent include ether solvents, such as diethyl ether, diisopropyl ether and methyl tert-butyl ether; aromatic hydrocarbon solvents, such as benzene and toluene; and acetic ester acetic acid solvents, such as ethyl acetate and isopropyl acetate. Among these solvents, aromatic hydrocarbon solvents are preferred, with toluene being more preferred among them. The compound (3) can be isolated in the form of a salt through the solution in a suitable solvent and treatment with an acidic compound. Examples of the acid compound include the same compounds as already described. Among these, p-toluenesulfonic acid is preferred. No particular limitation is imposed on the solvent. Examples of the solvent that may be employed include alcohol solvents, such as methanol, ethanol, and 2-propanol; ether solvents, such as diethyl ether, tetrahydrofuran and 1,4-dioxane; aromatic hydrocarbon solvents, such as benzene and toluene; acetonitrile; and acetic ester acetic acid solvents, such as ethyl acetate and isopropyl acetate. Among these solvents, alcohol solvents are preferred, with methanol being the most preferred. Step (C): The compound (3), or its salt, is reacted with a metal cyanide to then give 2-cyano-5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cjpyridine (in hereinafter referred to as "compound (4)") or its salt. Examples of the metal cyanide include sodium cyanide, potassium cyanide, lithium cyanide, copper cyanide and zinc cyanide. These metal cyanides can be used in combination of two or more species, and a combination of sodium cyanide and copper cyanide is preferred. The preferred metal cyanide is used in an amount of 1 to 3 equivalents, more preferably 1.5 equivalents based on 1 mole of the compound (3). No particular limitation is imposed on the reaction solvent, so long as the solvent is inert with respect to the reaction. Examples of the reaction solvent include amide solvents, such as N, N-dimethylformamide and N, N-dimethylacetamide.; aromatic hydrocarbon solvents, such as benzene and toluene; and dimethyl sulfoxide. Of these, N, N-dimethylacetamide is preferred. The reaction temperature is within the range of 0 to 200 ° C, preferably 140 to 160 ° C. The reaction is carried out for about 8 to 48 hours, preferably 13 to 20 hours, until complete completion. The compound (4) thus obtained can be isolated through the addition of aqueous sodium bicarbonate or a similar solution; extraction with a suitable solvent; evaporation under reduced pressure. No particular limitation is imposed on the extraction solvent. Examples of the extraction solvent that may be employed include ether solvents, such as diethyl ether, diisopropyl ether and methyl tert-butyl ether; aromatic hydrocarbon solvents, such as benzene and toluene; and acetic ester acetic acid solvents, such as ethyl acetate and isopropyl acetate. Among these solvents aromatic hydrocarbon solvents are preferred, with toluene being more preferred. Alternatively, the compound (4) can be isolated in the form of a salt of an acidic compound. Examples of the acid compound include the same as described above. Of these acidic compounds, hydrochloric acid is preferred. Step (D): The compound (4), or its salt, is hydrolysed to then give a compound (5) or its salt. The hydrolysis can be carried out by dissolving the compound (4) in a suitable solvent and treating the solution with an aqueous solution of alkali metal hydroxide. Examples of the alkali metal hydroxide include sodium hydroxide, lithium hydroxide and potassium hydroxide, with lithium hydroxide being the preferred. Examples of the solvent that may be employed include alcohol solvents, such as ethanol, methanol, and 2-propanol, acetone, and acetonitrile, with ethanol being preferred. The reaction temperature is within the range from 0 ° C to the boiling point of the solvent, preferably from 40 to 70 ° C. The reaction is carried out until reaching the total completion, for about 1 to 24 hours, preferably 5 to 10 hours. The compound (5) can be isolated in the form of a salt through the addition of an acidic compound to the reaction mixture. Examples of the acid compound include the same as already described. Of these, hydrochloric acid is preferred. Step (E): The compound (3), or its salt, is reacted with an alkyl lithium and carbon dioxide gas, to then give a compound (5) or its salt. The reaction consists of two sub-steps. The first sub-step is lithiation using an alkyl lithium. The alkyl lithium is preferably used in an amount of 1 to 2 equivalents, more preferably 1 to 1.2 equivalents based on 1 mole of the compound (3). The alkyl lithium is preferably n-butyllithium. The reaction temperature is within the range of -78 ° C to the boiling point of the solvent, preferably -78 to 0 ° C. The reaction is carried out for several minutes up to 24 hours, preferably several minutes up to 2 hours, until reaching the total completion. The second sub-step is a reaction between the lithium salt obtained in the first sub-step and carbon dioxide gas. Specifically, carbon dioxide is injected into the reaction mixture obtained through the above lithiation, or the reaction system is placed under carbon dioxide atmosphere. The reaction temperature is within the range of -78 ° C to the boiling point of the solvent, preferably -78 to 0 ° C. The reaction is carried out until complete completion, for several minutes up to 24 hours, preferably several minutes up to 2 hours. Preferably, in step (E), both sub-steps are carried out under nitrogen, argon or a similar inert gas. No particular limitation is imposed on the reaction solvent, so long as the solvent is inert with respect to the reaction. Examples of the reaction solvent include ether solvents, such as methyl tert-butyl ether, diisopropyl ether, tetrahydrofuran and 1,4-dioxane.; linear or cyclic saturated hydrocarbon solvents, such as n-hexane, n-heptane, and cyclohexane; and aromatic hydrocarbon solvents, such as benzene and toluene. Among these solvents, ether solvents are preferred, with tetrahydrofuran being more preferred. The compound (5) can be isolated in the form of a lithium salt by directly subjecting the reaction mixture to filtration. However, a lithium salt of compound (5) is unstable; therefore, preferably, the lithium salt is transformed into a free carboxylic acid, or, alternatively, a second suitable solvent is added to the resulting free carboxylic acid, and the solution is treated with an acidic compound, to then isolate the compound (5) as a salt. Examples of the acid compound include the same as already described, with hydrochloric acid being preferred. No particular limitation is imposed on the second solvent. Examples of the second solvent that can be employed include alcohol solvents, such as methanol, ethanol, and 2-propanol; acetonitrile; and acetic ester acetic acid solvents, such as ethyl acetate and isopropyl acetate. Among these solvents, alcohol solvents are preferred, with methanol being more preferred. Step (F): The compound (2), or its salt, is reacted with an alkali metal nitrite in the presence of a reducing agent in an aqueous solution of an acidic compound, to then give a compound (6) or its salt . Examples of the acid compound include the same compounds as already described, with sulfuric acid being preferred. Examples of the reducing agent include hydrogen, sodium borohydride, hypophosphorous acid and formic acid, with hypophosphorous acid being preferred. Examples of the alkali metal nitrite include sodium nitrite, potassium nitrite and lithium nitrite, with sodium nitrite being preferred. The reducing agent is preferably used in an amount of 1 to 3 equivalents, more preferably 2 equivalents based on 1 mole of the compound (2). The alkali metal nitrite is preferably used in an amount of 1 to 3 equivalents, more preferably 2 equivalents based on 1 mole of the compound (2). The reaction is carried out at a temperature falling within a range of -20 to 50 ° C, preferably -5 to 15 ° C, for about 1 to 36 hours, preferably 1 to 24 hours. The compound (6) can be isolated through the addition of an aqueous solution of an alkali metal hydroxide (for example, sodium hydroxide, potassium hydroxide, lithium hydroxide), preferably an aqueous solution of lithium hydroxide to alkalize the mixture (pH of 12 to 13 or approximately); extraction through the use of a suitable solvent; and evaporation under reduced pressure. No particular limitation is imposed on the extraction solvent. Examples of the extraction solvent that may be employed include ether solvents, such as diethyl ether, diisopropyl ether, and methyl tert-butyl ether; aromatic hydrocarbon solvents, such as benzene and toluene; acetic acid alkyl ester solvents, such as ethyl acetate and isopropyl acetate; and halohydrocarbon solvents, such as dichloromethane and chloroform. Among these solvents acetic acid alkyl ester solvents and halohydrocarbon solvents are preferred, ethyl acetate being more preferred. Alternatively, compound (6) can be isolated in the form of a salt through the addition of an acidic compound in a suitable solvent. No particular limitation is imposed on the solvent. Examples of the solvent that may be employed include alcohol solvents, such as methanol, ethanol and 2-propanol; ether solvents, such as diethyl ether, tetrahydrofuran and 1,4-dioxane; aromatic hydrocarbon solvents, such as benzene and toluene; acetonitrile; and acetic ester acetic acid solvents, such as ethyl acetate and isopropyl acetate. Among these solvents, alcohol solvents are preferred, 2-propanol being more preferred. Examples of the acid compound include the same compound as already described, with p-toluenesulfonic acid being preferred. Step (G): The compound (6) or its salt is reacted with a trihalogenoacetyl halide in the presence of a base, followed by hydrolysis, to then give a compound (5) or its salt. The trihalogenoacetyl halide is preferably used in an amount of 1 to 3 equivalents, more preferably 2 equivalents based on 1 mole of the compound (6). Examples of the trihalogenoacetyl halide include tribromoacetyl chloride and trichloroacetyl chloride, with trichloroacetyl chloride being preferred. No particular limitation is imposed as to the basis. Examples of the base that may be employed include tertiary amines, such as triethylamine, diisopropylethylamine and N-methylmorpholine.; alkali metal hydroxides, such as sodium hydroxide, potassium hydroxide and lithium hydroxide; and inorganic bases, such as carbonic acid salt and acid salt of carbon dioxide. Among these bases tertiary amines are preferred, and triethylamine, diisopropylethylamine and N-methylmorpholine are more preferred. The base is preferably used in an amount of 1 to 3 equivalents, more preferably 2 equivalents based on 1 mole of the compound (6).

No particular limitation is imposed on the reaction solvent. Examples of the reaction solvent that may be employed include ether solvents, such as diethyl ether, tetrahydrofuran and 1,4-dioxane; aromatic hydrocarbon solvents, such as benzene and toluene; amide solvents, such as N, N-dimethylformamide and N, N-dimethylacetamide; dimethyl sulfoxide; acetonitrile; and acetic ester acetic acid solvents, such as ethyl acetate and isopropyl acetate. Among these solvents aromatic hydrocarbon solvents, such as toluene and alkyl ester solvents of acetic acid, such as ethyl acetate and isopropyl acetate are preferred, and more preferred are toluene, ethyl acetate and isopropyl acetate. The reaction temperature, which differs depending on the solvent used, is typically within the range from -78 ° C to the boiling point of the solvent, preferably from 0 ° C to the boiling point of the solvent. The reaction is carried out for about 1 to 24 hours, preferably 1 to 5 hours until full completion is achieved. The hydrolysis can be carried out continuously by the addition of an aqueous solution of an alkali metal hydroxide to the reaction mixture. Examples of the alkali metal hydroxide include sodium hydroxide, lithium hydroxide and potassium hydroxide, with lithium hydroxide being preferred. The reaction temperature is typically within the range from -5 ° C to the boiling point of the solvent, preferably from 0 ° C to the boiling point of the solvent. The reaction is carried out for about 1 to 10 hours, preferably 1 to 5 hours until total completion is achieved. After completion of the hydrolysis, the organic layer and the aqueous layer are divided one from the other, whereby the compound (5) is collected in the aqueous layer, and impurities soluble in oil or other oil soluble substances are removed to the organic layer. The compound (5) thus collected can be isolated in the form of a salt by evaporation of the aqueous layer, addition of a second suitable solvent and addition of an acidic compound. No particular limitation is imposed on the second solvent.

Examples of the second solvent that can be employed include alcohol solvents, such as methanol, ethanol, and 2-propanol; acetonitrile; and acetic ester acetic acid solvents, such as ethyl acetate and isopropyl acetate. Among these solvents, alcohol solvents are preferred, and in particular methanol is preferred. Examples of the acid compound include the same compounds as described above, with hydrochloric acid being preferred. Next, a method for producing, from compound (5), a compound (8) which is useful as a preventive / therapeutic agent for thrombotic diseases will be described. The compound (8) can be produced from the compound (5) through a process described in the International Publication WO 2004/058715, or a similar procedure. Next, a representative procedure shown by the following reaction scheme will be described: (wherein R1, R2, R3, R4, Rk,, Q1, and Q2 have the same meanings as already described). Step (H): The compound (5) or its salt is reacted with a diamine compound (7), or its salt, to then give a compound (8) or its salt. The compound (5) can be transformed, before being subjected to the reaction, to a mixed acid anhydride, an acid halide or an active ester, according to the needs. The transformation reaction can be carried out with the use of a reagent under certain conditions, the reagent and the conditions that are normally employed in a peptide synthesis. When the compound (5) is converted to a mixed acid anhydride, for example, the compound (5) can be reacted with a chloroformate, such as ethyl chloroformate or sobutyl chloroformate in the presence of a base. When the compound (5) is transformed to an acid halide, the compound (5) can be treated with an acid halide, such as thionyl chloride or oxalyl chloride. A variety of active esters can be produced. For example, the compound (5) can be reacted with a phenol compound, such as p-nitrophenol or with N-hydroxybenzotriazole, N-hydroxysuccinimide, or a similar compound, using a condensing agent, such as N, N'- hydrochloride. dicyclohexylcarbodiimide or 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide. Alternatively, an active ester of compound (5) can be produced, inter alia, by reacting the compound (5) with pentafluorophenyl trifluoroacetate or a similar compound, by reacting the compound (5) with 1-benzotriazolyloxytripyrrolidinophosphonium hexafluorophosphite, reacting the compound (5) with diethyl cyanophosphate (the Shioiri method), or by reacting the compound (5) with triphenylphosphine and 2,2'-dipyridyldisulfide (the Mukaiyama method). The mixed acid anhydride thus obtained, acid halide or active ester of compound (5) is reacted with a diamine compound (7) in the presence of a suitable base in an inert solvent at a temperature of -78 ° C to 150 ° C, to then give a compound (8).

Specific examples of the base employed in step (H) described above include alkali metal and alkaline earth metal carbonates, alkali metal alkoxides, alkali metal hydroxides, and hydrides (eg, sodium carbonate and potassium carbonate, ethoxide sodium, potassium butoxide, sodium hydroxide, potassium hydroxide, sodium hydroxide and potassium hydroxide); alkyl lithiums, such as n-butyl lithium; organometallic bases, such as dialkylamino lithium (for example, lithium diisopropylamide); organometallic bis-silylamine bases, such as lithium bis (trimethylsilyl) amide; and organic bases, such as pyridine, 2,6-lutidine, collidine, 4-dimethylaminopyridine, triethylamine, N-methylmorpholine, diisopropylethylamine and diazabicyclo [5.4.0Jundec-7-ene (DBU). Examples of the inert solvent that is employed in the reaction include haloalkyl solvents, such as dichloromethane, chloroform and carbon tetrachloride; ether solvents, such as tetrahydrofuran, 1,2-dimethoxyethane and dioxane; aromatic solvents, such as benzene and toluene; amide solvents, such as N, N-dimethylformamide, N, N-dimethylacetamide and N-methylpyrrolidin-2-one. Additionally, in some cases, sulfoxide solvents, such as dimethyl sulfoxide and sulfolane, may be employed; and ketone solvents, such as acetone and methyl ethyl ketone. Step (I): The compound (5) or its salt is reacted with a diamine compound (9) or its salt, to then give a compound (10) or its salts. Examples of a protecting group for the amino group, represented by Rk, include alkanoyl, such as acetyl; alkoxycarbonyl, such as methoxycarbonyl, ethoxycarbonyl, and tert-butoxycarbonyl; arylmethoxycarbonyl, such as benzyloxycarbonyl, paramethoxybenzyloxycarbonyl and p- (or o-) nitrobenzyloxycarbonyl; benzyl; arylmethyl, such as triphenylmethyl; aroyl, such as benzoyl; and arylsulfonyl, such as 2,4-dinitrobenzenesulfonyl and ortonitrobenzenesulfonyl. The reaction of the compound (5) and the compound diamine (9) can be carried out in a manner similar to that described in relation to step (H). Step (J): The compound (10) or its salt is deprotected by removing the protection group (Rk), to then give a compound (11) or its salt. The deprotection reaction can be performed using a reagent under certain conditions, wherein the reagent and conditions are normally selected according to the type of the protection group. For example, when the protecting group is a tert-butoxycarbonyl group, the compound (10) or its salt can be treated at a temperature of -20 to 70 ° C with trifluoroacetic acid or a similar substance. Step (K): The compound (11) or its salt is reacted with a compound (12) or its salt, to then give a compound (8) or its salt. The reaction can be carried out in a manner similar to that described above in relation to step (H). Step (L): The compound (5) or its salt is reacted with a compound (13) or its salt, to then give a compound (14) or its salt. In the reaction, R1 is preferably a hydrogen atom.

The reaction can be carried out in a manner similar to that described above in relation to steps (I) or (H). Step (M): The compound (14) or its salt is reduced to then give a compound (11) or its salt, wherein R2 in the formula (11) is a hydrogen atom. The reduction can be carried out through catalytic reduction in the presence of a catalyst, such as platinum or palladium, if necessary by pressurization. It should be noted that the starting materials of steps (I) to (M); that is, the compounds (7), (9), (12) and (13) can be obtained by a method described in the document of International Publication WO 2004/058715. Next, the substituents of the compound represented by the formula (8) will be described.

Group Q2 Q2 means an aryl group which may have a substituent, an arylalkenyl group which may have a substituent, an arylalkynyl group which may have a substituent, a heteroaryl group which may have a substituent, a heteroarylalkenyl group which may have a substituent, a saturated or unsaturated, bicyclic or tricyclic fused hydrocarbon group which may have a substituent, or a saturated or unsaturated bicyclic or tricyclic fused heterocyclic group which may have a substituent.

In the group Q2, examples of the aryl group include C6-C14 aryl groups, such as phenyl, naphthyl, anthryl and phenanthryl. Arylalkenyl is a group composed of a C6-C14 aryl group and an alkenylene group of C2-C6, and specific examples include a styryl group. The arylalkynyl group is a group composed of a C6-C14 aryl group and a C2-C6 alkynylene group, and specific examples include a phenylethynyl group. The heteroaryl group is a monovalent aromatic group having at least one heteroatom selected from an oxygen atom, a sulfur atom and a nitrogen atom. Specific examples include heteroaryl groups having a total number of ring-forming atoms of 5 or 6, such as pyridyl, pyridazinyl, pyrazinyl, furyl, thienyl, pyrrolyl, thiazolyl, oxazolyl, pyrimidinyl and tetrazolyl. The heteroarylalkenyl group is a group composed of the above heteroaryl group and a C2-C6 alkenylene group, and specific examples include thienylethenyl and pyridylethenyl. The saturated or unsaturated bicyclic or tricyclic condensed hydrocarbon group is a monovalent group derived from saturated or unsaturated bicyclic or tricyclic condensed hydrocarbon. Saturated saturated or unscreened bicyclic or tricyclic hydrocarbon, is a bicyclic or tricyclic condensed hydrocarbon that is formed through the condensation of 2 or 3 cyclic hydrocarbons of 5 or 6 elements, saturated or unsaturated, which may be identical or different from each other . Examples of the 5 or 6 element cyclic hydrocarbon, saturated or unsaturated, include cyclopentane, cyclopentene, cyclohexane, cyclohexene, cyclohexadiene and benzene. Specific examples of the saturated or unsaturated bicyclic or tricyclic condensed hydrocarbon include indenyl, indanyl, tetrahydronaphthyl and naphthyl. No particular limitation is imposed on the position, in the saturated or unsaturated bicyclic or tricyclic condensed hydrocarbon group, in which T1 is bound. The saturated or unsaturated bicyclic or tricyclic fused heterocyclic group refers to a monovalent group derived from a saturated or unsaturated bicyclic or tricyclic fused heterocyclic ring. The term "saturated or unscreened bicyclic or tricyclic fused heterocyclic ring" refers to any of the following compounds 1) to 3): 1) bicyclic or tricyclic fused heterocyclic ring which is formed by condensation of 2 or 3 heterocyclic rings of 5 to 7 saturated or unsaturated elements which may be identical or different from each other, 2) bicyclic or tricyclic fused heterocyclic ring which is formed by condensation of a saturated or unsaturated 5 or 7-membered heterocyclic ring and 1 or 2 cyclic hydrocarbon rings of 5 or 6 elements saturated or unsaturated, and 3) tricyclic condensed heterocyclic ring that is formed by condensation of heterocyclic rings of 5 to 7 saturated or unsaturated elements and a saturated or unsaturated cyclic hydrocarbon ring of 5 or 6 elements.

No particular limitation is imposed, as regards position, in the aforementioned saturated or unsaturated bicyclic or tricyclic heterocyclic group in which T is bound. The aforementioned saturated or unsaturated heterocyclic ring of 5 to 7 elements refers to a heterocyclic ring having at least one heteroatom selected from an oxygen atom, a sulfur atom, and a nitrogen atom. Specific examples include furan, pyrrole, thiophene, pyrazole, midazole, oxazole, oxazolidine, thiazole, thiazole, furazane, pyrano, pyridine, pyrimidine, pyridazine, pyrrolidine, piperazine, piperidine, oxazine, oxadiazine, morpholine, thiazine, thiadiazine, thiomorpholine, tetrazol, triazole, triazine, thiadiazine, oxadiazine, azepine, diazepine, triazepine, thiazepine and oxazepine. The saturated or unsaturated cyclic hydrocarbon of 5 or 6 elements includes the same as that exemplified in relation to the saturated or unsaturated bicyclic or tricyclic hydrocarbon condensate group. Specific examples of the saturated or unsaturated bicyclic or tricyclic fused heterocyclic group include benzofuryl, isobenzofuryl, benzothienyl, indolyl, indolinyl, isoindolyl, isoindolinyl, indazolyl, quinolyl, dihydroquinolyl, 4-oxodihydroquinolyl (dihydroquinolin-4-one), tetrahydroquinolyl, isoquinolyl, tetrahydroisoquinolyl, chromenyl, chromanyl, isochromanyl, 4H- 4-oxobenzopiranilo, 3,4-dihydro-4H-4-oxobenzopiranilo, 4H-quinoliznilo, quinazolinyl, dihydroquinazolinyl, tetrahydroquinazolinyl, quinoxalinyl, tetrahydroquinoxalinyl, cinnolinyl, tetrahidrocinnolinilo, indolizinyl, tetrahydroindolizinyl, benzothiazolyl, tetrahydrobenzothiazolyl, benzoxazolyl, benzisothiazolyl, benzisoxazolyl, benzimidazolyl, naphthyridinyl, tetrahydronaphthyridinyl, thienopyridyl, tetrahidrotienopiridilo, tiazolpiridilo, tetrahidrotiazolpiridilo, tiazolpiridazinilo, tetrahidrotiazolpiridazinilo, pyrrolopyridyl, dihydropyrrolopyridyl, tetrahidropirrolopiridilo, pyrrolopyrimidinyl, dihidropirrolopirimidinilo, piridoquinazolinilo, dihidropiridoquinazolinilo, pyridopyrimidinyl, tetrahidropir idopirimidinilo, piranotiazolilo, dihidropiranotiazolilo, furopyridyl, tetrahidrofuropiridilo, oxazolpiridilo, tetrahidroxazolpiridilo, oxazolpiridazinilo, tetrahidroxazolpiridazinilo, pirrolotiazolilo, dihidropirrolotiazolilo, pirroloxazolilo, dihidropirroloxazolilo, tienopirrolilo, thiazolopyrimidinyl, 4-oxotetrahidrocinnolinilo, 1, 2,4-benzotiadiazinilo, 1, 1-dioxy-2H- 1, 2,4-benzotiadiazinilo, 1, 2,4-benzoxadiazinilo, cyclopentapyranyl, tienofuranilo, furopiranilo, piridoxazinilo, pirazolxazolilo, imidazothiazolyl, imidazopyridyl, tetrahidroimidazopiridilo, pyrazinopyridazinyl, benzisoquinolilo, furocinnolilo, pirazoltiazolpiridazinilo, tetrahidropirazoltiazolpiridazinilo, hexahidrotiazolpiridazinopiridazinilo, imidazotriazinyl, oxazolpiridilo, benzoxepinilo, benzazepinyl, tetrahydrobenzazepinyl, benzodiazepinyl, benzotriazepinyl, thienoazepinyl, tetrahydrothienoazepinyl, thienodiazepinyl, thienotriazepinyl, thiazolazepinyl, tetrahydrothiazolazepinyl, 4,5,6,7-tetrahydro-5,6- tetramethylenethiazolpyridazinyl, and 5,6-trimethylene-4,5,6,7-tetrahydrothiazolpyridazinyl. No particular limitation is imposed on the condensation form of the above condensed heterocyclic group.

Each of the aforementioned aryl, heteroaryl, arylalkenyl, heteroarylalkenyl, saturated or unsaturated bicyclic or tricyclic condensed hydrocarbon group, and saturated or unsaturated bicyclic or tricyclic fused heterocyclic group can have from 1 to 3 substituents. Examples of substituents include hydroxyl, halogen atoms, such as a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, halogenalkyl of C1-C6 containing from 1 to 3 halogen atoms, amino, cyano , aminoalkyl, nitro, hydroxyalkyl (e.g., hydroxymethyl and 2-hydroxyethyl), alkoxyalkyl (e.g., methoxymethyl and 2-methoxyethyl), carboxyl, carboxyalkyl (e.g., carboxymethyl and 2-carboxyethyl), alkoxycarbonylalkyl (e.g., methoxycarbonylmethyl and ethoxycarbonylmethyl), acyl (for example, alkanoyl, such as formyl, acetyl, and propionyl), amidino, hydroxyamidino (amino (hydroxymethyl) methyl), straight, branched or cyclic C1-C6 alkyl (for example, methyl and ethyl), linear, branched or cyclic C 1 -C 6 alkoxy (for example, methoxy and ethoxy), amidino which is substituted by straight, branched or cyclic C 1 -C 6 alkyl (for example, imino (methylamino) methyl ), amidino which is substituted by a C1-C6 alkoxy group linear, branched or cyclic (for example, amino (methoxyimino) methyl), amidino which is substituted by linear, branched or cyclic C2-C7 alkoxycarbonyl (for example, amino (methoxycarbonylimino) methyl and amino (ethoxycarbonylimino) methyl), alkenyl Linear, branched or cyclic C2-C6 (for example, vinyl and allyl), linear or branched C2-C6 alkynyl (for example, ethynyl and propynyl), linear, branched or cyclic C2-C6 alkoxycarbonyl (for example, methoxycarbonyl and ethoxycarbonyl), carbamoyl, mono or dialkylcarbamoyl which is substituted by a linear, branched or cyclic C 1 -C 6 alkyl group at the nitrogen atom thereof (for example, methylcarbamoyl, ethylcarbamoyl, dimethylcarbamoyl, and ethylmethylcarbamoyl), mono or dialkylamino which is substituted by linear, branched or cyclic C1-C6 alkyl (eg, ethylamino, dimethylamino, and methylethylamino) and 5- or 6-membered heterocyclic group containing nitrogen (eg, pyrrolidino, piperidino, piper) azino and morpholino). Among the groups described above, the group Q2 is preferably any of the following 12 groups from (a) to (I); (wherein each of R5 and R6 represents a hydrogen atom, cyano, a halogen atom, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl, carboxyalkyl, acyl, alkoxycarbonyl, alkoxycarbonylalkyl, or phenyl that can be substituted by cyano, hydroxyl , a halogen atom, alkyl, or alkoxy, and each of R7 and R8 represents a hydrogen atom, hydroxyl, nitro, amino, cyano, a halogen atom, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl , carboxyl, carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl, N, N-dialkylcarbamoyl, alkoxycarbonyl, amidino, or alkoxycarbonylalkyl); (wherein each of R9 and R10 represents a hydrogen atom, hydroxyl, nitro, amino, cyano, a halogen atom, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl, carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl, N, N-dialkylcarbamoyl, alkoxycarbonyl, amidino, or alkoxycarbonylalkyl); (wherein each of R11, R12, and R13 represents a hydrogen atom, hydroxyl, nitro, amino, cyano, a halogen atom, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl, carboxyalkyl, acyl , carbamoyl, N-alkylcarbamoyl, N, N-dialkylcarbamoyl, alkoxycarbonyl, amidino, or alkoxycarbonylalkyl); (wherein X1 represents CH2, CH, NH, NOH, N, O, or S, and each of R14, R15 and R16 represents a hydrogen atom, hydroxyl, nitro, amino, cyano, a halogen atom, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl, carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl, N, N-dialkylcarbamoyl, alkoxycarbonyl, amidino, or alkoxycarbonylalkyl); (wherein X2 represents NH, N, O, or S; X3 represents N, C, or CH; X4 represents N, C, or CH, and each of R17 and R18 represents a hydrogen, hydroxyl, nitro, amino atom , cyano, a halogen atom, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl, carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl, N, N-dialkylcarbamoyl, alkoxycarbonyl, amidino, or alkoxycarbonylalkyl, excluding the cases where X3 and X4 are combinations of C and CH, and both are C or CH; (wherein N denotes that one or two ring carbon ring atoms having R19 and which are represented by reference to "N" are substituted by nitrogen, each of R19, R20 and R21 represents a hydrogen atom, hydroxyl, nitro , amino, cyano, a halogen atom, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl, carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl, N, N-dialkylcarbamoyl, alkoxycarbonyl, amidino, or alkoxycarbonylalkyl); (where X5 represents CH2, CH, N, or NH; Z1 represents N, NH, or O; Z2 represents CH2, CH, C, or N; Z3 represents CH2, CH, S, S02, or C = 0; X5 -Z2 represents a portion in which X5 and Z2 are linked by a single bond or a double bond, each of R22 and R23 represents a hydrogen atom, hydroxyl, nitro, amino, cyano, a halogen atom, alkyl, alkenyl alkynyl, haloalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl, carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl, N, N-dialkylcarbamoyl, alkoxycarbonyl, amidino, or alkoxycarbonylalkyl; R 24 represents a hydrogen or alkyl atom); (wherein X6 represents O or S, and each of R25 and R26 represents a hydrogen atom, hydroxyl, nitro, amino, cyano, a halogen atom, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl , carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl, N, N-dialkylcarbamoyl, alkoxycarbonyl, amidino, or alkoxycarbonylalkyl); (wherein each of R27 and R28 represents a hydrogen atom, hydroxyl, nitro, amino, cyano, halogen atom, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl, carboxyalkyl, acyl, carbamoyl, N -alkylcarbamoyl, N, N-dialkylcarbamoyl, alkoxycarbonyl, amidino or alkoxycarbonylalkyl); (wherein each of E1 and E2 represents N or CH, and each of R29 and R30 represents a hydrogen atom, hydroxyl, nitro, amino, cyano, a halogen atom, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl, carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl, N, N-dialkylcarbamoyl, alkoxycarbonyl, amidino, or alkoxycarbonylalkyl); (wherein Y1 represents CH or N; Y2 represents -N (R33) - (Where R33 represents a hydrogen atom or C1-C6 alkyl), O, or S, each of R31 and R32 represents a hydrogen atom , hydroxyl, nitro, amino, cyano, a halogen atom, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl, carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl, N, N-dialkylcarbamoyl, alkoxycarbonyl, amidino, or alkoxycarbonylalkyl); Y 1 8 (where the numerals 1 to 8 indicate positions, each of N indicates that any of the carbon atoms in positions 1 to 4 and any of the carbon atoms in positions 5 to 8 has been replaced by a nitrogen atom, each of R34, R35, and R36 represents a hydrogen atom, hydroxyl, nitro, amino, cyano, a halogen atom, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl, carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl, N, N-dialkylcarbamoyl, alkoxycarbonyl, amidino, or alkoxycarbonylalkyl). Next, these groups will be described in detail. In the description of R5 to R36 in the above groups, the halogen atom is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom; the alkyl is linear, branched or cyclic C1-C6; the alkenyl is linear, branched or cyclic C2-C6; the alkynyl is straight or branched C2-C6; the hydroxyalkyl is a group corresponding to the above C6-C6 alkyl which has been replaced by a hydroxyl group; the alkoxy is linear, branched or cyclic C1-C6; the alkoxyalkyl is a group corresponding to the above C 1 -C 6 alkyl which has been replaced by the above C 1 -C 6 alkoxy group; the carboxyalkyl is a group corresponding to the above C1-C6 alkyl which has been replaced by a carboxyl group; the acyl is a C1-C6 alkanoyl (including formyl), aroyl, such as benzoyl or naphthoyl, or arylalkanoyl corresponding to the above C6 alkanoyl which has been replaced by the above C6-C-? 4 aryl; N-alkylcarbamoyl is a group corresponding to a carbamoyl group which has been replaced by the above C 6 alkyl group on the nitrogen atom of the carbamoyl group; N, N-dialkylcarbamoyl is a group corresponding to a carbamoyl group which has been replaced by two of the above CrC6 alkyl groups on the nitrogen atom of the carbamoyl group; the alkoxycarbonyl is a group composed of the above C- [alpha] -C6 alkoxy and carbonyl; the alkoxycarbonylalkyl is a group corresponding to the above CI-CT alkyl which has been replaced by one of the above-mentioned (C6-C6) alkoxycarbonyl groups, the halogenoalkyl is a group corresponding to the above CrC6 alkyl which has been replaced by 1 to 3 halogen atoms. In the above description, no particular limitation is imposed on the position of the substitution.

In the following group: (wherein R5, R6, R7, and R8 have the same meanings as already described, the numerals from 1 to 6 rsent positions), each of R5 and R6 is preferably a hydrogen atom, cyano, a halogen atom , alkyl, alkenyl, alkynyl, or haloalkyl, with a hydrogen and alkyl atom being most preferred. Of the alkyl groups, methyl is preferred. Preferably, one of R7 and R8 is a hydrogen atom, and the other group is a hydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl, or haloalkyl. Among the cases in which one of R7 and Rd is a hydrogen atom, the other group is more preferably a hydrogen atom, a halogen atom, alkyl, or alkynyl. In this case, the halogen atom is preferably a fluorine atom, a chlorine atom, or a bromine atom, and the alkyl group is preferably a methyl group. As alkynyl, ethynyl is preferred. Preferred examples of the groups rsented by the above formula include chlorostyril, fluorostyril, bromostyril and ethynylsilyl. No particular limitation is imposed as to the position, in any of these groups, in which a halogen, alkyl or alkynyl atom is linked. Among the positions of the group rsented by the above formula, position 4 is particularly preferred. Preferred examples of the groups include 4-chlorostyril, 4-fluorostyril, 4-bromostyril and 4-ethynylsilyl. In the following group: (wherein R9 and R10 have the same meanings as already described, and the numerals "1" to "6" rsent positions), each of R9 and R10 is preferably a hydrogen atom, a halogen atom, alkyl , or alkynyl. The case where R9 is a hydrogen atom and R0 is a hydrogen atom, a halogen, alkyl or alkynyl atom is more preferred. In the above case, the halogen atom is preferably fluorine, chlorine, or bromine, the alkyl group is preferably methyl, and the alkynyl group of particular preference is ethynyl. Preferred examples of the group rsented by the above formula include chlorophenylethynyl, fluorophenylethynyl, bromophenylethynyl, and ethynylphenylethynyl. No limitation is imposed as to the position, in any of these groups, in which a halogen, alkyl or alkynyl atom is bound. Among them, position 4 in particular is preferred. Specifically, 4-chlorophenylethynyl, 4-fluorophenylethynyl, 4-bromophenylethynyl and 4-ethynylphenylethynyl are preferred among others.

In the following group: (wherein R11, R12, and R13 have the same meanings as already described, and the numerals "1" through "8" rsent positions) each of R11, R12 and R13 is preferably a hydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl, or haloalkyl. R1 is preferably a hydrogen atom, alkyl, a halogen atom or hydroxyl, with a hydrogen atom being more preferred. Preferably, one of R12 and R13 is a hydrogen atom, and the other group is a hydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl or haloalkyl. Among the cases in which one of R12 and R13 is a hydrogen atom, the other group is more preferably a hydrogen atom, a halogen atom, alkyl or alkynyl. In this case, the halogen atom is preferably a fluorine atom, a chlorine atom or a bromine atom, and the alkyl group is preferably a methyl group. As alkynyl, ethynyl is preferred. In the naphthyl group, a 2-naphthyl group is preferred to a 1-naphthyl group. In the case of the 2-naphthyl group, the position substituted by a halogen atom, alkyl group or alkynyl group is preferably a 6 or 7 position in the above formula, although it should not be particularly limited, with a 6 position being preferred. Naphthyl groups are preferably substituted by a chlorine, fluorine or bromine atom, an alkynyl group, or the like. Of particular preference, these naphthyl groups are substituted with a chlorine, fluorine or bromine atom, an alkynyl group or the like. Specific examples include 6-chloro-2-naphthyl, 6-fluoro-2-naphthyl, 6-bromo-2-naphthyl, 6-ethynyl-2-naphthyl, 7-chloro-2-naphthyl, 7-fluoro-2-naphthyl , 7-bromo-2-naphthyl and 7-ethynyl-2-naphthyl. In the following group: (wherein X1, R14, R15, and R16 have the same meanings as already described, and the numerals "4" through "7" represent positions), X1 is preferably NH, NOH, N, O, or S, with NH, O, and S being the most preferred. R 14 is preferably a hydrogen atom, a halogen atom, acyl, N-alkylcarbamoyl, N, N-dialkylcarbamoyl or alkyl. Each of R15 and R16 is preferably a hydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl or haloalkyl. Preferably, one of R15 and R16 is a hydrogen atom or a halogen atom, with one fluorine atom or one chlorine atom being more preferred, and the other group being a hydrogen atom, cyano, a halogen atom, alkyl , alkenyl, alkynyl or haloalkyl. Among them, the other group of particular preference is a hydrogen atom, a halogen atom, alkyl or alkynyl. In this case, the halogen atom is preferably a fluorine atom, a chlorine atom or a bromine atom, the alkyl group is preferably methyl, and the alkynyl group is preferably ethynyl. No particular limitation is imposed on the position to which a halogen, alkyl or alkynyl atom is linked. Among them, positions 4, 5 and 6 are preferred. Preferred examples of the group represented by the above formula include 5-chloroindolyl, 5-fluoroindolyl, 5-bromoindolyl, 5-ethynylindolyl, 5-methylindolyl, 5-chloro-4-fluoroindolyl, 5-chloro-3-fluoroindolyl, 5-fluoro-3-chloroindolyl, 5-ethynyl-3-fluoroindolyl, 5-chloro-3- (N, N-dimethylcarbamoyl) indolyl, 5-fluoro-3- (N, N- dimethylcarbamoyl) indolyl, 5-Chloro-3- formilimidolilo, 5-fluoro-3-formilindolilo, 6-cloroindolilo, 6-fluoroindolilo, 6- bromoindolilo, 6-etinilindolilo, 6-methylindolyl, 5-clorobenzotienilo, 5-fluorobenzotienilo, 5- bromobenzotienilo, 5-etinilbenzotienilo, 5- metilbenzotienilo, 5-chloro-4-fluorobenzotienilo, 6-clorobenzotienilo, 6-fluorobenzotienilo, 6-bromobenzotienilo, 6-etinilbenzotienilo, 6-metilbenzotienilo, 5-clorobenzofurilo, 5-fluorobenzofurilo, 5-bromobenzofurilo, 5-ethynylbenzofuryl, 5-methylbenzofuryl, 5-chloro-4-fluorobenzofuryl, 6-chlorobenzofuryl, 6-fluorobenzofuryl, 6-bromobenzofuryl, 6-ethynylben zofuryl, and 6-methylbenzofuryl. No particular limitation is imposed as to the position, in any of these substituents, in which T1 is linked. In the above formula (d), position 2 and position 3 are preferred. Preferably, the group, among others, is 5-chloroindol-2-yl, 5-fluoroindol-2-yl, 5-bromoindol-2- ilo, 5-ethynylindol-2-yl, 5-methylindol-2-yl, 5-chloro-4-fluoroindol-2-yl, 5-chloro-3-fluoroindol-2-yl, 3-bromo-5-chloroindol- 2-yl, 3-chloro-5-fluoroindol-2-yl, 3-bromo-5-fluoroindol-2-yl, 5-bromo-3-chloroindol-2-yl, 5-bromo-3-fluoroindole-2- ilo, 5-chloro-3-formylindol-2-yl, 5-fluoro-3-formylindol-2-yl, 5-bromo-3-formylindol-2-yl, 5-ethynyl-3-formylindo (-2-yl) , 5-chloro-3- (N, N-dimethylcarbamoyl) indol-2-yl, 5-fluoro-3- (N, N-dimethylcarbamoyl) indol-2-yl, 5-bromo-3- (N, N- dimethylcarbamoyl) indol-2-yl, 5-ethynyl-3- (N, N-dimethylcarbamoyl) indol-2-yl, 6-chloroindol-2-yl, 6-fluoroindol-2-yl, 6-bromoindol- 2- ilo, 6-ethynylindol-2-yl, 6-methylindol-2-yl, 5-chloroindol-3-yl, 5-fluoroindol-3-yl, 5-bromoindol-3-yl, 5-ethynylindol-3-yl , 5-methylindol-3-yl, 5-chloro-4-fluoroindol-3-yl, 6-chloroindol-3-yl, 6-fluoroindol-3-yl the 6-bromoindole-3-yl, 6-etinilindol-3-yl yl 6-methylindole-3-yl 5-chlorobenzothiophen-2-yl 5-fluorobenzothiophen-2-yl 5-bromobenzotiofen-2-,,,,, 5-yl-2-etinilbenzotiofen, 5-methylbenzothiophen-2-yl, 5-chloro-4-fluorobenzothiophen-2-yl, 6-chlorobenzothiophen-2-yl, 6-fluorobenzothiophen-2-yl, 6-bromobenzotiofen-2- yl yl 6-methylbenzothiophen-2-, yl 6-etinilbenzotiofen-2-, 5-chlorobenzothiophen-3-yl, 5-fluorobenzothiophen-3-yl, 5-bromobenzotiofen-3-yl, 5-etinilbenzotiofen-3-yl, 5-methylbenzothiophen-3-yl, 5-chloro-4-fluorobenzothiophen-3-yl, 6-chlorobenzothiophen-3-¡lo, 6-fluorobenzothiophen-3-yl, 6-bromobenzotiofen-3-yl, 6-etinilbenzotiofen-3 -yl, 6-methylbenzothiophen-3-yl, 5-chlorobenzofuran-2-yl, 5-fluorobenzofuran-2-yl, 5-bromobenzofuran-2-yl, 5-ethynylbenzofuran-2-yl, 5-methylbenzofuran-2-yl, 5-chloro-4-fluorobenzofuran-2 -yl, 6-chlorobenzofuran-2-yl, 6-fluorobenzofuran-2-yl, 6-bromobenzofuran-2-yl, 6-ethynylbenzofuran-2-yl, 6-methylbenzofuran-2-yl, 5-chlorobenzofuran-3-yl , 5-fluorobenzofuran-3-yl, 5-bromobenzofuran-3-yl, 5-ethynylbenzofuran-3-yl, 5-methylbenzofuran-3-yl, 5-chloro-4-fluorobenzofuran-3-yl, 6-chlorobenzofuran 3-yl, 6-fluorobenzofuran-3-yl, 6-bromobenzofuran-3-yl, 6-ethynylbenzofuran-3-yl or 6-methylbenzofuran-3-yl. More preferably, the group, among others, is 5-chloroindol-2-yl, 5-fluoroindol-2-yl, 5-bromoindol-2-yl, 5-ethynylindol-2-yl, 5-methylindol-2-yl , 5-chloro-4-fluoroindol-2-yl, 6-chloro-nol-2-yl, 6-fluoroindol-2-yl, 6-bromoindol-2-yl, 6-etinylindol-2-yl, 6- methylindol-2-yl, 5-chloro-3-fluoroindol-2-yl, 3-bromo-5-chloroindol-2-yl, 3-chloro-5-fluoroindol-2-yl, 3-bromo-5-fluoroindole- 2-yl, 5-bromo-3-chloroindol-2-yl, 5-bromo-3-fluoroindol-2-yl, 5-chloro-3-formylindol-2-yl, 5-fluoro-3-formylindol-2 -yl, 5-bromo-3-formylindol-2-yl, 5-ethynyl-3-formylindol-2-yl, 5-chloro-3- (N, N-dimethylcarbamoyl) indol-2-yl, 5-fluoro- 3- (N, N-dimethylcarbamoyl) indol-2-yl, 5-bromo-3- (N, N-dimethylcarbamoyl) indol-2-yl, 5-ethynyl-3- (N, N-dimethylcarbamoyl) indole-2 -yl, 5-chlorobenzothiophen-2-yl, 5-fluorobenzothiophen-2-yl, 5-bromobenzothiophen-2-yl, 5-ethynylbenzothiophen-2-yl, 5-methylbenzothiophen-2-yl, 5-chloro-4-fluorobenzothiophen -2-yl, 6-chlorobenzothiophen-2-yl, 6-fluorobenzothiophen-2-yl, 6-bromobenzothiophen-2-yl it, 6-ethylenebenzothiophen-2-yl, 6-methylbenzothiophen-2-yl, 5-chlorobenzofuran-2-yl, 5-fluorobenzofuran-2-yl, 5-bromobenzofuran-2-yl, 5-ethinylbenzofuran- 2-yl, 5-methylbenzofuran-2-yl, 5-chloro-4-fluorobenzofuran-2-yl, 6-chlorobenzofuran-2-yl, 6-fluorobenzofuran-2-yl, 6-bromobenzofuran-2-yl, 6 -etinylbenzofuran-2-yl or 6-methylbenzofuran-2-yl.

In the following group: (wherein X2, X3, X4, R17, and R18 have the same meanings as already described, and the numerals "4" through "7" represent positions), X2 is preferably NH, O or S. Preferred is where any of X3 and X4 is CH or C, and particularly preferred is the case where one of X3 and X4 is C. Preferably, R17 and R18 each independently represents a hydrogen atom, cyano, a halogen atom , alkyl, alkenyl, alkynyl, or haloalkyl. Preferably, one of R17 and R18 is a hydrogen atom, and the other group is a hydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl or haloalkyl. Among the cases in which one of R17 and R18 is a hydrogen atom, the other group more preferably is a hydrogen atom, a halogen atom, alkyl or alkynyl. In this case, the halogen atom is preferably a fluorine atom, a chlorine atom or a bromine atom, the alkyl group is preferably a methyl group, and the alkylene group is preferably ethynyl. No particular limitation is imposed as to the position to which a halogen, alkyl or alkynyl atom is linked. Among them, position 5 or position 6 is preferred. Specific examples of preferred groups represented by the above formula include 5-chloroindazolyl, 5-fluoroindazolyl, 5-bromoindazolyl, 5-ethynylindazolyl, 6-chloroindazolyl, 6-fluoroindazolyl, 6-bromoindazolyl. 6-etinilindazoliIo, 5-cIorobenzimidazolilo, 5- fluorobenzimidazolilo, 5-bromobenzimidazolilo, 5-etinilbenzimidazolilo, 6- clorobenzimidazolilo, 6-fluorobenzimidazolilo, 6-bromobenzimidazolilo, 6- etinilbenzimidazolilo, 5-clorobenzotiazolilo, 5-fluorobenzotiazolilo, 5- bromobenzotiazolilo, 5 -etinylbenzothiazolyl, 6-chlorobenzothiazolyl, 6-fluorobenzothiazolyl, 6-bromobenzothiazolyl, 6-ethynylbenzothiazolyl, 5-chlorobenzoxazolyl, 5-fluorobenzoxazolyl, 5-bromobenzoxazolyl, 5-ethynylbenzoxazolyl, 6-chlorobenzoxazolyl, 6-fluorobenzoxazolyl, 6-bromobenzoxazolyl, 6-ethynylbenzoxazolyl , 5-chlorobenzoisothiazolyl, 5-fluorobenzisothiazolyl, 5-bromobenzisothiazolyl, 5-ethynylbenzoisothiazolyl, 6-chlorobenzoisothiazole lilo, 6-fluorobenzisothiazolyl, 6-bromobenzisothiazolyl, 6-ethynylbenzoisothiazolyl, 5-chlorobenzisoxazolyl, 5-fluorobenzisoxazolyl, 5-bromobenzisoxazolyl, 5-ethynylbenzoisoxazolyl, 6-chlorobenzisoxazolyl, 6-fluorobenzisoxazolyl, 6-bromobenzisoxazolyl, and 6-ethynylbenzoisoxazolyl. No particular limitation is imposed as to the position, in any of these substituents, in which T1 is linked. However, the group of preference is 5-chloroindazol-3-yl, 5-fluoroindazol-3-yl, 5-bromoindazol-3-yl, 5-ethynylindazol-3-yl, 6-chloroindazol-3-yl, 6- fluoroindazol-3-yl, 6-bromoindazol-3-yl, 6-ethynylindazol-3-yl, 5-chlorobenzimidazol-2-yl, 5-fluorobenzimidazol-2-yl, 5-bromobenzimidazol-2-yl, 5-ethynylbenzimidazole- 2-yl, 6-c-orobenzimidazol-2-yl, 6-fluorobenzimidazol-2-yl, 6-bromobenzimidazol-2-yl, 6-ethynylbenzimidazol-2-yl, 5-chlorobenzothiazol-2-yl, 5-fluorobenzothiazole- 2- ilo, 5-bromobenzothiazol-2-yl, 5-etini-benzothiazol-2-yl, 6-chlorobenzothiazol-2-yl, 6-fluorobenzothiazol-2-yl, 6-bromobenzothiazol-2-yl, 6-ethinylbenzothiazole- 2-yl, 5- chlorobenzoxazol-2-yl, 5-fluorobenzoxazol-2-yl, 5-bromobenzoxazol-2-yl, 5-ethynylbenzoxazol-2-yl, 6-chlorobenzoxazol-2-yl, 6-fluorobenzoxazol-2 ilo, 6- bromobenzoxazol-2-yl, 6-ethynylbenzoxazol-2-yl, 5-chlorobenzisothiazol-3-yl, 5-fluorobenzisothiazol-3-yl, 5-bromobenzisothiazol-3-yl, 5-ethynylbenzisothiazol-3-yl, 6-chlorobenzoisothiaz ol-3-yl, 6-fluorobenzisothiazol-3-yl, 6-bromobenzisothiazol-3-yl, 6-ethynyl-benzisothiazol-3-yl, 5-chloro-benzisoxazol-3-yl, 5-fluoro-benzisoxazol-3-yl, 5-bromobenzisoxazol- 3-yl, 5-ethynylbenzisoxazol-3-yl, 6-chlorobenzisoxazol-3-yl, 6-fluorobenzisoxazol-3-yl, 6-bromobenzisoxazol-3-yl or 6-ethynylbenzisoxazol-3-yl. The most preferred group is 5-chlorobenzimidazol-2-yl, 5-fluorobenzimidazol-2-yl, 5-bromobenzimidazol-2-yl, 5-ethynyl-benzamidazol-2-yl, 6-chlorobenzimidazol-2-yl, 6-fluorobenzimidazol-2-yl, 6-bromobenzimidazol-2-yl, 6- ethynylbenzimidazol-2-yl, 5-chlorobenzothiazol-2-yl, 5-fluorobenzotlazol-2-yl, 5-bromobenzothiazol-2-yl, 5-ethynylbenzothiazol-2-yl, 6-chlorobenzothiazol-2-yl, 6- fluorobenzothiazol-2-yl, 6-bromobenzothiazol-2-yl, 6-ethynylbenzothiazol-2-yl, 5-chlorobenzoxazol-2-yl, 5-fluorobenzoxazol-2-yl, 5-bromobenzoxazol-2-ylp, 5-ethynylbenzoxazole- 2-yl, 6-chlorobenzoxazol-2-yl, 6-fluorobenzoxazol-2-yl, 6-bromobenzoxazol-2-yl, and 6-ethynylbenzoxazol-2-yl, even more preferably 5-chlorobenzimidazol-2-yl, -fluorobenzimidazol-2-yl, 5-bromobenzimidazol-2-yl or 5-ethynylbenzimidazol-2-yl.

In the following group: (where N denotes that one or two carbon atoms in the ring that has R 9, and which are represented with reference "N", are substituted by nitrogen, R19, R20 and R21 have the same meanings as already described, and the numerals "5" to "8" represent positions) each of R19 , R20 and R21 represents a hydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl or haloalkyl. R19 is particularly preferably a hydrogen atom. Preferably, one of R20 and R21 is a hydrogen atom, and the other group is a hydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl or haloalkyl. Among the cases in which one of R20 and R21 is a hydrogen atom, the other group is more preferably a hydrogen atom, a halogen atom, alkyl or alkynyl. In this case, the halogen atom is preferably a fluorine atom, a chlorine atom or a bromine atom, the alkyl group is preferably a methyl group, and the alkynyl group is preferably an ethynyl group. No particular limitation is imposed on the position to which a halogen, alkyl or alkynyl atom is linked. Among them, position 6 or position 7 is preferred. Specific examples of the group represented by the above formula include quinolinyl, isoquinolinyl and cinnolinyl. Among them, the group of preference, among others, is 6-chloroquinolinyl, 6-fluoroquinolinyl, 6-bromoquinolinyl, 6-ethynylquinolinyl, 6-chloroisoquinolinyl, 6-fluoroisoquinolinyl, 6-bromoisoquinolinyl, 6-ethynylisoquinolinyl, 7-chlorocinnolinyl, 7- fluoroquinolinyl, 7-bromoquinolinyl or 7-ethynylcinnolinyl, more preferably, inter alia, 6-chloroquinolin-2-yl, 6-fluoroquinolin-2-yl, 6-bromoquinolin-2-yl, 6-ethynylcholn-n-2 -lo, 6-chloroquinolin-3-yl, 6-fluoroquinolin-3-yl, 6-bromoquinolin-3-yl, 6-ethynylquinolin-3-yl, 7-cyranoquinolin-2-yl, 7-fluoroquinolin-2- ilo, 7-bromoquinolin-2-yl, 7-ethynylquinolin-2-yl, 7-chloroquinolin-3-yl, 7-fluoroquinolin-3-yl, 7-bromoquinolin-3-yl, 7-ethynylquinolin-3-yl , 6-chloroisoquinolin-3-yl, 6-fluoroisoquinolin-3-yl, 6-bromoisoquinolin-3-yl, 6-ethynylisoquinolin-3-yl, 7-chloroisoquinolin-3-yl, 7-fluoroisoquinolin-3-yl, -bromoisoquinolin-3-yl, 7-ethynylisoquinolin-3-yl, 7-chloroquinolin-3-yl, 7-fluoroquinolin-3-yl, 7-bromine cinnolin-3-yl or 7-ethynylcinnolin-3-yl. Among them, the group with even greater preference is 6-chloroquinolin-2-yl, 6-fluoroquinolin-2-yl, 6-bromoquinolin-2-yl, 6-ethynylquinolin-2-yl, 7-chloroquinolin-3-yl, 7-fluoroquinolin-3-yl, 7-bromoquinolin-3-yl, 7-ethynylquinolin-3-yl, 7-chloroisoquinolin-3-yl, 7-fluoroisoquinolin-3-yl, 7-bromoisoquinolin-3-yl, 7- ethynylisoquinolin-3-ylo, 7-chloroquinolin-3-yl, 7-fluoroquinolin-3-yl, 7-bromocinnolin-3-yl or 7-ethynylcinnolin-3-yl.

In the following group: (where the numerals from "5" to "8" represent positions; X5 represents CH2, CH, N or NH; Z1 represents N, NH or O; Z2 represents CH2, CH, C or N; Z3 represents CH2, CH, S, S02 or C = 0; X5-Z2 represents a portion in which X5 and Z2 are linked through a single bond or a double bond, R22, R23 and R24 have the same meanings as described above) each of R22 and R23 is preferably a hydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl or haloalkyl. Preferably, one of R22 and R23 is a hydrogen atom, and the other group is a hydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl or haloalkyl. Among the cases in which one of R22 and R23 is a hydrogen atom, the other group is more preferably a hydrogen atom, a halogen atom, alkyl or alkynyl. In this case, the halogen atom is preferably a fluorine atom, a chlorine atom and a bromine atom, the alkyl group is preferably a methyl group, and the alkynyl group is preferably an ethynyl group. No particular limitation is imposed as to the position to which a halogen atom is bonded, alkyl or alkynyl. Among them, position 6 or position 7 is preferred. R 24 is preferably a hydrogen or alkyl atom. Among the alkyl groups, methyl is preferred. R 24 is particularly preferably a hydrogen atom. Specific examples of groups represented by the above formula include 4-oxodihydroquinolinyl, tetrahydroquinolinyl, 4-oxodihydroquinazolin-2-yl, 4-oxotetrahydrocinnolinyl, 4-oxobenzopyranyl, 4-oxobenzothiadiazinyl, 1,1-dioxy-4-oxobenzothiadiazinyl and benzoxadiazinyl. More specific examples of the group include 6-chloro-4-oxodihydroquinolinyl, 6-fluoro-4-oxodihydroquinolinyl, 6-bromo-4-oxodihydroquinolinyl, 6-ethynyl-4-oxodihydroquinolinyl, 7-chloro-4-oxodihydroquinolinyl, 7-fluoro- 4-Oxodihydroquinolinyl, 7-bromo-4-oxodihydroquinolinyl, 7-ethynyl-4-oxodihydroquinolinyl, 6-chloro-4-oxo-1,4-dihydroquinazolinyl, 6-fluoro-4-oxo-1,4-dihydroquinazolinyl, 6-bromo-4-oxo-1,4-dihydroquinazolinyl, 6-ethynyl-4-oxo-1,4-dihydroquinazolinyl, 7-chloro-4-oxo-1,4-dihydroquinazolinyl, 7-fluoro-4-oxo- 1,4-dihydroquinazolinyl, 7-bromo-4-oxo-1,4-dihydroquinazolinyl, 7-ethynyl-4-oxo-1,4-dihydroquinazole, 6-chloro-1, 2,3,4- tetrahydroquinolinyl, 6-fluoro-1, 2,3,4-tetrahydroquinolinyl, 6-bromo-1, 2,3,4-tetrahydroquinolinyl, 6-ethynyl-1, 2,3,4-tetrahydroquinolinyl, 7-chloro-1, 2,3,4-tetrahydroquinolinyl, 7-fluoro-1, 2,3,4-tetrahydroquinolinyl, 7-bromo-1, 2,3,4-tetrahydroquinolinyl, 7-ethynyl-1, 2,3,4-tetrahydroquinolinyl, 6-chloro-1, 2,3,4-tetra ahydro-4-oxoquinolinyl, 6-fluoro-1, 2,3,4-tetrahydro-4-oxoquinolinyl, 6-bromo-1, 2,3,4-tetrahydro-4-oxoquinolinyl, 6-ethinyl-1,2, 3,4-tetrahydro-4-oxoquinolinyl, 7-chloro-1, 2,3,4-tetrahydro-4-oxoquinolinyl, 7-fluoro-1, 2,3,4-tetrahydro-4-oxoquinolinyl, 7-bromo- 1, 2,3,4-tetrahydro-4-oxoquinolinyl, 7-ethynyl-1, 2,3,4-tetrahydro-4-oxoquinolinyl, 6-chloro-4H-4-oxobenzopyranyl, 6-fluoro-4H-4- oxobenzopyranyl, 6-bromo-4H-4-oxobenzopyranyl, 6-ethynyl-4H-4-oxobenzopyranyl, 7-chloro-4H-4-oxobenzopyranyl, 7-fluoro-4H-4-oxobenzopyranyl, 7-bromo-4H-4- oxobenzopyranyl, 7-ethynyl-4H-4-oxobenzopyranyl, 6-chloro-1, 1-dioxy-2H-1, 2,4-benzothiazinyl, 6-fluoro-1, 1-dioxy-2H-1, 2, 4-benzothiadiazinyl, 6-bromo-1,1-dioxy-2H-1, 2,4-benzothiadiazinyl, 6-ethynyl-1,1-dioxy-2H-1, 2,4-benzothiadiazinyl, 7-chloro-1, 1-Dioxy-2H-1, 2,4-benzothiadiazinyl, 7-fluoro-1, 1-dioxy-2H-1, 2,4-benzothiadiazinyl, 7-bromo-1, 1-dioxy-2H-1, 2, 4-benzothiadiazinyl, 7-ethynyl-1,1-dioxy-2H-1, 2,4-benzothiadiazinyl, 6- chloro-2H-1, 2,4-benzoxadiazinyl, 6-fluoro-2H-1, 2,4-benzoxadiazinyl, 6-bromo-2H-1, 2,4-benzoxadiazinyl, 6-ethynyl-2H-1, 2,4-benzoxadiazinyl, 7-chloro-2H-1, 2,4-benzoxadiazinyl, 7-fluoro-2H-1, 2,4-benzoxadiazinyl, 7-bromo-2H-1, 2,4-benzoxadiazinyl and 7- ethynyl-2H-1, 2,4-benzoxadiazinyl. Particularly preferred are, for example, 6-chloro-4-oxo-1,4-dihydroquinolin-2-yl, 6-fluoro-4-oxo-1,4-dihydroquinolin-2-yl, 6-bromo-4- oxo-1, 4-dihydroquinolin-2-yl, 6-ethynyl-4-oxo-1,4-dihydroquinolin-2-yl, 7-chloro-4-oxo-1,4-dihydroquinolin-2-yl, 7- fluoro-4-oxo-, 4-dihydroquinolin-2-yl, 7-bromo-4-oxo-1,4-dihydroquinolin-2-yl, 7-ethynyl-4-oxo-1,4-dihydroquinolin-2-yl , 6-chloro-4-oxo-1,4-dihydroquinazolin-2-yl, 6-fluoro-4-oxo-1,4-dihydroquinazolin-2-yl, 6-bromo-4-oxo-1,4-dihydroquinazolin -2-yl, 6-ethynyl-4-oxo-1,4-dihydroquinazolin-2-yl, 7-chloro-4-oxo-1,4-dihydroquinazolin-2-yl, 7-fluoro-4-oxo-1 , 4-dihydroquinazolin-2-yl, 7-bromo-4-oxo-1,4-dihydroquinazolin-2-yl, 7-ethynyl-4-oxo-1,4-dihydroquinazolin-2-yl, 6-chloro-1 , 2,3,4-tetrahydroquinolin-2-yl, 6-fluoro-1, 2,3,4-tetrahydroquinolin-2-yl, 6-bromo-1, 2,3,4-tetrahydroquinolin-2-yl, 6 - ethinyl-1, 2,3,4-tetrahydroquinolin-2-yl, 6-chloro-1, 2,3,4-tetrahydro-4-oxoquinolin-2-yl, 6-fluoro-1, 2,3,4 -tetrahydro-4-oxocinn olin-2-yl, 6-bromo-1, 2,3,4-tetrahydro-4-oxoquinolin-2-yl, 6-etinyl-1, 2,3,4-tetrahydro-4-oxoquinolin-2- It, 7-chloro-1, 2,3,4-tetrahydro-4-oxocinnolin-2-yl, 7-fluoro-1, 2,3,4-tetrahydro-4-oxocinnolin-2-yl, 7-bromo-1, 2,3,4-tetrahydro-4-oxokinolin-2-yl, 7-ethinyl-1, 2,3,4-tetrahydro-4-oxoquinolin-2-yl, 6- chloro-4H-4-oxobenzopyran-2-yl, 6-fluoro-4H-4-oxobenzopyran-2-yl, 6-bromo-4H-4-oxobenzopyran-2-yl, 6-ethynyl-4H-4-oxobenzopyran- 2-yl, 7-chloro-4H-4-oxobenzopyran-2-yl, 7-fluoro-4H-4-oxobenzopyran-2-yl, 7-bromo-4H-4-oxobenzopyran-2-yl, 7-ethynyl- 4H-4-oxobenzopyran-2-yl, 6-chloro-1,1-dioxy-2H-1, 2,4-benzothiadiazin-3-yl, 6-fluoro-1, 1-dioxy-2H-1, 2, 4-benzothiadiazin-3-yl, 6-bromo-1, 1-dioxy-2H-1, 2,4-benzothiadiazin-3-yl, 6-ethynyl-1,1-dioxy-2H-1, 2,4-benzothiadiazin-3-yl, 7-chloro-1,1-dioxy-2H-1, 2,4-benzothiadiazin-3-yl, 7-fluoro-1, 1-dioxy-2H-1, 2, 4-benzothiadiazin-3-yl, 7-bromo-1, 1-dioxy-2H-1, 2,4-benzothiadiazin-3-yl, 7-ethynyl-1,1-dioxy-2H-1, 2,4- benzothiadiazin-S-yl, 6-chloro-2H-1, 2,4-benzoxadiazin-3-yl, 6-fluoro-2H-1, 2,4-benzoxadiazin-3-yl, 6-bromo-2H-1, 2,4-benzoxadiazin-3-yl, 6-ethynyl-2H-1, 2,4-benzoxadiazin-3-yl, 7-chloro-2H-1, 2,4-benzoxadiazin-3-yl, 7 -fluoro-2H-1, 2,4-benzoxadiazin-3-yl, 7-bromo-2H-1, 2,4-benzoxadiazin-3-ylo and 7-ethynyl-2H-1, 2,4-benzoxadiazin- 3-ilo. Among them, 6-chloro-4-oxo-1,4-dihydroquinolin-2-yl, 6-fluoro-4-oxo-1,4-dihydroquinolin-2-yl, 6-bromo-4-oxo- 1,4-dihydroquinolin-2-yl, 6-ethynyl-4-oxo-1,4-dihydroquinolin-2-yl, 6-chloro-4-oxo-1,4-dihydroquinazolin-2-yl, 6-fluoro -4-oxo-1,4-dihydroquinazolin-2-yl, 6-bromo-4-oxo-1,4-dihydroquinazolin-2-ylo and 6-ethynyl-4-oxo-1,4-dihydroquinazolin-2 ilo. In the following group: (where X6 represents O or S, R25 and R26 have the same meanings as already described, and the numerals "5" to "8" represent positions), X6 is preferably O, and each of R25 and R26 are Preference is a hydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl or haloalkyl. Preferably, one of R25 and R26 is a hydrogen atom, and the other group is a hydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl or haloalkyl. Among the cases in which one of R25 and R26 is a hydrogen atom, the other group of particular preference is a hydrogen atom, a halogen atom, alkyl, or alkynyl. In this case, the halogen atom is preferably a fluorine atom, a chlorine atom or a bromine atom, the alkyl group is preferably a methyl group, and the alkynyl group is an ethynyl group. No particular limitation is imposed as to the position in which a halogen, alkyl or alkynyl atom is bound. Among them, position 6 or position 7 is preferred. Specific examples of preferred groups include 6-chloro-2H-chromen-3-yl, 6-fluoro-2H-chromen-3-yl, 6-bromo-2H-chromen- 3-lyl, 6-ethynyl-2H-chromen-3-yl, 7-chloro-2H-chromen-3-yl, 7-fluoro-2H-chromen-3-yl, 7-bromo-2H-chromen-3 ilo and 7-ethynyl-2H-chromen-3-yl. In particular, 7-chloro-2H-chromen-3-yl, 7-fluoro-2H-chromen-3-yl, 7-bromo-2H-chromen-3-yl and 7-ethynyl-2H-chromen-3 are preferred. ilo. In the following group: (wherein R27 and R28 have the same meanings as already described, and numerals "1" to "6" represent positions), preferably, one of R27 and R28 is a hydrogen atom or a halogen atom, and the other group is a hydrogen atom, cyano, nitro, amino, a halogen atom, alkyl, alkenyl, alkynyl, haloalkyl or N, N-dialkylcarbamoyl. Among the cases in which one of R27 and R28 is a hydrogen atom or a halogen atom, the other group of particular preference is a hydrogen atom, a halogen atom, alkyl or alkynyl. In this case, the halogen atom is preferably a fluorine atom, a chlorine atom or a bromine atom, the alkyl group is preferably a methyl group, and the alkynyl group of particular preference is an ethynyl group. Preferred examples of the group represented by the above formula include phenyl, chlorophenyl, fluorophenyl, bromophenyl, ethynylphenyl and chlorofluorophenyl. No particular limitation is imposed as to the position, in any of these groups, in which the halogen, alkyl or alkynyl atom (s) is (are) bonded. However, when these groups are mono-substituted, in particular position 3 and position 4 of the ring in the above formula are preferred; when these groups are di-substituted, in particular combinations of positions 4 and 2 and positions 4 and 3 of the ring in the above formula are preferred. Preferred examples of the group include phenyl, 4-chlorophenyl, 4-fluorophenyl, 4-bromophenyl, 4-ethynylphenyl, 3-chlorophenyl, 3-fluorophenyl, 3-bromophenyl, 3-ethynylphenyl, 3-chloro-4-fluorophenyl, 4-chloro-3-fluorophenyl, 4-chloro- 2- fluorofenyl, 2-chloro-4-fluorophenyl, 4-bromo-2-fluorophenyl, 2-bromo-4-fluorophenyl, 2,4-dichlorophenyl, 2,4-difluorophenyl, 2,4-dibromophenyl, 4-chloro-3- methylphenyl, 4-fluoro-3-methylphenyl, 4-bromo-3-methylphenyl, 4-chloro-2-methylphenyl, 4-fluoro-2-methylphenyl, 4-bromo-2-methylphenyl, 3,4-dichlorophenyl, 3, 4-difluorophenyl and 3,4-dibromophenyl. In the following formula: (wherein E1, E2, R29 and R30 have the same meanings as already described, and the numerals "1" to "6" represent positions), preferably, one of R29 and R30 is a hydrogen atom or an atom of halogen, and the other of the group is a hydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl or haloalkyl. Among the cases in which one of R29 and R30 is a hydrogen atom or a halogen atom, the other group of particular preference is a hydrogen atom, a halogen atom, alkyl or alkynyl. In this case, the halogen atom is preferably a fluorine atom, a chlorine atom or a bromine atom, the alkyl group is preferably a methyl group and the alkynyl group of particular preference is an ethynyl group. Specific examples of the group represented by the above formula include pyridyl, pyrimidyl and pyridazinyl. No particular limitation is imposed as to the position, in any of these groups, in which a halogen, alkyl or alkynyl atom is linked. However, when T1 is linked to the group in the 2-position of the ring in the above formula, in particular position 4 and position 5 of the ring in the above formula are preferred. Specifically, preferred examples of the group include 2-pyridyl, 3-pyridyl,. 4-pyridyl, 4-chloro-2-pyridyl, 4-fluoro-2-pyridyl, 4-bromo-2-pyridyl, 4-ethynyl-2-pyridyl, 4-chloro-3-pyridyl, 4-fluoro-3- pyridyl, 4-bromo-3-pyridyl, 4-ethynyl-3-pyridyl, 5-chloro-2-pyridyl, 5-fluoro-2-pyridyl, 5-bromo-2-pyridyl, 5-ethynyl-2-pyridyl, 4-chloro-5-fluoro-2-pyridyl, 5-chloro-4-fluoro-2-pyridyl, 5-chloro-3-pyridyl, 5-fluoro-3-pyridyl, 5-bromo-3-pyridyl, 5- ethynyl-3-pyridyl, 5-chloro-2-pyrimidyl, 5-fluoro-2-pyrimidyl, 5-bromo-2-pyrimidyl, 5-ethynyl-2-pyrimidyl, 4-chloro-3- pyridazinyl, 4-fluoro-3-pyridazinyl, 4-bromo-3-pyridazinyl, 4-ethynyl-3-pyridazinyl, 6-chloro-3-pyridazinyl, 6-fluoro-3-pyridazinyl, 6-bromo- 3-pyridazinyl and 6-ethynyl-3-pyridazinyl.

. Among them, 2-pyridyl, 3-pyridyl, 4-pyridyl, 4-chloro-2-pyridyl, 4-fluoro-2-pyridyl, 4-bromo-2-pyridyl, 4-ethynyl-2-pyridyl are particularly preferred. , 4-chloro-3-pyridyl, 4-fluoro-3-pyridyl, 4-bromo-3-pyridyl, 4-ethynyl-3-pyridyl, 5-chloro-2-pyridyl, 5-fluoro-2-pyridyl , 5-bromo-2-pyridyl, 5-ethynyl-2-pyridyl, 4-chloro-5-fluoro-2-pyridyl, 5-chloro-4-fluoro-2-pyridyl, 5-chloro-3 -pyridyl, 5-fluoro-3-pyridyl, 5-bromo-3-pyridyl, 5-ethynyl-3-pyridyl, 6-chloro-3-pyridazinyl, 6-fluoro-3-pyridazinyl, 6-bromo-3-pyridazinyl , 6-ethynyl-3-pyridazinyl, 4-chloro-3-pyridazinyl, 4-fluoro-3-pyridazinyl, 4-bromo-3-pyridazinyl and 4-ethynyl-3-pyridazinyl. Among them, 2-pyridyl, 3-pyridyl, 4-pyridyl, 5-chloro-2-pyridyl, 5-fluoro-2-pyridyl, 5-bromo-2-pyridyl, 5-ethynyl-2-pyridyl are further preferred. , 5-chloro-4-fluoro-2-pyridyl, 4-chloro-5-fluoro-2-pyridyl, 4-chloro-3-pyridazinyl, 4-fluoro-3-pyridazinyl, 4-bromo-3-pyridazinyl and -etinyl-3-pyridazinyl. In the following group: 1 (wherein Y1, Y2, R31 and R32 have the same meanings as already described, and the numerals "1" through "5" represent positions), preferably, one of R31 and R32 is a hydrogen atom or a halogen atom, and the other group is a hydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl or haloalkyl. Among the cases in which one of R31 and R32 is a hydrogen atom or a halogen atom, the other group of particular preference is a hydrogen atom, a halogen atom, alkyl or alkynyl. In these cases, the halogen atom is preferably a fluorine atom, a chlorine atom or a bromine atom, the alkyl group is preferably methyl, and the particularly preferred alkynyl group is ethynyl. Specific examples of the group represented by the above formula include thienyl, pyrrolyl, furyl, oxazolyl and thiazolyl. No particular limitation is imposed as to the position, in any of these groups, to which a halogen, alkyl or alkynyl atom is linked. Among them, position 4 and position 5 are particularly preferred. Specific examples of the group include 4-chloro-2-thienyl, 4-fluoro-2-thienyl, 4-bromo-2-thienyl, 4-ethynyl-2-thienyl. , 4-chloro-2-pyrrolyl, 4-fluoro-2-pyrrolyl, 4-bromo-2-pyrrolyl, 4-ethynyl-2-pyrrolyl, 4-chloro-2-furyl, 4-fluoro-2-furyl, -bromo-2-furyl, 4-ethynyl-2-furyl, 5-chloro-2-thienyl, 5-fluoro-2-thienyl, 5-bromo-2-thienyl, 5-ethynyl-2-thienyl, 5-chloro -2-thiazolyl, 5-fluoro-2-thiazolyl, 5-bromo-2-thiazolyl, 5-ethynyl-2-thiazolyl, 5-chloro-2-oxazolyl, 5-fluoro-2-oxazolyl, 5-bromo-2 -oxazolyl and 5-ethynyl-2-oxazolyl. Among them, 5-chloro-2-thiazolyl, 5-fluoro-2-thiazolyl, 5-bromo-2-thiazolyl and 5-ethynyl-2-thiazolyl are preferred.

Additionally, in the following group: 1 8 (where, the numerals from "1" to "8" represent positions, each N indicates that any of the carbon atoms in positions 1 to 4 and any of the carbon atoms in positions 5 to 8 have been substituted by a nitrogen atom, and R34 to R36 have the same meanings as already described), the nitrogen substituent atoms can be located at any of the positions, R34 is preferably a hydrogen atom or a halogen atom. One of R35 and R36 is a hydrogen atom or a halogen atom, and the other group is a hydrogen atom, cyano, halogen atom, alkyl, alkenyl, alkynyl or haloalkyl. Among the cases in which one of R35 and R36 is a hydrogen atom or a halogen atom, the other group of particular preference is a hydrogen atom, a halogen atom, alkyl or alkynyl. The halogen atom is preferably a fluorine atom, a chlorine atom or a bromine atom, the alkyl group is a methyl group, and the alkynyl group of particular preference is an ethynyl group. No particular limitation is imposed as to the position in which a halogen, alkyl or alkynyl atom is bound. Specific examples of the group represented by the above formula include 6-chloro-1, 5-naphthyridin-2-yl, 6-fluoro-1, 5-naphthyridin-2-yl, 6-bromo-1,5-naphthyridin-2-yl, 6-ethynyl-1, 5-naphthyridin-2-yl , 7-chloro-1, 5-naphthridin-2-yl, 7-fluoro-1, 5-naphthyridin-2-yl, 7-bromo-l, 5-naphthyridin-2-yl, 7-ethynyl -1, 5-naphthyridin-2-yl, 6-chloro-1, 5-naphthyridin-3-yl, 6-fluoro-1, 5-naphthyridin-3-yl, 6-bromo-1, 5-naphthyridin-3 -yl, 6-ethynyl-1, 5-naphthyridin-3-yl, 7-chloro-1, 5-naphthyridin-3-yl, 7-fluoro-1, 5-naphthyridin-3-yl, 7- Bromo-1, 5-naphthyridin-3-yl, 7-ethynyl-1, 5-naphthyridin-3-yl, 6-chloro-1, 7-naphthyridin-2-yl, 6-fluoro-1, 7-naphthyridine -2-yl, 6-bromo-1, 7-naphthyridin-2-yl, 6-ethynyl-l, 7-naphthyridin-2-yl, 6-chloro-l, 7-naphthyridin-3-yl, 6-fluoro -1,7-naphthyridin-3-yl, 6-bromo-l, 7-naphthyridin-3-yl, 6-ethynyl-l, 7-naphthyridin-3-yl, 6-chloro-l, 8-naphthyridin-2 -yl, 6-fluoro-1, 8-naphthyridin-2-yl, 6-bromo-1, 8-naphthyridin-2-yl, 6-ethynyl-1, 8-naphthyridin-2-yl, 7-chloro-1 , 8-naphthyridin-2-yl, 7-fluoro-1, 8-naphthyridin-2-yl, 7-bromo-1, 8-naphthyridin-2-yl, 7-ethynyl-1, 8-naphthyridin- 2-yl, 6-chloro-l, 8-naphthyridin-3-yl, 6-fluoro-l, 8-naphthyridin-3-yl, 6-bromo-l, 8-naphthyridin-3-yl, 6 -etinyl-1, 8-naphthyridin-3-yl, 7-chloro-1, 8-naphthyridin-3-yl, 7-fluoro-1, 8-naphthyridin-3-yl, 7-bromo-1,8-naphthyridine -3-yl, 7-ethynyl-1, 8-naphthyridin-3-yl, 6-chloro-2,5-naphthyridin-3-yl, 6-fluoro-2,5-naphthyridin-3-yl, 6-bromine -2,5-naphthyridin-3-yl, 6-ethynyl-2,5-naphthyridin-3-yl, 7-chloro-2,5-naphthyridin-3-yl, 7-fluoro-2,5-naphthyridin-3 -yl, 7-bromo-2,5-naphthyridin-3-yl, 7-ethynyl-2,5-naphthyridin-3-yl, 7-chloro-2,6-naphthyridin-3-yl, 7 -fluoro-2,6-naphthyridin-3-yl, 7-bromo-2,6-naphthyridin-3-yl, 7-ethynyl-2,6-naphthyridin-3-yl, 6-chloro-2, 8-naphthyridin-3-yl, 6-fluoro-2,8-naphthyridin-3-yl, 6-bromo-2,8-naphthyridin-3-yl, 6-ethynyl-2,8-naphthyridin-3-yl , 7-chloro-2,8-naphthyridin-3-yl, 7-fluoro-2,8-naphthyridin-3-yl, 7-bromo-2,8-naphthyridin-3-yl and 7-ethynyl-2,8 -naphyridin-3-yl.

Particular preferred examples of the group include 7-chloro-2,5-naphthyridin-3-yl, 7-fluoro-2,5-naphthyridin-3-yl, 7-bromo-2,5-naphthyridin-3-yl and 7-ethynyl-2,5-naphthyridin-3-yl. In addition to the above 12 groups (a) to (I), a thienopyrrolyl group that can be substituted is also preferred. The thienopyrrolyl group may have from 1 to 3 substituents, and examples of the substituent (s) include hydroxyl, nitro, amino, cyano, a halogen atom, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl , carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl, N, N-dialkylcarbamoyl, alkoxycarbonyl, amidino and alkoxycarbonylalkyl. Among them, cyano, a halogen atom, alkyl, alkenyl, alkynyl and haloalkyl are preferred. Specifically, preferred examples include 2-chlorothieno [2,3-bJpyrrol-5-yl, 2-fluorothieno [2,3-bJpirrol-5-yl, 2-bromothieno [2,3-b] pyrrole-5-yl] and 2-ethynylthieno [2,3-b-pyrrol-5-yl. The following group will be described in detail below: [where Q1, R3, and R4 have the same meanings as already described, and 1 and 2 denote positionsj. The portion having a cyclic structure containing the above Q1 group is a divalent hydrocarbon cyclic group of 3 to 10 elements which may have a double bond, or a divalent heterocyclic group of 5 to 12 elements having 2 heteroatoms. The preferred portion is a divalent hydrocarbon cyclic group of 3 to 8 elements or a divalent heterocyclic group of 5 to 8 elements, more preferably a divalent hydrocarbon cyclic group of 5 to 7 elements or a divalent heterocyclic group of 5 to 7 elements. Of these, a group is preferred in which Q represents a C3-C6 alkylene group or a group (CH2) m -CH2-A-CH2- (CH2) p- (wherein each of m and n is independently 0 or 1, and A has the same meaning as already described). In particular, a group in which Q 1 represents an alkylene group of C 4 is preferred. The cyclic or heterocyclic hydrocarbon group can have a cis formation or a trans formation with respect to the 1-position and the 2-position. In the case of a 5-membered ring, a trans-formation is preferred. In the case of a ring of 6 or 7 elements, both cis and trans formations are preferred. The above substituents R3 and R4 will be described in detail below. The halogen atom is a fluorine atom, chlorine atom, bromine atom or iodine atom. Examples of the alkyl group include a linear, branched or cyclic C- [alpha] -C6 alkyl (for example, methyl, cyclopropyl, isobutyl), examples of the haloalkyl group include a group corresponding to the above alkyl group which has been substituted by 1 to 3 halogen atoms (for example, chloromethyl, 1-bromoethyl, trifluoromethyl). Examples of the cyanoalkyl group include a group corresponding to the above C 1 -C 6 alkyl group which has been replaced by a single cyano group (for example, cyanomethyl, 1-cyanoethyl). Examples of the alkenyl group include a linear or branched C2-C6 alkenyl group having a single double bond (eg, vinyl, allyl). Examples of the alkynyl group include a linear or branched C2-C6 alkynyl group having a single triple bond (e.g., ethynyl, propynyl). Examples of the acyl group include an alkanoyl group of Cr Cβ (for example, formyl, acetyl), an aroyl group of C -C-? 5 (for example, benzoyl, naphthoyl), and an arylalkanoyl group corresponding to the alkanoyl group of CrCβ previous one that has been replaced by one of the aryl groups of C6-C? mentioned above (for example, phenacetyl). Examples of the acylalkyl group include a group corresponding to the above C6-C6 alkyl group which has been replaced by one of the aforementioned acyl groups (e.g., acetylmethyl). Examples of the alkoxy group include a linear, branched or cyclic C 1 -C 6 alkoxy group (e.g., methoxy, cyclopropoxy, isopropoxy). Examples of the alkoxyalkyl groups include a group corresponding to the above C6 alkyl group which has been replaced by one of the aforementioned C6-C6 alkoxy groups (e.g., methoxymethyl, ethoxymethyl). Examples of hydroxyalkyl groups include a group corresponding to the above C-C alkyl group which has been replaced by a simple hydroxyl group (e.g., hydroxymethyl, 1- hydroxyethyl). Examples of the carboxyalkyl groups include a group corresponding to the above C-Cß alkyl group which has been replaced by a single carboxyl group (eg, carboxymethyl, 1-carboxyethyl). Examples of the alkoxycarbonyl group include a group formed from the above C 1 -C 6 alkoxy groups and a carbonyl group (e.g., methoxycarbonyl, ethoxycarbonyl). Examples of the alkoxycarbonylalkyl group include a group corresponding to the above C-GCT alkyl group which has been replaced by one of the aforementioned alkoxycarbonyl groups (for example, methoxycarbonylethyl, ethoxycarbonylethyl). Examples of the carbamoylalkyl group include a group corresponding to the above C6 alkyl group which has been replaced by a carbamoyl group (eg, carbamoylmethyl, carbamoylethyl). The heterocyclic group of 3 to 6 elements which may have a substituent is a saturated or unsaturated heterocyclic group of 3 to 6 elements which may have from 1 to 3 heteroatoms (for example, nitrogen atom, oxygen atom, sulfur atom) , and the heterocyclic group may have a substituent, such as hydroxy, a halogen atom, amino, C6 alkyl, oxo or haloalkyl. Examples of the 3 to 6-membered heterocyclic group include pyrrolyl, thienyl, pyrazolyl, imidazolyl, pyrazolinyl, oxazolyl, oxazolnyl, oxadiazolyl, oxazolidinyl, thiazolyl, thiazolinyl, thiadiazolyl, furazanyl, pyranyl, pyridyl, pyrimidyl, pyridazinyl, pyrrolidinyl, piperazinyl, piperidinyl, oxazinyl, oxadiazinyl, morpholinyl, thiazinyl, thiadiazinyl, thiomorpholinyl, tetrazolyl, triazolyl and triazinyl. Specific examples of the 3 to 6 element heterocyclic group which may have a substituent include thiazolyl, 4,5-dihydrothiazolyl, oxazolyl, 4,5-dihydroxazolyl, 5-methyloxazolyl, imidazolyl, pyrrolidinyl, 3-hydroxypyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, 1, 1-dioxothiomorpholinyl, tetrahydropyranyl, pyridyl, 1,4-oxadiazolyl, 3-methyl-1, 2,4-oxadiazolyl, 5-methyl-1, 2,4-oxadiazolyl, 1, 3,4- oxadiazolyl, 5-methyl-1, 3,4-oxadiazolyl, 5- (trifluoromethyl) -1, 3,4-oxadiazolyl, 1,3-oxazolyl, 1,4-thiadiazolyl, 5-methyl-1,3, 4-thiadiazolyl and 1,3-oxazolidinyl. Examples of the 3 to 6-membered heterocyclic alkyl group which may have a substituent include a group corresponding to the above 3-6 membered heterocyclic group which may have a substituent, wherein said group has been replaced by a single alkyl group (e.g. , thiazolylmethyl, 4,5-dihydrothiazolymethyl, morpholinylmethyl, 1,1-dioxothiomorpholinylmethyl). Examples of the aryl group include C6-C14 aryl groups, such as phenyl and naphthyl, and the aryl group can be substituted by one to three groups selected from the above alkyl group of CrC6, the alkanoyl of C-? - C6 above, hydroxyl , nitro, cyano, halogen atoms, the above C2-C6 alkenyl, the C2-C6 alkynyl above, the halogenalkyl of C6 above, the C6 alkoxy above, carboxy, carbamoyl, the C6 alkoxycarbonyl above, and other groups. Examples of the aralkyl group include a group corresponding to the above d-Cß alkyl group which has been substituted by one of the C6-C14 aryl groups (for example, benzyl, phenethyl). It should be noted that, in the above description, no particular limitation is imposed as to the position of the substitution. Examples of the acylamino group which may have a substituent include a group corresponding to the acyl of C C6 above which has been replaced by an amino group (eg, formylamino and acetylamino) and also include an acyl group which has been replaced by a single group or a plurality of groups, such as halogen atoms, hydroxyl, C-C-alkoxy, amino, C-C6-N-alkylamino, N, N-di-alkylamino of CrC6, carboxyl and C2-C6 alkoxycarbonyl (e.g., 2-methoxyacetylamino, 3-aminopropionylamino). Examples of the acylaminoalkyl group include a group corresponding to the acylamino group of CrC6 above which has been replaced by the above alkyl group of CrC6 (for example, formylaminomethyl and acetylaminomethyl). Examples of the aminoalkyl group include a group corresponding to the above C-pCß alkyl which has been replaced by a single amino group (for example, aminomethyl and 1-aminoethyl). Examples of the N-alkylaminoalkyl group include a group corresponding to an amino- (C-? -C6 alkyl) group which has been replaced by a single C6 alkyl group at the nitrogen atom of the amino-C6 alkyl group (for example, N-methylaminomethyl, N-methylaminoethyl). Examples of the N, N-dialkylaminoalkyl group include a group corresponding to an amino- (Ci-Cß alkyl) group which has been replaced by two alkyl groups of CrC6 at the nitrogen atom of the N, N-diakylaminoalkyl group (e.g. , N, N-dlmethylaminomethyl and N-ethyl-N-methylaminoethyl). Examples of the N-alkenylcarbamoyl group include a group corresponding to a carbamoyl group which has been replaced by a linear or branched C2-C6 alkenyl group (eg, allylcarbamoyl). Examples of the N-alkenylcarbamoylalkyl group include a group corresponding to an alkyl group of C-i-Cβ which has been replaced by the group N- (C2-C6 alkenyl) carbamoyl above (for example, allylcarbamoylethyl). Examples of the N-alkenyl-N-alkylcarbamoyl group include a group corresponding to the group N- (C2-C6 alkenyl) carbamoyl which has been replaced by a linear or branched C6 alkyl group at the nitrogen atom of the N- group alkenyl-N-alkylcarbamoyl (for example, N-allyl-N-methylcarbamoyl). Examples of the N-alkenyl-N-alkylcarbamoylalkyl group include a group corresponding to the group N- (C2-C6 alkenyl) carbamoylalkyl above which has been replaced by a linear or branched d-C6 alkyl group on the nitrogen atom of the group N-alkenyl-N-alkylcarbamoylalkyl (for example, N-allyl-N-methylcarbamoylmethyl). Examples of the N-alkoxycarbamoyl group include a group corresponding to a carbamoyl group which has been replaced by a linear or branched C-α-C6 alkoxy group (e.g., methoxycarbamoyl). Examples of the N-alkoxycarbamoylalkyl include a group corresponding to a linear or branched C 1 -C 2 alkyl group which has been replaced by the group N- (C 6 alkoxy) carbamoyl above (for example, methoxycarbamoylmethyl). Examples of the N-alkyl-N-alkoxycarbamoyl group include a group corresponding to a carbamoyl group which has been substituted by linear or branched C-GCT alkoxy groups and alkyl of CrC6 (for example, N-ethyl-N-methoxycarbamoyl). Examples of the N-alkyl-N-alkoxycarbamoylalkyl group include a group corresponding to a linear or branched C6-C6 alkyl group which has been replaced by the group N- (CrC6 alkyl) -N- (CrC6 alkoxy) previous carbamoyl (e.g., N-ethyl-N-methoxycarbamoylmethyl). Examples of the carbazoyl group which can be substituted by 1 to 3 alkyl groups, a carbazoyl group and a group corresponding to a carbazoyl group which has been substituted by 1 to 3 straight or branched CrC6 alkyl groups (for example, 1-methylcarbazoyl and 1,2-dimethylcarbazoyl). Examples of the alkylsulfonyl group include an alkylsulfonyl group of linear, branched or cyclic CrC6 (for example, methanesulfonyl). Examples of the alkylsulfonylalkyl group include a group corresponding to a linear or branched C 1 -C 2 alkyl group which has been replaced by the above C 1 -C 5 alkylsulphonyl group (for example, methanesulfonylmethyl). Examples of the alkoxyimino group include an alkoxyimino group of C -? - C6 (for example, methoxyimino and ethoxyimino). Examples of the alkoxycarbonylalkylamino group include a group corresponding to an amino group which has been replaced by one of the above alkoxycarbonylalkyl groups of d-Cß (e.g., methoxycarbonylmethylamino and ethoxycarbonylpropylamino). Examples of the carboxyalkylamino group include a group corresponding to an amino group which has been replaced by one of the above C 6 C carboxyl alkyl groups (for example, carboxymethylamino and carboxyethylamino). Examples of the alkoxycarbonylamino group include a group corresponding to an amino group which has been replaced by one of the above C6-C6 alkoxycarbonyl groups (for example, methoxycarbonylamino and tert-butoxycarbonylamino). Examples of the alkoxycarbonylaminoalkyl group include a group corresponding to the above alkyl group which has been replaced by one of the above CrC6 alkoxycarbonylamino groups (for example, methoxycarbonylaminomethyl and tert-butoxycarbonylaminoethyl). The N-alkylcarbamoyl group, which alkyl may or may not be substituted, is a carbamoyl group which has been replaced by a linear, branched or cyclic CrC6 alkyl group which may be substituted, for example, by hydroxyl, amino, N-alkylamino of CrC6, amidino, halogen atom, carboxyl, cyano, carbamoyl, CrC6 alkoxy, CrCß alkanoyl, CrC6 alkanoylamino, or C6-C6 alkylsulfonylamino. Examples include N-methylcarbamoyl, N-ethylcarbamoyl, N-isopropylcarbamoyl, N-cyclopropylcarbamoyl, N- (2-hydroxyethyl) carbamoyl, N- (2-fluoroethyl) carbamoyl, N- (2-cyanoethyl) carbamoyl, N- (2- methoxyethyl) carbamoyl, N-carboxymethylcarbamolyl, N- (2-aminoethyl) carbamoyl and N- (2-amidinoethyl) carbamoyl. The N, N-dialkylcarbamoyl group, which alkyl may or may not be substituted, is a carbamoyl group which has been replaced by two linear, branched or cyclic CrC6 alkyl groups which may be substituted, for example, by hydroxy, amino , N-alkylamino of C -? - C6, amidino, halogen atom, carboxyl, cyano, carbamoyl, CrC6 alkoxy, CrC6 alkanoyl, CrC6 alkanoylamino and C? -C6 alkylsulfonylamino. Examples include N, N-dimethylcarbamoyl, N, N-diethylcarbamoyl, N-ethyl-N-methylcarbamoyl, N-isopropyl-N-methylcarbamoyl, N- (2-hydroxyethyl) -N-methylcarbamoyl, N, N-bis (2- hydroxyethyl) carbamoyl, N, N-bis (2-fluoroethyl) carbamoyl, N- (2-cyanoethyl) -N-methylcarbamoyl, N- (2-methoxyethyl) -N-methylcarbamoyl, N-carboxymethyl-N-methylcarbamoyl and N, N-bis (2-aminoethyl) carbamoyl. Examples of the N-alkylcarbamoylalkyl group, which alkyl may or may not be substituted, include a group corresponding to a linear or branched CrC6 alkyl group which has been replaced by the above N-alkylcarbamoyl group, which C6-C6 alkyl may or can not be substituted (for example, N-methylcarbamoylmethyl and N- (2-hydroxyethyl) carbamoylmethyl). Examples of the N, N-dialkylcarbamoylalkyl group, which alkyl may or may not be substituted, include a group corresponding to a linear or branched CrC 6 alkyl group which has been replaced by the above NN-dialkylcarbamoyl group, whose CrCß alkyl can or it can not be substituted (for example, N, N-dimethylcarbamoylmethyl and N- (2-hydroxyethyl) -N-methylcarbamoylmethyl). Examples of the 3 to 6-membered heterocyclic carbonyl group, which may have a substituent, include a group formed from a carbonyl group and the above 3-6 membered heterocyclic group which may have a substituent (eg, aziridinylcarbonyl, azetidinylcarbonyl, 3- hydroxyazetidylcarbonyl, 3-methoxyazetidylcarbonyl, pyrrolidinylcarbonyl, 3-hydroxypyrrolidinylcarbonyl, 3-fluoropyrrolidinylcarbonyl, piperidylcarbonyl, piperazinylcarbonyl, morpholinylcarbonyl, thiomorpholinylcarbonyl, 1,1-dioxothiomorpholinylcarbonyl, tetrahydropyranylcarbonyl, pyridylcarbonyl, furoyl, and thiophenecarbonyl). Examples of the 3 to 6-member heterocyclic carbonyl alkyl group, which may have a substituent, include a group corresponding to the above CrC 6 alkyl group which has been replaced by one of the heterocyclic carbonyl groups of 3 to 6 above elements, which may have a substituent (for example, azetidinylcarbonylmethyl and pyrrolidinylcarbonylethyl). Examples of the heterocyclic carbonyloxyalkyl group of 3 to 6 elements, which may have a substituent, include a group corresponding to the above d-Cß alkyl group which has been replaced by one of the 3 to 6-member heterocyclic carbonyloxy groups, formed of an oxygen atom and the heterocyclic carbonyl group of 3 to 6 elements above, which may have a substituent (eg, piperidinylcarbonyloxyethyl and morpholinylcarbonyloxymethyl). Examples of the carbamoyloxyalkyl group include a group corresponding to the above CrC6 alkyl group which has been replaced by one of the carbamoyloxy groups of a carbamoyl group and an oxygen atom (for example, carbamoyloxymethyl and carbamoyloxyethyl). Examples of the N-alkylcarbamoyloxyalkyl group include a group corresponding to the above C-Cß alkyl group which has been replaced by one of the N-alkylcarbamoyloxy groups formed from an oxygen atom and the above N-alkylcarbamoyl group, whose d-Cß alkyl it may or may not be substituted (for example, N-methylcarbamoyloxymethyl and N-methylcarbamoyloxyethyl). Examples of the N, N-dialkylcarbamoyloxyalkyl group include a group corresponding to the above CrCß alkyl group which has been replaced by one of the N, N-dialkylcarbamoyloxy groups formed of an oxygen atom and the above N, N-dialkylcarbamoyl group, which CrCß alkyl may or may not be substituted (for example, N, N-dimethylcarbamoyloxymethyl and N-ethyl-N-methylcarbamoyloxyethyl). Examples of the alkylsulfonylamino group include a group corresponding to an amino group which has been replaced by one of the above alkylsulfonyl groups having an alkyl group of CrC6 (for example, methylsulfonylamino and isopropylsulfonylamino). Examples of the arylsulfonylamino group include a group corresponding to an amino group which has been replaced by one of the above arylsulfonyl groups having an aryl group (for example, phenylsulfonylamino and naphthylsulfonylamino). Examples of the alkylsulfonylaminoalkyl group include a group corresponding to the above CrC6 alkyl group which has been replaced by one of the above alkylsulfonylamino groups of CrC6 (for example, methylisulfonylaminomethyl and methylsulfonylaminoethyl). Examples of the arylsulfonylaminoalkyl group include a group corresponding to the above C C_ alkyl group which has been replaced by one of the above arylsulfonylamino groups (for example, phenylsulfonylaminomethyl and naphthylsulfonylaminoethyl). Examples of the alkylsulfonylaminocarbonyl group include a group formed from the above alkylsulfonylamino group of CrC6 and a carbonyl group (for example, methylsulfonylaminocarbonyl and isopropylsulfonylaminocarbonyl). Examples of the arylsulfonylaminocarbonyl group include a group formed from the above arylsulfonylamino group and a carbonyl group (for example, phenylsulfonylaminocarbonyl and naphthylsulfonylaminecarbonyl). Examples of the alkylsulfonylaminocarbonylalkyl group include a group corresponding to the CrC6 alkyl group which has been replaced by the above alkyl CrC6 alkylsulphonylaminocarbonyl group (for example, methylsulfonylaminocarbonylmethyl and isopropylsulfonylaminocarbonylmethyl). Examples of the arylsulfonylaminocarbonylalkyl group include a group corresponding to the above CrCß alkyl group which has been replaced by the above arylsulfonylaminocarbonyl group (for example, phenylsulfonylaminocarbonylmethyl and naphthylsulfonylaminocarbonylmethyl). Examples of the alkoxycarbonylalkyloxy group include a group corresponding to the above CrCß alkoxy group which has been replaced by the above alkoxycarbonyl group (for example, methoxycarbonylmethyloxy). The acyloxy group is a group formed from the above acyl group and an oxygen atom (for example, formyloxy and acetyloxy). Examples of the acyloxyalkyl group include a group corresponding to the above d-Cß alkyl group which has been replaced by the above acyloxy group (for example, for -loxymethyl and acetyloxymethyl). Examples of the aralkyloxy group include a group corresponding to the above CrCß alkoxy group which has been replaced by the above aryl group (e.g., benzyloxy and naphthylmethoxy). Examples of the carboxyalkyloxy group include a group corresponding to the above alkoxy group which has been replaced by a carboxyl group (for example, carboxymethoxy and carboxyethoxy).

Examples of the arylsulfonyl group include a C 6 -C 4 arylsulfonyl group (for example, phenylsulfonyl and naphthylsulfonyl). Examples of the alkoxycarbonylalkyl-sulfonyl group include a group formed from the alkoxycarbonylalkyl group of CrC6 above and a sulfonyl group (for example, methoxycarbonylethylsulfonyl and ethoxycarbonylethylsulfonyl). Examples of the carboxyalkylsulfonyl group include a group formed from the above carboxyalkyl group and a sulfonyl group (for example, carboxymethylsulfonyl and carboxyethylsulfonyl). Examples of the alkoxycarbonylacyl group include a group formed from the above alkoxycarbonylalkyl group and a carbonyl group (e.g., methoxycarbonylmethylcarbonyl and ethoxycarbonylmethylcarbonyl). Examples of the alkoxyalkyloxycarbonyl group include a group corresponding to the above alkoxycarbonyl group which has been replaced by one of the alkoxy groups of C C6 above (e.g., methoxymethyloxycarbonyl and methoxyethyl-oxycarbonyl).

Examples of the hydroxyacyl group include a group corresponding to the above acyl group (including CrCß and aroyl alkanoyl) which has been replaced by a hydroxyl group (eg, glycolyl, lactoyl and benzyloyl). Examples of the alkoxyacyl group include a group corresponding to the above acyl group which has been replaced by one of the above CrC 6 alkoxy groups (for example, methoxyacetyl and ethoxyacetyl). Examples of the halogenoacyl group include a group formed from the above halogenoalkyl group and a carbonyl group (for example, chloromethylcarbonyl and trifluoromethylcarbonyl). Examples of the carboxyalkyl group include a group corresponding to the above acyl group which has been replaced by a carboxyl group (for example, carboxyacetyl and 2-carboxypropionyl). Examples of the aminoacyl group include a group corresponding to the above acyl group (including C6 alkanoyl and aroyl) which has been replaced by an amino group (for example, aminomethylcarbonyl and 1-aminoethylcarbonyl). Examples of the acyloxyacyl group include a group formed from the above acyloxyalkyl group and a carbonyl group (for example, formyloxymethylcarbonyl and acetyloxymethylcarbonyl). Examples of the acyloxyalkylsulfonyl group include a group formed from the above acyloxyalkyl group and a sulfonyl group (for example, formyloxymethylsulfonyl and acetyloxymethylsulfonyl). Examples of the hydroxyalkylsulfonyl group include a group formed from the hydroxyalkyl group of C Cß above and a sulfonyl group (e.g., hydroxymethylsulfonyl and 1-hydroxyethylsulfonyl). Examples of the alkoxyalkylsulfonyl group include a group formed from the above C 6 C alkoxyalkyl group and a sulfonyl group (e.g., methoxymethylsulfonyl and ethoxyethylsulfonyl). Examples of the 3 to 6-member heterocyclic sulfonyl group that may have a substituent include a group consisting of a sulfonyl group and the above 3-6 membered heterocyclic ring which may have a substituent (eg, aziridinylsulfonyl, azetidinylsulfonyl, pyrrolidinylsulfonyl, piperidylsulfonyl, piperazinylsulfonyl, morpholinylsulfonyl, and tetrahydropyranylsulfonyl). Examples of the 3-6 membered heterocyclic oxy group that may have a substituent include a group formed from an oxygen atom and the above 3-6 membered heterocyclic ring which may have a substituent (eg, tetrahydrofuranyloxy). Examples of the N-alkylaminoacyl include a group corresponding to the aminoacyl group, whose nitrogen atom has been replaced by one of the above CrC6 alkyl groups (for example, N-methylaminoacetyl and N-ethylaminoacetyl). Examples of N, N-dialkylaminoacyl include a group corresponding to the above aminoacyl group, whose nitrogen atom has been replaced by two alkyl groups of CrC6 (for example, N, N-dimethylaminoacetyl and N-ethyl-N-methylaminoacetyl). Examples of the N, N-diacylcarbamoylacyl group, which alkyl groups may or may not be substituted, include a group corresponding to the acyl group which has been replaced by the N group, N-dialkylcarbamoyl above, whose CrCß alkyl groups may or may not be substituted (for example, N-dimethylcarbamoylacetyl, N, N-diethylcarbamoylacetyl and N-ethyl-N-methylcarbamoylacetyl). Examples of the N, N-dialkylcarbamoylallylsulfonyl group, which alkyl groups may or may not be substituted include a group consisting of a sulfonyl group and the above N, N-dialkylcarbamoyl group, whose CrCß alkyl groups may or may not be substituted (e.g. , N, N-dimethylcarbamoylmethylsulfonyl and N- (2-hydroxyethyl) -N-methylcarbamoylmethylsulfonyl). Examples of the alkylsulfonylacyl group include a group corresponding to an acyl group which has been replaced by one of the above alkylsulfonyl groups having an alkyl group of CrC6 (for example, methylsulfonylacetyl and isopropylsulfonylacetyl). Examples of the N-arylcarbamoyl group include a group corresponding to a carbamoyl group which has been replaced by the above aryl group (e.g., phenylcarbamoyl and naphthylcarbamoyl). Examples of the carbamoyl group N- (3- to 6-membered heterocyclic) include a group corresponding to a carbamoyl group which has been replaced by the above 3-6 membered heterocyclic group which may have a substituent (eg, pyridylcarbamoyl and thienylcarbamoyl) . Examples of the N-alkyl-N-arylcarbamoyl group include a group corresponding to the above N-arylcarbamoyl group, whose nitrogen atom has been replaced by a linear or branched CrC6 alkyl group (eg, N-methyl-N-phenylcarbamoyl) . Examples of the carbamoyl group N-alkyl-N- (heterocyclic of 3 to 6 elements) include a group corresponding to the carbamoyl group N- (heterocyclic of 3 to 6 elements) above whose nitrogen atom has been replaced by an alkyl group of C C6 linear or branched (for example, N-methyl-N-thienylcarbamoyl). Examples of the N-arylcarbamoylalkyl group include a group corresponding to a linear or branched d-Cβ alkyl group which has been replaced by the above N-arylcarbamoyl group (e.g., phenylcarbamoylmethyl). Examples of the N-heterocyclic carbamoylalkyl group of 3 to 6 elements include a group corresponding to a linear or branched CrCß alkyl group which has been replaced by the carbamoyl group N- (3 to 6-membered heterocyclic) above (eg, pyridylcarbamoylmethyl) . Examples of the N-alkyl-N-arylcarbamoylalkyl group include a group corresponding to the above N-arylcarbamoylalkyl group, whose nitrogen atom has been replaced by a linear or branched CrC6 alkyl group (eg, N-methyl-N-phenylcarbamoylmethyl) . Examples of the carbamoylalkyl group N-alkyl-N- (3 to 6-membered heterocyclic) include a group corresponding to the above carbamoylalkyl group N- (heterocyclic of 3 to 6 elements) whose nitrogen atom has been replaced by an alkyl group of CrCβ linear or branched (for example, N-methyl-N-thienylcarbamoylmethyl). The aminocarbothioyl group is the group represented by -C (= S) -NH 2. The N-alkylaminocarbothioyl group is an aminothiocarbonyl group which has been replaced by one of the above alkyl groups, such as (methylamino) carbothioyl or (ethylamino) carbothioyl. The N, N-dialkylaminocarbothioyl group is an aminothiocarbonyl group which has been replaced by two of the above alkyl groups, such as (dimethylamino) carbothioyl, or (diethylamino) carbothioyl, (ethylmethylamino) carbothioyl. Examples of the alkylthioalkyl group include a group corresponding to a linear, branched or cyclic d-C6 alkylthio group which has been replaced by a linear, branched or cyclic d-C6 alkyl group (for example, methylthiomethyl and 1-methylthioethyl). Examples of the N-acyl-N-alkylaminoalkyl group include a group corresponding to an amino-alkyl group of CrC6, whose nitrogen atom has been replaced by an alkyl group of CrC6 (for example, N-acetyl-N-methylaminomethyl). Examples of the alkoxyalkyl (thiocarbonyl) group is a group formed from the above alkoxyalkyl group and a thiocarbonyl group, such as 2-ethoxyethanothioyl. The alkylene group is a linear or branched C1-C5 alkylene group, such as methylene, ethylene or propylene. The alkenylene group is a C2-C5 alkenylene group having a double bond, such as vinylene or propenylene. Examples of the alkylenedioxy group include C 1 -C 5 alkylenedioxy groups, such as methylenedioxy, ethylenedioxy and propylenedioxy. The carbonildioxy group is the group represented by -0-C (= 0) -0-. It should be noted that, in the foregoing description, no particular limitation is imposed as to the position of the substitution. Among these substituents represented by R 3 or R 4, there are preferred, for example, hydrogen atom, hydroxyl, alkyl, alkenyl, alkynyl, halogen atom, haloalkyl, amino, hydroxyimino, alkoxyimino, aminoalkyl, N-alkylaminoalkyl, N, N-dialkylaminoalkyl acyl, acylalkyl, acylamino which may have a substituent, acylaminoalkyl, alkoxy, alkoxyalkyl, hydroxyalkyl, carboxyl, carboxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkoxycarbonylamino, alkoxycarbonylaminoalkyl, carbamoyl, N-alkylcarbamoyl groups whose alkyl group may or may not be substituted, N groups , N-dialkylcarbamoyl whose alkyl groups may or may not be substituted, N-alkenylcarbamoyl, N-alkenylcarbamoylalkyl, N-alkenyl-N-alkylcarbamoyl, N-alkenyl-N-alkylcarbamoylalkyl, N-alkoxycarbamoyl, N-alkyl-N-alkoxycarbamoyl, N-alkoxycarbamoylalkyl, N-alkyl-N-alkoxycarbamoylalkyl, carbazoyl groups which can be substituted by 1 to 3 alkyl groups, alkylsulfon ilo, alkylsulfonylalkyl, heterocyclic carbonyl groups of 3 to 6 elements which may have a substituent, heterocyclic carbonyloxyalkyl groups of 3 to 6 elements which may have a substituent, heterocyclic groups of 3 to 6 elements which may have a substituent, carbamoylalkyl, carbamoyloxyalkyl, N -alkylcarbamoyloxyalkyl, N, N-dialkylcarbamoyloxyalkyl, N-alkylcarbamoylalkyl groups whose alkyl group may or may not be substituted, N, N-dialkylcarbamoylalkyl groups whose alkyl group may or may not be substituted, alkylsulfonylamino, alkylsulfonylaminoalkyl, oxo, acyloxy, acyloxyalkyl, aryisulfonyl , alcoxicarbonilalquilsulfonilo, carboxialquilsulfonilo, alcoxicarbonilacilo, carboxyacyl, alcoxialquiloxicarbonilo, halogenoacilo, N, N-dialkylaminoacyl, acyloxyacyl, hydroxyacyl, alkoxyacyl, alcoxialquilsulfonilo, N, N- dialquilcarbamoilacilo, N, N-dialquilcarbamoilalquilsulfonilo, alquilsulfonilacilo, aminocarbotioilo, N-alquilaminocarbotioi N, N-dialkylcarbonyloxy, and alkoxyalkyl (thiocarbonyl). Further preferred are alkylene, alkenylene, alkylenedioxy, carbonyldioxy and other groups which are formed by R3 and R4 together. The case in which R3 is a hydrogen atom is preferred, and R4 is any of the aforementioned substituents as preferred examples thereof. In this case, R 4 is more preferably a hydrogen atom, hydroxyl, alkyl, halogen atom, hydroxyimino, N-alkylaminoalkyl, N, N-dialkylaminoalkyl, acyl, acylamino groups which may have a substituent, acylaminoalkyl, alkoxy, alkoxyalkyl, hydroxyalkyl, carboxyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkoxycarbonylamino, carbamoyl, N-alkylcarbamoyl groups, which alkyl group may or may not be substituted, N, N-dialkylcarbamoyl groups whose alkyl group may or may not be substituted, N-alkenylcarbamoyl, N -alkenylcarbamoylalkyl, N-alkenyl-N-alkylcarbamoyl, N-alkenyl-N-alkylcarbamoylalkyl, N-alkoxycarbamoyl, N-alkyl-N-alkoxycarbamoyl, N-alkyl-N-alkoxycarbamoylalkyl, carbazoyl group which can be substituted by 1 to 3 groups alkyl, alkylsulfonyl, alkylsulfonylalkyl, heterocyclic carbonyl group of 3 to 6 elements which may have a substituent, heterocyclic carbonyloxyalkyl group of 3 to 6 elements which may have r a substituent, heterocyclic group of 3 to 6 elements that can have a substituent, Carbamoyl, N, N-dialquilcarbamoiloxialquilo group, N- alkylcarbamoylalkyl whose group can alkyl or may not be substituted, N, N-dialquilcarbamollalquilo whose alkyl group may or may not be substituted, alkylsulfonylamino, alkylsulfonylaminoalkyl, acyloxy, ariisulfonilo, alcoxicarbonilalquilsulfonilo I carboxialquilsulfonilo , alkoxycarbonylacyl, carboxyacyl, alkoxyalkyloxycarbonyl, halogenoacyl, N, N-dialkylaminoacyl, acyloxyacyl, hydroxyacyl, alkoxyacyl, alkoxyalkylsulfonyl, N, N-dialkylcarbamoylacyl, N, N-dialkylcarbamoalkyl sulfonyl, alkylsulfonylacyl, aminocarbothioyl, N-alkylaminocarbothioyl, N, N -dialkylaminocarbothioyl and alkoxyalkyl (thiocarbonyl), among others. Among these groups, as R 4, a hydrogen, hydroxyl, alkyl, N, N-dialkylaminoalkyl, acylamino group that may have a substituent, acylaminoalkyl, alkoxy, alkoxyalkyl, hydroxyalkyl, alkoxycarbonyl, alkoxycarbonylamino, carbamoyl, N-alkylcarbamoyl is more preferred. whose alkyl group may or may not be substituted, N, N-dialkylcarbamoyl whose alkyl group may or may not be substituted, N-alkenylcarbamoyl, N-alkenylcarbamoylalkyl, N-alkenyl-N-alkylcarbamoyl, N-alkenyl-N-alkylcarbamoylalkyl, N -alkyl-N-alkoxycarbamoyl, carbazoyl which can be substituted by 1 to 3 alkyl, alkylsulfonyl, alkylsulfonylalkyl, heterocyclic carbonyl groups of 3 to 6 elements which may have a substituent, heterocyclic group of 3 to 6 elements which may have a substituent, N, N-dialkylcarbamoyloxyalkyl, N-alkylcarbamoylalkyl whose alkyl group may or may not be substituted, N, N-dialkylcarbamoylalkyl whose alkyl group may or may not be substituted, alkylsulfonylamino, alkylsulfonylaminoalkyl, acyloxy, acyl, alcoxialquiloxicarbonilo, halogenoacilo, N, N-dialkylaminoacyl, hydroxyacyl, alkoxyacyl, aminocarbotioilo, N-alquilaminocarbotioilo, N, N- dialquilaminocarbotioilo, and alkoxyalkyl (thiocarbonyl), among others. Preferred examples of the substituent of R3 or R4 include a hydrogen, hydroxyl, methyl, ethyl, isopropyl, N, N-dimethylaminomethyl, N, N-dimethylaminoethyl, N, N-diethylaminomethyl, acetylamino, methoxyacetylamino, acetylaminomethyl, acetylaminoethyl, methoxy, ethoxy, methoxymethyl, methoxyethyl, hydroxymethyl, 2-hydroxyethyl, 1-hydroxy-1-methylethyl, methoxycarbonyl, ethoxycarbonyl, methoxycarbonylamino, ethoxycarbonylamino, N-alilcarbamoilo, N-alilcarbamoilmetilo, N-allyl-N-methylcarbamoyl, N-allyl-N- methylcarbamoylmethyl, N-methoxy-N-methylcarbamoyl, N, N-dimetilcarbazoilo, N, N, N'-trimetilcarbazoilo, methanesulfonyl, methanesulfonylmethyl, etanosulfonilmetilo, N-methylcarbamoyl, N-ethylcarbamoyl, N-propylcarbamoyl, N-isopropylcarbamoyl, N-tert -butylcarbamoyl, N-cyclopropylcarbamoyl, N-cyclopropylmethylcarbamoyl, N- (1-ethoxycarbonylcyclopropyl) carbamoyl, N- (2-hydroxyethyl) carbamoyl, N- (2-fluoroethyl) carbamoyl, N- (2-methoxyethyl) ) carbamoyl, N- (carboxymethyl) carbamoyl, N- (2-aminoethyl) ca rbamoyl, N- (2-amidinoethyl) carbamoyl, N, N-dimethylcarbamoyl, N, N-diethylcarbamoyl, N-ethyl-N-methylcarbamoyl, N-isopropyl-N-methylcarbamoyl, N-methyl-N-propylcarbamoyl, N- ( 2-hydroxyethyl) -N-methylcarbamoyl, N- (2-fluoroethyl) -N-methylcarbamoyl, N, N-bis (2-hydroxyethyl) carbamoyl, N, N-bis (2-fluoroethyl) carbamoyl, N- (2- methoxyethyl) -N- methylcarbamoyl, N-carboxymethyl-N-methylcarbamoyl, N, N-bis (2-aminoethyl) carbamoyl, azetidinocarbonilo, 3-metoxiazetidinocarbonilo, 3- hidroxiazetidinocarbonilo, pyrrolidinocarbonyl, 3-hidroxipirrolidinocarbonilo, 3-fluoropirrolidinocarbonilo, 3.4 -dimetoxipirrolidinocarbonilo, piperidinocarbonyl, piperazinocarbonyl, morpholinocarbonyl, (tetrahydropyran-4-¡l) carbonyl, benzoyl, pyridylcarbonyl, thiazolyl, 4,5-dihydrothiazolyl, oxazolyl, 4,5-dihydroxazolyl, 5-methyloxazolyl, imidazolyl, pyrrolidinyl, 3-hydroxypyrrolidinyl , piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, 1,1-dioxothiomorpholinyl, tetrahydropyranyl, pyridyl, 1,4-oxadiazoyl, 3-methyl-1, 2,4-oxadiazolyl, 5-met.il-1, 2,4-oxadiazolyl, 1, 3,4-oxadiazolyl, 5-met¡l-1, 3,4-oxadiazolyl, 5 - (trifluoromethyl) -1, 3,4-oxadiazolyl, 1, 3-oxazolyl, 1, 3,4-thiadiazolyl, 5-methyl-1, 3,4-thiadiazolyl, 1,3-oxazolidinyl, N-methylcarbamoylmethyl, N -metilcarbamoiletilo, N-ethylcarbamoylmethyl, N- (2-fluoroethyl) carbamoylmethyl, N- (2-methoxyethyl) carbamoylmethyl, N, N-dimetilcarbamo¡lmetilo, N, N-dimetilcarbamoiletilo, N- (2-fluoroethyl) -N-methylcarbamoylmethyl , N- (2-methoxyethyl) -N-methylcarbamoylmethyl, N, N-dimetilcarbamoiloximetilo, 2- (N-ethyl-N-methylcarbamoyloxy) ethyl, methylsulfonylamino, etilsuífonilamino, metiisulfonilaminometilo, metilsulfonilaminoetilo, acetyl, propionyl, isobutylyl, 2-methoxyethoxycarbonyl, trifluoroacetyl, N, N-dimetilaminoacet¡lo, N-ethyl-N- methylaminoacetyl, hydroxyacetyl, 1, 1-dimethyl-2-hydroxyethylcarbonyl, methoxyacetyl, 1,1-dimethyl-2-metoxietilcarbon¡lo, aminocarbotioilo, (dimethylamino) carbotioilo and 2-methoxyethanothioyl. As described above, the case in which R3 represents a hydrogen atom is preferred, and R4 is any of the groups already mentioned as specific examples or a similar group. In particular, the N, N-dialkylcarbamoyl group which may have a substituent on the alkyl group thereof is preferred. Of these, N, N-dimethylcarbamoyl is preferred. However, R3 and R4 are not limited to the groups mentioned above as specific examples thereof.

Group T1 T1 represents carbonyl, sulfonyl, -C (= 0) -C (= 0) -N (R ') -, -C (= S) -C (= 0) -N (R') -, -C (= 0) -C (= S) -N (R ') -, -C (= S) -C (= S) -N (R') - (where R 'represents a hydrogen atom, hydroxyl, alkyl, or alkoxy), -C (= 0) -A1-N (R ") - (wherein A1 represents a C 1 -C 5 alkylene group which may have a substituent, R" represents a hydrogen, hydroxyl, alkyl atom or alkoxy), -C (= 0) -NH-, -C (= S) -NH-, -C (= 0) -NH-NH-, -C (= 0) -A2-C (= 0) - (wherein A2 represents a single bond or an alkylene group of C1-C5), -C (= 0) -A3-C (= 0) -NH- (where A3 represents an alkylene of C1-C5), - C (= 0) -C (= NORa) -N (Rb) -, -C (= S) -C (= NORa) -N (Rb) - (where Ra represents a hydrogen atom, alkyl or alkanoyl, Rb represents a hydrogen, hydroxyl, alkyl or alkoxy atom), -C (= 0) -N = N-, -C (= S) -N = N-, -C (= NORc) -C (= 0) - N (Rd) - (where Rc represents a hydrogen, alkyl, alkanoyl, aryl or aralkyl atom, Rd represents a hydrogen, hydroxyl, alkyl or alkoxy atom), -C (= NN (Re) (Rf)) -C (= 0) -N (R9) - (wherein Re and Rf each independently represents a hydrogen, alkyl, alkanoyl or alkyl (thiocarbonyl) atom, R9 represents a hydrogen, hydroxyl, alkyl or alkoxy atom), -C (= 0) -NH-C (= 0) -, -C (= S) -NH-C (= 0) -, -C (= 0) -NH-C (= S) -, -C (= S) - NHC (= S) -, -C (= 0) -NH-S02-, -S02-NH-, -C (= NCN) -NH-C (= 0) -, -C (= S) -C (= 0) -, or thiocarbonyl . In the above groups, the alkylene group of C1-C5 in A1, A2 or A3 is a linear, branched or cyclic C1-C5 alkylene group, such as methylene, ethylene, propylene, cyclopropylene or 1,3-cyclopentylene. In R ', R ", Ra, Rb, Rc, Rd, Re, Rf and R9, the alkyl group is a linear, branched or cyclic C1-C6 alkyl group, such as methyl or ethyl.The alkoxy group is a group linear, branched or cyclic C 1 -C 6 alkoxy, such as methoxy or ethoxy In Ra, Rc, Re, and Rf, the alkanoyl group is a group composed of a linear, branched or cyclic C 1 -C 6 alkyl and a carbonyl group , such as acetyl or propionyl In Rc, the aryl group is a C6-C14 aryl group, such as phenyl or naphthyl The aralkyl group is a group corresponding to a linear, branched or cyclic C1-C6 alkyl group it has been replaced by a C6-C14 aryl group, such as benzyl or phenethyl.

T1 is preferably carbonyl, -C (= 0) -C (= 0) -N (R ') -, -C (= S) -C (= 0) -N (R') -, -C (= 0) -C (= S) -N (R ') -, -C (= S) -C (= S) -N (R') -, or -C (= 0) -CH2-N (R ") ) -, particularly preferably carbonyl, -C (= 0) -C (= 0) -N (R ') -, -C (= S) -C (= 0) -N (R') -, -C (= 0) -C (= S) -N (R ') - or -C (= S) -C (= S) -N (R') -.

Groups R1 v R2 R1 and R2 each independently represent a hydrogen, hydroxyl, alkyl or alkoxy atom, preferably a hydrogen or alkyl atom, more preferably a hydrogen atom. In R1 and R2, the alkyl group is a linear, branched or cyclic C1-C6 alkyl group, such as methyl or ethyl. The alkoxy group is a linear, branched or cyclic C 1 -C 6 alkoxy group, such as methoxy or ethoxy. The case in which R1 and R2 each independently represents a hydrogen atom or an alkyl group is preferred, and the case where both are hydrogen atoms is more preferred. When T1 is a carbonyl group or a sulfonyl group, and Q1 is an alkylene group of C1-C8 or an alkenylene group of C2-C8, Q2 is preferably, among the 12 groups mentioned above, any of the groups (b) , (f), (g), (h), (i), (j), (k) and (I) (where, in group (f), N denotes that two of the carbon atoms that form the ring substituted by R 9 are replaced by nitrogen atoms). When T1 is a carbonyl group or a sulfonyl group, and Q is a C1-C8 alkylene group or a C2-C8 alkenylene group, the substituent (s) of the Q1-containing ring is preferably N-alkylcarbamoyl or N, N-dialkylcarbamoyl. When T1 is -C (= 0) -C (= 0) -N (R ') -, -C (= S) -C (= 0) -N (R') -, - C (= 0) - C (= S) -N (R ') - or -C (= S) -C (= S) -N (R') -, and Q1 is an alkylene group of C1-C8 or an alkenylene group of C2- C8, Q2 is preferably any of groups (i), (j) and (k), among the 12 groups mentioned above. When T1 is -C (= 0) -C (= 0) -N (R ') -, -C (= S) -C (= 0) -N (R ') -, - C (= 0) -C (= S) -N (R') - or -C (= S) -C ( = S) -N (R, and Q1 is an alkylene group of C1-C8 or an alkenylene group of C2-C8, the substituent of the ring containing Q1 is preferably N-alkylcarbamoyl or N, N-dialkylcarbamoyl. The compound represented by the formula (8) resides in the combination of T1 and Q2. In general, the compound (8) is divided into the following two types (I) and (II): (I) T1 represents carbonyl, sulfonyl, - C (= 0) -NH-C (= 0) -, -C (= S) -NH-C (= 0) -, -C (= 0) -NH-C (= S) -, -C ( = S) -NHC (= S) -, -C (= 0) -NH-S02-, -S02-NH-, -C (= NCN) -NH-C (= 0) -, -C (= S ) -C (= 0) - or thiocarbonyl, and the group containing Q1 is represented by the following formula: (wherein Q1 represents - (CH2) m-CH2-A-CH2- (CH2) n- (where m and n are each independently 0 or an integer from 1 to 3, and A represents an oxygen atom, nitrogen atom , sulfur atom, -SO-, -S02-, -NH-, - O-NH-, -NH-NH-, -S-NH-, -SO-NH-, or S02-NH-), and ( II) T1 represents -C (= 0) -C (= 0) -N (R ') -, -C (= S) -C (= 0) -N (R') -, - C (= 0) -C (= S) -N (R ') -, -C (= S) -C (= S) -N (R') - (where R 'represents a hydrogen, hydroxyl, alkyl or alkoxy atom) , -C (= 0) -A1-N (R ") - (wherein A1 represents a C1-C5 alkylene group which may have a substituent, R" represents a hydrogen, hydroxyl, alkyl or alkoxy atom), - C (= 0) -NH-, -C (= S) -NH-, -C (= 0) -NH-NH-, -C (= 0) -A2-C (= 0) - (where A2 represents a single bond or an alkylene group of C1-C5), -C (= 0) -A3-C (= 0) -NH- (where A3 represents a C1-C5 alkylene), -C (= 0) -C (= NORa) -N (Rb) -, -C (= S) -C (= NORa) -N (Rb) - (where Ra represents a hydrogen atom, alkyl or alkanoyl, Rb represents a hydrogen atom) hydrogen, hydroxyl, alkyl or lcoxy), -C (= 0) -N = N-, -C (= S) -N = N-, -C (= NORc) -C (= 0) -N (Rd) - (where Rc represents a hydrogen, alkyl, alkanoyl, aryl or aralkyl atom, Rd represents a hydrogen, hydroxyl, alkyl or alkoxy atom), -C (= NN (Re) (Rf)) -C (= 0) -N (R9) - (wherein Re and Rf each independently represents a hydrogen, alkyl, alkanoyl or alkyl (thiocarbonyl) atom, R9 represents a hydrogen, hydroxyl, alkyl or alkoxy atom), -C (= 0) -NH-C ( = 0) -, -C (= S) -NH-C (= 0) -, -C (= 0) -NH-C (= S) -, -C (= S) -NHC (= S) - , -C (= 0) -NH-S02-, -S02-NH-, -C (= NCN) -NH-C (= 0) -, -C (= S) -C (= 0) - or thiocarbonyl; and the group that contains Q1 is represented by the following formula: (wherein Q1 represents a C1-C8 alkylene, C2-C8 alkenylene or - (CH2) m-CH2-A-CH2- (CH2) n- (wherein m and n are each independently 0 or an integer of 1 to 3, and A represents an oxygen atom, nitrogen atom, sulfur atom, -SO-, -S02-, -NH-, -O-NH-, -NH-NH-, -S-NH-, -SO -NH- or S02-NH-) In points (I) and (II) above, for example, the following subsections (i) and (¡i) are preferred, respectively: (i) R1 and R2 each independently represents a hydrogen atom or an alkyl group, Q1 represents - (CH2) m-CH2-A-CH2- (CH2) n- (where m and n are each independently 0 or 1, and A has the same meaning as already described), Q2 is, among the 12 groups mentioned above, a group selected from the 9 groups (a) to (h), and (I), and T1 represents a carbonyl group or a sulfonyl group, and (ii) R1 and R2 each independently represents a hydrogen atom or an alkyl group, Q1 represents an alkylene group of C3-C6 or - (CH2) m-CH2- A-CH2- (CH2) n- (where m and n are each independently 0 or 1, and A has the same meaning as already described), Q2 is, among the 12 groups mentioned above, a selected group of the three groups (i), (j) and (k), and T1 represents -C (= 0) -C (= 0) - N (R ') -, -C (= S) -C (= 0) -N (R, -C (= 0) -C (= S) -N (R ') - or -C (= S) -C (= S) -N (R') -. The compound represented by the formula (8) can have stereochemical isomers and corresponding optical isomers based on asymmetric carbon atoms. The present invention encompasses any of the stereochemical isomers, the optical isomers and mixtures thereof. No particular limitation is imposed on the salt of the compound represented by the formula (8), as long as the salt is pharmaceutically acceptable. Examples of the salt include mineral acid salts, such as hydrochloride, hydrobromide, hydroiodide, phosphate, nitrate and sulfate, benzoate, organic sulfates, such as methanesulfonate, 2-hydroxyethanesulfonate, and p-toluenesulfonate, and organic carboxylates, such as acetate, salt of propanoic acid, oxalate, malonate, succinate, glutarate, adipate, tartrate, maleate, malate, citrate and mandelate. When the compound represented by the formula (8) has an acidic group, the compound can form a salt with an alkali metal ion or an alkaline earth metal ion. The compound represented by the formula (8) or its salt can form a solvate. No particular limitation is imposed on the solvate, as long as the solvate is pharmaceutically acceptable, and examples of the solvate include hydrates and solvates with ethanol. When the compound represented by the formula (8) includes a nitrogen atom, the compound can form an N-oxide.

The compound represented by the formula (8) is particularly preferably any of the following compounds, a salt thereof or similar compounds. 1) N - ((1 R *, 2S *) - 2- { [(5-chloroindol-2-yl) carbonyl] amino} cyclopropyl) -5-methyl-4,5,6, 7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide 2) N - ((1 R *, 2 S *) - 2-. {[[(5-chloroindol-2-yl) carbonyl] amino]. cyclobutyl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide 3) N - ((1 R *, 2R *) - 2-. { [(5-chloroindol-2-yl) carbonylJamino] cyclopentyl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cjpyridine-2-carboxamide 4) N - (( 1 R *, 2S *) - 2- { [(5-Chloroindol-2-yl) sulfonyl] amino} cyclohexyl) -5-methyl-4,5,6,7-tetrahydrothiazole [ 5,4-c] pyridine-2-carboxamide 5) N - ((1 R *, 2R *) - 2-. {[[(5-chloroindol-2-yl) carbonyl] amino.} Cyclohexyl) -5 -methyl-4,5,6,7-tetrahydrothioazo [5,4-c] pyridine-2-carboxamide 6) N - ((1 R *, 2S *) - 2- { [(5-chloroindole -2-yl) carbonyl] amino.}. Cyclohexyl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide 7) N-. { (1 R *, 2S *) - 2 - [(6-chloro-2-naphthoyl) amino-cyclohexyl} -5-methylene-4,5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide] carbonylJamino} cyclohexyl) -5-methyl-4,5,6,7-tetrahydrothiazole [514-c-pyridine-2-carboxamide 9) N - ((1R *, 2R *) - 2-. {[[(5- fluoroindol-2-yl) carbonylJamino.} cyclohexyl) -5-methyl-4,5,6,7-tetrahydrothiazo [5,4-c] pyridine-2-carboxamide 10) N - ((1 R *, 2R *) -2- { [(5-Chloro-6-fluoroindol-2-yl) carbonylJamino} cyclohexyl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cJpyridin- 2- carboxamide 11) N - ((1 R *, 2S *) - 2- { [(5-bromoindol-2-yl) carbonyl] amino.} Cyclohexyl) -5-methyl-4,5,6 , 7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide 12) N - ((1 R *, 2S *) - 2- { [(5-ethynylindol-2-yl) carbonyl] amino .) cyclohexyl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cjpyridine-2-carboxamide 13) N - ((1 R *, 2R *) - 2- { [( 5-chloroindol-2-yl) carbonyl] amino.}. Cycloheptyl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cJpyridine-2-carboxamide 14) N - ((1 R *, 2S *) -2- { [(5-chloroindol-2-yl) carbonyl] amino} cyclooctyl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cJpyridin- 2-carboxamide 15) N - ((1 R *, 2R 2-. {[[(5-chloroindol-2-yl) carbon] IJamino.} -4-methoxycyclope Nethyl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide 16) 5-methyl-N - ((1 R, 2S > 2-. { [(5-methylindol-2-yl) carbonyl] amino} cyclohexyl) -4,5,6,7-tetrahydrothiazole [5,4-cJpyridine-2-carboxamide 17) ethyl ester of the acid (1R *, 3S *, 4R *) - 4-. { [(5-chloro-indo-2-yl) carbonyl] amino} -3-. { [(5-methyl-4,5,6,7-tetrahydrothioazo [5,4-cjpyridin-2-yl) carbonyl] amino} cyclohexanecarboxylic acid 18) ethyl ester of (1S, 3R, 4S) -4- acid. { [(5-chloroindol-2-yl) carbonyl] amino} -3-. { [(5-methyl-4,5,6,7-tetrahydrothiazo [5,4-cJpyridin-2-yl] carbonylJamino} cyclohexanecarboxylic acid 19) methyl ester of the acid (1 R *, 3R *, 4S *) - 3-. { [(5-chloroindol-2-yl) carbonyl] amino} -4-. { [(5-methyl-4,5,6,7-tetrahydrothiazo [5,4-cJpyrdin-2-yl] carbonyl] amino} cyclohexanecarboxylic acid 20) ethyl ester of the acid (1 R *, 3S *, 4R *) - 3. { [(5-chloroindol-2-yl) carbonyl] amino} -4-. { [(5-methyl-4,5,6,7-tetrahydrothioazo [5,4-c] pyridin-2-yl) carbonylJamino} cyclohexanecarboxylic acid 21) methyl ester of the acid (1 R *, 3R *, 4S *) - 4-. { [(5-chloroindol-2-yl) carbonyl] amino} -3-. { [(5-methyl-4,5,6,7-tetrahydrothiazo [5,4-cJpyridin-2-yl] carbonylJamino} cyclohexanecarboxylic acid 22) methyl ester of the acid (1R, 3R, 4S) -4-. { [(5-chloroindol-2-l) carbonylJamino} -3-. { [(5-methyl-4,5,6,7-tetrahydrothioazo [5,4-cJpyrdin-2-yl] carbonyl] amino} cyclohexanecarboxylic acid 23) N - ((1 R *, 2S *, 5S *) - 5- (aminocarbonyl) -2-. {[[(5-chloroindol-2-yl) carbonyl] amino} cyclohexyl) - 5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide 24) acid (1 R *, 3S *, 4R *) - 4. { [(5-chloroindol-2-yl) carbonylJamino} -3-. { [(5-methyl-4,5,6,7-tetrahydrothiazo [5,4-cJpyridin-2-yl] carbonyl] amino} cyclohexanecarboxylic 25) N-. { (1 R *, 2S *, 5S *) - 2-. { [(5-chloroindol-2-yl) carbonyl] amino} -5 - [(dimethylamino) carbonyl] cyclohexyl} -5-methyl-4,5,6,7-tetrahydrothioazo [5,4-c] pyridin-2-carboxamide 26) (1S, 3R, 4S) -4- acid. { [(5-chloroindol-2-yl) carbonyl] amino} -3-. { [(5- methyl-4,5,6,7-tetrahydrothiazo [5,4-c] pyridin-2-yl) carbonyl] amino} cyclohexanecarboxylic acid 27) N-. { (1 R, 2S, 5S) -2-. { [(5-chloroindol-2-yl) carbonylJamino} -5- [(cyclopropylamino) carbonyl] cyclohexyl} -5-methyl-4, 5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide 28) N - [(1 R, 2S, 5S) -2-. { [(5-chloroindol-2-yl) carbonyljamino} -5- (pyrrolidin-1-ylcarbonyl) cyclohexyl-5-methyl-4,5,6,7-tetrahydrothiazo [5,4-c] pyridine-2-carboxamide 29) N - [(1 R *, 2S *, 5S 2- {[[(5-chloroindol-2-yl) carbonyl] amino} -5- (4-morpholinylcarbonyl) cyclohexyl-5-methyl-4,5,6,7- tetrahydrothiazole [5,4-cJpyridine-2-carboxamide 30) N-. { (1 R, 2S, 5S) -2-. { [(5-chloroindol-2-yl) carbonyl] amlno} -5 - [(ethylamino) carbonyl] -cyclohexyl} -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridin-2-carboxamide 31) N-. { (1 R, 2S, 5S) -2-. { [(5-chloroindol-2-yl) carbonylJamino} -5 - [(dimethylamino) carbonylJ-cyclohexyl} -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cJpyridine-2-carboxamide 32) N - ((1 R, 2S, 5S) -2- { [(5-chloroindol-2 -yl) carbonylJamino.} -5-. {[[(2-methoxyethyi] methyl) aminocarbonyl] cyclohexyl) -5-methyl-4,5,6,7-tetrahydric acid [ 5,4-cJpyridine-2-carboxamide 33) N - ((1R, 2S, 5S) -2-. {[[(5-chlorolndol-2-yl) carbonylJamino]. -5- { [( 2-hydroxyethyl) (methyl) aminoncarbonyl, cyclohexyl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cJpyridine-2-carboxamide 34) N - ((1 R, 2S, 5S) -5- (1-azetidinylcarbonyl) -2-. {[[(5-chloroindol-2-yl) carbon-amino] cyclohexyl) -5-methyl-4,5,6,7 -tetrahydrothiazole [5,4-cJpyridine-2-carboxamide 35) N - ((1R, 2S, 5S) -2-. {[[(5-chloroindol-2-yl) carbonyl] amino.}. -5- { [(3S) -3-fluoropyrrolidinylJcarbonyl.} Cyclohexyl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridin-2-carboxamide 36) acid (1 R) *, 3R *, 4S *) - 3-. { [(5-chloroindol-2-yl) carbonyl] amino} -4- . { [(5-methyl-4,5,6,7-tetrahydrothiazo [5,4-cJpyridin-2-yl] carbonyl] amino} cyclohexanecarboxylic 37) N-. { (1 R *, 2S *, 4S *) - 2-. { [(5-chloroindol-2-yl) carbonyl] amino} -4 - [(dimethylamino) carbonyl] cyclohexyl} -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide 38) N - ((1 R, 2S, 5S) -2- { [(5-chloroindole -2-yl) carbonyljamino. -5- { [(3R) -3-h'droxypyrrolidinyl] carbonyl} cyclohexyl) -5-methylene-4,5,6,7 - tetrahydroxyazol [5,4-c] pyridin-2-carboxamide 39) N - ((1 R *, 2S *) - 2-. {[[(5-chloroindol-2-yl) carbonyl] ] amino.}. -5,5-dimethoxycyclohexyl) -5-methyl-4,5,6,7-tetrahydroxyazo [5,4-c] pyridine-2-carboxamide, N - ((1 R *, 2S *) -2- { [(5-chloroindol-2-yl) carbonyl-Jamino} -4,4-d-methoxycyclohexyl) -5-methyl-4,5 6,7-tetrahydrothiazole [5,4-cJpyridine-2-carboxamide 40) N - ((1R *, 2S *) - 2- { [(5-chloroindol-2-yl) carbonyl] amino.} .5-oxocyclohexyl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide, N- ((1 R *, 2S *) -2-. [(5-chloroindol-2-yl) carbonyl] amino] -4-oxocyclohexyl) -5-methylene-4,5,6,7-tetrahydrothiazo [5,4-c] pyridine-2-carboxamide 41 ) N - [(1 R *, 2S *) - 2-. { [(5-chloroindol-2-yl) carbonyl] amino} -5- (hydroxy-amino) -cyclohexyl] -5-methyl-4,5,6,7-tetrahydrothioazo [5,4-c] pyridine-2-carboxamide, N - [(1) R *, 2S *) - 2-. { [(5-chloroindol-2-yl) carbonyl] amino} -4- (hydroxyimino) cyclohexyl] -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide 42) N - ((7R *, 8S 8-. { . [(5-chloroindol-2-yl) carbonylJamino] -1, 4-dioxaspiro [4.5Jdec-7-yl] -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide, N - ((7R *, 8S *) - 7-. {[[(5-chloroindol-2-yl) carbonylJamino] -1,4-dioxaspiro [4.5] dec-8-il ) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cJpyridine-2-carboxamide 43) N - [(1 R *, 2S *) - 2-. { [(5-chloroindol-2-yl) carbonylJamino} -5- (methoxyimino) -cyclohexyl-5-methyl-4,5,6,7-tetrahydro-azole [5,4-c] pyridin-2-carboxamide, N - [(1 R *, 2S *) - 2-. { [(5-chloroindol-2-yl) carbonylJamino} -4- (methoxyimino) cyclohexyl-5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide 44) N - ((1 R *, 2S *) - 2 - { [(5-chloroindol-2-yl) carbonyl] amino] -5-hydroxycyclohexyl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cjpyridin -2-carboxamide, N - ((1R *, 2S *) - 2- { [(5-chloroindol-2-yl) carbonyl] amino.} -4-hydroxycyclohexyl) -5-methyl -4,5,6, 7-tetrahydrothiazole [5,4-cJpyridine-2-carboxamide 45) N - ((1R *, 2S *) - 2- { [(5-chloroindol-2-yl ) carbonyl Jamino.) .5-hydroxy-5-methylcyclohexyl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide, N- ((1 R *, 2S *) - 2- { [(5-Chloroindol-2-yl) carbonyl-Jamal} -4-hydroxy-4-methyl-cyclohexyl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cJpyridine-2-carboxamide 46) N - [(1 R *, 2R *, 5S *) - 2-. { [(5-chloroindol-2-yl) carbonyl] amino} -5- (hydroxymethyl) cyclohexyl] -5-methyl-4,5,6,7-tetrahldrothiazole [5,4-c] pyridine-2-carboxamide 47) N - [(1 R *, 2S *, 5S 2- { [(5-chloroindol-2-yl) carbonylJamino] -5- (methoxymethyl) cyclohexyl] -5-methyl-4,5,6,7-tetrahydroxy [5]. 4-c] pyridn-2-carboxamide 48) N - ((1R *, 2S *, 5S *) - 2-. {[[(5-chloroindol-2-yl) carbonylJamino] -5- { [(Methylsulfonyl) amino] methyl.}. Cyclohexyl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cjpyridine-2-carboxamide 49) N-. { (1 R *, 2S *, 5S 2- { [(5-chloroindol-2-yl) carbonyl] amino}. -5 - [(d-methylammon) methylCyclohexyl] - 5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide 50) tert-butyl ester of (3R *, 4S *) - 4- acid. { [(5-chloroindol-2-yl) carbonylJamino} -3-. { [(5-methyl-4,5,6,7-tetrahydrothiazo [5,4-c] pyridin-2-yl) carbonyl] amino} cyclohexylcarbamic acid tert-butyl ester (3R *, 4S *) - 3-. { [(5-chloroindol-2-yl) carbonyl] amine} -4-. { [(5-methyl-4,5,6,7-tetrahydrothioazo [5,4-c] pyridin-2-yl) carbonylJamino} cyclohexylcarbamate 51) N - ((1 R *, 2S *) - 5-amino-2-. {[[(5-chloroindol-2-yl) carbonyl] amino.}. cyclohexyl) -5-methyl-4,5,6,7-tetrahydroxyazol [5,4-c] pyridine-2-carboxamide, N - ((1 R *, 2S *) - 4-amino-2-. [(5-chloroindol-2-yl) carbonyl] amino] cyclohexyl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridin-2-carboxamide 52) N- [(1 R *, 2S *) - 2-. { [(5-chloroindol-2-yl) carbonyljamino} -5- [(methylsulfonyl) amino] cyclohexyl} -5-methylene-4,5,6,7-tetrahydrothiazole [5,4-cJpyridin-2-carboxamide, N - [(1 R *, 2S *) - 2-. { [(5-chloroindol-2-yl) carbonylJamino} -4- [(methylsulfonyl) amino] cyclohexyl} -5-methyl-4,5,6,7-tetrahydroxyazole [5,4-c] pyridine-2-carboxamide 53) N - ((1 R *, 2S 5- (acetylamino) -2-. [(5-Chloroindol-2-yl) carbonyl] amino] cyclohexyl) -5-methyl-4,5,6,7-tetrahydroxyazole [5,4-c-pyridyl] 2-carboxamide, N - ((1 R *, 2S *) - 4- (acetylamino) -2-. {[[(5-chloroindol-2-yl) carbonyl] amino] cyclohexyl) -5-methyl- 4,5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide 54) N - ((1 R, 2S, 5S) -2- { [(5-chloroindol-2-yl) carbonyl] amino.}. -5-. {[[methoxy (methyl) amino] carbonyl} cyclohexyl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cJpyridine-2-carboxamide] ) N-. { (1 R, 2S, 5S) -2-. { [(5-chloroindol-2-yl) carbonyl] amino} -5 - [(2,2-dimethylhydrazino) carbonyl] cyclohexyl} -5-methyl-4,5,6,7-tetrahydrothiazole [5, 4-c-pyridine-2-carboxamide 56) 6-chloro-N - ((1 S, 2R, 4S) -4 - [(dimethylamino) carbonyl J-2-. {[[(5-methylene-4,5 , 6,7-tetrahydrothiazole [5,4-c] pyridin-2-yl) carbonylJamino, cyclohexyl) -2-quinolinecarboxamide 57) N-. { (1 R, 2S, 5S) -2-. { [(5-chloro-4-fluoroindol-2-yl) carbonyl] amino} - 5 - [(dimethylamino) carbonyl] cyclohexyl} -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cJpyridine-2-carboxamide 58) 7-chloro-N - ((1S, 2R, 4S) -4 - [(dimethylamino) carbonylJ-2 - { [(5-methyl-4,5,6,7-tetrahydrothiazolo [5,4-c] pyridin-2-yl) carbonylJamino}. Cyclohexyl) -soquinoline-3-carboxamide 59) N - (( 3R *, 4S *) - 4- { [(5-chloroindol-2-yl) carbonyl] amino.}. Tetrahydrofuran-3-yl) -5-methyl-4,5,6,7-tetrahydrothiazole [5 , 4-cJpyridine-2-carboxamide 60) N - ((3S, 4S) -4- { [(5-chloroindol-2-yl) carbonylJamino.] Tetrahydrofuran-3-yl) -5-methyl-4 , 5,6,7-tetrahydrothiazole [5,4-cJpyridine-2-carboxamide 61) N - ((3R, 4R) -4-. {[[(5-chloroindol-2-yl) carbonyl] amine}. tetrahydrofuran-3-yl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cJpyridine-2-carboxamide 62) tert-butyl ester of (3R, 4R) -3- . { [(5-chloroindol-2-yl) carbonyl] amino} -4-. { [(5-methyl-4,5,6,7-tetrahydroxyazol [5,4-cJpyridin-2-yl] carbonyl] amine} pyrrolidine-1-carboxylic acid 63) N - ((3R, 4R) -4-. {[[(5-chloroindol-2-yl) carbonyl] amino} pyrrolidin-3-yl) - d-methyl ^ .dd-tetrahydrothiazolfd ^ -cjpiridin ^ -carboxamide 64) N - ((3S, 4S) -4-. {[[(5-chloroindol-2-yl) carbonyl] amino.} - 5-oxotetrahydrofuran -3-yl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cJpyridine-2-carboxamide 65) N - ((3S, 4S) -4- { [(5-chloroindole -2-yl) carbonyl] amino.} -2- oxotetrahydrofuran-3-yl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide 66) (3S, 4R) -2- (3. {[[(5-chloroindol-2-yl) carbonylJamino] ethyl ester} -4- { [(5-methyl-4,5,6, 7-tetrahydrothiazol [5,4-c] pyridin-2-yl) carbonyl] amino.} -2-oxopyrrolidin-1-yl) acetic acid 67) N - ((3R, 4S) -4- { [( 5-chloroindol-2-yl) carbonyl] amine.} - 1-methyl-5-oxopyrrolidin-3-yl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4- pyridine-2-carboxamide 68) 2 - [((3R, 4R) -3-. {[[(5-Chloroindol-2-yl) carbonyl] amino acid} -4- { [( 5-Methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridin-2-yl) carbonyl] Jamin or.}. pyrrolidin-1-yl) sulfonyl-acetic acid 69) 2 - [((3R, 4R) -3- acid. { [(5-chloroindol-2-yl) carbonyl] amino} -4-. { [(5-methyl-4,5,6,7-tetrahydro-azoz [5,4-c] pyridin-2-yl) carbonyl] amino} pyrrolidin-1-yl) its, butyl-phenyl-acetic acid 70) 2 - ((3R, 4R) -3-. {[[(5-chloroindol-2-yl) carbonyl] amino] -4- { (5-methyI-4,5,6,7-tetrahydrothiazole [5,4-cjpyridn-2-yl) carbonyl] amino] pyrrolidin-1-yl) acetic acid 71) 2- ( (3R, 4R) -3- { [(5-chloroindol-2-yl) carbonyl] amino.} -4-. {[[(5-methyl-4,5,6,7-tetrah Drotiazol [5,4-c] pyridin-2-yl) carbonyl] amino} pyrrolidin-1-yl) acetic acid 72) 3 - ((3R, 4R) methyl ester - 3-. {[[(5-chloroindol-2-yl) carbonyl-Jamino} -4-. {[[(5-methyl-4,5,6,7-tetrahydrothiazo [5,4-c] py! din-2-yl) carbonylJamino} pyrrolidin-1-yl) propionic acid 73) 3 - ((3R, 4R) -3-. {[[(5-chloroindol-2-yl) carbonyl] amino]}. -4- { [(5- methyM.d ^ -tetrahydrothiazoltd ^ -cJpiridin ^ -iOcarbonylJaminoJpyrrolidin-1-yl) propionic 74) 3 - ((3R, 4R) -3-,. 5-chloroindol-2-yl) carbonylJamino} -4-. {[[(5-methyl-4,5,6,7-tetrahydrothiazole [d, 4-cJpyridin-2-yl) carbonylJamino} pyrrolidin-1-yl) -3-oxopropionic acid 75) 3 - ((3R, 4R) -3- { [(5-chloroindol-2-yl) carbonylJamino acid} -4-. { [(d-methyl-4,5,6,7-tetrahydroxy [5,4-cJpyridin-2-yl) carbon] amino]} pyrrolidin-1-yl) -3-oxopropionic acid 76) 1 - [((3R, 4R) -3-. {[[(5-chloroindol-2-yl) carbonyl] amino] methyl ester. { [(5-Methyl-4,5,6,7-tetrahydrothiazolo [5,4-c] pyridin-2-yl) carbonylJamino] pyrrolidin-1-yl) methyl] cyclopropanecarboxylic acid 77) 1 - [((3R, 4R) -3- { [(5-chloroindol-2-yl) carbonyl] amino.} -4-. {[[(5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridin-2-yl) carbonyl] amino} pyrrolidin-1-yl) meth ylcyclopropanecarboxylic acid 78) tert-butyl ester of (3R *, 4S *) - 4 acid -. { [(5-Chloroindol-2-yl) carbonyl] amino} -3-. { [(5-methyl-4,5,6,7-tetrahydrothiazo [5,4-cJpyridin-2-yl] carbonylJamino} piperidin-1 -carboxylic acid 79) N - ((3R *, 4S *) - 4-. {[[(5-chloro-undol-2-yl) carbonyl] amino} piperidin-3-yl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cJpyridine-2-carboxamide 80) tert-butyl ester of (3R *, 4S *) - 3- acid. { [(5-chloroindol-2-yl) carbonylJamino} -4-. { [(5-methyl-4, 5,6,7-tetrahydrothiazo [5,4-c] pyridin-2-yl) carbonyl] amino} piperidin-1 -carboxylic acid 81) N - ((3R *, 4S *) - 3 { [(5-chloroindol-2-yl) carbonyl] amino.}. piperidin-4-yl) -5-methyl- 4,5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide 82) tert-butyl ester of (3R *, 4S *) - 4. { [(5-fluoroindol-2-yl) carbonylJamino} -3-. { [(5-methyl-4,5,6,7-tetrahydrothiazo [5,4-cJpyridin-2-yl] carbonyl] amino} piperidin-1-carboxylic acid 83) N - ((3R *, 4S *) - 4- { [(5-fluoroindol-2-yl) carbonylJamino}. piperidin-3-yl) -5-methyl-4, 5,6,7-tetrahydrothiazole [5,4-cJpyridine-2-carboxamide 84) N - ((3R *, 4S *) - 1 -acetyl-4-. {[[(5-chloroindol-2-yl) carbonylJamino .}. piperidin-3-yl) -5-methyl-4,5,6,7-tetrahydrothiazo [5,4-c] pyridine-2-carboxamide 85) N - ((3R *, 4S *) - 1 - acetyl-3- { [(5-chloroindol-2-yl) carbonylJamino.] piperidin-4-yl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridine- 2-carboxamide 86) N - ((3R *, 4S 1 -acetyl-4. {[[(5-fluoroindol-2-yl) carbonyl] amino.}. Piperidin-3-yl) -5-methyl-4 , 5,6,7-tetrahydrothiazole [5,4-cJpyridine-2-carboxamide 87) N - [(3R *, 4S *) - 4. { [(5-chloroindol-2-yl) carbonyljamino} -1- (methylsulfonyl) piperidin-3-yl] -5-methyl-4,5,6,7-tetrahydrothiazo [5,4-c] pyridine-2-carboxamide 88) N - [(3R *, 4S *) -3-. { [(5-chloroindol-2-yl) carbonyl] amino} -1- (Methylsulfonyl) piperidin-4-yl] -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-cJpyridine-2-carboxamide 89) N - [(3R *, 4S *) - 4 -. { [(5-fluoroindol-2-yl) carbonylJamino} 1- (Methylsulfonyl) piperazin-3-yl-5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridin-2-carboxamide 90) (3R * methyl ester, 4S *) - 4-. { [(5-Chloroindol-2-yl) carbonyl] amine} -3-. { [(5-methyl-4,5,6,7-tetrahydrothiazo [5,4-c] pyridin-2-yl) carbonyl] amino} piperidin-1 -carboxylic 91) ethyl ester of the acid (3R *, 4S *) - 4-. { [(5-chloroindol-2-yl) carbonyl] amino} -3-. { [(5-methyl-4,5,6,7-tetrahydrothiazo [5,4-c] pyridin-2-yl) carbonyl] amino} piperidine-1-carboxylic acid 92) 2-methoxyethyl ester of (3R *, 4S4) -4- acid. { [(5-chloroindol-2-yl) carbonylJamino} -3-. { [(5-methyl-4,5,6,7-tetrahydrothiazo [5,4-cJpyridin-2-yl] carbonylJamino} piperdin-1-carboxyl 93) ethyl ester of the acid (3R *, 4S *) - 3-. { [(5-chloroindol-2-yl) carbonyl] amino} -4-. { [(5-methyl-4,5,6,7-tetrahydrothiazol [5,4-c] pyridin-2-yl) carbonyl] -amino} piperidin-1-carboxylic acid 94) N - ((3R *, 4S 4 { [(5-chloroindol-2-yl) carbonyl] amino.} -1-propionylp.peridin-3-yl) -5- methyl-4,5,6,7-tetrahydrothiazoI [5,4-cJpyridine-2-carboxamide 95) N - ((3R *, 4S *) - 4- { [(5-chloroindol-2-yl) carbonyl ] amino.} -1-isobutyl-piperidin-3-yl) -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide 96) N- [(3R *, 4S 4-. {[[(5-chloroindol-2-yl) carbonylJamino} -1- (2,2-d.methylpropanoyl) p¡perdin-3-1] -5 -methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide 97) N - [(3R *, 4S *) - 4. { [(5-chloroindol-2-yl) carbonyl] amino} -1- (3,3-d.methylbutanoyl) piperidin-3-ylJ-5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridin-2-carboxamide 98) N- [ (3R *, 4S >;4-. { [(5-chloroindol-2-yl) carbonyl] amino} -1- (2,2,2-TrifluoroacetiI) piperidin-3-ylJ-5-methyl-4,5,6,7-tetrahldrothiazole [5,4-c] pyridyl-2-carboxamide 99 ) N - [(3R *, 4S *) - 4-. { [(5-chlorolindole-2-yl) carbonyl] amino} -1- (cyclopropylcarbonyl) piperidn-3-ylJ-5-methyl-4,5,6,7-tetrahydroxyazole [5,4-cJpyridine-2-carboxamide 100) N - [(3R *, 4S 4-. {[[(5-chloroindol-2-yl) carbonyl] amino} -1- (cyclobutylcarbonyl) piperidin-3-ylJ-5-methyl-4,5,6,7-tetrahydrothiazole [5,4- c] pyridine-2-carboxamide 101) N - [(3R *, 4S *) - 4. { [(5-chloroindol-2-yl) carbonylJamino} -1- (Cyclopentylcarbonyl) piperidin-3-yl] -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide 102) 2 - ((3R *) acetate 4S *) - 4-. {[[(5-chloroindol-2-yl) carbonyl] amino]} -3-. {[[(5-methyl-4,5,6,7-tetrahydrothiazole [5.4 -cJpyridin-2-yl) carbonylJamino.}. piperidin-1-yl) -2-oxoethyl * * 103) N - ((3R, 4S) -4-. {[[(5-chloroindol-2-yl) carbonylJamino .}. -1. - glycolylpiperidin-Si -d-methyl-4-d-tetrahydrothiazole-4-pyridine-carboxamide 104) N - [(3R *, 4S-4 { [(5-chloroindol-2-yl. ) carbonylJamino.} -1- (2-d-methoxyacetyl) p -peridin-3-yl] -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine-2-carboxamide 10d) N - [(3R *, 4S *) - 4-. { [(d-fluoroindol-2-yl) carbonyl] amino} -1- (2-methoxy-acetyl) piperidin-3-yI] -d-methi-4, d, 6,7-tetrahydrothiazole [d, 4-cJpyridine-2-carboxamide 0106) N- ( (3R *, 4S *) - 1- (3. {[[Tert-butyl (d-phenyl) silyl] oxy} -2,2-dimethylpropane] -4- { [(d-chloro-undol-2-yl) carbonyl] amino.}. piperidin-3-yl) -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine-2-carboxam Da 107) N - [(3R *, 4S *) - 4-. { [(5-chloroindol-2-yl) carbonylJamino} -1- (3-hydroxy-2,2-dimethylpropanoyl) piperidin-3-yl-5-methyl-4, d, 6,7-tetrahydrothiazoI [d, 4-d-c-pyridine-2-carboxamide 108) N- [ (3R *, 4S 4-. {[[(5-chloroindol-2-yl) carbonyl] amino.} -1- (3-methoxy-2,2-dimethylpropane] piperidin-3-yl-5- methyl-4, d, 6,7-tetrahydrothiazole [d, 4- c] pyridn-2-carboxamide 109) 2 - ((3R *, 4S *) - 4- { [ (d-chloroindol-2-yl) carbonylJamino.} -0 3-. {[[(d-methyl-4,5,6,7-tetrahydrothiazo [5,4-c] pyridin-2- L) carbonyl] amino.}. Piperidin-1-yl) -1,1-dimethyl-2-oxoethyl 110) N - [(3R *, 4S *) - 4. { [(d-chloroindol-2-yl) carbonylJamino} -1- (2-hydroxy-2-methylpropane-1) pyrimidin-3-yl] -5-methyl-4, d, 6,7-tetrahydrothiazole [d, 4- cjpyridin-2- carboxamide 111) N-. { (3R *, 4S 4-. {[[(D-chloroindol-2-yl) carbonyl] amino] -1 - [(3-d hydroxycyclobutyl) carbonyl-Jpiperidin-3-yl] -5-methyl -4, d, 6,7-tetrahydrothiazole [d, 4- c] pyridine-2-carboxamide 112) N-. { (3R *, 4S *) - 4-. { [(d-chloroindol-2-yl) carbonyl] amino} -1- [(methoxycyclobutyl) carbonyl Jpiperidin-3-yl} -d-methyl-4, d, 6,7-tetrahydroxyazol [5,4-c] pyridine-2-carboxamide 0 113) N-. { (3R *, 4S 4. {[[(D-chloroindol-2-yl) carbonyl] amino] -1- [3-methoxy-2- (methoxymethyl) propanoyl] piperidin-3-yl}. -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cJpyridine-2-carboxamide 114) N - [(3R *, 4S 4 { [(d-chloroindol-2-yl) carbonyl ] amino.}. -1 - (tetrahydro-2H-pyran-4-ylcarbonyl) piperidin-3-yl] -d-methyl-4, d, 6,7-d tetrahydrothiazole [d, 4-c] pyridin-2 -carboxamide 11 d) N - ((3R *, 4S 1 -benzoyl-4. {[[(d-chloroindol-2-yl) carbonyl] amino.} piperidin-3-yl) -d- methyl-4, d, 6,7-tetrahydroxy [d, 4-c] pyridine-2-carboxamide 116) N-. { (3R *, 4S 4 { [(D-chloroindol-2-yl) carbonylJamino.} -1 - [(dimethylamino) carbonyljpiperidin-3-yl.}. -d-methyl-4, d, 6, 7-tetrahydrothiazole [d, 4- cJpyridine-2-carboxamide 117) N-. { (3R *, 4S *) - 4-. { [(d-chloroindol-2-yl) carbonyl] amino} -1 - [(ethylamino) carbonylJp] peridn-3-yl} -d-methyl-4, d, 6,7-tetrahydroxy [d, 4-c] pyridin-2-carboxamide 118) N - ((3R *, 4S *) - 1 - [(tert-butylamino ) carbonyl] -4- { [(5-chloroindol-2-5 yl) carbonylJamino.] piperidin-3-yl) -5-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] ] pyridine-2-carboxamide 119) 2 - ((3R *, 4S *) - 4-. {[[(d-chloroindol-2-yl) carbonyl] -3- methyl ester { [(d-Methyl-4,5,6,7-tetrahydrothiazol [d, 4-c] pyridin-2-yl) carbonyl-Jamino} piperidin-3-yl) acetic acid 0 120) acid 2- ((3R *, 4S *) - 4- { [(D-chloroindol-2-yl) carbonyl] amino.}. -3- { [(D-methyl-4, d, 6,7- tetrahydrothiazole [d, 4-cJpyridin-2-yl) carbonylJamino.] piperidin-3-yl) acetic acid 121) N - [(3R *, 4S) -4-. { [(d-chloroindol-2-yl) carbonyl] amino} -1- (2-methoxyethyl) piperidin-3-yl] -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cJpyridin-2-d carboxamide 122) N - [(3R *, 4S 4-. {[[(D-chloroindol-2-yl) carbonyl] amino} -1- (2-fluoroethyl) piperidin-3-yl] -d-methyl-4, 5,6,7-tetrahydrothiazole [5,4-c] pyridine-2-carboxamide 123) N - ((3R, 4S) -1-acetyl-4-. {[[(5-chloroindoi-2-yl)] carbonylJamino.}. piperidin-3-yl) -5-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine-2-carboxamide 124) N - ((3R, 4R) -1 -acetyl -4- { [(D-Chloroindol-2-yl) carbonyl] amino.}. Piperidin-3-yl) -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cJpirid N-2-carboxamide 125) N - [(3R, 4S) -4-. { [(5-chloroindol-2-yl) carbonyl] amino} -1- (2-5-methoxyacetyl) piperdin-3-yl] -d-methyl-4, d, 6,7-tetrahydroxyazole [d, 4-c] pyridine-2-carboxamide 126) N - [(3R, 4R) -4-. { [(d-chloroindol-2-yl) carbonylJamino} -1- (2-methoxyacetyl) piperidin-3-yl] -5-methyl-4,5,6,7-tetrahydroxyazol [d, 4-c] pyridine-2-carboxamide 0 127) N - (( 3R, 4R) -4- { [(D-chloroindol-2-yl) carbonyl] amino] -6-oxotetrahydro-2H-pyran-3-yl) -d-methyl-4, d, 6, 7-tetrahydrothiazole [d, 4-cJpyridine-2-carboxamide 128) N - ((3R, 4S) -4-. {[[(D-chloroindol-2-yl) carbonyl] amino] -6- oxotetrahydro-2H-pyran-3-yl) -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine-2-d carboxamide 129) (3R, 4S) -d ethyl ester -. { [tert-butyl (diphenyl) sil] Ioxox} -3- . { [(d-chloroindol-2-yl) carbonyl] amino} -4-. { [(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cJpyridin-2-yl) carbonylJamino} valeric 130) ethyl ester of (3R, 4S) -3- acid. { [(d-chloroindol-2-yl) carbonyl] amino} -d-hydroxy-4-. { [(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cJpyridin-2-yl) carbonyl] amino} valeric 131) N - ((3S, 4R) -4- { [(d-chloroindol-2-yl) carbonyl] amino] -6-oxotetrahydro-2H-pyran-3-yl) -d-met L-4, d, 6,7-tetrahydrothiazole [d, 4-cJpyridine-2-carboxamide 132) N - ((3R *, 4R *) - 4-. {[[(D-chloroindol-2-yl)] carbonyl Jamino.) -1, 1 -d-dioxohexahydro-1-thian-3-yl) -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine-2-carboxamide 133) N- ((3R *, 4R *) - 4-. {[[(D-fluoroindol-2-yl) carbonyl] amino.} -1, 1-dioxohexahydro-1-thian-3-yl) -5-methyl- 4, d, 6,7-tetrahydrothiazoI [d, 4-c] pyridine-2-carboxamide 0 134) N - ((3R *, 4R *) - 3. {[[(D-chloroindol-2-yl) carbonyl] amino.} -1, 1- dioxohexahydro-1-thian-4-yl) -5-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine-2-carboxamide 13d ) N - ((3R *, 4S *) - 4-. {[[(D-chloroindol-2-yl) carbonylJamino} -1, 1-dioxohexahydro-1-thian-3-yl) -d-methyl -4, d, 6,7-tetrahydrothiazoI [d, 4-c] pyridine-2-d carboxamide 136) N - ((3R *, 4S *) - 4- { [(5-fluoroindol-2-yl carbonyl] amino.} -1, 1-dioxohexahydro-1-thian-3-yl) -d-methyl-4, d, 6,7-tetrahydrothioazo [d, 4-c] pyridine- 2- carboxamide 137) N - ((3R 4R *) - 3. { [(d-fluoroindol-2-yl) carbonyl] amino} -1, 1-0 dioxohexahydro-1-thian-4-yl) -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cJpyridin-2-carboxamide 138) N - ((3S, 4R) -4- { [(D-Cloroindol-2-yl) carbonylJamino.} -1-methyl-6-oxopiperidin-3-yl) -d-methyl-4, d, 6,7-tetrahydrothiazole [ d, 4-c] pyridine-2-carboxamide, N - ((3R, 4R) -4-. {[[(d-chloroindol-2-yl) carbonyl] amino]} -1-methyl-6- oxopiperidin-3-yl) -d-methyI-4, d, 6,7-tetrahydrothiazole [d, 4-c] plridin-2-carboxamide 139) N 1 - (4-chlorophenyl) -N 2 - ((1 S, 2R , 4S) -4 - [(dimethylamino) carbonyl] -2-. {[[(D-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-d-yl) carbon) "IJamino.") Cyclohexyl) ethanediamide 140) N 1 - (d-chloridin-2-yl) -N 2 - ((1 S, 2R, 4S) -4- [(dimethylamino) carbon I] -2-. [(5-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] amino] cyclohexyl) ethanediamide "141) N 1 - (3-chlorophenyl) ) -N2 - ((1S, 2R, 4S) -4 - [(d -methylamino) carbonyl] -0 2-. {[[(D-methyI-4, d, 6,7-tetrahydrothiazole [d] , 4-c] pyridin-2-yl) carbonyl, amino, cyclohexyl) ethanediamide 142) N 1 - ((1 S, 2R, 4S) -4 - [(dimethylamino) carbonyl ] -2- { [(D-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] amino} cyclohexyl) -N 2 - (4-fluorophen-1) ethanediamide d 143) N 1 - (4-bromophenyl) -N 2 - ((1 S, 2R, 4S) -4 - [(dimethylamino) carbonl] -2- { [(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridin-2-yl) carbonyl] amine} cyclohexyl) ethanediamide 144) N 1 - (4-chloro-2-) methylphenyl) -N2 - ((1S, 2R, 4S) -4- [(dimethylamino) carbonyl] -2-. {[[(d-methyl-4,6,6-tetrahydrothiazole [d]] , 4-pyridin-2-yl) carbonyl-amino) cyclohexyl) ethanediamide 145) N 1 - (4-chloro-3-methylphenyl) -N 2 - ((1 S, 2R, 4S) -4- [(dimethylamine) carbonyl] -2. {[[(d-methyl-4,6,6-tetrahydrothiazole [d, 4-cjpyridin-2-yl] carbonyl] amino] cyclohexyl. ) ethanediamide 146) N 1 - (4-chloro-2-fluorophenyl) -N 2 - ((1 S, 2R, 4S) -4- [(dimethylamino) carbonyl] -2-. {[[(d-methyl- 4, d, 6, 7-tetrahydrothiazole [d, 4-cjpyridin-2-yl) carbonyl] amino} cyclohexyl) ethanediamide 147) N 1 - (2,4-dichlorophenyl) -N 2 - ((1 S, 2R, 4S) -4-5 [(dimethylamino) carbonyl] -2-. {[[(5-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyljamino, cyclohexyl) ethanediamide 148) N 1 - (3,4-dichlorophenyl) -N 2 - ((1S, 2R, 4S ) -4- [(dimethylaminoJcarbonylj ^ -íKd-methyl-tetrahydrothiazoltd ^ -cjpyridin ^ -yl) carbonyljamino} cyclohexyl) ethanediamide 0 149) N1- (2,4-difluorophenyl) -N2 - (( 1S, 2R, 4S) -4- [(dimethylamino) carbonyl] -2-. {[[(5-methyl-4, d, 6,7-tetrahydrothiazo [5,4-c] pyridin-2-yl) carbonyl] ] amino.}. cyclohexyl) ethanediamide 150) N 1 - (3,4-d? fluorophenyl) -N 2 - ((1 S, 2R, 4S) -4- [(dimethylamino) carbonyl] -2- { [( d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-d-yl) carbonyl] amino.}. cyclohexyl) ethanediamide 151) N 1 - ((1 S, 2R, 4S) -4 - [(dimethylamino) carbonyl] -2-. {[[(5-methyl-4, d, 617-tetrahydrothiazole [d, 4-cjpyridin-2-yl) carbonyl] amine} cyclohexyl) -N2- (pyridin-4-yl) ethanediamide 152) N1- (5-bromopyridin-2-yl) -N2 - ((1S, 2R, 4S) -4- [(dimethylamine ) carbonilj-2- { [(5-meti) l-4,5,6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyljamino} cyclohexyl) ethanediamide 153) N 1 - (6-chloropyridin-3-yl) -N 2 - ((1S, 2R, 4S) -4- [(dimethylamino) carbonyl] -2-. {[[(d-methyl- 4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] amino.}. Cyclohexyl) ethanediamide 154) N 1 - (6-chloropyridazin-3-yl) -N 2 - ((1 S, 2R, 4S) -4-d [(dimethylamino) carbpnjl-2 { [(D-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpirdin -2- yl) carbonyljamino.) Cyclohexyl) ethanediamide 1 dd) N 1 - (d-chlorothiazol-2-yl) -N 2 - ((1 S, 2R, 4S) -4- [(dimethylamine) carbonyl ] -2- { [(D-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cypyridin-2-yl) carbonyl] amino.}. Cyclohexyl) ethanediamide 0 1 d6) N-. { (1 R, 2S, dS) -2-. { [2- (4-chloroanilino) acetyl] amino} -d- [(dimethylamino) carbonyl] cyclohexyI} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine-2-carboxamide 157) N-. { (1 R, 2S, dS) -2-. { [2- (4-chloro-2-fluoroanilino) acetyl-amino} -d- [(dimethylamino) carbonyl] cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine-d 2-carboxamide 1 dd) N-. { (1 R, 2S, dS) -2-. { [(d-chloro-4-fluoroindol-2-yl) carbonyljamino} - d - [(dimethylamino) carbonyl] cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridine-2-carboxamide 1 d9) N-. { (1 R, 2S, dS) -2-. { [(d-chloro-3-fluoroindoI-2-yl) carbonyl] amino} - d - [(dimethylamino) carbonyl-cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridine-2-carboxamide 160) N-. { (1 R, 2S, dS) -2-. { [(3-bromo-d-chloroindol-2-l) carbonyljamino} -d - [(dimethylamino) carbonyl] cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine-2-carboxamide 161) N-. { (1 R, 2S, dS) -2-. { [(3-Chloro-5-fluoroindol-2-yl) carbonyl] amino} -d d - [(dimethylamino) carbonyl] cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridine-2-carboxamide 162) N-. { (1 R, 2S, dS) -2-. { [(d-chloro-3-formylindol-2-? l) carboniI] amino} - d - [(dimethylamino) carbonyl] cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4- c] pyridine-2-carboxamide 0 163) d-chloro-N 2 - ((1 S, 2R, 4S) -4 - [(dimethylamine No carbon) -2- {[[d-metiM.d.ej-tetrahydrothiazolCd ^ -cjpiridin ^ -i carbonylJaminoJcicheohexy-N3 ^ 3- dimethylindoI-2,3-dicarboxamide 164) N-. {( 1 R, 2S, 5S) -2 - [(6-chloro-2-naphthoyl) amino] -5- [(dimethylamino) carbonyl] cyclohexyl.] .d -methyl-4, d, 6.7- tetrahydrothiazole [d, 4-c] pyridine-d 2-carboxamide 16d) 7-chloro-N - ((1 S, 2R, 4S) -4 - [(dimethylamino) carbonyl] -2-. {[[(d- methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cJpyridin-2-yl) carbonyl] amino.}. cyclohexyl) cinnoline-3-carboxamide 166) N-. { (1 R, 2S, dS) -2-. { [(d-chlorobenzimidazol-2-yl) carbonyl] amino} - d - [(dimethylamino) carbonyl] cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridine-2-carboxamide 167) N - ((1 S, 2R, 4S) -4 - [(dimethylamino) carbonylj-2- . {[[(d-methyl-4,6,6-tetrahydrothiazole [d, 4-cjpyridin-2-yl] carbonyl] amino] cyclohexyl) -7-fluoroisoquinoline-3-carboxamide 168) N -. { (1 R, 2S, dS) -2-. { [(7-chloro-2 H -chromen-3-yl) carbonyl] amino} -d d - [(dimethylamino) carbonyl] cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazo [5,4-c] pyridine-2-carboxamide 169) N-. { (1 R, 2S, dS) -2-. { [(E) -3- (4-chlorophenyl) -2-propenoyl] amino} -d- [(dimethylamine) carbonyl] cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridine-2-carboxamide 0 170) 6-chloro-N - ((1 S, 2R, 4S) -4 - [(dimethylamino carbonyl] -2- { [(d-metl-4), d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] amine} cyclohexyl) -4-oxo-1,4-dihydroquinoline-2-carboxamide 171) 7-chloro-N - ((1 S, 2R, 4S) -4- { [ethyl (methyl) amino] carbon 1.) -2- { [(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-d-yl) carbonyl] amino.}. cyclohexyl. isoquinoline-3-carboxamide 172) N-. { (1 R *, 2S *, dS 2-. {[[(D-chloroindol-2-yl) carbonyl] amino.}. -d- [2- (dimethylamino) -2-oxoethyl] cyclohexyl. -methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine-2-carboxamide 173) N-. { (1 R, 2S, dS) -2-. { [(d-chloroindol-2-yl) carboniIjamino} -d- [(methylsulfonyl) methyljcyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cypyridin-2-carboxamide 174) N-. { (1 R, 2S, dS) -2-. { [(2-chloro-6H-thieno [2,3-b] pyrrol-d-yl) carbonyl-amino} -d - [(dimethylamino) carbonyl] cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridine-2-carboxamide 175) N-. { (1 R, 2S, 5S) -2-. { [3- (4-chlorophenyl) -2-propinoylJamino} -5-d [(dimethylamino) carbonyl] cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridine-2-carboxamide 176) 6-chloro-N- ((1 S, 2R, 4S) -4 - [(dimethylamino) carbonyl- 2- { [(D-methyl-4, d, 6,7-tetrahydrothiazol [d, 4-c] pyridin-2-yl) carbonyljamino} cyclohexyl) -4-oxo-1,4-dihydroquinazolin- 2-carboxamide 0 177) N-. { (1 R, 2S, dS) -2-. { [2- (4-chloroanilino) -2-oxoethanethioyljamino} - d - [(dimethylamino) carbonyl] cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridine-2-carboxamide 178) N-. { (1 R, 2S, dS) -2- ( {2 - [(d-chloropyridin-2-yl) amino] -2-oxoethanethiol). Amino) -d - [(dimethylamino) carbonyl ] cyclohexyl} -d-methyl-4, d, 6,7-d tetrahydrothiazole [d, 4-cjpyridine-2-carboxamide 179) N-. { (1 R, 2S, dS) -2- ( {2 - [(d-chloropyridin-2-yl) amino] -2-thioxoacetyl}. Amino) -5 - [(dimethylamino) carbonyl] cyclohexyl} -5-methyl-4, d, 6,7-tetrahydrothiazo [d, 4-c] pyridine-2-carboxamide 180) N 1 - (d-chloro-2-thienyl) -N 2 - ((1 S , 2R, 4S) -4- [(dimethylamino) carbonyl] -2-. {[[(D-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridn-2-yl] carbonyljamino.}. cyclohexyl) ethanediamide 181) N-. { (1 R, 2S, dS) -2-. { [(4-chloroanilino) carbonyl] amino} -d- [(dimethylamino) carbonyl-cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine-2-carboxamide 182) N1 - ((1 S, 2R, 4S) -4 - [(dimethylamino) carbonyl] -2 - { [(d-methyl-d 4, d, 6,7-tetrahydrothiazol [d, 4-c] pyridin-2-yl) carbonyljamino.} cyclohexyl) -N 2 - (d-fluoropyridin-2-yl. ) ethanediamide 183) N 1 - [4-chloro-2- (trifluoromethyl) phenyl] -N 2 - ((1 S, 2R, 4S) -4- [(d-methylamino) carbonyl] -2-. { [(d-methyl-4, d, 6,7-tetrahydroxy] [d, 4-c] pyridin-2-yl) carbonyl] amino} cyclohexyl) ethanediamide 0 184) N 1 -. { 4-chloro-2 - [(dimethylamino) carbonyljphenyl} -N2 - ((1 S, 2R, 4S) -4 - [(dimethylamino) carbonyl] -2-. {[[(D-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine 2-yl) carbonyl] amino.}. Cyclohexyl) ethanediamide 185) N 1 - [4-chloro-2- (hydroxymethyl) phenyl] -N 2 - ((1 S, 2R, 4S) -4- [(d-methyl) Lamno) carbonyl] -2-. {[[(D-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridin-2-d-yl] carbonyl] amino} cyclohexyl) ethane amide 186) N 1 - (4-chloro-2-methoxyphenyl) -N 2 - ((1 S, 2R, 4S) -4- [(dimethylamino) carbonyl] -2-. {[[(d-methyl-4 , d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] amino.}. cyclohexyl) ethanediamide 187) N-. { (1 R, 2S, dS) -2-. { [2- (4-chloroanilino) -2-0 (hydroxyamino) acetyl] amino} -d - [(dimethylamino) carbonyl] cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-carboxamide 188) N 1 - (4-chlorophenyl) -N 2 - ((3R, 4S) -1 - (2-methoxyacetyl) -3- { [(5-methyl-4,5,6,7-tetrahydrothiazo [5,4-c] pyridin-2-yl) carbonyl] amino.}. Piperidin-4- il) ethanediamide 189) N1- (5-chloropyridin-2-yl) -N2 - ((3R, 4S) -1 - (2-methoxyacetyl) -3-. {[[(dd methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] amino.}. Piperidin-4-yl) ethanediamide 190) N 1 - (d-bromopyridin-2-yl) -N 2 - ((3R , 4S) -1 - (2-methoxyacetyl) -3-. {[[(D-methyl-4, d, 6,7-tetrahydrozolo [d, 4-cJpyridin-2-yl] carbonyl] amino] .}. piperidin-4-yl) ethanediamide 0 191) N 1 - (4-chlorophenyl) -N 3 - ((1 S, 2R, 4S) -4 - [(dimethylamino) carbonyl] -2-. {[[(d -methyl-4, d, 6,7-tetrahydroxyazol [5,4-c] pyridin-2-yl) carbonyljamino} cyclohexyl) malonamide 192) N 1 - (3-chlorophenyl) -N 3 - (( 1S, 2R, 4S) -4 - [(dimethylamino) carbonylj- 2-. {[[(5-methyl-4,5,6,7-tetrahydrothiazol [5,4-c] pyridin-2-yl) carbonyl] amino} cyclohexyl) malonamide 193) N1- (d-chloropyridin-2-yl) -N2 - ((1 S, 2R, 4S) -4- { [ethyl (methyl) amino) carbonyl} -2-. { [(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] amino} cyclohexyl) ethanediamide 194) N 1 - (4-chlorophenyl) -N 2 - ((1 S, 2R, 4S) -4- { [et.l (met.l) aminojcarbon.l.} -2-. { . [(d-methyl-4, d, 6,7-tetrahydrothioazo [d, 4-c] pyridin-2-yl) carbonyl] amino] cyclohexyl) ethanediamide 195) N 1 - (d -bromopyridin- 2-yl) -N 2 - ((1S, 2R, 4S) -4-. {[[Ethyl (methyI) amino] carbonyl] -2-. {[[(D-methyl-4, d, 6 , 7-tetrahydrothiazole [d, 4-cjpyridin-2-yl) carbonyljamino} cyclohexyl) ethanediamide 196) N 1 - (4-chloro-3-fluorophenyl) -N 2 - ((1S, 2R, 4S) -4-d [(dimethylamino) carbonl] -2-. {[[(d-methyl-4, d, 6,7-tetrahydrothiazo [5,4-c] pyridn-2-yl) carbonyl] amino.}. cyclohexyl) ethanediamide 197) N-. { (1 R, 2S, 5S) -2-. { [3- (4-chlorophenyl) -3-oxopropanoyl] amino} -d- [(dimethylamino) carbonylcyclohexy]} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridine-2-carboxamide 0 198) N 1 - [(d-chloropyridin-2-yl) amino] -N 2 - ((1 R , 2R, 4S) -4- [(dimethylamino) carbonyl] -2-. {[[(D-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] amino.}. cyclohexyl) ethanediamide 199) N 1 - (4-chlorophenyl) -N 2 - ((1 R, 2R, 4S) -4 - [(dimethylamine) carbonyl] -2-. {[[(d -methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-d yl) carbonyljamino, cyclohexyl) ethanediamide 200) N 1 - (d-chloropyridin-2-yl) -N 2 - ( (1 S, 2R, 4S) -4- [(dimethylamino) carbonyl] -2-. {[[(D-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridin-2-yl] carbonyl] amino]. cyclohexyl) -N 1 -methylenedianediamide 201) N 1 - (d-chloropyrimidin-2-yl) -N 2 - ((1 S, 2R, 4S) -4- [(dimethylamino) carbonyl-2- { [(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridin-2-yl] carbonyljamino] cyclohexyl) ethanediamide 202) N 1 - (4-chloro-3-methoxyphenyl) -N2- ((1S, 2R, 4S) -4- [(dimethylamino) carbonylj-2-. {[[(D-methyl-4, d, 6,7-tetrahydro-azothazole [d, 4-cjpyridin- 2- il) carbonyljamino.) Cyclohexyl) ethanediamide 203) N1- (4-cl orophenyl) -N2 - ((1 R *, 2R >;2-. { [(d-methyl-4, d, 6,7-d-tetrahydrothiazole [d, 4-cjpyridin-2-yl) carbonyl] amine} cyclopentyl) ethanediamide 204) N 1 - (d-cyoropyridin-2-yl) -N 2 - ((1 R *, 2 R> 2-. {[[(d-methyl-4, d, 6, 7- tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] amino} cyclopentyl) ethanediamide 20d) N 1 - ((1 S, 2R, 4S) -4 - [(dimethylamino) carbonylj-2 - { [(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyljamino}. cyclohexyl) -N2- (4-0-ethynylphenyl) ethanediamide 206) N1- (d-chloropyrazin-2-yl) -N2 - ((1 S, 2R, 4S) -4- [(dimethylamino) carbonyl] -2-. {[[(D-methyl-4, d, 6, 7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyljamino} cyclohexyl) ethanedi amide 207) N 1 - (4-chloro-3-nitrophenyl) -N 2 - ((1 S, 2R, 4S) -4-d [(d.methylamino) carbonyl] -2-. {[[(D-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carboni amino] .) cyclohexyl) ethanediamide 208) N 1 - (4-chloro-2-nitrophenyl) -N 2 - ((1 S, 2R, 4S) -4- [(dimethylamine) carbonyl] -2-. [(d-methylene-4,6,6-tetrahydroxy] [d, 4-cypyridin-2-yl] carbonyl] amino] cyclohexyl) ethanediamide 209) N 1 - (3- amino-4-chlorophenyl) -N2 - ((1S, 2R, 4S) -4- [(dimethylamino) carbonylj-2-. {[[(d-methy 1-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridin-2-yl) carbonyl] amino} cyclohexyl) ethanediamide 210) N 1 - (2-amino-4-chlorophenyl) -N 2 - ((1 S, 2R, 4S) -4- [(dimethylamino) carbonyl] -2-. {[[(d -methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridin-2-yl) carbonyl] amino.}. cyclohexyl) ethanedimamide 211) N 1 - (6-chloro-4) -methylpyridin-3-yl) -N 2 - ((1 S, 2 R, 4 S) -4-d [(dimethylamino) carbonyl] -2-. {[[(5-methyl-4,5, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyljamino, cyclohexyl) ethanediamide 212) N-. { (1 R, 2S, dS) -2- ( { [(E) -2- (4-chlorophenyl) diazenyl] carbonyl}. Amino) -5 - [(dimethylamino) carbonyl] cyclohexyl} -d-methyl-4) d, 6,7-tetrahydrothiazoI [d, 4-c] pyridine-2-carboxamide 0 213) N-. { (1 R, 2S, dS) -2- ( { [2- (4-chlorophenyl) hydrazino] carbonyl}. Amino) -5 - [(dimethylamino) carbonyl] cyclohexyl} -5-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine-2-carboxamide 214) N 1 - (d-chloropyridin-2-yl) -N 2 - ((1 S, 2R, 4S ) -4- [(d -methylamino) carbonyl] -2-. {[[(4, d, 6,7-tetrahydrothiazol [d, 4-c] pyridin-2-d yl) carbonyl] amino.}. Cyclohexyl. ) ethanediamide 215) N-. { (3R *, 4S *) - 4-. { [(d-chloroindol-2-yl) carbonyl] amino} -1 - [(1-Hydroxycyclopropyl) carbonyljpiperidin-3-yl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridine-2-carboxamide 216) N-. { (3R *, 4S *) - 4-. { [(d-chloroindol-2-yl) carbonyl] amino} -1 - [(1- methoxychloropropyl) carbonyljpiperdin-3-yl} -5-methyl-4, d, 6,7-tetrahydroxy [d, 4-cjpyridine-2-carboxamide 217) 7-chloro-N - ((3R, 4S) -1 - (2-methoxyacetyl) -3- { [(5-methyl-4, d, 6,7-tetrahydrothiazol [d, 4-c] pyridin-2-yl) carbonyljamino.] Piperidin-4-yl) -3-isoquinolinecarboxamide 218) N1- (4-chloro-3-fluorophenyl) -N2 - ((3R, 4S) -1 - (2-methoxyacetyl) -3-d. {[[(D-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridin-2-yl) carbonyljamino] p.peridin-4-yl) ethanediamide 219) N 1 - (d-chloro-2-thienyl) -N 2 - ((3R, 4S) -1- (2-methoxyacetyl) -3-. {[[(D-methyl-4,5,6,7-tetrahydrothiazole [d, 4-cjpyridin-2-yl) carbonyl] amino. piperidin-4-yl) ethanediamide 0 220) N-. { (1 R, 2S, dS) -2-. { [2- (4-chlorophenoxy) acetyl] amino} -d- [(dimethylamino) carbonyl-cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridin-2-carboxamide 221) N-. { (1 R, 2S, dS) -2-. { [(6-chloro-4-oxo-4H-chromen-2-yl) carbonyl] amino} -d - [(dimethylamino) carbonyl] cyclohexyl} -d-methyl-4, d, 6,7-d tetrahydrothiazole [d, 4-c] pyridine-2-carboxamide 222) 7-chloro-N - ((3R, 4S) -1- (2-methoxyacetyl) - 3-. {[[(D-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] -amino}. Piperidin-4-yl) -3 - cinnolinecarboxamide 223) N - ((1R, 2S, 5S) -d - [(dimethylamino) carbonyl] -2- { [2- (4-fluoroanilino) -2-oxoethanothioyl] amino.} - cyclohexyl) - d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine-2-carboxamide 224) N - [(1 R, 2S, dS) -5 - [(dimethylamino) carbonyl] -2- ( {2 - [(d-fluoropyridin-2-yl) amino-2-oxoethanothioyl}. Amino) cyclohexyl-d-methyl-4, d, 6,7-tetrahydrothiozo [d, 4- c] pyridine-2-carboxamide 225) N-. { (1 R, 2S, dS) -2 - [( { [(4-5 chlorophenyl) sulfonyl] amino} carbonyl) aminoj-5 - [(dimethylamino) carbonylcyclohexyl} -5- methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine-2-carboxamide 226) N 1 - (d-chloropyridin-2-yl) -N 2 - ((1 S, 2R , 4S) -4- [(dimethylamino) carbonylj-2-. {[[(D-methyl-4,5,6,7-tetrahydrothiazo [5,4-cjpyridin-2-yl] carbonyl] amino.}. Cyclohexyl. ) ethanediamide 0 227) N1- (d-chloropyridin-2-yl) -N2 - ((1S, 2R, 4S) -4- [(d -methylamino) carbonl] -2-. { [(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] amino} cyclohexyl) ethanediamide 228) N 1 - (d-chloropyridin-2-yl) -N 2 - ((1 S, 2R, 4S) -4- [(methylamino) carbonyl] -2-. {[[(d -methyl-4, d, 6,7-tetrahydroxyazole [d, 4-cjpyridin-2-d-yl) carbonyl] amino] cyclohexyl) ethanediamide 229) N-. { (1 R, 2S, dS) -d - [(dimethylamino) carbonyl] -2- (. {2 - [(d-methylpyridin-2-yl) amino] -2-oxoethanothioyl} amino) cyclohexyl} -5-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridine-2-carboxamide 230) N - [(3R, 4S) -4-. { [2- (4-chloroanilino) -2-oxoethanethiol] amino} -1- (2-methoxyacetyl) piperidin-3-yl] -d-methyl-4, d, 6,7-tetrahydroxy [d, 4-c] pyridine-2-carboxamide 231) N1- (d-chloropyridin-2-yl) -N2 - ((1S, 2R, 4S) -4- [(dimethylamino) carbothioyl] -2-. {[[(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyljamino.] cyclohexyl) ethanediamide 232) N 1 - (d-chloropyridin-2-yl) -N 2 - ((3R, 4S) -1- (2-methoxyethanothioyl) -3-d { [(D-methyl-4, d, 6,7-tetrahydroxyazol [d, 4-cjp¡r¡d¡n-2-yl) carbonyljamino.} Piperidin-4-yl. ) ethanediamide 233) 2,2-trichloroethyl ester of '(1S, 3R, 4S) -4- (. {2 - [(d-chloropyridin-2-yl) amino] -2-oxoacet} L.}. Amino) -3-. { [(5-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] amino} cyclohexanecarboxylic acid 0 234) (1S, 3R, 4S) -4- (. {2 - [(d-chloropyridin-2-yl) amino-2-oxoacetyl} -amino) -3- acid. { [(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridin-2-l] carbonyljamino} cyclohexanecarboxylic acid 23d) N-. { (1 R, 2S, dS) -2-. { [2- (4-chloroanilino) -1-methoxyimino-2-oxoethyl] amino} -d - [(dimethylamine) carbonyl-cyclohexyl} -5-methyl-4, d, 6,7-d tetrahydrothiazole [d, 4-c] pyridine-2-carboxamide 236) N1 - ((1 S, 2R, 4S) -4 - [(dimethylamine) carbonylj-2 - { [(d-Methyl-4,5,6,7-tetrahydrothiazolo [5,4-c] pyridin-2-yl) carbonyl] amino.}. c. cyclohexyl) -N 2 - (d- ethynylpyrid) n-2-yl) ethanodiamida 237) N-. { (1 R, 2S, dS) -2- ( {2 - [(6-chloropyridazin-3-yl) amino] -2-0-oxoethanothioyl}. Amino) -d - [(dimethylamino) carbonyl-cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine-2-carboxamide 238) N-. { (1 R, 2S, dS) -2- ( {2 - [(6-chloropyridin-3-yl) amino] -2-oxoethanothioyl}. Amino) -d - [(dimethylamino) carbonyl-cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine-2-carboxamide 239) N1 - ((1 S, 2R, 4S) -4 - [(dimethylamino) carbonyl] -2 - { [(d-methyl-d 4, d, 6,7-tetrahydrothiazo [5,4-cJpyridin-2-yl) carbonyl] amino.}. cyclohexyl) -N2- (d-methylpyridin-2-yl) ) ethanediamide 240) N1 - ((1 S, 2R, 4S) -4 - [(dimethylamino) carbonyl] -2-. {[[(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4- cjpyridin-2-yl) carbonyljamino.) cyclohexyl) -N 2 - (4-methylphenyl) ethanediamide 0 241) N 1 - (d-chloropyridin-2-yl) -N 2 - ((1S, 2R, 4S) -4- [ (methylamino) carbothioylj-2- { [(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridin-2-yl) carbonyl] amino.}. cyclohexyl) ethanediamide 242 ) N-. { (1 R, 2S, dS) -2-. { [(4-chloroanilino) suiofonyl] amino} -d- [(dimethylamino) carbonyl-J-cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazo [d, 4-c] pyridine-2-carboxamide 243) N-. { (1 R, 2S, 5S) -2- ( {2 - [(d-chloropyrimidin-2-yl) amino] -2-oxoethanothioyl}. Amino) -d - [(dimethylamino) carbonyl-cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine-2-carboxamide 244) N-. { (1 R, 2S, dS) -2-. { [2- (4-chloro-3-nitroanilino) -2-oxoethanethioyl-amino} -d - [(dimethylamino) carbonyljcyclohexyl} -d-methyl-4, d, 6,7-tetrahydroxyazol [d, 4-cjpyridn-2-carboxamide 24d) N-. { (1 R, 2S, dS) -2-. { [2- (3-amino-4-chloroanilino) -2-oxoethanethioyl-amino} -d - [(dimethylamino) carbonyl] cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridine-2-carboxamide 246) N-. { (1 R, 2S, dS) -2-. { [(7-chloroquinolin-3-yl) carbothioyl] amino} -d-d [(dimethylamino) carbonyl] cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine-2-carboxamide 247) N-. { (1 R, 2S, dS) -2- ( { [(4-chlorobenzoyl) amino] carbonyl}. Amino) -d- [(dimethylamino) carbonyl] cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine-2-carboxamide 0 248) N-. { (1 R, 2S, dS) -2-. { [(E) -3- (d-chloropyridin-2-yl) acryloyl-amino} -d- [(dimethyl) carbonyl] cyclohexyl} -d-methyl-4,5,6,7-tetrahydrothioazo [5,4-cjpyridin-2-carboxamide 249) N-YÍI R ^ S.dS ^ -ÍKZJ-S ^ -chloropheni ^ -fluoroacryloyljamino} - 5 - [(dimethylamino) carbonyl-cyclohexyl} -5-methyl-4,5,6,7-tetrahydrothiazole [5,4-d cjpyridine-2-carboxamide 2d0) N-. { (1 R, 2S, dS) -2- ( {2 - [(d-chloropyridin-2-yl) aminoj-2-oxoethanothioyl}. Amino) -d - [(methylamino) carbonyl] cyclohexyl} -d-methyl-4, d, 6,7- tetrahydrothiazoI [5,4-cjpyridine-2-carboxamide 2d1) tert-butyl ester of (3- {[[((1S, 2R, 4S) -4-0 [(dimethylamine carbonyl] -2- { [(d-methyl-4, d, 6,7-tetrahydrothiazole [5,4-cjpyridin-2-yl] carbonyljamino, cyclohexyl) aminojcarbonyl, phenyl) (imino) methylcarbamic 2d2) N-. { (1 R, 2S, dS) -2- ( { 3- [amino (imino) methyl] benzoyl.}. Amino) -d- [(dimethylamino) carbonyl] cyclohexyl} -5-methyl-4,5,6,7-tetrahydrothiazo [5,4-c] pyridine-2-carboxamide 253) N-. { (1 R, 2S, dS) -2 - [(3-cyanobenzoyl) amino-d-d [(dimethylamino) carbonyl] cyclohexyl} -d-methyl-4, d, 6,7-tetrahydro-azole [d, 4-c] pyridine-2-carboxamide 2d4) N-. { (1 R, 2S, dS) -2- ({3 - [amino (hydroxyamino) methyl] benzoyl}. Amino) -d - [(dimethylamino) carbonyl-cyclohexyl} - d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-carboxamide 0 2dd) ethyl ester of the acid (3- {[((1S, 2R, 4S) -4- [(dimethylamino) carbon.lj-2-. {[[(D-methyl-4, d, 6,7-tetrahydro-diazole [d, 4-cjpyridin-2-yl] carbonyl] amino.}. cyclohexyl) amino] carbonyl, phenyl, (meth) methylcarbamic, 256) N - [(1 R, 2S, 5S) -d - [(dimethylamino) carbonylj-2- ( {.3- [imino (methylamino) methylbenzoyl}., Amino) cyclohexyl] -d-methyl-4, d, 6,7-d tetrahydrothiazole [d, 4-cjpyridine-2-carboxamide 2d7) N -. { (1R, 2S, dS) -2- (. {3- [Amino (methoxyimino) methyl] benzoyl} amino) -d - [(dimethylamino) carbonyl] cyclohexyl} - d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-carboxamide 2d8) N-. { (1 R, 2S, dS) -2-. { [(Z) -3- (d-chlorothien-2-yl) -2-fluoro-2-propenoyl] amino} -d - [(dimethylamino) carbonyl] cyclohexyl} -d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridine-2-carboxamide 2d9) tert-butyl ester of (1S, 3R, 4S) -4- (. {2- [(d-chloropyridin-2-yl) aminoj-2-oxoethanothioyl.] amino) -3-. { [(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4 c] pyridin-2-yl) carbonyljamino} cyclohexanecarboxylic acid 260) (1S, 3R, 4S) -4- (. {2 - [(d-Chloro-2-pyridinyl) amino] -2-d-oxoethanethyl] -amino) -3-. { [(d-methyI-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] amino} cyclohexanecarboxylic acid 261) N 1 - (d-chloropyridin-2-yl) -N 2 - [(1 S, 2R, 4R) -2-. { [(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] amino} -4- (thiazol-2-yl) -cyclohexyl-triethanediamide, N 1 - (d-chloropyridin-2-yl) -N 2 - [(1S, 2R, 4S) -2-. { [(d-methyl-0 4, dI6,7-tetrahydroxy [d, 4-cjpyridin-2-yl) carbonyl] amino} -4- (tiazol-2-yl) cyclohexyl] ethanediamide 262) N 1 - (d-chloropyridin-2-yl) -N 2 - [(1S, 2R, 4S) -2-. { [(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridin-2-yl) carbonyl] amino} -4- (1, 2,4-oxadiazol-3-yl) cyclohexyl] ethanediamide d 263) N 1 - (d-chloropyridin-2-yl) -N 2 - [(1 S, 2R, 4S) -2-. { [(d-methyl-4, d, 6,7-tetrahydrothiazol [5,4-c] pyridin-2-yl) carbonyl] amino} -4- (d-methyl-1, 3,4-oxadiazol-2-yl) cyclohexyl] ethanediamide 264) N 1 - (d-chloropyridin-2-yl) -N 2 - [(1S, 2R, 4S) - 2-. { [(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] amino} -4- (1, 3,4-oxadiazol-2-yl) cyclohexyl] ethanediamide 26d) N 1 - (5-chloropyridin-2-yl) -N 2 - [(1S, 2R, 4S) -2-. { [(5-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyljamino} -4- (1, 3-oxazol-2-yl) cyclohexyl] ethanodiamide 266) N 1 - (d-chloropyridin-2-yl) -N - ((1 S, 2R, 4S) -4- (d-methyl- 1, 3,4-oxadiazol-2-yl) -2-. {[[(D-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] -amino. cyclohexyl) ethanediamide 267) N 1 - (d-chloropyridin-2-yl) -N 2 - [(1S, 2R, 4S) -2-. { [(d-methyl-4, d, 6,7-d-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] amino} -4- (1, 3,4-thiadiazol-2-yl) cyclohexyl-ketanediamine 268) N - [(1 R, 2S, dS) -5 - [(dimethylamino) carbonyl] -2- (. {2 - [( 5-fluoropyridin-2-yl) aminoj-2-oxoethanethiol.] Amino) cyclohexyl-d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridine-2-carboxamide 0 269) N - [(1 R, 2S, dS) -d - [(dimethylamino) carbonyl] -2- (. {2 - [(d-fluoropyridin-2-yl) amino] -2-oxoethanethioyl}. amino) cyclohexyl] -5-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-carboxamide 270) N 1 - (d-chloropyridin-2-yl) -N 2- [(1S, 2R, 4S) -2-. { [(d-methyl-4, d, 6,7-tetrahydrothiazo [5,4-c] pyridin-2-yl) carbonyl] amino} -4- (5-methyl-1, 3,4-thiadiazol-2-yl) cyclohexyl] ethanediamide 271) N 1 - (5-chloropyridin-2-yl) -N 2 - [(1 S ^ R ^ S ^ -ÍKd -methyl ^^ J- tetrahydrothiazo [5,4-c] pyridin-2-yl) carbonyl] amino} -4- (1,3-oxazol-5-yl) cyclohexyl] ethanediamide 272) N 1 - (5-chloropyridin-2-yl) -N 2 - ((1 S, 2R, 4S) -4- (d-methyl- 1, 2,4-oxadiazol-3-yl) -2- { [(D-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridn-2-yl) carbonyljamino} cyclohexyl) ethanediamide 273) N 1 - (dc] oropyridin-2-yl) -N 2 - ((1S, 2R, 4S) -2-. {[[(d-methyl-4, d, 6,7-tetrahydrot Azol [d, 4-c] pyridn-2-yl) carbonyl] amino.} -4- (4H-1, 2,4-triazole-4-yl) cyclohexyl) ethanediamide 274) N 1 - (d-chloro-2-thienyl) -N 2 - ((1 S, 2R, 4S) -4- (d-methyl-1, 3,4-5 oxadiazol-2-yl) -2-. [(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridn-2-yl) carbonyl] amino] cyclohexyl) ethanediamide 27d) N 1 - (d- bromo-2-pyridinyl) -N2 - ((1 S, 2R, 4S) -4- (d-methyl-1, 3,4-oxadiazole-2-yl) -2-. {[[(d -met.l-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridin-2-yl) carbonyl] amino.}. cyclohexyl) ethanediamide 0 276) N 1 - (4-chlorophenyl) -N 2 - ((1S , 2R, 4S) -4- (d-methyl-1, 3,4-oxadiazol-2-yl) -2-. {[[(D-methyl-4, d, 6,7-tetrahydrothiazole [d, 4 -cjpyridin-2-yl) carbonamino.}. cyclohexyl) ethanediamide 277) N - [(1R, 2S, dS) -2-. { [(d-chloro-1 H-indol-2-yl) carbonyl] amino} -d- (d-methyl-1, 3,4-oxadiazol-2-yl) cyclohexyl-d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-dc] pyridin-2-carboxamide 278 N1 - ((1 S, 2R, 4S) -4- (5-methyl-1, 3,4-oxadiazol-2-yl) -2-. {[[(D-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] amino., Cyclohexyl) -N2-. { d- [2- (trimethylsilyl) ethynyl] pyridin-2-yl} ethanediamida 279) N1- (d-ethynylpyridin-2-yl) -N2 - ((1 S, 2R, 4S) -4- (5-methyl-1, 3,4-oxadiazole-2-yl) -2- { [(D-methyl-4, d, 6,7-tetrahydrozolo [d, 4-c] pyridin-2-yl) carbonyljamino} cyclohexyl) ethanediamide 280) 7-chloro-N - ((1 S, 2R, 4S) -4- (d-methyl-1, 3,4-oxadiazol-2-yl) -2- { [(D-methyl-4,5,6,7- tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonylamino] cyclohexyl) -3-cinnolinecarboxamide 281) N - [(1 R, 2S, dS) -2-. { [(Z) -3- (4-chlorophenyl) -2-fluoroacryloyl-amino} -d d- (d-methyl-1, 3,4-oxadiazol-2-yl) c-chlorhexyl-d-methyl-4, d, 6,7-tetrahydrothiazole [5,4-cjpyridin-2 -carboxamide 282) 7-chloro-N- ((1 S, 2R, 4S) -4- (d-methyl-1, 3,4-oxadiazol-2-yl) -2-. {[[(d-methyl) -4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] amino}. C.clohexyl) -3- isoquinolinecarboxamide 0 283) 6-chloro-N - ((1S, 2R, 4S) -4- (d-methyl-1, 3,4-oxadiazol-2-yl) -2-. {[[(D-methyl-4, d, 6, 7-tetrahydrothiazole [d, 4-c] pyridyl-2-yl) carbonyl] amino} cyclohexyl) -4-oxo-1,4-dihydro-2-quinazolinecarboxamide 284) N1- (d-chloropyridin-2-yl) -N2 - [(1S, 2R, 4S) -2-. { [(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyljamino} -4- (1, 2,4-oxadiazoI-d-d-yl) cyclohexyl] -Jethanedi-dia 28 d) N 1 - (d-chloropyridin-2-yl) -N 2 -. { (1S, 2R, 4S) -2-. { [(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridin-2-yl) carbonyl] amine} -4- [d- (trifluoromethyl) -1, 3,4-oxadiazol-2-ylcyclohexyl} ethanedi amide 286) N1- (5-chloro-2-thienyl) -N2 - ((1 S, 2R, 4S) -4- (3-methyl-1, 2,4-oxadiazol-5-yl) - 2- { [(D-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl] amino.}. Cyclohexyl) ethanediamide 287) N - (6- chloropyridazin-3-yl) -N2 - ((1 S, 2R, 4S) -4- (3-methyl-1, 2,4-oxadiazol-d-yl) -2-. {[[(d-methyl- 4,5,6,7-tetrahydrothiazole [5,4-c] pyridin-2-yl) carbonyljamino} cyclohexyl) ethanediamide 288) N 1 - (d-chloropyridin-2-yl) -N 2 - [(1S, 2R , 4S) -2-. { [(d-methyl-4,5,6,7-d-tetrahydrothiazole [d, 4-c] pyridin-2-yl) carbonyl-amino} -4- (2-oxo-1,3-oxazolidin-3-yl) cyclohexyl-J-ethanediamide 289) N 1 - (d-chloropyridin-2-yl) -N 2 - [(1S, 2R, 4S) -2- . { [(d-methyl-4,5,6,7-tetrahydrothiazole [d, 4-cjpyridin-2-yl] carbonyljamino} -4- (tetrazol-1-yl) cyclohexyl] ethanedi amide 0 290) N 1 - (d-chloropyridin-2-yl) -N 2 - [(1 S, 2R, 4S) -2-. { [(d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridin-2-yl] carbonyl] amino} -4- (1 H-pyrrol-1-yl) -cyclohexyl-diene-thiamine-291) N 1 - (d-chloropyridin-2-yl) -N 2 - [(1 S, 2 R, 4 S) -2-. { [(d-methyl-4, d, 6,7-tetrahydrothiazo [5,4-c] pyridin-2-yl) carbonyl] amino} -4- (1, 2,4-triazol-d-d-yl) cyclohexyl-trienedi amide 292) N1- (d-chloropyridin-2-yl) -N2 - [(1S, 2R, 4S) -2-. { [(d-methyl-4, d, 6,7-tetrahydrothiazo [5,4-c] pyridin-2-yl) carbonyl] amino} -4- (1-methyl-1 H-1, 2,4-triazol-5-yl) cyclohexyl-trienedi amide 293) 7-chloro-N- ((1 S, 2R, 4S) -4- (3-methyl) -1, 2,4-oxadiazol-d-yl) -2- { [(D-methyl-4, d, 6,7-tetrahydrothioazo [d, 4-c] pyridin-2-yl) carbonyl ] amino.}. cyclohexyl) -3- cinnolinecarboxamide 294) N1- (5-chloropyridin-2-yl) -N2 - ((3R, 4S) -3- { [(5-methyl-4,5 , 6,7-tetrahydrothiazole [d, 4-cJpyridin-2-yl) carbonyl] amino.} -1- (thiazol-2-yl) p -peridin-4-yl) ethanediamide Each of these compounds can produced using the compound d (d) as starting material through a method described in the Examples of the International Publication WO2004 / 0d8728.

EXAMPLES To further illustrate the present invention in more detail the following examples will be given; however, it will be understood that the present invention is not limited thereto.

EXAMPLE OF PRODUCTION 1 d 2-Cyano-5-methyl-4,5,6-tetrahydrothiazole 5,4-chloropyridine monohydrate hydrochloride • N N, N-dimethylacetamide (2d mL) was added to a cyanide mixture of copper (2.88 g) and sodium cyanide (1.68 g), and the resulting mixture was heated to 150 ° C until all the ingredients were completely dissolved to give a clear colorless solution. 2-Bromo-5-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cjpyridine (d.00 g) was added to the solution, and the resulting mixture was stirred at 1 ° C for 18 hours . The reaction mixture was allowed to cool to room temperature and toluene and saturated aqueous sodium bicarbonate were added thereto. After having filtered any insoluble material, the toluene layer was separated from the aqueous layer, and the aqueous layer was further extracted with toluene twice. The toluene layers were combined, and the combined toluene layer was dried over anhydrous sodium sulfate. After having filtered any insoluble material, the filtrate was concentrated under reduced pressure, and the concentrated residue was dissolved in ethanol (3d mL). To the solution was added 1 N HCl dropwise in ethanol (2d mL) at room temperature, to then form a hydrochloride salt, and the resulting mixture was stirred at 0 ° C for 1 hour. The precipitated crystals were collected by filtration, and washed with ethanol (20 mL). The wet crystal thus obtained was dried at room temperature under reduced pressure, to then give 3.0d g of the title compound. 1 H-NMR (D 20) dppm: 4.72 (br, 2H), 3.77 (br, 2H), 3.36-3.29 (t, 2H.J = 6.2Hz), 3.13 (s, 3H). MS (FAB) m / z: 180 (M + H) + Elemental Analysis: as C18H? 2CIN3OS, Calculated: C, 41.11; H, 5.18; CI, 15.17; N, 17.98; S, 13.72 Found: C, 41.22; H, 4.99; CI, 15.26; N, 17.95; S, 13.69 EXAMPLE OF PRODUCTION 2 2-Cyano-5-methyl-4,5,6-tetrahydrothiazole | [5,4-clpyridine A solution of sodium bicarbonate (272.33 mg) in water (d mL) was added to 2-cyano-d-methyl-4,5,6,7-tetrahydrothiazole [5,4-cjpyridine monohydrate (600.30 mg) hydrochloride) At room temperature, and after dissolving all the ingredients completely, the resulting solution was extracted with toluene three times (10 mL * 3). The toluene layers were combined, and the combined toluene layer was dried over anhydrous sodium sulfate (2.00 g). After having filtered any insoluble material, the filtrate was concentrated at 40 ° C under reduced pressure, to then give 384.28 mg of the title compound. 1 H-NMR (CDCl 3) dppm: 3.76-3.73 (t, 2 H, J = 1.5 Hz), 3.03-2.98 (dt, 2H, J = 1.5.5.9Hz), 2.89-2.84 (t, 2H, J = 5.9Hz), 2.62 (s, 3H). MS (FAB) m / z: 180 (M + H) + Elemental Analysis: as C8HgN3S, Calculated: C, d3.61; H, d.06; N, 23.44; S, 17.89 Found: C, d3.40; H, d.08; N, 23.41; S, 17.89 EXAMPLE OF PRODUCTION 3 5-Methyl-4,5,6-tetrahydrothiazoyl-5,4-clpyridine-2-carboxylic acid hydrochloride To 2-cyano-d-methyl-4, d, 6,7-tetrahydrothiazole [5,4-cjpyridine monohydrate (500.61 mg) hydrochloride) were added ethanol (5 mL) and aqueous 4N lithium hydroxide (1.34 mL) at room temperature. environment, and the resulting mixture was stirred at d0 ° C for 7 hours. After cooling the reaction mixture with ice water, 1 N HCl in ethanol (7.d mL) was added, to then form a hydrochloride salt, followed by stirring at the same temperature for 1.5 hours. The precipitated crystals were collected by filtration, and washed with ethanol (2 mL). The wet crystal was dried at room temperature under reduced pressure, to then give 466.98 mg of the title compound. 1 H-NMR (D 20) dppm: 4.82-4.88 (d, 1 H, J = 16.0 Hz), 4.51-4.57 (d, 1 H, J = 16.0 Hz), 3.88-3.96 (m, 1 H), 3.60- 3.70 (m, 1 H), 3.22-3.33 (m, 2H), 3.15 (s, 3H). MS (EI) m / z: 198 (M) + Elemental Analysis: as CSH-HCIN ^ S, Calculated: C, 40.94,?, 4.72; CI, 15.11; N, 11.94; S, 13.66 Found: C, 40. d0; H, 4.66; CI, 1d.31; N, 11.97; S, 13.68 EXAMPLE OF PRODUCTION 4 5-Methyl-4,5-6,7-tetrahydrothiazoir-5,4-clpyridine-2-carboxylic acid hydrochloride A 2-cyano-5-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine (199.30 mg) were added ethanol (2 mL) and aqueous 4N lithium hydroxide (0.42 mL) at room temperature, and the mixture was stirred at dO ° C for 10 hours. The reaction mixture was cooled with ice water, and 1N HCl in ethanol (2.8 mL) was added, to then form a hydrochloride salt. The precipitated crystals were collected by filtration, and washed with ethanol (1 mL). The wet material was dried at room temperature under reduced pressure, to then give 216.37 mg of the title compound. 1 H-NMR (D 20) dppm: 4.82-4.88 (d, 1 H, J = 16.0 Hz), 4.51-4.57 (d, 1H, J = 16.0Hz), 3.88-3.96 (m, 1H), 3.60-3.70 (m, 1H), 3.22-3.33 (m, 2H), 3.15 (s, 3H). MS (EI) m / z: 198 (M) + EXAMPLE OF PRODUCTION 5 5-Methyl-4,5,6-tetrahydrothiazolf-5,4-c1pyridine 2-Amino-5-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-cJpyridine (10.00 g) was dissolved in a mixture of sulfuric acid (2d mL), hypophosphorous acid (60%, 13 mL) and water (100 mL) from 15 to 18 ° C, to then give an orange solution. To the solution was added dropwise a solution of sodium nitrite (8.15 g) in water (30 mL) at -2 to 3 ° C for 30 minutes. After stirring the resulting mixture at 0 to 10 ° C for 2.5 hours, 8N aqueous potassium hydroxide (130 mL) was added dropwise, and the pH was found to be 12.6. The precipitated potassium sulfate was filtered and washed with ethyl acetate (200 mL). The aqueous layer was separated from the filtrate, and extracted further with ethyl acetate twice (200 mL 2). The organic layers were combined, and the combined organic layer was dried over anhydrous sodium sulfate (30.00 g). After having filtered any insoluble material and washed it with ethyl acetate (100 mL), the filtrate was concentrated under reduced pressure, to then give 6.15 g of the title compound. 1 H-NMR (CDCl 3) dppm: 8.62 (s, 1 H), 3.71-3.67 (t, 2 H, J = 1.7 Hz), 3. 01-2.95 (dt, 2H, J = 1.7Hz, 5.9Hz), 2.84-2.80 (t, 2H, J = d.9Hz), 2.61 (s, 3H).

EXAMPLE OF PRODUCTION 6 Salt of 5-methyl-4,5,6,7-tetrahydrothiazole-5,4-c-pyridine p-toluenesulfonic acid d-Methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine (1.00 g) was dissolved in 2-propanol (10 mL) at room temperature, and p-toluenesulfonic acid monohydrate (1.23 g) was added at room temperature, followed by stirring at room temperature for 20 minutes. When the resulting mixture was cooled to 0 ° C, a salt crystallized from the mixture. After the resulting mixture had been stirred at 0 ° C for 2 hours, the precipitated salt was collected by filtration and washed with 2-propanol (2 mmoles). The wet material was dried at room temperature under reduced pressure, to then give 1.91 g of the title compound. 1 H-NMR (D 20) dppm: 9.00 (s, 1 H), 7.68-7.65 (d, 2H, J = 8.1 Hz), 7.3d- 7.32 (d, 2H, J = 8.1 Hz), 4.2d-4.8d (br, 2H), 3.40-3.96 (br, 2H), 3.26-3.18 (t, 2H, J = 6.0Hz), 3.08 (s, 3H), 2.38 (s, 3H). MS (EI) m / z: 1d4 (M) + Elemental Analysis: as C? 4H18N203S2, Calculated: C, d1.d1; H, 5.d6; N, 8.d8; S, 19.6d Found: C, d1 .24; H, d.d2; N, 8.81; S, 19.37 EXAMPLE OF PRODUCTION 7 5-Methyl-4,5,6,7-tetrahydrothiazoir-5,4-c1pyridine-2-carboxylic acid d-Methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine (1.00 g) was dissolved in toluene (10 mL) at room temperature, and triethylamine (1.81 mL) and trichloroacetyl chloride (1.46 mL) were added sequentially at room temperature , followed by stirring at room temperature for 4 hours. To the resulting mixture was added a solution of lithium hydroxide monohydrate (1.22 g) in water (10 mL) in order to perform a hydrolysis. The organic layer was separated from the aqueous layer, and extracted further with water (10 mL). The aqueous layers were combined, and the combined aqueous layer was concentrated in a 60 ° C bath under reduced pressure. Ethanol (10 mL) was added, and the resulting mixture was concentrated once more under reduced pressure. Ethanol (15 mL) was added to the concentrated residue, and the resulting mixture was cooled with ice water. Concentrated hydrochloric acid (2.7 mL) was added dropwise to then form a hydrochloride salt, and the resulting mixture was stirred at the same temperature for 1.5 hours. The precipitated crystals were collected by filtration, and washed with ethanol (4 mL). The wet material was dried at room temperature under reduced pressure, to then give 1.2d g of the title compound. 1 H-NMR (D 20) dppm: 4.82-4.88 (d, 1 H, J = 16.0 Hz), 4.61-4.67 (d, 1 H, J = 16.0 Hz), 3.88-3.96 (m, 1 H), 3.60- 3.70 (m, 1 H), 3.22-3.33 (m, 2H), 3.15 (s, 3H) MS (FAB) m / z: 199 (M + H) + d EXAMPLE OF PRODUCTION 8 2-Amino-5-me .il-4,5,6,7-tetrahydrothiazoir5,4-c1pyridine A solution of 1-methyl-4-piperidone (180.0 g) in 2-propanol (1.44 L) was heated to 60 ° C, and a solution of cyanamide (67.0 g) in 2-propanol (360 ° C) was sequentially added to the solution. mL) and sulfur powder (61.0 g). After adding a catalytic amount of pyrrolidine (13.3 mL), the resulting mixture was stirred at or above 50 ° C for 2 hours, and allowed to cool to room temperature, followed by stirring overnight. The resulting mixture was cooled to or below 10 ° C in an ice water bath, and stirred for 1 hour at the same temperature. The precipitated crystals were collected by filtration, and washed with 2-propanol (640 mL). The wet crystal was dried at 40 ° C under reduced pressure, to then give 209.9 g of the title compound. 1 H-NMR (CDCl 3) dppm: 4.86 (br, 2 H), 3.47-3.46 (t, 2 H, J = 1.9 Hz), 2.78-2.71 (m, 2 H), 2.71-2.65 (m, 2 H), 2.47 (s) , 3H).

MS (FAB) m / z: 170 (M + H) + Elemental Analysis: as C7HnN3S, Calculated: C, 49.68; H, 6.55; N, 24.83; S, 18.95 Found: C, 49.70; H, 6.39; N, 24.91; S, 19.00 EXAMPLE OF PRODUCTION 9 2-Amino-5-methyl-4,5,6,7-tetrahydrothiazolf5,4-c1pyridine dihydrobromide 1-Methyl-4-piperidone (100.0 g) was dissolved in 2-propanol (800 mL) at room temperature, and the solution was heated to an internal temperature of 50 ° C in a water bath. To the resulting mixture was added sequentially a solution of cyanamide (37.16 g) in 2-propanol (200 mL) and sulfur powder (28.34 g) at 50 ° C. A catalytic amount of pyrrolidine (7.4 mL) was added thereto, and the resulting mixture was stirred at 60 to 64 ° C for 1 hour. After the resulting mixture was allowed to cool to room temperature, 48% hydrobromic acid (358.0 g) of 30 to 40 ° C was added dropwise, and the mixture was cooled to or below 10 ° C in a water bath freezing, followed by stirring at the same temperature for 1.5 hours. The precipitated crystals were collected by filtration, and washed with 2-propanol (500 mL). The wet crystal was dried at 40 ° C under reduced pressure, to then give 258.2 g of the title compound. 1 H-NMR (D 20) dppm: 4.46-4.63 (d, 1 H, J = 1d.2Hz), 4.20-4.26 (d, 1 H, J = 15.2Hz), 3.76-3.90 (m, 1 H), 3.60 -3.67 (m, 1 H), 3.10 (s, 3H), 2.91-3.18 (m, 2H). Elemental Analysis: as C7H-.3Br2N3S, Calculated: C, 2d.39; H, 3.96; Br, 48.27; N, 12.69; S, 9.69 Found: C, 2d.d4; H, 3.93; Br) 48.09; N, 12.62; S, 9.72 EXAMPLE OF PRODUCTION 10 2-Bromo-5-methyl-4,5,6,7-tetrahydrothiazoir5,4-clpiridine 2-Amino-d-methyl-4, d, 6,7-tetrahydrothiazole [d, 4-c] pyridine (600.0 g) was suspended in water (6.0 L), and 48 hydrobromic acid was added dropwise. % (4.2 L) from 5 to 15 ° C. A solution of sodium nitrite (367.2 g) in water (1.8 L) from 0 to d ° C was added dropwise over 1.5 hours, and the reaction mixture was heated to 30 ° C, followed by stirring for 24 hours. The resulting mixture was made strongly basic (pH 12.5) with aqueous 5N sodium hydroxide (6.0 L). The aqueous layer was extracted with toluene twice (12.0 L, 6.0 L), and the toluene layers were combined. The combined toluene layer was dried over anhydrous sodium sulfate (1202.0 g), and after filtering any insoluble material, the mother liquor was concentrated at 40 ° C under reduced pressure, to then give 667.6 g of the title compound. 1 H-NMR (CDCl 3) dppm: 3.58-3.67 (t, 3 H, J = 1.8 Hz), 2.92-2.87 (m, 2 H), 2.81-2.76 (m, 2 H), 2.49 (s, 3 H).

EXAMPLE OF PRODUCTION 11 Salt of 2-bromo-5-metH-4,5,6-tetrahydrothiazoir-5,4-clpyridine p-toluenesulfonic acid 2-Bromo-5-methyl-4, d, 6,7-tetrahydrothiazole [5,4-c] pyridine (567.6 g) was dissolved in methanol (3.9 L), and a solution was added dropwise to the solution. Solution of p-toluenesulfonic acid monohydrate (500.0 g) in methanol (1.7 L) at 30 ° C. The resulting mixture was stirred at the same temperature for 1 hour, and then at or below 10 ° C for 2 hours. The precipitated crystals were collected by filtration, and washed with methanol (1.1 L), followed by drying at 40 ° C under reduced pressure, to then give 861.9 g of the title compound. 1 H-NMR (DMSO-d 6) dppm: 10.16 (br, 1 H), 7.47-7.43 (d, 2H, J = 8.2Hz), 7.09-7.07 (d.2H.J = 8.2Hz), 4.47 (s, 2H), 3.58 (s, 2H) 3.04 (t, 2H, J = 6.1 Hz), 2.96 (s, 3H), 2.29 (s, 3H). Elemental analysis: as C14H? 7BrN203S2, Calculated: C, 41.48; H, 4.23; Br, 19.71; N, 6.91; S, 15.82 Found: C, 41.52; H, 4.33; Br, 19.80; N, 6.99; S, 15.90 EXAMPLE OF PRODUCTION 12 Salt of 2-bromo-5-methyl-4,5,6-7-tetrahydrothiazoir-5,4-clpiridin p-toluenesulfonic acid Dihydrobromide of 2-amino-5-methyl-4, d, 6,7-tetrahydrothiazole [5,4-cjpyridine (60.01 g) was suspended in a mixture of water (260 mL) and 48% hydrobromic acid (175 mL) at room temperature. After the suspension had cooled to an internal temperature of 10 ° C or lower, a solution of sodium nitrite (15.63 g) in water (75 mL) was added dropwise for 1.5 hours, while the internal temperature was maintained at or above below 10 ° C. After having stirred the resulting mixture at or below 10 ° C for 20 hours, 10N aqueous sodium hydroxide (175 mL) was added dropwise, while keeping at or below 20 ° C, to then make it a basic solution, and it was found that the pH of the resulting solution was 13.1. Subsequently, the aqueous layer was extracted with toluene twice (375 mL, 250 mL), and the toluene layers were combined. A quarter of the amount of the combined toluene layer was used for the following procedures. The toluene layer was concentrated, and the concentrated residue was dissolved in methanol (43.8 mL). A solution of p-toluenesulfonic acid monohydrate (5.03 g) in methanol (18.8 mL) was added dropwise at room temperature, and the mixture was cooled to or below 10 ° C, followed by stirring at the same temperature for 1.5 hours. . The precipitated crystals were collected by filtration, and washed with methanol (18.8 mL). The wet crystal was dried at 40 ° C under reduced pressure, to then give 9.05 g of the title compound. 1 H-NMR (DMSO-d 6) dppm: 10.16 (br, 1 H), 7.47-7.43 (d, 2H, J = 8.2Hz), 7.09-7.07 (d, 2H, J = 8.2Hz), 4.47 (s, 2H), 3.68 (s, 2H), 3.04 (t, 2H, J = 6.1 Hz) , 2.96 (s, 3H), 2.29 (s, 3H). Elemental analysis: as C? 4H? 7BrN203S2, Calculated: C, 41.48; H, 4.23; Br, 19.71; N, 6.91; S, 1 d.82 Found: C.41.d4; H, 4.18; Br, 19.83; N, 7.03; S, 16.02 EXAMPLE OF PRODUCTION 13 5-Methyl-4,5,6,7-tetrahydrothiazoir-5,4-clpyridine-2-carboxylate lithium To the salt of 2-bromo-5-methyl-4,5,6,7-tetrahydrothiazole [d, 4-cjpyridine p-toluenesulfonic acid (490.0 g) was added 2N aqueous sodium hydroxide (2.4dL), and the The mixture was stirred at room temperature for 30 minutes. The resulting mixture was extracted with toluene twice (4.9 L x 2), and the organic layer was dried over anhydrous sodium sulfate (979.8 g). After having filtered any insoluble material, the mother liquor was concentrated at or below 40 ° C under reduced pressure, to then give 2-bromo-d-methyl-4,5,6,7-tetrahydrothiazole [5,4-c ] pyridine (284.0 g) as an oily brown compound. The resulting 2-bromo-5-methy [4,5,6,7-tetrahydroxyazole [5,4-c] pyridine (284.0 g) was dissolved in anhydrous tetrahydrofuran (2.84 L). After purging the system with argon, n-butyllithium (as 1.59 mol / L solution of n-hexane, 766 mL) was added dropwise to the solution of -40 to -30 ° C, and the resulting mixture was stirred at the same temperature for 1 hour. After passing carbon dioxide gas through the reaction mixture of -40 to -25 ° C, the mixture was stirred under carbon dioxide atmosphere at the same temperature for 1 hour. The resulting mixture was warmed to room temperature, and ethyl acetate (1.42 L) was added thereto. The precipitated solid was filtered and washed with ethyl acetate (0.85 L). The solid material thus obtained was dried at 40 ° C under reduced pressure and pulverized, to then give 235.1 g of the title compound. 1 H-NMR (DMSO-d 6) dppm: 3.54 (s, 2 H), 2.65-2.85 (m, 4 H), 2.36 (s, 3 H).

EXAMPLE OF PRODUCTION 14 5-Methyl-4,5,6-tetrahydrothiazolf-5,4-clpyridine-2-carboxylic acid hydrochloride A 5-methyl-4,5,6,7-tetrahydrothiazole [5,4-c] pyridin-2 -lithium carboxylate (3.00 g) was added 1 N HCl in ethanol (36 mL), and the mixture was stirred at room temperature for 1 hour. The precipitated crystals were collected by filtration and washed with ethanol (9 mL). The wet crystal was dried at room temperature under reduced pressure, to then give 2.76 g of the title compound. 1 H-NMR (D 20) dppm: 4.82-4.88 (d, 1 H, J = 16.0Hz), 4.51-4.67 (d, 1H, J = 16.0Hz), 3.88-3.96 (m, 1H), 3.60-3.70 ( m, 1H), 3.22-3.33 (m, 2H), 3.15 (s, 3H). Elemental analysis: as C8HnCIN202S, Calculated: C, 40.94; H, 4.72; N, 11.94; S, 13.66 Found: C, 40.51; H, 4.65; N, 11.79; S, 13.63 EXAMPLE OF PRODUCTION 15 5-Methyl-4,5,6-tetrahydrothiazoyl-5,4-clpyridine-2-carboxylic acid hydrochloride Salt of 2-bromo-5-methyl-4,5,6,7-tetrahydrothiazole [d, 4-c] pyridine p-toluenesulfonic acid (40.00 g) was mixed with 1 N aqueous sodium hydroxide (200 mL) at room temperature environment, and the mixture was stirred for 30 minutes. The aqueous layer was extracted with toluene twice (400 mL x 2), and the organic layers were combined. The combined organic layer was washed with 5% brine (200 mL) and concentrated to 80 mL at an outside temperature of 50 ° C or lower under reduced pressure. A sample of a water content measurement was taken from the resulting mixture (weight of the mixture after concentration: 91.03 g, weight of the mixture after taking the sample: 87.68 g). The sample of the concentrated mixture was subjected to water content measurement with a Karl-Fischer moisture titrant, and the water content was found to be 0.0231% (in a weight-to-weight ratio). The remaining portion of the concentrated mixture after taking the sample was dissolved in anhydrous tetrahydrofuran (231 mL). After purging the system with argon, the reaction mixture was cooled to an internal temperature of -30 ° C or lower, and n-butyllithium (as 1.59 mol / L n-hexane solution) was added to the solution. , 61.7 mL) while the internal temperature was maintained at or below -30 ° C, followed by stirring at the same temperature for 1 hour. After passing carbon dioxide gas through the resulting mixture, while the internal temperature was maintained at or below -30 ° C, the reaction mixture was stirred under carbon dioxide atmosphere for 1 hour. The resulting mixture was heated to an internal temperature of 1 d ° C, and methanol (193 mL) was added, to then dissolve the precipitated solid, and concentrated hydrochloric acid (19.3 mL) was added dropwise, while the internal temperature was maintained at or below 20 ° C. The resulting mixture was cooled to an internal temperature of 10 ° C or lower, and stirred at the same temperature for 1 hour. The precipitated crystals were collected by filtration, and washed with methanol (68 mL). The wet crystal was dried at room temperature under reduced pressure, to then give 21.20 g of the title compound. 1 H-NMR (D 20) dppm: 4.82-4.88 (d, 1 H, J = 16.0 Hz), 4.51- 4.57 (d, 1 H, J = 16.0 Hz), 3.88-3.96 (m, 1 H), 3.60- 3.70 (m, 1 H), 3.22-3.33 (m, 2H), 3.1d (s, 3H). MS (EI) m / z: 198 (M) + Elemental Analysis: as C8HnCIN202S, Calculated: C, 40.94; H, 4.72; CI, 1d.11; N, 11.94; S, 13.66 Found: C, 40.83; H, 4.66; CI, 14.81; N, 11.91; S, 13.87 EXAMPLE OF PRODUCTION 16 N1- (5-Chloropyridine-2-in-N2 - ((1S, 2R.4S) -4-r (dimethylamino) carbonin-2- ( r (5- methyl-4,5,6,7-tetrahydrothiazoyl-5,4-clpyridin-2-yl) carbonyl-amino} -cy cheryl) ethanediamide N1-. { (1S, 2R, 4S) -2-Amino-4 - [(dimethylamino) carbonyl] cyclohexyl} -N2-0 (5-chloropyridin-2-yl) ethanediamide (653.4 mg) was dissolved in dimethylacetamide (7 mL), and to the solution were added 1-hydroxybenzotriazole monohydrate (245.1 mg), 5-methyl-4-hydrochloride. , 5,6,7-tetrahydrothiazole [5,4-cjpyridine-2-carboxylic acid (386.0 mg) and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (34d.O mg) at room temperature. The resulting mixture was stirred for 13 hours, and triethylamine and water were added thereto. The precipitated crystals were collected by filtration and dried, to then give 674.1 mg of the title compound. 1 H-NMR (CDCl 3) dppm: 1.60-1.98 (3H, m), 2.00--2.16 (3H, m), 2.52 (3H, s), 2.78-2.90 (3H, m), 2.92-2.98 (2H, m), 2.95 (3H, s), 3.06 (3H, s), 3.69 (1H, d, J = 15.4Hz) , 3.75 (1 H, d, J = 15.4 Hz), 4.07-4.16 (1 H, m), 4.66-4.72 (1 H, m), 7. 40 (1 H, d.J = 8.8.0.6Hz), 7.68 (1 H, dd, J = 8.8.2.4Hz), 8.03 (1 H, d, J = 7.8Hz), 8.16 (1 H, dd, J = 8.8,0.6Hz), 8.30 (1H, dd, J = 2.4,0.6Hz), 9.72 (1H, s). MS (ESI) m / z: 648 (M + H) +.

Claims (14)

1. NOVELTY OF THE INVENTION CLAIMS 5 1. A process for producing a compound of the formula (d) or its salt: Or said process being characterized by comprising the reaction of a compound of the formula (3) or its salt: d with a metal cyanide, to then obtain a compound of the formula (4) or its salt: and hydrolyzing the obtained compound or its salt.
2. 2. A process for producing a compound of the formula (4) or its salt: said process being characterized as comprising the reaction of a compound of the formula (3) or its salt: with a metal cyanide.
3. 3. A process for producing a compound of the formula (d) or its salt: said process being characterized by comprising the hydrolysis of a compound of the formula (4) or its salt.
4. 4. The process according to claim 1 or 2, further characterized in that the metal cyanide is a mixture of sodium cyanide and copper cyanide.
5. 5. The process according to claim 1 or 3, further characterized in that the hydrolysis is carried out through treatment with an aqueous solution of an alkali metal hydroxide.
6. 6. The process according to claim 5, characterized in that the alkali metal hydroxide is lithium hydroxide.
7. 7. A process for producing a compound of the formula (5) or its salt: said process being characterized by comprising the reaction of a compound of the formula (2) or its salt: with an alkali metal nitrite in the presence of a reducing agent in an aqueous solution of an acidic compound, to then obtain a compound of the formula (6) or its salt: and reacting the obtained compound or its salt with trihalogenoacetyl halide in the presence of a base, followed by hydrolysis.
8. 8. A process for producing a compound of the formula (6) or its salt: said process being characterized by comprising the reaction of a compound of the formula (2) or its salt: with an alkali metal nitrite in the presence of a reducing agent in an aqueous solution of an acidic compound.
9. 9. A process for producing a compound of the formula (5) or its salt: said process being characterized by comprising the reaction of a compound of the formula (6) or its salt: with trihalogenoacetyl halide in the presence of a base, followed by hydrolysis.
10. 10. The process according to claim 7 or 8, further characterized in that the reducing agent is hypophosphorous acid.
11. 11. The process according to claim 7 or 8, further characterized in that the alkali metal nitrite is sodium nitrite.
12. 12. The process according to claim 7 or 9, further characterized in that the base is a tertiary amine.
13. 13. The process according to claim 7 or 9, further characterized in that the trihalogenoacetyl halide is trichloroacetyl chloride.
14. 14. The process according to claim 7 or 9, further characterized in that the hydrolysis is carried out by treatment with an aqueous solution of an alkali metal hydroxide. 16. The process according to claim 14, further characterized in that the alkali metal hydroxide is lithium hydroxide. 16. A process for producing a compound of the formula (5) or its salt: said process being characterized as comprising the reaction of a compound d of the formula (1) or its salt: with sulfur powder and cyanamide in the presence of a secondary amine, to then obtain a compound of the formula (2) or its salt: and reacting the obtained compound or its salt of hydrobromic acid and alkali metal nitrite, to then obtain a compound of the formula (3) d or its salt: and reacting the obtained compound or its salt with alkyl lithium and carbon dioxide. 17. A process for producing a compound of the formula (2) or its salt: said process being characterized by comprising the reaction of a compound of the formula (1) or its salt: with sulfur powder and cyanamide in the presence of a secondary amine. 18. A process for producing a compound of formula 0 (3) or its salt: said process being characterized by comprising the reaction of a d compound of the formula (2) or its salt: with hydrobromic acid and an alkali metal nitrite. 19. The process according to claim 16, further characterized in that the lithium alkyl is n-butyllithium. 20. The process according to claim 16 or 17, further characterized in that the secondary amine is pyrrolidine. 21. The process according to claim 16 or 17, further characterized in that the alkali metal nitrite is sodium nitrite. 22. A salt formed between an acid compound and a compound of the formula (4). 23. - A salt formed between an acid compound and a compound of the formula (5). 24. - A salt formed between an acid compound and a compound of the formula (6). 26. - A salt formed between an acid compound and a compound of the formula (2). (2) 26. - A salt formed between an acid compound and a compound of the formula (3). 27. - The salt according to claim 22 or 23, further characterized in that the acid compound is hydrochloric acid. 28. The salt according to claim 24 or 26, further characterized in that the acid compound is p-toluenesulfonic acid. 29. The salt according to claim 2d, further characterized in that the acid compound is hydrobromic acid. 30. A process for producing a compound of the formula (8) or its salt: (wherein each of R1 and R2 represents a hydrogen, hydroxyl, alkyl or alkoxy atom; Q1 represents C1-C8 alkylene, C2-C8 alkenylene, or - (CH2) m -CH2-A-CH2- (CH2 ) n- (where each of m and n represents 0 or an integer from 1 to 3 and A represents an oxygen atom, a nitrogen atom, a sulfur atom, -SO-, -S02-, -NH-, - O-NH-, -NH-NH-, -S-NH-, -SO-NH-, or S02-NH-), each of R3 and R4, which is a substituent bonded to a carbon atom, an atom of nitrogen, or a sulfur atom forming the ring containing Q1, represents a hydrogen atom, hydroxyl, alkyl, alkenyl, alkynyl, a halogen atom, halogenalkyl, cyano, cyanoalkyl, amino, aminoalkyl, N-alkylaminoalkyl, N , N-dialkylaminoalkyl, acyl, acylalkyl, acylamino which may have a substituent, alkoxyimino, hydroxyimino, acylaminoalkyl, alkoxy, alkoxyalkyl, hydroxyalkyl, carboxyl, carboxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkoxycarbonylalkylamino or, carboxyalkylamino, alkoxycarbonylamino, alkoxycarbonylaminoalkyl, carbamoyl, N-alkylcarbamoyl whose alkyl may or may not be substituted, N, N-dialkylcarbamoyl whose alkyl may or may not be substituted, N-alkenylcarbamoyl, N-alkenylcarbamoylalkyl, N-alkenyl-N- alkylcarbamoyl, N-alkenyl-N-alkylcarbamoylalkyl, N-alkoxycarbamoyl, N-alkyl-N-alkoxycarbamoyl, N-alkoxycarbamoylalkyl, N-alkyl-N-alkoxycarbamoylalkyl, carbazoyl which can be substituted by 1 to 3 alkyl groups, alkylsulfonyl, alkylsulfonylalkyl, heterocyclic carbonyl of 3 to 6 elements which may have a substituent, carbamoylalkyl, N-alkylcarbamoylalkyl whose alkyl may or may not be substituted, N, N-dialkylcarbamoylalkyl whose alkyl may or may not be substituted, carbamoyloxyalkyl, N-alkylcarbamoyloxyalkyl, N, N -dialkylcarbamoyloxyalkyl, carbonylalkyl heterocyclic of 3 to 6 elements which may have a substituent, heterocyclic carbonyloxyalkyl of 3 to 6 ements which may have a substituent, aryl, aralkyl, heterocyclic group of 3 to 6 elements which may have a substituent, heterocyclic alkyl of 3 to 6 elements which may have a substituent, alkylsulfonylamino, arylsulfonylamino, alkylsulfonylaminoalkyl, arylsulfonylaminoalkyl, alkylsulfonylaminocarbonyl, arylsulfonylaminocarbonyl, alkylsulfonylaminocarbonylalkyl, Arilsulfonilaminocarbonilalquilo, oxo, carbamoyloxy, aralkyloxy, carboxyalkyloxy, alcoxicarbonilalquiloxi, acyloxy, acyloxyalkyl, ariisulfonilo, alcoxicarbonilalquilsulfonilo, carboxialquilsulfonilo, alcoxicarbonilacilo, alcoxialquiloxicarbonilo, hydroxyacyl, alkoxyacyl, halogenoacilo, carboxyacyl, aminoacyl, acyloxyacyl, aciloxialquilsulfonilo, hydroxyalkylsulfonyl, alcoxialqullsulfonilo, sulfonyl heterocyclic 3 6 elements that may have a substituent, heterocyclic oxy of 3 to 6 elements which may have a substituent, N-alkylaminoacyl, N, N-dialkylaminoacyl, N, N-dialkylcarbamoylacyl whose alkyl may or may not be substituted, N, N-dialkylcarbamoylalkysulfonyl whose alkyl may or may not be substituted, alkylsulfonylated, N-arylcarbamoyl, N-heterocyclic carbamoyl of 3 to 6 elements, N-alkyl-N-arylcarbamoyl, N-alkyl-N-heterocyclic carbamoyl of 3 to 6 elements, N-arylcarbamoylalkyl , carbamoylalkyl N-heterocyclic from 3 to 6 element s, N-alkyl-N-arylcarbamoylalkyl, carbamoylalkyl N-alkyl-N-heterocyclic of 3 to 6 elements, aminocarbothioyl, N-alkylaminocarbothioyl, N, N-dialkylaminocarbothioyl, alkoxyalkyl (thiocarbonyl), alkylthioalkyl, or N-acyl-N- alkylaminoalkyl; when R3 and R4 are linked to form a group, the group represents C1-C5 alkylene, C2-C6 alkenylene, C1-C5 alkylenedioxy, or carbonyldioxy; Q2 represents aryl which may have a substituent, arylalkenyl which may have a substituent, arylalkynyl which may have a substituent, heteroaryl which may have a substituent, heteroarylalkenyl which may have a substituent, a saturated or unsaturated, bicyclic or tricyclic condensed hydrocarbon group, which may have a substituent, or a saturated or unsaturated, bicyclic or tricyclic condensed heterocyclic group, which may have a substituent; T1 represents carbonyl, sulfonyl, -C (= 0) -C (= 0) -N (R ') -, -C (= S) -C (= 0) -N (R') -, -C (= 0) -C (= S) -N (R ') -, -C (= S) -C (= S) -N (R') - (wherein R 'represents a hydrogen atom, hydroxyl, alkyl, or alkoxy), -C (= 0) -A1-N (R ") - (wherein A1 represents a C1-C6 alkylene which may have a substituent and R" represents a hydrogen, hydroxyl, alkyl, or alkoxy atom ), -C (= 0) -NH-, -C (= S) -NH-, -C (= 0) -NH-NH-, -C (= 0) -A2-C (= 0) - ( wherein A2 represents a single bond or C1-C6 alkylene), -C (= 0) -A3-C (= 0) -NH- (where A3 represents C1-C6 alkylene), -C (= 0) -C (= NORa) -N (Rb) -, -C (= S) -C (= N0R3) -N (Rb) - (where Ra represents a hydrogen atom, alkyl, or aikanoyl and Rb represents an atom of hydrogen, hydroxyl, alkyl, or alkoxy), -C (= 0) -N = N-, -C (= S) -N = N-, -C (= NORc) -C (= 0) -N ( Rd) - (wherein Rc represents a hydrogen, alkyl, alkanoyl, aryl, or aralkyl atom and Rd represents a hydrogen, hydroxyl, alkyl, or alkoxy atom), -C (= NN (Re) (Rf)) - C (= 0) -N (R9) - (where, each of Re and Rf represents a hydrogen atom, alkyl, alkanoyl, or alkyl (thiocarbonyl) and R9 represents a hydrogen, hydroxyl, alkyl, or alkoxy), -C (= 0) -NH-C (= 0) -, -C (= S) -NH-C (= 0) -, -C (= 0) -NH-C (= S) -, -C (= S) -NHC (= S) -, -C (= 0) -NH-S02-, -S02-NH-, -C (= NCN) -NH-C (= 0) -, -C (= S) -C (= 0) -, or thiocarbonyl), wherein the process is characterized in that it comprises the reaction of a compound represented by formula (d) and that is produced by a process according to claim 1, 3, 7, 9 or 16, or its salt: with diamines of the formula (7) or its salt: (wherein R1, R2, R3, R4, T1, Q1, and Q2 have the same meanings as already described). 31. A process for producing a compound of the formula (8) or its salt: (wherein each of R and R2 represents a hydrogen, hydroxyl, alkyl or alkoxy atom; Q1 represents C1-C8 alkylene, C2-C8 alkenylene, or - (CH2) m-CH2-A-CH2- (CH2 ) n- (where each of m and n represents 0 or an integer from 1 to 3 and A represents an oxygen atom, a nitrogen atom, a sulfur atom, -SO-, -S02-, -NH-, - O-NH-, -NH-NH-, -S-NH-, -SO-NH-, or S02-NH-), each of R3 and R4, which is a substituent bonded to a carbon atom, an atom of nitrogen, or a sulfur atom forming the ring containing Q1, represents a hydrogen atom, hydroxyl, alkyl, alkenyl, alkynyl, a halogen atom, halogenalkyl, cyano, cyanoalkyl, amino, aminoalkyl, N-alkylaminoalkyl, N , N-dialkylaminoalkyl, acyl, acylalkyl, acylamino which may have a substituent, alkoxyimino, hydroxyimino, acylaminoalkyl, alkoxy, alkoxyalkyl, hydroxyalkyl, carboxyl, carboxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkoxycarbonylalkylamino or, carboxyalkylamino, alkoxycarbonylamino, alkoxycarbonylaminoalkyl, carbamoyl, N-alkylcarbamoyl whose alkyl may or may not be substituted, N, N-dialkylcarbamoyl whose alkyl may or may not be substituted, N-alkenylcarbamoyl, N-alkenylcarbamoylalkyl, N-alkenyl-N- alkylcarbamoyl, N-alkenyl-N-alkylcarbamoylalkyl, N-alkoxycarbamoyl, N-alkyl-N-alkoxycarbamoyl, N-alkoxycarbamoylalkyl, N-alkyl-N-alkoxycarbamoylalkyl, carbazoyl which can be substituted by 1 to 3 alkyl groups, alkylsulfonyl, alkylsulfonylalkyl, heterocyclic carbonyl of 3 to 6 elements which may have a substituent, carbamoylalkyl, N-alkylcarbamoylalkyl whose alkyl may or may not be substituted, N, N-dialkylcarbamoylalkyl whose alkyl may or may not be substituted, carbamoyloxyalkyl, N-alkylcarbamoyloxyalkyl, N, N -dialkylcarbamoyloxyalkyl, heterocyclic carbonylalkyl of 3 to 6 elements which may have a substituent, heterocyclic carbonyloxyalkyl of 3 to 6 elements which may have a substituent, aryl, aralkyl, heterocyclic group of 3 to 6 elements which may have a substituent, heterocyclic alkyl of 3 to 6 elements which may have a substituent, alkylsulfonylamino, arylsulfonylamino, alkylsulfonylaminoalkyl, arylsulfonylaminoalkyl, alkylsulfonylaminocarbonyl, arylsulfonylaminocarbonyl, alkylsulfonylaminocarbonylalkyl , arilsulfonilaminocarbonilalquilo, oxo, carbamoyloxy, aralkyloxy, carboxyalkyloxy, alcoxicarbonilalquiloxi, acyloxy, acyloxyalkyl, ariisulfonilo, alcoxicarbonilalquilsulfonilo, carboxialquilsulfonilo, alcoxicarbonilacilo, alcoxialquiloxicarbonilo, hydroxyacyl, alkoxyacyl, halogenoacilo, carboxyacyl, aminoacyl, acyloxyacyl, aciloxialquilsulfonilo, hydroxyalkylsulfonyl, alcoxialquilsulfonilo, sulfonyl heterocyclic 3 6 elements that may have a substituent, heterocyclic oxy of 3 to 6 elements that may have a substituent, N-alkylaminoacyl, N, N-dialkylaminoacyl, N, N-dia alkylcarbamoylazyl whose alkyl may or may not be substituted, N, N-dialkylcarbamoylalkyl-sulfonyl whose alkyl may or may not be substituted, alkylsulfonylacyl, N-arylcarbamoyl, carbamoyl N-heterocyclic of 3 to 6 elements, N-alkyl-N-arylcarbamoyl, carbamoyl N -alkyl-N-heterocyclic of 3 to 6 elements, N-arylcarbamoylalkyl, carbamoylalkyl N-heterocyclic of 3 to 6 elements, N-alkyl-N-arylcarbamoylalkyl, carbamoylalkyl N-alkyl-N-heterocyclic of 3 to 6 elements, aminocarbothioyl, N-alkylaminocarbothioyl, N, N-dialkylaminocarbothioyl, alkoxyalkyl (thiocarbonyl), alkylthioalkyl, or N-acyl-N-alkylaminoalkyl; when R3 and R4 are linked to form a group, the group represents C1-C6 alkylene, C2-C5 alkenylene, C1-C6 alkylenedioxy, or carbonyldioxy; Q2 represents aryl which may have a substituent, arylalkenyl which may have a substituent, arylalkynyl which may have a substituent, heteroaryl which may have a substituent, heteroarylalkenyl d which may have a substituent, a saturated or unsaturated, bicyclic or tricyclic fused hydrocarbon group , which may have a substituent, or a saturated or unsaturated, bicyclic or tricyclic condensed heterocyclic group, which may have a substituent; T1 represents carbonyl, sulfonyl, -C (= 0) -C (= 0) -N (R ') -, -C (= S) -C (= 0) -N (R') -, -C (= 0) -C (= S) -N (R ') -, -C (= S) -C (= S) -N (R') - 0 (wherein R 'represents a hydrogen atom, hydroxyl, alkyl , or alkoxy), - C (= 0) -A1-N (R ") - (wherein A1 represents a C1-C5 alkylene which may have a substituent and R" represents a hydrogen, hydroxyl, alkyl, or alkoxy), -C (= 0) -NH-, -C (= S) -NH-, -C (= 0) -NH-NH-, -C (= 0) -A2-C (= 0) - (wherein A2 represents a single bond or C1-C5 alkylene), -C (= 0) -A3-d C (= 0) -NH- (where A3 represents C1-C6 alkylene), -C (= 0) -C (= NORa) - N (Rb) -, -C (= S) -C (= NORa) -N (Rb) - (where Ra represents a hydrogen atom, alkyl, or alkanoyl and Rb represents a hydrogen atom, hydroxyl, alkyl, or alkoxy), -C (= 0) -N = N-, -C (= S) -N = N-, -C (= NORc) -C (= 0) - N (Rd) - (wherein Rc represents a hydrogen, alkyl, alkanoyl, aryl, or aralkyl atom and Rd represents a hydrogen, hydroxyl, alkyl, or alkoxy atom), -C (= NN (Re) (Rf) )) - C (= 0) -N (R9) - (where, cad to one of Re and Rf represents a hydrogen atom, alkyl, alkanoyl, or alkyl (thiocarbonyl) and R9 represents a hydrogen, hydroxyl, alkyl, or alkoxy), -C (= 0) -NH- C (= 0 ) -, -C (= S) -NH-C (= 0) -, -C (= 0) -NH-C (= S) -, -C (= S) -NHC (= S) -, - C (= 0) -NH- S02-, -S02-NH-, -C (= NCN) -NH-C (= 0) -, -C (= S) -C (= 0) -, or thiocarbonyl) , wherein the method is characterized by comprising the reaction of a compound that is represented by the formula (5) and that is produced through a process according to claim 1, 3, 7, 9, or 16 or its salt : with diamines of the formula (9) or its salt: (wherein Rk is a protecting group of an amino group and R1, R2, R3, R4, and Q1 have the same meanings as already described), to then obtain a compound of the formula (10): (wherein R1, R2, R3, R4, Q1, and R? have the same meanings as already described), and the removal of Rk of the obtained compound or its salt, then produces a compound of the formula (11) or its salt: d (wherein R1, R2, R3, R4, and Q have the same meanings as already described), and reacting the obtained compound or its salt with a compound of the formula (12) or its salt: HO_TI_Q2 (1 2) (where T and Q2 have the same meanings that were already described). 32.- A procedure to produce a compound of the formula (8 '): (wherein R1 represents a hydrogen, hydroxyl, alkyl or alkoxy atom; Q1 represents C1-C8 alkylene, C2-C8 alkenylene, or - (CH2) m-CH2-A-CH2- (CH2) n- (en where each of m and n represents 0 or an integer of 1 to 3 and A represents an oxygen atom, a nitrogen atom, a sulfur atom, -SO-, -S02-, -NH-, -O-NH-, -NH-NH-, -S-NH-, -SO-NH-, or S02-NH-), each of R3 and R4, which is a substituent bonded to a carbon atom, a nitrogen atom, or a sulfur atom forming the ring containing Q1, represents a hydrogen atom, hydroxyl, alkyl, alkenyl, alkynyl, a halogen atom, halogenalkyl, cyano, cyanoalkyl, amino, aminoalkyl, N-alkylaminoalkyl, N, N-dialkylaminoalkyl, acyl, acylalkyl, acylamino which may have a substituent, alkoxyimino, hydroxyimino, acylaminoalkyl, alkoxy, alkoxyalkyl, hydroxyalkyl, carboxyl, carboxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkoxycarbonylalkylamino, carboxyalkylamino mino, alkoxycarbonylamino, alkoxycarbonylaminoalkyl, carbamoyl, N-alkylcarbamoyl whose alkyl may or may not be substituted, N, N-dialkylcarbamoyl whose alkyl may or may not be substituted, N-alkenylcarbamoyl, N-alkenylcarbamoylalkyl, N-alkenyl-N-alkylcarbamoyl, N-alkenyl-N-alkylcarbamoylalkyl, N-alkoxycarbamoyl, N-alkyl-N-alkoxycarbamoyl, N-alkoxycarbamoylalkyl, N-alkyl-N-alkoxycarbamoylalkyl, carbazoyl which can be substituted by 1 to 3 alkyl groups, alkylsulfonyl, alkylsulfonylalkyl, heterocyclic carbonyl from 3 to 6 elements that may have a substituent, carbamoylalkyl, N-alkylcarbamoylalkyl whose alkyl may or may not be substituted, NN-dialkylcarbamoylalkyl whose alkyl may or may not be substituted, carbamoyloxyalkyl, N-alkylcarbamoyloxyalkyl, N, N-dialkylcarbamoyloxyalkyl, carbonylalkyl heterocyclic of 3 to 6 elements that can have a substituent, carbonyloxyalkyl heterocyclic of 3 to 6 elements that can ede have a substituent, aryl, aralkyl, heterocyclic group of 3 to 6 elements which may have a substituent, 3-6 membered heterocyclic alkyl which may have a substituent, alkylsulfonylamino, arylsulfonylamino, alkylsulfonylaminoalkyl, arylsulfonylaminoalkyl, alkylsulfonylaminocarbonyl, arylsulfonylaminocarbonyl, alkylsulfonylaminocarbonylalkyl, arylsulfonylaminocarbonylalkyl , oxo, carbamoyloxy, aralkyloxy, carboxyalkyloxy, alcoxicarbonilalquiloxi, acyloxy, acyloxyalkyl, ariisulfonilo, alcoxicarbonilalquilsulfonilo, carboxialquilsulfonilo, alcoxicarbonilacilo, alcoxialquiloxicarbonilo, hydroxyacyl, alkoxyacyl, halogenoacilo, carboxyacyl, aminoacyl, acyloxyacyl, aciloxialquilsulfonilo, hydroxyalkylsulfonyl, alcoxialquilsulfonilo, sulfonyl heterocyclic 3 to 6-membered which may have a substituent, heterocyclic oxy of 3 to 6 elements which may have a substituent, N-alkylaminoacyl, N, N-dialkylaminoacyl, N, N-dialkylcarbamoyl cyl whose alkyl may or may not be substituted, N, N-dialkylcarbamoylalkyl-sulfonyl whose alkyl may or may not be substituted, alkylsulfonylacyl, N-arylcarbamoyl, carbamoyl N-heterocyclic of 3 to 6 elements, N-alkyl-N-arylcarbamoyl, carbamoyl N -alkyl-N-heterocyclic of 3 to 6 elements, N-arylcarbamoylalkyl, carbamoylalkyl N-heterocyclic of 3 to 6 elements, N-alkyl-N-arylcarbamoylalkyl, carbamoylalkyl N-alkyl-N-heterocyclic of 3 to 6 elements, aminocarbothioyl, N-alkylaminocarbothioyl, N, N-dialkylaminocarbothioyl, alkoxyalkyl (thiocarbonyl), alkylthioalkyl, or N-acyl-N-alkylaminoalkyl; when R3 and R4 are linked to form a group, the group represents C1-C5 alkylene, C2-C6 alkenylene, C1-C6 alkylenedioxy, or carbonyldioxy; Q2 represents aryl which may have a substituent, arylalkenyl which may have a substituent, arylalkynyl which may have a substituent, heteroaryl which may have a substituent, heteroarylalkenyl which may have a substituent, a saturated or unsaturated, bicyclic or tricyclic condensed hydrocarbon group, which may have a substituent, or a saturated or unsaturated, bicyclic or tricyclic condensed heterocyclic group, which may have a substituent; T1 represents carbonyl, sulfonyl, -C (= 0) -d C (= 0) -N (R ') -, -C (= S) -C (= 0) -N (R') -, -C ( = 0) -C (= S) -N (R ') -, -C (= S) -C (= S) -N (R') - (where R 'represents a hydrogen atom, hydroxyl, alkyl , or alkoxy), - C (= 0) -A1-N (R ") - (wherein A1 represents a C1-C6 alkylene which may have a substituent and R" represents a hydrogen, hydroxyl, alkyl, or alkoxy), -C (= 0) -NH-, -C (= S) -NH-, -C (= 0) -NH-NH-, -C (= 0) -A2-C (= 0) - 0 (wherein A2 represents a single bond or C1-C5 alkylene), -C (= 0) -A3- C (= 0) -NH- (where A3 represents C1-C6 alkylene), -C (= 0) -C (= NORa) - N (Rb) -, -C (= S) -C (= NORa) -N (R) - (where Ra represents a hydrogen atom, alkyl, or alkanoyl and Rb represents a hydrogen atom, hydroxyl, alkyl, or alkoxy), -C (= 0) -N = N-, -C (= S) -N = N-, -C (= NORc) -C (= 0) - d N (Rd) - (wherein Rc represents a hydrogen, alkyl, alkanoyl, aryl, or aralkyl atom and Rd represents a hydrogen, hydroxyl, alkyl, or alkoxy atom), -C (= NN (Re) (Rf )) - C (= 0) -N (R9) - (where, each one of Re and Rf represents a hydrogen atom, alkyl, alkanoyl, or alkyl (thiocarbonyl) and R9 represents a hydrogen, hydroxyl, alkyl, or alkoxy atom), -C (= 0) -NH- C (= 0) -, -C (= S) -NH-C (= 0) -, -C (= 0) -NH-C (= S) -, -C (= S) -NHC (= S) -, -C (= 0) -NH- S02-, -S02-NH-, -C (= NCN) -NH-C (= 0) -, -C (= S) -C (= 0) -, or thiocarbonyl), wherein the process is characterized by comprising the reaction of a compound that is represented by the formula (5) and that is produced through a process according to claim 1, 3, 7, 9, or 16 or its salt: with diamines of the formula (13) or its salt: (wherein R1, R3, R4, and Q1 have the same meanings as already described) to then obtain a compound of the formula (14) or its salt: (wherein R1, R3, R4, and Q1 have the same meanings as already described), and reducing the obtained compound or its salt, to then produce a compound of the formula (11 ') or its salt: (wherein R1, R3, R4, and Q have the same meanings as already described), and reacting the obtained compound or its salt with a compound of the formula (12) or its salt: HO-T1-Q2 (1 2 ) (where T1 and Q2 have the same meanings that were already described).