KR100292070B1 - Thiourea derivatives capable of inhibiting the growth of ras mutant and nontoxic salt thereof - Google Patents

Abstract

PURPOSE: Thiourea derivatives capable of inhibiting the growth of Ras mutant and nontoxic salt thereof are provided. The derivative can be useful for treatment of various cancers. CONSTITUTION: The thiourea derivatives are represented by formula(I), wherein R1 is hydrogen, optionally substituted linear or branched chain C1-C8-alkyl, C2-C6-alkenyl, C1-C4-alkoxycarbonyl, C3-C6-cycloalkyl, phenyl, phenyl having 1 to 3 substituents, phenyl-C1-C4-alkyl, naphthyl, di(C1-C4 alkyl)amino-substituted naphthyl, benzoyl, pyridyl, halogen or C1-C6-alkoxy-substituted pyridyl or adamantyl; R2 and R3 are independently hydrogen, linear or branched chain C1-C6-alkyl, C3-C6-cycloalkyl, or benzyloxy benzyl; R4 is C1-C6-alkyl, phenyl-C1-C4-alkyl, phenyl having 1 to 3 substituents-substituted C1-C4-alkyl, naphthyl-C1-C4-alkyl, thiophenyl-C1-C4-alkyl, pyridyl-C1-C6-alkyl, oxypyridyl-C1-C6-alkyl, C1-C6-alkoxy-C1-C6-alkyl, C1-C6-alkylthio-C1-C6-alkyl, or C2-C6-alkynyl; and X is nitro or cyano.

Description

[Name of invention]

Thiourea derivatives or nontoxic salts thereof that inhibit the growth of Lars mutant cells

Detailed description of the invention

[Purpose of invention]

[Technical field to which the invention belongs and the prior art in that field]

The present invention relates to novel thiourea derivatives, pharmaceutically acceptable non-toxic salts thereof or stereoisomers thereof that inhibit the growth of Ras mutant cells. The present invention also relates to a las mutant cell growth inhibitory composition containing the preparation method thereof and an active ingredient thereof.

Ras protein is called Farnesyltransferase, or Farnesyl protein transferase (FPTase) or Geranylgeranyl protein transferase (GGPTase). By farnesylation (Farnesylation) or geranylgeranylation (Geranylgeranylation) is moved to the inner wall to be present in the inactivated state combined with GDP or activated state combined with GTP. When the Ras protein is activated, it transmits signals outside the cell into the nucleus by activating the lower level signaling system step by step. This information activates transcription factors (myc, jun, fos, etc.) to grow cells or This series of information transmission systems is called the Ras signaling system (M. Barbacid, Annu. Rev. Biochem., 56, 779, 1987, P J. Casey et al., Proc. Natl. Acad). Sci. USA 86, 8323, 1989).

When mutations in Ras genes (e.g., H-Ras, N-Ras, K-RasA, K-RasB, etc.) produce variant Ras proteins, they bind to GTP and remain active, Will cause cancer. Among many human cancers, especially in patients with colorectal cancer and pancreatic cancer, these mutant Ras genes are found to be about 50% and 90%, respectively, and Ras genes mutated at high frequency in lung cancer (50%) or thyroid cancer (30%). (S. Rodenhuis, Semin. Cancer Biol. 3, 241, 1992).

Therefore, many studies have been conducted to develop mutant cell inhibitors due to mutant Ras proteins. In particular, much research is being conducted on FPTase inhibitors that can block the migration of the mutant Ras protein into the cell wall. For example, Cys-Val-Phe-Met, which has a structure similar to the carboxylic acid residue (Cys-A1-A2-Met) of the las protein, has been disclosed to act as an inhibitor of FPTase (JL Goldstein et al., J Biol. Chem., 266, 15575, 1991; AM Garcia et al., J. Biol. Chem., 268, 18415, 1993; SL Graham et al., J. Med. Chem., 37, 725, 1994). .

In addition, a number of derivatives are under development with Cys-Ile-Phe-Met as the basic structure, and there are reports that a compound in which Phe-Met moiety is replaced with an aromatic alkylamine selectively inhibits FPTase as compared to GGPTase. (SJ Desolms et al., J. Med. Chem., 38, 3967, 1995), that carbonylamide compounds that bind aminomethylnaphthalene to cysteine and trans-3 (S) -ethylproline show inhibitory effects on FPTase It has been disclosed (WO9606609, 1996), and similar peptide compounds obtained by converting cysteine to imidazole ethyl groups have also been reported to have FPTase inhibitory effects (JH Hunt et al., J. Med. Chem., 39, 353, 1996; WO9610035, 1996; WO9610034, 1996; WO9609836, 1996). In addition, Merck reports that a compound obtained by converting cysine from Cys-Ile-Phe-Met to p-cyanobenzylimidazole acetate and phenylalanine to N-naphthylmethyl has an inhibitory effect on FPTase (WO9639173, 1996).

[Technical problem to be achieved]

However, such conventional developing FPTase inhibitors do not effectively inhibit farnesylation in K-Ras mutant cells found in most human cancers. The reason is that the F-ptase inhibitors fail to inhibit the prenylation of the K-Ras protein in the cell because the K-ras protein inhibited by the FPTase inhibitor maintains the activity of the K-ras protein using GGPTase even if the FPTase is inhibited. Has been reported (GL James et al., J. Biol. Chem. 270, 6221, 1995).

Therefore, the present inventors have conducted a lot of research to develop a Ras mutant cell growth inhibitor that can inhibit the prenylation of K-Ras protein, as well as inhibit the prenylation of K-Ras protein as well as the growth of Ras-mutant cells themselves. New thiourea derivatives that inhibit

[Configuration and Function of Invention]

The present invention provides novel thiourea derivatives and their non-toxic salts having a las mutant cell growth inhibitory effect.

The present invention also provides a novel thiourea derivative and a method for preparing the nontoxic salt thereof.

The present invention also provides a Ras mutant cell growth inhibitory composition comprising a novel thiourea derivative and its nontoxic salt as an active ingredient and comprising a pharmaceutically acceptable carrier.

Hereinafter, the present invention will be described in more detail.

The present invention includes thiourea derivatives represented by the following general formula (I), pharmaceutically acceptable salts containing them, or stereoisomers thereof.

R ₁ is hydrogen; Substituted or unsubstituted straight or branched C ₁ -C ₈ -alkyl; C ₂ -C ₆ -alkenyl; C ₁ -C ₄ -alkoxycarbonyl; C ₃ -C ₆ -cycloalkyl; Phenyl; Phenyl having 1 to 3 substituents; Phenyl-C ₁ -C ₄ -alkyl; Naphthyl; Naphthyl substituted with di (C ₁ -C ₄ -alkyl) amino; Benzoyl; pyridyl; Pyridyl substituted with halogen or C ₁ -C ₆ -alkoxy; Or adamantyl,

R ₂ and R ₃ are each independently hydrogen; Straight or branched C ₁ -C ₆ -alkyl; C ₃ -C ₆ -cycloalkyl; Or benzyloxybenzyl,

R ₄ is C ₁ -C ₆ -alkyl; Phenyl-C ₁ -C ₄ -alkyl; C ₁ -C ₄ -alkyl substituted with phenyl having 1 to 3 substituents; Naphthyl-C ₁ -C ₄ -alkyl; Thiophenyl-C ₁ -C ₄ -alkyl; Pyridyl-C ₁ -C ₆ -alkyl; Oxypyridyl-C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy-C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkylthio-C ₁ -C ₆ -alkyl; Or C ₂ -C ₆ -alkynyl,

X represents nitro or cyano.

The thiourea derivatives according to the invention may be in the form of pharmaceutically acceptable salts, which salts may be in the form of non-toxic salts commonly used in the field of anticancer agents, for example salts formed from non-toxic inorganic or organic acids. . Such conventional non-toxic salts include salts derived from inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, sulfamic acid, phosphoric acid, nitric acid and the like and acetic acid, propionic acid, succinic acid, glycolic acid, stearic acid, pamoic acid, maleic acid, hydroxymale Salts prepared from organic acids such as acids, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid, sulfanilic acid, 2-acetoxy-benzoic acid, fumaric acid, toluenesulfonic acid, methanedisulfonic acid, ethanedisulfonic acid, oxalic acid, trifluoroacetic acid, and the like. do.

Compounds of general formula (I) according to the present invention may be present as racemates, diastereomer mixtures or stereospecific isomers, because asymmetric carbons may be present depending on substituents. . Thus, the present invention includes these stereoisomers and mixed solutions thereof.

Among the compounds according to the present invention, more preferable compounds are as follows.

R ₁ is phenyl; Phenyl having 1 to 3 substituents; Pyridyl; Or pyridyl substituted with halogen or C ₁ -C ₆ -alkoxy,

R ₂ and R ₃ are each independently hydrogen; Or straight or branched C ₁ -C ₆ -alkyl,

R ₄ is phenyl-C ₁ -C ₄ -alkyl; Or C ₁ -C ₄ -alkyl substituted with phenyl having 1 to 3 substituents,

X represents nitro or cyano.

The present invention includes a thiourea derivative represented by the following general formula (I) and a method for producing a nontoxic salt thereof. Compounds of the following general formula (I) can be prepared by the following two methods.

Scheme 1

Scheme 2

In Schemes 1 and 2, R ₁ , R ₂ , R ₃ , R ₄ and X are the same as defined above, and P and P ′ each represent a different aminoprotecting group.

The aminoprotecting group used in the present invention may use conventional aminoprotecting groups such as fluoromethyloxycarbonyl (Fmoc), t-butoxycarbonyl (Boc) and benzyloxycarbonyl (Cbz).

Referring to the preparation method shown in the reaction schemes 1 and 2 step by step as follows.

Reaction 1. Reductive alkylation reaction

Aldehyde derivatives protected with t-butoxycarbonyl (Boc) of the general formula (II) as starting materials were prepared by known preparation methods (Org. Syn. Vol. 67, 1988, 69 and Synthesis, 1983, 676). And a reductive alkylation reaction is carried out by adding R4-amine in the presence of sodium cyanoborohydride or other known reducing agent to prepare a compound of formula III. At this time, the reaction can be promoted by adding KOAc or AcOH and 3A molecular sieve.

Reaction 2. Amino group protection reaction

The compound of formula (III) is reacted with 9-fluorenylmethylchloroformate (Fmoc-chloride) or a conventional amino protecting group to prepare a compound of formula (IV).

Reaction 3. Deprotector Reaction

The compound of formula (IV) having two different amino protecting groups is dissolved in a suitable organic solvent such as methylene chloride, and then reacted with a deprotecting agent such as trifluoroacetic acid to selectively remove the protecting group.

Reaction 4. Amide bond formation reaction

The compound of formula (VI) may be prepared by reacting a compound of formula (V) with an imidazole-5-monoacetic acid hydrochloride having a substituent with an appropriate fusing agent. Suitable bases such as hydroxybenzotriazole, dialkylcarbodiimide and triethylamine can be used as the fusion agent for promoting the reaction. Dimethylformamide, methylene chloride, or a mixed solution thereof may be used as the solvent.

Reaction 5. Deprotector and addition reaction

The compound of formula (VI) having an amino protecting group is dissolved in a suitable organic solvent such as dimethylformamide, methylene chloride and the like, followed by reaction with a deprotecting agent such as piperidine to remove the protecting group. The deprotected compound is dissolved in methylene chloride and reacted with isothiocyanate of formula (VIII) having a substituent to prepare a compound of formula (I).

Reaction 6. Side reaction

A compound of formula (III) having an amino group and an isothiocyanate having a substituent represented by formula (VIII) are reacted with a solvent such as dimethylformamide, methylene chloride or acetonitrile to obtain a compound of formula (VII). Manufacture.

Reaction 7. Deprotection group and amide bond formation reaction

The compound of formula (VII) having an amino protecting group is dissolved in a suitable organic solvent such as dimethylformamide, methylene chloride, and then reacted with a deprotecting agent such as piperidine to remove the protecting group, and then the substituent represented by formula (IX). The compound of formula (I) may be prepared by reacting an imidazole-5-ylacetic acid hydrochloride having an appropriate fusion agent. Suitable bases such as hydroxybenzotriazole, dialkylcarbodiimide and triethylamine can be used as the fusion agent for promoting the reaction. Dimethylformamide, methylene chloride, or a mixed solution thereof may be used as the solvent.

Pharmaceutically acceptable non-toxic salts of the compounds according to the invention can be prepared by conventional methods from compounds of the general formula (I) containing a basic moiety. In general, salts can be prepared by reacting an organic base in a stoichiometric amount or in excess of the desired salt-forming inorganic or organic acid in a suitable solvent or various combinations of solvents.

The present invention includes a lath mutant cell growth inhibitory composition comprising a thiourea derivative represented by formula (I) as an active ingredient and a pharmaceutically acceptable carrier. The composition according to the invention may comprise excipients such as lactose, corn starch, lubricants such as magnesium stearate, emulsifiers, suspending agents, buffers, isotonic agents and the like which are well known and can be used, and in some cases sweetening and / or flavoring It may include the agent.

The compositions according to the invention can be administered orally or parenterally, including intravenous, intraperitoneal, subcutaneous, rectal and topical administration. That is, the composition according to the present invention can be administered in the form of tablets or capsules, or as an aqueous solvent or suspending agent. In the case of oral tablets, carriers commonly used include lactose and corn starch, and a lubricant such as magnesium stearate may be generally added. Useful diluents for capsule form may include lactose and dry corn powder. If an aqueous suspension is required for oral use, the active ingredient may include an emulsifier and a suspension. If desired, certain sweetening and / or flavoring agents may be added. For intramuscular, intraperitoneal, subcutaneous and intravenous administration, a sterile solution of the active ingredient is usually prepared and may be included as a buffer to suitably adjust the pH of the solution. For intravenous administration, the total concentration of the solute is It may include isotonic agents that can be adjusted to impart isotonicity to the formulation. In addition, the composition according to the present invention may be in the form of an aqueous solution containing a pharmaceutically acceptable carrier such as saline having a pH of 7.4, and may be locally introduced into the patient's intramuscular blood flow in the form of a solution. have.

The compound according to the present invention can be administered to cancer patients such as colon cancer, rectal cancer, pancreatic cancer, or myeloid leukemia by effectively inhibiting the growth of las mutant cells, and the dosage is usually determined according to the age, weight and symptoms of each patient. According to the dosages that can be generally varied, for example from about 0.1 mg / kg to about 20 mg / kg per day, preferably from 0.5 mg / kg to about 10 mg / kg per day.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, this does not limit the scope of the invention.

Reference Example 1

1- (4-nitrobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride

[Step 1]

1H-imidazol-4-ylacetic acid methyl ester hydrochloride

Hydrochloric acid gas was saturated in a methanol (200 ml) solution of 1H-imidazol-4-ylacetic acid hydrochloride (10.0 g, 61.3 mmol). The solution was left at room temperature for 18 hours and then the solvent was concentrated under reduced pressure to give the title compound (11.6 g, 100%) as a white solid.

¹ H-NMR (DMSO-d ₆ ): δ 9.05 (s, 1H), 7.50 (s, 1H), 3.90 (s, 2H), 3.60 (s, 3H).

[Step 2]

1- (triphenylmethyl) -1H-imidazol-4-ylacetic acid methyl ester

Triethylamine (27.4 ml, 196.6 mmol) and triphenylmethyl chloride in a suspension of dichloromethane (350 ml) and dimethylformamide (50 ml) of 1H-imidazol-4-ylacetic acid methyl ester hydrochloride (11.6 g, 65.6 mmol). (21.9 g, 78.6 mmol) was added and stirred for 15 hours. The reaction mixture was washed with water and saturated brine, the organic layer was dried over anhydrous magnesium sulfate, and the residue was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / n-hexane = 2/1, v / v) to obtain a white solid. The title compound (7.44 g, 74%) was prepared.

TLC: R _f = 0.20 (ethyl acetate / n-hexane = 1/1)

¹ H-NMR (CDCl ₃ ): δ 7.45 (s, 1H), 7.05-7.45 (m, 15H), 6.75 (s, 1H), 3.70 (s, 2H)

[Step 3]

1- (4-nitrobenzyl) -1H-imidazol-5-ylacetic acid methyl ester

To a solution of acetonitrile (100 ml) of 1- (triphenylmethyl) -1H-imidazol-4-ylacetic acid methyl ester (4.96 g, 13.0 mmol) was added 4-nitrobenzylbromide (2.80 g, 13.0 mmol). Warmed to 65 ° C. for 24 h and stirred. The reaction solution was cooled to room temperature, the solvent was concentrated under reduced pressure, and the residue was dissolved in methanol (150 ml) and stirred at reflux for 1 hour. Concentration under reduced pressure to 50 ml solution and crystallization in methanol to give the title compound (3.27 g, 92%) as a white solid.

TLC: R _f = 0.50 (dichloromethane / methanol = 9/1)

¹ H-NMR (DMSO-d ₆ ): δ 9.35 (s, 1H), 8.25 (d, 2H), 7.70 (s, 1H), 7.60 (d, 2H), 5.70 (s, 2H), 3.95 (s , 2H), 3.50 (s, 3H)

[Step 4]

1- (4-nitrobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride

1- (4-nitrobenzyl) -1H-imidazol-5-ylacetic acid methyl ester (3.30 g) was dissolved in 1N hydrochloric acid (25 ml) and warmed to 60 ° C. for 4 hours. The solution was concentrated under reduced pressure and crystallized in methanol to give the title compound (1.64 g, 53%) as a white solid.

¹ H-NMR (DMSO-d ₆ ): δ 9.45 (s, 1H), 8.30 (d, 2H), 7.70 (s, 1H), 7.60 (d, 2H), 5.70 (s, 2H), 3.80 (s , 2H)

Reference Example 2

1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride

[Step 1]

1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid methyl ester

1- (triphenylmethyl) -1H-imidazol-4-ylacetic acid methyl ester (1.43 g, 3.74 mmol) and 4-cyanobenzylbromide (0.81 g, 4.11 mmol) prepared in Step 2 of Reference Example 1 were prepared. To give the title compound (0.89 g, 93%) in the white solid phase in the same manner as in Step 3 of Reference Example 1.

¹ H-NMR (DMSO-d ₆ ): δ 9.30 (s, 1H), 7.95 (d, 2H), 7.70 (s, 1H), 7.52 (d, 2H), 5.65 (s, 2H), 3.92 (s , 2H), 3.50 (s, 3H)

[Step 2]

1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride

White in the same manner as in Step 4 of Reference Example 1, using 1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid methyl ester (0.86 g, 3.37 mmol) and 1.0 N hydrochloric acid (50 ml). The title compound (0.76 g, 90%) was prepared as a solid.

¹ H-NMR (DMSO-d ₆ ): δ 14.60 (bs, 1H), 12.95 (bs, 1H), 9.35 (s, 1H), 7.95 (d, 2H), 7.65 (s, 1H), 5.60 (s , 2H), 3.80 (s, 2H)

Reference Example 3

N-t-butoxycarbonyl-L-isoleucine aldehyde

[Step 1]

N-t-butoxycarbonyl-L-isoleucine-N'-methoxy-N'-methylamide

To a suspension of N, O-dimethylhydroxylamine hydrochloride (6.1 g, 62.5 mmol) in dichloromethane (60 ml) was added dropwise N-methylmorpholine (7.6 ml, 69.1 mmol) at −10 ° C. and stored at the same temperature. In another vessel Nt-butoxycarbonyl-L-isorucin (15.0 g, 62.4 mmol) was dissolved in dichloromethane (300 ml) and the temperature was cooled to -20 ° C, followed by N-methylmorpholine (7.6 ml, 69.1 mmol) and isobutylchloroformate (8.1 ml, 62.4 mmol) were added dropwise maintaining -20 ° C. After 5 minutes, the first prepared N, O-dimethylhydroxylamine solution was added dropwise and stirred overnight at room temperature. Water (100 ml) was added to the reaction mixture and extracted. The extracted organic layer was washed with water (100 ml x 2) and saturated aqueous salt solution (100 ml), dehydrated with anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / n-hexane = 1/4, v / v) to give the title compound (15.1 g, 89%) as an oil.

TLC: R _f = 0.25 (ethyl acetate / n-hexane / ethanol = 25/100/2)

¹ H-NMR (CDCl ₃ ): δ 5.20 (d, 1H), 4.60 (m, 1H), 3.70 (d, 3H), 3.20 (d, 3H), 2.00 (m, 1H), 1.40 (s, 9H ), 1.00 (m, 8H)

[Step 2]

N-t-butoxycarbonyl-L-isoleucine aldehyde

The solution in which lithium aluminum hydride (2.4 g, 54.7 mmol) was suspended in anhydrous tetrahydrofuran (300 ml) was cooled to -45 ° C, and Nt-butoxycarbonyl-L-isoleucine-N'-methoxy -N'-methylamide (15 g, 54.7 mmol) was dissolved in 30 ml of anhydrous tetrahydrofuran and added dropwise in small portions while maintaining the temperature of the reaction solution between -45 ° C and -35 ° C. After completion of the dropwise addition, the mixture was left at 5 ° C., and then the reaction solution was cooled to −35 ° C. and an aqueous potassium hydrogen sulfate solution (12.7 g / 35 ml) was added dropwise. After dropping, the cooling vessel was removed, the temperature was kept at room temperature, and stirred for 1 hour. Then, celite was added to collect aluminum salts and filtered out. The organic layer was washed with distilled water, dehydrated with anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give an oily title compound (8.2 g, 69%).

TLC: R _f = 0.55 (ethyl acetate / n-hexane / ethanol = 25/100/2)

¹ H-NMR (CDCl ₃ ): δ 9.70 (s, 1H), 5.20 (d, 1H), 4.30 (m, 1H), 2.00 (m, 1H), 1.50 (s, 9H), 1.00 (m, 8H )

Reference Example 4

N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

[Step 1]

N- (2,3-dichlorobenzyl) -2 (S)-(t-butoxycarbonyl) amino-3 (S) -methylpentylamine

Nt-butoxycarbonyl-L-isorucin aldehyde (4.52 g, 21.0 mmol) prepared in Reference Example 3 was dissolved in methanol (50 ml) and 2,3-dichlorobenzylamine (4.07 g, 23.1 mmol), acetic acid (0.5 ml) and 3A molecular sieves (molecular sieves, 5 g) were added. Sodium cyanoborohydride (1.45 g, 21.0 mmol) was added dropwise to this mixed solution, followed by stirring overnight at room temperature. The precipitate of the reaction mixture was filtered and the filtrate was concentrated under reduced pressure. Water (100 ml) was added to the concentrate, followed by extraction with ethyl acetate (100 ml). The organic layer was dehydrated with anhydrous magnesium sulfate and the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / n-hexane = 1/3, v / v) to give the title compound (5.0 g, 63%) as a yellow oil.

TLC: R _f = 0.49 (dichloromethane / methanol = 10/1)

¹ H-NMR (CDCl ₃ ): δ 7.08-7.40 (m, 3H), 4.70 (d, 1H), 3.83 (m, 2H), 3.60 (m, 1H), 2.45-2.75 (m, 2H), 1.30 -1.60 (m, 11H), 0.97-1.20 (m, 1H), 0.75-0.95 (m, 6H)

[Step 2]

N- (2,3-dichlorobenzyl) -N- (9-fluorenylmethyloxycarbonyl) -2 (S)-(t-butoxycarbonyl) amino-3 (S) -methylpentylamine

N- (2,3-dichlorobenzyl) -2 (S)-(t-butoxycarbonyl) amino-3 (S) -methylpentylamine (2.79 g, 7.39 mmol) was dissolved in dichloromethane (30 ml) Triethylamine (1.54 ml, 11.08 mmol) was added. The reaction mixture was cooled to 0 ° C. and a solution of 9-fluorenylmethylchloroformate (2.29 g, 8.87 mmol) in dichloromethane (20 ml) was added dropwise. After stirring the reaction solution at room temperature overnight, dichloromethane (100 ml) was added, and the mixture was washed with 5% aqueous hydrochloric acid solution, saturated aqueous sodium bicarbonate solution and saturated aqueous salt solution. The organic layer was dehydrated with anhydrous magnesium sulfate and the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / n-hexane = 1/5, v / v) to give the title compound (2.42 g, 55%) in the form of a white foam.

TLC: R _f = 0.29 (ethyl acetate / n-hexane = 1/4)

¹ H-NMR (CDCl ₃ ): δ 7.52-7.83 (m, 3H), 7.23-7.52 (m, 5H), 7.00-7.22 (m, 2H), 6.85 (d, 1H), 4.62-4.95 (m, 2H), 4.28-4.62 (m, 3H), 4.02-4.28 (m, 1H), 3.40-4.00 (m, 2H), 2.45-2.90 (m, 1H), 1.42 (d, 9H), 0.97-1.41 ( m, 3H), 0.70-0.95 (m, 6H)

[Step 3]

N- (2,3-dichlorobenzyl) -N- (9-fluorenylmethyloxycarbonyl) -2 (S) -amino-3 (S) -methylpentylamine trifluoroacetic acid salt

N- (2,3-dichlorobenzyl) -N- (9-fluorenylmethyloxycarbonyl) -2 (S)-(t-butoxycarbonyl) amino-3 (S) -methylpentylamine (2.42 g) was dissolved in dichloromethane (30 ml) and trifluoroacetic acid (10 ml) was added dropwise. After stirring the reaction solution at room temperature for 2 hours, the solution was concentrated under reduced pressure to prepare an oily title compound, which was used in the next reaction without further purification.

[Step 4]

N- (2,3-dichlorobenzyl) -N- (9-fluorenylmethyloxycarbonyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

1- (4-nitrobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride (1.05 g, 3.54 mmol) prepared in Reference Example 1 was dissolved in anhydrous dichloromethane (50 ml) solution, and 1-hydroxybenzotriazole ( 0.82 g, 5.31 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (1.0 g, 4.60 mmol) and triethylamine (1.69 ml, 10.6 mmol) were added dropwise. After stirring the reaction mixture for 1 hour, N- (2,3-dichlorobenzyl) -N- (9-fluorenylmethyloxycarbonyl) -2 (S) -amino-3 (S) -methylpentylamine Trifluoroacetic acid salt (2.46 g, 4.03 mmol) was added. The reaction mixture was stirred overnight at room temperature, then water was added and the organic layer was extracted. The organic extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to prepare the title compound.

[Step 5]

N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

N- (2,3-dichlorobenzyl) -N- (9-fluorenylmethyloxycarbonyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazole prepared in step 4 -5-yl] acetyl} amino-3 (S) -methylpentylamine was dissolved in dimethylformamide (14 ml) and piperidine (6 ml) was added. After stirring the reaction solution at room temperature for 4 hours, the solvent was concentrated under reduced pressure and purified by silica gel column chromatography (dichloromethane / methanol = 9/1, v / v) to give the title compound (430 mg) as a white foam.

TLC: R _f = 0.20 (dichloromethane / methanol = 10/1)

¹ H-NMR (CDCl ₃ ): δ 8.20 (d, 2H), 7.58 (s, 1H), 7.40 (m, 1H), 7.12-7.36 (m, 4H), 7.05 (s, 1H), 5.70-6.00 (m, 1H), 5.33 (s, 2H), 3.75-4.10 (m, 3H), 3.38 (s, 2H), 2.62 (d, 2H), 1.78 (bs, 1H), 1.42-1.65 (m, 1H ), 1.22-1.42 (m, 1H), 0.96-1.22 (m, 1H), 0.75-0.95 (m, 6H)

Reference Example 5

N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Step 4 and Step 5 of Reference Example 4, using 1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride.

TLC: R _f = 0.35 (dichloromethane / methanol = 10/1)

¹ H-NMR (CDCl ₃ ): δ 7.62 (d, 2H), 7.53 (s, 1H), 7.40 (m, 3H), 7.00-7.35 (m, 5H), 5.92 (d, 1H), 5.22 (s , 2H), 3.75-4.05 (m, 3H), 3.38 (s, 2H), 2.62 (m, 2H), 1.82 (bs, 1H), 1.42-1.65 (m, 2H), 1.22-1.42 (m, 1H ), 0.96-1.22 (m, 1H), 0.75-0.95 (m, 6H)

Reference Example 6

N- (1-naphthylmethyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

[Step 1]

N- (1-naphthylmethyl) -2 (S)-(t-butoxycarbonyl) amino-3 (S) -methylpentylamine

Dissolve 1-naphthylmethylamine (0.90 g, 5.71 mmol) in methanol (10 ml) and adjust to pH 6 with triethylamine, then sodium cyanoborohydride (1M in THF, 8.60 ml), Potassium Acetate ( 562 mg, 5.71 mmol) and 3A molecular sieves (molecular sieves, 2.00 g) were added dropwise at 0 ° C. under a nitrogen stream. After stirring for 30 minutes, a solution of Nt-butoxycarbonyl-L-isorucin aldehyde (1.23 g, 5.71 mmol) prepared in Reference Example 3 in methanol (10 ml) was added dropwise and added under 20 ° C. nitrogen stream. Stir for hours. The solvent of the reaction mixture was concentrated under reduced pressure, water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium hydrogen carbonate solution, dehydrated with anhydrous magnesium sulfate and the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / n-hexane = 1/3, v / v) to give the title compound (0.74 g, 36%) as a white oil.

TLC: R _f = 0.20 (Ethyl acetate / n-hexane = 1/2)

¹ H-NMR (CDCl ₃ ): δ 7.40-8.25 (m, 7H), 4.65 (d, 1H), 4.15-4.40 (m, 2H), 3.60-3.80 (m, 1H), 2.70-2.90 (m, 2H), 1.40-1.70 (m, 13H), 0.80-1.00 (m, 6H)

[Step 2]

N- (1-naphthylmethyl) -N- (9-fluorenylmethyloxycarbonyl) -2 (S)-(t-butoxycarbonyl) amino-3 (S) -methylpentylamine

N- (1-naphthylmethyl) -2 (S)-(t-butoxycarbonyl) amino-3 (S) -methylpentylamine (1.00 g, 2.81 mmol) was dissolved in dichloromethane (10 ml) and Ethylamine (0.47 ml, 3.37 mmol) was added. The reaction mixture was cooled to 0 ° C., a solution of 9-fluorenylmethylchloroformate (798 mg, 3.09 mmol) in dichloromethane (5 ml) was added dropwise, and the reaction solution was stirred at room temperature for 2 hours. The solvent of the reaction mixture was concentrated under reduced pressure, 5% aqueous hydrochloric acid solution was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution, dehydrated with anhydrous magnesium sulfate and the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / n-hexane = 1/5, v / v) to give the title compound (1.39 g, 86%) as a white oil.

TLC: R _f = 0.36 (Ethyl acetate / n-hexane = 1/5)

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 15H), 5.33 (m, 1H), 4.62-5.05 (m, 2H), 4.40-4.60 (m, 1H), 4.10-4.38 (m, 1H), 3.80-4.08 (m, 2H), 2.40-3.00 (m, 2H), 1.43 (d, 9H), 0.95-1.40 (m, 3H), 0.50-0.95 (m, 6H)

[Step 3]

N- (1-naphthylmethyl) -N- (9-fluorenylmethyloxycarbonyl) -2 (S) -amino-3 (S) -methylpentylamine trifluoroacetic acid salt

N- (1-naphthylmethyl) -N- (9-fluorenylmethyloxycarbonyl) -2 (S)-(t-butoxycarbonyl) amino-3 (S) -methylpentylamine (827 mg , 1.43 mmol) was dissolved in dichloromethane (30 ml) and trifluoroacetic acid (10 ml) was added dropwise. After stirring the reaction solution at room temperature for 2 hours, the solution was concentrated under reduced pressure to prepare an oily title compound, which was used in the next reaction without further purification.

[Step 4]

N- (1-naphthylmethyl) -N- (9-fluorenylmethyloxycarbonyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

1- (4-nitrobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride (140 mg, 0.54 mmol) prepared in Reference Example 1 was dissolved in anhydrous dichloromethane and dimethylformamide (50 ml / 3 ml) solution. 1-hydroxybenzotriazole (109 mg, 0.80 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (154 mg, 0.80 mmol) and triethylamine (0.19 ml, 1.34 mmol) It was added dropwise. The reaction mixture was stirred for 30 minutes and then N- (1-naphthylmethyl) -N- (9-fluorenylmethyloxycarbonyl) -2 (S) -amino-3 (S) -methylpentylamine tri Fluoroacetic acid salt (318 mg, 0.54 mmol) was added. The reaction mixture was stirred overnight at room temperature, the solvent was concentrated under reduced pressure, water and ethyl acetate were added and extracted. The organic layer was washed with saturated sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane / methanol = 10/1, v / v) to give the title compound (249 mg, 63%) as a white solid.

TLC: R _f = 0.50 (dichloromethane / methanol = 10/1)

¹ H-NMR (CDCl ₃ ): δ 6.90-8.25 (m, 21H), 6.28 (d, 1H), 5.31 (s, 2H), 5.20 (dd, 2H), 4.02 (bs, 1H), 4.08-4.97 (m, 3H), 3.78 (t, 1H), 2.93 (d, 2H), 1.48 (m, 1H), 1.26 (m, 1H), 0.68-1.16 (m, 7H)

[Step 5]

N- (1-naphthylmethyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

N- (1-naphthylmethyl) -N- (9-fluorenylmethyloxycarbonyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazole- prepared in step 4 5-yl] acetyl} amino-3 (S) -methylpentylamine (249 mg, 0.34 mmol) was dissolved in dimethylformamide (8 ml) and piperidine (2 ml) was added. After the reaction solution was stirred at room temperature for 2 hours, the solvent was concentrated under reduced pressure and purified by silica gel column chromatography (dichloromethane / methanol = 10/1, v / v) to obtain the title compound (116 mg, 68%) as a white solid. Prepared.

TLC: R _f = 0.40 (dichloromethane / methanol = 10/1)

¹ H-NMR (CDCl ₃ ): δ 6.90-8.20 (m, 13H), 5.80 (d, 1H), 5.04 (dd, 2H), 4.22 (s, 2H), 3.90 (bs, 1H), 3.18 (dd , 2H), 2.78 (d, 2H), 1.48 (m, 1H), 1.26 (m, 1H), 1.04 (m, 1H), 0.87 (m, 6H)

Example 1

N- (2,3-dichlorobenzyl) -N- (benzylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine After reacting a 0.02M solution (1 ml, 0.02 mmol) diluted with methane and a 0.1M solution (0.2 ml, 0.02 mmol) diluted with dichloromethane with benzyl isothiocyanate at room temperature for 5 hours, the reaction solution was a short silica gel tube. Purification by chromatography (dichloromethane / methanol = 9/1) gave the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 6.90-8.20 (m, 14H), 6.02 (bs, 1H), 5.32 (s, 2H), 5.15 (m, 1H), 4.80 (d, 2H), 4.60 (m , 2H), 4.15 (m, 1H), 3.25 (s, 2H), 3.04 (dd, 1H), 1.60 (m, 1H), 1.42 (m, 1H), 1.05 (m, 1H), 0.92 (d, 6H)

Example 2-26.

Corresponds to N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine Each title compound was prepared in the same manner as in Example 1 using isothiocyanate.

Example 2

N- (2,3-dichlorobenzyl) -N- (2-bromophenyl) thiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-8.18 (m, 13H), 5.32 (s, 2H), 5.10 (m, 2H), 4.78 (dd, 1H), 4.35 (m, 1H), 3.40 (s , 2H), 3.10 (dd, 1H), 1.60 (m, 1H), 1.40 (m, 1H), 1.05 (m, 1H), 0.92 (m, 6H)

Example 3

N- (2,3-dichlorobenzyl) -N- (3-bromophenyl) thiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.20 (m, 13H), 5.35 (s, 2H), 4.82 (m, 2H), 4.65 (dd, 1H), 4.18 (m, 1H), 3.35 (s , 2H), 3.10 (dd, 1H), 1.65 (m, 1H), 1.42 (m, 1H), 1.05 (m, 1H), 0.92 (m, 6H)

Example 4

N- (2,3-dichlorobenzyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.20 (m, 13H), 5.32 (s, 2H), 4.90-5.22 (m, 2H), 4.65 (dd, 1H), 4.20 (m, 1H), 3.37 (s, 2H), 3.10 (dd, 1H), 1.65 (m, 1H), 1.42 (m, 1H), 1.05 (m, 1H), 0.90 (m, 6H)

Example 5

N- (2,3-dichlorobenzyl) -N- (ethylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-8.22 (m, 9H), 5.40 (d, 2H), 4.75-5.10 (m, 2H), 4.55 (dd, 1H), 4.10 (m, 1H), 3.62 (m, 2H), 3.38 (s, 2H), 3.00 (dd, 1H), 1.65 (m, 1H), 1.45 (m, 1H), 1.10 (m, 3H), 1.05 (m, 1H), 0.92 ( m, 6H)

Example 6

N- (2,3-dichlorobenzyl) -N- (2-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-8.20 (m, 13H), 5.38 (s, 2H), 5.10 (m, 2H), 4.72 (dd, 1H), 4.22 (m, 1H), 3.38 (s , 2H), 3.10 (dd, 1H), 1.62 (m, 1H), 1.43 (m, 1H), 1.10 (m, 1H), 0.90 (m, 6H)

Example 7

N- (2,3-dichlorobenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-8.18 (m, 13H), 5.35 (d, 2H), 4.90-5.20 (m, 2H), 4.65 (dd, 1H), 4.18 (m, 1H), 3.38 (s, 2H), 3.15 (dd, 1H), 1.60 (m, 1H), 1.42 (m, 1H), 1.10 (m, 1H), 0.92 (m, 6H)

Example 8

N- (2,3-dichlorobenzyl) -N- (4-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.80-8.18 (m, 13H), 5.38 (d, 2H), 4.95-5.20 (m, 2H), 4.68 (dd, 1H), 4.15 (m, 1H), 3.38 (s, 2H), 3.10 (dd, 1H), 1.60 (m, 1H), 1.42 (m, 1H), 1.10 (m, 1H), 0.92 (t, 6H)

Example 9

N- (2,3-dichlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.82-8.20 (m, 13H), 5.35 (s, 2H), 5.05 (m, 2H), 4.68 (dd, 1H), 4.18 (m, 1H), 3.78 (s , 3H), 3.35 (s, 2H), 3.08 (dd, 1H), 1.60 (m, 1H), 1.40 (m, 1H), 1.10 (m, 1H), 0.90 (m, 6H)

Example 10

N- (2,3-dichlorobenzyl) -N- (methylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-8.20 (m, 9H), 5.38 (s, 2H), 4.70-5.10 (m, 2H), 4.50 (dd, 1H), 4.10 (m, 1H), 3.35 (s, 2H), 3.10 (d, 2H), 3.00 (dd, 1H), 1.55 (m, 1H), 1.40 (m, 1H), 1.04 (m, 1H), 0.85 (m, 6H)

Example 11

N- (2,3-dichlorobenzyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.18 (m, 13H), 5.40 (m, 2H), 4.85 (m, 2H), 4.65 (dd, 1H), 4.18 (m, 1H), 3.38 (s , 2H), 3.15 (d, 2H), 1.60 (m, 1H), 1.42 (m, 1H), 1.05 (m, 1H), 0.90 (m, 6H)

Example 12

N- (2,3-dichlorobenzyl) -N- (allylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.10 (m, 12H), 5.10-5.28 (m, 4H), 4.80 (dd, 1H), 4.25 (m, 1H), 3.35 (s, 2H), 3.18 (dd, 1H), 1.62 (m, 1H), 1.40 (m, 1H), 1.05 (m, 1H), 0.90 (m, 6H)

Example 13

N- (2,3-dichlorobenzyl) -N- (1-naphthylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.85-8.18 (m, 16H), 5.38 (d, 2H), 5.05 (bs, 1H), 4.40 (d, 2H), 4.05 (m, 1H), 3.28 (s , 2H), 2.95 (dd, 1H), 1.60 (m, 1H), 1.40 (m, 1H), 1.05 (m, 1H), 0.88 (m, 6H)

Example 14

N- (2,3-dichlorobenzyl) -N- (2-phenylethylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.25 (m, 14H), 5.42-5.95 (m, 3H), 4.74-5.25 (m, 2H), 4.60 (dd, 1H), 4.20 (m, 1H) , 3.78 (m, 1H), 3.60 (m, 1H), 3.42 (s, 2H), 3.07 (dd, 1H), 1.60 (m, 1H), 1.42 (m, 1H), 1.05 (m, 1H), 0.90 (m, 6 H)

Example 15

N- (2,3-dichlorobenzyl) -N- (n-butylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.20 (m, 9H), 6.40 (bs, 1H), 5.48 (s, 2H), 4.82-5.08 (m, 5H), 4.45 (m, 1H), 3.55 (s, 2H), 3.20 (m, 1H), 1.30-1.72 (5H), 1.38 (m, 1H), 1.40 (m, 1H), 1.05 (m, 1H), 0.80-1.00 (m, 9H)

Example 16

N- (2,3-dichlorobenzyl) -N- (2-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.80-8.20 (m, 13H), 5.35 (s, 2H), 5.00 (m, 2H), 4.65 (dd, 1H), 4.20 (m, 1H), 3.82 (s , 3H), 3.32 (s, 2H), 3.05 (dd, 1H), 1.60 (m, 1H), 1.42 (m, 1H), 1.12 (m, 1H), 0.92 (m, 6H)

Example 17

N- (2,3-dichlorobenzyl) -N- (benzoylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-8.40 (m, 14H), 5.58 (d, 2H), 5.05-5.42 (m, 2H), 4.82 (dd, 1H), 4.38 (m, 1H), 3.42 (s, 2H), 3.24 (dd, 1H), 1.65 (m, 1H), 1.45 (m, 1H), 1.15 (m, 1H), 1.00 (m, 6H)

Example 18

N- (2,3-dichlorobenzyl) -N- (cyclohexylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.40 (m, 9H), 5.62 (d, 2H), 4.82-5.42 (m, 2H), 4.75 (dd, 1H), 4.42 (m, 1H), 4.30 (m, 1H), 3.50 (s, 2H), 3.20 (dd, 1H), 1.08-2.22 (m, 13H), 1.05 (m, 6H)

Example 19

N- (2,3-dichlorobenzyl) -N-[(4-dimethylamino) -1-naphthylthiocarbamoyl] -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazole -5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.25 (m, 15H), 5.25 (m, 3H), 4.78-5.20 (dd, 2H), 4.28 (m, 1H), 3.40 (s, 2H), 3.18 (dd, 1H), 2.90 (s, 6H), 1.65 (m, 1H), 1.42 (m, 1H), 1.08 (m, 1H), 1.05 (m, 6H)

Example 20

N- (2,3-dichlorobenzyl) -N- (phenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.22-8.38 (m, 14H), 5.22-5.58 (m, 4H), 4.92 (dd, 1H), 4.40 (m, 1H), 3.38 (s, 2H), 3.28 (dd, 1H), 1.64 (m, 1H), 1.40 (m, 1H), 1.03 (m, 1H), 1.00 (m, 6H)

Example 21

N- (2,3-dichlorobenzyl) -N- (n-propylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.10-8.22 (m, 9H), 5.90 (bs, 1H), 5.60 (d, 2H), 4.85-5.40 (m, 2H), 4.75 (dd, 1H), 4.30 (m, 1H), 3.64-3.85 (m, 2H), 3.55 (s, 2H), 3.20 (dd, 1H), 1.42-1.85 (m, 4H), 1.22 (m, 1H), 1.05 (m, 6H ), 1.00 (q, 3H)

Example 22

N- (2,3-dichlorobenzyl) -N- (4-azidophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.20-8.40 (m, 13H), 5.55 (d, 2H), 5.04-5.45 (m, 2H), 4.90 (dd, 1H), 4.38 (m, 1H), 3.57 (s, 2H), 3.30 (dd, 1H), 1.70 (m, 1H), 1.40 (m, 1H), 1.10 (m, 1H), 0.98 (m, 6H)

Example 23

N- (2,3-dichlorobenzyl) -N- (4-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.20-8.40 (m, 13H), 5.56 (d, 2H), 5.32 (m, 2H), 4.96 (dd, 1H), 4.42 (m, 1H), 3.58 (s , 2H), 3.33 (dd, 1H), 1.70 (m, 1H), 1.40 (m, 1H), 1.10 (m, 1H), 0.98 (m, 6H)

Example 24

N- (2,3-dichlorobenzyl) -N- (2-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-8.20 (m, 13H), 5.80 (m, 1H), 5.38 (m, 2H), 4.65-5.04 (m, 2H), 4.50 (dd, 1H), 4.05 -4.38 (m, 2H), 3.28 (s, 2H), 3.00 (dd, 1H), 1.65 (m, 1H), 1.38 (m, 1H), 1.05 (m, 1H), 0.88 (m, 6H)

Example 25

N- (2,3-dichlorobenzyl) -N- (3-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-8.18 (m, 13H), 5.30 (m, 2H), 4.82-5.24 (m, 2H), 4.62 (dd, 1H), 4.18 (m, 1H), 3.35 (s, 2H), 3.06 (dd, 1H), 1.68 (m, 1H), 1.40 (m, 1H), 1.00 (m, 1H), 0.85 (m, 6H)

Example 26

N- (2,3-dichlorobenzyl) -N- (2,4-dichlorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 12H), 5.30 (m, 2H), 5.05 (m, 2H), 4.70 (dd, 1H), 4.22 (m, 1H), 3.35 (s , 2H), 3.12 (dd, 1H), 1.65 (m, 1H), 1.40 (m, 1H), 1.00 (m, 1H), 0.85 (m, 6H)

Example 27

N- (2,3-dichlorobenzyl) -N- (benzylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S prepared in Reference Example 5 ) -Methylpentylamine diluted with dichloromethane (0.02M, 1ml, 0.02mmol) and benzyl isothiocyanate diluted with dichloromethane (0.1M 0.2ml, 0.02mmol) were reacted at room temperature for 2 hours. The reaction solution was then purified by short silica gel column chromatography (dichloromethane / methanol = 9/1) to obtain the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 6.82-7.58 (m, 14H), 6.05 (t, 1H), 5.22 (d, 2H), 5.05 (m, 1H), 4.42-4.80 (m, 4H), 4.05 (m, 1H), 3.20 (s, 2H), 3.00 (dd, 1H), 1.58 (m, 1H), 1.37 (m, 1H), 1.00 (m, 1H), 0.82 (m, 6H)

Example 28-67

N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine Each title compound was prepared in the same manner as in Example 27 using the corresponding isothiocyanate.

Example 28

N- (2,3-dichlorobenzyl) -N- (2-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.65 (m, 13H), 5.20 (d, 2H), 4.62-5.10 (m, 3H), 4.20 (m, 1H), 3.32 (s, 2H), 3.05 (dd, 1H), 1.55 (m, 1H), 1.38 (m, 1H), 0.98 (m, 1H), 0.80 (m, 6H)

Example 29

N- (2,3-dichlorobenzyl) -N- (3-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 13H), 4.85-5.28 (m, 4H), 4.05 (d, 1H), 3.35 (s, 2H), 3.10 (dd, 1H), 1.65 (m, 1H), 1.44 (m, 1H), 0.84-1.08 (m, 7H)

Example 30

N- (2,3-dichlorobenzyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-8.00 (m, 13H), 4.60-5.28 (m, 5H), 4.08 (m, 1H), 3.25 (s, 2H), 3.05 (dd, 1H), 1.60 (m, 1H), 1.38 (m, 1H), 0.85-1.05 (m, 7H)

Example 31

N- (2,3-dichlorobenzyl) -N- (ethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.80-7.60 (m, 9H), 5.68 (t, 1H), 5.22 (dd, 2H), 4.98 (t, 1H), 4.38-4.75 (dd, 2H), 4.00 (m, 1H), 3.58 (m, 2H), 3.25 (s, 2H), 2.88 (dd, 1H), 1.58 (m, 1H), 1.38 (m, 1H), 1.02 (t, 3H), 0.80- 1.00 (m, 7H)

Example 32

N- (2,3-dichlorobenzyl) -N- (2-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.95-7.55 (m, 13H), 5.02-5.25 (m, 3H), 4.60-5.00 (dd, 2H), 3.28 (s, 2H), 3.02 (dd, 1H) , 1.60 (m, 1 H), 1.38 (m, 1 H), 0.85-1.05 (m, 7 H)

Example 33

N- (2,3-dichlorobenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-8.18 (m, 13H), 5.25 (d, 1H), 4.88 (q, 1H), 4.63, 5.20 (dd, 2H), 4.15 (m, 1H), 3.35 (s, 2H), 3.10 (dd, 1H), 1.62 (m, 1H), 1.44 (m, 1H), 0.85-1.05 (m, 7H)

Example 34

N- (2,3-dichlorobenzyl) -N- (4-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-7.68 (m, 13H), 5.20 (d, 1H), 4.85 (bs, 1H), 4.60, 5.10 (dd, 2H), 4.08 (m, 1H), 3.25 (s, 2H), 3.08 (dd, 1H), 1.60 (m, 1H), 1.38 (m, 1H), 0.85-1.05 (m, 7H)

Example 35

N- (2,3-dichlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.82-7.60 (m, 13H), 5.28 (d, 1H), 4.65-5.18 (m, 3H), 4.18 (m, 1H), 3.78 (s, 3H), 3.32 (s, 2H), 3.05 (dd, 1H), 1.62 (m, 1H), 1.45 (m, 1H), 0.85-1.10 (m, 7H)

Example 36

N- (2,3-dichlorobenzyl) -N- (methylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-7.65 (m, 9H), 6.05 (bs, 1H), 5.30 (dd, 1H), 5.05 (t, 1H), 4.40-4.80 (dd, 2H), 4.10 (m, 1H), 3.32 (s, 2H), 3.10 (d, 3H), 3.00 (dd, 1H), 1.60 (m, 1H), 1.45 (m, 1H), 0.85-1.10 (m, 7H)

Example 37

N- (2,3-dichlorobenzyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.95-8.20 (m, 13H), 4.55-5.38 (m, 5H), 4.08 (m, 1H), 3.28 (s, 2H), 3.05 (dd, 1H), 1.60 (m, 1H), 1.40 (m, 1H), 0.85-1.10 (m, 7H)

Example 38

N- (2,3-dichlorobenzyl) -N- (allylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.85-7.65 (m, 9H), 5.92 (t, 1H), 5.78 (m, 1H), 5.35 (d, 2H), 5.10 (m, 3H), 4.42-4.78 (dd, 2H), 4.25 (m, 2H), 4.10 (m, 1H), 3.32 (s, 2H), 3.00 (dd, 1H), 1.62 (m, 1H), 1.44 (m, 1H), 0.85- 1.15 (m, 7H)

Example 39

N- (2,3-dichlorobenzyl) -N- (pyridin-4-ylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.2 (s, 2H), 6.8-7.6 (m, 11H), 5.5 (t, 1H), 5.2 (m, 3H), 4.6 (m, 2H), 4.1 (bs , 1H), 3.4 (s, 2H), 3.1 (m, 1H), 0.8-1.7 (m, 9H)

Example 40

N- (2,3-dichlorobenzyl) -N- (isobutylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.65 (m, 9H), 6.91 (d, 1H), 5.74 (bs, 1H), 5.30 (m, 2H), 5.05-5.20 (m, 1H), 4.62 (dd, 2H), 4.05-4.13 (m, 1H), 3.45-3.58 (m, 1H), 3.25 (m, 2H), 3.02 (m, 1H), 1.83 (m, 1H), 1.62 (bs, 1H ), 1.45 (m, 1H), 1.05 (m, 1H), 0.90 (m, 6H), 0.75 (m, 6H)

Example 41

N- (2,3-dichlorobenzyl) -N- (n-butylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.75-7.65 (m, 9H), 5.75 (bs, 1H), 5.32 (d, 2H), 5.10 (t, 1H), 4.60 (dd, 2H), 4.08 (m , 1H), 3.45 (m, 2H), 3.30 (s, 2H), 3.00 (dd, 1H), 1.65 (m, 1H), 1.45 (m, 3H), 1.20 (m, 2H), 1.05 (m, 1H), 0.86 (m, 6H)

Example 42

N- (2,3-dichlorobenzyl) -N- (ethoxycarbonylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.65 (m, 9H), 6.20 (bs, 1H), 5.24-5.35 (m, 3H), 4.45 4.76 (dd, 2H), 4.18 (m, 3H), 3.35 (d, 2H), 3.00 (dd, 1H), 1.30-1.65 (m, 2H), 1.22 (t, 3H), 1.05 (m, 1H), 0.82 (m, 6H)

Example 43

N- (2,3-dichlorobenzyl) -N- (1-naphthylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.95-7.80 (m, 16H), 5.10-5.30 (m, 4H), 4.80 (d, 1H), 4.22 (m, 1H), 3.32 (s, 2H), 3.18 (dd, 1H), 1.40-1.66 (m, 2H), 1.05 (m, 1H), 0.90 (m, 6H)

Example 44

N- (2,3-dichlorobenzyl) -N- (2-phenylethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.70-7.60 (m, 14H), 5.50 (bs, 1H), 5.35 (d, 2H), 5.08 (t, 1H), 4.40 (d, 2H), 4.05 (m , 1H), 3.80 (m, 2H), 3.30 (s, 2H), 2.98 (dd, 1H), 2.80 (t, 2H), 1.60 (m, 1H), 1.42 (m, 1H), 1.05 (m, 1H), 0.90 (m, 6H)

Example 45

N- (2,3-dichlorobenzyl) -N- (benzoylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-7.80 (m, 14H), 6.38 (bs, 1H), 5.35 (s, 2H), 4.70-5.20 (bs, 3H), 4.30 (bs, 1H), 3.45 (s, 2H), 3.20 (bs, 1H), 2.00 (bs, 1H), 1.50 (m, 1H), 1.00 (m, 1H), 0.80 (m, 6H)

Example 46

N- (2,3-dichlorobenzyl) -N- (cyclohexylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-7.70 (m, 9H), 5.38 (d, 2H), 5.10 (t, 1H), 4.42-4.80 (dd, 2H), 4.25 (m, 1H), 4.06 (m, 1H), 3.35 (s, 2H), 3.00 (dd, 1H), 1.05-2.00 (m, 13H), 0.90 (m, 6H)

Example 47

N- (2,3-dichlorobenzyl) -N-[(4-dimethylamino) -1-naphthylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imid Dazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 15H), 5.08-5.28 (m, 3H), 4.80 (d, 1H), 4.22 (m, 1H), 3.35 (s, 2H), 3.17 (dd, 2H), 2.85 (s, 6H), 1.65 (m, 1H), 1.42 (m, 1H), 0.90 (m, 6H)

Example 48

N- (2,3-dichlorobenzyl) -N- (2-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.80-8.24 (m, 13H), 5.32 (m, 1H), 5.20 (s, 2H), 4.62-5.00 (dd, 2H), 4.22 (m, 1H), 3.56 (s, 3H), 3.35 (s, 2H), 3.10 (dd, 1H), 1.64 (bs, 1H), 1.42 (m, 1H), 0.92 (m, 6H)

Example 49

N- (2,3-dichlorobenzyl) -N- (4-nitrophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.95-8.18 (m, 13H), 5.42 (m, 1H), 5.28 (s, 2H), 4.65 (d, 2H), 4.16 (m, 1H), 3.38 (s , 2H), 3.17 (dd, 1H), 1.64 (bs, 1H), 1.42 (m, 1H), 0.92 (m, 6H)

Example 50

N- (2,3-dichlorobenzyl) -N- (phenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.80 (m, 14H), 5.28 (d, 2H), 5.02-5.18 (m, 2H), 4.65 (d, 1H), 4.18 (bs, 1H), 3.34 (s, 2H), 3.10 (dd, 1H), 1.64 (bs, 1H), 1.42 (m, 1H), 0.94 (m, 6H)

Example 51

N- (2,3-dichlorobenzyl) -N- (n-propylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.75 (m, 9H), 5.35 (d, 2H), 5.10 (m, 1H), 4.42-4.80 (dd, 2H), 4.08 (m, 1H), 3.68 (t, 2H), 3.32 (s, 2H), 3.02 (dd, 1H), 1.62 (m, 1H), 1.50 (m, 2H), 1.40 (m, 1H), 1.05 (m, 1H), 0.94 ( m, 6H), 0.78 (t, 3H)

Example 52

N- (2,3-dichlorobenzyl) -N- (3-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.65 (m, 13H), 5.30 (d, 2H), 5.20 (m, 1H), 4.70 5.04 (dd, 2H), 4.20 (m, 1H), 3.32 ( s, 2H), 3.12 (dd, 1H), 2.12 (s, 3H), 1.64 (bs, 1H), 1.42 (m, 1H), 1.05 (m, 1H), 0.90 (m, 6H)

Example 53

N- (2,3-dichlorobenzyl) -N- (2-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.65 (m, 13H), 5.28 (d, 2H), 5.02-5.20 (m, 2H), 4.65 (d, 1H), 4.15 (m, 1H), 3.35 (s, 2H), 3.08 (dd, 1H), 2.34 (s, 3H), 1.36-1.70 (m, 2H), 1.05 (m, 1H), 0.88 (m, 6H)

Example 54

N- (2,3-dichlorobenzyl) -N- (4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.65 (m, 13H), 5.30 (d, 2H), 5.02-5.22 (m, 2H), 4.65 (d, 1H), 4.15 (m, 1H), 3.32 (s, 2H), 3.08 (dd, 1H), 2.35 (s, 3H), 1.35-1.70 (m, 2H), 1.05 (m, 1H), 0.88 (m, 6H)

Example 55

N- (2,3-dichlorobenzyl) -N- (4-azidophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.90 (m, 13H), 5.28 (d, 2H), 4.90-5.22 (m, 2H), 4.62 (d, 1H), 4.10 (m, 1H), 3.30 (s, 2H), 3.08 (dd, 1H), 1.35-1.70 (m, 2H), 1.05 (m, 1H), 0.88 (m, 6H)

Example 56

N- (2,3-dichlorobenzyl) -N- (4-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-7.60 (m, 13H), 5.22 (d, 2H), 4.95 (t, 1H), 4.62 5.10 (dd, 2H), 4.10 (m, 1H), 3.30 ( s, 2H), 3.08 (dd, 1H), 1.35-1.70 (m, 2H), 1.05 (m, 1H), 0.88 (m, 6H)

Example 57

N- (2,3-dichlorobenzyl) -N- (2-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.70 (m, 13H), 5.24 (s, 2H), 5.18 (m, 1H), 4.74 5.10 (dd, 2H), 4.24 (m, 1H), 3.35 ( s, 2H), 3.10 (dd, 1H), 1.62 (bs, 1H), 1.42 (m, 1H), 1.05 (m, 1H), 0.92 (m, 6H)

Example 58

N- (2,3-dichlorobenzyl) -N- (3-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.60 (m, 13H), 5.25 (sm, 3H), 4.96 (bs, 1H), 4.62 (d, 1H), 4.17 (m, 1H), 3.34 (s , 2H), 3.10 (dd, 1H), 1.62 (bs, 1H), 1.42 (m, 1H), 1.05 (m, 1H), 0.92 (m, 6H)

Example 59

N- (2,3-dichlorobenzyl) -N- (2,4-dichlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.65 (m, 12H), 5.28 (d, 2H), 5.10 (bs, 2H), 4.70 (d, 1H), 4.21 (m, 1H), 3.35 (s , 2H), 3.15 (dd, 1H), 1.62 (bs, 1H), 1.40 (m, 1H), 1.04 (m, 1H), 0.90 (m, 6H)

Example 60

N- (2,3-dichlorobenzyl) -N- (2-methoxypyridin-5-ylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole- 5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.84 (m, 12H), 6.68 (d, 1H), 5.28 (d, 2H), 4.98-5.20 (bs, 2H), 4.68 (d, 1H), 4.18 (m, 1H), 3.87 (s, 3H), 3.30 (s, 2H), 3.12 (dd, 1H), 1.40-1.62 (m, 2H), 1.02 (m, 1H), 0.90 (m, 6H)

Example 61

N- (2,3-dichlorobenzyl) -N- (3-ethoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.80-7.65 (m, 10H), 5.38 (d, 2H), 5.20 (m, 1H), 4.52 (d, 2H), 4.05 (m, 1H), 3.70 (m , 2H), 3.40 (m, 2H), 3.32 (s, 2H), 3.06-3.28 (m, 4H), 2.93 (dd, 1H), 1.75 (t, 3H), 1.60 (bs, 1H), 1.40 ( m, 1H), 1.04 (m, 1H), 0.85 (m, 6H)

Example 62

N- (2,3-dichlorobenzyl) -N- (4-aminophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.25-8.20 (m, 5H), 6.92-7.25 (m, 6H), 6.40-6.90 (m, 3H), 4.78-5.40 (m, 4H), 4.60 (m, 1H), 4.07 (m, 1H), 2.80-3.40 (m, 3H), 1.95 (m, 1H), 1.25-1.70 (m, 2H), 0.90 (m, 6H)

Example 63

N- (2,3-dichlorobenzyl) -N- (2-methoxyethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.82-7.65 (m, 10H), 5.95 (bs, 1H), 5.38 (d, 2H), 5.18 (m, 1H), 4.60 (dd, 2H), 4.10 (m , 1H), 3.72 (t, 2H), 3.40 (t, 2H), 3.28 (s, 2H), 3.15 (s, 3H), 3.02 (dd, 1H), 1.63 (bs, 1H), 1.42 (m, 1H), 1.04 (m, 1H), 0.88 (m, 6H)

Example 64

N- (2,3-dichlorobenzyl) -N- (cyclopentylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.80-7.65 (m, 9H), 5.55 (bs, 1H), 5.38 (d, 2H), 5.05 (m, 1H), 4.62 (m, 1H), 4.42-4.78 (dd, 2H), 4.06 (m, 1H), 3.32 (s, 2H), 3.00 (dd, 1H), 2.00 (m, 4H), 1.40-1.65 (m, 6H), 1.05 (m, 1H), 0.92 (m, 6 H)

Example 65

N- (2,3-dichlorobenzyl) -N- (cyclopropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.85-7.65 (m, 9H), 6.08 (bs, 1H), 5.32 (d, 2H), 4.88 (m, 1H), 4.42-4.82 (dd, 2H), 4.05 (m, 1H), 3.30 (s, 2H), 3.08 (m, 1H), 2.98 (dd, 1H), 1.38-1.64 (m, 2H), 1.05 (m, 1H), 0.80-0.92 (m, 10H )

Example 66

N- (2,3-dichlorobenzyl) -N- (ethoxycarbonylmethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.65 (m, 9H), 6.45 (bs, 1H), 5.30 (d, 2H), 4.90 (m, 1H), 4.50-4.88 (dd, 2H), 4.35 (m, 2H), 4.08 (m, 3H), 3.34 (s, 2H), 3.02 (dd, 1H), 1.38-1.64 (m, 2H), 1.22 (t, 3H), 1.05 (m, 1H), 0.88 (m, 6H)

Example 67

N- (2,3-dichlorobenzyl) -N-[(4-dimethylamino) phenylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.65-7.62 (m, 13H), 5.32 (d, 2H), 5.20 (m, 1H), 4.62-5.02 (dd, 2H), 4.18 (m, 1H), 3.55 (s, 2H), 3.05 (dd, 1H), 2.97 (s, 6H), 1.38-1.65 (m, 2H), 1.22 (t, 3H), 1.05 (m, 1H), 0.90 (m, 6H)

Example 68

N- (2,3-dichlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine hydrochloride

The compound (500 mg) prepared in Example 35 was added to saturated hydrochloric acid-ethanol solution (6N, 5 ml) and stirred at room temperature for 2 hours. The solvent was concentrated under reduced pressure, and the residue was crystallized with a dichloromethane / ethyl ether (1/10, v / v) mixed solution and dried to prepare the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 8.83 (s, 1H), 7.60 (d, 2H), 7.48 (s, 1H), 7.34 (m, 3H), 7.20 (m, 1H), 7.07 (d, 3H ), 6.72 (d, 2H), 5.50 (s, 2H), 4.82-5.20 (m, 2H), 3.80-4.50 (m, 2H), 3.40-3.80 (m, 5H), 3.20 (s, 2H), 0.97-1.60 (m, 3H), 0.70-0.97 (m, 6H)

Example 69

N- (2,3-dichlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine methanesulfonate

The compound (500 mg) prepared in Example 35 was dissolved in dichloromethane (10 ml), methanesulfonic acid (3 ml) and distilled water (0.5 ml) were added, followed by stirring at room temperature for 30 minutes. The organic layer was dehydrated with anhydrous magnesium sulfate, and the residue was concentrated under reduced pressure, and the residue was crystallized with a dichloromethane / ethyl ether (1/10, v / v) mixed solution. The resulting solid was dried to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 14.9 (s, 1H), 8.30-8.80 (m, 2H), 7.37-7.80 (m, 4H), 7.10-7.35 (m, 4H), 6.82 (d, 2H) , 5.40-5.80 (m, 3H), 4.40-4.80 (m, 2H), 4.22 (m, 1H), 3.80 (s, 3H), 3.40-3.77 (m, 2H), 3.23 (m, 1H), 2.00 -2.40 (bs, 2H), 2.76 (s, 3H), 1.10-1.90 (m, 3H), 0.80-1.05 (m, 6H)

Example 70

N- (2,3-dichlorobenzyl) -N- (cyclohexylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine hydrochloride

The title compound was prepared in the same manner as in Example 68, using the compound prepared in Example 46.

¹ H-NMR (CDCl ₃ ): δ 8.10-8.14 (m, 1H), 7.70 (d, 2H), 7.41-7.49 (m, 5H), 7.20 (t, 1H), 7.00 (d, 1H), 5.76 (bs, 2H), 4.95-4.73 (m, 2H), 4.06-4.25 (m, 2H), 3.58 (bs, 2H), 3.03-3.13 (m, 1H), 1.87 (bs, 2H), 1.55-1.61 (m, 3H), 1.02-1.36 (m, 9H), 0.91-0.94 (m, 6H)

Example 71

N- (2,3-dichlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (R)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (R) -methylpentylamine hydrochloride

N- (2,3-dichlorobenzyl) -2 (R)-{[1- (4-cyanobenzyl) in the same manner as in Reference Example 4 using Nt-butoxycarbonyl-D-isoleucine aldehyde The title compound was prepared in the same manner as in Example 27 and Example 68 by preparing -1H-imidazol-5-yl] acetyl} amino-3 (R) -methylpentylamine.

¹ H-NMR (CDCl ₃ ): δ 8.9 (s, 1H), 7.2 (d, 2H), 7.5 (s, 1H), 7.4-7.5 (m, 3H), 7.3 (t, 1H), 7.2 (d , 3H), 6.8 (d, 2H), 5.6 (s, 2H), 5.2 (dd, 2H), 4.9 (s, 3H), 4.3 (m, 1H), 4.2 (m, 1H), 1.6-1.8 ( m, 4H), 1.5-1.6 (m, 2H), 1.2 (m, 1H), 0.8-0.9 (m, 6H)

Example 72

N- (2,3-dichlorobenzyl) -N- (thiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

[Step 1]

N- (2,3-dichlorobenzyl) -N- (thiocarbamoyl) -2 (S)-(t-butoxycarbonyl) amino-3 (S) -methylpentylamine

N- (2,3-dichlorobenzyl) -2 (S)-(t-butoxycarbonyl) amino-3 (S) -methylpentylamine (2.15 g, 5.7 mmol) and benzoylisothiocyanate (0.93 g , 5.7 mmol) was dissolved in dichloromethane (50 ml) and stirred at room temperature for 2 hours. The reaction solvent was concentrated under reduced pressure, methanol (50 ml) and 2N sodium hydroxide (50 ml) were added to the residue, followed by stirring under reflux for 24 hours. The solvent was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (dichloromethane / methanol = 10/1, v / v) to give the title compound (1.15 g).

[Step 2]

N- (2,3-dichlorobenzyl) -N- (thiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

N- (2,3-dichlorobenzyl) -N-thiocarbamoyl-2 (S)-(t-butoxycarbonyl) amino-3 (S) -methylpentylamine (90 mg, 0.21 mmol) in dichloromethane (7 ml), trifluoroacetic acid (3 ml) was added, followed by stirring at room temperature for 1 hour. The reaction solution was washed with saturated sodium bicarbonate solution, the organic layer was dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure. The title compound (20 mg) was obtained in the same manner as in Step 4 of Reference Example 4, using the obtained residue and 1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride (69 mg, 0.25 mmol). Prepared.

¹ H-NMR (CDCl ₃ ): δ 6.88-7.65 (m, 9H), 6.60 (bs, 2H), 5.35 (q, 2H), 4.60-5.18 (br, 2H), 4.50 (dd, 1H), 4.18 (m, 1H), 3.36 (d, 2H), 2.98 (dd, 1H), 1.06-1.65 (m, 3H), 0.86 (m, 6H)

Example 73

N- (2,3-dichlorobenzyl) -N- (allylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropyl Amine

[Step 1]

N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropylamine

N- (t-butoxycarbonyl) -L-alanine aldehyde was prepared in the same manner as in Reference Example 3 using Nt-butoxycarbonyl-L-alanine, and then 1- (4-nitrobenzyl) -1H The title compound was prepared in the same manner as in Reference Example 4, using 1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride instead of imidazol-5-ylacetic acid hydrochloride.

¹ H-NMR (CDCl ₃ ): δ 6.99-7.62 (m, 9H), 6.17 (d, 1H), 5.25 (s, 2H), 3.98 (m, 1H), 3.85 (s, 2H), 3.33 (s , 2H), 2.59 (d, 2H), 1.09 (d, 3H)

[Step 2]

N- (2,3-dichlorobenzyl) -N- (allylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropyl Amine

A solution of N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropylamine diluted with dichloromethane ( 0.02M, 1ml, 0.02mmol) and a solution of allyl isothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) were reacted at room temperature for 1 hour, and then the reaction solution was subjected to short silica gel column chromatography (dichloromethane). / Methanol = 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 6.93-7.66 (m, 9H), 6.52 (bs, 1H), 5.85 (m, 1H), 5.30 (s, 2H), 5.15 (d, 1H), 5.08 (m , 2H), 4.65 (bs, 1H), 4.60 (d, 1H), 4.29 (bs, 2H), 4.10 (m, 1H), 3.32 (s, 2H), 2.95 (dd, 1H), 1.19 (d, 3H)

Example 74-116

N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropylamine and the corresponding isothiocyanate The title compound was prepared in the same manner as Step 2 of Example 73.

Example 74

N- (2,3-dichlorobenzyl) -N- (benzylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropyl Amine

¹ H-NMR (CDCl ₃ ): δ 6.92-7.62 (m, 14H), 5.30 (s, 2H), 5.26 (d, 1H), 4.86 (s, 2H), 4.72 (bs, 1H), 4.62 (d , 1H), 4.08 (m, 1H), 3.25 (s, 2H), 2.97 (dd, 1H), 1.19 (d, 3H)

Example 75

N- (2,3-dichlorobenzyl) -N- (2-biphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.95-7.67 (m, 18H), 6.69 (d, 1H), 5.25 (d, 1H), 5.23 (s, 2H), 4.47 (bs, 1H), 4.47 (m , 1H), 3.94 (s, 1H), 3.29 (s, 2H), 2.86 (dd, 1H), 1.13 (d, 3H)

Example 76

N- (2,3-dichlorobenzyl) -N- (2-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.04 (bs, 1H), 6.97-7.67 (m, 13H), 5.30 (s, 2H), 5.28 (d, 1H), 4.81 (bs, 1H), 4.77 (d , 1H), 4.29 (m, 1H), 3.36 (s, 2H), 3.07 (dd, 1H), 1.21 (d, 3H)

Example 77

N- (2,3-dichlorobenzyl) -N- (3-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 9.12 (bs, 1H), 6.93-7.59 (m, 13H), 5.70 (d, 1H), 5.30 (s, 2H), 4.70 (d, 1H), 4.48 (m , 1H), 4.13 (m, 1H), 3.33 (s, 2H), 2.98 (dd, 1H), 1.25 (d, 3H)

Example 78

N- (2,3-dichlorobenzyl) -N- (4-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.85 (bs, 1H), 6.93-7.59 (m, 13H), 5.61 (d, 1H), 5.24 (s, 2H), 4.71 (d, 1H), 4.52 (m , 1H), 4.12 (m, 1H), 3.33 (s, 2H), 2.98 (dd, 1H), 1.24 (d, 3H)

Example 79

N- (2,3-dichlorobenzyl) -N- (n-butylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.93-7.67 (m, 9H), 6.38 (bs, 1H), 5.34 (s, 2H), 5.14 (d, 1H), 4.70 (m, 1H), 4.59 (d , 1H), 4.09 (m, 1H), 3.61 (m, 2H), 3.33 (s, 2H), 2.94 (dd, 1H), 1.54 (m, 2H), 1.27 (m, 2H), 1.20 (d, 3H), 0.89 (t, 3H)

Example 80

N- (2,3-dichlorobenzyl) -N- (isobutylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Propylamine

¹ H-NMR (CDCl ₃ ): δ 6.94-7.67 (m, 9H), 6.31 (bs, 1H), 5.34 (s, 2H), 5.10 (d, 1H), 4.76 (m, 1H), 4.60 (d , 1H), 4.11 (m, 1H), 3.45 (m, 2H), 3.32 (s, 2H), 2.97 (dd, 1H), 1.92 (m, 1H), 1.18 (d, 3H), 0.81 (t, 6H)

Example 81

N- (2,3-dichlorobenzyl) -N- (2-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.05 (bs, 1H), 6.97-7.66 (m, 13H), 5.27 (d, 1H), 5.25 (s, 2H), 4.81 (bs, 1H), 4.77 (d , 1H), 4.27 (m, 1H), 3.33 (s, 2H), 3.07 (dd, 1H), 1.21 (d, 3H)

Example 82

N- (2,3-dichlorobenzyl) -N- (3-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 9.10 (bs, 1H), 6.93-7.59 (m, 13H), 5.69 (d, 1H), 5.28 (s, 2H), 4.70 (d, 1H), 4.48 (m , 1H), 4.13 (m, 1H), 3.33 (s, 2H), 2.99 (dd, 1H), 1.25 (d, 3H)

Example 83

N- (2,3-dichlorobenzyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.81 (bs, 1H), 6.94-7.59 (m, 13H), 5.60 (d, 1H), 5.24 (s, 2H), 4.71 (d, 1H), 4.52 (m , 1H), 4.13 (m, 1H), 3.33 (s, 2H), 2.99 (dd, 1H), 1.24 (d, 3H)

Example 84

N- (2,3-dichlorobenzyl) -N- (3-chloro-4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.93 (bs, 1H), 6.94-7.60 (m, 12H), 5.63 (d, 1H), 5.29 (s, 2H), 4.71 (d, 1H), 4.53 (bs , 1H), 4.15 (m, 1H), 3.33 (s, 2H), 2.99 (dd, 1H), 2.35 (s, 3H), 1.25 (d, 3H)

Example 85

N- (2,3-dichlorobenzyl) -N- (cyclohexylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Propylamine

¹ H-NMR (CDCl ₃ ): δ 6.91-7.66 (m, 9H), 5.98 (bs, 1H), 5.33 (s, 2H), 5.16 (d, 1H), 4.73 (m, 1H), 4.58 (d , 1H), 4.27 (m, 1H), 4.06 (m, 1H), 3.33 (s, 2H), 2.92 (dd, 1H), 1.93 (m, 2H), 1.01-1.63 (m, 8H), 1.16 ( d, 3H)

Example 86

N- (2,3-dichlorobenzyl) -N- (cyclopentylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Propylamine

¹ H-NMR (CDCl ₃ ): δ 6.93-7.66 (m, 9H), 6.21 (bs, 1H), 5.33 (s, 2H), 5.17 (d, 1H), 4.68 (m, 1H), 4.58 (d , 1H), 4.05 (m, 1H), 3.32 (s, 2H), 2.91 (dd, 1H), 2.02 (m, 2H), 1.25-1.56 (m, 6H), 1.18 (d, 3H)

Example 87

N- (2,3-dichlorobenzyl) -N- (2,4-dichlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.28 (bs, 1H), 6.94-7.62 (m, 12H), 5.27 (d, 1H), 5.24 (s, 2H), 4.75 (d, 1H), 4.71 (m , 1H), 4.25 (m, 1H), 3.32 (s, 2H), 3.06 (dd, 1H), 1.21 (d, 3H)

Example 88

N- (2,3-dichlorobenzyl) -N- [2- (dimethylamino) ethylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.98-7.66 (m, 9H), 5.41 (d, 1H), 5.29 (s, 2H), 4.90 (m, 1H), 4.64 (d, 1H), 4.20 (m , 1H), 3.59 (m, 2H), 3.28 (dd, 2H), 3.12 (dd, 1H), 2.54 (m, 2H), 2.10 (s, 6H), 1.17 (d, 3H)

Example 89

N- (2,3-dichlorobenzyl) -N- [4- (dimethylamino) phenylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 7.96 (bs, 1H), 6.63-7.60 (m, 13H), 5.29 (s, 2H), 5.20 (d, 1H), 4.86 (m, 1H), 4.73 (d , 1H), 4.18 (m, 1H), 3.32 (s, 2H), 3.02 (dd, 1H), 2.95 (s, 6H), 1.20 (d, 3H)

Example 90

N- (2,3-dichlorobenzyl) -N- [3- (dimethylamino) propylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.91 (bs, 1H), 6.80-7.66 (m, 9H), 5.44 (d, 1H), 5.36 (s, 2H), 4.95 (m, 1H), 4.55 (d , 2H), 4.12 (m, 1H), 3.68 (m, 2H), 3.32 (dd, 2H), 2.92 (dd, 1H), 2.41 (m, 2H), 1.72 (m, 2H), 1.90 (s, 6H), 1.13 (d, 3H)

Example 91

N- (2,3-dichlorobenzyl) -N- (3-ethoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 7.75 (bs, 1H), 6.84-7.67 (m, 9H), 5.35 (s, 2H), 4.94 (t, 1H), 4.66 (dd, 2H), 4.12 (m , 1H), 3.74 (bs, 2H), 3.42 (m, 2H), 3.32 (s, 2H), 3.21 (m, 2H), 2.94 (dd, 1H), 1.78 (bs, 2H), 1.14 (d, 3H), 0.90 (t, 3H)

Example 92

N- (2,3-dichlorobenzyl) -N- (ethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropyl Amine

¹ H-NMR (CDCl ₃ ): δ 6.92-7.66 (m, 9H), 6.45 (bs, 1H), 5.34 (s, 2H), 5.18 (d, 1H), 4.63 (m, 1H), 4.58 (d , 1H), 4.07 (m, 1H), 3.66 (m, 2H), 3.32 (s, 2H), 2.91 (dd, 1H), 1.18 (d, 3H), 1.16 (t, 3H)

Example 93

N- (2,3-dichlorobenzyl) -N- (2-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.28 (bs, 1H), 6.95-7.60 (m, 13H), 5.36 (d, 1H), 5.25 (s, 2H), 4.79 (m, 1H), 4.75 (d , 1H), 4.22 (m, 1H), 3.32 (s, 2H), 3.04 (dd, 1H), 1.21 (d, 3H)

Example 94

N- (2,3-dichlorobenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.98 (bs, 1H), 6.86-7.59 (m, 13H), 5.66 (d, 1H), 5.26 (s, 2H), 4.70 (d, 1H), 4.52 (m , 1H), 4.13 (m, 1H), 3.33 (s, 2H), 2.99 (dd, 1H), 1.25 (d, 3H)

Example 95

N- (2,3-dichlorobenzyl) -N- (4-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.56 (bs, 1H), 6.96-7.60 (m, 13H), 5.52 (d, 1H), 5.26 (s, 2H), 4.72 (d, 1H), 4.59 (m , 1H), 4.14 (m, 1H), 3.32 (s, 2H), 3.00 (dd, 1H), 1.23 (d, 3H)

Example 96

N- (2,3-dichlorobenzyl) -N- (4-hydroxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.69-7.75 (m, 13H), 5.37 (s, 2H), 5.32 (d, 1H), 5.00 (d, 1H), 4.24 (m, 1H), 4.10 (m , 1H), 3.43 (dd, 1H), 3.41 (s, 2H), 1.17 (d, 3H)

Example 97

N- (2,3-dichlorobenzyl) -N- (4-isopropylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.22 (bs, 1H), 6.98-7.59 (m, 13H), 5.39 (d, 1H), 5.26 (s, 2H), 4.76 (m, 1H), 4.72 (d , 1H), 4.17 (m, 1H), 3.32 (s, 2H), 3.01 (dd, 1H), 2.90 (m, 1H), 1.23 (d, 9H)

Example 98

N- (2,3-dichlorobenzyl) -N- (2-methoxyethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.88-7.66 (m, 9H), 6.26 (bs, 1H), 5.34 (s, 2H), 4.91 (d, 1H), 4, .86 (t, 1H), 4.61 (d, 2H), 4.13 (m, 1H), 3.78 (m, 2H), 3.44 (m, 2H), 3.32 (s, 2H), 3.17 (s, 3H), 3.02 (dd, 1H), 1.16 (d, 3H)

Example 99

N- (2,3-dichlorobenzyl) -N- (2-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.18 (d, 1H), 6.79-7.62 (m, 13H), 5.23 (s, 2H), 5.11 (m, 1H), 5.01 (d, 1H), 4.76 (d , 1H), 4.30 (m, 1H), 3.60 (s, 3H), 3.35 (s, 2H), 3.12 (dd, 1H), 1.20 (d, 3H)

Example 100

N- (2,3-dichlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.26 (bs, 1H), 6.84-7.59 (m, 13H), 5.38 (d, 1H), 5.26 (s, 2H), 4.75 (m, 1H), 4.72 (d , 1H), 4.16 (m, 1H), 3.79 (s, 3H), 3.31 (s, 2H), 3.01 (dd, 1H), 1.21 (d, 3H).

Example 101

N- (2,3-dichlorobenzyl) -N- (3-methoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 7.82 (bs, 1H), 6.81-7.67 (m, 9H), 5.36 (dd, 2H), 4.98 (t, 1H), 4.62 (dd, 2H), 4.13 (m , 1H), 3.68 (m, 2H), 3.37 (m, 2H), 3.31 (s, 2H), 2.96 (dd, 1H), 2.91 (s, 3H), 1.76 (m, 2H), 1.14 (d, 3H)

Example 102

N- (2,3-dichlorobenzyl) -N- (2-methoxypyridin-5-ylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole- 5-yl] acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.80 (bs, 1H), 6.71-7.97 (m, 12H), 5.59 (d, 1H), 5.26 (s, 2H), 4.73 (d, 1H), 4.60 (m , 1H), 4.16 (m, 1H), 3.91 (s, 3H), 3.32 (s, 2H), 3.01 (dd, 1H), 1.24 (d, 3H)

Example 103

N- (2,3-dichlorobenzyl) -N- (methylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropyl Amine

¹ H-NMR (CDCl ₃ ): δ 6.92-7.67 (m, 9H), 6.56 (bs, 1H), 5.29 (s, 2H), 5.13 (d, 1H), 4.65 (m, 1H), 4.58 (d , 1H), 4.09 (m, 1H), 3.32 (s, 2H), 3.11 (s, 3H), 2.92 (dd, 1H), 1.18 (d, 3H)

Example 104

N- (2,3-dichlorobenzyl) -N- (4-methylthiophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.59 (bs, 1H), 6.94-7.59 (m, 13H), 5.50 (d, 1H), 5.24 (s, 2H), 4.71 (d, 1H), 4.61 (m , 1H), 4.14 (m, 1H), 3.31 (s, 2H), 2.99 (dd, 1H), 2.46 (s, 3H), 1.22 (d, 3H)

Example 105

N- (2,3-dichlorobenzyl) -N- (2-naphthylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.89 (bs, 1H), 6.96-7.81 (m, 16H), 5.57 (d, 1H), 5.19 (s, 2H), 4.74 (d, 1H), 4.62 (m , 1H), 4.19 (m, 1H), 3.32 (s, 2H), 3.00 (dd, 1H), 1.22 (d, 3H)

Example 106

N- (2,3-dichlorobenzyl) -N- (4-nitrophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 9.54 (bs, 1H), 6.64-8.19 (m, 13H), 5.86 (d, 1H), 5.25 (s, 2H), 4.72 (d, 1H), 4.19 (d , 1H), 4.09 (m, 1H), 3.39 (s, 2H), 3.00 (dd, 1H), 1.29 (d, 3H)

Example 107

N- (2,3-dichlorobenzyl) -N- (n-pentylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.93-7.66 (m, 9H), 6.21 (bs, 1H), 5.33 (s, 2H), 5.07 (d, 1H), 4.77 (m, 1H), 4.59 (d , 1H), 4.12 (m, 1H), 3.63 (m, 1H), 3.48 (t, 2H), 3.31 (s, 1H), 2.97 (dd, 1H), 1.68 (m, 1H), 1.17 (d, 3H), 0.74-1.30 (m, 8H)

Example 108

N- (2,3-dichlorobenzyl) -N- (2-phenylethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.73-7.65 (m, 14H), 5.99 (bs, 1H), 5.30 (s, 2H), 4.80 (d, 1H), 4.75 (m, 1H), 4.45 (d , 1H), 4.05 (m, 1H), 3.85 (m, 2H), 3.30 (s, 2H), 2.92 (dd, 1H), 2.84 (t, 2H), 1.14 (d, 3H)

Example 109

N- (2,3-dichlorobenzyl) -N- (phenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropyl Amine

¹ H-NMR (CDCl ₃ ): δ 8.51 (bs, 1H), 6.95-7.57 (m, 14H), 5.48 (d, 1H), 5.25 (s, 2H), 4.72 (d, 1H), 4.68 (m , 1H), 4.17 (m, 1H), 3.32 (s, 2H), 3.00 (dd, 1H), 1.22 (d, 3H)

Example 110

N- (2,3-dichlorobenzyl) -N- (n-propylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.93-7.67 (m, 9H), 6.35 (bs, 1H), 5.33 (s, 2H), 5.14 (d, 1H), 4.72 (m, 1H), 4.59 (d , 1H), 4.09 (m, 1H), 3.59 (m, 2H), 3.33 (s, 2H), 2.93 (dd, 1H), 1.58 (dd, 2H), 1.25 (m, 2H), 1.18 (d, 3H), 0.85 (t, 3H)

Example 111

N- (2,3-dichlorobenzyl) -N- (3-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.28 (bs, 1H), 6.98-7.56 (m, 13H), 5.44 (d, 1H), 5.26 (s, 2H), 4.72 (d, 1H), 4.71 (m , 1H), 4.17 (m, 1H), 3.33 (s, 2H), 3.01 (dd, 1H), 2.33 (s, 3H), 1.22 (d, 3H)

Example 112

N- (2,3-dichlorobenzyl) -N- (2-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 7.87 (bs, 1H), 6.96-7.60 (m, 13H), 5.31 (d, 1H), 5.27 (s, 2H), 4.81 (m, 1H), 4.75 (d , 1H), 4.20 (m, 1H), 3.31 (s, 2H), 3.06 (dd, 1H), 2.11 (s, 3H), 1.20 (d, 3H)

Example 113

N- (2,3-dichlorobenzyl) -N- (4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.29 (bs, 1H), 6.96-7.58 (m, 13H), 5.43 (d, 1H), 5.26 (s, 2H), 4.72 (d, 1H), 4.70 (m , 1H), 4.17 (m, 1H), 3.32 (s, 2H), 3.00 (dd, 1H), 2.33 (s, 3H), 1.21 (d, 3H)

Example 114

N- (2,3-dichlorobenzyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 9.44 (bs, 1H), 6.92-7.85 (m, 13H), 5.81 (d, 1H), 5.27 (s, 2H), 4.71 (d, 1H), 4.43 (m , 1H), 4.13 (m, 1H), 3.33 (s, 2H), 3.00 (dd, 1H), 1.28 (d, 3H)

Example 115

N- (2,3-dichlorobenzyl) -N- (2,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 7.85 (bs, 1H), 6.96-7.60 (m, 12H), 5.27 (s, 2H), 5.20 (d, 1H), 4.85 (m, 1H), 4.74 (d , 1H), 4.20 (m, 1H), 3.31 (s, 2H), 3.05 (dd, 1H), 2.31 (s, 3H), 2.07 (s, 3H), 1.20 (d, 3H)

Example 116

N- (2,3-dichlorobenzyl) -N- (3,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.20 (bs, 1H), 6.98-7.60 (m, 12H), 5.38 (d, 1H), 5.26 (s, 2H), 4.74 (m, 1H), 4.72 (d , 1H), 4.17 (m, 1H), 3.32 (s, 2H), 3.01 (dd, 1H), 2.22 (s, 6H), 1.21 (d, 3H)

Example 117

N- (2,3-dichlorobenzyl) -N- (allylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3-methylbutylamine

[Step 1]

N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3-methylbutylamine

Nt-butoxycarbonyl-L-valine aldehyde was prepared in the same manner as in Reference Example 3 using Nt-butoxycarbonyl-L-valine, and then 1- (4-nitrobenzyl) -1H-imidazole- The title compound was prepared in the same manner as in Reference Example 4 using 1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride instead of 5-ylacetic acid hydrochloride.

¹ H-NMR (CDCl ₃ ): δ 7.01-7.62 (m, 9H), 6.10 (d, 1H), 5.26 (s, 2H), 3.83 (s, 2H), 3.80 (m, 1H), 3.37 (s , 2H), 2.64 (d, 2H), 1.74 (m, 1H), 0.83 (t, 6H)

[Step 2]

N- (2,3-dichlorobenzyl) -N- (allylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3-methylbutylamine

N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3-methylbutylamine to dichloromethane The diluted solution (0.02M, 1ml, 0.02mmol) and the allyl isothiocyanate diluted solution with dichloromethane (0.1M, 0.2ml, 0.02mmol) were reacted at room temperature for 1 hour, and then the reaction solution was subjected to a short silica gel column chromatography. Purification by chromatography (dichloromethane / methanol = 9/1, v / v) gave the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 6.89-7.66 (m, 9H), 6.02 (bs, 1H), 5.79 (m, 1H), 4.98-5.09 (m, 2H), 4.80 (d, 1H), 4.52 (d, 1H), 4.27 (m, 2H), 4.05 (m, 1H), 3.32 (s, 2H), 3.03 (dd, 1H), 1.79 (m, 1H), 0.90 (d, 6H)

Example 118-160

N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3-methylbutylamine and the corresponding iso The title compound was prepared in the same manner as in Step 2 of Example 117 using thiocyanate.

Example 118

N- (2,3-dichlorobenzyl) -N- (benzylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.91-7.64 (m, 14H), 6.31 (bs, 1H), 5.26 (d, 2H), 5.07 (t, 1H), 4.81 (m, 2H), 4.54 (d , 1H), 4.06 (m, 1H), 3.26 (s, 2H), 3.05 (dd, 1H), 1.83 (m, 1H), 1.90 (d, 6H)

Example 119

N- (2,3-dichlorobenzyl) -N- (2-biphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.64-7.75 (m, 18H), 5.26 (s, 2H), 4.84 (m, 1H), 4.80 (d, 1H), 4.48 (d, 1H), 4.03 (m , 1H), 3.34 (s, 2H), 2.98 (dd, 1H), 1.82 (m, 1H), 0.87 (dd, 6H)

Example 120

N- (2,3-dichlorobenzyl) -N- (2-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.93-7.72 (m, 13H), 5.24 (s, 2H), 5.13 (d, 1H), 5.12 (m, 1H), 4.73 (d, 1H), 4.20 (m , 1H), 3.36 (s, 2H), 3.14 (dd, 1H), 1.86 (m, 1H), 0.91 (dd, 6H)

Example 121

N- (2,3-dichlorobenzyl) -N- (3-bromophenylthiocarbamoyl) 2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.28 (bs, 1H), 6.85-7.60 (m, 13H), 5.26 (d, 1H), 5.24 (d, 2H), 4.88 (t, 1H), 4.65 (d , 1H), 4.08 (m, 1H), 3.32 (s, 2H), 3.10 (dd, 1H), 1.88 (m, 1H), 0.91 (t, 6H)

Example 122

N- (2,3-dichlorobenzyl) -N- (4-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.48 (bs, 1H), 6.88-7.60 (m, 13H), 5.33 (d, 1H), 5.26 (s, 2H), 4.84 (t, 1H), 4.66 (d , 1H), 4.09 (m, 1H), 3.34 (s, 2H), 3.11 (dd, 1H), 1.91 (m, 1H), 0.92 (dd, 6H)

Example 123

N- (2,3-dichlorobenzyl) -N- (n-butylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.89-7.67 (m, 9H), 5.93 (bs, 1H), 5.35 (d, 2H), 5.04 (t, 1H), 4.65 (dd, 2H), 4.04 (m , 1H), 3.68 (m, 1H), 3.48 (m, 1H), 3.33 (s, 2H), 3.02 (dd, 1H), 1.84 (m, 1H), 1.47 (m, 2H), 1.18 (m, 2H), 0.89 (m, 6H), 0.85 (t, 3H)

Example 124

N- (2,3-dichlorobenzyl) -N- (isobutylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-7.66 (m, 9H), 5.91 (bs, 1H), 5.35 (d, 2H), 5.07 (t, 1H), 4.64 (dd, 2H), 4.04 (m , 1H), 3.52 (m, 1H), 3.32 (s, 2H), 3.24 (m, 1H), 3.03 (dd, 1H), 1.83 (m, 2H), 0.91 (m, 6H), 0.75 (t, 6H)

Example 125

N- (2,3-dichlorobenzyl) -N- (2-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.94-7.69 (m, 13H), 5.25 (s, 2H), 5.11 (d, 1H), 5.07 (m, 1H), 4.72 (d, 1H), 4.19 (m , 1H), 3.36 (s, 2H), 3.14 (dd, 1H), 1.85 (m, 1H), 0.91 (m, 6H)

Example 126

N- (2,3-dichlorobenzyl) -N- (3-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.47 (bs, 1H), 6.89-7.60 (m, 13H), 5.34 (d, 1H), 5.26 (s, 2H), 4.58 (t, 1H), 4.66 (d , 1H), 4.09 (m, 1H), 3.33 (s, 2H), 3.11 (dd, 1H), 1.89 (m, 1H), 0.92 (m, 6H)

Example 127

N- (2,3-dichlorobenzyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.33 (bs, 1H), 6.90-7.61 (m, 13H), 5.30 (d, 1H), 5.24 (s, 2H), 4.89 (t, 1H), 4.66 (d , 1H), 4.08 (m, 1H), 3.32 (s, 2H), 3.11 (dd, 1H), 1.88 (m, 1H), 0.91 (t, 6H)

Example 128

N- (2,3-dichlorobenzyl) -N- (3-chloro-4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl] amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.33 (bs, 1H), 6.97-7.60 (m, 12H), 5.29 (d, 1H), 5.26 (s, 2H), 4.89 (t, 1H), 4.65 (d , 1H), 4.09 (m, 1H), 3.33 (s, 2H), 3.10 (dd, 1H), 2.32 (s, 3H), 1.88 (m, 1H), 0.91 (t, 6H)

Example 129

N- (2,3-dichlorobenzyl) -N- (cyclohexylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.88-7.66 (m, 9H), 5.98 (bs, 1H), 5.34 (d, 2H), 5.06 (t, 1H), 4.64 (dd, 1H), 4.25 (m , 1H), 4.01 (m, 1H), 3.33 (s, 2H), 3.00 (dd, 1H), 1.84 (m, 1H), 0.88-1.98 (m, 10H), 0.91 (t, 6H)

Example 130

N- (2,3-dichlorobenzyl) -N- (cyclopentylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.88-7.66 (m, 9H), 6.25 (d, 1H), 5.34 (d, 2H), 5.03 (t, 1H), 4.65 (dd, 1H), 4.65 (dd , 1H), 4.02 (m, 1H), 3.33 (s, 2H), 3.01 (dd, 1H), 1.84 (m, 1H), 1.18-2.06 (m, 8H), 0.90 (dd, 6H)

Example 131

N- (2,3-dichlorobenzyl) -N- (2,4-dichlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.81 (bs, 1H), 6.84-7.63 (m, 12H), 5.25 (s, 2H), 5.14 (d, 1H), 5.01 (t, 1H), 4.71 (d , 1H), 4.17 (m, 1H), 3.34 (s, 2H), 3.15 (dd, 1H), 1.83 (m, 1H), 0.90 (t, 6H)

Example 132

N- (2,3-dichlorobenzyl) -N- [2- (dimethylamino) ethylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl] amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.91-7.68 (m, 9H), 6.76 (bs, 1H), 5.39 (dd, 2H), 5.08 (t, 1H), 4.65 (dd, 2H), 4.08 (m , 1H), 3.53 (m, 2H), 3.35 (s, 2H), 3.14 (dd, 1H), 2.53 (m, 2H), 2.00 (s, 6H), 1.88 (m, 1H), 0.93 (d, 6H)

Example 133

N- (2,3-dichlorobenzyl) -N- [4- (dimethylamino) phenylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl] amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.60-7.61 (m, 13H), 5.28 (s, 2H), 5.13 (t, 1H), 5.03 (d, 1H), 4.66 (d, 1H), 4.09 (m , 1H), 3.33 (s, 2H), 3.08 (dd, 1H), 2.93 (s, 6H), 1.85 (m, 1H), 0.91 (dd, 6H)

Example 134

N- (2,3-dichlorobenzyl) -N- [3- (dimethylamino) propylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl] amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.88 (bs, 1H), 6.81-7.67 (m, 9H), 5.40 (dd, 2H), 5.11 (t, 1H), 4.52 (s, 2H), 4.05 (m , 1H), 3.67 (m, 2H), 3.33 (dd, 2H), 2.93 (dd, 1H), 2.40 (m, 2H), 1.87 (s, 6H), 1.83 (m, 1H), 1.77 (m, 2H), 0.90 (d, 6H)

Example 135

N- (2,3-dichlorobenzyl) -N- (3-ethoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.76-7.67 (m, 9H), 5.37 (dd, 2H), 5.15 (t, 1H), 4.54 (d, 2H), 4.03 (m, 1H), 3.72 (m , 2H), 3.43 (m, 2H), 3.33 (s, 2H), 3.18 (m, 2H), 2.93 (dd, 1H), 1.78 (m, 1H), 1.75 (m, 2H), 0.88 (m, 6H), 0.86 (t, 3H)

Example 136

N- (2,3-dichlorobenzyl) -N- (ethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.87-7.66 (m, 9H), 5.94 (bs, 1H), 5.34 (dd, 2H), 5.00 (t, 1H), 4.65 (dd, 2H), 4.02 (m , 1H), 3.63 (m, 2H), 3.32 (s, 2H), 3.00 (dd, 1H), 1.84 (m, 1H), 1.10 (t, 3H), 0.91 (m, 6H)

Example 137

N- (2,3-dichlorobenzyl) -N- (2-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-7.62 (m, 13H), 5.26 (s, 2H), 5.11 (d, 1H), 5.07 (t, 1H), 4.70 (d, 1H), 4.15 (m , 1H), 3.36 (s, 2H), 3.11 (dd, 1H), 1.85 (m, 1H), 0.91 (dd, 6H)

Example 138

N- (2,3-dichlorobenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.21 (bs, 1H), 6.82-7.61 (m, 13H), 5.30 (d, 1H), 5.26 (s, 2H), 4.89 (t, 1H), 4.66 (d , 1H), 4.09 (m, 1H), 3.34 (s, 2H), 3.11 (dd, 1H), 1.87 (m, 1H), 0.92 (dd, 6H)

Example 139

N- (2,3-dichlorobenzyl) -N- (4-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.10 (bs, 1H), 6.97-7.63 (m, 13H), 5.31 (s, 2H), 5.22 (d, 1H), 4.95 (t, 1H), 4.68 (d , 1H), 4.10 (m, 1H), 3.34 (s, 2H), 3.13 (dd, 1H), 1.89 (m, 1H), 0.92 (dd, 6H)

Example 140

N- (2,3-dichlorobenzyl) -N- (4-hydroxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.67-7.71 (m, 13H), 5.39 (s, 2H), 5.03 (dd, 2H), 4.29 (m, 1H), 3.87 (m, 1H), 3.67 (d , 1H), 3.44 (s, 3H), 3.31 (s, 2H), 2.68 (m, 1H), 1.77 (m, 1H), 0.89 (t, 6H)

Example 141

N- (2,3-dichlorobenzyl) -N- (4-isopropylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-7.77 (m, 13H), 5.27 (s, 2H), 5.12 (d, 1H), 5.08 (t, 1H), 4.67 (d, 1H), 4.11 (m , 1H), 3.35 (s, 2H), 3.11 (dd, 1H), 2.89 (m, 1H), 1.86 (m, 1H), 1.23 (d, 6H), 0.92 (dd, 6H)

Example 142

N- (2,3-dichlorobenzyl) -N- (2-methoxyethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.88-7.66 (m, 9H), 6.01 (bs, 1H), 5.35 (d, 2H), 5.16 (1, 1H), 4.62 (dd, 1H), 4.07 (m , 1H), 3.82 (m, 1H), 3.68 (m, 1H), 3.41 (m, 2H), 3.33 (s, 2H), 3.13 (s, 3H), 3.06 (dd, 1H), 1.83 (m, 1H), 0.91 (d, 6H)

Example 143

N- (2,3-dichlorobenzyl) -N- (2-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.27 (d, 1H), 6.77-7.58 (m, 13H), 5.26 (m, 1H), 5.19 (s, 2H), 4.82 (dd, 2H), 4.18 (m , 1H), 3.57 (s, 3H), 3.36 (s, 2H), 3.12 (dd, 1H), 1.83 (m, 1H), 0.93 (d, 6H)

Example 144

N- (2,3-dichlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.80 (bs, 1H), 6.81-7.61 (m, 13H), 5.27 (dd, 2H), 5.11 (m, 1H), 5.10 (d, 1H), 4.66 (d , 1H), 4.09 (m, 1H), 3.78 (s, 3H), 3.32 (s, 2H), 3.09 (dd, 1H), 1.86 (m, 1H), 0.90 (t, 6H)

Example 145

N- (2,3-dichlorobenzyl) -N- (3-methoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.81-7.67 (m, 9H), 5.37 (dd, 2H), 5.17 (t, 1H), 4.52 (dd, 2H), 4.04 (m, 1H), 3.42 (m , 2H), 3.32 (s, 2H), 3.29 (m, 2H), 2.96 (dd, 1H), 2.88 (s, 3H), 1.83 (m, 1H), 1.75 (m, 2H), 0.90 (d, 6H)

Example 146

N- (2,3-dichlorobenzyl) -N- (2-methoxypyridin-5-ylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole- 5-yl] acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.35 (bs, 1H), 6.66-7.89 (m, 12H), 5.26 (d, 2H), 5.24 (d, 1H), 4.95 (t, 1H), 4.67 (d , 1H), 3.87 (s, 3H), 3.30 (s, 2H), 3.12 (dd, 1H), 1.88 (m, 1H), 0.91 (t, 6H)

Example 147

N- (2,3-dichlorobenzyl) -N- (methylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.88-7.68 (m, 9H), 6.25 (bs, 1H), 5.36 (dd, 2H), 4.99 (t, 1H), 4.64 (dd, 2H), 4.04 (m , 1H), 3.33 (s, 2H), 3.08 (s, 3H), 3.01 (dd, 1H), 1.85 (m, 1H), 0.92 (dd, 6H)

Example 148

N- (2,3-dichlorobenzyl) -N- (4-methylthiophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.10 (bs, 1H), 6.96-7.60 (m, 13H), 5.25 (d, 2H), 5.19 (d, 1H), 4.98 (t, 1H), 4.66 (d , 1H), 4.08 (m, 1H), 3.32 (s, 2H), 3.10 (dd, 1H), 2.45 (s, 3H), 1.87 (m, 1H), 0.91 (t, 6H)

Example 149

N- (2,3-dichlorobenzyl) -N- (2-naphthylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.37 (bs, 1H), 6.94-7.81 (m, 16H), 5.19 (d, 1H), 5.17 (d, 2H), 5.01 (t, 1H), 4.71 (d , 1H), 4.12 (m, 1H), 3.34 (s, 2H), 3.11 (dd, 1H), 1.87 (m, 1H), 0.91 (t, 6H)

Example 150

N- (2,3-dichlorobenzyl) -N- (4-nitrophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 9.24 (bs, 1H), 6.79-8.15 (m, 13H), 5.54 (d, 1H), 5.27 (s, 2H), 4.67 (d, 1H), 4.65 (m , 1H), 4.08 (m, 1H), 3.38 (s, 2H), 3.18 (dd, 1H), 1.95 (m, 1H), 0.93 (t, 6H)

Example 151

N- (2,3-dichlorobenzyl) -N- (n-pentylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-7.66 (m, 9H), 5.78 (bs, 1H), 5.35 (dd, 2H), 5.09 (t, 1H), 4.63 (dd, 2H), 4.05 (m , 1H), 3.32 (s, 2H), 3.19-3.74 (m, 2H), 3.04 (dd, 1H), 1.84 (m, 1H), 1.60 (m, 1H), 1.16 (m, 1H), 1.06 ( m, 2H), 0.91 (dd, 6H), 0.81 (m, 2H), 0.71 (t, 3H)

Example 152

N- (2,3-dichlorobenzyl) -N- (2-phenylethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.68-7.64 (m, 14H), 5.60 (bs, 1H), 5.33 (dd, 2H), 5.03 (t, 1H), 4.44 (dd, 2H), 4.00 (m , 1H), 3.84 (m, 2H), 3.31 (s, 2H), 2.97 (dd, 1H), 2.80 (t, 2H), 1.81 (m, 1H), 0.89 (d, 6H)

Example 153

N- (2,3-dichlorobenzyl) -N- (phenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.32 (bs, 1H), 6.94-7.58 (m, 14H), 5.23 (s, 1H), 5.20 (d, 1H), 5.07 (t, 1H), 4.67 (d , 1H), 4.10 (m, 1H), 3.31 (s, 2H), 3.13 (dd, 1H), 1.86 (m, 1H), 0.91 (dd, 6H)

Example 154

N- (2,3-dichlorobenzyl) -N- (n-propylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.88-7.66 (m, 9H), 5.89 (bs, 1H), 5.35 (dd, 2H), 5.04 (t, 1H), 4.64 (dd, 2H), 4.03 (m , 1H), 3.63 (m, 1H), 3.47 (m, 1H), 3.32 (s, 2H), 3.01 (dd, 1H), 1.84 (m, 1H), 1.51 (m, 2H), 0.91 (m, 6H), 0.79 (t, 3H)

Example 155

N- (2,3-dichlorobenzyl) -N- (3-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.83 (bs, 1H), 7.01-7.59 (m, 13H), 5.25 (s, 2H), 5.14 (d, 1H), 5.02 (t, 1H), 4.67 (d , 1H), 4.10 (m, 1H), 3.35 (s, 2H), 3.10 (dd, 1H), 2.31 (s, 3H), 1.87 (m, 1H), 0.91 (dd, 6H)

Example 156

N- (2,3-dichlorobenzyl) -N- (2-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.99-7.62 (m, 13H), 5.28 (s, 2H), 5.13 (t, 1H), 5.08 (d, 1H), 4.70 (d, 1H), 4.13 (m , 1H), 3.33 (s, 2H), 3.13 (dd, 1H), 2.05 (s, 3H), 1.87 (m, 1H), 0.90 (dd, 6H)

Example 157

N- (2,3-dichlorobenzyl) -N- (4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.97 (bs, 1H), 6.95-7.60 (m, 13H), 5.25 (s, 2H), 5.14 (d, 1H), 5.05 (t, 1H), 4.66 (d , 1H), 4.09 (m, 1H), 3.32 (s, 2H), 3.16 (dd, 1H), 2.32 (s, 3H), 1.86 (m, 1H), 0.90 (t, 6H)

Example 158

N- (2,3-dichlorobenzyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.81 (bs, 1H), 6.87-7.64 (m, 13H), 5.47 (d, 1H), 5.25 (s, 2H), 4.71 (m, 1H), 4.66 (d , 1H), 4.09 (m, 1H), 3.34 (s, 2H), 3.14 (dd, 1H), 1.92 (m, 1H), 0.93 (dd, 6H)

Example 159

N- (2,3-dichlorobenzyl) -N- (2,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.89-7.62 (m, 13H), 5.28 (s, 2H), 5.11 (t, 1H), 5.06 (d, 1H), 4.69 (d, 1H), 4.12 (m , 1H), 3.34 (s, 2H), 3.12 (dd, 1H), 2.30 (s, 3H), 2.01 (s, 3H), 1.85 (m, 1H), 0.90 (dd, 6H)

Example 160

N- (2,3-dichlorobenzyl) -N- (3,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.91-7.72 (m, 13H), 5.27 (s, 2H), 5.11 (d, 1H), 5.06 (t, 1H), 4.66 (d, 1H), 4.10 (m , 1H), 3.35 (s, 2H), 3.09 (dd, 1H), 2.20 (s, 6H), 1.86 (m, 1H), 0.91 (dd, 6H)

Example 161

N- (2,3-dichlorobenzyl) -N- (allylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 4-methylpentylamine

[Step 1]

N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-4-methylpentylamine

Nt-butoxycarbonyl-L-leucine aldehyde was prepared in the same manner as in Reference Example 3 using Nt-butoxycarbonyl-L-leucine, and then 1- (4-nitrobenzyl) -1H-imidazole. The title compound was prepared in the same manner as in Reference Example 4, using 1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride instead of -5-ylacetic acid hydrochloride.

¹ H-NMR (CDCl ₃ ): δ 6.99-7.63 (m, 9H), 6.17 (d, 1H), 5.27 (s, 2H), 4.08 (m, 1H), 3.85 (s, 2H), 3.35 (s , 2H), 2.61 (d, 2H), 1.52 (m, 1H), 1.27 (m, 2H), 0.88 (d, 6H)

Step 2

N- (2,3-dichlorobenzyl) -N- (allylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 4-methylpentylamine

N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-4-methylpentylamine to dichloromethane The diluted solution (0.02M, 1ml, 0.02mmol) and the allyl isothiocyanate diluted solution with dichloromethane (0.1M, 0.2ml, 0.02mmol) were reacted at room temperature for 2 hours, and then the reaction solution was subjected to a short silica gel column chromatography. Purification by chromatography (dichloromethane / methanol = 9/1, v / v) gave the title compound as a white solid.

¹ H-NMR (CDCl ₃ ) δ: 6.95-7.68 (m, 9H), 6.48 (bs, 1H), 5.82 (m, 1H), 5.31 (m, 3H), 5.05 (m, 2H), 4.62 (m , 2H), 4.26 (m, 3H), 3.31 (s, 2H), 3.01 (dd, 1H), 1.25-1.53 (m, 3H), 0.87 (d, 6H)

Example 162-204

N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-4-methylpentylamine and corresponding iso The title compound was prepared in the same manner as Step 2 of Example 161 using thiocyanate.

Example 162

N- (2,3-dichlorobenzyl) -N- (benzylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.78-7.62 (m, 14H), 4.57-5.29 (m, 7H), 4.21 (m, 1H), 3.24 (s, 2H), 3.01 (dd, 1H), 1.25 -1.56 (m, 3H), 0.86 (dd, 6H)

Example 163

N- (2,3-dichlorobenzyl) -N- (2-biphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.65-7.72 (m, 19H), 5.21 (s, 2H), 5.01 (d, 1H), 4.55 (m, 2H), 4.15 (m, 1H), 3.31 (s , 2H), 2.94 (dd, 1H), 1.25-1.51 (m, 3H), 0.85 (d, 6H)

Example 164

N- (2,3-dichlorobenzyl) -N- (2-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.98 (bs, 1H), 6.65-7.71 (m, 13H), 5.32 (m, 3H), 4.79 (m, 2H), 4.38 (m, 1H), 3.35 (s , 2H), 3.09 (dd, 1H), 1.25-1.54 (m, 3H), 0.89 (d, 6H)

Example 165

N- (2,3-dichlorobenzyl) -N- (3-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.91 (bs, 1H), 6.75-7.59 (m, 13H), 5.53 (d, 1H), 5.25 (s, 2H), 4.75 (d, 1H), 4.51 (m , 1H), 4.18 (m, 1H), 3.35 (s, 2H), 3.04 (dd, 1H), 1.25-1.55 (m, 3H), 0.88 (dd, 6H)

Example 166

N- (2,3-dichlorobenzyl) -N- (4-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.67 (bs, 1H), 6.67-7.61 (m, 13H), 5.48 (d, 1H), 5.22 (s, 2H), 4.75 (d, 1H), 4.52 (m , 1H), 4.19 (m, 1H), 3.33 (s, 2H), 3.04 (dd, 1H), 1.26-1.52 (m, 3H), 0.88 (dd, 6H)

Example 167

N- (2,3-dichlorobenzyl) -N- (n-butylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.84-7.66 (m, 9H), 6.24 (bs, 1H), 5.31 (q, 2H), 5.02 (d, 1H), 4.62 (m, 2H), 4.16 (m , 1H), 3.69 (m, 1H), 3.52 (m, 1H) 3.32 (s, 2H), 2.96 (dd, 1H), 1.16-1.58 (m, 7H), 0.87 (m, 9H)

Example 168

N- (2,3-dichlorobenzyl) -N- (isobutylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.88-7.67 (m, 9H), 6.24 (bs, 1H), 5.31 (q, 2H), 5.02 (d, 1H), 4.69 (m, 2H), 4.19 (m , 1H), 3.55 (m, 1H), 3.32 (m, 3H), 3.01 (dd, 1H), 1.87 (m, 1H), 1.27-1.58 (m, 3H), 0.83 (m, 12H)

Example 169

N- (2,3-dichlorobenzyl) -N- (2-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.93 (bs, 1H), 6.63-7.68 (m, 13H), 5.22 (m, 3H), 4.78 (m, 2H), 4.37 (m, 1H), 3.35 (s , 2H), 3.11 (dd, 1H), 1.25-1.54 (m, 3H), 0.91 (d, 6H)

Example 170

N- (2,3-dichlorobenzyl) -N- (3-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.93 (bs, 1H), 6.63-7.68 (m, 13H), 5.22 (m, 3H), 4.78 (m, 2H), 4.37 (m, 1H), 3.35 (s , 2H), 3.11 (dd, 1H), 1.25-1.54 (m, 3H), 0.91 (d, 6H)

Example 171

N- (2,3-dichlorobenzyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.69 (bs, 1H), 6.72-7.61 (m, 13H), 5.48 (d, 1H), 5.22 (s, 2H), 4.76 (d, 1H), 4.55 (m , 1H), 4.21 (m, 1H), 3.33 (s, 2H), 3.05 (dd, 1H), 1.25-1.54 (m, 3H), 0.88 (dd, 6H)

Example 172

N- (2,3-dichlorobenzyl) -N- (3-chloro-4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.69 (bs, 1H), 6.78-7.61 (m, 12H), 5.48 (d, 1H), 5.26 (s, 2H), 4.76 (d, 1H), 4.55 (m , 1H), 4.21 (m, 1H), 3.35 (s, 2H), 3.05 (dd, 1H), 2.34 (s, 3H), 1.26-1.54 (m, 3H), 0.88 (dd, 6H

Example 173

N- (2,3-dichlorobenzyl) -N- (cyclohexylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.81-7.67 (m, 9H), 5.87 (bs, 1H), 5.31 (s, 2H), 5.05 (d, 1H), 4.62 (m, 2H), 4.21 (m , 2H), 3.33 (s, 2H), 2.96 (dd, 1H), 1.09-1.97 (m, 13H), 0.88 (dd, 6H)

Example 174

N- (2,3-dichlorobenzyl) -N- (cyclopentylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.81-7.67 (m, 9H), 6.05 (bs, 1H), 5.31 (dd, 2H), 5.11 (d, 1H), 4.63 (m, 3H), 4.15 (m , 1H), 3.33 (s, 2H), 2.96 (dd, 1H), 1.26-2.05 (m, 11H), 0.87 (m, 6H)

Example 175

N- (2,3-dichlorobenzyl) -N- (2,4-dichlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.19 (bs, 1H), 6.58-7.62 (m, 12H), 5.22 (m, 3H), 4.74 (m, 2H), 4.36 (m, 1H), 3.35 (s , 2H), 3.09 (dd, 1H), 1.26-1.54 (m, 3H), 0.89 (d, 6H)

Example 176

N- (2,3-dichlorobenzyl) -N- [2- (dimethylamino) ethylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.87-7.66 (m, 9H), 5.32 (dd, 2H), 4.56-4.82 (m, 3H), 4.29 (m, 1H), 3.56 (m, 1H), 3.32 (d, 2H), 3.12 (dd, 1H), 2.77 (m, 1H), 2.52 (m, 2H), 2.07 (s, 6H), 1.24-1.61 (m, 3H), 0.92 (d, 6H)

Example 177

N- (2,3-dichlorobenzyl) -N- [4- (dimethylamino) phenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.81 (bs, 1H), 6.57-7.59 (m, 13H), 5.25 (m, 3H), 4.77 (m, 2H), 4.27 (m, 1H), 3.33 (s , 2H), 3.01 (m, 7H), 1.27-1.59 (m, 3H), 0.91 (d, 6H)

Example 178

N- (2,3-dichlorobenzyl) -N- [3- (dimethylamino) propylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.79 (bs, 1H), 6.87-7.68 (m, 9H), 5.36 (m, 3H), 4.63 (m, 2H), 4.28 (m, 1H), 3.65 (m , 2H), 3.32 (m, 2H), 2.94 (dd, 1H), 1.24-2.56 (m, 15H), 0.89 (d, 6H)

Example 179

N- (2,3-dichlorobenzyl) -N- (3-ethoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.86-7.66 (m, 9H), 5.33 (dd, 2H), 4.88 (m, 1H), 4.59 (m, 2H), 4.23 (m, 1H), 3.73 (q , 2H), 3.11-3.55 (m, 6H), 2.96 (dd, 1H), 1.77 (m, 2H), 1.15-1.57 (m, 3H), 0.89 (m, 9H)

Example 180

N- (2,3-dichlorobenzyl) -N- (ethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.88-7.66 (m, 9H), 6.39 (bs, 1H), 5.31 (dd, 2H), 5.06 (d, 1H), 4.58 (m, 2H), 4.14 (m , 1H), 3.68 (m, 2H), 3.31 (s, 2H), 2.96 (dd, 1H), 1.11-1.54 (m, 6H), 0.88 (m, 6H)

Example 181

N- (2,3-dichlorobenzyl) -N- (2-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.21 (bs, 1H), 6.79-7.61 (m, 13H), 5.23 (m, 3H), 4.71 (m, 2H), 4.34 (m, 1H), 3.34 (s , 2H), 3.05 (dd, 1H), 1.29-1.54 (m, 3H), 0.88 (d, 6H)

Example 182

N- (2,3-dichlorobenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.84 (bs, 1H), 6.81-7.59 (m, 13H), 5.51 (d, 1H), 5.24 (s, 2H), 4.75 (d, 1H), 4.58 (m , 1H), 4.19 (m, 1H), 3.34 (s, 2H), 3.05 (dd, 1H), 1.25-1.53 (m, 3H), 0.88 (m, 6H)

Example 183

N- (2,3-dichlorobenzyl) -N- (4-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.54 (bs, 1H), 6.76-7.61 (m, 13H), 5.23-5.47 (m, 3H), 4.74 (m, 2H), 4.21 (m, 1H), 3.32 (s, 2H), 3.05 (dd, 1H), 1.25-1.515 (m, 3H), 0.87 (m, 6H)

Example 184

N- (2,3-dichlorobenzyl) -N- (4-hydroxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.93-7.66 (m, 13H), 5.42 (d, 2H), 5.02 (dd, 2H), 4.33 (m, 1H), 3.92 (m, 1H), 3.46 (dd , 1H), 3.31 (d, 2H), 1.33-1.58 (m, 3H), 0.87 (m, 6H)

Example 185

N- (2,3-dichlorobenzyl) -N- (4-isopropylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.19 (bs, 1H), 6.82-7.59 (m, 9H), 5.31 (m, 3H), 4.75 (m, 2H), 4.25 (m, 1H), 3.34 (s , 2H), 3.05 (dd, 1H), 2.89 (m, 1H), 1.03-1.56 (m, 9H), 0.88 (d, 6H)

Example 186

N- (2,3-dichlorobenzyl) -N- (2-methoxyethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.89-7.66 (m, 13H), 6.28 (bs, 1H), 5.33 (dd, 2H), 4.84 (m, 2H), 4.39 (d, 1H), 4.25 (m , 1H), 3.01-3.86 (m, 10H), 1.25-1.58 (m, 3H), 0.89 (d, 6H)

Example 187

N- (2,3-dichlorobenzyl) -N- (2-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.21 (d, 1H), 6.77-7.64 (m, 13H), 5.17 (s, 2H), 5.03 (m, 2H), 4.73 (d, 1H), 4.41 (m , 1H), 3.57 (s, 3H), 3.35 (s, 2H), 3.12 (dd, 1H), 1.25-1.61 (m, 3H), 0.91 (d, 6H)

Example 188

N- (2,3-dichlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.21 (bs, 1H), 6.81-7.61 (m, 13H), 5.25 (m, 3H), 4.74 (m, 2H), 4.27 (m, 1H), 3.78 (s , 3H), 3.32 (s, 2H), 3.05 (dd, 1H), 1.25-1.55 (m, 3H), 0.88 (d, 6H)

Example 189

N- (2,3-dichlorobenzyl) -N- (3-methoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.83-7.66 (m, 9H), 5.33 (dd, 2H), 4.93 (m, 1H), 4.59 (dd, 2H), 4.24 (m, 1H), 3.65 (m , 2H), 2.91-3.47 (m, 8H), 1.19-1.78 (m, 5H), 0.87 (d, 6H)

Example 190

N- (2,3-dichlorobenzyl) -N- (2-methoxypyridin-5-ylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole- 5-yl] acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.81 (bs, 1H), 6.67-7.94 (m, 12H), 5.31 (m, 3H), 4.69 (m, 2H), 4.23 (m, 1H), 3.87 (s , 3H), 3.32 (s, 2H), 3.07 (dd, 1H), 1.25-1.55 (m, 3H), 0.87 (d, 6H)

Example 191

N- (2,3-dichlorobenzyl) -N- (methylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.93-7.66 (m, 9H), 6.71 (bs, 1H), 5.31 (dd, 2H), 5.05 (d, 1H), 4.58 (m, 2H), 4.14 (m , 1H), 3.31 (s, 3H), 3.08 (d, 2H), 2.93 (dd, 1H), 1.25-1.58 (m, 3H), 0.87 (m, 6H)

Example 192

N- (2,3-dichlorobenzyl) -N- (4-methylthiophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.48 (bs, 1H), 6.78-7.59 (m, 13H), 5.29 (m, 3H), 4.71 (m, 2H), 4.22 (m, 1H), 3.33 (s , 2H), 3.04 (dd, 1H), 2.45 (s, 3H), 1.25-1.55 (m, 3H), 0.87 (m, 6H)

Example 193

N- (2,3-dichlorobenzyl) -N- (2-naphthylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.72 (bs, 1H), 6.78-7.89 (m, 16H), 5.31 (m, 3H), 4.81 (m, 2H), 4.29 (m, 1H), 3.36 (s , 2H), 3.07 (dd, 1H), 1.27-1.54 (m, 3H), 0.89 (d, 6H)

Example 194

N- (2,3-dichlorobenzyl) -N- (4-nitrophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 9.46 (bs, 1H), 6.69-8.16 (m, 13H), 5.73 (d, 1H), 5.24 (s, 2H), 4.74 (d, 1H), 4.32 (m , 1H), 4.16 (m, 1H), 3.38 (s, 2H), 3.06 (dd, 1H), 1.25-1.55 (m, 3H), 0.88 (d, 6H)

Example 195

N- (2,3-dichlorobenzyl) -N- (n-pentylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.91-7.66 (m, 9H), 6.21 (bs, 1H), 5.33 (dd, 2H), 5.04 (d, 1H), 4.62 (m, 2H), 4.18 (m , 1H), 2.95-3.73 (m, 5H), 0.74-1.71 (m, 18H)

Example 196

N- (2,3-dichlorobenzyl) -N- (2-phenylethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.74-7.64 (m, 14H), 5.93 (bs, 1H), 5.29 (dd, 2H), 4.69 (m, 2H), 4.45 (d, 1H), 4.17 (m , 1H), 3.86 (m, 2H), 3.29 (s, 2H), 2.79-3.02 (m, 3H), 1.23-1.56 (m, 3H), 0.88 (d, 6H)

Example 197

N- (2,3-dichlorobenzyl) -N- (phenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.38 (bs, 1H), 6.79-7.57 (m, 14H), 5.29 (m, 3H), 4.75 (m, 2H), 4.26 (m, 1H), 3.33 (s , 2H), 3.05 (dd, 1H), 1.25-1.55 (m, 3H), 0.87 (m, 6H)

Example 198

N- (2,3-dichlorobenzyl) -N- (n-propylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.89-7.66 (m, 9H), 6.35 (bs, 1H), 5.31 (dd, 2H), 5.05 (d, 1H), 4.63 (m, 2H), 4.16 (m , 1H), 3.66 (m, 1H), 3.49 (m, 1H), 3.32 (s, 2H), 2.93 (dd, 1H), 1.26-1.61 (m, 5H), 0.87 (m, 9H)

Example 199

N- (2,3-dichlorobenzyl) -N- (3-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.19 (bs, 1H), 6.76-7.57 (m, 13H), 5.29 (m, 3H), 4.71 (m, 2H), 4.27 (m, 1H), 3.34 (s , 2H), 3.05 (dd, 1H), 2.31 (m, 3H), 1.25-1.55 (m, 3H), 0.91 (d, 6H)

Example 200

N- (2,3-dichlorobenzyl) -N- (2-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-4-methylpentylamine

1 H-NMR (CDCl 3): δ 7.78 (bs, 1H), 6.78-7.61 (m, 13H), 5.29 (m, 3H), 4.81 (m, 2H), 4.29 (m, 1H), 3.33 (s, 2H ), 3.09 (dd, 1H), 2.09 (s, 3H), 1.25-1.53 (m, 3H), 0.91 (d, 6H)

Example 201

N- (2,3-dichlorobenzyl) -N- (4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.21 (bs, 1H), 6.81-7.61 (m, 13H), 5.31 (m, 3H), 4.75 (m, 2H), 4.26 (m, 1H), 3.34 (s , 2H), 3.06 (dd, 1H), 2.34 (s, 3H), 1.26-1.56 (m, 3H), 0.89 (d, 6H)

Example 202

N- (2,3-dichlorobenzyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 9.16 (bs, 1H), 6.71-7.78 (m, 13H), 5.64 (d, 1H), 5.25 (s, 2H), 4.78 (d, 1H), 4.46 (m , 1H), 4.16 (m, 1H), 3.34 (s, 2H), 3.06 (dd, 1H), 1.26-1.54 (m, 3H), 0.89 (m, 6H)

Example 203

N- (2,3-dichlorobenzyl) -N- (2,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.81-7.61 (m, 12H), 5.25 (m, 3H), 4.79 (m, 2H), 4.31 (m, 1H), 3.34 (s, 2H), 3.08 (dd , 1H), 2.31 (s, 3H), 2.05 (s, 3H), 1.26-1.54 (m, 3H), 0.89 (d, 6H)

Example 204

N- (2,3-dichlorobenzyl) -N- (3,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.01 (bs, 1H), 6.79-7.61 (m, 12H), 5.29 (m, 3H), 4.76 (m, 2H), 4.28 (m, 1H), 3.36 (s , 2H), 3.06 (dd, 1H), 2.23 (m, 6H), 1.27-1.53 (m, 3H), 0.91 (d, 6H)

Example 205

N- (2,3-dichlorobenzyl) -N- (allylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methyl Propylamine

[Step 1]

N- (2,3-dichlorobenzyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methylpropylamine

2- (t-butoxycarbonyl) amino-2-methylpropion aldehyde was prepared in the same manner as in Reference Example 3 using 2- (t-butoxycarbonyl) amino-2-methylpropionic acid, and then 1- Title compound in the same manner as in Reference Example 4, using 1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride instead of (4-nitrobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride Was prepared.

¹ H-NMR (CDCl ₃ ): δ 7.61 (d, 2H), 7.53 (s, 1H), 7.22 (d, 2H), 7.16 (d, 2H), 7.01 (s, 1H), 6.43 (bs, 1H ), 5.26 (s, 2H), 3.82 (s, 2H), 3.35 (s, 2H), 2.58 (s, 2H), 1.23 (s, 6H)

[Step 2]

N- (2,3-dichlorobenzyl) -N- (allylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methyl Propylamine

A solution of N- (2,3-dichlorobenzyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methylpropylamine diluted with dichloromethane (0.02M, 1ml, 0.02mmol) and a solution of allyl isothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) were reacted at room temperature for 2 hours, and then the reaction solution was subjected to short silica gel column chromatography (dichloro Methane / Methanol = 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 8.20 (bs, 1H), 7.65 (d, 2H), 7.45 (m, 2H), 7.20 (m, 3H), 7.00 (s, 1H), 6.95 (d, 1H ), 6.40 (bs, 1H), 5.80 (m, 1H), 5.35 (s, 2H), 5.10 (m, 2H), 4.98 (m, 2H), 4.24 (t, 2H), 3.98 (s, 2H) , 3.25 (s, 2H), 1.40 (s, 6H)

Example 206-251

N- (2,3-dichlorobenzyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methylpropylamine and the corresponding isothiocyanate The title compound was prepared in the same manner as Step 2 of Example 205 using.

Example 206

N- (2,3-dichlorobenzyl) -N- (benzylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methyl Propylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.45 (m, 2H), 7.25 (m, 4H), 7.15 (m, 4H), 6.95 (m, 2H), 5.30 (s, 2H ), 5.00 (s, 2H), 4.80 (d, 2H), 4.00 (s, 2H), 1.40 (s, 6H)

Example 207

N- (2,3-dichlorobenzyl) -N- (2-biphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 3H), 7.38 (m, 4H), 7.30 (s, 7H), 7.10 (d, 3H), 6.95 (s, 1H), 6.70 (d, 1H ), 5.27 (s, 2H), 4.82 (s, 2H), 3.95 (s, 2H), 3.20 (s, 2H), 1.40 (s, 6H)

Example 208

N- (2,3-dichlorobenzyl) -N- (2-bromophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (m, 4H), 7.45 (m, 2H), 7.30 (m, 3H), 7.15 (m, 4H), 6.95 (s, 1H), 5.30 (s, 2H ), 5.10 (s, 2H), 4.10 (s, 2H), 3.20 (s, 2H), 1.50 (s, 6H)

Example 209

N- (2,3-dichlorobenzyl) -N- (3-bromophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.45 (m, 4H), 7.25 (m, 3H), 7.10 (d, 3H), 6.95 (s, 1H), 5.30 (s, 2H ), 5.25 (s, 2H), 3.98 (s, 2H), 3.27 (s, 2H), 1.45 (s, 6H)

Example 210

N- (2,3-dichlorobenzyl) -N- (4-bromophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.43 (m, 4H), 7.22 (m, 4H), 7.08 (d, 3H), 6.95 (s, 1H), 5.22 (s, 4H ), 3.98 (s, 2H), 3.25 (s, 2H), 1.44 (s, 6H)

Example 211

N- (2,3-dichlorobenzyl) -N- (n-butylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2 -Methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.45 (m, 2H), 7.20 (m, 3H), 7.00 (s, 1H), 6.90 (d, 1H), 6.06bs, 1H) , 5.37 (s, 2H), 4.98 (s, 2H), 3.98 (s, 2H), 3.58 (q, 2H), 3.27 (s, 2H), 1.50 (m, 2H), 1.40 (s, 6H), 1.20 (m, 2 H), 0.86 (t, 3 H)

Example 212

N- (2,3-dichlorobenzyl) -N- (isobutylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2- Methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.45 (m, 2H), 7.20 (m, 3H), 7.00 (s, 1H), 6.95 (d, 1H), 6.00 (bs, 1H ), 5.38 (s, 2H), 4.90 (s, 2H), 4.00 (s, 2H), 3.40 (t, 2H), 3.25 (s, 2H), 1.80 (m, 1H), 1.40 (s, 6H) , 0.80 (d, 6H)

Example 213

N- (2,3-dichlorobenzyl) -N- (t-butylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2 -Methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.48 (m, 2H), 7.20 (m, 3H), 7.00 (s, 1H), 6.95 (d, 1H), 5.40 (s, 2H ), 4.80 (s, 2H), 4.02 (s, 2H), 3.25 (s, 2H), 1.45 (s, 6H), 1.40 (s, 9H)

Example 214

N- (2,3-dichlorobenzyl) -N- (2-chlorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 3H), 7.20-7.50 (m, 7H), 7.12 (d, 3H), 6.97 (s, 1H), 5.35 (s, 2H), 5.15 (s , 2H), 4.10 (s, 2H), 3.25 (s, 2H), 1.48 (s, 6H)

Example 215

N- (2,3-dichlorobenzyl) -N- (3-chlorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.43 (d, 2H), 7.28 (m, 5H), 7.10 (d, 3H), 6.95 (s, 1H), 5.30 (s, 2H ), 5.27 (s, 2H), 3.98 (s, 2H), 3.27 (s, 2H), 1.47 (s, 6H)

Example 216

N- (2,3-dichlorobenzyl) -N- (4-chlorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.45 (s, 2H), 7.28 (s, 5H), 7.08 (d, 3H), 6.95 (s, 1H), 5.25 (s, 2H ), 5.20 (s, 2H), 3.98 (s, 2H), 3.25 (s, 2H), 1.43 (s, 6H)

Example 217

N- (2,3-dichlorobenzyl) -N- (3-chloro-4-methylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.45 (m, 2H), 7.23 (m, 2H), 7.20 (s, 2H), 7.10 (d, 2H), 6.95 (s, 1H ), 6.40 (bs, 1H), 5.80 (m, 1H), 5.35 (s, 2H), 5.22 (s, 2H), 3.98 (s, 2H), 3.25 (s, 2H), 2.39 (s, 3H) , 1.45 (s, 6H)

Example 218

N- (2,3-dichlorobenzyl) -N- (cyclohexylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2- Methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.53 (s, 1H), 7.45 (d, 1H), 7.20 (t, 3H), 7.00 (s, 1H), 6.95 (d, 1H ), 5.70 (bs, 1H), 5.50 (s, 2H), 4.90 (s, 2H), 4.20 (m, 1H), 3.98 (s, 2H), 3.25 (s, 2H), 1.90 (m, 2H) , 1.60 (m, 2H), 1.40 (s, 6H), 1.15 (m, 2H), 1.10 (m, 4H)

Example 219

N- (2,3-dichlorobenzyl) -N- (cyclopentylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2- Methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.52 (s, 1H), 7.45 (d, 1H), 7.20 (t, 3H), 7.00 (s, 1H), 6.95 (d, 1H ), 5.90 (bs, 1H), 5.38 (s, 2H), 4.92 (s, 2H), 4.62 (q, 1H), 3.98 (s, 2H), 3.25 (s, 2H), 2.00 (m, 4H) , 1.53 (m, 4H), 1.40 (s, 6H)

Example 220

N- (2,3-dichlorobenzyl) -N- (2,4-dichlorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.45 (t, 2H), 7.40 (m, 2H), 7.24 (m, 2H), 7.10 (d, 3H), 6.95 (s, 1H ), 5.30 (s, 2H), 5.15 (s, 2H), 4.06 (s, 2H), 3.22 (s, 2H), 1.45 (s, 6H)

Example 221

N- (2,3-dichlorobenzyl) -N- [2- (dimethylamino) ethylthiocarbamoyl] -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.51 (s, 1H), 7.45 (d, 1H), 7.20 (d, 3H), 7.00 (s, 1H), 6.90 (d, 1H ), 5.40 (s, 2H), 4.80 (s, 2H), 4.10 (s, 2H), 3.50 (s, 2H), 3.26s, 2H), 2.40 (t, 2H), 2.00 (s, 6H), 1.45 (s, 6 H)

Example 222

N- (2,3-dichlorobenzyl) -N- [4- (dimethylamino) phenylthiocarbamoyl] -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.58 (d, 2H), 7.45 (m, 2H), 7.27 (m, 1H), 7.10 (m, 2H), 7.05 (m, 3H), 6.65 (d, 2H ), 5.35 (s, 2H), 5.10 (s, 2H), 4.04 (s, 2H), 3.25 (s, 2H), 2.95 (s, 6H), 1.45 (s, 6H)

Example 223

N- (2,3-dichlorobenzyl) -N- (ethoxycarbonylmethylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.47 (s, 2H), 7.20 (t, 3H), 6.98 (m, 2H), 5.35 (s, 2H), 5.00 (s, 2H ), 4.34 (d, 2H), 4.20 (q, 2H), 3.98 (s, 2H), 3.25 (s, 2H), 1.44 (s, 6H), 1.25 (t, 3H)

Example 224

N- (2,3-dichlorobenzyl) -N- (3-ethoxypropylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.45 (m, 2H), 7.20 (t, 3H), 7.00 (s, 1H), 6.95 (s, 1H), 6.80 (d, 1H ), 5.40 (s, 2H), 4.80 (s, 2H), 3.98 (s, 2H), 3.73 (q, 2H), 3.42 (t, 2H), 3.25 (m, 4H), 1.78 (p, 2H) , 1.42 (s, 6H), 1.00 (t, 3H)

Example 225

N- (2,3-dichlorobenzyl) -N- (ethylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methyl Propylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.45 (m, 2H), 7.20 (t, 3H), 7.00 (s, 1H), 6.95 (d, 1H), 6.20 (bs, 1H ), 5.38 (s, 2H), 4.98 (s, 2H), 3.98 (s, 2H), 3.62 (p, 2H), 3.25 (s, 2H), 1.40 (s, 6H), 1.14 (t, 3H)

Example 226

N- (2,3-dichlorobenzyl) -N- (2-fluorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.40 (m, 3H), 7.27 (m, 2H), 7.20 (m, 5H), 6.95 (s, 1H), 5.35 (s, 2H ), 5.18 (s, 2H), 4.04 (s, 2H), 3.25 (s, 2H), 1.45 (s, 6H)

Example 227

N- (2,3-dichlorobenzyl) -N- (3-fluorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.45 (m, 2H), 7.04-7.30 (m, 7H), 7.20 (m, 3H), 6.95 (m, 2H), 5.32 (s , 2H), 5.28 (s, 2H), 3.98 (s, 2H), 3.30 (s, 2H), 1.46 (s, 6H)

Example 228

N- (2,3-dichlorobenzyl) -N- (4-fluorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.45 (m, 2H), 7.22 (m, 3H), 7.10 (d, 3H), 7.00 (s, 1H), 6.95 (s, 1H ), 5.30 (s, 2H), 5.20 (s, 2H), 4.00 (s, 2H), 3.25 (s, 2H), 1.40 (s, 6H)

Example 229

N- (2,3-dichlorobenzyl) -N- (4-hydroxyphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.58 (d, 2H), 7.40 (d, 2H), 7.25 (m, 2H), 7.10 (d, 3H), 6.95 (s, 2H), 6.75 (d, 2H ), 5.30 (s, 2H), 5.05 (s, 2H), 4.00 (bs, 2H), 3.25 (s, 2H), 1.45 (s, 6H)

Example 230

N- (2,3-dichlorobenzyl) -N- (4-isopropylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.45 (s, 2H), 7.25 (s, 2H), 7.20 (s, 3H), 7.10 (d, 3H), 6.95 (s, 1H ), 5.30 (s, 2H), 5.10 (s, 2H), 4.05 (s, 2H), 3.25 (s, 2H), 2.90 (q, 1H), 1.45 (s, 6H), 1.12 (d, 6H)

Example 231

N- (2,3-dichlorobenzyl) -N- (2-methoxyethylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.45 (m, 2H), 7.20 (t, 3H), 7.00 (s, 1H), 6.95 (d, 1H), 6.25 (bs, 1H ), 5.40 (s, 2H), 4.90 (s, 2H), 4.04 (s, 2H), 3.75 (q, 2H), 3.40 (t, 2H), 3.25 (s, 2H), 3.13 (s, 3H) , 1.40 (s, 6H)

Example 232

N- (2,3-dichlorobenzyl) -N- (2-methoxyphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.10 (d, 1H), 7.65 (s, 1H), 7.60 (d, 2H), 7.48 (s, 2H), 7.25 (t, 1H), 7.12 (d, 3H ), 7.00 (t, 3H), 6.90 (d, 1H), 5.38 (s, 2H), 5.00 (s, 2H), 4.20 (s, 2H), 3.60 (s, 3H), 3.25 (s, 2H) , 1.45 (s, 6H)

Example 233

N- (2,3-dichlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.45 (s, 2H), 7.27 (m, 1H), 7.10 (m, 5H), 7.00 (s, 1H), 6.85 (d, 2H ), 5.30 (s, 2H), 5.10 (s, 2H), 4.00 (s, 2H), 3.80 (s, 3H), 3.25 (s, 2H), 1.42 (s, 6H)

Example 234

N- (2,3-dichlorobenzyl) -N- (3-methoxypropylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.45 (m, 2H), 7.20 (t, 3H), 7.00 (s, 2H), 6.90 (d, 1H), 5.40 (s, 2H ), 4.80 (s, 2H), 4.00 (s, 2H), 3.68 (q, 2H), 3.40 (t, 2H), 3.25 (s, 2H), 3.00 (s, 3H), 1.76 (p, 2H) , 1.40 (s, 6H)

Example 235

N- (2,3-dichlorobenzyl) -N- (2-methoxypyridin-5-ylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.90 (s, 1H), 7.60 (d, 3H), 7.40 (m, 2H), 7.25 (t, 1H), 7.10 (d, 3H), 6.90 (s, 1H ), 6.80 (d, 1H), 5.30 (s, 2H), 5.20 (s, 2H), 4.00 (s, 2H), 3.90 (s, 3H), 3.25 (s, 2H), 1.45 (s, 6H)

Example 236

N- (2,3-dichlorobenzyl) -N- (methylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methyl Propylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.45 (s, 2H), 7.20 (t, 3H), 7.00 (s, 1H), 6.90 (d, 1H), 6.55 (bs, 1H ), 5.40 (s, 2H), 4.95 (s, 2H), 3.98 (s, 2H), 3.25 (s, 2H), 3.08 (d, 3H), 1.40 (s, 6H)

Example 237

N- (2,3-dichlorobenzyl) -N- (4-methylthiophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.45 (s, 2H), 7.28 (s, 1H), 7.20 (s, 4H), 7.10 (d, 2H), 6.95 (s 1H) , 5.25 (s, 2H), 5.20 (s, 2H), 4.00 (s, 2H), 3.25 (s, 2H), 2.45 (s, 3H), 1.40 (s, 6H)

Example 238

N- (2,3-dichlorobenzyl) -N- (2-naphthylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60-7.85 (m, 4H), 7.45 (m, 7H), 7.30 (t, 2H), 7.15 (d, 1H), 6.95 (d, 3H), 5.28 (s , 2H), 5.20 (s, 2H), 4.00 (s, 2H), 3.25 (s, 2H), 1.45 (s, 6H)

Example 239

N- (2,3-dichlorobenzyl) -N- (4-nitrophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.18 (d, 2H), 7.73 (d, 2H), 7.47 (t, 3H), 7.42 (d, 1H), 7.25 (m, 1H), 7.10 (d, 3H ), 6.00 (s, 1H), 5.37 (s, 2H), 5.25 (s, 2H), 3.92 (s, 2H), 3.35 (s, 2H), 1.42 (s, 6H)

Example 240

N- (2,3-dichlorobenzyl) -N- (n-pentylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2 -Methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.45 (m, 2H), 7.20 (t, 3H), 7.00 (s, 1H), 6.95 (d, 1H), 5.95 (bs, 1H ), 5.40 (s, 2H), 5.10 (m, 2H), 4.90 (s, 2H), 3.42 (m, 2H), 3.25 (s, 2H), 1.60 (p, 2H), 1.40 (s, 6H) , 1.10 (m, 2H), 0.80 (m, 5H)

Example 241

N- (2,3-dichlorobenzyl) -N- (2-phenylethylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.45 (m, 2H), 7.18 (d, 6H), 7.00 (s, 1H), 6.95 (m, 2H), 6.72 (d, 1H ), 5.80 (bs, 1H), 5.50 (s, 2H), 4.70 (s, 2H), 3.98 (s, 2H), 3.82 (q, 2H), 3.25 (s, 2H), 2.80 (t, 2H) , 1.40 (s, 6H)

Example 242

N- (2,3-dichlorobenzyl) -N- (phenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methyl Propylamine

¹ H-NMR (CDCl ₃ ): δ 7.55 (d, 2H), 7.45 (s, 2H), 7.30 (m, 5H), 7.10 (t, 3H), 6.95 (s, 1H), 5.30 (s, 2H ), 5.20 (s, 2H), 400 (s, 2H), 3.25 (s, 2H), 1.44 (s, 6H)

Example 243

N- (2,3-dichlorobenzyl) -N- (n-propylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2 -Methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.45 (m, 2H), 7.20 (t, 3H), 7.00 (s, 1H), 6.95 (d, 1H), 6.10 (bs, 1H ), 5.40 (s, 2H), 4.95 (s, 2H), 4.00 (s, 2H), 3.55 (q, 2H), 3.25 (s, 2H), 1.54 (q, 2H), 1.40 (s, 6H) , 0.80 (t, 3H)

Example 244

N- (2,3-dichlorobenzyl) -N- (3-methylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2 -Methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.45 (d, 2H), 7.25 (m, 3H), 7.08 (d, 5H), 6.97 (s, 1H), 5.28 (s, 2H ), 5.17 (s, 2H), 4.02 (s, 2H), 3.25 (s, 2H), 2.38 (s, 3H), 1.40 (s, 6H)

Example 245

N- (2,3-dichlorobenzyl) -N- (2-methylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2 -Methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.45 (m, 2H), 7.25 (m, 4H), 7.10 (t, 4H), 6.95 (s, 1H), 5.30 (s, 2H ), 5.10 (s, 2H), 4.10 (s, 2H), 3.25 (s, 2H), 2.10 (s, 3H), 1.40 (s, 6H)

Example 246

N- (2,3-dichlorobenzyl) -N- (4-methylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2 -Methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.57 (d, 2H), 7.45 (s, 2H), 7.26 (t, 2H), 7.12 (m, 6H), 6.95 (s, 1H), 5.30 (s, 2H ), 5.17 (s, 2H), 4.00 (s, 2H), 3.25 (s, 2H), 2.38 (s, 3H), 1.40 (s, 6H)

Example 247

N- (2,3-dichlorobenzyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.78 (bs, 1H), 7.60 (d, 3H), 7.45 (m, 4H), 7.26 (t, 1H), 7.10 (t, 4H), 6.95 (s, 1H ), 5.30 (s, 4H), 3.95 (s, 2H), 3.25 (s, 2H), 1.45 (s, 6H)

Example 248

N- (2,3-dichlorobenzyl) -N- (2,4-dimethylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.45 (m, 2H), 7.24 (d, 1H), 7.12 (d, 3H), 7.00 (bs, 2H), 6.95 (d, 2H ), 5.30 (s, 2H), 5.10 (s, 2H), 4.10 (s, 2H), 3.25 (s, 2H), 2.32 (s, 3H), 2.05 (s, 3H), 1.45 (s, 6H)

Example 249

N- (2,3-dichlorobenzyl) -N- (3,4-dimethylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.57 (d, 2H), 7.45 (s, 2H), 7.25 (m, 1H), 7.10 (d, 4H), 6.95 (s, 3H), 5.30 (s, 2H ), 5.10 (s, 2H), 4.23 (s, 2H), 3.25 (s, 2H), 2.24 (s, 6H), 1.40 (s, 6H)

Example 250

N- (2,3-dichlorobenzyl) -N- (3-dimethylaminopropylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 9.20 (bs, 1H), 7.56 (d, 2H), 7.42-7.48 (m, 2H), 7.16-7.23 (m, 3H), 7.00 (s, 3H), 6.90 (d, 2H), 5.50 (s, 2H), 4.80 (s, 2H), 3.90 (bs, 2H), 3.71 (m, 2H), 2.40 (t, 2H), 1.95 (s, 6H). 1.45 (s, 6 H)

Example 251

N- (2,3-dichlorobenzyl) -N- (ethoxycarbonylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.50-7.75 (m, 5H), 7.43-7.46 (m, 1H), 7.18-7.25 (m, 2H), 7.00 (s, 1H), 5.28-5.33 (m, 4H), 5.15 (bs, 2H), 4.19-4.25 (m, 4H), 3.50 (s, 2H), 1.42 (s, 6H), 1.25 (t, 3H)

Example 252

N- (2,3-dichlorobenzyl) -N- (allylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutyl Amine

[Step 1]

N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutylamine

L-2- (t-butoxycarbonyl) aminobutyric aldehyde was prepared in the same manner as in Reference Example 3 using L-2- (t-butoxycarbonyl) aminobutyric acid, and then 1- (4 Preparation of the title compound in the same manner as in Reference Example 4 using 1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride instead of -nitrobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride It was.

¹ H-NMR (CDCl ₃ ) δ 7.61 (d, 2H), 7.52 (s, 1H), 7.38 (dd, 2H), 7.11-7.21 (m, 4H), 7.01 (s, 1H), 6.08 (d, 1H), 5.26 (s, 2H), 3.83-3.92 (m, 3H), 3.35 (s, 2H), 2.62 (d, 2H), 1.33-1.51 (m, 2H), 0.84 (t, 3H)

[Step 2]

N- (2,3-dichlorobenzyl) -N- (allylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutyl Amine

A solution of N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutylamine diluted with dichloromethane ( 0.02M, 1ml, 0.02mmol) and a solution of allyl isothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) were reacted at room temperature for 2 hours, and then the reaction solution was subjected to short silica gel column chromatography (dichloromethane). / Methanol = 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.50 (s, 1H), 7.41 (d, 1H), 7.18 (m, 3H), 7.05 (d, 1H), 7.00 (m, 2H ), 6.42 (bs, 1H), 5.85 (m, 1H), 5.33 (q, 2H), 5.07 (m, 3H), 4.75 (m, 1H), 4.68 (d, 1H), 4.30 (q, 2H) , 4.01 (m, 1H), 3.32 (s, 2H), 3.00 (dd, 1H), 1.55 (m, 2H), 0.90 (t, 3H)

Example 253-297

N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutylamine and the corresponding isothiocyanate To provide the title compound in the same manner as in Step 2 of Example 252.

Example 253

N- (2,3-dichlorobenzyl) -N- (benzylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutyl Amine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.42 (s, 2H), 7.40 (s, 1H), 7.18 (m, 8H), 6.95 (m, 2H), 6.80 (bs, 1H ), 5.23 (d, 2H), 5.10 (d, 1H), 4.85 (m, 2H), 4.80 (m, 1H), 4.60 (d, 1H), 4.05 (m, 1H), 3.27 (s, 2H) , 1.57 (m, 2H), 0.90 (t, 3H)

Example 254

N- (2,3-dichlorobenzyl) -N- (2-biphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.68 (d, 1H), 7.58 (d, 2H), 7.41 (1, 1H), 7.30 (m, 8H), 7.12 (d, 2H), 7.01 (s, 1H ), 6.98 (s, 2H), 6.69 (d, 1H), 5.21 (s, 2H), 5.12 (bs, 1H), 4.51 (d, 2H), 3.90 (bs, 1H), 3.32 (s, 2H) , 2.95 (dd, 1H), 1.60 (m, 1H), 1.40 (m, 1H), 0.85 (t, 3H)

Example 255

N- (2,3-dichlorobenzyl) -N- (2-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ) δ: 8.00 (bs, 1H), 7.65 (d, 1H), 7.58 (d, 3H), 7.44 (s, 2H), 7.30 (m, 2H), 7.18 (m, 4H ), 6.98 (m, 2H), 5.33 (m, 1H), 5.24 (s, 2H), 4.85 (m, 1H), 4.78 (d, 1H), 4.20 (m, 1H), 3.39 (s, 2H) , 3.12 (dd, 1H), 1.60 (m, 2H), 0.90 (t, 3H)

Example 256

N- (2,3-dichlorobenzyl) -N- (3-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ: 9.00 (bs, 1H), 7.60 (d, 2H), 7.50 (m, 1H), 7.41 (m, 3H), 7.30 (m, 1H), 7.20 (d, 2H), 7.10 (m, 3H), 6.96 (s, 2H), 5.63 (d, 1H), 5.23 (s, 2H), 4.68 (d, 1H), 4.52 (m, 1H), 4.01 (m, 1H ), 3.38 (s, 2H), 3.05 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 (t, 3H)

Example 257

N- (2,3-dichlorobenzyl) -N- (4-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.70 (bs, 1H), 7.60 (d, 2H), 7.41 (d, 4H), 7.24 (m, 3H), 7.10 (t, 3H), 7.00 (s, 1H ), 6.85 (d, 1H), 5.55 (d, 1H), 5.23 (s, 2H), 4.68 (d, 1H), 4.58 (m, 1H), 4.01 (m, 1H), 3.36 (s, 2H) , 3.05 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 (t, 3H)

Example 258

N- (2,3-dichlorobenzyl) -N- (n-butylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.50 (s, 1H), 7.41 (d, 1H), 7.18 (m, 4H), 7.00 (s, 1H), 6.95 (s, 1H ), 6.22 (bs, 1H), 5.33 (q, 2H), 5.07 (d, 1H), 4.75 (m, 1H), 4.58 (d, 1H), 4.01 (m, 1H), 3.60 (m, 2H) , 3.32 (s, 2H), 3.00 (dd, 1H), 1.55 (m, 4H), 1.21 (m, 2H), 0.89 (q, 6H)

Example 259

N- (2,3-dichlorobenzyl) -N- (isobutylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Butylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.50 (s, 1H), 7.41 (d, 1H), 7.18 (m, 4H), 6.95 (m, 2H), 6.20 (bs, 1H ), 5.33 (q, 2H), 5.00 (d, 1H), 4.80 (m, 1H), 4.58 (d, 1H), 4.01 (m, 1H), 3.52 (t, 1H), 3.32 (s, 3H) , 3.00 (dd, 1H), 1.90 (m, 1H), 1.58 (m, 2H), 0.90 (t, 3H), 0.80 (t, 6H)

Example 260

N- (2,3-dichlorobenzyl) -N- (t-butylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.52 (s, 1H), 7.41 (t, 2H), 7.18 (m, 3H), 7.05 (s, 1H), 6.90 (d, 2H ), 5.38 (q, 2H), 5.07 (m, 1H), 4.65 (q, 2H), 4.01 (m, 1H), 3.32 (s, 2H), 3.00 (dd, 1H), 1.55 (m, 2H) , 1.40 (s, 9H), 0.90 (t, 6H)

Example 261

N- (2,3-dichlorobenzyl) -N- (2-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.00 (bs, 1h), 7.60 (m, 3H), 7.40 (m, 3H), 7.20 (m, 6H), 6.95 (s, 2H), 5.33 (s, 1H ), 5.20 (s, 2H), 4.85 (m, 1H), 4.75 (d, 1H), 4.20 (m, 1H), 3.36 (s, 2H), 3.12 (dd, 1H), 1.58 (m, 2H) , 0.90 (t, 3H)

Example 262

N- (2,3-dichlorobenzyl) -N- (3-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.95 (bs, 1H), 7.60 (d, 2H), 7.40 (m, 4H), 7.25 (m, 3H), 7.15 (m, 3H), 6.95 (m, 2H ), 5.60 (d, 1H), 5.25 (s, 2H), 4.68 (d, 1H), 4.50 (m, 1H), 4.01 (m, 1H), 3.39 (s, 2H), 3.05 (dd, 1H) , 1.70 (m, 1 H), 1.50 (m, 1 H), 0.90 (t, 3 H)

Example 263

N- (2,3-dichlorobenzyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.70 (bs, 1H), 7.60 (d, 2H), 7.45 (m, 2H), 7.30 (s, 4H), 7.10 (m, 3H), 7.95 (m, 1H ), 6.85 (d, 1H), 5.55 (d, 1H), 5.23 (s, 2H), 4.70 (d, 1H), 4.55 (m, 1H), 4.01 (m, 1H), 3.37 (s, 2H) , 3.05 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 (t, 3H)

Example 264

N- (2,3-dichlorobenzyl) -N- (3-chloro-4-methylphenyl) thiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.80 (bs, 1H), 7.60 (d, 2H), 7.45 (d, 2H), 7.30 (d, 2H), 7.25 (s, 2H), 7.10 (d, 3H ), 6.95 (s, 2H), 5.55 (d, 1H), 5.25 (s, 2H), 4.68 (d, 1H), 4.59 (m, 1H), 4.01 (m, 1H), 3.38 (s, 2H) , 3.04 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.92 (t, 3H)

Example 265

N- (2,3-dichlorobenzyl) -N- (cyclohexylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Butylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.53 (s, 1H), 7.41 (d, 1H), 7.18 (m, 4H), 7.02 (d, 1H), 6.92 (d, 2H ), 5.85 (bs, 1H), 5.33 (q, 2H), 5.05 (m, 1H), 4.80 (m, 1H), 4.60 (d, 1H), 4.30 (m, 1H), 4.00 (m, 1H) , 3.36 (s, 2H), 3.00 (dd, 1H), 2.00 (m, 2H), 1.20-1.70 (m, 8H), 1.10 (m, 2H), 0.90 (t, 3H)

Example 266

N- (2,3-dichlorobenzyl) -N- (cyclopentylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Butylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.55 (s, 1H), 7.41 (d, 1H), 7.18 (d, 3H), 7.08 (d, 1H), 7.05 (m, 1H ), 6.95 (d, 1H), 6.05 (s, 1H), 5.35 (q, 2H), 5.07 (d, 1H), 4.70 (h, 1H), 4.58 (d, 1H), 4.00 (m, 1H) , 3.36 (s, 2H), 3.00 (dd, 1H), 2.00 (m, 2H), 1.23-1.65 (m, 8H), 0.90 (t, 3H)

Example 267

N- (2,3-dichlorobenzyl) -N- (2,4-dichlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.20 (bs, 1H), 7.60 (t, 2H), 7.45 (m, 3H), 7.25 (d, 2H), 7.10 (d, 3H), 6.95 (s, 1H ), 6.90 (d, 1H), 5.35 (m, 1H), 5.25 (s, 2H), 4.75 (d, 2H), 4.19 (m, 1H), 3.38 (s, 2H), 3.12 (dd, 1H) , 1.55 (m, 2H), 0.90 (t, 3H)

Example 268

N- (2,3-dichlorobenzyl) -N-[(2-dimethylamino) ethylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.50 (s, 1H), 7.35 (m, 2H), 7.20 (d, 2H), 7.05 (s, 1H), 6.90 (d, 2H ), 5.38 (q, 2H), 4.90 (m, 2H), 4.60 (d, 1H), 4.10 (m, 1H), 3.55 (m, 2H), 3.35 (s, 2H), 3.12 (dd, 1H) , 2.48 (m, 2H), 1.80 (s, 6H), 1.55 (m, 2H), 0.90 (t, 3H)

Example 269

N- (2,3-dichlorobenzyl) -N-[(4-dimethylamino) phenylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.90 (bs, 1H), 7.60 (d, 2H), 7.45 (m, 2H), 7.20 (m, 1H), 7.10 (m, 4H), 7.00 (d, 2H ), 6.62 (d, 2H), 5.28 (s, 2H), 5.20 (d, 1H), 4.90 (m, 1H), 4.70 (d, 1H), 4.10 (m, 1H), 3.38 (s, 2H) , 3.08 (dd, 1H), 2.95 (s, 6H), 1.55 (m, 2H), 0.90 (t, 3H)

Example 270

N- (2,3-dichlorobenzyl) -N-[(3-dimethylamino) propylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.95 (bs, 1H), 7.65 (d, 3H), 7.50 (s, 1H), 7.41 (d, 1H), 7.18 (d, 3H), 7.03 (s, 1H ), 6.90 (d, 1H), 6.42 (bs, 1H), 5.40 (q, 2H), 5.04 (m, 1H), 4.58 (s, 2H), 4.03 (m, 1H), 3.64 (m, 2H) , 3.32 (q, 2H), 2.96 (dd, 1H), 2.37 (m, 2H), 1.78 (s, 8), 1.55 (m, 2H), 0.90 (t, 3H)

Example 271

N- (2,3-dichlorobenzyl) -N- (ethoxycarbonylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.43 (m, 2H), 7.18 (m, 3H), 7.00 (m, 4H), 5.32 (s, 2H), 5.10 (d, 1H ), 4.75 (m, 1H), 4.65 (d, 1H), 4.33 (m, 2H), 4.15 (q, 3H), 3.38 (s, 2H), 3.02 (dd, 1H), 1.55 (m, 2H) , 1.25 (t, 3H), 0.90 (t, 3H)

Example 272

N- (2,3-dichlorobenzyl) -N- (3-ethoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.52 (s, 1H), 7.41 (d, 2H), 7.18 (m, 3H), 7.03 (s, 1H), 86 (d, 2H ), 5.36 (q, 2H), 5.00 (t, 1H), 4.60 (q, 2H), 4.05 (m, 1H), 3.72 (q, 2H), 3.42 (h, 2H), 3.32 (s, 2H) , 3.20 (t, 2H), 2.96 (dd, 1H), 1.76 (q, 2H), 1.50 (m, 2H), 0.90 (m, 6H)

Example 273

N- (2,3-dichlorobenzyl) -N- (ethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutyl Amine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.50 (s, 1H), 7.41 (d, 1H), 7.18 (m, 4H), 6.96 (m, 2H), 6.40 (bs, 1H ), 5.35 (q, 2H), 5.10 (d, 1H), 4.70 (m, 1H), 4.55 (d, 1H), 4.00 (m, 1H), 3.62 (h, 2H), 3.35 (s, 2H) , 2.98 (dd, 1H), 1.55 (m, 2H), 1.15 (t, 3H), 0.90 (t, 3H)

Example 274

N- (2,3-dichlorobenzyl) -N- (2-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.18 (bs, 1H), 7.60 (d, 2H), 7.40 (m, 3H), 7.22 (m, 2H), 7.10 (m, 3H), 7.00 (s, 1H ), 5.38 (m, 1H), 5.44 (s, 2H), 4.82 (m, 1H), 4.71 (d, 1H), 4.12 (m, 1H), 3.38 (s, 2H), 3.10 (dd, 1H) , 1.55 (m, 2H), 0.90 (t, 3H)

Example 275

N- (2,3-dichlorobenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.88 (s, 1H), 7.60 (d, 2H), 7.45 (m, 2H), 7.02-7.50 (m, 7H), 6.92 (m, 3H), 5.60 (d , 1H), 5.28 (q, 2H), 4.70 (d, 1H), 4.58 (m, 1H), 4.03 (m, 1H), 3.40 (s, 2H), 3.06 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 (t, 3H)

Example 276

N- (2,3-dichlorobenzyl) -N- (4-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.58 (s, 1H), 7.60 (d, 2H), 7.45 (m, 2H), 7.25 (m, 3H), 7.10 (m, 4H), 6.98 (m, 3H ), 5.50 (d, 1H), 5.25 (q, 2H), 4.70 (d, 1H), 4.60 (m, 1H), 4.04 (m, 1H), 3.36 (s, 2H), 3.10 (dd, 1H) , 1.70 (m, 1 H), 1.50 (m, 1 H), 0.90 (t, 1 H)

Example 277

N- (2,3-dichlorobenzyl) -N- (4-hydroxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.50 (s, 1H), 7.45 (d, 1H), 7.18 (m, 7H), 7.00 (s, 1H), 6.90 (d, 2H ), 5.50 (d, 1H), 5.35 (s, 2H), 4.80 (d, 1H), 4.50 (m, 1H), 4.01 (m, 1H), 3.40 (s, 2H), 3.18 (dd, 1H) , 1.70 (m, 1 H), 1.50 (m, 1 H), 0.95 (t, 3 H)

Example 278

N- (2,3-dichlorobenzyl) -N- (4-isopropylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.18 (s, 1H), 7.60 (d, 2H), 7.45 (m, 2H), 7.20 (m, 5H), 7.10 (m, 3H), 7.00 (s, 2H ), 5.40 (d, 1H), 5.25 (s, 2H), 4.80 (m, 1H), 4.68 (d, 1H), 4.08 (m, 1H), 3.38 (s, 2H), 3.08 (dd, 1H) , 2.90 (p, 1H), 1.55 (m, 2H), 1.25 (d, 6H), 0.92 (t, 3H)

Example 279

N- (2,3-dichlorobenzyl) -N- (2-methoxyethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.52 (s, 1H), 7.41 (d, 1H), 7.18 (m, 4H), 7.00 (s, 1H), 6.92 (d, 1H ), 6.25 (bs, 1H), 5.35 (q, 2H), 4.90 (m, 2H), 4.60 (d, 1H), 4.10 (m, 1H), 3.78 (m, 2H), 3.43 (m, 2H) , 3.33 (s, 2H), 3.20 (s, 3H), 3.10 (dd, 1H), 1.55 (m, 2H), 0.90 (t, 3H)

Example 280

N- (2,3-dichlorobenzyl) -N- (2-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.20 (d, 1H), 7.65 (s, 1H), 7.55 (d, 2H), 7.45 (m, 2H), 6.90-7.21 (m, 7H), 6.80 (d , 1H), 5.20 (s, 2H), 5.05 (m, 2H), 4.75 (d, 1H), 4.20 (m, 1H), 3.60 (s, 3H), 3.38 (s, 2H), 3.15 (dd, 1H), 1.58 (m, 2H), 0.90 (t, 3H)

Example 281

N- (2,3-dichlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.18 (s, 1H), 7.60 (d, 2H), 7.41 (m, 2H), 7.18 (m, 6H), 7.00 (s, 1H), 6.85 (d, 2H ), 5.38 (m, 1H), 5.26 (s, 2H), 4.80 (m, 1H), 4.70 (d, 1H), 4.10 (m, 1H), 3.80 (s, 3H), 3.36 (s, 2H) , 3.07 (dd, 1H), 1.55 (m, 2H), 0.90 (t, 3H)

Example 282

N- (2,3-dichlorobenzyl) -N- (3-methoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.51 (s, 1H), 7.40 (d, 2H), 7.20 (m, 3H), 7.00 (s, 1H), 6.92 (s, 1H ), 6.85 (d, 1H), 5.38 (q, 2H), 5.00 (t, 1H), 4.60 (q, 2H), 4.10 (m, 1H), 3.70 (m, 2H), 3.40 (m, 1H) , 3.32 (s, 2H), 3.00 (dd, 1H), 2.92 (s, 3H), 1.75 (q, 2H), 1.55 (m, 2H), 0.90 (t, 3H)

Example 283

N- (2,3-dichlorobenzyl) -N- (2-methoxypyridin-5-ylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole- 5-yl] acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.82 (s, 1H), 7.78 (d, 1H), 7.62 (m, 3H), 7.40 (m, 2H), 7.25 (m, 1H), 7.10 (m, 4H ), 6.95 (s, 1H), 6.70 (d, 1H), 5.50 (d, 1H), 5.28 (q, 2H), 4.70 (m, 2H), 4.05 (m, 1H), 3.90 (s, 3H) , 3.38 (s, 2H), 3.10 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.92 (t, 3H)

Example 284

N- (2,3-dichlorobenzyl) -N- (methylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutyl Amine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.47 (s, 1H), 7.40 (d, 1H), 7.18 (m, 4H), 6.95 (m, 2H), 6.70 (bs, 1H ), 5.35 (q, 2H), 5.10 (d, 3H), 4.70 (m, 1H), 4.58 (d, 1H), 4.01 (m, 1H), 3.35 (s, 2H), 3.12 (d, 3H) , 3.00 (dd, 1H), 1.55 (m, 2H), 0.90 (t, 3H)

Example 285

N- (2,3-dichlorobenzyl) -N- (4-methylthiophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.50 (s, 1H), 7.60 (d, 2H), 7.43 (m, 2H), 7.21 (m, 4H), 7.10 (m, 3H), 6.98 (s, 2H ), 5.45 (d, 1H), 5.2 (s, 2H), 4.70 (d, 2H), 4.05 (m, 1H), 3.38 (s, 2H), 3.07 (dd, 1H), 2.48 (s, 3H) , 1.55 (m, 2H), 0.90 (t, 3H)

Example 286

N- (2,3-dichlorobenzyl) -N- (2-naphthylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.78 (s, 1H), 7.60-7.85 (m, 4H), 7.35-7.55 (m, 7H), 7.20 (m, 2H), 6.97 (m, 4H), 5.51 (d, 1H), 5.20 (q, 2H), 4.72 (d, 2H), 4.10 (m, 1H), 3.39 (s, 2H), 3.10 (dd, 1H), 1.70 (m, 1H), 1.50 ( m, 1H), 0.90 (t, 3H)

Example 287

N- (2,3-dichlorobenzyl) -N- (4-nitrophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 9.58 (s, 1H), 8.18 (d, 2H), 7.75 (d, 2H), 7.58 (d, 2H), 7.45 (m, 2H), 7.41 (d, 1H ), 7.20 (d, 1H), 7.12 (t, 4H), 7.00 (s, 1H), 6.80 (d, 1H), 5.80 (d, 1H), 5.28 (s, 2H), 4.70 (d, 1H) , 4.37 (m, 1H), 4.00 (s, 1H), 3.40 (s, 2H), 3.10 (dd, 1H), 1.75 (m, 1H), 1.55 (m, 1H), 0.90 (t, 3H)

Example 288

N- (2,3-dichlorobenzyl) -N- (n-pentylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.52 (s, 1H), 7.43 (d, 1H), 7.18 (d, 3H), 7.12 (s, 1H), 7.00 (s, 1H ), 6.95 (d, 1H), 6.03 (s, 1H), 5.33 (q, 2H), 4.90 (m, 2H), 4.55 (d, 1H), 4.01 (m, 1H), 3.65 (m, 1H) , 3.45 (m, 1H), 3.32 (s, 2H), 3.00 (dd, 1H), 1.55 (m, 2H), 1.10 (m, 2H), 0.90 (m, 5H), 0.85 (t, 3H)

Example 289

N- (2,3-dichlorobenzyl) -N- (2-phenylethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.48 (s, 1H), 7.39 (d, 1H), 7.18 (m, 6H), 7.00 (m, 4H), 6.95 (d, 1H ), 5.97 (bs, 1H), 5.31 (q, 2H), 4.78 (m, 2H), 4.45 (d, 1H), 3.98 (m, 1H), 3.78 (m, 2H), 3.32 (s, 2H) , 3.00 (dd, 1H), 2.85 (t, 2H), 1.55 (m, 2H), 0.90 (t, 3H)

Example 290

N- (2,3-dichlorobenzyl) -N- (phenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutyl Amine

¹ H-NMR (CDCl ₃ ): δ 8.43 (s, 1H), 7.60 (d, 2H), 7.45 (m, 2H), 7.30 (m, 5H), 7.10 (m, 4H), 7.009m, 2H) , 5.45 (d, 1H), 5.25 (q, 2H), 4.70 (d, 2H), 4.10 (m, 1H), 3.38 (s, 2H), 3.10 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1 H), 0.90 (t, 3 H)

Example 291

N- (2,3-dichlorobenzyl) -N- (n-propylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.50 (s, 1H), 7.41 (d, 1H), 7.18 (m, 4H), 6.97 (m, 2H), 6.32 (bs, 1H ), 5.33 (q, 2H), 5.008 (d, 1H), 4.75 (m, 1H), 4.59 (d, 1H), 4.01 (m, 1H), 3.59 (m, 2H), 3.38 (s, 2H) , 3.00 (dd, 1H), 1.57 (m, 4H), 0.90 (p, 6H)

Example 292

N- (2,3-dichlorobenzyl) -N- (3-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.28 (s, 1H), 7.60 (d, 2H), 7.45 (m, 2H), 7.18 (d, 2H), 7.10 (m, 6H), 7.00 (m, 2H ), 5.40 (d, 1H), 5.25 (s, 2H), 4.70 (d, 2H), 4.10 (m, 1H), 3.39 (s, 2H), 3.10 (dd, 1H), 2.35 (s, 3H) , 1.70 (m, 1 H), 1.50 (m, 1 H), 0.90 (t, 3 H)

Example 293

N- (2,3-dichlorobenzyl) -N- (2-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.82 (s, 1H), 7.60 (d, 2H), 7.45 (m, 2H), 7.05-7.24 (m, 7H), 7.00 (s, 1H), 5.30 (s , 3H), 4.90 (m, 1H), 4.74 (d, 1H), 4.12 (m, 1H), 3.37 (s, 2H), 3.10 (dd, 1H), 2.12 (s, 3H), 1.55 (m, 2H), 0.90 (t, 3H)

Example 294

N- (2,3-dichlorobenzyl) -N- (4-methylphenylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Butylamine

¹ H-NMR (CDCl ₃ ): δ 8.22 (s, 1H), 7.59 (d, 2H), 7.42 (m, 2H), 7.10 (m, 8H), 7.00 (s, 2H), 5.38 (d, 1H ), 5.25 (s, 2H), 4.90 (m, 1H), 4.71 (d, 1H), 4.10 (m, 1H), 3.38 (s, 2H), 3.07 (dd, 1H), 2.35 (s, 3H) , 1.60 (m, 2H), 0.90 (t, 3H)

Example 295

N- (2,3-dichlorobenzyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 9.40 (s, 1H), 7.82 (d, 1H), 7.62 (s, 1H), 7.55 (d, 2H), 7.42 (s, 4H), 7.18 (m, 5H ), 6.95 (s, 1H), 5.78 (d, 1H), 5.30 (s, 2H), 4.70 (d, 1H), 4.43 (m, 1H), 4.01 (s, 1H), 3.38 (s, 2H) , 3.10 (dd, 1H), 1.75 (m, 1H), 1.55 (m, 1H), 0.90 (t, 3H)

Example 296

N- (2,3-dichlorobenzyl) -N- (2,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (bs, 1H), 7.60 (d, 2H), 7.45 (m, 2H), 7.18 (m, 4H), 7.00 (m, 5H), 5.30 (m, 3H ), 4.90 (m, 1H), 4.72 (d, 1H), 4.12 (m, 1H), 3.38 (s, 2H), 3.12 (dd, 1H), 2.35 (s, 3H), 2.05 (s, 3H) , 1.60 (m, 2H), 0.90 (t, 3H)

Example 297

N- (2,3-dichlorobenzyl) -N- (3,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.10 (s, 1H), 7.58 (d, 2H), 7.45 (m, 2H), 7.41 (d, 1H), 7.18 (m, 5H), 7.00 (s, 4H ), 5.27 (m, 3H), 4.72 (m, 2H), 4.10 (m, 1H), 3.39 (s, 2H), 3.06 (dd, 1H), 2.25 (s, 6H), 1.60 (m, 2H) , 0.90 (t, 3H)

Example 298

N- (2,3-dichlorobenzyl) -N- (allylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3- (4-benzyloxy) phenylpropylamine

[Step 1]

N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3- (4-benzyloxy) phenyl Propylamine

N- (t-butoxycarbonyl) -O-benzyl-L-tyrosinealdehyde was prepared in the same manner as in Reference Example 3 using N- (t-butoxycarbonyl) -O-benzyl-L-tyrosine. Then, the same as in Reference Example 4 using 1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride instead of 1- (4-nitrobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride The title compound was prepared by the method.

¹ H-NMR (CDCl ₃ ): δ 7.57 (d, 1H), 7.28-7.43 (m, 7H), 7.18-7.20 (m, 2H), 6.97-7.03 (m, 5H), 6.83 (d, 2H) , 6.13 (d, 1H), 5.04 (s, 2H), 4.87 (d, 1H), 4.16-4.23 (m, 1H), 3.82 (d, 2H), 3.27 (t, 2H), 2.57-2.73 (m , 4H)

[Step 2]

N- (2,3-dichlorobenzyl) -N- (allylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3- (4-benzyloxy) phenylpropylamine

N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3- (4-benzyloxy) phenyl A solution of dichloromethane diluted with dichloromethane (0.02M, 1ml, 0.02mmol) and a solution of allyl isothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) were reacted at room temperature for 1 hour and then reacted. The solution was purified by short silica gel column chromatography (dichloromethane / methanol = 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.25-7.45 (m, 7H), 7.17 (t, 2H), 6.85-7.05 (m, 7H), 6.75 (d, 1H), 6.40 (s, 1H), 5.85 (m, 1H), 5.15 (s, 2H), 5.05 (s, 3H), 4.52-4.85 (m, 4H), 4.25 (t, 3H), 3.50 (t, 1H), 3.35 (m, 1H), 3.10 (m, 1H), 2.85 (m, 1H), 2.65 (m, 1H)

Example 299-343

N- (2,3-dichlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3- (4-benzyloxy) phenyl The title compound was prepared in the same manner as in Step 2 of Example 298, using isothiocyanate corresponding to propylamine.

Example 299

N- (2,3-dichlorobenzyl) -N- (benzylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 3H), 7.05-7.45 (m, 13H), 6.85-7.05 (m, 7H), 6.70 (m, 2H), 5.05 (s, 3H), 4.52 -4.90 (m, 6H), 4.30 (m, 1H), 3.48 (t, 1H), 3.30 (m, 1H), 3.10 (m, 1H), 2.85 (m, 1H), 2.65 (m, 1H)

Example 300

N- (2,3-dichlorobenzyl) -N- (2-biphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.70 (d, 1H), 7.58 (d, 2H), 7.25-7.45 (m, 15H), 6.85-7.05 (m, 9H), 6.70 (m, 2H), 5.05 (s, 3H), 4.52-4.80 (m, 4H), 4.20 (m, 1H), 3.48 (t, 1H), 3.32 (m, 1H), 3.05 (m, 1H), 2.85 (m, 1H), 2.60 (m, 1 H)

Example 301

N- (2,3-dichlorobenzyl) -N- (2-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 1H), 7.58 (d, 3H), 7.25-7.45 (m, 8H), 7.20 (m, 4H), 6.85-7.05 (m, 7H), 6.65 (d, 1H), 5.35 (d, 1H), 5.05 (s, 2H), 4.65-4.90 (m, 4H), 4.50 (m, 1H), 3.48 (t, 1H), 3.30 (m, 1H), 3.18 (m, 1 H), 2.85 (m, 1 H), 2.65 (m, 1 H)

Example 302

N- (2,3-dichlorobenzyl) -N- (3-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.75 (bs, 1H), 7.58 (d, 3H), 7.10-7.50 (m, 12H), 6.95 (m, 7H), 6.42 (d, 1H), 5.60 (d , 1H), 5.07 (s, 2H), 4.50-4.80 (m, 4H), 4.25 (m, 1H), 3.48 (t, 1H), 3.30 (m, 1H), 3.18 (m, 1H), 2.95 ( m, 1H), 2.65 (m, 1H)

Example 303

N- (2,3-dichlorobenzyl) -N- (4-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.60 (bs, 1H), 7.58 (d, 2H), 7.38-7.50 (m, 5H), 7.30 (m, 6H), 7.15 (m, 2H), 6.95 (m , 7H), 6.40 (d, 1H), 5.55 (d, 1H), 5.05 (s, 2H), 4.50-4.80 (m, 4H), 4.25 (m, 1H), 3.48 (t, 1H), 3.30 ( m, 1H), 3.18 (m, 1H), 2.95 (m, 1H), 2.65 (m, 1H)

Example 304

N- (2,3-dichlorobenzyl) -N- (n-butylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.25-7.45 (m, 7H), 7.18 (t, 1H), 6.85-7.05 (m, 8H), 6.78 (d, 1H), 6.22 (bs, 1H), 5.50 (s, 1H), 5.05 (s, 2H), 4.50-4.85 (m, 4H), 4.20 (m, 3H), 3.65 (m, 2H), 3.48 (t, 1H), 3.30 (m, 1H), 3.05 (m, 1H), 2.85 (m, 1H), 2.65 (m, 1H), 1.30 (m, 4H), 0.85 (t, 3H)

Example 305

N- (2,3-dichlorobenzyl) -N-isobutylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 -(4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.25-7.45 (m, 6H), 7.30 (m, 6H), 7.17 (t, 2H), 6.80-7.05 (m, 9H), 6.20 (s, 1H), 5.08 (s, 2H), 5.00 (d, 1H), 4.80 (m, 3H), 4.55 (m, 1H), 4.25 (m, 1H), 3.50 (t, 2H), 3.35 ( m, 2H), 3.10 (m, 1H), 2.85 (m, 1H), 2.65 (m, 1H) 1.90 (m, 1H), 0.80 (m, 6H)

Example 306

N- (2,3-dichlorobenzyl) -N- (t-butylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.30-7.45 (m, 6H), 7.22 (m, 2H), 7.15 (t, 2H), 7.00 (m, 4H), 6.86 (m , 3H), 5.38 (s, 1H), 5.05 (s, 2H), 4.95 (d, 2H), 4.60 (q, 2H), 4.30 (m, 1H), 3.50 (t, 1H), 3.33 (m, 1H), 3.05 (m, 1H), 2.75 (d, 2H), 1.40 (s, 9H)

Example 307

N- (2,3-dichlorobenzyl) -N- (2-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.95 (bs, 1H), 7.65 (d, 1H), 7.58 (d, 2H), 7.10-7.50 (m, 12H), 6.95 (m, 7H), 6.62 (d , 1H), 5.30 (d, 1H), 5.05 (s, 2H), 4.65-4.85 (m, 4H), 4.45 (m, 1H), 3.48 (t, 1H), 3.30 (m, 1H), 3.18 ( m, 1H), 2.90 (m, 1H), 2.65 (m, 1H)

Example 308

N- (2,3-dichlorobenzyl) -N- (3-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.70 (bs, 1H), 7.58 (d, 2H), 7.45 (m, 5H), 7.38 (m, 5H), 7.18 (m, 3H), 6.95 (m, 7H ), 6.40 (d, 1H), 5.50 (d, 1H), 5.07 (s, 2H), 4.50-4.85 (m, 4H), 4.28 (m, 1H), 3.48 (t, 1H), 3.33 (m, 1H), 3.18 (m, 1H), 2.95 (m, 1H), 2.65 (m, 1H)

Example 309

N- (2,3-dichlorobenzyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.60 (bs, 1H), 7.58 (d, 2H), 7.10-7.45 (m, 13H), 6.95 (m, 7H), 6.42 (d, 1H), 5.56 (d , 1H), 5.05 (s, 2H), 4.50-4.82 (m, 4H), 4.25 (m, 1H), 3.48 (t, 1H), 3.30 (m, 1H), 3.18 (m, 1H), 2.95 ( m, 1H), 2.65 (m, 1H)

Example 310

N- (2,3-dichlorobenzyl) -N- (3-chloro-4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Yl] amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.60 (bs, 1H), 7.58 (d, 2H), 7.10-7.50 (m, 13H), 6.95 (m, 7H), 6.50 (d, 1H), 5.55 (d , 1H), 5.07 (s, 2H), 4.50-4.85 (m, 4H), 4.30 (m, 1H), 3.48 (t, 1H), 3.32 (m, 1H), 3.18 (m, 1H), 2.95 ( m, 1H), 2.65 (m, 1H), 2.40 (s, 3H)

Example 311

N- (2,3-dichlorobenzyl) -N- (cyclohexylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.25-7.50 (m, 6H), 7.18 (t, 2H), 6.80-7.05 (m, 7H), 5.90 (s, 1H), 5.07 (s, 2H), 5.00 (d, 1H), 4.80 (m, 3H), 4.55 (d, 1H), 4.25 (m, 2H), 3.50 (t, 1H), 3.35 (m, 1H), 3.05 ( m, 1H), 2.85 (m, 1H), 2.65 (m, 1H), 2.00 (m, 2H), 1.30-1.70 (m, 6H), 1.10 (m, 2H)

Example 312

N- (2,3-dichlorobenzyl) -N- (cyclopentylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.40 (m, 6H), 7.15 (t, 2H), 6.95 (m, 7H), 6.80 (d, 1H), 6.05 (s, 1H ), 5.07 (s, 3H), 4.50-4.90 (m, 5H), 4.25 (m, 1H), 3.48 (t, 1H), 3.33 (m, 1H), 3.05 (m, 1H), 2.85 (m, 1H), 2.65 (m, 1H), 2.10 (m, 2H), 1.55 (m, 4H), 1.35 (m, 2H)

Example 313

N- (2,3-dichlorobenzyl) -N- (2,4-dichlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.10 (bs, 1H), 7.58 (d, 3H), 7.10-7.50 (m, 11H), 6.95 (m, 7H), 6.50 (d, 1H), 5.40 (d , 1H), 5.07 (s, 2H), 4.60-4.80 (m, 4H), 4.42 (m, 1H), 3.48 (t, 1H), 3.30 (m, 1H), 3.18 (m, 1H), 2.95 ( m, 1H), 2.65 (m, 1H)

Example 314

N- (2,3-dichlorobenzyl) -N-[(2-dimethylamino) ethylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Yl] amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.62 (d, 3H), 7.38 (m, 7H), 7.08 (m, 6H), 6.90 (d, 3H), 6.78 (s, 1H), 4.90-5.10 (m , 2H), 4.60 (q, 2H), 4.38 (m, 1H), 3.50 (m, 2H), 3.25 (m, 3H), 2.76 (m, 2H), 2.18 (m, 2H), 1.98 (s, 6H)

Example 315

N- (2,3-dichlorobenzyl) -N-[(4-dimethylamino) phenylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Yl] amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.80 (bs, 1H), 7.58 (d, 2H), 7.30-7.45 (m, 7H), 7.00-7.22 (m, 9H), 6.81 (m, 3H), 6.65 (d, 2H), 5.20 (d, 1H), 5.07 (s, 2H), 4.85 (m, 3H), 4.72 (d, 1H), 4.35 (m, 1H), 3.48 (t, 1H), 3.35 ( m, 1H), 3.15 (m, 1H), 2.95 (s, 3H), 2.80 (m, 2H)

Example 316

N- (2,3-dichlorobenzyl) -N-[(3-dimethylamino) propylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Yl] amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.90 (bs, 1H), 7.63 (d, 2H), 7.58 (s, 1H), 7.40 (m, 7H), 7.10 (m, 6H), 6.85 (d, 3H ), 5.05 (m, 5H), 4.52 (s, 2H), 4.39 (m, 1H), 3.40 (m, 3H), 3.25 (m, 3H), 3.05 (m, 1H), 2.75 (m, 2H) , 2.40 (m, 2H), 1.90 (s, 6H)

Example 317

N- (2,3-dichlorobenzyl) -N- (ethoxycarbonylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.62 (d, 2H), 7.40 (m, 7H), 6.98-7.20 (m, 8H), 6.929 m, 2H), 6.42 (bs, 1H), 5.07 (s, 2H), 4.85 (m, 3H), 4.609d, 1H), 4.35 (m, 1H), 4.20 (q, 1H), 3.48 (t, 1H), 3.30 (m, 1H), 3.08 (m, 1H) , 2.95 (m, 1 H), 2.65 (m, 1 H), 1.30 (t. 3 H)

Example 318

N- (2,3-dichlorobenzyl) -N- (3-ethoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.62 (d, 2H), 7.40 (m, 7H), 7.08 (m, 7H), 6.85 (m, 4H), 5.07 (s, 2H), 4.98 (m, 3H ), 4.60 (q, 2H), 4.30 (m, 1H), 3.759d, 2H, 3.44 (m, 4H), 3.25 (m, 4H), 3.05 (m, 1H), 2.75 (d, 2H), 1.80 (m, 2 H), 0.92 (t, 3 H)

Example 319

N- (2,3-dichlorobenzyl) -N- (ethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.25-7.45 (m, 7H), 7.17 (t, 1H), 6.87-7.05 (m, 8H), 6.75 (d, 1H), 6.35 (s, 1H), 5.20 (d, 1H), 5.05 (s, 2H), 4.80 (q, 2H), 4.60 (d, 2H), 4.25 (t, 3H), 4.67 (p, 2H), 3.50 ( t, 1H), 3.35 (m, 1H), 3.05 (m, 1H), 2.85 (m, 1H), 2.65 (m, 1H), 1.18 (t, 3H)

Example 320

N- (2,3-dichlorobenzyl) -N- (2-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.00 (bs, 1H), 7.58 (d, 2H), 7.40 (m, 4H), 7.30 (m, 5H), 7.18 (m, 4H), 6.95 (m, 7H ), 6.62 (d, 1H), 5.36 (d, 1H), 5.07 (s, 2H), 4.78 (m, 4H), 4.40 (m, 1H), 3.48 (t, 1H), 3.33 (m, 1H) , 3.18 (m, 1H), 2.90 (m, 1H), 2.65 (m, 1H)

Example 321

N- (2,3-dichlorobenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.65 (bs, 1H), 7.58 (d, 2H), 7.42 (m, 3H), 7.30 (m, 6H), 7.19 (m, 3H), 6.95 (m, 8H ), 6.42 (d, 1H), 5.50 (d, 1H), 5.07 (s, 2H), 4.78 (m, 3H), 4.60 (m, 1H), 4.30 (m, 1H), 3.48 (t, 1H) , 3.33 (m, 1H), 3.18 (m, 1H), 2.95 (m, 1H), 2.65 (m, 1H)

Example 322

N- (2,3-dichlorobenzyl) -N- (4-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.42 (bs, 1H), 7.58 (d, 2H), 7.42 (m, 4H), 7.30 (m, 5H), 7.10 (m, 4H), 6.95 (m, 7H ), 6.50 (d, 1H), 5.50 (d, 1H), 5.07 (s, 2H), 4.70 (m, 4H), 4.30 (m, 1H), 3.48 (t, 1H), 3.33 (m, 1H) , 3.18 (m, 1 H), 2.95 (m, 1 H), 2.65 (m, 1 H)

Example 323

N- (2,3-dichlorobenzyl) -N- (4-hydroxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.10 (bs, 1H), 7.58 (d, 2H), 7.38 (m, 7H), 7.18 (t, 2H), 6.95 (m, 10H), 6.68 (d, 2H ), 5.16 (d, 1H), 5.05 (s, 2H), 4.90 (m, 3H), 4.62 (d, 1H), 4.38 (bs, 1H), 3.48 (t, 1H), 3.33 (t, 1H) , 3.11 (m, 1 H), 2.77 (d, 2 H)

Example 324

N- (2,3-dichlorobenzyl) -N- (4-isopropylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.13 (bs, 1H), 7.58 (d, 2H), 7.41 (m, 3H), 7.30 (m, 5H), 7.20 (s, 4H), 7.15 (m, 2H ), 6.95 (m, 6H), 6.70 (d, 1H), 5.38 (d, 1H), 5.07 (s, 2H), 4.78 (m, 4H), 4.30 (m, 1H), 3.48 (t, 1H) , 3.33 (m, 1H), 3.18 (m, 1H), 2.90 (m, 1H), 2.65 (m, 1H)

Example 325

N- (2,3-dichlorobenzyl) -N- (2-methoxyethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.14 (bs, 1H), 7.7.60 (m, 2H), 7.38 (m, 5H), 7.20 (m, 3H), 6.95 (m, 7H), 6.70 (d , 1H), 6.28 (s, 1H), 5.36 (d, 1H), 5.07 (d, 2H), 4.85 (m, 3H), 4.60 (m, 1H), 4.30 (m, 1H), 3.80 (m, 1H), 3.48 (m, 2H), 3.33 (m, 1H), 3.18 (m, 3H), 2.90 (m, 1H), 2.70 (m, 1H), 1.12 (d, 3H)

Example 326

N- (2,3-dichlorobenzyl) -N- (2-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.20 (d, 1H), 7.60 (m, 3H), 7.38 (m, 7H), 7.18 (m, 2H), 7.00 (m, 7H), 6.90 (m, 4H ), 5.15 (d, 1H), 5.05 (s, 2H), 4.92 (m, 3H), 4.70 (d, 1H), 4.45 (m, 1H), 3.60 (s, 3H), 3.48 (t, 1H) , 3.33 (m, 1H), 3.18 (m, 1H), 2.80 (d, 2H)

Example 327

N- (2,3-dichlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.10 (bs, 1H), 7.58 (d, 3H), 7.40 (m, 7H), 7.20 (m, 4H), 6.95 (m, 8H), 6.75 (d, 1H ), 5.36 (d, 1H), 5.07 (s, 2H), 4.78 (m, 4H), 4.32 (m, 1H), 3.80 (s, 3H), 3.48 (t, 1H), 3.33 (m, 1H) , 3.18 (m, 1H), 2.90 (m, 1H), 2.65 (m, 1H)

Example 328

N- (2,3-dichlorobenzyl) -N- (3-methoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.61 (d, 2H), 7.38 (m, 8H), 7.05 (m, 6H), 6.90 (s, 2H), 6.82 (m, 2H), 5.00 (m, 5H ), 4.58 (q, 2H), 4.32 (m, 1H), 3.70 (m, 2H), 3.48 (t, 1H), 3.38 (m, 3H), 3.08 (m, 1H), 2.92 (s, 3H) , 2.75 (d, 2H)

Example 329

N- (2,3-dichlorobenzyl) -N- (2-methoxypyridin-5-ylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole- 5-yl] acetyl} amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.60 (bs, 1H), 8.00 (s, 1H), 7.63 (m, 1H), 7.58 (d, 2H), 7.40 (m, 3H), 7.07-7.37 (m , 7H), 6.95 (m, 6H), 6.72 (d, 1H), 6.58 (d, 1H), 5.52 (d, 1H), 5.07 (s, 2H), 4.78 (m, 4H), 4.31 (m, 1H), 3.90 (s, 3H), 3.48 (t, 1H), 3.33 (m, 1H), 3.18 (m, 1H), 2.95 (m, 1H), 2.65 (m, 1H)

Example 330

N- (2,3-dichlorobenzyl) -N- (methylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.61 (d, 2H), 7.40 (m, 8H), 7.15 (t, 1H), 6.95 (m, 8H), 6.70 (d, 1H), 5.20 (d, 1H ), 5.07 (s, 2H), 4.80 (q, 2H), 4.60 (m, 2H), 4.21 (m, 1H), 3.48 (t, 1H), 3.33 (m, 1H), 3.13 (d, 3H) , 3.05 (m, 1H), 2.90 (m, 1H), 2.65 (m, 1H)

Example 331

N- (2,3-dichlorobenzyl) -N- (4-methylthiophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.40 (bs, 1H), 7.58 (d, 2H), 7.42 (m, 4H), 7.25 (m, 8H), 7.18 (m, 2H), 6.95 (m, 6H ), 6.60 (d, 1H), 5.42 (d, 1H), 5.07 (s, 2H), 4.70 (m, 4H), 4.30 (m, 1H), 3.48 (t, 1H), 3.33 (m, 1H) , 3.18 (m, 1H), 2.92 (m, 1H), 2.70 (m, 1H), 2.45 (s, 3H)

Example 332

N- (2,3-dichlorobenzyl) -N- (2-naphthylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.60 (bs, 1H), 7.78 (m, 4H), 7.15-7.55 (m, 15H), 6.95 (m, 6H), 6.60 (d, 1H), 5.50 (d , 1H), 5.07 (s, 2H), 4.78 (m, 4H), 4.40 (m, 1H), 3.48 (t, 1H), 3.33 (m, 1H), 3.18 (m, 1H), 2.90 (m, 1H), 2.65 (m, 1H)

Example 333

N- (2,3-dichlorobenzyl) -N- (4-nitrophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 9.40 (s, 1H), 8.20 (d, 2H), 7.78 (d, 2H), 7.58 (d, 2H), 7.15-7.45 (m, 10H), 6.95 (m , 6H), 6.28 (d, 1H), 5.80 (d, 1H), 5.07 (s, 2H), 4.80 (d, 1H), 4.62 (q, 2H), 4.40 (m, 1H), 4.20 (m, 1H), 3.48 (t, 1H), 3.33 (m, 1H), 3.11 (m, 1H), 3.00 (m, 1H), 2.65 (m, 1H)

Example 334

N- (2,3-dichlorobenzyl) -N- (n-pentylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.40 (m, 8H), 7.15 (t, 1H), 7.00 (m, 5H), 6.88 (m, 3H), 6.12 (s, 1H ), 5.07 (s, 2H), 4.99 (d, 1H), 4.80 (m, 3H), 4.59 (d, 1H), 4.30 (m, 1H), 3.65 (m, 1H), 3.48 (t, 1H) , 3.33 (m, 2H), 3.11 (m, 1H), 2.85 (m, 1H), 2.65 (m, 1H), 1.70 (m, 2H), 1.10 (m, 2H), 0.80 (m, 5H)

Example 335

N- (2,3-dichlorobenzyl) -N- (2-phenylethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.40 (m, 7H), 7.18 (m, 3H), 6.85-7.10 (m, 11H), 6.76 (d, 1H), 5.95 (s , 1H), 5.07 (s, 2H), 4.80 (m, 4H), 4.42 (d, 1H), 4.24 (m, 1H), 3.85 (m, 2H), 3.48 (t, 1H), 3.33 (m, 1H), 3.03 (m, 1H), 2.82 (t, 2H), 2.70 (m, 2H)

Example 336

N- (2,3-dichlorobenzyl) -N- (phenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.30 (bs, 1H), 7.58 (d, 2H), 7.20-7.45 (m, 13H), 7.18 (m, 2H), 6.95 (m, 6H), 6.62 (d , 1H), 5.41 (d, 1H), 5.07 (s, 2H), 4.73 (m, 4H), 4.32 (m, 1H), 3.48 (t, 1H), 3.33 (m, 1H), 3.18 (m, 1H), 2.90 (m, 1H), 2.65 (m, 1H)

Example 337

N- (2,3-dichlorobenzyl) -N- (n-propylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.62 (d, 2H), 7.42 (m, 4H), 7.32 (m, 3H), 7.18 (t, 1H), 7.00 (m, 6H), 6.90 (m, 2H ), 6.79 (d, 1H), 6.30 (s, 1H), 5.15 (d, 1H), 5.07 (s, 2H), 4.80 (q, 2H), 4.58 (d, 2H), 4.25 (m, 1H) , 3.51 (m, 3H), 3.33 (m, 1H), 3.08 (m, 1H), 2.90 (m, 1H), 2.65 (m, 1H), 1.55 (q, 2H), 0.85 (t, 3H)

Example 338

N- (2,3-dichlorobenzyl) -N- (3-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.12 (bs, 1H), 7.58 (d, 2H), 7.42 (m, 3H), 7.32 (m, 4H), 7.18 (m, 6H), 6.95 (m, 7H ), 6.65 (d, 1H), 5.40 (d, 1H), 5.07 (s, 2H), 4.78 (m, 4H), 4.35 (m, 1H), 3.48 (t, 1H), 3.33 (m, 1H) , 3.18 (m, 1H), 2.90 (m, 1H), 2.65 (m, 1H), 2.32 (s, 3H)

Example 339

N- (2,3-dichlorobenzyl) -N- (2-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.68 (bs, 1H), 7.58 (d, 2H), 7.42 (m, 3H), 7.30 (m, 4H), 7.19 (m, 5H), 6.95 (m, 9H ), 5.25 (d, 1H), 5.07 (s, 2H), 4.79 (m, 4H), 4.40 (m, 1H), 3.48 (t, 1H), 3.33 (m, 1H), 3.18 (m, 1H) , 2.85 (m, 1H), 2.75 (m, 1H), 2.12 (s, 3H)

Example 340

N- (2,3-dichlorobenzyl) -N- (4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.15 (bs, 1H), 7.58 (d, 2H), 7.38 (m, 7H), 7.18 (s, 6H), 6.95 (m, 7H), 6.70 (d, 1H ), 5.36 (d, 1H), 5.07 (s, 2H), 4.79 (m, 4H), 4.36 (m, 1H), 3.48 (t, 1H), 3.33 (m, 1H), 3.18 (m, 1H) ), 2.85 (m, 1H), 2.70 (m, 1H), 2.34 (s, 3H)

Example 341

N- (2,3-dichlorobenzyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 9.02 (bs, 1H), 7.72 (m, 2H), 7.40-7.55 (m, 7H), 7.11-7.38 (m, 6H), 6.95 (m, 7H), 6.40 (d, 1H), 5.70 (d, 1H), 5.07 (s, 2H), 4.71 (m, 3H), 4.52 (m, 1H), 4.28 (m, 1H), 3.48 (t, 1H), 3.33 (m, 1H), 3.20 (m, 1H), 3.00 (m, 1H), 2.65 (m, 1H)

Example 342

N- (2,3-dichlorobenzyl) -N- (2,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.58 (d, 3H), 7.25-7.50 (m, 8H), 7.18 (m, 2H), 7.00 (m, 7H), 6.88 (m, 3H), 5.21 (d , 1H), 5.07 (s, 2H), 4.79 (m, 4H), 4.40 (m, 1H), 3.48 (t, 1H), 3.33 (m, 1H), 3.18 (m, 1H), 2.85 (m , 1H), 2.75 (m, 1H), 2.31 (s, 3H), 2.10 (s, 3H)

Example 343

N- (2,3-dichlorobenzyl) -N- (3,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3- (4-benzyloxy) phenylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.00 (bs, 1H), 7.58 (d, 2H), 7.42 (m, 3H), 7.32 (m, 4H), 7.15 (m, 3H), 6.95 (m, 9H ), 6.72 (d, 1H), 5.32 (d, 1H), 5.07 (s, 2H), 4.79 (m, 4H), 4.37 (m, 1H), 3.48 (t, 1H), 3.33 (m, 1H) , 3.18 (m, 1H), 2.85 (m, 1H), 2.75 (m, 1H), 2.25 (s, 6H)

Example 344

N- (2,3-dichlorobenzyl) -N- (allylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

[Step 1]

N- (2,3-dichlorobenzyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

N- (t-butoxycarbonyl) -glycine aldehyde was prepared in the same manner as in Reference Example 3 using N- (t-butoxycarbonyl) -glycine, and then 1- (4-nitrobenzyl) -1H The title compound was prepared in the same manner as in Reference Example 4, using 1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride instead of imidazol-5-ylacetic acid hydrochloride.

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.53 (s, 1H), 7.38 (dd, 1H), 7.13-7.21 (m, 4H), 6.98 (s, 1H), 6.61 (bs , 1H), 5.27 (s, 2H), 3.84 (s, 2H), 3.36 (s, 2H), 3.25 (q, 2H), 2.70 (t, 2H)

[Step 2]

N- (2,3-dichlorobenzyl) -N- (allylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

N- (2,3-dichlorobenzyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine diluted with dichloromethane (0.02M, 1 ml, 0.02 mmol) and a solution of allyl isothiocyanate diluted with dichloromethane (0.1 M, 0.2 ml, 0.02 mmol) were reacted at room temperature for 2 hours, and then the reaction solution was subjected to short silica gel column chromatography (dichloromethane / methanol). 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 7.63 (d, 2H), 7.51 (s, 1H), 7.42 (d, 1H), 7.25 (d, 1H), 7.16 (d, 2H), 7.04 (d, 1H ), 6.96 (s, 1H), 6.66 (bs, 1H), 5.80-5.96 (m, 1H), 5.27 (s, 2H), 5.12 (dd, 2H), 4.94 (d, 2H), 4.30 (t, 2H), 3.29-3.39 (m, 4H)

Example 345-387

N- (2,3-dichlorobenzyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine with corresponding isothiocyanate The title compound was prepared in the same manner as Step 2 of Example 344.

Example 345

N- (2,3-dichlorobenzyl) -N- (benzylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 7.58 (d, 2H), 7.45 (s, 1H), 7.40 (d, 1H), 7.03-7.32 (m, 9H), 6.91 (s, 1H), 5.12 (s , 2H), 4.94 (d, 2H), 4.88 (d, 2H), 3.85 (t, 2H), 3.29-3.37 (m, 4H)

Example 346

N- (2,3-dichlorobenzyl) -N- (2-biphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethyl Amine

¹ H-NMR (CDCl ₃ ): δ 7.99 (bs, 1H), 7.62 (d, 1H), 7.57 (d, 2H), 7.46 (s, 1H), 7.29-7.42 (m, 8H), 7.16 (d , 2H), 7.04 (d, 2H), 6.91 (s, 1H), 5.77 (d, 1H), 5.18 (s, 2H), 4.86 (s, 2H), 3.72 (t, 2H), 3.29 (s, 2H), 3.18-3.25 (m, 2H)

Example 347

N- (2,3-dichlorobenzyl) -N- (2-bromophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Ethylamine

¹ H-NMR (CDCl ₃ ): δ 8.17 (bs, 1H), 7.53-7.67 (m, 4H), 7.43-7.46 (m, 2H), 7.29-7.38 (m, 3H), 7.09-7.19 (m, 3H), 6.95 (s, 1H), 5.21 (s, 2H), 5.07 (s, 2H), 3.96 (t, 2H), 3.43-3.52 (m, 2H), 3.36 (s, 2H)

Example 348

N- (2,3-dichlorobenzyl) -N- (3-bromophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Ethylamine

¹ H-NMR (CDCl ₃ ): δ 9.11 (bs, 1H), 7.40-7.59 (m, 6H), 7.15-7.32 (m, 4H), 7.09 (d, 2H), 6.92 (s, 1H), 5.24 (s, 2H), 5.19 (s, 2H), 3.72 (t, 2H), 3.32-3.37 (m, 4H)

Example 349

N- (2,3-dichlorobenzyl) -N- (4-bromophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Ethylamine

¹ H-NMR (CDCl ₃ ): δ 8.91 (bs, 1H), 7.57 (d, 2H), 7.40-7.46 (m, 4H), 7.34 (s, 1H), 7.19-7.30 (m, 3H), 7.07 (d, 2H), 6.92 (s, 1H), 5.19 (s, 2H), 5.18 (s, 2H), 3.73 (t, 2H), 3.32-3.37 (m, 4H

Example 350

N- (2,3-dichlorobenzyl) -N- (n-butylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 7.64 (d, 2H), 7.52 (s, 1H), 7.41 (d, 1H), 7.13-7.23 (m, 3H), 7.04 (d, 1H), 6.98 (s , 1H), 6.50 (bs, 1H), 5.28 (s, 2H), 4.93 (s, 2H), 3.81 (t, 2H), 3.62 (q, 2H), 3.36 (s, 2H), 3.27-3.33 ( m, 2H), 1.49-1.60 (m, 2H), 1.22-1.30 (m, 2H), 0.89 (t, 3H)

Example 351

N- (2,3-dichlorobenzyl) -N- (isobutylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 7.64 (d, 2H), 7.52 (s, 1H), 7.42 (d, 1H), 7.14-7.24 (m, 3H), 7.05 (d, 1H), 6.98 (s , 1H), 6.45 (bs, 1H), 5.28 (s, 2H), 4.92 (s, 2H), 3.85 (t, 2H), 3.45 (t, 2H), 3.36 (s, 2H), 3.29-3.32 ( m, 2H), 1.91-1.94 (m, 1H), 0.84 (d, 6H)

Example 352

N- (2,3-dichlorobenzyl) -N- (t-butylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 7.64 (d, 2H), 7.55 (s, 1H), 7.44 (d, 1H), 7.15-7.32 (m, 3H), 7.03 (s, 1H), 6.97 (d , 1H), 5.55 (bs, 1H), 5.30 (s, 2H), 4.76 (s, 2H), 3.99 (t, 2H), 3.86-3.36 (m, 2H), 3.36 (s, 2H), 1.43 ( s, 9H)

Example 353

N- (2,3-dichlorobenzyl) -N- (2-chlorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethyl Amine

¹ H-NMR (CDCl ₃ ): δ 8.20 (bs, 1H), 7.56-7.67 (m, 3H), 7.40-7.46 (m, 3H), 7.08-7.37 (m, 6H), 6.95 (s, 1H) , 5.21 (s, 2H), 5.07 (s, 2H), 3.96 (t, 2H), 3.42-3.50 (m, 2H), 3.36 (s, 2H)

Example 354

N- (2,3-dichlorobenzyl) -N- (3-chlorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethyl Amine

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.47 (s, 1H), 7.37-7.45 (m, 3H), 7.12-7.29 (m, 6H), 6.95 (s, 1H), 5.33 (s, 2H), 5.23 (s, 2H), 3.68-3.78 (m, 4H), 3.37 (m, 2H)

Example 355

N- (2,3-dichlorobenzyl) -N- (4-chlorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethyl Amine

¹ H-NMR (CDCl ₃ ): δ 8.85 (bs, 1H), 7.57 (d, 2H), 7.40-7.55 (m, 3H), 7.21-7.35 (m, 4H), 6.99-7.10 (m, 3H) , 6.94 (s, 1H), 5.20 (s, 2H), 5.18 (s, 2H), 3.74 (t, 2H), 3.33-3.37 (m, 4H)

Example 356

N- (2,3-dichlorobenzyl) -N- (3-chloro-4-methylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 8.89 (bs, 1H), 7.57 (d, 2H), 7.46 (s, 1H), 7.37-7.43 (m, 2H), 7.20-7.27 (m, 3H), 7.08 -7.15 (m, 3H), 6.93 (s, 1H), 5.23 (s, 2H), 5.17 (s, 2H), 3.75 (t, 2H), 3.32-3.38 (m, 4H), 2.34 (s, 3H )

Example 357

N- (2,3-dichlorobenzyl) -N- (cyclohexylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 7.64 (d, 2H), 7.55 (s, 1H), 7.42 (d, 1H), 7.01-7.23 (m, 5H), 6.14 (bs, 1H), 5.29 (s , 2H), 4.91 (s, 2H), 4.25-4.33 (m, 1H), 3.81 (t, 2H), 3.37 (s, 2H), 3.26-3.31 (m, 2H), 1.96-2.02 (m, 2H ), 1.63 (bs, 2H), 1.05-1.35 (m, 6H)

Example 358

N- (2,3-dichlorobenzyl) -N- (cyclopentylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 7.64 (d, 2H), 7.54 (s, 1H), 7.42 (d, 1H), 6.99-7.23 (m, 5H), 6.37 (bs, 1H), 5.29 (s , 2H), 4.95 (s, 2H), 4.70 (q, 1H), 3.77 (t, 2H), 3.37 (s, 2H), 3.25-3.31 (m, 2H), 1.98-2.11 (m, 2H), 1.53-1.63 (m, 4H), 1.37-1.50 (m, 2H)

Example 359

N- (2,3-dichlorobenzyl) -N- (2,4-dichlorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 8.30 (bs, 1H), 7.55-7.62 (m, 3H), 7.47 (s, 1H), 7.41 (dd, 1H), 7.16-7.30 (m, 3H), 7.12 (d, 2H), 6.98 (bs, 1H), 6.94 (s, 1H), 5.21 (s, 2H), 5.09 (s, 2H), 3.31 (t, 2H), 3.44 (q, 2H), 3.36 ( s, 2H)

Example 360

N- (2,3-dichlorobenzyl) -N- (4-dimethylaminophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Ethylamine

¹ H-NMR (CDCl ₃ ): δ 8.11 (bs, 1H), 7.56 (d, 2H), 7.46 (s, 1H), 7.43 (d, 1H), 7.25 (d, 2H), 7.10 (d, 3H ), 6.96 (s, 1H), 6.25 (d, 1H), 5.22 (s, 2H), 5.05 (s, 2H), 3.91 (t, 2H), 3.42 (q, 2H), 3.35 (s, 2H) , 2.93 (s, 6H)

Example 361

N- (2,3-dichlorobenzyl) -N- (ethoxycarbonylmethylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Ethylamine

¹ H-NMR (CDCl ₃ ): δ 7.64 (d, 2H), 7.50 (s, 1H), 7.41 (dd, 1H), 7.05-7.24 (m, 4H), 6.97 (s, 1H), 5.26 (s , 2H), 4.96 (s, 2H), 4.38 (d, 2H), 4.18 (q, 2H), 3.85 (t, 2H), 3.41-3.44 (m, 2H), 3.38 (s, 2H), 1.27 ( t, 3H)

Example 362

N- (2,3-dichlorobenzyl) -N- (3-ethoxypropylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Ethylamine

¹ H-NMR (CDCl ₃ ): δ 7.64 (d, 2H), 7.54 (s, 1H), 7.42 (d, 2H), 7.15-7.23 (m, 2H), 7.02 (s, 1H), 6.03 (d , 1H), 5.31 (s, 2H), 4.72 (s, 2H), 3.98 (t, 2H), 3.71 (q, 2H), 3.38-3.47 (m, 4H), 3.36 (s, 2H), 3.24 ( q, 2H), 1.77-1.83 (m, 2H), 0.92 (t, 3H)

Example 363

N- (2,3-dichlorobenzyl) -N- (ethylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 7.64 (d, 2H), 7.53 (s, 1H), 7.41 (d, 1H), 7.03-7.24 (m, 4H), 6.98 (s, 1H), 6.56 (bs , 1H), 5.28 (s, 2H), 4.94 (s, 2H), 3.78 (t, 2H), 3.65 (q, 2H), 3.37 (s, 2H), 3.31 (q, 2H), 1.91 (t, 3H)

Example 364

N- (2,3-dichlorobenzyl) -N- (2-fluorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Ethylamine

¹ H-NMR (CDCl ₃ ): δ 8.30 (bs, 1H), 7.58 (d, 2H), 7.41-7.51 (m, 3H), 7.03-7.29 (m, 8H), 6.94 (s, 1H), 5.21 (s, 2H), 5.10 (s, 2H), 3.90 (t, 2H), 3.41 (q, 2H), 3.36 (s, 2H)

Example 365

N- (2,3-dichlorobenzyl) -N- (3-fluorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Ethylamine

¹ H-NMR (CDCl ₃ ): δ 8.98 (bs, 1H), 7.57 (d, 2H), 7.47 (s, 1H), 7.40-7.45 (m, 1H), 7.22-7.30 (m, 6H), 7.09 (d, 2H), 6.93 (s, 1H), 6.85-6.91 (m, 1H), 5.22 (s, 2H), 5.20 (s, 2H), 3.78 (t, 2H), 3.30-3.36 (m, 2H ), 3.38 (s, 2 H)

Example 366

N- (2,3-dichlorobenzyl) -N- (4-fluorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Ethylamine

¹ H-NMR (CDCl ₃ ): δ 8.68 (bs, 1H), 7.58 (d, 2H), 7.41-7.47 (m, 1H), 7.19-7.37 (m, 6H), 7.08 (d, 2H), 7.02 (s, 1H), 6.14 (s, 1H), 5.20 (s, 2H), 5.15 (s, 2H), 3.78 (t, 2H), 3.37 (s, 2H), 3.34 (q, 2H)

Example 367

N- (2,3-dichlorobenzyl) -N- (4-hydroxyphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Ethylamine

¹ H-NMR (CD ₃ OD) δ: 7.74 (s, 1H), 7.64 (d, 2H), 7.48 (d, 1H), 7.32 (t, 1H), 7.22 (d, 2H), 7.14 (d, 1H), 7.08 (d, 2H), 6.95 (s, 1H), 6.72 (d, 2H), 5.35 (s, 2H), 5.14 (s, 2H), 3.76 (t, 2H), 3.31-3.43 (m , 2H), 3.30 (s, 2H)

Example 368

N- (2,3-dichlorobenzyl) -N- (4-isopropylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Ethylamine

¹ H-NMR (CDCl ₃ ): δ 8.39 (bs, 1H), 7.56 (d, 2H), 7.47 (s, 1H), 7.39-7.46 (m, 1H), 7.11-7.31 (m, 5H), 7.03 (d, 2H), 6.96 (s, 1H), 5.21 (s, 2H), 5.12 (s, 2H), 3.84 (t, 2H), 3.36 (bs, 4H), 2.83-2.96 (m, 1H), 1.23 (d, 6H)

Example 369

N- (2,3-dichlorobenzyl) -N- (2-methoxyethylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Ethylamine

¹ H-NMR (CDCl ₃ ): δ 7.64 (d, 2H), 7.54 (s, 1H), 7.43 (d, 1H), 7.16-7.23 (m, 3H), 7.01 (s, 1H), 6.98 (d , 1H), 6.41 (bs, 1H), 5.29 (s, 2H), 4.83 (s, 2H), 3.95 (t, 2H), 3.79 (q, 2H), 3.40-3.50 (m, 4H), 3.36 ( s, 2H), 3.21 (s, 3H)

Example 370

N- (2,3-dichlorobenzyl) -N- (2-methoxyphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Ethylamine

¹ H-NMR (CDCl ₃ ): δ 8.14 (d, 1H), 7.45-7.61 (m, 5H), 7.20-7.28 (m, 2H), 7.09-7.16 (m, 3H), 7.01 (s, 1H) , 6.81 (d, 1H), 5.23 (s, 2H), 4.29 (s, 2H), 4.14 (t, 2H), 3.60 (s, 3H), 3.52 (q, 2H), 3.37 (s, 2H)

Example 371

N- (2,3-dichlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Ethylamine

¹ H-NMR (CDCl ₃ ): δ 8.38 (bs, 1H), 7.57 (d, 2H), 7.46 (s, 1H), 7.41-7.45 (m, 1H), 7.16-7.14 (m, 4H), 7.09 (d, 2H), 6.95 (s, 1H), 6.85 (d, 2H), 5.21 (s, 2H), 5.10 (s, 2H), 3.85 (t, 2H), 3.79 (s, 3H), 3.37 ( q, 2H), 3.36 (s, 2H)

Example 372

N- (2,3-dichlorobenzyl) -N- (3-methoxypropylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Ethylamine

¹ H-NMR (CDCl ₃ ): δ 7.64 (d, 2H), 7.54 (s, 1H), 7.43 (d, 1H), 7.16-7.23 (m, 3H), 7.03 (s, 1H), 6.91 (bs , 1H), 6.89 (d, 1H), 5.31 (s, 2H), 4.67 (s, 2H), 4.02 (t, 2H), 3.66 (q, 2H), 3.38-3.45 (m, 4H), 3.36 ( s, 2H), 2.94 (s, 3H), 1.74-1.80 (m, 2H)

Example 373

N- (2,3-dichlorobenzyl) -N- (2-methoxy-pyridin-5ylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 8.86 (bs, 1H), 8.01 (d, 1H), 7.71 (dd, 1H), 7.59 (d, 2H), 7.45 (s, 1H), 7.41-7.44 (m , 1H), 7.19-7.28 (m, 2H), 7.10 (d, 2H), 6.93 (s, 1H), 6.73 (d, 2H), 5.21 (s, 2H), 5.17 (s, 2H), 3.90 ( s, 3H), 3.80 (t, 2H), 3.36 (bs, 4H)

Example 374

N- (2,3-dichlorobenzyl) -N- (methylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 7.64 (d, 2H), 7.51 (s, 1H), 7.41 (d, 1H), 7.15-7.23 (m, 3H), 7.04 (d, 1H), 6.97 (d , 1H), 6.78 (bs, 1H), 5.27 (s, 2H), 4.93 (s, 2H), 3.79 (t, 2H), 3.37 (s, 2H), 3.27-3.37 (m, 2H), 3.11 ( d, 2H)

Example 375

N- (2,3-dichlorobenzyl) -N- (4-methylthiophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Ethylamine

¹ H-NMR (CDCl ₃ ): δ 8.67 (bs, 1H), 7.56 (d, 2H), 7.46 (s, 1H), 7.41-7.45 (m, 1H), 7.18-7.49 (m, 5H), 7.08 (d, 2H), 6.94 (s, 1H), 5.20 (s, 2H), 5.14 (s, 2H), 3.78 (t, 2H), 3.37 (bs, 4H), 2.46 (s, 3H)

Example 376

N- (2,3-dichlorobenzyl) -N- (2-naphthylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethyl Amine

¹ H-NMR (CDCl ₃ ): δ 8.93 (bs, 1H), 7.69-7.80 (m, 3H), 7.58 (dd, 1H), 7.41-7.48 (m, 5H), 7.23-7.30 (m, 2H) , 7.06-7.12 (m, 1H), 6.94-7.00 (m, 3H), 5.16 (s, 2H), 5.14 (s, 2H), 3.78 (t, 2H), 3.34 (bs, 4H)

Example 377

N- (2,3-dichlorobenzyl) -N- (4-nitrophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethyl Amine

¹ H-NMR (CDCl ₃ ): δ 9.52 (bs, 1H), 8.17 (d, 2H), 7.83 (d, 2H), 7.53-7.59 (m, 3H), 7.42-7.46 (m, 1H), 7.24 -7.27 (m, 2H), 7.09 (d, 2H), 6.97 (s, 1H), 6.82-6.89 (m, 1H), 5.29 (s, 2H), 5.21 (s, 2H), 3.65 (t, 2H) ), 3.44 (s, 2H), 3.30-3.34 (m, 2H)

Example 378

N- (2,3-dichlorobenzyl) -N- (n-pentylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 7.64 (d, 2H), 7.53 (s, 1H), 7.42 (d, 1H), 7.02-7.23 (m, 4H), 6.99 (s, 1H), 6.29 (bs , 1H), 5.28 (s, 2H), 4.89 (s, 2H), 3.88 (t, 2H), 3.43-3.61 (m, 2H), 3.36 (bs, 4H), 1.67-1.74 (m, 1H), 1.04-1.29 (m, 2H), 0.78-0.89 (m, 5H)

Example 379

N- (2,3-dichlorobenzyl) -N- (2-phenylethylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethyl Amine

¹ H-NMR (CDCl ₃ ): δ 7.62 (d, 2H), 7.50 (s, 1H), 7.38 (d, 1H), 7.11-7.17 (m, 6H), 6.99-7.07 (m, 3H), 6.84 (d, 1H), 6.07 (bs, 1H), 5.27 (s, 2H), 4.69 (s, 2H), 3.81-3.90 (m, 4H), 3.28-3.34 (m, 4H), 2.86 (t, 3H )

Example 380

N- (2,3-dichlorobenzyl) -N- (phenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 8.57 (bs, 1H), 7.55 (d, 2H), 7.47 (s, 1H), 7.33-7.45 (m, 5H), 7.17-7.29 (m, 3H), 7.08 (d, 2H), 6.95 (s, 1H), 5.20 (s, 2H), 5.14 (s, 2H), 3.82 (t, 2H), 3.37 (bs, 4H)

Example 381

N- (2,3-dichlorobenzyl) -N- (n-propylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 7.64 (d, 2H), 7.53 (s, 1H), 7.42 (d, 1H), 7.02-7.23 (m, 4H), 6.99 (s, 1H), 6.46 (bs , 1H), 5.28 (s, 2H), 4.92 (s, 2H), 3.81 (t, 2H), 3.54-3.64 (m, 2H), 3.36 (s, 2H), 3.27-3.33 (m, 2H), 1.55-1.65 (m, 2H), 0.87 (t, 3H)

Example 382

N- (2,3-dichlorobenzyl) -N- (3-methylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 8.43 (bs, 1H), 7.56 (d, 2H), 7.47 (s, 1H), 7.41-7.45 (m, 1H), 7.01-7.29 (m, 8H), 6.96 (s, 1H), 5.21 (s, 2H), 5.12 (s, 2H), 3.83 (t, 2H), 3.37 (bs, 4H), 2.33 (s, 3H)

Example 383

N- (2,3-dichlorobenzyl) -N- (2-methylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 8.02 (bs, 1H), 7.57 (d, 2H), 7.47 (s, 1H), 7.43-7.46 (m, 1H), 7.20-7.30 (m, 6H), 7.10 (d, 2H), 6.14 (s, 1H), 5.21 (s, 2H), 5.07 (s, 2H), 3.93 (t, 2H), 3.39-3.42 (m, 2H), 3.34 (s, 2H), 2.15 (s, 3 H)

Example 384

N- (2,3-dichlorobenzyl) -N- (4-methylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 8.44 (bs, 1H), 7.56 (d, 2H), 7.46 (s, 1H), 7.41-7.44 (m, 1H), 7.07-7.28 (m, 8H), 6.95 (s, 1H), 5.21 (s, 2H), 5.11 (s, 2H), 3.84 (t, 2H), 3.37-3.39 (m, 2H), 3.36 (s, 2H), 2.34 (s, 3H)

Example 385

N- (2,3-dichlorobenzyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 9.33 (bs, 1H), 7.85-7.89 (m, 1H), 7.69 (s, 1H), 7.56 (d, 2H), 7.38-7.59 (m, 3H), 7.24 -7.28 (m, 2H), 7.05-7.14 (m, 3H), 6.92 (s, 1H), 5.24 (s, 4H), 3.72 (t, 2H), 3.37 (bs, 4H)

Example 386

N- (2,3-dichlorobenzyl) -N- (2,4-dimethylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 7.91 (bs, 1H), 7.57 (d, 2H), 7.47 (s, 1H), 7.42-7.46 (m, 1H), 7.20-7.30 (m, 3H), 7.15 (d, 2H), 7.01 (s, 2H), 6.94 (s, 1H), 5.22 (s, 2H), 5.05 (s, 2H), 3.94 (t, 2H), 3.40-3.45 (m, 2H), 3.34 (s, 2H), 2.30 (s, 3H), 2.11 (s, 3H)

Example 387

N- (2,3-dichlorobenzyl) -N- (3,4-dimethylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 8.33 (bs, 1H), 7.56 (d, 2H), 7.47 (s, 1H), 7.41-7.45 (m, 1H), 7.08-7.29 (m, 7H), 6.96 (s, 1H), 5.21 (s, 2H), 5.09 (s, 2H), 3.85 (t, 2H), 3.40-3.43 (m, 2H), 3.36 (s, 2H), 2.22 (s, 6H)

Example 388

N- (1-naphthylmethyl) -N-allylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) Methylpentylamine

N- (1-naphthylmethyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine with dichloromethane The solution diluted with dichloromethane (0.02M, 1ml, 0.02mmol) and allyl isothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) at room temperature for 2 hours, and then the reaction solution was reacted with a short silica gel tube. Purification by chromatography (dichloromethane / methanol = 9/1, v / v) gave the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 7.02-8.20 (m, 13H), 5.65 (m, 2H), 5.22-5.40 (m, 4H), 5.00 (m, 2H), 4.22 (bs, 2H), 3.35 (s, 2H), 3.10 (dd, 1H), 1.60 (m, 1H), 1.42 (bs, 1H), 0.85-1.15 (m, 7H)

Example 389-417

Corresponding to N- (1-naphthylmethyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine The title compound was prepared in the same manner as in Example 388 using isothiocyanate.

Example 389

N- (1-naphthylmethyl) -N-benzylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-8.20 (m, 18H), 5.95 (t, 1H), 5.30 (m, 3H), 5.02 (m, 2H), 4.80 (d, 2H), 4.22 (bs , 1H), 3.28 (s, 2H), 3.15 (dd, 1H), 1.60 (m, 1H), 1.42 (bs, 1H), 0.85-1.15 (m, 7H)

Example 390

N- (1-naphthylmethyl) -N- (2-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-8.18 (m, 17H), 5.10-5.45 (m, 5H), 4.35 (m, 1H), 3.40 (d, 2H), 3.22 (dd, 2H), 1.60 (m, 1H), 1.42 (bs, 1H), 0.85-1.15 (m, 7H)

Example 391

N- (1-naphthylmethyl) -N- (3-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-8.18 (m, 17H), 5.10-5.40 (m, 5H), 4.25 (m, 1H), 3.38 (s, 2H), 3.20 (dd, 2H), 1.60 (m, 1H), 1.40 (bs, 1H), 0.80-1.10 (m, 7H)

Example 392

N- (1-naphthylmethyl) -N- (n-butylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.20 (m, 13H), 5.25-5.62 (dd, 2H), 4.95 (d, 1H), 4.20 (m, 1H), 3.64 (m, 1H), 3.15 (dd, 2H), 1.65 (m, 3H), 1.40 (m, 3H), 1.15 (m, 3H), 0.90 (m, 7H), 0.80 (t, 3H)

Example 393

N- (1-naphthylmethyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 17H), 5.10-5.42 (m, 5H), 4.25 (m, 1H), 3.40 (s, 2H), 3.20 (dd, 2H), 1.60 (m, 1H), 1.40 (m, 1H), 1.05 (m, 1H), 0.90 (t, 6H)

Example 394

N- (1-naphthylmethyl) -N- (ethoxycarbonylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.10-8.22 (m, 13H), 6.30 (d, 1H), 5.35 (m, 3H), 5.00 (d, 2H), 4.25 (m, 1H), 4.15 (q , 2H), 3.40 (s, 2H), 3.05 (dd, 2H), 1.60 (m, 1H), 1.20-1.40 (m, 5H), 0.80 (m, 6H)

Example 395

N- (1-naphthylmethyl) -N-ethylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.20 (m, 13H), 5.55 (t, 1H), 5.20-5.40 (m, 3H), 4.95 (d, 2H), 4.20 (m, 1H), 3.60 (q, 2H), 3.40 (s, 2H), 3.05 (dd, 2H), 1.60 (m, 1H), 1.40 (m, 1H), 1.20 (m, 1H), 1.02 (t, 3H), 0.85 ( t, 6H)

Example 396

N- (1-naphthylmethyl) -N- (2-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.20 (m, 17H), 5.20-5.40 (m, 5H), 4.35 (m, 1H), 3.42 (s, 2H), 3.20 (dd, 2H), 1.65 (m, 2H), 1.40 (m, 1H), 1.15 (m, 1H), 0.90 (m, 6H)

Example 397

N- (1-naphthylmethyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.20 (m, 17H), 5.20-5.40 (m, 5H), 4.30 (m, 1H), 3.38 (s, 2H), 3.20 (dd, 2H), 1.60 (m, 2H), 1.40 (m, 1H), 1.15 (m, 1H), 0.90 (m, 6H)

Example 398

N- (1-naphthylmethyl) -N- (4-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 17H), 5.20-5.40 (m, 5H), 4.25 (m, 1H), 3.38 (s, 2H), 3.20 (dd, 2H), 1.60 (m, 2H), 1.40 (m, 1H), 1.15 (m, 1H), 0.90 (m, 6H)

Example 399

N- (1-naphthylmethyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.80-8.18 (m, 17H), 5.20-5.40 (m, 5H), 4.23 (m, 1H), 3.78 (s, 3H), 3.40 (s, 2H), 3.20 (dd, 2H), 1.60 (m, 2H), 1.40 (m, 1H), 1.15 (m, 1H), 0.90 (m, 6H)

Example 400

N- (1-naphthylmethyl) -N-methylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.22 (m, 13H), 5.20-5.45 (m, 3H), 5.00 (d, 2H), 4.20 (m, 1H), 3.38 (s, 2H), 3.15 (dd, 2H), 3.10 (d, 3H), 1.60 (m, 2H), 1.40 (m, 1H), 1.15 (m, 1H), 0.90 (m, 6H)

Example 401

N- (1-naphthylmethyl) -N- (1-naphthylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.15 (m, 20H), 5.20-5.60 (m, 5H), 4.40 (m, 1H), 3.42 (s, 2H), 3.15 (dd, 2H), 3.10 (d, 3H), 1.60 (m, 2H), 1.40 (m, 1H), 1.15 (m, 1H), 0.90 (m, 6H)

Example 402

N- (1-naphthylmethyl) -N- (2-phenylethylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.75-8.20 (m, 18H), 5.20-5.60 (m, 3H), 4.80 (s, 2H), 4.20 (m, 1H), 3.90 (m, 1H), 3.70 (m, 1H), 3.38 (s, 2H), 3.05 (dd, 2H), 2.70 (t, 2H), 1.60 (m, 2H), 1.40 (m, 1H), 1.15 (m, 1H), 0.90 ( m, 6H)

Example 403

N- (1-naphthylmethyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 17H), 5.20-5.60 (m, 5H), 4.25 (m, 1H), 3.38 (s, 2H), 3.20 (dd, 2H), 1.60 (m, 2H), 1.40 (m, 1H), 1.15 (m, 1H), 0.90 (m, 6H)

Example 404

N- (1-naphthylmethyl) -N-benzoylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.10-8.20 (m, 18H), 6.20 (bs, 1H), 5.20-5.55 (m, 3H), 5.00 (d, 2H), 4.45 (m, 1H), 3.50 (s, 2H), 3.15 (dd, 1H), 1.80 (m, 2H), 1.45 (m, 1H), 0.85-1.12 (m, 7H)

Example 405

N- (1-naphthylmethyl) -N-cyclohexylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S ) -Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.10-8.20 (m, 13H), 5.40 (d, 2H), 4.96 (d, 2H), 4.20 (m, 2H), 3.40 (s, 2H), 3.10 (dd , 1H), 1.85 (bs, 6H), 1.22-1.60 (bs, 7H), 0.85-1.12 (m, 7H)

Example 406

N- (1-naphthylmethyl) -N- (4-dimethylamino-1-naphthylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazole-5- Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 19H), 5.20-5.55 (m, 5H), 4.38 (m, 1H), 3.45 (s, 2H), 3.25 (dd, 1H), 2.80 (ss, 6H), 1.80 (m, 1H), 1.40 (bs, 1H), 1.10 (m, 1H), 0.85 (m, 6H)

Example 407

N- (1-naphthylmethyl) -N- (2-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-8.18 (m, 17H), 6.80 (s, 1H), 5.20-5.40 (m, 3H), 5.10 (d, 2H), 4.35 (m, 1H), 3.40 (s, 2H), 3.20 (dd, 1H), 3.20 (s, 3H), 1.80 (m, 1H), 1.40 (bs, 1H), 1.10 (m, 1H), 0.85 (m, 6H)

Example 408

N- (1-naphthylmethyl) -N- (4-nitrophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 17H), 5.60 (m, 1H), 5.38 (d, 2H), 5.10 (d, 2H), 4.25 (m, 1H), 3.40 (s , 2H), 3.20 (dd, 1H), 1.80 (m, 1H), 1.40 (bs, 1H), 1.10 (m, 1H), 0.85 (m, 6H)

Example 409

N- (1-naphthylmethyl) -N- (n-propylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 13H), 5.60 (m, 1H), 5.40 (d, 2H), 5.25 (m, 1H), 4.98 (d, 2H), 4.20 (m , 1H), 3.60 (m, 1H), 3.42 (m, 1H), 3.40 (s, 2H), 3.10 (dd, 1H), 1.80 (m, 1H), 1.60 (bs, 1H), 1.40 (m, 2H), 1.10 (m, 1H), 0.85 (m, 6H), 0.70 (t, 3H)

Example 410

N- (1-naphthylmethyl) -N- (2-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 17H), 5.25-5.42 (m, 3H), 5.10 (d, 2H), 4.30 (m, 1H), 3.40 (s, 2H), 3.22 (dd, 1H), 2.00 (s, 3H), 1.80 (m, 1H), 1.40 (m, 1H), 1.10 (m, 1H), 0.90 (m, 6H)

Example 411

N- (1-naphthylmethyl) -N- (3-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.96-8.20 (m, 17H), 5.40 (d, 1H), 5.20 (m, 1H), 5.10 (d, 2H), 4.25 (m, 1H), 3.40 (s , 2H), 3.18 (dd, 1H), 2.30 (s, 3H), 2.00 (m, 1H), 1.40 (m, 1H), 1.10 (m, 1H), 0.90 (m, 6H)

Example 412

N- (1-naphthylmethyl) -N- (4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 17H), 5.40 (d, 1H), 5.20 (m, 1H), 5.10 (d, 2H), 4.30 (m, 1H), 3.38 (s , 2H), 3.20 (dd, 1H), 2.30 (s, 3H), 2.00 (m, 1H), 1.40 (m, 1H), 1.10 (m, 1H), 0.90 (m, 6H)

Example 413

N- (1-naphthylmethyl) -N- (4-azidophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.80-8.10 (m, 17H), 4.95-5.38 (m, 5H), 4.20 (m, 1H), 3.27 (s, 2H), 3.08 (dd, 1H), 1.58 (bs, 1H), 1.32 (m, 1H), 1.00 (m, 1H), 0.92 (m, 6H)

Example 414

N- (1-naphthylmethyl) -N- (4-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.10 (m, 17H), 4.92-5.40 (m, 5H), 4.20 (m, 1H), 3.25 (s, 2H), 3.05 (dd, 1H), 1.57 (bs, 1H), 1.34 (m, 1H), 0.98 (m, 1H), 0.82 (m, 6H)

Example 415

N- (1-naphthylmethyl) -N- (2-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.15 (m, 17H), 5.00-5.38 (m, 5H), 4.24 (m, 1H), 3.32 (s, 2H), 3.13 (dd, 1H), 1.58 (bs, 1H), 1.36 (m, 1H), 1.00 (m, 1H), 0.80 (m, 6H)

Example 416

N- (1-naphthylmethyl) -N- (3-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.10 (m, 17H), 4.98-5.22 (m, 5H), 4.20 (m, 1H), 3.28 (s, 2H), 3.10 (dd, 1H), 1.56 (bs, 1H), 1.35 (m, 1H), 1.00 (m, 1H), 0.80 (m, 6H)

Example 417

N- (1-naphthylmethyl) -N- (2,4-dichlorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.15 (m, 16H), 5.00-5.18 (m, 5H), 4.25 (m, 1H), 3.30 (s, 2H), 3.14 (dd, 1H), 1.60 (bs, 1H), 1.34 (m, 1H), 1.00 (m, 1H), 0.82 (m, 6H)

Example 418

N- (1-naphthylmethyl) -N- (2-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

[Step 1]

N- (1-naphthylmethyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

Nt-butoxycarbonyl-L-isoleucine aldehyde was prepared in the same manner as in Reference Example 3 using Nt-butoxycarbonyl-L-isoleucine, and then 2,3-dichlorobenzylamine and 1- ( Reference Example 4 Using 1-naphthylmethylamine and 1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride instead of 4-nitrobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride In the same manner as the title compound was prepared.

¹ H-NMR (CDCl ₃ ): δ 6.80-8.20 (m, 13H), 5.95 (d, 1H), 4.80-5.12 (dd, 2H), 4.15-4.20 (m, 2H), 3.80-4.00 (m, 1H), 3.15 (m, 2H), 2.60-2.80 (m, 2H), 2.24 (bs, 1H), 1.20-1.60 (m, 2H), 0.92-1.20 (m, 1H), 0.60-0.92 (m, 6H)

[Step 2]

N- (1-naphthylmethyl) -N- (2-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

Dichloro N- (1-naphthylmethyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine Methane-diluted solution (0.02M, 1ml, 0.02mmol) and 2-bromophenylisothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) were reacted at room temperature for 4 hours, and then reacted. The solution was purified by short silica gel column chromatography (dichloromethane / methanol = 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 7.10-8.00 (m, 17H), 5.40 (m, 2H), 5.20 (d, 4H), 4.40 (m, 2H), 4.05 (bs, 1H), 3.40 (s , 2H), 3.25 (dd, 1H), 1.80 (m, 1H), 1.42 (bs, 1H), 0.80-1.10 (m, 7H)

Example 419-447

Corresponds to N- (1-naphthylmethyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine The title compound was prepared in the same manner as in Step 2 of Example 418, using isothiocyanate.

Example 419

N- (1-naphthylmethyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.10-8.00 (m, 17H), 5.00-5.40 (m, 4H), 4.25 (m, 1H), 4.05 (bs, 1H), 3.36 (s, 2H), 3.20 (dd, 1H), 1.80 (m, 1H), 1.42 (bs, 1H), 0.80-1.10 (m, 7H)

Example 420

N- (1-naphthylmethyl) -N- (2-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-7.95 (m, 17H), 5.05-5.40 (m, 4H), 4.35 (m, 1H), 4.10 (bs, 1H), 3.40 (s, 2H), 3.20 (dd, 1H), 1.80 (m, 1H), 1.42 (bs, 1H), 0.80-1.10 (m, 7H)

Example 421

N- (1-naphthylmethyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-7.95 (m, 17H), 5.05-5.50 (m, 5H), 4.25 (m, 1H), 3.38 (s, 2H), 3.18 (dd, 1H), 1.60 (m, 1H), 1.40 (bs, 1H), 1.05 (m, 1H), 0.80 (t, 6H)

Example 422

N- (1-naphthylmethyl) -N- (4-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.95 (m, 17H), 5.30 (d, 2H), 5.20-5.42 (m, 1H), 5.15 (m, 2H), 4.20 (m, 1H), 3.40 (s, 2H), 3.20 (dd, 1H), 1.80 (m, 1H), 1.40 (m, 1H), 1.04 (m, 1H), 0.85 (t, 6H)

Example 423

N- (1-naphthylmethyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.80-7.95 (m, 17H), 5.25-5.40 (m, 3H), 5.10 (m, 2H), 4.25 (m, 1H), 3.75 (s, 3H), 3.40 (s, 2H), 3.20 (dd, 1H), 1.80 (m, 1H), 1.40 (m, 1H), 1.04 (m, 1H), 0.85 (m, 6H)

Example 424

N- (1-naphthylmethyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.90 (m, 17H), 5.05-5.50 (m, 5H), 4.30 (m, 1H), 3.35 (s, 2H), 3.20 (dd, 1H), 1.80 (m, 1H), 1.40 (m, 1H), 1.04 (m, 1H), 0.85 (m, 6H)

Example 425

N- (1-naphthylmethyl) -N- (2-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.88-8.20 (m, 17H), 4.85-5.35 (m, 5H), 4.30 (m, 1H), 3.40 (s, 2H), 3.22 (s, 3H), 3.20 (dd, 1H), 1.75 (m, 1H), 1.40 (m, 1H), 1.05 (m, 1H), 0.90 (m, 6H)

Example 426

N- (1-naphthylmethyl) -N- (4-nitrophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.15 (m, 17H), 5.55 (m, 1H), 5.30 (d, 2H), 5.05 (d, 2H), 4.24 (m, 1H), 3.38 (s , 2H), 3.20 (dd, 1H), 1.75 (m, 1H), 1.40 (m, 1H), 1.05 (m, 1H), 0.90 (m, 6H)

Example 427

N- (1-naphthylmethyl) -N- (2-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.20 (m, 17H), 5.30 (m, 3H), 5.10 (dd, 2H), 3.40 (s, 2H), 3.20 (dd, 1H), 1.98 (s , 3H), 1.60 (m, 1H), 1.40 (m, 1H), 1.10 (m, 1H), 0.95 (m, 6H)

Example 428

N- (1-naphthylmethyl) -N- (3-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-7.90 (m, 17H), 5.35 (m, 3H), 5.10 (d, 2H), 3.38 (s, 2H), 3.20 (dd, 1H), 2.25 (s , 3H), 1.60 (m, 1H), 1.40 (m, 1H), 1.10 (m, 1H), 0.95 (m, 6H)

Example 429

N- (1-naphthylmethyl) -N- (4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-7.95 (m, 17H), 5.30 (m, 3H), 5.10 (dd, 2H), 3.40 (s, 2H), 3.18 (dd, 1H), 2.30 (s , 3H), 1.55 (m, 1H), 1.42 (m, 1H), 1.05 (m, 1H), 0.85 (m, 6H)

Example 430

N- (1-naphthylmethyl) -N-allylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S ) -Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-7.95 (m, 13H), 5.60 (t, 1H), 5.35 (m, 3H), 4.98 (d, 2H), 4.20 (m, 1H), 3.65 (m , 1H), 3.42 (m, 1H), 3.38 (s, 2H), 3.10 (dd, 1H), 1.65 (m, 1H), 1.40 (m, 1H), 1.10 (m, 1H), 0.85 (m, 6H)

Example 431

N- (1-naphthylmethyl) -N-benzylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S ) -Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-7.90 (m, 18H), 6.00 (t, 1H), 5.30 (s, 2H), 5.20 (m, 1H), 5.05 (dd, 2H), 4.80 (d , 2H), 4.24 (m, 1H), 3.28 (s, 2H), 3.15 (dd, 1H), 1.58 (m, 1H), 1.40 (m, 1H), 1.05 (m, 1H), 0.85 (t, 6H)

Example 432

N- (1-naphthylmethyl) -N- (3-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.10-7.95 (m, 17H), 5.60 (m, 1H), 5.30 (s, 2H), 5.10 (m, 2H), 4.30 (m, 1H), 3.38 (s , 2H), 3.20 (dd, 1H), 1.60 (m, 1H), 1.40 (m, 1H), 1.05 (m, 1H), 0.85 (t, 6H)

Example 433

N- (1-naphthylmethyl) -N- (n-butylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-7.95 (m, 13H), 5.70 (m, 3H), 5.38 (m, 2H), 4.95 (m, 2H), 4.20 (m, 3H), 3.35 (s , 2H), 3.10 (dd, 1H), 1.60 (m, 1H), 1.42-1.55 (m, 3H), 1.05-2.22 (m, 3H), 0.85 (m, 9H)

Example 434

N- (1-naphthylmethyl) -N-ethylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S ) -Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-7.95 (m, 13H), 5.62 (m, 1H), 5.35 (m, 2H), 5.00 (m, 2H), 4.20 (m, 1H), 3.60 (m , 2H), 3.35 (s, 2H), 3.10 (dd, 1H), 1.60 (m, 1H), 1.40 (m, 1H), 1.10 (m, 1H), 1.04 (t, 3H), 0.85 (m, 6H)

Example 435

N- (1-naphthylmethyl) -N- (4-azidophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.95-7.95 (m, 17H), 5.04-5.42 (m, 5H), 4.25 (m, 1H), 3.36 (s, 2H), 3.18 (dd, 1H), 1.60 (m, 1H), 1.40 (m, 1H), 1.08 (m, 1H), 0.85 (t, 6H)

Example 436

N- (1-naphthylmethyl) -N- (4-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-7.90 (m, 17H), 5.04-5.48 (m, 5H), 4.28 (m, 1H), 3.38 (s, 2H), 3.20 (tt, 1H), 1.60 (m, 1H), 1.40 (m, 1H), 1.05 (m, 1H), 0.86 (t, 6H)

Example 437

N- (1-naphthylmethyl) -N- (2-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-7.90 (m, 17H), 5.08-5.46 (m, 5H), 4.40 (m, 1H), 3.40 (s, 2H), 3.22 (tt, 1H), 1.62 (m, 1H), 1.41 (m, 1H), 1.07 (m, 1H), 0.85 (m, 6H)

Example 438

N- (1-naphthylmethyl) -N-methylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S ) -Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.95 (m, 13H), 5.78 (m, 1H), 5.20-5.40 (m, 2H), 5.00 (m, 2H), 4.20 (m, 1H), 3.60 (m, 2H), 3.34 (s, 2H), 3.10 (dd, 1H), 3.00 (d, 3H), 1.60 (m, 1H), 1.40 (m, 1H), 1.10 (m, 1H), 0.85 ( m, 6H)

Example 439

N- (1-naphthylmethyl) -N- (1-naphthylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.00 (m, 20H), 5.55 (dd, 1H), 5.25 (d, 2H), 5.20 (d, 2H), 4.40 (m, 1H), 3.40 (s , 2H), 3.25 (dd, 1H), 3.00 (d, 3H), 1.60 (m, 1H), 1.40 (m, 1H), 1.10 (m, 1H), 0.85 (t, 6H)

Example 440

N- (1-naphthylmethyl) -N- (2-phenylethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.80-7.95 (m, 18H), 5.50 (m, 1H), 5.35 (d, 2H), 4.80 (d, 2H), 4.20 (m, 1H), 3.90 (m , 1H), 3.70 (m, 1H), 3.35 (s, 2H), 3.05 (dd, 3H), 2.70 (m, 2H), 1.40 (m, 1H), 1.10 (m, 1H), 0.85 (t, 6H)

Example 441

N- (1-naphthylmethyl) -N-benzoylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S ) -Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-7.90 (m, 18H), 6.20 (m, 1H), 5.40 (d, 2H), 5.00 (dd, 2H), 4.40 (m, 1H), 3.52 (d , 2H), 3.05 (m, 3H), 1.60 (m, 1H), 1.40 (m, 1H), 1.10 (m, 1H), 0.80 (m, 6H)

Example 442

N- (1-naphthylmethyl) -N-cyclohexylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 ( S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.20-7.98 (m, 13H), 5.22-5.40 (m, 3H), 5.00 (m, 2H), 4.22 (m, 2H), 3.35 (s, 2H), 3.05 (dd, 3H), 1.92 (bs, 4H), 1.30-1.62 (m, 6H), 1.10 (m, 3H), 0.90 (m, 6H)

Example 443

N- (1-naphthylmethyl) -N- (4-dimethylamino-1-naphthylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 19H), 5.20-5.60 (m, 5H), 4.42 (m, 1H), 3.40 (s, 2H), 3.25 (dd, 1H), 2.85 (s, 6H), 1.60 (m, 1H), 1.40 (m, 1H), 1.05 (m, 1H), 0.84 (t, 6H)

Example 444

N- (1-naphthylmethyl) -N-phenylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S ) -Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-7.95 (m, 18H), 5.22-5.44 (m, 3H), 5.10 (dd, 2H), 4.30 (m, 1H), 3.38 (s, 2H), 3.18 (dd, 1H), 1.60 (m, 1H), 1.40 (m, 1H), 1.10 (m, 1H), 0.85 (t, 6H)

Example 445

N- (1-naphthylmethyl) -N- (n-propylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-7.95 (m, 13H), 5.60 (t, 1H), 5.20-5.38 (m, 3H), 4.98 (d, 2H), 4.25 (m, 1H), 3.60 (m, 1H), 3.42 (m, 1H), 3.38 (s, 2H), 3.10 (tt, 1H), 1.60 (m, 1H), 1.42 (q, 2H), 1.40 (m, 1H), 1.10 ( m, 1H), 0.85 (t, 6H). 0.70 (t, 3H)

Example 446

N- (1-naphthylmethyl) -N- (3-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-7.92 (m, 17H), 5.00-5.55 (m, 5H), 4.32 (m, 1H), 3.38 (s, 2H), 3.18 (tt, 1H), 1.60 (m, 1H), 1.40 (m, 1H), 1.08 (m, 1H), 0.88 (m, 6H)

Example 447

N- (1-naphthylmethyl) -N- (2,4-dichlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-7.90 (m, 16H), 5.05-5.45 (m, 5H), 4.38 (m, 1H), 3.38 (s, 2H), 3.20 (tt, 1H), 1.65 (m, 1H), 1.42 (m, 1H), 1.08 (m, 1H), 0.86 (t, 6H)

Example 448

N- (1-naphthylmethyl) -N-allylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3-methylbutyl Amine

[Step 1]

N- (1-naphthylmethyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3-methylbutylamine

Nt-butoxycarbonyl-L-valine aldehyde was prepared in the same manner as in Reference Example 3 using Nt-butoxycarbonyl-L-valine, and then 1-naphthylmethylamine instead of 2,3-dichlorobenzylamine To prepare a title compound in the same manner as in Reference Example 4.

TLC: R _f = 0.31 (dichloromethane / methanol = 10/1)

¹ H-NMR (CDCl ₃ ): δ 8.00-8.20 (m, 3H), 7.70-7.95 (m, 2H), 7.23-7.60 (m, 5H), 6.90-7.06 (m, 3H), 5.80 (d, 1H), 5.10 (d, 1H), 4.20 (s, 2H), 3.70-3.90 (m, 1H), 3.00-3.30 (dd, 2H), 2.85-3.00 (m, 1H), 2.65-2.83 (m, 2H), 2.00 (b, 1H), 1.60-1.80 (m, 1H), 0.75-1.00 (m, 6H)

[Step 2]

N- (1-naphthylmethyl) -N-allylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3-methylbutyl Amine

N- (1-naphthylmethyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3-methylbutylamine diluted with dichloromethane The solution (0.02M, 1ml, 0.02mmol) and the solution of allyl isothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) were reacted at room temperature for 4 hours, and then the reaction solution was subjected to short silica gel column chromatography ( Dichloromethane / methanol = 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 7.05-8.20 (m, 13H), 5.70 (m, 2H), 5.40 (d, 2H), 5.20 (m, 1H), 4.22 (m, 3H), 3.38 (s , 2H), 3.10 (dd, 1H), 1.80 (m, 1H), 0.90 (d, 6H)

Example 449-463

N- (1-naphthylmethyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3-methylbutylamine and the corresponding isothiocia The title compound was prepared in the same manner as in Step 2 of Example 448, using a nate.

Example 449

N- (1-naphthylmethyl) -N-benzylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3-methylbutyl Amine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.20 (m, 18H), 6.00 (t, 1H), 5.20-5.38 (m, 3H), 5.05 (d, 2H), 4.82 (d, 2H), 4.18 (m, 1H), 3.35 (s, 2H), 3.17 (dd, 1H), 1.80 (m, 1H), 0.85 (d, 6H)

Example 450

N- (1-naphthylmethyl) -N- (2-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.10-8.20 (m, 17H), 5.05-5.45 (m, 5H), 4.30 (m, 1H), 3.42 (s, 2H), 3.20 (dd, 1H), 1.82 (m, 1H), 0.90 (dd, 6H)

Example 451

N- (1-naphthylmethyl) -N- (3-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.10-8.20 (m, 17H), 5.25-5.42 (m, 3H), 5.15 (m, 2H), 4.20 (m, 1H), 3.40 (s, 2H), 3.20 (dd, 1H), 1.85 (m, 1H), 0.90 (dd, 6H)

Example 452

N- (1-naphthylmethyl) -N- (n-butylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.20 (m, 13H), 5.45 (d, 2H), 5.22 (m, 1H), 4.96 (d, 2H), 4.18 (m, 1H), 3.65 (m , 1H), 3.42 (s, 2H), 3.40 (s, 2H), 3.15 (dd, 1H), 1.80 (m, 1H), 1.38 (q, 2H), 1.10 (q, 2H), 0.90 (dd, 6H), 0.78 (t, 3H)

Example 453

N- (1-naphthylmethyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino -3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.20 (m, 17H), 5.22-5.45 (m, 3H), 5.10 (d, 2H), 4.20 (m, 1H), 3.65 (m, 1H), 3.38 (s, 2H), 1.82 (m, 1H), 0.85 (dd, 6H)

Example 454

N- (1-naphthylmethyl) -N-ethoxycarbonylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 -Methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.10-8.22 (m, 13H), 6.20 (d, 1H), 5.18-5.45 (m, 3H), 4.95 (d, 1H), 4.22 (m, 1H), 4.15 (q, 2H), 3.70 (s, 2H), 3.42 (s, 2H), 3.08 (dd, 1H), 1.65 (m, 1H), 1.22 (t, 2H), 0.75 (t, 6H)

Example 455

N- (1-naphthylmethyl) -N-ethylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3-methylbutyl Amine

¹ H-NMR (CDCl ₃ ): δ 7.05-7.95 (m, 13H), 5.43 (d, 2H), 5.20 (m, 1H), 4.97 (d, 2H), 4.15 (m, 1H), 3.60 (m , 2H), 3.40 (s, 2H), 3.10 (dd, 1H), 1.78 (m, 1H), 1.00 (t, 2H), 0.87 (t, 6H)

Example 456

N- (1-naphthylmethyl) -N- (2-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.98-8.18 (m, 17H), 5.05-5.42 (m, 5H), 4.25 (m, 1H), 3.43 (s, 2H), 3.20 (dd, 1H), 1.80 (m, 1H), 0.90 (t, 6H)

Example 457

N- (1-naphthylmethyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.85-8.18 (m, 17H), 5.05-5.45 (m, 5H), 4.20 (m, 1H), 3.40 (s, 2H), 3.20 (dd, 1H), 1.85 (m, 1H), 0.90 (d, 6H)

Example 458

N- (1-naphthylmethyl) -N- (4-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-8.20 (m, 17H), 5.20-5.42 (m, 3H), 5.05 (d, 2H), 4.20 (m, 1H), 3.38 (s, 2H), 3.20 (dd, 1H), 1.82 (m, 1H), 0.87 (m, 6H)

Example 459

N- (1-naphthylmethyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.80-8.20 (m, 17H), 5.20-5.45 (m, 3H), 5.05 (d, 2H), 4.22 (m, 1H), 3.78 (s, 3H), 3.40 (s, 2H), 3.20 (dd, 1H), 1.82 (m, 1H), 0.87 (d, 6H)

Example 460

N- (1-naphthylmethyl) -N-methylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3-methylbutyl Amine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.22 (m, 13H), 5.15-5.45 (m, 3H), 4.98 (d, 2H), 4.18 (m, 1H), 3.44 (s, 2H), 3.15 (dd, 1H), 3.08 (s, d), 1.82 (m, 1H), 0.87 (d, 6H)

Example 461

N- (1-naphthylmethyl) -N- (1-naphthylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino -3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.04-8.15 (m, 20H), 5.18-5.60 (m, 5H), 4.30 (m, 1H), 3.40 (s, 2H), 3.22 (dd, 1H), 1.80 (m, 1 H), 0.85 (m, 6 H)

Example 462

N- (1-naphthylmethyl) -N- (2-phenylethylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino -3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.78-8.20 (m, 18H), 5.45 (m, 1H), 5.40 (d, 2H), 5.25 (dd, 2H), 4.10 (m, 1H), 3.92 (m , 1H), 3.70 (m, 1H), 3.38 (s, 2H), 3.10 (dd, 1H), 2.72 (m, 2H), 1.80 (m, 1H), 0.90 (d, 6H)

Example 463

N- (1-naphthylmethyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.92-8.18 (m, 17H), 5.55 (d, 1H), 5.30 (d, 2H), 5.15 (m, 2H), 4.22 (m, 1H), 3.40 (s , 2H), 3.20 (dd, 1H), 1.84 (m, 1H), 0.95 (t, 6H)

Example 464

N- (1-naphthylmethyl) -N- (3-bromophenylthiocarbamoyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

[Step 1]

N- (1-naphthylmethyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

N (t-butoxycarbonyl) -L-glycine aldehyde was prepared in the same manner as in Reference Example 3 using Nt-butoxycarbonyl-L-glycine, and then 1-nap instead of 2,3-dichlorobenzylamine. The title compound was prepared in the same manner as in Reference Example 4 using methylmethylamine.

TLC: R _f = 0.15 (dichloromethane / methanol = 5/1)

¹ H-NMR (CDCl ₃ ): δ 8.10 (d, 3H), 7.65-7.95 (m, 2H), 7.40-7.43 (m, 5H), 7.08 (d, 2H), 6.95 (s, 1H), 6.23 (b, 1H), 5.18 (s, 2H), 4.23 (s, 2H), 3.20-3.30 (m, 4H), 2.80 (t, 2H), 1.97-2.20 (b, 1H)

[Step 2]

N- (1-naphthylmethyl) -N- (3-bromophenylthiocarbamoyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

N- (1-naphthylmethyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine diluted with dichloromethane (0.02M, 1ml, 0.02 mmol) and 3-bromophenyl isothiocyanate diluted with dichloromethane (0.1 M, 0.2 ml, 0.02 mmol) were reacted at room temperature for 3 hours, and then the reaction solution was subjected to a short silica gel column chromatography (dichloromethane / Methanol = 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 17H), 6.48 (bs, 1H), 5.50 (s, 2H), 5.25 (s, 2H), 3.80 (t, 2H), 3.32 (s , 2H), 3.00 (t, 2H)

Example 465-469

N- (1-naphthylmethyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine with the corresponding isothiocyanate The title compound was prepared in the same manner as Step 2 of Example 464.

Example 465

N- (1-naphthylmethyl) -N- (4-chlorophenylthiocarbamoyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.18 (m, 17H), 6.60 (bs, 1H), 5.45 (s, 2H), 5.23 (s, 2H), 3.82 (t, 2H), 3.35 (s , 2H), 3.02 (t, 2H)

Example 466

N- (1-naphthylmethyl) -N- (3-fluorophenylthiocarbamoyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 6.85-8.40 (m, 17H), 6.58 (bs, 1H), 5.48 (s, 2H), 5.25 (s, 2H), 3.80 (t, 2H), 3.35 (s , 2H), 3.02 (t, 2H)

Example 467

N- (1-naphthylmethyl) -N- (4-fluorophenylthiocarbamoyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.15 (m, 17H), 6.64 (bs, 1H), 5.42 (s, 2H), 5.24 (s, 2H), 3.85 (t, 2H), 3.34 (s , 2H), 3.10 (t, 2H)

Example 468

N- (1-naphthylmethyl) -N- (4-methoxyphenylthiocarbamoyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 6.85-8.18 (m, 17H), 5.40 (s, 2H), 5.28 (s, 2H), 4.00 (t, 2H), 3.78 (s, 3H), 3.38 (s , 2H), 3.12 (t, 2H)

Example 469

N- (1-naphthylmethyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} aminoethyl Amine

¹ H-NMR (CDCl ₃ ): δ 6.92-8.15 (m, 17H), 6.42 (bs, 1H), 5.55 (s, 2H), 5.28 (s, 2H), 3.75 (s, 2H), 2.98 (t , 2H)

Example 470

N- (1-naphthylmethyl) -N- (3-bromophenylthiocarbamoyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-2 -Methylpropylamine

[Step 1]

2- (t-butoxycarbonyl) amino-2-methylpropionic acid

2-amino-2-methylpropionic acid (15 g, 146 mmol) was dissolved in dioxane (290 ml) and distilled water (145 ml) and 1N-sodium hydroxide aqueous solution (146 ml) was added on an ice-water bath. Di-t-butyl pyrocarbonate (36.76 ml, 160 mmol) was added dropwise to the reaction mixture, which was stirred for 30 minutes at room temperature. The reaction solution was concentrated under reduced pressure to 200 ml, and a small amount of ethyl acetate (30 ml) was added thereto, followed by acidification (pH 2-3) with a dilute aqueous solution of potassium bisulfate. The organic layer was washed with saturated sodium bicarbonate and saturated brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to give the title compound (25.1 g, 85%) as a white solid.

¹ H-NMR (CDCl ₃ ): δ 9.40-10.60 (bs, 1H), 5.00-5.40 (bs, 1H), 1.58 (s, 6H), 1.43 (s, 9H)

[Step 2]

2- (t-butoxycarbonyl) amino-2-methylpropanol

2- (t-butoxycarbonyl) amino-2-methylpropionic acid (9.54 g, 47 mmol) was dissolved in anhydrous tetrahydrofuran solvent (250 ml) and triethylamine (6.54 ml 47 mmol) was added. The reaction temperature was maintained at 5 ° C. and ethylchloroformate (5.38 ml, 56 mmol) was slowly added dropwise. After stirring at 5 ° C. for 30 minutes, the precipitate was filtered and a solution of sodium borohydride (3.55 g, 94 mmol) in distilled water (50 ml) in the filtrate was slowly added dropwise while maintaining it at 0 ° C. After completion of the dropwise addition, the reaction mixture was stirred at room temperature for 1 hour and concentrated under reduced pressure. The residue was dissolved in 2N aqueous hydrochloric acid solution (100 ml), ethyl acetate extracted, the organic layer was washed with distilled water, saturated sodium bicarbonate and saturated brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (n-hexane / ethyl acetate = 2/1, v / v) to give the title compound (7.10 g, 80%) as a white solid.

TLC: R _f = 0.038 (ethyl acetate n-hexane = 1/2)

¹ H-NMR (CDCl ₃ ): δ 4.60-4.80 (b, 1H), 3.58 (s, 2H), 1.43 (s, 9H), 1.25 (s, 6H)

[Step 3]

2- (t-butoxycarbonyl) amino-2-methylpropion aldehyde

Oxalylchloride (4.39 ml, 50.3 mmol) was dissolved in dichloromethane (90 ml) and cooled to -60 ° C to 70 ° C, and then dimethylsulfoxide (7.14 ml, 101 mmol) of dichloromethane (20 ml) diluted solution was -60 ° C. It was slowly added dropwise for 5 minutes while maintaining at ~ 70 ℃. After completion of the dropwise addition, the mixture was stirred for 30 minutes at this temperature, and 2- (t-butoxycarbonyl) amino-2-methylpropanol (8.65 g, 457 mmol) of dichloromethane (40 ml) was diluted slowly. The reaction mixture was kept at -60 ° C, stirred for 1 hour and triethylamine (31.85 ml, 229 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 1 hour, dichloromethane (100 ml) was added, and the organic layer was washed with 5% aqueous hydrochloric acid solution and saturated aqueous sodium hydrogen carbonate solution. The organic layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography (n-hexane / ethyl acetate = 2/1, v / v) to obtain the title compound (7.96 g, 93%) as a white solid.

¹ H-NMR (CDCl ₃ ): δ 9.44 (s, 1H), 5.03 (b, 1H), 1.44 (s, 9H), 1.33 (s, 6H)

[Step 4]

N- (1-naphthylmethyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methylpropylamine

2 (t-butoxycarbonyl) amino-2-methylpropionaldehyde and 1-naphthylmethylamine instead of N- (t-butoxycarbonyl) -L-isorucin aldehyde and 2,3-dichlorobenzylamine To prepare the title compound in the same manner as in Reference Example 4.

TLC: R _f = 0.31 (dichloromethane / methanol = 9/1)

¹ H-NMR (CDCl ₃ ): δ 7.92-8.20 (dd, 3H), 7.62-7.90 (m, 2H), 7.25-7.60 (m, 5H), 7.03 (d, 2H), 6.82 (s, 1H) , 6.23 (s, 1H), 5.20 (s, 2H), 4.20 (s, 2H), 3.02 (s, 2H), 2.62 (s, 2H), 2.18 (b, 1H), 1.23 (s, 6H)

[Step 5]

N- (1-naphthylmethyl) -N- (3-bromophenylthiocarbamoyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-2 -Methylpropylamine

A solution of N- (1-naphthylmethyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methylpropylamine diluted with dichloromethane (0.02 M, 1 ml, 0.02 mmol) and 3-bromophenyl isothiocyanate diluted with dichloromethane (0.1 M, 0.2 ml, 0.02 mmol) were reacted at room temperature for 4 hours, and then the reaction solution was subjected to a short silica gel column chromatography. Purification with (dichloromethane / methanol = 9/1, v / v) gave the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 17H), 5.45 (s, 2H), 5.34 (s, 2H), 4.14 (s, 2H), 3.22 (s, 2H), 1.45 (s , 6H)

Example 471-475

Using isothiocyanate corresponding to N- (1-naphthylmethyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methylpropylamine The title compound was prepared in the same manner as in Step 2 of Example 470.

Example 471

N- (1-naphthylmethyl) -N- (4-chlorophenylthiocarbamoyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-2- Methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.18 (m, 17H), 5.48 (s, 2H), 5.32 (s, 2H), 4.15 (s, 2H), 3.22 (s, 2H), 1.45 (s , 6H)

Example 472

N- (1-naphthylmethyl) -N- (2-fluorophenylthiocarbamoyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-2 -Methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 17H), 5.45 (s, 2H), 5.35 (s, 2H), 4.20 (s, 2H), 3.22 (s, 2H), 1.48 (s , 6H)

Example 473

N- (1-naphthylmethyl) -N- (3-fluorophenylthiocarbamoyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-2 -Methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-8.20 (m, 17H), 5.50 (s, 2H), 5.35 (s, 2H), 4.18 (s, 2H), 3.22 (s, 2H), 1.48 (s , 6H)

Example 474

N- (1-naphthylmethyl) -N- (4-fluorophenylthiocarbamoyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-2 -Methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 17H), 5.48 (s, 2H), 5.38 (s, 2H), 4.20 (s, 2H), 3.22 (s, 2H), 1.52 (s , 6H)

Example 475

N- (1-naphthylmethyl) -N- (4-methoxyphenylthiocarbamoyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-2 -Methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 6.80-8.20 (m, 17H), 5.42 (s, 2H), 5.40 (s, 2H), 4.20 (bs, 2H), 3.78 (s, 3H), 3.22 (s , 2H), 1.50 (s, 6H)

Example 476

N- (1-naphthylmethyl) -N-benzylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} aminopentylamine

[Step 1]

N- (1-naphthylmethyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} aminopentylamine

Nt-butoxycarbonyl-L-norvaline aldehyde was prepared in the same manner as in Reference Example 3 using Nt-butoxycarbonyl-L-norvaline, and then 1-naphthyl instead of 2,3-dichlorobenzylamine The title compound was prepared in the same manner as in Reference Example 4 using methylamine.

TLC: R _f = 0.39 (dichloromethane / methanol = 10/1)

¹ H-NMR (CDCl ₃ ): δ 8.14 (m, 3H), 7.70-8.00 (m, 2H), 7.37-7.62 (m, 5H), 7.03 (d, 2H), 6.92 (s, 1H), 5.81 (d, 1H), 5.10 (dd, 2H), 4.20 (s, 2H), 3.90-4.10 (m, 1H), 3.17 (dd, 2H), 2.72 (m, 2H), 1.82 (s, 1H), 1.30-1.50 (m, 4H), 0.80-1.00 (m, 3H)

[Step 2]

N- (1-naphthylmethyl) -N-benzylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} aminopentylamine

N- (1-naphthylmethyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} aminopentylamine diluted with dichloromethane (0.02M , 1 ml, 0.02 mmol) and a solution of benzyl isothiocyanate diluted with dichloromethane (0.1 M, 0.2 ml, 0.02 mmol) were reacted at room temperature for 2 hours, and then the reaction solution was subjected to a short silica gel column chromatography (dichloromethane / methanol). = 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 18H), 5.35 (d, 2H), 5.20 (m, 1H), 5.02 (m, 2H), 4.82 (d, 2H), 4.24 (m , 1H), 3.25 (s, 2H), 3.12 (dd, 1H), 1.40 (m, 4H), 0.85 (t, 3H)

Example 477-487

N- (1-naphthylmethyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} aminopentylamine with the corresponding isothiocyanate The title compound was prepared in the same manner as Step 2 of Example 476.

Example 477

N- (1-naphthylmethyl) -N- (2-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Aminopentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.18 (m, 17H), 5.50 (d, 2H), 5.35 (s, 2H), 5.18 (m, 2H), 4.40 (m, 1H), 3.40 (s , 2H), 3.22 (dd, 1H), 1.44 (m, 4H), 0.85 (t, 3H)

Example 478

N- (1-naphthylmethyl) -N- (3-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Aminopentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.20 (m, 17H), 5.60 (d, 1H), 5.32 (s, 2H), 5.08 (d, 1H), 4.82 (bs, 1H), 4.25 (m , 1H), 3.38 (s, 2H), 3.16 (dd, 1H), 1.42 (m, 4H), 0.85 (t, 3H)

Example 479

N- (1-naphthylmethyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} aminophen Tilamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.20 (m, 17H), 5.34 (d, 2H), 5.05-5.60 (dd, 2H), 4.90 (bs, 1H), 4.25 (m, 1H), 3.38 (s, 2H), 3.20 (dd, 1H), 1.40 (m, 4H), 0.84 (t, 3H)

Example 480

N- (1-naphthylmethyl) -N-ethylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} aminopentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.20 (m, 13H), 5.40 (d, 2H), 4.90-5.30 (m, 3H), 4.20 (m, 1H), 3.58 (m, 2H), 3.35 (s, 2H), 3.05 (dd, 1H), 1.40 (m, 4H), 1.05 (t, 3H), 0.84 (t, 3H)

Example 481

N- (1-naphthylmethyl) -N- (2-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Aminopentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.18 (m, 17H), 5.32 (s, 2H), 5.00-5.52 (m, 3H), 4.35 (bs, 1H), 3.40 (s, 2H), 3.20 (dd, 1H), 1.42 (m, 4H), 0.86 (t, 3H)

Example 482

N- (1-naphthylmethyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Aminopentylamine

¹ H-NMR (CDCl ₃ ): δ 6.85-8.20 (m, 17H), 5.58 (d, 2H), 5.35 (s, 2H), 5.10 (d, 1H), 4.90 (bs, 1H), 4.25 (m , 1H), 3.38 (s, 2H), 3.18 (dd, 1H), 1.42 (m, 4H), 0.85 (t, 3H)

Example 483

N- (1-naphthylmethyl) -N- (4-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Aminopentylamine

¹ H-NMR (CDCl ₃ ): δ 6.98-8.20 (m, 17H), 5.35 (s, 2H), 5.02-5.58 (m, 2H), 4.95 (bs, 1H), 4.25 (bs, 1H), 3.35 (s, 2H), 3.20 (dd, 1H), 1.42 (m, 4H), 0.85 (t, 3H)

Example 484

N- (1-naphthylmethyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Aminopentylamine

¹ H-NMR (CDCl ₃ ): δ 6.80-8.20 (m, 17H), 5.45 (m, 1H), 5.38 (d, 2H), 5.10 (d, 2H), 4.30 (bs, 1H), 3.38 (s , 2H), 3.18 (dd, 1H), 1.40 (m, 4H), 0.85 (t, 3H)

Example 485

N- (1-naphthylmethyl) -N-methylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} aminopentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 13H), 5.40 (d, 2H), 4.90-5.30 (m, 3H), 4.20 (bs, 1H), 3.35 (s, 2H), 3.10 (dd, 1H), 3.07 (d, 3H), 1.40 (m, 4H), 0.85 (t, 3H)

Example 486

N- (1-naphthylmethyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl } Aminopentylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-8.18 (m, 17H), 5.72 (d, 1H), 5.30 (s, 2H), 5.10 (d, 1H), 4.75 (bs, 1H), 4.22 (bs , 1H), 3.38 (s, 2H), 3.16 (dd, 1H), 1.30-1.50 (m, 4H), 0.88 (t, 3H)

Example 487

N- (1-naphthylmethyl) -N-allylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} aminopentylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-8.20 (m, 13H), 5.78 (m, 1H), 5.40 (d, 2H), 4.90-5.30 (m, 5H), 4.22 (m, 3H), 3.35 (s, 2H), 3.10 (dd, 1H), 1.30-1.50 (m, 4H), 0.88 (t, 3H)

Example 488

N- (1-naphthylmethyl) -N- (2-bromophenylthiocarbamoyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-2 Cyclohexylethylamine

[Step 1]

N- (1-naphthylmethyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-cyclohexylethylamine

N- (t-butoxycarbonyl) -2-amino-2-cyclohexylacetaldehyde was prepared in the same manner as in Reference Example 3 using Nt-butoxycarbonyl-2-amino-2-cyclohexyl acetic acid. Then, the title compound was prepared in the same manner as in Reference Example 4 using 1-naphthylmethylamine instead of 2,3-dichlorobenzylamine.

[Step 2]

N- (1-naphthylmethyl) -N- (2-bromophenylthiocarbamoyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-2 Cyclohexylethylamine

A solution of N- (1-naphthylmethyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-cyclohexylethylamine diluted with dichloromethane ( 0.02M, 1ml, 0.02mmol) and 2-bromophenyl isothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) were reacted at room temperature for 2 hours, and then the reaction solution was subjected to a short silica gel column chromatography. Purification by chromatography (dichloromethane / methanol = 9/1, v / v) gave the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 6.95-8.15 (m, 17H), 5.54 (s, 2H), 5.22 (s, 2H), 4.26 (bs, 2H), 3.15 (s, 2H), 2.40 (bs , 2H), 1.20-1.75 (bs, 8H)

Examples 489-491

N- (1-naphthylmethyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-cyclohexylethylamine and the corresponding isothiocyanate To prepare the title compound in the same manner as in Step 2 of Example 488.

Example 489

N- (1-naphthylmethyl) -N- (4-fluorophenylthiocarbamoyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-2 Cyclohexylethylamine

¹ H-NMR (CDCl ₃ ): δ 6.95-8.18 (m, 17H), 5.60 (bs, 2H), 5.20 (s, 2H), 4.12 (bs, 2H), 3.18 (s, 2H), 2.28 (bs , 2H), 1.20-1.75 (bs, 8H)

Example 490

N- (1-naphthylmethyl) -N- (4-methoxyphenylthiocarbamoyl) -2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-2 Cyclohexylethylamine

¹ H-NMR (CDCl ₃ ): δ 6.80-8.15 (m, 17H), 5.58 (bs, 2H), 5.20 (s, 2H), 4.18 (bs, 2H), 3.18 (s, 2H), 2.32 (bs , 2H), 1.40-1.85 (bs, 8H)

Example 491

N- (1-naphthylmethyl) -N-methylthiocarbamoyl-2-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-cyclohexylethylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-8.20 (m, 13H), 5.42 (s, 2H), 5.38 (s, 2H), 4.10 (bs, 2H), 3.20 (s, 2H), 3.02 (s , 3H), 2.30 (bs, 2H), 1.40-2.00 (bs, 8H)

Example 492

N-benzyl-N-benzylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

[Step 1]

N-benzyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

N (t-butoxycarbonyl) -L-isorucin aldehyde was prepared in the same manner as in Reference Example 3 using Nt-butoxycarbonyl-L-isoleucine, and then 2,3-dichlorobenzylamine was used instead. The title compound was prepared in the same manner as in Reference Example 4 using benzylamine.

TLC: R _f = 0.20 (dichloromethane / methanol = 9/1)

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 11H), 6.08 (d, 1H), 5.06 (dd, 2H), 3.90 (m, 1H), 3.76 (dd, 2H), 3.38 (dd , 2H), 2.78 (m, 3H), 1.48 (m, 1H), 1.26 (m, 1H), 1.04 (m, 1H), 0.85 (m, 6H)

[Step 2]

N-benzyl-N-benzylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

N-benzyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine diluted with dichloromethane ( 0.02M, 1ml, 0.02mmol) and a solution of benzyl isothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) were reacted for 3 hours at room temperature, and then the reaction solution was subjected to short silica gel column chromatography (dichloromethane / Methanol = 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 16H), 5.80 (t, 1H), 5.20-5.40 (m, 3H), 4.78 (t, 2H), 4.55 (s, 2H), 4.15 (m, 1H), 3.25 (s, 2H), 3.18 (dd, 2H), 1.62 (m, 1H), 1.45 (m, 1H), 1.05 (m, 1H), 0.90 (t, 6H)

Example 493-508

Using isothiocyanate corresponding to N-benzyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine In the same manner as in Step 2 of Example 492, the title compound was prepared.

Example 493

N-benzyl-N- (2-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.20 (m, 15H), 5.30 (m, 3H), 4.65-4.92 (dd, 2H), 4.25 (m, 1H), 3.38 (s, 2H), 3.22 (dd, 2H), 1.65 (m, 1H), 1.45 (m, 1H), 1.05 (m, 1H), 0.90 (t, 6H)

Example 494

N-benzyl-N- (3-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 15H), 5.35 (d, 2H), 4.95-5.22 (m, 2H), 4.60 (d, 1H), 4.20 (m, 1H), 3.35 (s, 2H), 3.20 (dd, 2H), 1.64 (m, 1H), 1.45 (m, 1H), 1.05 (m, 1H), 0.90 (m, 6H)

Example 495

N-benzyl-N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S)- Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.18 (m, 15H), 5.34 (d, 2H), 5.20 (m, 1H), 4.60-4.95 (dd, 2H), 4.18 (m, 1H), 3.34 (s, 2H), 3.22 (dd, 2H), 1.65 (m, 1H), 1.45 (m, 1H), 1.08 (m, 1H), 0.92 (m, 6H)

Example 496

N-benzyl-N-ethylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-8.20 (m, 11H), 5.40 (d, 2H), 5.20 (m, 1H), 4.52 (s, 2H), 4.10 (m, 1H), 3.58 (m , 2H), 3.32 (s, 2H), 3.10 (dd, 2H), 1.65 (m, 1H), 1.42 (m, 1H), 1.08 (m, 1H), 1.05 (t, 3H), 0.95 (m, 6H)

Example 497

N-benzyl-N- (2-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.20 (m, 15H), 5.35 (d, 2H), 5.20 (m, 1H), 4.62-4.95 (dd, 2H), 4.22 (m, 1H), 3.35 (s, 2H), 3.20 (dd, 2H), 1.62 (m, 1H), 1.45 (m, 1H), 1.10 (m, 1H), 0.90 (t, 6H)

Example 498

N-benzyl-N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.85-8.18 (m, 15H), 5.38 (d, 2H), 5.17 (m, 1H), 4.58-4.98 (dd, 2H), 4.20 (m, 1H), 3.34 (s, 2H), 3.22 (dd, 2H), 1.60 (m, 1H), 1.43 (m, 1H), 1.08 (m, 1H), 0.90 (m, 6H)

Example 499

N-benzyl-N- (4-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.95-8.20 (m, 15H), 5.35 (d, 2H), 5.20 (t, 1H), 4.60-4.95 (dd, 2H), 4.20 (m, 1H), 3.35 (s, 2H), 3.20 (dd, 2H), 1.60 (m, 1H), 1.44 (m, 1H), 1.06 (m, 1H), 0.92 (m, 6H)

Example 500

N-benzyl-N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.84-8.20 (m, 15H), 5.36 (d, 2H), 5.22 (m, 1H), 4.60-4.88 (dd, 2H), 4.18 (m, 1H), 3.80 (s, 3H), 3.38 (s, 2H), 3.20 (dd, 2H), 1.62 (m, 1H), 1.45 (m, 1H), 1.06 (m, 1H), 0.92 (t, 6H)

Example 501

N-benzyl-N-methylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 11H), 5.72 (t, 1H), 5.40 (d, 2H), 5.18 (t, 1H), 4.52 (d, 2H), 4.15 (m , 1H), 3.32 (s, 2H), 3.12 (dd, 1H), 3.08 (d, 3H), 1.62 (m, 1H), 1.44 (m, 1H), 1.04 (m, 1H), 0.95 (t, 6H)

Example 502

N-benzyl-N- (3-trifluoromethylphenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S ) -Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-8.18 (m, 15H), 5.35 (d, 2H), 5.08 (m, 1H), 4.60-5.12 (dd, 2H), 4.20 (m, 1H), 3.35 (s, 2H), 3.24 (dd, 1H), 1.65 (m, 1H), 1.45 (m, 1H), 1.02 (m, 1H), 0.95 (m, 6H)

Example 503

N-benzyl-N-allylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 11H), 5.60 (m, 1H), 5.05-5.42 (m, 2H), 4.95 (m, 1H), 4.52 (s, 2H), 4.18 (m, 2H), 3.27 (s, 2H), 3.08 (dd, 1H), 1.38-1.65 (m, 2H), 1.05 (m, 1H), 0.82 (m, 6H)

Example 504

N-benzyl-N- (1-naphthylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S)- Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.15 (m, 18H), 5.28 (m, 4H), 4.85 (q, 1H), 4.24 (m, 1H), 3.35 (s, 2H), 3.10 (dd , 1H), 1.35-1.60 (m, 2H), 1.05 (m, 1H), 0.88 (m, 6H)

Example 505

N-benzyl-N- (2-phenylethylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S)- Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-8.20 (m, 16H), 5.04-5.55 (m, 5H), 4.38 (s, 2H), 4.12 (m, 1H), 3.90 (m, 1H), 3.72 (m, 1H), 3.25 (s, 2H), 3.04 (dd, 1H), 2.72 (t, 2H), 1.38-1.62 (m, 2H), 1.02 (m, 1H), 0.84 (m, 6H)

Example 506

N-benzyl-N- (n-butylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methyl Pentylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-8.20 (m, 11H), 5.18-5.52 (m, 5H), 4.46 (s, 2H), 4.08 (m, 1H), 3.62 (m, 1H), 3.42 (m, 1H), 3.35 (s, 2H), 3.10 (dd, 1H), 1.38-1.62 (m, 2H), 1.35 (m, 2H), 1.05 (m, 2H), 0.90 (m, 6H), 0.82 (t, 3 H)

Example 507

N-benzyl-N-cyclohexylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.22 (m, 11H), 4.85-5.10 (m, 3H), 4.50 (s, 2H), 4.10 (m, 2H), 3.18 (s, 2H), 3.12 (dd, 1H), 0.92-1.73 (m, 13H), 0.85 (m, 6H)

Example 508

N-benzyl-N-phenylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.18-8.22 (m, 16H), 5.20-5.48 (m, 3H), 4.80 (q, 2H), 4.20 (m, 2H), 3.38 (s, 2H), 3.25 (dd, 1H), 0.35-0.60 (m, 2H), 1.03 (m, 1H), 0.92 (m, 6H)

Example 509

N- (thiophen-2-ylmethyl) -N-benzylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 ( S) -methylpentylamine

[Step 1]

N- (thiophen-2-ylmethyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

N- (t-butoxycarbonyl) -L-isorucin aldehyde was prepared in the same manner as in Reference Example 3 using Nt-butoxycarbonyl-L-isoleucine, and then 2,3-dichlorobenzylamine Instead, the title compound was prepared in the same manner as in Reference Example 4 using thiophen-2-ylmethylamine.

TLC: R _f = 0.20 (dichloromethane / methanol = 10/1)

¹ H-NMR (CDCl ₃ ): δ 8.20 (d, 2H), 7.59 (s, 1H), 7.15-7.40 (m, 3H), 7.08 (s, 1H), 6.84-7.00 (m, 2H), 5.70 -6.03 (m, 1H), 5.34 (s, 2H), 3.80-4.15 (m, 3H), 3.38 (s, 2H), 2.60-2.80 (m, 2H), 1.82 (bs, 1H), 1.22-1.65 (m, 2H), 0.97-1.22 (m, 1H), 0.75-0.95 (m, 6H)

[Step 2]

N- (thiophen-2-ylmethyl) -N-benzylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 ( S) -methylpentylamine

N- (thiophen-2-ylmethyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine A solution diluted with dichloromethane (0.02M, 1ml, 0.02mmol) and a solution of benzyl isothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) were reacted at room temperature for 4 hours, and then the reaction solution was shortened. Purification by silica gel column chromatography (dichloromethane / methanol = 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 6.84-8.20 (m, 14H), 6.18-6.35 (tt, 1H), 5.35 (d, 2H), 5.00 (m, 1H), 4.60-4.82 (m, 4H) , 4.18 (m, 1H), 3.25 (s, 2H), 3.20 (dd, 1H), 1.38-1.62 (m, 2H), 1.05 (m, 1H), 0.95 (d, 6H)

Example 510-520

N- (thiophen-2-ylmethyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine The title compound was prepared in the same manner as in Step 2 of Example 509, using the corresponding isothiocyanate.

Example 510

N- (thiophen-2-ylmethyl) -N- (2-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.18 (m, 13H), 5.35 (d, 2H), 5.02-5.20 (m, 2H), 4.80 (d, 1H), 4.32 (m, 1H), 3.38 (s, 2H), 3.32 (dd, 1H), 1.40-1.62 (m, 2H), 1.10 (m, 1H), 0.97 (d, 6H)

Example 511

N- (thiophen-2-ylmethyl) -N- (3-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.05-8.18 (m, 13H), 6.58,6.82 (dd, 1H), 5.35 (s, 2H), 4.63-4.88 (m, 3H), 4.18 (m, 1H) , 3.36 (s, 2H), 3.25 (dd, 1H), 1.35-1.60 (m, 2H), 1.12 (m, 1H), 0.98 (m, 6H)

Example 512

N- (thiophen-2-ylmethyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-8.20 (m, 13H), 5.18-5.42 (m, 3H), 4.75 (m, 2H), 4.20 (m, 1H), 3.38 (s, 2H), 3.28 (dd, 1H), 1.35-1.60 (m, 2H), 1.10 (m, 1H), 0.98 (m, 6H)

Example 513

N- (thiophen-2-ylmethyl) -N-ethylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 ( S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-8.22 (m, 9H), 5.86-6.05 (tt, 1H), 5.40 (m, 2H), 4.58-5.00 (m, 3H), 4.16 (m, 1H) , 3.65 (m, 2H), 3.34 (s, 2H), 3.20 (dd, 1H), 1.42-1.65 (m, 2H), 1.16 (m, 3H), 1.14 (m, 1H), 0.97 (m, 6H )

Example 514

N- (thiophen-2-ylmethyl) -N- (2-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-8.20 (m, 13H), 5.36 (d, 2H), 5.00-5.22 (m, 2H), 4.80 (d, 1H), 4.28 (m, 1H), 3.40 (s, 2H), 3.32 (dd, 1H), 1.35-1.64 (m, 2H), 1.14 (m, 1H), 0.97 (d, 6H)

Example 515

N- (thiophen-2-ylmethyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 13H), 5.35 (d, 2H), 4.84-5.22 (m, 2H), 4.70 (d, 1H), 4.20 (m, 1H), 3.38 (s, 2H), 3.26 (dd, 1H), 1.32-1.65 (m, 2H), 1.12 (m, 1H), 0.98 (m, 6H)

Example 516

N- (thiophen-2-ylmethyl) -N- (4-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-8.20 (m, 13H), 5.36 (m, 2H), 4.90-5.22 (m, 2H), 4.72 (d, 1H), 4.20 (m, 1H), 3.38 (s, 2H), 3.24 (dd, 1H), 1.32-1.65 (m, 2H), 1.12 (m, 1H), 0.98 (m, 6H)

Example 517

N- (thiophen-2-ylmethyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.85-8.20 (m, 13H), 5.38 (m, 2H), 4.85-5.25 (m, 2H), 4.75 (d, 1H), 4.20 (m, 1H), 3.80 (s, 3H), 3.38 (s, 2H), 3.26 (dd, 1H), 1.40-1.65 (m, 2H), 1.15 (m, 1H), 0.98 (d, 6H)

Example 518

N- (thiophen-2-ylmethyl) -N-methylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 ( S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-8.20 (m, 9H), 6.06-6.30 (tt, 1H), 5.40 (m, 2H), 4.85 (m, 2H), 4.58 (dd, 1H), 4.10 (m, 1H), 3.32 (s, 2H), 3.22 (dd, 1H), 3.08 (d, 3H), 1.38-1.65 (m, 2H), 1.12 (m, 1H), 0.94 (d, 6H)

Example 519

N- (thiophen-2-ylmethyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-8.18 (m, 13H), 5.20-5.58 (m, 3H), 4.70 (d, 2H), 4.18 (m, 1H), 3.38 (s, 2H), 3.28 (d, 1H), 1.35-1.60 (m, 2H), 1.10 (m, 1H), 0.96 (m, 6H)

Example 520

N- (thiophen-2-ylmethyl) -N-allylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 ( S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.85-8.22 (m, 9H), 5.88-6.15 (tt, 1H), 5.38 (d, 2H), 4.85-5.10 (m, 2H), 4.62 (t, 1H) , 4.20 (m, 2H), 3.35 (s, 2H), 3.22 (dd, 1H), 1.35-1.60 (m, 2H), 1.10 (m, 1H), 0.95 (d, 6H)

Example 521

N- [2- (thiophen-2-yl) ethyl] -N-benzylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

[Step 1]

N- [2- (thiophen-2-yl) ethyl] -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S)- Methylpentylamine

N- (t-butoxycarbonyl) -L-isorucin aldehyde was prepared in the same manner as in Reference Example 3 using Nt-butoxycarbonyl-L-isoleucine, and then 2,3-dichlorobenzylamine Instead, the title compound was prepared in the same manner as in Reference Example 4 using 2- (thiophen-2-yl) ethylamine.

TLC: R _f = 0.20 (dichloromethane / methanol = 10/1)

¹ H-NMR (CDCl ₃ ): δ 8.20 (d, 2H), 7.59 (s, 1H), 7.15-7.40 (m, 3H), 7.08 (s, 1H), 6.84-7.00 (m, 2H), 5.70 -6.03 (m, 1H), 5.34 (s, 2H), 3.80-4.15 (m, 3H), 3.38 (s, 2H), 2.60-2.80 (m, 2H), 1.82 (bs, 1H), 1.22-1.65 (m, 2H), 0.97-1.22 (m, 1H), 0.75-0.95 (m, 6H)

[Step 2]

N- [2- (thiophen-2-yl) ethyl] -N-benzylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

N- [2- (thiophen-2-yl) ethyl] -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S)- After diluting methylpentylamine with dichloromethane (0.02M, 1ml, 0.02mmol) and benzyl isothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) at room temperature for 4 hours, The reaction solution was purified by short silica gel column chromatography (dichloromethane / methanol = 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 6.75-8.20 (m, 14H), 5.25 (d, 2H), 4.95 (bs, 1H), 4.20 (m, 1H), 4.05 (m, 1H), 3.64 (bs , 1H), 3.25-3.34 (bs, 4H), 3.20 (dd, 1H), 1.30-1.70 (m, 2H), 1.10 (m, 1H), 0.90 (m, 6H)

Example 522-525

N- [2- (thiophen-2-yl) ethyl] -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S)- The title compound was prepared in the same manner as in Step 2 of Example 521, using methylpentylamine and the corresponding isothiocyanate.

Example 522

N- [2- (thiophen-2-yl) ethyl] -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazole-5 -Yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.85-8.15 (m, 13H), 5.30 (dd, 2H), 4.86 (bs, 1H), 4.16 (m, 1H), 3.95 (bs, 1H), 3.60 (m , 1H), 3.28 (s, 2H), 3.18 (m, 2H), 3.05 (dd, 1H), 1.30-1.70 (m, 2H), 1.10 (m, 1H), 0.90 (m, 6H)

Example 523

N- [2- (thiophen-2-yl) ethyl] -N-ethylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.80-8.20 (m, 9H), 5.40 (m, 2H), 4.95 (bs, 1H), 4.08 (m, 1H), 3.35-3.80 (m, 4H), 3.26 (s, 2H), 2.98 (m, 2H), 2.86 (dd, 1H), 1.30-1.70 (m, 2H), 1.10 (m, 1H), 0.90 (m, 6H)

Example 524

N- [2- (thiophen-2-yl) ethyl] -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazole- 5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.85-8.10 (m, 13H), 5.30 (d, 2H), 5.22 (bs, 1H), 4.80 (bs, 1H), 4.18 (m, 2H), 4.02 (m , 1H), 3.55 (m, 1H), 3.30 (s, 2H), 3.18 (m, 2H), 3.05 (dd, 1H), 1.30-1.70 (m, 2H), 1.05 (m, 1H), 0.92 ( m, 6H)

Example 525

N- [2- (thiophen-2-yl) ethyl] -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazole- 5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.85-8.20 (m, 13H), 5.35 (m, 2H), 5.00 (bs, 1H), 4.15 (m, 1H), 3.95 (m, 1H), 3.65 (m , 1H), 3.28 (s, 2H), 3.18 (m, 2H), 3.02 (dd, 1H), 1.30-1.70 (m, 2H), 1.05 (m, 1H), 0.92 (m, 6H)

Example 526

N- (2-trifluoromethylbenzyl) -N-benzylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

[Step 1]

N- (2-Trifluoromethylbenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

Nt-butoxycarbonyl-L-isorucin aldehyde was prepared in the same manner as in Reference Example 3 using Nt-butoxycarbonyl-L-isorucin, and then 2,3-dichlorobenzylamine and 1- ( Reference is made using 2-trifluoromethylbenzylamine and 1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride instead of 4-nitrobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride The title compound was prepared in the same manner as in Example 4.

TLC: R _f = 0.40 (dichloromethane / methanol = 10/1)

1 H-NMR (CDCl 3): δ 7.6 (m, 3H), 7.5 (m, 3H), 7.4 (m, 1H), 7.1 (d, 2H), 7.0 (s, 1H), 5.3 (s, 2H), 4.0 (m, 3H), 3.4 (s, 2H), 2.7 (m, 2H), 1.0-1.5 (m, 3H), 0.8-0.9 (m, 6H)

[Step 2]

N- (2-trifluoromethylbenzyl) -N-benzylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

N- (2-Trifluoromethylbenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine Reacted with dichloromethane (0.02M, 1ml, 0.02mmol) and benzyl isothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) at room temperature for 4 hours. Purification by short silica gel column chromatography (dichloromethane / methanol = 9/1, v / v) gave the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 7.00-7.68 (m, 15H), 5.28 (d, 2H), 4.62-5.18 (m, 5H), 4.12 (m, 1H), 3.24 (s, 2H), 3.05 (dd, 1H), 1.38-1.70 (bs, 2H), 1.06 (m, 1H), 0.88 (m, 6H)

Example 527-580

N-(-trifluoromethylbenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine The title compound was prepared in the same manner as in Step 2 of Example 526, using the corresponding isothiocyanate.

Example 527

N- (2-trifluoromethylbenzyl) -N- (2-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.75 (m, 14H), 5.25 (d, 2H), 4.98-5.35 (bs, 2H), 4.86 (d, 1H), 4.23 (m, 1H), 3.35 (d, 2H), 3.16 (dd, 1H), 1.35-1.65 (bs, 2H), 1.04 (m, 1H), 0.90 (m, 6H)

Example 528

N- (2-trifluoromethylbenzyl) -N- (3-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.88-7.70 (m, 14H), 5.52 (bs, 1H), 5.22 (s, 2H), 4.78 (dd, 2H), 4.15 (m, 1H), 3.35 (s , 2H), 3.10 (dd, 1H), 1.35-1.65 (bs, 2H), 1.04 (m, 1H), 0.92 (m, 6H)

Example 529

N- (2-trifluoromethylbenzyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.88-7.70 (m, 14H), 5.45 (bs, 1H), 5.25 (d, 2H), 4.80 (dd, 2H), 4.18 (m, 1H), 3.32 (s , 2H), 3.13 (dd, 1H), 1.30-1.68 (bs, 2H), 1.02 (m, 1H), 0.86 (m, 6H)

Example 530

N- (2-trifluoromethylbenzyl) -N-ethylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.95-7.78 (m, 10H), 5.45 (bs, 1H), 5.84-6.02 (bs, 1H), 5.36 (dd, 2H), 5.02 (bs, 1H), 4.64 -4.95 (dd, 2H), 4.08 (m, 1H), 3.60 (m, 2H), 3.35 (s, 2H), 3.04 (dd, 1H), 1.30-1.70 (bs, 2H), 1.03 (m, 2H) ), 0.85 (m, 6H)

Example 531

N- (2-trifluoromethylbenzyl) -N- (2-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.88-7.75 (m, 14H), 5.25 (d, 2H), 4.98-5.24 (bs, 2H), 4.64 (d, 1H), 4.20 (m, 1H), 3.35 (s, 2H), 3.12 (dd, 1H), 1.30-1.70 (bs, 2H), 1.05 (m, 1H), 0.85 (m, 6H)

Example 532

N- (2-trifluoromethylbenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.80-7.80 (m, 14H), 5.44 (bs, 1H), 5.24 (s, 2H), 4.83 (dd, 2H), 4.17 (m, 1H), 3.37 (s , 2H), 3.14 (dd, 1H), 1.30-1.70 (bs, 2H), 1.05 (m, 1H), 0.85 (m, 6H)

Example 533

N- (2-trifluoromethylbenzyl) -N- (4-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.75 (m, 14H), 5.38 (bs, 1H), 5.25 (m, 2H), 4.75-5.02 (bs, 2H), 4.15 (m, 1H), 3.35 (s, 2H), 3.12 (dd, 1H), 1.30-1.75 (bs, 2H), 1.05 (m, 1H), 0.90 (m, 6H)

Example 534

N- (2-trifluoromethylbenzyl) -N-methylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.85-7.75 (m, 10H), 6.25-6.44 (bs, 1H), 5.35 (d, 2H), 4.80-5.10 (bs, 2H), 4.63 (dd, 1H) , 4.08 (m, 1H), 3.32 (s, 2H), 3.08 (s, 3H), 3.00 (dd, 1H), 1.30-1.75 (bs, 2H), 1.05 (m, 1H), 0.88 (m, 6H )

Example 535

N- (2-trifluoromethylbenzyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-7.75 (m, 14H), 5.62 (bs, 1H), 5.25 (s, 2H), 4.78 (dd, 2H), 4.13 (m, 1H), 3.32 (s , 2H), 3.14 (dd, 1H), 1.30-1.75 (bs, 2H), 1.05 (m, 1H), 0.90 (m, 6H)

Example 536

N- (2-trifluoromethylbenzyl) -N-allylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.75 (m, 10H), 6.00-6.20 (bs, 1H), 5.78 (m, 1H), 5.35 (dd, 2H), 5.05 (d, 2H), 4.62 -4.95 (dd, 2H), 4.24 (m, 1H), 4.15 (m, 1H), 3.30 (s, 2H), 3.08 (dd, 1H), 1.30-1.70 (m, 2H), 1.05 (m, 1H) ), 0.86 (m, 6H)

Example 537

N- (2-trifluoromethylbenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.8 (d, 1H), 7.6 (d, 2H), 7.5 (m, 2H), 7.3 (m, 2H), 7.1 (s, 1H), 6.9 (d, 2H ), 5.3 (m, 2H), 4.9 (d, 2H), 4.2 (m, 1H), 3.8 (s, 2H), 3.4 (s, 2H), 3.2 (dd, 2H), 1.0-1.8 (m, 3H), 0.9 (m, 6H)

Example 538

N- (2-trifluoromethylbenzyl) -N- (tbutylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.78 (m, 10H), 5.32 (m, 3H), 4.68 (bs, 2H), 4.10 (m, 1H), 3.35 (s, 2H), 3.02 (dd , 1H), 1.30-1.70 (m, 2H), 1.05 (m, 1H), 0.88 (m, 6H)

Example 539

N- (2-trifluoromethylbenzyl) -N- (1-adamantylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.60-7.75 (m, 3H), 7.35-7.59 (m, 4H), 7.02-7.22 (m, 3H), 5.39 (m, 2H), 5.25 (s, 1H) , 5.12 (d, 1H), 4.70 (s, 2H), 4.10 (m, 1H), 3.35 (s, 2H) 2.95 (dd, 1H), 1.85-2.10 (m, 9H), 1.60 (m, 7H) , 1.10 (m, 2H), 0.90 (m, 6H)

Example 540

N- (2-trifluoromethylbenzyl) -N- (4-azidophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.60 (d, 4H), 7.45 (d, 1H), 7.25-7.39 (m, 3H), 6.90-7.18 (m, 6H), 5.20 -5.70 (m, 4H), 4.80 (m, 2H), 4.18 (m, 1H), 3.40 (s, 2H), 3.12 (dd, 1H), 1.65 (m, 1H), 1.00-1.50 (m, 2H ), 0.90 (t, 6H)

Example 541

N- (2-trifluoromethylbenzyl) -N- (2-biphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.50-7.65 (m, 5H), 7.20-7.40 (m, 9H), 7.15 (m, 3H), 7.05 (s, 1H), 6.85 (m, 1H), 6.00 (s, 1H), 5.25 (s, 2H), 4.65 (m, 2H), 4.10 (m, 1H), 3.38 (s, 2H), 3.00 (dd, 1H), 1.60 (m, 1H), 0.95- 1.45 (m, 2H), 0.85 (m, 6H)

Example 542

N- (2-trifluoromethylbenzyl) -N- (n-butylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.75 (s, 1H), 7.65 (d, 3H), 7.40-7.55 (m, 2H), 7.20 (d, 3H), 7.05 (s, 1H), 5.90-6.20 (m, 2H), 5.40 (m, 2H), 4.90-5.10 (m, 2H), 4.65 (m, 1H), 4.10 (m, 1H), 3.40-3.70 (m, 2H), 3.20 (s, 2H ), 3.05 (dd, 1H), 1.62 (m, 1H), 1.45 (m, 3H), 1.30 (m, 1H), 1.15 (m, 3H), 0.85 (m, 6H), 0.80 (m, 3H)

Example 543

N- (2-trifluoromethylbenzyl) -N-(-butylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.75 (s, 1H), 7.65 (d, 2H), 7.54 (s, 1H), 7.40-7.50 (m, 3H), 7.20 (d, 2H), 7.05 (s , 1H), 5.20-5.40 (m, 4H), 4.70 (m, 2H), 4.65 (m, 1H), 4.10 (m, 1H), 3.35 (s, 2H), 3.00 (dd, 1H), 1.40- 1.62 (m, 2H), 1.35 (s, 9H), 1.10 (m, 1H), 0.85 (m, 6H)

Example 544

N- (2-trifluoromethylbenzyl) -N- (2-chloroethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.70 (s, 1H), 7.65 (d, 2H), 7.54 (s, 1H), 7.25-7.52 (m, 3H), 7.20 (d, 2H), 7.05 (s , 1H), 5.38 (s, 2H), 4.70 (s, 2H), 4.00 (m, 3H), 3.40 (m, 1H), 3.35 (s, 2H), 2.95 (dd, 1H), 1.62 (m, 1H), 1.35 (m, 3H), 1.10 (m, 1H), 0.85 (m, 6H)

Example 545

N- (2-trifluoromethylbenzyl) -N- (3-chloro-4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.70 (d, 1H), 7.60 (m, 3H), 7.25-7.50 (m, 4H), 7.18 (m, 4H), 7.05 (s, 1H), 5.20-5.40 (m, 3H), 4.80 (m, 2H), 4.20 (m, 1H), 3.40 (s, 2H), 3.15 (dd, 1H), 2.30 (s, 3H), 1.65 (m, 1H), 1.10- 1.55 (m, 2H), 0.85 (m, 6H)

Example 546

N- (2-trifluoromethylbenzyl) -N-cyclohexylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.80 (s, 1H), 7.70 (s, 1H), 7.65 (d, 2H), 7.40-7.60 (m, 2H), 7.10-7.30 (m, 4H), 5.60 (m, 1H), 5.50 (s, 2H), 5.00 (m, 2H), 4.65 (m, 1H), 4.15 (m, 2H), 3.40 (s, 2H), 3.15 (dd, 1H), 1.80 ( m, 2H), 1.20-1.62 (m, 6H), 1.10 (s, 3H), 0.85 (m, 6H)

Example 547

N- (2-trifluoromethylbenzyl) -N- (2,4-dichlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.75 (d, 1H), 7.60 (d, 2H), 7.50 (m, 1H), 7.20-7.40 (m, 3H), 7.15 (d, 2H), 7.00 (s , 1H), 6.90 (d, 1H), 5.30 (s, 2H), 4.90 (m, 2H), 4.30 (m, 1H), 3.38 (s, 2H), 3.20 (dd, 1H), 1.64 (m, 1H), 1.10-1.40 (m, 2H), 0.85 (t, 6H)

Example 548

N- (2-trifluoromethylbenzyl) -N- (4-isopropylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (m, 2H), 7.60 (m, 3H), 7.30-7.50 (m, 3H), 7.00-7.20 (m, 6H), 5.70 (bs, 1H), 5.35 (m, 2H), 4.80 (m, 2H), 4.20 (m, 1H), 3.40 (s, 2H), 3.10 (dd, 1H), 2.90 (m, 1H), 1.65 (m, 1H), 1.40 ( m, 1H), 1.20 (d, 6H), 1.15 (m, 1H), 0.85 (t, 6H)

Example 549

N- (2-trifluoromethylbenzyl) -N- (3-methoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.75 (s, 1H), 7.70 (d, 2H), 7.45 (m, 2H), 7.25 (d, 2H), 7.10 (s, 2H), 6.90 (d, 1H ), 5.75 (bs, 1H), 5.45 (d, 2H), 5.10 (m, 1H), 4.70 (m, 2H), 4.10 (m, 1H), 3.70 (m, 2H), 3.50 (t, 1H) , 3.40 (s, 3H), 3.34 (m, 1H), 2.95 (dd, 1H), 2.80 (d, 2H), 1.80 (m, 2H), 1.64 (m, 1H), 1.10-1.40 (m, 2H ), 0.90 (d, 6H)

Example 550

N- (2-trifluoromethylbenzyl) -N- (2-naphthylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.60-7.80 (m, 5H), 7.25-7.60 (m, 9H), 7.00 (m, 3H), 5.60 (m, 1H), 5.20 (s, 2H), 4.90 (m, 2H), 4.20 (m, 1H), 3.38 (s, 2H), 3.15 (dd, 1H), 1.64 (m, 1H), 1.00-1.40 (m, 2H), 0.85 (t, 6H)

Example 551

N- (2-trifluoromethylbenzyl) -N-ethoxycarbonylmethylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (m, 3H), 7.45 (m, 3H), 7.20 (m, 3H), 7.00 (s, 1H), 5.35 (s, 5H), 4.70 (m, 1H ), 4.35 (m, 2H), 4.16 (q, 2H), 3.38 (s, 2H), 3.05 (dd, 1H), 1.36-1.64 (m, 2H), 1.25 (t, 3H), 1.10 (m, 1H), 0.85 (t, 6H)

Example 552

N- (2-trifluoromethylbenzyl) -N- (4-methylthiophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.75 (d, 1H), 7.60 (d, 2H), 7.50 (m, 3H), 7.15-7.38 (m, 5H), 7.10 (d, 2H), 7.00 (s , 1H), 5.42 (m, 1H), 5.30 (s, 2H), 4.80 (m, 2H), 3.90-4.20 (m, 2H), 3.38 (s, 2H), 3.15 (dd, 1H), 2.45 ( s, 3H), 1.64 (m, 1H), 1.00-1.40 (m, 2H), 0.85 (t, 6H)

Example 553

N- (2-trifluoromethylbenzyl) -N-isopropylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.75 (s, 2H), 7.65 (d, 2H), 7.50 (m, 2H), 7.22 (d, 3H), 7.05 (s, 1H), 5.90 (bs, 1H ), 5.40 (m, 2H), 5.00 (m, 2H), 4.65 (m, 1H), 4.15 (m, 1H), 3.50 (m, 1H), 3.38 (s, 2H), 3.25 (m, 1H) , 3.10 (dd, 1H), 1.52-1.80 (m, 2H), 1.40 (m, 1H), 1.10 (m, 1H), 0.90 (m, 6H), 0.75 (p, 6H)

Example 554

N- (2-trifluoromethylbenzyl) -N- (2-methoxyethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.75 (s, 1H), 7.65 (d, 3H), 7.45 (m, 2H), 7.15-7.30 (m, 3H), 7.10 (s, 1H), 6.15 (bd , 1H), 5.80 (bs, 1H), 5.30 (m, 2H), 4.80-5.10 (m, 2H), 4.65 (m, 1H), 4.20 (m, 1H), 3.74 (m, 2H), 3.40 ( s, 4H), 3.20 (d, 3H), 1.40-1.64 (m, 2H), 1.10 (m, 1H), 0.87 (d, 6H)

Example 555

N- (2-Trifluoromethylbenzyl) -N-cyclopropylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.75 (s, 1H), 7.65 (d, 3H), 7.45 (m, 2H), 7.10-7.25 (m, 4H), 6.55 (bd, 1H), 5.80 (bs , 1H), 5.40 (s, 2H), 5.15 (m, 1H), 4.80 (m, 1H), 4.65 (m, 2H), 4.05 (m, 1H), 3.40 (s, 2H), 3.05 (m, 2H), 1.60 (m, 1H), 1.10-1.45 (m, 2H), 0.85 (t, 6H), 0.80 (m, 2H), 0.40 (m, 2H)

Example 556

N- (2-trifluoromethylbenzyl) -N- [2- (dimethylamino) ethylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.75 (s, 1H), 7.65 (d, 2H), 7.55 (s, 1H), 7.45 (t, 2H), 7.20 (d, 3H), 7.00 (s, 1H ), 5.40 (d, 2H), 4.70-5.10 (m, 3H), 4.20 (m, 1H), 3.64 (m, 2H), 3.40 (m, 2H), 3.15 (dd, 1H), 2.65 (m, 2H), 2.20 (bs, 4H), 1.35-1.65 (m, 2H), 1.28 (s, 1H), 1.10 (m, 1H), 0.87 (t, 6H)

Example 557

N- (2-trifluoromethylbenzyl) -N- (3-ethoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.80 (s, 1H), 7.65 (d, 2H), 7.45 (m, 2H), 7.25 (d, 2H), 7.10 (s, 2H), 6.85 (m, 1H ), 5.80 (bs, 1H), 5.45 (d, 2H), 5.10 (m, 1H), 4.60-4.90 (m, 2H), 4.10 (m, 1H), 3.74 (q, 2H), 3.30-3.56 ( m, 4H), 3.15 (m, 2H), 1.30-1.84 (m, 4H), 1.00-1.25 (m, 3H), 0.84 (m, 10H)

Example 558

N- (2-trifluoromethylbenzyl) -N- [4- (dimethylamino) phenylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.70 (m, 2H), 7.58 (d, 2H), 7.40 (m, 3H), 7.15 (d, 2H), 7.05 (m, 2H), 6.60 (d, 2H ), 6.20 (bs, 1H), 5.30 (m, 2H), 4.80 (m, 1H), 4.20 (m, 1H), 3.40 (s, 2H), 3.10 (dd, 1H), 2.90 (s, 6H) , 1.60 (m, 1H), 1.10-1.44 (m, 2H), 0.87 (t, 6H)

Example 559

N- (2-trifluoromethylbenzyl) -N- (n-pentylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (m, 3H), 7.45 (m, 2H), 7.22 (d, 3H), 7.05 (m, 2H), 5.50-6.00 (m, 2H), 5.40 (m , 2H), 4.80-5.10 (m, 2H), 4.65 (m, 1H), 4.10 (m, 1H), 3.64 (m, 1H), 3.40 (s, 4H), 3.10 (dd, 1H), 1.40- 1.64 (m, 2H), 1.10-1.30 (m, 2H), 0.87 (m, 6H), 0.60-0.84 (m, 6H)

Example 560

N- (2-trifluoromethylbenzyl) -N- (4-nitrophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.10 (m, 2H), 7.52-7.75 (m, 6H), 7.28-7.50 (m, 2H), 7.12 (d, 2H), 7.00 (s, 1H), 6.85 (d, 1H), 5.70-5.90 (m, 1H), 5.30 (s, 2H), 4.80 (m, 1H), 4.55 (bs, 1H), 4.10 (m, 2H), 3.40 (s, 2H), 3.10 (dd, 1H), 1.64 (m, 1H), 1.10-1.50 (m, 2H), 0.87 (m, 6H)

Example 561

N- (2-trifluoromethylbenzyl) -N (octylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.70 (m, 2H), 7.65 (d, 2H), 7.50 (s, 1H), 7.45 (t, 2H), 7.20 (d, 2H), 7.05 (s, 1H ), 5.40 (d, 2H), 5.25 (s, 1H), 4.70 (m, 2H), 4.10 (m, 1H), 3.34 (q, 2H), 3.00 (m, 1H), 2.10 (m, 2H) , 1.60 (m, 1H), 1.35 (d, 6H), 1.05 (m, 2H), 0.87 (m, 6H), 0.80 (m, 9H)

Example 562

N- (2-trifluoromethylbenzyl) -N-phenylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.70 (d, 1H), 7.57 (m, 4H), 7.20-7.50 (m, 7H), 7.10 (d, 2H), 7.00 (s, 1H), 5.40-5.60 (m, 2H), 5.24 (s, 1H), 4.80-5.00 (m, 2H), 4.20 (m, 1H), 3.40 (s, 2H), 3.10 (dd, 1H), 1.64 (m, 1H), 1.00-1.50 (m, 2H), 0.87 (m, 6H)

Example 563

N- (2-trifluoromethylbenzyl) -N- (n-propylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (m, 3H), 7.45 (m, 2H), 7.22 (d, 3H), 7.05 (s, 2H), 6.10 (m, 1H), 5.40 (m, 2H ), 4.80-5.10 (m, 2H), 4.65 (m, 1H), 4.10 (m, 1H), 3.54 (m, 2H), 3.40 (s, 2H), 3.10 (dd, 1H), 1.40-1.64 ( m, 3H), 1.00-1.30 (m, 2H), 0.87 (t, 6H), 0.75 (m, 3H)

Example 564

N- (2-trifluoromethylbenzyl) -N- (2-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.75 (d, 1H), 7.60 (m, 4H), 7.45 (m, 3H), 7.15 (m, 6H), 7.00 (s, 1H), 5.30 (m, 3H ), 4.85 (m, 2H), 4.20 (m, 1H), 3.40 (s, 2H), 3.20 (dd, 1H), 2.05 (d, 3H), 1.64 (m, 1H), 1.00-1.50 (m, 2H), 0.87 (t, 6H)

Example 565

N- (2-trifluoromethylbenzyl) -N- (2,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.75 (m, 2H), 7.60 (m, 3H), 7.40 (m, 2H), 7.15 (d, 2H), 7.05 (s, 1H), 6.95 (m, 3H ), 5.95 (bs, 1H), 5.30 (m, 2H), 4.85 (m, 2H), 4.20 (m, 1H), 3.40 (s, 2H), 3.20 (dd, 1H), 2.30 (s, 3H) , 2.00 (d, 3H), 1.64 (m, 1H), 1.00-1.50 (m, 2H), 0.87 (t, 6H)

Example 566

N- (2-trifluoromethylbenzyl) -N- (3,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.75 (d, 1H), 7.60 (m, 3H), 7.40 (m, 2H), 7.15 (d, 3H), 7.05 (s, 1H), 6.95 (d, 2H ), 5.40 (m, 3H), 4.80 (m, 2H), 4.20 (m, 1H), 3.40 (s, 2H), 3.15 (dd, 1H), 2.20 (d, 6H), 1.64 (m, 1H) , 1.00-1.50 (m, 2H), 0.87 (t, 6H)

Example 567

N- (2-trifluoromethylbenzyl) -N- (3-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.70 (m, 2H), 7.55 (m, 4H), 7.35 (m, 1H), 6.95-7.20 (m, 7H), 6.20 (s, 1H), 5.30 (m , 2H), 4.80 (m, 2H), 4.20 (m, 1H), 3.40 (s, 2H), 3.15 (dd, 1H), 2.30 (s, 3H), 1.64 (m, 1H), 1.00-1.50 ( m, 2H), 0.87 (t, 6H)

Example 568

N- (2-trifluoromethylbenzyl) -N- (4-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.70 (d, 1H), 7.60 (m, 4H), 7.45 (m, 3H), 7.30 (m, 3H), 7.10 (d, 3H), 7.00 (s, 1H ), 5.60 (m, 1H), 5.20 (m, 2H), 4.80 (m, 2H), 4.20 (m, 1H), 3.40 (s, 2H), 3.15 (dd, 1H), 1.64 (m, 1H) , 1.00-1.50 (m, 2H), 0.87 (t, 6H)

Example 569

N- (2-trifluoromethylbenzyl) -N- (2-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.75 (m, 2H), 7.60 (m, 4H), 7.40 (m, 4H), 7.15 (m, 4H), 7.00 (s, 1H), 5.80 (bs, 1H ), 5.30 (m, 2H), 4.85 (m, 2H), 4.20 (m, 1H), 3.40 (s, 2H), 3.20 (dd, 1H), 1.64 (m, 1H), 1.00-1.50 (m, 2H), 0.87 (t, 6H)

Example 570

N- (2-trifluoromethylbenzyl) -N- (3-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

1 H-NMR (CDCl 3): δ 7.75 (d, 1H), 7.60 (m, 4H), 7.20-7.50 (m, 5H), 7.15 (m, 4H), 7.00 (s, 1H), 5.65 (m, 1H ), 5.30 (m, 2H), 4.80 (m, 2H), 4.20 (m, 1H), 3.40 (s, 2H), 3.15 (dd, 1H), 1.64 (m, 1H), 1.00-1.50 (m, 2H), 0.87 (t, 6H)

Example 571

N- (2-trifluoromethylbenzyl) -N- (4-dimethylamino-1-naphthylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole -5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.20 (d, 1H), 7.75 (d, 1H), 7.20-7.60 (m, 9H), 7.00 (m, 4H), 5.85 (s, 1H), 5.30 (m , 2H), 5.20 (d, 2H), 4.95 (m, 1H), 4.30 (m, 1H), 3.40 (s, 2H), 3.20 (dd, 1H), 2.90 (s, 6H), 1.64 (m, 1H), 1.00-1.50 (m, 2H), 0.87 (t, 6H)

Example 572

N- (2-trifluoromethylbenzyl) -N- (2-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.25 (d, 1H), 7.80 (d, 1H), 7.60 (m, 6H), 7.30 (m, 1H), 7.10 (m, 4H), 6.95 (t, 1H ), 6.80 (d, 1H), 5.30 (m, 3H), 4.85 (m, 2H), 4.30 (m, 1H), 3.55 (s, 3H), 3.40 (s, 2H), 3.20 (dd, 1H) , 2.05 (d, 3H), 1.64 (m, 1H), 1.00-1.50 (m, 2H), 0.92 (d, 6H)

Example 573

N- (2-trifluoromethylbenzyl) -N- (4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.75 (d, 1H), 7.60 (d, 3H), 7.40 (m, 3H), 7.15 (m, 5H), 7.00 (s, 1H), 5.30 (m, 3H ), 4.75-5.10 (m, 3H), 4.20 (m, 1H), 3.40 (s, 2H), 3.10 (dd, 1H), 2.35 (s, 3H), 1.64 (m, 1H), 1.00-1.50 ( m, 2H), 0.87 (t, 6H)

Example 574

N- (2-trifluoromethylbenzyl) -N- (2-phenylethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (d, 2H), 7.60 (s, 1H), 7.40 (t, 2H), 7.30 (m, 2H), 7.20 (d, 2H), 7.15 (m, 4H ), 7.00 (m, 2H), 5.70-6.20 (m, 2H), 5.30 (m, 2H), 4.85 (m, 2H), 4.60 (m, 1H), 4.10 (m, 1H), 3.80 (m, 2H), 3.40 (s, 2H), 3.05 (m, 1H), 2.80 (m, 2H), 1.64 (m, 1H), 1.00-1.50 (m, 2H), 0.87 (t, 6H)

Example 575

N- (2-trifluoromethylbenzyl) -N- (2-methoxypyridin-4-ylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole -5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.95 (m, 1H), 7.75 (m, 2H), 7.60 (d, 3H), 7.45 (m, 1H), 7.30 (m, 2H), 7.15 (d, 2H ), 7.00 (s, 1H), 6.70 (d, 1H), 6.00 (bs, 1H), 5.30 (m, 2H), 4.80 (m, 2H), 4.20 (m, 1H), 3.85 (s, 3H) , 3.40 (s, 2H), 3.20 (dd, 1H), 1.64 (m, 1H), 1.00-1.50 (m, 2H), 0.87 (t, 6H)

Example 576

N- (2-trifluoromethylbenzyl) -N- [3- (dimethylamino) propylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.75 (m, 1H), 7.65 (d, 2H), 7.45 (m, 3H), 7.20 (d, 2H), 7.10 (m, 1H), 7.00 (s, 1H ), 5.40 (d, 2H), 4.80 (m, 3H), 4.20 (m, 1H), 3.70 (m, 3H), 3.35 (m, 2H), 2.95 (m, 1H), 2.55 (m, 2H) , 2.00 (m, 6H), 1.64 (m, 1H), 1.00-1.50 (m, 5H), 0.87 (m, 6H)

Example 577

N- (2-trifluoromethylbenzyl) -N- (2-hydroxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (s, 1H), 7.60 (d, 3H), 7.55 (m, 4H), 7.40 (d, 2H), 7.15 (d, 3H), 7.00 (s, 1H ), 6.85 (m, 1H), 6.00 (bs, 1H), 5.25 (s, 2H), 3.95 (m, 1H), 3.90 (s, 2H), 3.40 (s, 2H), 2.65 (m, 2H) , 1.85 (bs, 2H), 1.64 (m, 1H), 1.00-1.50 (m, 2H), 0.87 (m, 6H)

Example 578

N- (2-trifluoromethylbenzyl) -N- (4-hydroxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.70 (d, 2H), 7.25-7.60 (m, 5H), 7.10 (m, 2H), 6.95 (m, 3H), 6.60 (d, 2H), 5.30 (m , 3H), 4.80 (m, 2H), 4.20 (m, 1H), 3.40 (m, 2H), 3.10 (d, 1H), 1.64 (m, 1H), 1.00-1.50 (m, 3H), 0.87 ( t, 6H)

Example 579

N- (2-trifluoromethylbenzyl) -N- (2-chloropyridin-5-ylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole- 5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.30 (d, 1H), 8.00 (t, 1H), 7.75 (d, 1H), 7.60 (d, 2H), 7.45 (m, 2H), 7.30 (m, 2H ), 7.10 (d, 2H), 7.00 (s, 1H), 6.60 (m, 1H), 5.75 (m, 1H), 5.25 (m, 2H), 4.80 (m, 1H), 4.10 (m, 1H) , 3.40 (s, 2H), 3.20 (dd, 1H), 1.64 (m, 1H), 1.00-1.50 (m, 2H), 0.87 (t, 6H)

Example 580

N- (2-Trifluoromethylbenzyl) -N-cyclopentylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.80 (s, 1H), 7.65 (d, 3H), 7.45 (m, 2H), 7.20 (d, 3H), 7.10 (s, 1H), 5.90 (bs, 1H ), 5.40 (s, 2H), 5.00 (m, 2H), 4.60 (m, 2H), 4.10 (m, 1H), 3.40 (s, 2H), 3.10 (dd, 1H), 1.95 (m, 2H) , 1.00-1.80 (m, 9H), 0.87 (t, 6H)

Example 581

N- (2-trifluoromethylbenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine hydrochloride

Example 537 The compound was dissolved in ethyl acetate, passed through hydrochloric acid gas, and crystallized with diethyl ether. The resulting solid was filtered and then recrystallized with ethanol to give the white crystalline title compound.

¹ H-NMR (CD ₃ OD): δ 9.18 (s, 1H), 7.85 (m, 4H), 7.80 (s, 1H), 7.64 (m, 4H), 7.39 (d, 2H), 7.02 (d, 2H), 5.80 (s, 2H), 5.35 (dd, 2H), 4.30 (m, 1H), 3.92-3.98 (m, 5H), 3.50 (s, 2H), 1.20-1.82 (m, 3H), 1.06 (m, 6H)

Example 582

N- (2-trifluoromethylbenzyl) -N-allylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropylamine

[Step 1]

N- (2-trifluoromethylbenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropylamine

N- (t-butoxycarbonyl) -L-alanine aldehyde was prepared in the same manner as in Reference Example 3 using Nt-butoxycarbonyl-L-alanine, and then 2,3-dichlorobenzylamine and 1- 2-trifluoromethylbenzylamine and 1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride instead of (4-nitrobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride The title compound was prepared in the same manner as in Reference Example 4.

¹ H-NMR (CDCl ₃ ): δ 7.00-7.66 (m, 10H), 6.29 (d, 1H), 5.27 (s, 2H), 4.00 (m, 1H), 3.90 (s, 2H), 3.35 (s , 2H), 2.64 (d, 2H), 1.10 (d, 3H)

[Step 2]

N- (2-trifluoromethylbenzyl) -N-allylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropylamine

A solution of N- (2-trifluoromethylbenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropylamine diluted with dichloromethane (0.02M, 1ml, 0.02mmol) and a solution of allyl isothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) were reacted at room temperature for 2 hours, and then the reaction solution was subjected to a short silica gel column chromatography (dichloro Methane / methanol = 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 6.99-7.71 (m, 9H), 6.51 (bs, 1H), 5.84 (m, 1H), 5.30 (s, 2H), 5.15 (d, 1H), 5.06 (m , 2H), 4.70 (d, 1H), 4.50 (d, 1H), 4.29 (bs, 2H), 4.09 (m, 1H), 3.32 (s, 2H), 2.96 (dd, 1H), 1.17 (d, 3H)

Example 583-625

N- (2-trifluoromethylbenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropylamine and the corresponding isothiocyanate Using to prepare the title compound in the same manner as in Step 2 of Example 582.

Example 583

N- (2-trifluoromethylbenzyl) -N-benzylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.95-7.67 (m, 14H), 5.36 (d, 1H), 5.22 (s, 1H), 4.86 (d, 2H), 4.72 (d, 1H), 4.68 (s , 1H), 4.08 (m, 1H), 3.26 (s, 2H), 2.98 (dd, 1H), 1.16 (d, 3H)

Example 584

N- (2-trifluoromethylbenzyl) -N- (2-biphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.95-7.62 (m, 18H), 5.25 (d, 1H), 5.21 (s, 2H), 4.63 (d, 1H), 4.43 (s, 1H), 3.94 (bs , 1H), 3.27 (s, 2H), 2.83 (dd, 1H), 1.11 (d, 3H)

Example 585

N- (2-trifluoromethylbenzyl) -N- (2-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.99-7.73 (m, 13H), 5.57 (bs, 1H), 5.28 (d, 1H), 5.24 (s, 2H), 4.83 (d, 1H), 4.72 (bs , 1H), 4.28 (m, 1H), 3.34 (s, 2H), 3.08 (dd, 1H), 1.21 (d, 3H)

Example 586

N- (2-trifluoromethylbenzyl) -N- (3-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 9.17 (bs, 1H), 6.94-7.70 (m, 13H), 5.95 (d, 1H), 5.29 (s, 2H), 4.77 (d, 1H), 4.32 ( m, 1H), 4.09 (m, 1H), 3.33 (s, 2H), 2.96 (dd, 1H), 1.24 (d, 3H)

Example 587

N- (2-trifluoromethylbenzyl) -N- (4-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.95 (bs, 1H), 6.95-7.71 (m, 13H), 5.87 (d, 1H), 5.24 (s, 2H), 4.79 (d, 1H), 4.36 (m , 1H), 4.10 (m, 1H), 3.34 (s, 2H), 2.97 (dd, 1H), 1.23 (d, 3H)

Example 588

N- (2-trifluoromethylbenzyl) -N- (n-butylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.71 (m, 9H), 6.27 (bs, 1H), 5.33 (s, 2H), 5.21 (d, 1H), 4.69 (d, 1H), 4.62 (m , 1H), 4.08 (m, 1H), 3.60 (m, 2H), 3.33 (s, 2H), 2.97 (dd, 1H), 1.49 (m, 2H), 1.26 (m, 2H), 1.18 (d, 3H), 0.85 (t, 3H)

Example 589

N- (2-trifluoromethylbenzyl) -N-isobutylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropyl Amine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.72 (m, 9H), 6.18 (bs, 1H), 5.34 (s, 2H), 5.22 (d, 1H), 4.76 (m, 1H), 4.71 (d , 1H), 4.10 (m, 1H), 3.44 (m, 2H), 3.33 (s, 2H), 3.02 (dd, 1H), 1.84 (m, 1H), 1.18 (d, 3H), 0.76 (d, 6H)

Example 590

N- (2-trifluoromethylbenzyl) -N- (2-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.99-7.73 (m, 13H), 5.53 (d, 1H), 5.24 (s, 2H), 4.88 (d, 1H), 4.72 (m, 1H), 4.26 (m , 1H), 3.34 (s, 2H), 3.08 (dd, 1H), 1.21 (d, 3H)

Example 591

N- (2-trifluoromethylbenzyl) -N- (3-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 9.18 (bs, 1H), 6.94-7.70 (m, 13H), 5.94 (d, 1H), 5.28 (s, 2H), 4.77 (d, 1H), 4.33 ( m, 1H), 4.09 (m, 1H), 3.33 (s, 2H), 2.96 (dd, 1H), 1.23 (d, 3H)

Example 592

N- (2-trifluoromethylbenzyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.68 (bs, 1H), 7.00-7.72 (m, 13H), 5.82 (d, 1H), 5.24 (s, 2H), 4.80 (d, 1H), 4.38 (m , 1H), 4.11 (m, 1H), 3.35 (s, 2H), 2.99 (dd, 1H), 1.22 (d, 3H)

Example 593

N- (2-trifluoromethylbenzyl) -N- (3-chloro-4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 7.01-7.72 (m, 12H), 5.85 (d, 1H), 5.29 (s, 2H), 4.80 (d, 1H), 4.42 (m, 1H), 4.13 (m , 1H), 3.36 (s, 2H), 2.99 (dd, 1H), 2.36 (s, 3H), 1.24 (d, 3H)

Example 594

N- (2-trifluoromethylbenzyl) -N-cyclohexylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropyl Amine

¹ H-NMR (CDCl ₃ ): δ 7.03-7.72 (m, 9H), 5.94 (bs, 1H), 5.30 (s, 2H), 5.18 (d, 1H), 4.88 (m, 1H), 4.68 (d , 1H), 4.22 (m, 1H), 4.07 (m, 1H), 3.33 (s, 2H), 2.98 (dd, 1H), 0.85-1.90 (m, 10H), 1.16 (d, 3H)

Example 595

N- (2-trifluoromethylbenzyl) -N-cyclopentylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropyl Amine

¹ H-NMR (CDCl ₃ ): δ 7.03-7.71 (m, 9H), 5.98 (bs, 1H), 5.34 (s, 2H), 5.23 (d, 1H), 4.67 (d, 1H), 4.55 (m , 1H), 4.07 (m, 1H), 3.33 (s, 2H), 2.98 (dd, 1H), 1.25-1.96 (m, 6H), 1.20 (d, 3H)

Example 596

N- (2-trifluoromethylbenzyl) -N- (2,4-dichlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-7.92 (m, 12H), 5.25 (s, 2H), 5.20 (d, 1H), 4.86 (d, 1H), 4.75 (m, 1H), 4.24 (m , 1H), 3.32 (s, 2H), 3.08 (dd, 1H), 1.22 (d, 3H)

Example 597

N- (2-trifluoromethylbenzyl) -N- [2- (dimethylamino) ethylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.72 (m, 9H), 5.40 (d, 1H), 5.36 (s, 2H), 4.97 (m, 1H), 4.78 (d, 1H), 4.21 (m , 1H), 3.59 (m, 2H), 3.35 (d, 2H), 3.12 (dd, 1H), 2.59 (m, 2H), 2.03 (s, 6H), 1.17 (d, 3H)

Example 598

N- (2-trifluoromethylbenzyl) -N- [4- (dimethylamino) phenylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.58-7.73 (m, 13H), 5.29 (s, 2H), 5.40 (d, 1H), 4.86 (m, 1H), 4.84 (d, 1H), 4.18 (m , 1H), 3.35 (s, 2H), 3.04 (dd, 1H), 2.96 (d, 6H), 1.30 (d, 3H)

Example 599

N- (2-trifluoromethylbenzyl) -N- [3- (dimethylamino) propylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 7.03-7.70 (m, 9H), 5.39 (d, 1H), 5.24 (s, 2H), 4.85 (m, 1H), 4.79 (d, 1H), 4.14 (m , 1H), 3.74 (m, 2H), 3.33 (bs, 2H), 2.95 (dd, 1H), 2.63 (m, 2H), 2.18 (m, 2H), 1.89 (s, 6H), 1.11 (m, 3H)

Example 600

N- (2-trifluoromethylbenzyl) -N- (3-ethoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.86-7.71 (m, 9H), 5.35 (s, 2H), 4.89 (m, 1H), 4.80 (dd, 2H), 4.09 (m, 1H), 3.74 (bs , 2H), 3.41 (m, 2H), 3.32 (s, 2H), 3.15 (m, 2H), 2.92 (dd, 1H), 1.77 (bs, 2H), 1.12 (d, 3H), 0.82 (t, 3H)

Example 601

N- (2-trifluoromethylbenzyl) -N-ethylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-7.71 (m, 9H), 6.24 (bs, 1H), 5.30 (s, 2H), 5.14 (d, 1H), 4.68 (d, 1H), 4.58 (m , 1H), 4.08 (m, 1H), 3.65 (m, 2H), 3.33 (s, 2H), 2.94 (dd, 1H), 1.27 (m, 2H), 1.18 (m, 3H), 1.16 (d, 3H)

Example 602

N- (2-trifluoromethylbenzyl) -N- (2-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.93-7.83 (m, 13H), 5.36 (d, 1H), 5.25 (s, 2H), 4.86 (d, 1H), 4.71 (m, 1H), 4.21 (m , 1H), 3.37 (s, 2H), 3.05 (dd, 1H), 1.21 (d, 3H)

Example 603

N- (2-trifluoromethylbenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.85 (bs, 1H), 6.73-7.94 (m, 13H), 5.87 (d, 1H), 5.27 (s, 2H), 4.80 (d, 1H), 4.43 (m , 1H), 4.12 (m, 1H), 3.36 (s, 2H), 2.99 (dd, 1H), 1.24 (d, 3H)

Example 604

N- (2-trifluoromethylbenzyl) -N- (4-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.66 (bs, 1H), 6.97-7.72 (m, 13H), 5.79 (d, 1H), 5.25 (s, 2H), 4.81 (d, 1H), 4.45 (m , 1H), 4.12 (m, 1H), 3.34 (s, 2H), 2.99 (dd, 1H), 1.22 (d, 3H)

Example 605

N- (2-trifluoromethylbenzyl) -N- (4-hydroxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminopropylamine

¹ H-NMR (CD ₃ OD): δ 6.72-7.73 (m, 13H), 5.70 (d, 2H), 5.35 (s, 2H), 5.05 (d, 1H), 4.19 (m, 1H), 3.99 ( m, 1H), 3.41 (s, 2H), 3.25 (dd, 1H), 1.18 (d, 3H)

Example 606

N- (2-trifluoromethylbenzyl) -N- (4-isopropylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.33 (bs, 1H), 6.98-7.71 (m, 13H), 5.64 (d, 1H), 5.25 (s, 2H), 4.81 (d, 1H), 4.65 (m , 1H), 4.15 (m, 1H), 3.33 (s, 2H), 3.01 (dd, 1H), 2.90 (m, 1H), 1.23 (m, 9H)

Example 607

N- (2-trifluoromethylbenzyl) -N- (2-methoxyethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-7.72 (m, 9H), 6.25 (bs, 1H), 5.33 (s, 2H), 5.06 (d, 1H), 4, .86 (m, 1H), 4.72 (d, 1H), 4.13 (m, 1H), 3.74 (m, 2H), 3.42 (m, 2H), 3.33 (s, 2H), 3.11 (s, 3H), 3.04 (dd, 1H), 1.16 (d, 3H)

Example 608

N- (2-trifluoromethylbenzyl) -N- (2-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.21 (d, 1H), 6.78-7.78 (m, 13H), 5.23 (s, 2H), 5.15 (m, 1H), 5.09 (m, 1H), 4.91 (d , 1H), 4.30 (m, 1H), 3.54 (s, 3H), 3.35 (s, 2H), 3.14 (dd, 1H), 1.20 (d, 3H)

Example 609

N- (2-trifluoromethylbenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.30 (bs, 1H), 6.83-7.71 (m, 13H), 5.63 (d, 1H), 5.28 (s, 2H), 4.82 (d, 1H), 4.60 (m , 1H), 4.14 (m, 1H), 3.80 (s, 3H), 3.33 (s, 2H), 3.01 (dd, 1H), 1.21 (d, 3H)

Example 610

N- (2-trifluoromethylbenzyl) -N- (3-methoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 7.82 (bs, 1H), 6.96-7.73 (m, 9H), 5.35 (d, 2H), 4.93 (d, 1H), 4.70 (d, 1H), 4.11 (m , 1H), 3.70 (m, 2H), 3.40 (m, 2H), 3.32 (s, 2H), 2.95 (dd, 1H), 2.83 (s, 3H), 1.78 (m, 2H), 1.13 (d, 3H)

Example 611

N- (2-trifluoromethylbenzyl) -N- (2-methoxypyridin-5-ylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole -5-yl] acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.72-8.11 (m, 12H), 5.87 (d, 1H), 5.25 (s, 2H), 4.81 (d, 1H), 4.43 (m, 1H), 4.13 (m , 1H), 3.92 (s, 3H), 3.33 (s, 2H), 2.99 (dd, 1H), 1.23 (d, 3H)

Example 612

N- (2-trifluoromethylbenzyl) -N-methylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.98-7.70 (m, 9H), 6.74 (bs, 1H), 5.29 (s, 2H), 5.21 (d, 1H), 4.68 (d, 1H), 4.51 (m , 1H), 4.05 (m, 1H), 3.33 (s, 2H), 3.12 (s, 3H), 2.91 (dd, 1H), 1.16 (d, 3H)

Example 613

N- (2-trifluoromethylbenzyl) -N- (4-methylthiophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.66 (bs, 1H), 6.95-7.71 (m, 13H), 5.78 (d, 1H), 5.24 (s, 2H), 4.801 (d, 1H), 4.46 (m , 1H), 4.12 (m, 1H), 3.31 (s, 2H), 2.98 (dd, 1H), 2.47 (s, 3H), 1.21 (d, 3H)

Example 614

N- (2-trifluoromethylbenzyl) -N- (2-naphthylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.99 (bs, 1H), 6.87-7.81 (m, 16H), 5.84 (d, 1H), 5.18 (s, 2H), 4.83 (d, 1H), 4.49 (m , 1H), 4.16 (m, 1H), 3.33 (s, 2H), 2.99 (dd, 1H), 1.22 (d, 3H)

Example 615

N- (2-trifluoromethylbenzyl) -N- (4-nitrophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ9.66 (bs, 1H), 6.66-8.19 (m, 13H), 6.09 (d, 1H), 5.25 (s, 2H), 4.78 (d, 1H), 4.17 ( m, H), 4.10 (m, 1H), 3.39 (s, 2H), 2.99 (dd, 1H), 1.27 (d, 3H)

Example 616

N- (2-trifluoromethylbenzyl) -N- (n-pentylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 7.70-7.72 (m, 9H), 6.81 (bs, 1H), 5.33 (s, 2H), 5.21 (d, 1H), 4.78 (m, 1H), 4.70 (d , 1H), 4.10 (m, 1H), 3.57 (m, 1H), 3.48 (s, 1H), 3.32 (s, 2H), 3.02 (dd, 1H), 1.60 (m, 1H), 1.17 (d, 3H), 0.69-1.25 (m, 8H)

Example 617

N- (2-trifluoromethylbenzyl) -N- (2-phenylethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.99-7.64 (m, 14H), 6.22 (bs, 1H), 5.30 (s, 2H), 5.12 (d, 1H), 4.63 (m, 1H), 4.61 (d , 1H), 4.02 (m, 1H), 3.89 (m, 2H), 3.31 (s, 2H), 2.91 (dd, 1H), 2.86 (t, 2H), 1.13 (d, 3H)

Example 618

N- (2-trifluoromethylbenzyl) -N-phenylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.62 (bs, 1H), 6.96-7.71 (m, 14H), 5.74 (d, 1H), 5.24 (s, 2H), 4.81 (d, 1H), 4.55 (m , 1H), 4.14 (m, 1H), 3.33 (s, 2H), 3.00 (dd, 1H), 1.21 (d, 3H)

Example 619

N- (2-trifluoromethylbenzyl) -N- (n-propylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.99-7.71 (m, 9H), 6.30 (bs, 1H), 5.32 (s, 2H), 5.27 (d, 1H), 4.69 (d, 1H), 4.64 (m , 1H), 4.08 (m, 1H), 3.57 (m, 2H), 3.33 (s, 2H), 2.96 (dd, 1H), 1.53 (dd, 1H), 1.17 (d, 3H), 0.79 (t, 3H)

Example 620

N- (2-trifluoromethylbenzyl) -N- (2-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.42 (bs, 1H), 6.97-7.71 (m, 13H), 5.69 (d, 1H), 5.25 (s, 2H), 4.81 (d, 1H), 4.62 (m , 1H), 4.15 (m, 1H), 3.34 (s, 2H), 3.01 (dd, 1H), 2.33 (s, 3H), 1.21 (d, 3H)

Example 621

N- (2-trifluoromethylbenzyl) -N- (3-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 7.82 (bs, 1H), 6.97-7.73 (m, 13H), 5.51 (d, 1H), 5.26 (s, 2H), 4.86 (d, 1H), 4.75 (m , 1H), 4.20 (m, 1H), 3.32 (s, 2H), 3.07 (dd, 1H), 2.09 (s, 3H), 1.21 (d, 3H)

Example 622

N- (2-trifluoromethylbenzyl) -N- (4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.39 (bs, 1H), 6.97-7.71 (m, 13H), 5.66 (d, 1H), 5.25 (s, 2H), 4.81 (d, 1H), 4.63 (m , 1H), 4.15 (m, 1H), 3.33 (s, 2H), 3.00 (dd, 1H), 2.34 (s, 3H), 1.21 (d, 3H)

Example 623

N- (2-trifluoromethylbenzyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 9.51 (bs, 1H), 6.92-7.89 (m, 13H), 6.06 (d, 1H), 5.27 (s, 2H), 4.78 (d, 1H), 4.30 (m , 1H), 4.12 (m, 1H), 3.33 (s, 2H), 2.97 (dd, 1H), 1.25 (d, 3H)

Example 624

N- (2-trifluoromethylbenzyl) -N- (2,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 6.97-7.72 (m, 12H), 5.46 (d, 1H), 5.27 (s, 2H), 4.85 (d, 1H), 4.75 (m, 1H), 4.19 (m , 1H), 3.32 (s, 2H), 3.07 (dd, 1H), 2.31 (s, 3H), 2.05 (s, 3H), 1.20 (d, 3H)

Example 625

N- (2-trifluoromethylbenzyl) -N- (3,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} aminopropylamine

¹ H-NMR (CDCl ₃ ): δ 8.30 (bs, 1H), 6.98-7.71 (m, 12H), 5.64 (d, 1H), 5.26 (s, 2H), 4.81 (d, 1H), 4.62 (m , 1H), 4.15 (m, 1H), 3.33 (s, 2H), 3.01 (dd, 1H), 2.23 (s, 6H), 1.20 (d, 3H)

Example 626

N- (2-trifluoromethylbenzyl) -N-allylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 -Methylbutylamine

[Step 1]

N- (2-trifluoromethylbenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3-methylbutylamine

Nt-butoxycarbonyl-L-valine aldehyde was prepared in the same manner as in Reference Example 3 using Nt-butoxycarbonyl-L-valine, followed by 2,3-dichlorobenzylamine and 1- (4-nitro 2-trifluoromethylbenzylamine and 1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride instead of benzyl) -1H-imidazol-5-ylacetic acid hydrochloride In the same manner, the title compound was prepared.

¹ H-NMR (CDCl ₃ ): δ 7.00-7.65 (m, 10H), 6.23 (d, 1H), 5.27 (s, 2H), 3.88 (s, 2H), 3.81 (m, 1H), 3.37 (s , 2H), 2.68 (d, 2H), 1.76 (m, 1H), 0.84 (t, 6H)

[Step 2]

N- (2-trifluoromethylbenzyl) -N-allylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 -Methylbutylamine

N- (2-trifluoromethylbenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3-methylbutylamine with dichloromethane The solution diluted with dichloromethane (0.02M, 1ml, 0.02mmol) and allyl isothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) for 2 hours at room temperature Purification by chromatography (dichloromethane / methanol = 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 7.00-7.73 (m, 9H), 5.96 (bs, 1H), 5.81 (m, 1H), 5.35 (d, 2H), 5.02 (m, 2H), 4.97 (d , 1H), 4.65 (d, 1H), 4.26 (m, 1H), 4.04 (m, 1H), 3.33 (s, 2H), 3.08 (dd, 1H), 1.87 (m, 1H), 0.91 (t, 6H)

Example 627-669

Corresponding to N- (2-trifluoromethylbenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3-methylbutylamine The title compound was prepared in the same manner as Step 2 of Example 626 using isothiocyanate.

Example 627

N- (2-trifluoromethylbenzyl) -N-benzylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 -Methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.99-7.68 (m, 14H), 6.21 (bs, 1H), 5.27 (d, 2H), 5.05 (t, 1H), 4.96 (d, 1H), 4.81 (dd , 2H), 4.67 (d, 1H), 4.05 (m, 1H), 3.28 (s, 2H), 3.10 (dd, 1H), 1.83 (m, 1H), 1.90 (dd, 6H)

Example 628

N- (2-trifluoromethylbenzyl) -N- (2-biphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.89-7.71 (m, 18H), 5.25 (s, 2H), 5.20 (m, 1H), 4.76 (m, 1H), 4.62 (d, 1H), 3.97 (m , 1H), 3.33 (s, 2H), 2.99 (dd, 1H), 1.84 (m, 1H), 0.85 (dd, 6H)

Example 629

N- (2-trifluoromethylbenzyl) -N- (2-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-7.76 (m, 13H), 5.26 (s, 2H), 5.20 (d, 1H), 5.17 (m, 1H), 4.88 (d, 1H), 4.39 (m , 1H), 3.38 (s, 2H), 3.20 (dd, 1H), 1.88 (m, 1H), 0.91 (dd, 6H)

Example 630

N- (2-trifluoromethylbenzyl) -N- (3-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.47 (bs, 1H), 6.795-7.72 (m, 13H), 5.54 (d, 1H), 5.27 (s, 2H), 4.76 (d, 1H), 4.72 (m , 1H), 4.05 (m, 1H), 3.35 (s, 2H), 3.14 (dd, 1H), 1.90 (m, 1H), 0.90 (t, 6H)

Example 631

N- (2-trifluoromethylbenzyl) -N- (4-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.28 (bs, 1H), 6.80-7.74 (m, 13H), 5.47 (d, 1H), 5.28 (d, 2H), 4.79 (m, 1H), 4.78 (d , 1H), 4.07 (m, 1H), 3.36 (s, 2H), 3.16 (dd, 1H), 1.91 (m, 1H), 0.91 (m, 6H)

Example 632

N- (2-trifluoromethylbenzyl) -N- (n-butylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.01-7.73 (m, 9H), 5.71 (bs, 1H), 5.35 (d, 2H), 5.05 (t, 1H), 4.75 (dd, 2H), 4.02 (m , 1H), 3.53 (m, 2H), 3.33 (s, 2H), 3.07 (dd, 1H), 1.87 (m, 1H), 1.40 (m, 2H), 1.07 (m, 2H), 0.91 (dd, 6H), 0.80 (t, 3H)

Example 633

N- (2-trifluoromethylbenzyl) -N-isobutylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-7.74 (m, 9H), 5.69 (bs, 1H), 5.37 (d, 2H), 5.14 (t, 1H), 4.76 (dd, 2H), 4.05 (m , 1H), 3.48 (m, 1H), 3.34 (s, 2H), 3.28 (m, 1H), 3.12 (dd, 1H), 1.87 (m, 1H), 1.76 (m, 1H), 0.93 (dd, 6H), 0.70 (m, 6H)

Example 634

N- (2-trifluoromethylbenzyl) -N- (2-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.96-7.76 (m, 13H), 5.28 (d, 2H), 5.17 (d, 1H), 5.09 (m, 1H), 4.87 (d, 1H), 4.19 (m , 1H), 3.38 (d, 2H), 3.19 (dd, 1H), 1.90 (m, 1H), 0.92 (t, 6H)

Example 635

N- (2-trifluoromethylbenzyl) -N- (3-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.45 (bs, 1H), 6.82-7.74 (m, 13H), 5.55 (d, 1H), 5.29 (d, 2H), 4.78 (d 1H), 4.74 (m, 1H), 4.07 (m, 1H), 3.37 (s, 2H), 3.16 (dd, 1H), 1.92 (m, 1H), 0.92 (t, 6H)

Example 636

N- (2-trifluoromethylbenzyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.26 (bs, 1H), 6.81-7.73 (m, 13H), 5.46 (d, 1H), 5.25 (d, 2H), 4.80 (m, 1H), 4.77 (d , 1H), 4.05 (m, 1H), 3.35 (s, 2H), 3.14 (dd, 1H), 1.90 (m, 1H), 0.90 (t, 6H)

Example 637

N- (2-trifluoromethylbenzyl) -N- (3-chloro-4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.29 (bs, 1H), 6.87-7.73 (m, 12H), 5.49 (d, 1H), 5.28 (s, 2H), 4.79 (m, 1H), 4.77 (d , 1H), 4.07 (m, 1H), 3.36 (s, 2H), 3.14 (dd, 1H), 2.34 (s, 3H), 1.91 (m, 1H), 0.91 (t, 6H)

Example 638

N- (2-trifluoromethylbenzyl) -N-cyclohexylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.04-7.74 (m, 9H), 5.98 (bs, 1H), 5.36 (s, 2H), 5.12 (t, 1H), 4.75 (dd, 1H), 4.18 (m , 1H), 4.01 (m, 1H), 3.34 (s, 2H), 3.08 (dd, 1H), 1.84 (m, 1H), 0.83-1.98 (m, 10H), 0.90 (t, 6H)

Example 639

N- (2-Trifluoromethylbenzyl) -N-cyclopentylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.03-7.73 (m, 9H), 5.54 (bs, 1H), 5.35 (d, 2H), 5.03 (t, 1H), 4.75 (dd, 2H), 4.61 (m , 1H), 4.01 (m, 1H), 3.34 (s, 2H), 3.08 (dd, 1H), 1.85 (m, 1H), 1.09-2.06 (m, 8H), 0.91 (dd, 6H)

Example 640

N- (2-trifluoromethylbenzyl) -N- (2,4-dichlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl] amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.82-7.75 (m, 12H), 5.28 (d, 1H), 5.26 (s, 2H), 4.92 (m, 1H), 4.85 (d, 1H), 4.16 (m , 1H), 3.35 (s, 2H), 3.19 (dd, 1H), 1.87 (m, 1H), 0.90 (t, 6H)

Example 641

N- (2-trifluoromethylbenzyl) -N- [2- (dimethylamino) ethylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-7.71 (m, 9H), 6.82 (bs, 1H), 5.36 (dd, 2H), 4.79 (m, 3H), 4.28 (m, 1H), 3.56 (m , 2H), 3.33 (d, 2H), 3.14 (dd, 1H), 2.44 (m, 2H), 1.97 (s, 6H), 1.88 (m, 1H), 0.89 (d, 6H)

Example 642

N- (2-trifluoromethylbenzyl) -N- [4- (dimethylamino) phenylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.61-7.73 (m, 13H), 5.29 (s, 2H), 5.18 (d, 1H), 5.14 (m, 1H), 4.79 (d, 1H), 4.08 (m , 1H), 3.35 (s, 2H), 3.12 (dd, 1H), 2.93 (s, 6H), 1.88 (m, 1H), 0.90 (dd, 6H)

Example 643

N- (2-trifluoromethylbenzyl) -N- [3- (dimethylamino) propylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.87 (bs, 1H), 7.04-7.72 (m, 13H), 5.41 (dd, 2H), 4.92 (m, 1H), 4.74 (s, 2H), 4.01 (m , 1H), 3.73 (m, 2H), 3.35 (d, 2H), 2.92 (dd, 1H), 2.44 (m, 2H), 1.89 (s, 6H), 1.83 (m, 1H), 1.80 (m, 2H), 0.88 (dd, 6H)

Example 644

N- (2-trifluoromethylbenzyl) -N- (3-ethoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.04-7.72 (m, 9H), 6.75 (bs, 1H), 5.38 (dd, 2H), 5.09 (t, 1H), 4.70 (dd, 2H), 4.01 (m , 1H), 3.75 (m, 2H), 3.39 (m, 2H), 3.36 (s, 2H), 3.14 (m, 2H), 2.95 (dd, 1H), 1.85 (m, 1H), 1.81 (m, 2H), 0.88 (dd, 6H), 0.80 (t, 3H)

Example 645

N- (2-trifluoromethylbenzyl) -N-ethylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 -Methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.72 (m, 9H), 5.80 (bs, 1H), 5.35 (dd, 2H), 4.98 (t, 1H), 4.93 (d, 1H), 4.62 (d , 1H), 4.02 (m, 1H), 3.60 (m, 2H), 3.33 (s, 2H), 3.05 (dd, 1H), 1.87 (m, 1H), 1.06 (t, 3H), 0.90 (m, 6H)

Example 646

N- (2-trifluoromethylbenzyl) -N- (2-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.93-7.75 (m, 13H), 5.29 (d, 1H), 5.27 (s, 2H), 5.01 (t, 1H), 4.83 (d, 1H), 4.13 (m , 1H), 3.37 (s, 2H), 3.151 (dd, 1H), 1.88 (m, 1H), 0.90 (t, 6H)

Example 647

N- (2-trifluoromethylbenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.35 (bs, 1H), 6.82-7.73 (m, 13H), 5.50 (d, 1H), 5.27 (s, 2H), 4.80 (m, 1H), 4.77 (d , 1H), 4.06 (m, 1H), 3.36 (s, 2H), 3.15 (dd, 1H), 1.89 (m, 1H), 0.91 (t, 6H)

Example 648

N- (2-trifluoromethylbenzyl) -N- (4-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.05 (bs, 1H), 6.87-7.73 (m, 13H), 5.38 (d, 1H), 5.27 (s, 2H), 4.82 (m, 1H), 4.78 (d , 1H), 4.06 (m, 1H), 3.34 (s, 2H), 3.15 (dd, 1H), 1.88 (m, 1H), 0.90 (t, 6H)

Example 649

N- (2-trifluoromethylbenzyl) -N- (4-hydroxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CD ₃ OD): δ 6.69-7.75 (m, 13H), 5.43 (d, 1H), 5.37 (s, 2H), 5.05 (d, 1H), 4.25 (m, 2H), 3.49 ( dd, 2H), 2.68 (m, 1H), 1.77 (m, 1H), 0.90 (d, 6H)

Example 650

N- (2-trifluoromethylbenzyl) -N- (4-isopropylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-7.73 (m, 13H), 5.27 (s, 2H), 5.18 (d, 1H), 5.04 (t, 1H), 4.79 (d, 1H), 4.08 (m , 1H), 3.35 (s, 2H), 3.14 (dd, 1H), 2.89 (m, 1H), 1.87 (m, 1H), 1.22 (d, 6H), 0.91 (t, 6H)

Example 651

N- (2-trifluoromethylbenzyl) -N- (2-methoxyethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.03-7.73 (m, 9H), 5.96 (bs, 1H), 5.36 (dd, 2H), 5.11 (t, 1H), 4.73 (dd, 1H), 4.13 (m , 1H), 3.70 (m, 2H), 3.37 (m, 2H), 3.34 (s, 2H), 3.09 (dd, 1H), 3.07 (s, 3H), 1.86 (m, 1H), 0.91 (d, 6H)

Example 652

N- (2-trifluoromethylbenzyl) -N- (2-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.28 (d, 1H), 6.76-7.78 (m, 13H), 5.20 (s, 2H), 5.19 (t, 1H), 5.01 (dd, 2H), 4.18 (m , 1H), 3.52 (s, 3H), 3.37 (s, 2H), 3.15 (dd, 1H), 1.87 (m, 1H), 0.94 (d, 6H)

Example 653

N- (2-trifluoromethylbenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.82-7.73 (m, 13H), 5.30 (s, 2H), 5.25 (d, 1H), 4.99 (s, 1H), 4.79 (d, 1H), 4.07 (m , 1H), 3.78 (s, 3H), 3.35 (s, 2H), 3.13 (dd, 1H), 1.88 (m, 1H), 0.90 (t, 6H)

Example 654

N- (2-trifluoromethylbenzyl) -N- (3-methoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.81-7.73 (m, 9H), 5.38 (dd, 2H), 5.11 (t, 1H), 4.68 (s, 2H), 4.02 (m, 1H), 3.70 (m , 2H), 3.39 (m, 2H), 3.33 (s, 2H), 2.97 (dd, 1H), 2.80 (s, 3H), 1.83 (m, 1H), 1.77 (m, 2H), 0.89 (d, 6H)

Example 655

N- (2-trifluoromethylbenzyl) -N- (2-methoxypyridin-5-ylthiocarbamoyl) 2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole- 5-yl] acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.28 (bs, 1H), 6.69-7.91 (m, 12H), 5.45 (d, 1H), 5.27 (d, 2H), 4.81 (m, 1H), 4.78 (d , 1H), 4.07 (m, 1H), 3.90 (s, 3H), 3.33 (s, 2H), 3.14 (dd, 1H), 1.91 (m, 1H), 0.90 (t, 6H)

Example 656

N- (2-trifluoromethylbenzyl) -N-methylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 -Methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.97-7.71 (m, 9H), 6.20 (bs, 1H), 5.35 (dd, 2H), 4.96 (d, 1H), 4.91 (t, 1H), 4.61 (d , 1H), 4.00 (m, 1H), 3.33 (s, 2H), 3.08 (s, 3H), 3.04 (dd, 1H), 1.86 (m, 1H), 0.90 (t, 6H)

Example 657

N- (2-trifluoromethylbenzyl) -N- (4-methylthiophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.94 (bs, 1H), 6.88-7.73 (m, 13H), 5.36 (d, 1H), 5.26 (d, 2H), 4.92 (t, 1H), 4.78 (d , 1H), 4.06 (m, 1H), 3.35 (s, 2H), 3.14 (dd, 1H), 2.46 (s, 3H), 1.88 (m, 1H), 0.90 (t, 6H)

Example 658

N- (2-trifluoromethylbenzyl) -N- (2-naphthylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.21 (bs, 1H), 6.85-7.82 (m, 16H), 5.44 (d, 1H), 5.20 (d, 2H), 4.97 (m, 1H), 4.83 (d , 1H), 4.11 (m, 1H), 3.37 (s, 2H), 3.16 (dd, 1H), 1.89 (m, 1H), 0.91 (t, 6H)

Example 659

N- (2-trifluoromethylbenzyl) -N- (4-nitrophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 9.13 (bs, 1H), 6.62-8.17 (m, 13H), 5.73 (d, 1H), 5.26 (s, 2H), 4.76 (d, 1H), 4.56 (m , 1H), 4.03 (m, 1H), 3.38 (s, 2H), 3.19 (dd, 1H), 1.96 (m, 1H), 0.91 (dd, 6H)

Example 660

N- (2-trifluoromethylbenzyl) -N- (n-pentylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-7.74 (m, 9H), 5.59 (bs, 1H), 5.36 (dd, 2H), 5.17 (t, 1H), 4.74 (dd, 2H), 4.04 (m , 1H), 3.33 (s, 2H), 3.19-3.74 (m, 2H), 3.11 (dd, 1H), 1.87 (m, 1H), 1.51 (m, 1H), 1.14 (m, 1H), 1.06 ( m, 2H), 0.92 (dd, 6H), 0.87 (m, 2H), 0.64 (t, 3H)

Example 661

N- (2-trifluoromethylbenzyl) -N- (2-phenylethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.97-7.68 (m, 14H), 5.70 (bs, 1H), 5.34 (dd, 2H), 4.99 (t, 1H), 4.64 (dd, 2H), 3.99 (m , 1H), 3.86 (m, 2H), 3.32 (s, 2H), 3.01 (dd, 1H), 2.80 (t, 2H), 1.83 (m, 1H), 0.89 (dd, 6H)

Example 662

N- (2-trifluoromethylbenzyl) -N-phenylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 -Methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.94 (bs, 1H), 6.94-7.73 (m, 14H), 5.36 (d, 1H), 5.26 (s, 2H), 4.98 (t, 1H), 4.80 (d , 1H), 4.08 (m, 1H), 3.35 (s, 2H), 3.14 (dd, 1H), 1.87 (m, 1H), 0.90 (dd, 6H)

Example 663

N- (2-trifluoromethylbenzyl) -N- (n-propylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.72 (m, 9H), 5.74 (bs, 1H), 5.35 (dd, 2H), 5.05 (t, 1H), 4.76 (dd, 2H), 4.02 (m , 1H), 3.58 (m, 1H), 3.48 (m, 1H), 3.33 (s, 2H), 3.07 (dd, 1H), 1.85 (m, 1H), 1.45 (m, 2H), 0.91 (dd, 6H), 0.72 (t, 3H)

Example 664

N- (2-trifluoromethylbenzyl) -N- (2-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.94-7.75 (m, 13H), 5.35 (d, 1H), 5.28 (s, 2H), 5.00 (t, 1H), 5.02 (t, 1H), 4.81 (d , 1H), 4.10 (m, 1H), 3.37 (s, 2H), 3.15 (dd, 1H), 2.33 (s, 3H), 1.89 (m, 1H), 0.92 (dd, 6H)

Example 665

N- (2-trifluoromethylbenzyl) -N- (3-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.01-7.75 (m, 13H), 5.30 (s, 2H), 5.23 (d, 1H), 5.10 (t, 1H), 4.84 (d, 1H), 4.14 (m , 1H), 3.36 (s, 2H), 3.18 (dd, 1H), 2.01 (s, 3H), 1.91 (m, 1H), 0.91 (t, 6H)

Example 666

N- (2-trifluoromethylbenzyl) -N- (4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 7.76 (bs, 1H), 7.00-7.73 (m, 13H), 5.27 (s, 2H), 5.23 (d, 1H), 5.00 (t, 1H), 4.79 (d , 1H), 4.08 (m, 1H), 3.35 (s, 2H), 3.13 (dd, 1H), 2.32 (s, 3H), 1.87 (m, 1H), 0.90 (t, 6H)

Example 667

N- (2-trifluoromethylbenzyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl] amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 8.82 (bs, 1H), 6.75-7.73 (m, 13H), 5.67 (d, 1H), 5.26 (s, 2H), 4.77 (d, 1H), 4.62 (m , 1H), 4.06 (m, 1H), 3.36 (s, 2H), 3.17 (dd, 1H), 1.92 (m, 1H), 0.91 (t, 6H)

Example 668

N- (2-trifluoromethylbenzyl) -N- (2,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl] amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.92-7.75 (m, 13H), 5.29 (s, 2H), 5.21 (d, 1H), 5.15 (m, 1H), 4.83 (d, 1H), 4.12 (m , 1H), 3.35 (s, 2H), 3.17 (dd, 1H), 2.30 (s, 3H), 1.96 (s, 3H), 1.90 (m, 1H), 0.90 (t, 6H)

Example 669

N- (2-trifluoromethylbenzyl) -N- (3,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl] amino-3-methylbutylamine

¹ H-NMR (CDCl ₃ ): δ 6.93-7.73 (m, 13H), 5.28 (s, 2H), 5.22 (d, 1H), 5.02 (t, 1H), 4.79 (d, 1H), 4.10 (m , 1H), 3.36 (s, 2H), 3.13 (dd, 1H), 2.21 (s, 6H), 1.86 (m, 1H), 0.90 (t, 6H)

Example 670

N- (2-trifluoromethylbenzyl) -N-allylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-4 Methylpentylamine

[Step 1]

N- (2-trifluoromethylbenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-4-methylpentylamine

Nt-butoxycarbonyl-L-leucine aldehyde was prepared in the same manner as in Reference Example 3 using Nt-butoxycarbonyl-L-leucine, followed by 2,3-dichlorobenzylamine and 1- (4- Reference Example 4 Using 2-trifluoromethylbenzylamine and 1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride instead of nitrobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride In the same manner as the title compound was prepared.

¹ H-NMR (CDCl ₃ ): δ 7.00-7.66 (m, 10H), 6.14 (d, 1H), 5.27 (s, 2H), 4.08 (m, 1H), 3.90 (s, 2H), 3.35 (s , 2H), 2.65 (d, 2H), 1.52 (m, 1H), 1.27 (m, 2H), 0.88 (d, 6H)

[Step 2]

N- (2-trifluoromethylbenzyl) -N-allylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-4 Methylpentylamine

N- (2-trifluoromethylbenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-4-methylpentylamine with dichloromethane The solution diluted with dichloromethane (0.02M, 1ml, 0.02mmol) and the allyl isothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) at room temperature for 3 hours, and then the reaction solution was a short silica gel tube. Purification by chromatography (dichloromethane / methanol = 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 6.78-7.71 (m, 11H), 6.40 (bs, 1H), 5.85 (m, 2H), 5.33 (d, 2H), 4.69-5.07 (dd, 2H), 4.69 (bs, 1H), 4.33 (d, 2H), 4.15 (m, 1H), 3.31 (s, 2H), 3.05 (dd, 1H), 1.25-1.52 (m, 3H), 0.85 (d, 6H)

Example 671-713

Corresponding to N- (2-trifluoromethylbenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-4-methylpentylamine The title compound was prepared in the same manner as Step 2 of Example 670 using isothiocyanate.

Example 671

N- (2-trifluoromethylbenzyl) -N-benzylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-4 Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.72-7.67 (m, 14H), 6.75 (bs, 1H), 5.22 (d, 2H), 4.63-4.98 (m, 3H), 4.17 (m, 1H), 3.25 (s, 2H), 3.05 (dd, 1H), 1.25-1.62 (m, 3H), 0.85 (d, 6H)

Example 672

N- (2-trifluoromethylbenzyl) -N- (2-biphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.93-7.71 (m, 19H), 6.66 (bs, 1H), 5.12-5.21 (m, 3H), 4.67-4.76 (d, 1H), 4.09 (m, 1H) , 3.29 (s, 2H), 2.92 (dd, 1H), 1.10-1.62 (m, 3H), 0.83 (d, 6H)

Example 673

N- (2-trifluoromethylbenzyl) -N- (2-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.99-7.82 (m, 13H), 6.65 (bs, 1H), 5.48 (m, 1H), 5.29 (s, 1H), 5.22 (s, 2H), 4.87-4.96 (d, 1H), 4.71 (m, 1H), 4.36 (m, 1H), 3.35 (s, 2H), 3.14 (dd, 1H), 1.25-1.62 (m, 3H), 0.89 (d, 6H)

Example 674

N- (2-trifluoromethylbenzyl) -N- (3-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.95 (bs, 1H), 6.96-7.71 (m, 13H), 6.66 (d, 1H), 5.75 (bd, 1H), 5.26 (s, 2H), 4.86 (d , 1H), 4.40 (m, 1H), 4.13 (m, 1H), 3.34 (s, 2H), 3.03 (dd, 1H), 1.26-1.70 (m, 3H), 0.86 (d, 6H)

Example 675

N- (2-trifluoromethylbenzyl) -N- (4-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.73 (bs, 1H), 6.95-7.71 (13H), 6.63 (d, 1H), 5.70 (d, 1H), 5.21 (s, 2H), 4.85 (d, 1H ), 4.47 (m, 1H), 4.14 (m. 1H), 3.34 (s, 2H), 3.03 (dd, 1H), 1.26-1.70 (m, 3H), 0.86 (d, 6H)

Example 676

N- (2-trifluoromethylbenzyl) -N- (n-butylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.98-7.82 (m, 9H), 6.86 (d, 1H), 6.22 (bs, 1H), 5.00-5.42 (m, 3H), 4.70 (d, 1H), 4.14 (m, 1H), 3.40-3.78 (m, 2H), 3.32 (s, 2H), 2.99 (dd, 1H), 1.11-1.70 (m, 8H), 0.88 (m, 10H)

Example 677

N- (2-trifluoromethylbenzyl) -N-isobutylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.86-7.82 (m, 10H), 6.11 (bs, 1H), 4.98-5.52 (m, 3H), 4.66-4.75 (d, 2H), 4.18 (bs, 1H) , 3.47-3.80 (m, 1H), 3.31 (s, 2H), 3.03 (dd, 1H), 1.75-1.96 (m, 2H), 1.21-1.68 (m, 3H), 0.89 (d, 6H), 0.75 (d, 6H)

Example 678

N- (2-trifluoromethylbenzyl) -N- (2-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.98-7.74 (m, 13H), 6.66 (bs, 1H), 5.38-5.60 (bs, 1H), 5.22 (s, 2H), 4.90 (d, 1H), 4.70 (m, 1H), 4.35 (m, 1H), 3.35 (s, 2H), 3.12 (dd, 1H), 1.25-1.60 (m, 3H), 0.89 (d, 6H)

Example 679

N- (2-trifluoromethylbenzyl) -N- (3-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.93 (bs, 1H), 6.95-7.71 (13H), 6.70 (d, 1H), 5.75 (bd, 1H), 5.25 (s, 2H), 4.90 (d, 1H ), 4.39 9m, 1H), 4.15 (m, 1H), 3.34 (s, 2H), 3.02 (dd, 1H), 1.25-1.68 (m, 3H), 0.86 (d, 6H)

Example 680

N- (2-trifluoromethylbenzyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.71 (1H, br), 6.95-7.71 (m, 13H), 6.63 (d, 1H), 5.70 (bd, 1H), 5.22 (s, 2H), 4.46 (m , 1H), 4.16 (m, 1H), 3.34 (s, 2H), 3.04 (dd, 1H), 1.25-1.70 (m, 3H), 0.86 (d, 6H)

Example 681

N- (2-trifluoromethylbenzyl) -N- (3-chloro-4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.71 (bs, 1H), 6.96-7.71 (m, 2H), 6.70 (d, 1H), 5.70 (bd, 1H), 5.25 (s, 2H), 4.88 (d , 1H), 4.30 (m, 1H), 4.15 (m, 1H), 3.34 (s, 2H), 3.03 (dd, 1H), 2.34 (s, 3H), 1.26-1.70 (m, 3H), 0.86 ( d, 6H)

Example 682

N- (2-trifluoromethylbenzyl) -N-cyclohexylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.96-7.72 (m, 9H), 6.86 (bd, 1H), 5,86 (bs, 1H), 5.10-5.30 (m, 3H), 4.70 (d, 2H) , 4.20 (m, 2H), 3.32 (s, 2H), 3.03 (dd, 1H), 1.72-2.10 (m, 3H), 1.20-1.70 (m, 8H), 0.86 (d, 6H)

Example 683

N- (2-Trifluoromethylbenzyl) -N-cyclopentylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.96-7.72 (m, 9H), 6.85 (bd, 1H), 5.95 (bs, 1H), 5.10-5.42 (m, 3H), 4.66 (m, 2H), 4.15 (m, 1H), 3.32 (s, 2H), 3.03 (dd, 1H), 1.80-2.10 (m, 3H), 1.10-1.72 (m, 9H), 0.86 (d, 6H)

Example 684

N- (2-trifluoromethylbenzyl) -N- (2,4-dichlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.98-7.73 (m, 12H), 6.55 (bd, 1H), 5.52 (m, 1H), 5.22 (s, 2H), 4.90 (d, 1H), 4.59 (m , 1H), 4.32 (m, 1H), 3.34 (s, 2H), 3.10 (dd, 1H), 1.25-1.62 (m, 3H), 0.87 (d, 6H)

Example 685

N- (2-trifluoromethylbenzyl) -N- [2- (dimethylamino) ethylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.03-7.72 (m, 10H), 6.72 (bs, 1H), 5.39 (dd, 2H), 5.07 (m, 1H), 4.74 (m, 2H), 4.08 (m , 1H), 3.52 (bs, 2H), 3.36 (s, 2H), 3.13 (dd, 1H), 2.45 (m, 2H), 2.32 (bs, 2H), 1.91 (s, 6H), 0.92 (d, 6H)

Example 686

N- (2-trifluoromethylbenzyl) -N- [4- (dimethylamino) phenylthiocarbamoyl)]-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole- 5-yl] acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.83 (bs, 1H), 6.58-7.72 (m, 14H), 5.38 (d, 1H), 5.26 (s, 2H), 4.86 (d, 1H), 4.74 (m , 1H), 4.24 (m, 1H), 3.34 (s, 2H), 3.07 (dd, 1H), 2.94 (s, 6H), 1.26-1.57 (m, 3H), 0.88 (d, 6H)

Example 687

N- (2-trifluoromethylbenzyl) -N- [3- (dimethylamino) propylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.75 (bs, 1H), 7.02-7.71 (m, 10H), 5.38 (dd, 2H), 4.82 (m, 3H), 4.24 (m, 1H), 3.71 (m , 2H), 3.32 (dd, 2H), 2.94 (dd, 1H), 2.55 (m, 4H), 2.02 (bs, 6H), 1.49 (m, 2H), 1.19 (m, 1H), 0.86 (d, 6H)

Example 688

N- (2-trifluoromethylbenzyl) -N- (3-ethoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.03-7.71 (m, 10H), 6.87 (bs, 1H), 5.35 (dd, 2H), 4.80 (m, 3H), 4.20 (m, 1H), 3.75 (m , 2H), 3.41 (m, 2H), 3.31 (s, 2H), 3.16 (m, 2H), 2.95 (dd, 1H), 1.80 (m, 2H), 1.17-1.54 (m, 3H), 0.85 ( m, 9H)

Example 689

N- (2-trifluoromethylbenzyl) -N-ethylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-4 Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.78-7.71 (m, 10H), 6.28 (bs, 1H), 5.32 (d, 2H), 5.22 (d, 1H), 4.70 (d, 1H), 4.60 (m , 1H), 3.64 (m, 2H), 3.32 (s, 2H), 2.99 (dd, 1H), 2.94 (s, 6H), 1.26-1.57 (m, 3H), 1.11 (t, 3H), 0.87 ( m, 6H)

Example 690

N- (2-trifluoromethylbenzyl) -N- (2-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.12 (bs, 1H), 6.69-7.72 (m, 14H), 5.52 (d, 1H), 5.23 (s, 2H), 4.90 (d, 1H), 4.66 (m , 1H), 4.30 (m, 1H), 3.08 (dd, 1H), 1.26-1.58 (m, 3H), 0.88 (d, 6H)

Example 691

N- (2-trifluoromethylbenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.85 (bs, 1H), 6.69-7.71 (m, 14H), 5.81 (q, 1H), 5.24 (s, 2H), 4.88 (d, 1H), 4.49 (m , 1H), 4.07 (m, 1H), 3.34 (d, 2H), 3.04 (dd, 1H), 1.21-1.60 (m, 3H), 0.88 (d, 6H)

Example 692

N- (2-trifluoromethylbenzyl) -N- (4-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.52 (bs, 1H), 6.65-7.71 (m, 14H), 5.62 (d, 1H), 5.23 (s, 2H), 4.88 (d, 1H), 4.51 (m , 1H), 4.17 (m, 1H), 3.34 (d, 2H), 3.05 (dd, 1H), 1.26-1.58 (m, 3H), 0.87 (dd, 6H)

Example 693

N- (2-trifluoromethylbenzyl) -N- (4-hydroxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.18 (bs, 1H), 6.69-7.70 (m, 14H), 5.38 (d, 1H), 5.23 (d, 2H), 4.86 (d, 1H), 4.78 (m , 1H), 4.23 (m, 1H), 3.33 (s, 2H), 3.04 (dd, 1H), 1.26-1.58 (m, 3H), 0.87 (d, 6H)

Example 694

N- (2-trifluoromethylbenzyl) -N- (4-isopropylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.20 (bs, 1H), 6.74-7.71 (m, 14H), 5.51 (d, 1H), 5.23 (s, 2H), 4.87 (d, 1H), 4.69 (m , 1H), 4.20 (m, 1H), 3.34 (s, 2H), 3.07 (dd, 1H), 2.90 (m, 1H), 1.23 (d, 6H), 1.14-1.58 (m, 3H), 0.89 ( m, 6H)

Example 695

N- (2-trifluoromethylbenzyl) -N- (2-methoxyethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.92-7.72 (m, 10H), 6.24 (bs, 1H), 5.33 (dd, 2H), 4.86 (dd, 2H), 4.78 (m, 1H), 4.23 (m , 1H), 3.73 (m, 2H), 3.39 (m, 2H), 3.32 (s, 2H), 3.10 (s, 3H), 3.08 (dd, 1H), 1.26-1.58 (m, 3H), 0.89 ( d, 6H)

Example 696

N- (2-trifluoromethylbenzyl) -N- (2-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.77-8.26 (m, 14H), 5.19 (s, 2H), 5.06 (m, 1H), 5.03 (dd, 2H), 4.39 (m, 1H), 3.54 (s , 3H), 3.36 (s, 2H), 3.16 (dd, 1H), 1.26-1.62 (m, 3H), 0.92 (d, 6H)

Example 697

N- (2-trifluoromethylbenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.20 (bs, 1H), 6.78-7.72 (m, 14H), 5.51 (d, 1H), 5.24 (m, 1H), 4.87 (d, 1H), 4.65 (m , 1H), 4.23 (m, 1H), 3.79 (s, 3H), 3.33 (s, 2H), 3.06 (dd, 1H), 1.26-1.58 (m, 3H), 0.87 (d, 6H)

Example 698

N- (2-trifluoromethylbenzyl) -N- (3-methoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.02-7.73 (m, 10H), 6.91 (bs, 1H), 5.35 (d, 2H), 4.85 (m, 1H), 4.78 (dd, 2H), 4.21 (m , 1H), 3.70 (m, 2H), 3.39 (m, 2H), 3.40 (m, 2H), 3.31 (s, 2H), 2.98 (dd, 1H), 2.83 (s, 3H), 1.77 (m, 2H), 1.18-1.56 (m, 3H), 0.87 (d, 6H)

Example 699

N- (2-trifluoromethylbenzyl) -N- (2-methoxypyridin-5-ylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole -5-yl] acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.75 (bs, 1H), 6.69-7.99 (m, 13H), 5.69 (d, 1H), 5.24 (s, 2H), 4.88 (d, 1H), 4.49 (m , 1H), 4.18 (m, 1H), 3.91 (s, 3H), 3.33 (s, 2H), 3.05 (dd, 1H), 1.26-1.58 (m, 3H), 0.87 (dd, 6H)

Example 700

N- (2-trifluoromethylbenzyl) -N-methylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-4 Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.21 (bs, 1H), 6.69-7.72 (m, 10H), 5.53 (d, 1H), 5.23 (s, 2H), 4.87 (d, 1H), 4.66 (m , 1H), 4.24 (m, 1H), 3.35 (s, 2H), 3.06 (dd, 1H), 2.32 (s, 3H), 1.26-1.58 (m, 3H), 0.88 (d, 6H)

Example 701

N- (2-trifluoromethylbenzyl) -N- (4-methylthiophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.51 (bs, 1H), 6.72-7.71 (m, 14H), 5.62 (d, 1H), 5.22 (s, 2H), 4.87 (d, 1H), 4.56 (m , 1H), 4.20 (m, 1H), 3.34 (s, 2H), 3.05 (dd, 1H), 2.47 (s, 3H), 1.26-1.58 (m, 3H), 0.88 (dd, 6H)

Example 702

N- (2-trifluoromethylbenzyl) -N- (2-naphthylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.73 (bs, 1H), 6.72-7.80 (m, 17H), 5.69 (d, 1H), 5.16 (s, 2H), 4.91 (d, 1H), 4.61 (m , 1H), 4.24 (m, 1H), 3.35 (s, 2H), 3.07 (dd, 1H), 1.26-1.58 (m, 3H), 0.88 (dd, 6H)

Example 703

N- (2-trifluoromethylbenzyl) -N- (4-nitrophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 9.51 (bs, 1H), 6.64-8.18 (m, 14H), 5.89 (d, 1H), 5.23 (s, 2H), 4.90 (d, 1H), 4.26 (m , 1H), 4.11 (m, 1H), 3.39 (s, 2H), 3.07 (dd, 1H), 1.26-1.53 (m, 3H), 0.86 (t, 6H)

Example 704

N- (2-trifluoromethylbenzyl) -N- (n-pentylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.88-7.72 (m, 10H), 6.01 (bs, 1H), 5.24 (m, 3H), 4.78 (m, 1H), 4.71 (d, 1H), 4.20 (m , 1H), 3.61 (m, 1H), 3.48 (m, 1H), 3.32 (s, 2H), 3.06 (dd, 1H), 0.68-1.60 (m, 12H), 0.90 (d, 6H)

Example 705

N- (2-trifluoromethylbenzyl) -N- (2-phenylethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.99-7.67 (m, 14H), 6.88 (bs, 1H), 5.30 (d, 2H), 4.98 (d, 1H), 4.63 (d, 1H), 4.62 (m , 1H), 4.14 (m, 1H), 3.88 (m, 2H), 3.30 (s, 2H), 2.97 (dd, 1H), 2.84 (t, 2H), 1.22-1.54 (m, 3H), 0.86 ( dd, 6H)

Example 706

N- (2-trifluoromethylbenzyl) -N-phenylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-4 Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.27 (bs, 1H), 6.64-7.72 (m, 15H), 5.54 (d, 1H), 5.23 (s, 2H), 4.88 (d, 1H), 4.66 (m , 1H), 4.23 (m, 1H), 3.34 (s, 2H), 3.07 (dd, 1H), 2.84 (t, 2H), 1.26-1.59 (m, 3H), 0.87 (dd, 6H)

Example 707

N- (2-trifluoromethylbenzyl) -N- (n-propylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.82-7.71 (m, 10H), 6.23 (bs, 1H), 5.32 (d, 2H), 5.17 (d, 1H), 4.70 (d, 1H), 4.64 (m , 1H), 4.16 (m, 1H), 3.58 (m, 2H), 3.32 (s, 2H), 3.01 (dd, 1H), 1.51 (m, 2H), 1.26-1.60 (m, 3H), 0.88 ( m, 6H), 0.77 (t, 3H)

Example 708

N- (2-trifluoromethylbenzyl) -N- (2-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.21 (bs, 1H), 6.69-7.72 (m, 14H), 5.53 (d, 1H), 5.23 (s, 2H), 4.87 (d, 1H), 4.66 (m , 1H), 4.24 (m, 1H), 3.35 (s, 2H), 3.06 (dd, 1H), 2.32 (s, 3H), 1.26-1.58 (m, 3H), 0.88 (d, 6H)

Example 709

N- (2-trifluoromethylbenzyl) -N- (3-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.69-7.72 (m, 10H), 5.47 (d, 1H), 5.24 (s, 2H), 4.89 (d, 1H), 4.73 (m, 1H), 4.28 (m , 1H), 3.34 (s, 2H), 3.11 (dd, 1H), 2.08 (s, 3H), 1.26-1.60 (m, 3H), 0.89 (d, 6H)

Example 710

N- (2-trifluoromethylbenzyl) -N- (4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.24 (bs, 1H), 6.74-7.72 (m, 14H), 5.53 (d, 1H), 5.24 (s, 2H), 4.88 (d, 1H), 4.68 (m , 1H), 4.24 (m, 1H), 3.34 (s, 2H), 3.07 (dd, 1H), 2.34 (s, 3H), 1.26-1.58 (m, 3H), 0.88 (d, 6H)

Example 711

N- (2-trifluoromethylbenzyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 9.26 (bs, 1H), 6.64-7.83 (m, 14H), 5.85 (d, 1H), 5.24 (s, 2H), 4.90 (d, 1H), 4.34 (m , 1H), 4.13 (m, 1H), 3.34 (s, 2H), 3.04 (dd, 1H), 2.32 (s, 3H), 1.26-1.58 (m, 3H), 0.86 (t, 6H)

Example 712

N- (2-trifluoromethylbenzyl) -N- (2,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.82-7.73 (m, 13H), 5.37 (d, 1H), 5.25 (s, 2H), 4.88 (d, 1H), 4.72 (m, 1H), 4.28 (m , 1H), 3.34 (s, 2H), 3.10 (dd, 1H), 2.31 (s, 3H), 2.03 (s, 3H), 1.26-1.58 (m, 3H), 0.88 (d, 6H)

Example 713

N- (2-trifluoromethylbenzyl) -N- (3,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.11 (bs, 1H), 6.75-7.72 (m, 13H), 5.49 (d, 1H), 5.24 (s, 2H), 4.87 (d, 1H), 4.67 (m , 1H), 4.24 (m, 1H), 3.35 (s, 2H), 3.06 (dd, 1H), 2.22 (s, 6H), 1.26-1.58 (m, 3H), 0.88 (d, 6H)

Example 714

N- (2-trifluoromethylbenzyl) -N-allylthiocarbamoyl-2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methylpropyl Amine

[Step 1]

N- (2-trifluoromethylbenzyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methylpropylamine

2- (Nt-butoxycarbonylamino) -2-methylpropion aldehyde was prepared in the same manner as in Reference Example 3 using 2- (Nt-butoxycarbonylamino) -2-methylpropionic acid. 2-trifluoromethylbenzylamine and 1- (4-cyanobenzyl) -1H-imidazole- A title compound was prepared in the same manner as in Reference Example 4 using 5-monoacetic acid hydrochloride.

¹ H-NMR (CDCl ₃ ): δ 7.38-7.68 (m, 7H), 7.17 (d, 2H), 6.98 (s, 1H), 6.42 (bs, 1H), 5.26 (s, 2H), 3.91 (s , 2H), 3.28 (s, 2H), 2.59 (s, 2H), 1.27 (s, 6H)

[Step 2]

N- (2-trifluoromethylbenzyl) -N-allylthiocarbamoyl-2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methylpropyl Amine

N- (2-trifluoromethylbenzyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methylpropylamine diluted with dichloromethane The solution (0.02M, 1ml, 0.02mmol) and the solution of allyl isothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) were reacted at room temperature for 3 hours, and then the reaction solution was subjected to short silica gel column chromatography ( Dichloromethane / methanol = 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.65 (d, 2H), 7.55 (m, 3H), 7.17 (d, 3H), 7.00 (s, 1H), 5.80 (m, 1H ), 5.35 (s, 2H), 5.07 (m, 4H), 4.20 (t, 2H), 4.00 (s, 2H), 3.25 (s, 2H), 1.40 (s, 6H)

Example 715-760

N- (2-trifluoromethylbenzyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methylpropylamine and the corresponding isothiocia The title compound was prepared in the same manner as in Step 2 of Example 714 using Nate.

Example 715

N- (2-trifluoromethylbenzyl) -N-benzylthiocarbamoyl-2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methylpropyl Amine

¹ H-NMR (CDCl ₃ ): δ 7.63 (m, 5H), 7.45 (m, 2H), 7.20 (m, 6H), 7.05 (bs, 1H), 7.00 (s, 1H), 5.30 (s, 2H ), 5.05 (s, 2H), 4.80 (d, 2H), 4.20 (t, 2H), 4.00 (s, 2H), 3.20 (s, 2H), 1.40 (s, 6H)

Example 716

N- (2-trifluoromethylbenzyl) -N- (2-biphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (m, 3H), 7.25-7.50 (m, 11H), 7.10 (d, 3H), 7.00 (s, 2H), 5.28 (s, 2H), 5.00 (s , 2H), 3.90 (bs, 2H), 3.20 (s, 2H), 1.40 (s, 6H)

Example 717

N- (2-trifluoromethylbenzyl) -N- (2-bromophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.75 (d, 1H), 7.45-7.70 (m, 6H), 7.37 (m, 3H), 7.12 (d, 3H), 7.00 (s, 1H), 5.30 (s , 4H), 4.14 (s, 2H), 3.27 (s, 2H), 1.45 (s, 6H)

Example 718

N- (2-trifluoromethylbenzyl) -N- (3-bromophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.40-7.65 (m, 6H), 7.20-7.37 (m, 4H), 7.10 (d, 2H), 6.95 (s, 1H), 5.40 (s, 2H), 5.30 (s, 2H), 3.96 (s, 2H), 3.28 (s, 2H), 1.43 (s, 6H)

Example 719

N- (2-trifluoromethylbenzyl) -N- (4-bromophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.60 (d, 3H), 7.42 (d, 4H), 7.27 (m, 3H), 7.07 (d, 2H), 6.95 (s, 1H ), 5.40 (s, 2H), 5.22 (s, 2H), 3.95 (s, 2H), 3.25 (s, 2H), 1.40 (s, 6H)

Example 720

N- (2-trifluoromethylbenzyl) -N- (n-butylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.60 (d, 2H), 7.55 (m, 3H), 7.17 (d, 3H), 7.00 (s, 1H), 5.40 (s, 2H ), 5.00 (s, 2H), 4.00 (s, 2H), 3.25 (s, 2H), 1.40 (s, 6H), 1.30 (m, 2H), 1.10 (q, 2H), 0.82 (t, 3H)

Example 721

N- (2-trifluoromethylbenzyl) -N-isobutylthiocarbamoyl-2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methyl Propylamine

¹ H-NMR (CDCl ₃ ): δ 7.40-7.68 (m, 5H), 7.15 (m, 3H), 7.00 (s, 1H), 5.38 (s, 2H), 5.00 (s, 2H), 4.08 (s , 2H), 3.38 (m, 2H), 3.25 (s, 2H), 1.75 (m, 1H), 1.42 (s, 6H), 0.66 (d, 6H)

Example 722

N- (2-trifluoromethylbenzyl) -N- (t-butylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.90 (s, 1H), 7.73 (d, 1H), 7.65 (d, 2H), 7.55 (m, 3H), 7.20 (m, 3H), 7.02 (s, 1H ), 5.40 (s, 2H), 4.90 (s, 2H), 4.10 (s, 2H), 3.27 (s, 2H), 1.45 (s, 6H), 1.28 (s, 9H)

Example 723

N- (2-trifluoromethylbenzyl) -N- (2-chlorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.60 (d, 2H), 7.45 (m, 2H), 7.20-7.40 (m, 4H), 7.15 (d, 2H), 7.00 (s , 1H), 5.30 (s, 4H), 4.12 (s, 2H), 3.25 (s, 2H), 1.45 (s, 6H)

Example 724

N- (2-trifluoromethylbenzyl) -N- (3-chlorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.58 (d, 3H), 7.25-7.50 (m, 6H), 7.17 (m, 1H), 7.05 (d, 2H), 6.95 (s , 1H), 5.40 (s, 2H), 5.30 (s, 2H), 3.95 (s, 2H), 3.25 (s, 2H), 1.40 (s, 6H)

Example 725

N- (2-trifluoromethylbenzyl) -N- (4-chlorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.58 (d, 3H), 7.45 (m, 2H), 7.22 (m, 5H), 7.05 (d, 2H), 6.95 (s, 1H ), 5.40 (s, 2H), 5.20 (S, 2H), 3.98 (s, 2H), 3.25 (s, 2H), 1.40 (s, 6H)

Example 726

N- (2-trifluoromethylbenzyl) -N- (3-chloro-2-methylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.58 (d, 3H), 7.43 (m, 2H), 7.28 (m, 2H), 7.20 (m, 2H), 7.07 (d, 2H ), 6.95 (s, 1H), 5.35 (s, 2H), 5.30 (s, 2H), 3.98 (s, 2H), 3.25 (s, 2H), 2.38 (s, 3H), 1.42 (s, 6H)

Example 727

N- (2-trifluoromethylbenzyl) -N-cyclohexylthiocarbamoyl-2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methyl Propylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.40-7.65 (m, 5H), 7.17 (m, 3H), 7.00 (s, 1H), 5.40 (s, 1H), 5.25 (s , 1H), 5.00 (s, 1H), 4.10 (m, 2H), 3.90 (s, 1H), 3.25 (s, 2H), 1.90 (m, 4H), 1.40 (s, 6H), 1.25 (s, 6H)

Example 728

N- (2-trifluoromethylbenzyl) -N-cyclopentylthiocarbamoyl-2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methyl Propylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.20-7.50 (m, 5H), 7.17 (m, 3H), 7.00 (s, 1H), 5.40 (s, 2H), 4.95 (s , 2H), 4.58 (m, 1H), 4.05 (s, 2H), 3.25 (s, 2H), 2.00 (m, 4H), 1.40 (s, 6H), 1.25 (s, 4H)

Example 729

N- (2-trifluoromethylbenzyl) -N- (2,4-dichlorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.60 (d, 4H), 7.45 (m, 2H), 7.30 (m, 3H), 7.12 (d, 3H), 7.00 (s, 1H ), 5.30 (s, 2H), 4.10 (s, 2H), 3.25 (s, 2H), 1.40 (s, 6H)

Example 730

N- (2-trifluoromethylbenzyl) -N- [2- (dimethylamino) ethylthiocarbamoyl] -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.90 (bs, 1H), 7.73 (d, 1H), 7.62 (d, 2H), 7.45 (m, 3H), 7.17 (d, 3H), 7.05 (s, 1H ), 5.92 (bs, 1H), 5.50 (s, 2H), 5.00 (s, 2H), 4.05 (s, 2H), 3.50 (s, 2H), 3.25 (s, 2H), 2.38 (m, 2H) , 1.82 (s, 6H), 1.40 (s, 6H)

Example 731

N- (2-trifluoromethylbenzyl) -N- [4- (dimethylamino) phenylthiocarbamoyl] -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.60 (m, 4H), 7.45 (m, 2H), 7.35 (d, 1H), 7.12 (d, 2H), 7.00 (s, 1H ), 6.98 (s, 2H), 6.65 (d, 2H), 5.35 (s, 2H), 5.22 (s, 2H), 4.05 (s, 2H), 3.25 (s, 2H), 2.95 (s, 6H) , 1.45 (s, 6H)

Example 732

N- (2-trifluoromethylbenzyl) -N- [3- (dimethylamino) propylthiocarbamoyl] -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 9.12 (bs, 1H), 7.73 (d, 1H), 7.65 (d, 2H), 7.45 (m, 3H), 7.19 (d, 2H), 7.03 (m, 2H ), 5.40 (s, 2H), 4.96 (s, 2H), 3.90 (s, 2H), 3.70 (m, 2H), 3.25 (s, 2H), 2.40 (m, 2H), 1.90 (s, 6H) , 1.72 (m, 2 H), 1.40 (s, 6 H)

Example 733

N- (2-trifluoromethylbenzyl) -N-ethoxycarbonylthiocarbamoyl-2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2 -Methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.50-7.70 (m, 6H), 7.40 (m, 1H), 7.17 (d, 2H), 7.00 (m, 1H), 5.35 (m, 4H), 5.00 (bs , 2H), 4.20 (q, 4H), 3.30 (s, 2H), 1.40 (s, 6H), 1.25 (d, 3H)

Example 734

N- (2-trifluoromethylbenzyl) -N-ethoxycarbonylmethylthiocarbamoyl-2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.62 (d, 2H), 7.40-7.58 (m, 3H), 7.18 (d, 3H), 7.00 (s, 1H), 5.38 (s , 2H), 5.12 (s, 2H), 4.33 (d, 2H), 4.19 (q, 2H), 4.00 (s, 2H), 3.25 (s, 2H), 1.40 (s, 6H), 1.25 (t, 3H)

Example 735

N- (2-trifluoromethylbenzyl) -N- (3-ethoxypropylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.90 (bs, 1H), 7.73 (d, 1H), 7.65 (d, 2H), 7.55 (m, 3H), 7.20 (d, 2H), 7.05 (m, 2H ), 5.82 (s, 1H), 5.40 (s, 2H), 5.00 (s, 2H), 3.97 (s, 2H), 3.72 (q, 2H), 3.40 (t, 2H), 3.25 (s, 2H) , 3.20 (t, 2H), 1.80 (q, 2H), 1.40 (s, 6H), 0.90 (t, 3H)

Example 736

N- (2-trifluoromethylbenzyl) -N-ethylthiocarbamoyl-2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methylpropyl Amine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.65 (d, 2H), 7.45 (m, 3H), 7.17 (d, 3H), 7.00 (s, 1H), 5.40 (s, 2H ), 5.05 (s, 2H), 4.00 (s, 2H), 3.60 (m, 2H), 3.25 (s, 2H), 1.40 (s, 6H), 1.07 (t, 3H)

Example 737

N- (2-trifluoromethylbenzyl) -N- (2-fluorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.60 (m, 3H), 7.45 (m, 3H), 7.20 (m, 1H), 7.12 (d, 4H), 6.95 (s, 1H ), 5.30 (s, 4H), 3.96 (s, 2H), 3.25 (s, 2H), 1.44 (s, 6H)

Example 738

N- (2-trifluoromethylbenzyl) -N- (3-fluorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.58 (d, 3H), 7.45 (m, 2H), 7.10-7.32 (m, 4H), 7.07 (d, 2H), 6.92 (m , 2H), 5.40 (bs, 2H), 5.25 (s, 2H), 3.97 (s, 2H), 3.26 (s, 2H), 1.42 (s, 6H)

Example 739

N- (2-trifluoromethylbenzyl) -N- (4-fluorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.60 (d, 3H), 7.45 (m, 3H), 7.25 (m, 4H), 7.10 (d, 2H), 7.00 (d, 2H ), 5.30 (s, 2H), 5.25 (s, 2H), 4.00 (s, 2H), 3.25 (s, 2H), 1.41 (s, 6H)

Example 740

N- (2-trifluoromethylbenzyl) -N- (4-hydroxyphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): 7.73 (d, 1H), 7.60 (d, 3H), 7.43 (m, 2H), 7.30 (d, 1H), 7.10 (m, 4H), 6.95 (s, 1H) , 6.80 (d, 2H), 5.35 (s, 2H), 5.30 (s, 2H), 4.00 (s, 2H), 3.25 (s, 2H), 1.41 (s, 6H)

Example 741

N- (2-trifluoromethylbenzyl) -N- (4-isopropylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.58 (m, 3H), 7.45 (m, 2H), 7.30 (m, 2H), 7.20 (s, 3H), 7.10 (d, 2H ), 7.00 (s, 1H), 5.30 (s, 4H), 4.00 (s, 2H), 3.25 (s, 2H), 2.90 (q, 1H), 1.43 (s, 6H), 1.12 (d, 6H)

Example 742

N- (2-trifluoromethylbenzyl) -N- (2-methoxyethylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.60 (bs, 1H), 7.73 (d, 1H), 7.60 (d, 2H), 7.50 (m, 3H), 7.17 (d, 3H), 7.00 (s, 1H ), 6.20 (bs, 1H), 5.50 (s, 2H), 5.00 (s, 2H), 4.03 (s, 2H), 3.70 (q, 2H), 3.37 (t, 2H), 3.25 (s, 2H) , 3.06 (s, 3H), 1.42 (s, 6H)

Example 743

N- (2-trifluoromethylbenzyl) -N- (2-methoxyphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.70 (s, 1H), 8.12 (d, 1H), 7.76 (d, 1H), 7.63 (m, 1H), 7.57 (d, 2H), 7.50 (m, 2H ), 7.30 (d, 1H), 7.17 (d, 3H), 7.00 (m, 2H), 6.80 (d, 1H), 5.38 (s, 2H), 5.20 (s, 2H), 4.20 (s, 2H) , 3.52 (s, 3H), 3.25 (s, 2H), 1.45 (s, 6H)

Example 744

N- (2-trifluoromethylbenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.60 (m, 3H), 7.45 (m, 2H), 7.30 (d, 1H), 7.12 (d, 4H), 7.00 (s, 1H ), 6.85 (d, 2H), 5.30 (s, 4H), 4.00 (s, 2H), 3.80 (s, 3H), 3.25 (s, 2H), 1.45 (s, 6H)

Example 745

N- (2-trifluoromethylbenzyl) -N- (3-methoxypropylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 9.00 (bs, 1H), 7.73 (d, 1H), 7.65 (d, 2H), 7.45 (m, 3H), 7.17 (d, 2H), 7.05 (m, 3H ), 5.40 (s, 2H), 4.95 (s, 2H), 4.00 (s, 2H), 3.70 (q, 2H), 3.35 (t, 2H), 3.25 (s, 2H), 2.85 (s, 3H) , 1.78 (p, 2H), 1.40 (s, 6H)

Example 746

N- (2-trifluoromethylbenzyl) -N- (2-methoxypyridin-5-ylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl] amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.90 (bs, 1H), 7.73 (d, 1H), 7.60 (d, 4H), 7.45 (m, 2H), 7.30 (d, 1H), 7.10 (d, 2H ), 6.95 (s, 1H), 6.75 (d, 1H), 5.80 (m, 1H), 5.38 (s, 2H), 5.25 (s, 2H), 4.00 (s, 2H), 3.93 (s, 3H) , 3.25 (s, 2H), 1.42 (s, 6H)

Example 747

N- (2-trifluoromethylbenzyl) -N-methylthiocarbamoyl-2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methylpropyl Amine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.65 (d, 2H), 7.45 (m, 4H), 7.17 (d, 2H), 7.12 (s, 1H), 7.00 (s, 1H ), 5.38 (s, 2H), 5.10 (s, 2H), 3.95 (s, 2H), 3.25 (s, 2H), 3.08 (d, 3H), 1.40 (s, 6H)

Example 748

N- (2-trifluoromethylbenzyl) -N- (4-methylthiophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.58 (d, 3H), 7.45 (m, 3H), 7.30 (d, 1H), 7.20 (s, 3H), 7.10 (d, 2H ), 6.95 (s, 1H), 5.80 (m, 1H), 5.35 (s, 2H), 5.25 (s, 2H), 4.00 (s, 2H), 3.25 (s, 2H), 2.48 (s, 3H) , 1.42 (s, 6H)

Example 749

N- (2-trifluoromethylbenzyl) -N- (2-naphthylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.60-7.82 (m, 6H), 7.45 (m, 7H), 7.12 (d, 1H), 7.00 (s, 3H), 5.40 (s, 2H), 5.20 (s , 2H), 4.00 (s, 2H), 3.25 (s, 2H), 1.45 (s, 6H)

Example 750

N- (2-trifluoromethylbenzyl) -N- (4-nitrophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.18 (d, 2H), 7.72 (d, 2H), 7.55 (m, 4H), 7.45 (q, 2H), 7.30 (s, 1H), 7.10 (d, 2H ), 6.95 (s, 1H), 5.42 (s, 2H), 5.25 (s, 2H), 3.90 (s, 2H), 3.33 (s, 2H), 1.43 (s, 6H)

Example 751

N- (2-trifluoromethylbenzyl) -N- (n-pentylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 8.70 (bs, 1H), 7.73 (d, 1H), 7.65 (d, 2H), 7.50 (m, 3H), 7.19 (d, 3H), 7.00 (s, 1H ), 5.40 (s, 2H), 5.00 (s, 2H), 4.10 (s, 2H), 3.43 (m, 2H), 3.25 (s, 2H), 1.43 (s, 6H), 1.25 (m, 2H) , 0.95 (m, 3H), 0.79 (t, 2H), 0.61 (d, 2H)

Example 752

N- (2-trifluoromethylbenzyl) -N- (2-phenylethylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.69 (s, 1H), 7.6d (d, 2H), 7.45 (m, 3H), 7.17 (d, 5H), 7.00 (s, 2H), 6.68 (s, 2H), 5.35 (s, 2H), 4.90 (s, 2H), 4.00 (s, 2H), 3.85 (q, 2H), 3.25 (s, 2H), 2.80 (t, 2H), 1.40 (s, 6H )

Example 753

N- (2-trifluoromethylbenzyl) -N-phenylthiocarbamoyl-2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-2-methylpropyl Amine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.58 (m, 3H), 7.45 (m, 2H), 7.25 (m, 6H), 7.07 (d, 2H), 7.00 (s, 1H ), 5.35 (s, 2H), 5.25 (s, 2H), 4.00 (s, 2H), 3.25 (s, 2H), 1.42 (s, 6H)

Example 754

N- (2-trifluoromethylbenzyl) -N- (n-propylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.65 (d, 2H), 7.50 (m, 3H), 7.17 (d, 3H), 7.00 (s, 1H), 5.37 (s, 2H ), 5.00 (s, 2H), 4.00 (s, 2H), 3.50 (q, 2H), 3.25 (s, 2H), 1.40 (s, 6H) 1.25 (m, 2H), 0.70 (t, 3H)

Example 755

N- (2-trifluoromethylbenzyl) -N- (3-methylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.65 (m, 1H), 7.58 (d, 2H), 7.45 (m, 2H), 7.32 (d, 1H), 7.20 (d, 1H ), 7.10 (m, 5H), 7.00 (s, 1H), 5.30 (s, 2H), 4.00 (s, 2H), 3.25 (s, 2H), 2.37 (s, 3H), 1.40 (s, 6H)

Example 756

N- (2-trifluoromethylbenzyl) -N- (2-methylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.65 (m, 1H), 7.55 (d, 2H), 7.40 (m, 3H), 7.20 (s, 3H), 7.12 (d, 3H ), 6.95 (s, 1H), 5.30 (s, 2H), 5.20 (s, 2H), 4.10 (s, 2H), 3.25 (s, 2H), 2.00 (s, 3H), 1.40 (s, 6H)

Example 757

N- (2-trifluoromethylbenzyl) -N- (4-methylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.65 (m, 1H), 7.57 (d, 2H), 7.45 (m, 2H), 7.36 (d, 1H), 7.17 (s, 6H ), 7.00 (s, 1H), 5.30 (s, 4H), 4.00 (s, 2H), 3.25 (s, 2H), 2.36 (s, 3H), 1.42 (s, 6H)

Example 758

N- (2-trifluoromethylbenzyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.73 (d, 1H), 7.62 (d, 1H), 7.55 (d, 3H), 7.45 (m, 4H), 7.36 (d, 1H), 7.07 (d, 3H ), 6.94 (s, 1H), 5.42 (s, 2H), 5.25 (s, 2H), 3.95 (s, 2H), 3.28 (s, 2H), 1.40 (s, 6H)

Example 759

N- (2-trifluoromethylbenzyl) -N- (2,4-dimethylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.75 (d, 2H), 7.65 (d, 1H), 7.60 (d, 2H), 7.50 (s, 2H), 7.39 (d, 1H), 7.17 (d, 2H ), 7.00 (m, 3H), 5.38 (s, 2H), 5.20 (s, 2H), 4.00 (s, 2H), 3.25 (s, 2H), 2.33 (s, 3H), 2.00 (s, 3H) , 1.40 (s, 6H)

Example 760

N- (2-trifluoromethylbenzyl) -N- (3,4-dimethylphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-2-methylpropylamine

¹ H-NMR (CDCl ₃ ): δ 7.75 (d, 1H), 7.65 (d, 1H), 7.58 (d, 2H), 7.45 (s, 2H), 7.35 (d, 1H), 7.12 (d, 3H ), 7.00 (s, 3H), 5.30 (s, 4H), 4.00 (s, 2H), 3.25 (s, 2H), 2.26 (s, 6H), 1.40 (s, 6H)

Example 761

N- (2-trifluoromethylbenzyl) -N-allylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutylamine

[Step 1]

N- (2-trifluoromethylbenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutylamine

2 (S)-(Nt-butoxycarbonyl) aminobutyric aldehyde was prepared in the same manner as in Reference Example 3 using 2 (S)-(Nt-butoxycarbonyl) aminobutyric acid. 2-trifluoromethylbenzylamine and 1- (4-cyanobenzyl) -1H-imidazole- instead of 3-dichlorobenzylamine and 1- (4-nitrobenzyl) -1H-imidazol-5-monoacetic acid hydrochloride The title compound was prepared in the same manner as in Reference Example 4 using 5-monoacetic acid hydrochloride.

¹ H-NMR (CDCl ₃ ): δ 7.64 (d, 1H), 7.59 (d, 2H), 7.51 (s, 3H), 7.13 (d, 2H), 7.00 (s, 1H), 6.23 (d, 1H ), 5.28 (s, 2H), 3.83-3.93 (m, 3H), 3.36 (s, 2H), 2.66 (d, 2H), 1.35-1.49 (m, 2H), 0.85 (t, 3H)

[Step 2]

N- (2-trifluoromethylbenzyl) -N-allylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutylamine

A solution of N- (2-trifluoromethylbenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutylamine diluted with dichloromethane (0.02M, 1ml, 0.02mmol) and a solution of allyl isothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) were reacted at room temperature for 3 hours, and then the reaction solution was subjected to short silica gel column chromatography (dichloro Methane / Methanol = 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 7.65 (m, 3H), 7.47 (m, 3H), 7.18 (m, 3H), 7.00 (s, 2H), 6.41 (bs, 1H), 5.85 (m, 1H ), 5.35 (q, 3H), 5.05 (m, 2H), 4.70 (d, 2H), 4.30 (t, 2H), 4.00 (q, 1H), 3.35 (s, 2H), 3.03 (dd, 1H) , 1.65 (m, 1 H), 1.45 (m, 1 H), 0.90 (t, 3 H)

Example 762-806

N- (2-trifluoromethylbenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutylamine and the corresponding isothiocyanate Using to prepare the title compound in the same manner as in Step 2 of Example 761.

Example 762

N- (2-trifluoromethylbenzyl) -N-benzylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.70 (s, 1H), 7.60 (d, 2H), 7.45 (m, 3H), 7.23 (m, 4H), 7.15 (m, 4H), 7.00 (m, 2H ), 6.70 (bs, 1H), 5.25 (m, 3H), 4.85 (d, 2H), 4.70 (d, 2H), 4.00 (q, 1H), 3.25 (s, 2H), 3.05 (dd, 1H) , 1.58 (m, 2H), 0.88 (t, 3H)

Example 763

N- (2-trifluoromethylbenzyl) -N- (2-biphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.60 (m, 4H), 7.45 (s, 1H), 7.30 (m, 10H), 7.12 (d, 2H), 6.98 (m, 2H), 5.45 (bs, 1H ), 5.20 (s, 2H), 4.62 (bs, 1H), 3.80 (s, 1H), 3.30 (s, 2H), 2.90 (dd, 1H), 1.60 (m, 1H), 0.85 (t, 3H)

Example 764

N- (2-trifluoromethylbenzyl) -N- (2-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.72 (t, 3H), 7.55 (m, 4H), 7.40 (m, 3H), 7.32 (m, 1H), 7.12 (m, 3H), 7.00 (s, 2H ), 5.45 (bs, 1H), 5.25 (s, 2H), 4.85 (d, 2H), 4.20 (m, 1H), 3.40 (s, 2H), 3.15 (dd, 1H), 1.70 (m, 1H) , 1.50 (m, 1 H), 0.90 (t, 3 H)

Example 765

N- (2-trifluoromethylbenzyl) -N- (3-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 9.10 (s, 1H), 7.70 (d, 1H), 7.55 (m, 4H), 7.45 (s, 2H), 7.20-7.40 (m, 4H), 7.10 (d , 2H), 6.95 (s, 1H), 6.85 (d, 1H), 5.90 (d, 1H), 5.29 (s, 2H), 4.74 (d, 1H), 4.40 (s, 1H), 4.00 (s, 1H), 3.40 (s, 2H), 3.02 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 ((t, 3H)

Example 766

N- (2-trifluoromethylbenzyl) -N- (4-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.80 (s, 1H), 7.70 (d, 1H), 7.56 (d, 2H), 7.45 (d, 4H), 7.35 (m, 3H), 7.08 (d, 2H ), 6.95 (s, 1H), 6.80 (d, 1H), 5.80 (d, 1H), 5.22 (s, 2H), 4.76 (d, 1H), 4.41 (s, 1H), 4.00 (m, 1H) , 3.39 (s, 2H), 3.04 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 (t, 3H)

Example 767

N- (2-trifluoromethylbenzyl) -N- (n-butylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.66 (m, 3H), 7.45 (m, 3H), 7.20 (m, 3H), 7.10 (m, 3H), 7.00 (s, 1H), 6.20 (bs, 1H ), 5.35 (m, 3H), 4.70 (d, 2H), 4.00 (m, 1H), 3.60 (m, 2H), 3.34 (s, 2H), 3.02 (dd, 1H), 1.60 (m, 1H) , 1.50 (m, 3H), 1.18 (m, 2H), 0.88 (m, 6H)

Example 768

N- (2-Trifluoromethylbenzyl) -N-isobutylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutyl Amine

¹ H-NMR (CDCl ₃ ): δ 7.65 (m, 3H), 7.52 (m, 2H), 7.40 (m, 2H), 7.18 (m, 3H), 7.00 (s, 1H), 6.00 (s, 1H ), 5.34 (q, 2H), 5.12 (m, 1H), 4.85 (m, 1H), 4.70 (d, 1H), 4.02 (s, 1H), 3.50 (m, 1H), 3.34 (s, 3H) , 3.05 (dd, 1H), 1.80 (m, 1H), 1.50 (m, 2H), 0.90 ((t, 3H), 0.75 (m, 6H)

Example 769

N- (2-trifluoromethylbenzyl) -N- (t-butylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.71 (m, 1H), 7.65 (d, 2H), 7.55 (m, 2H), 7.45 (m, 2H), 7.18 (d, 2H), 7.05 (s, 1H ), 5.36 (q, 2H), 5.15 (m, 1H), 4.75 (q, 2H), 4.00 (m, 1H), 3.35 (s, 2H), 3.05 (dd, 1H), 1.55 (m, 2H) , 1.31 (s, 9H), 0.90 ((t, 3H)

Example 770

N- (2-trifluoromethylbenzyl) -N- (2-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.90 (bs, 1H), 7.72 (t, 2H), 7.60 (m, 3H), 7.42 (m, 4H), 7.25 (m, 2H), 7.10 (d, 2H ), 7.00 (s, 1H), 6.95 (bs, 1H), 5.46 (bs, 1H), 5.25 (s, 2H), 4.85 (d, 1H), 4.80 (s, 1H), 4.20 (m, 1H) , 3.40 (s, 2H), 3.12 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 ((t, 3H)

Example 771

N- (2-trifluoromethylbenzyl) -N- (3-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 9.05 (bs, 1H), 7.70 (d, 1H), 7.60 (d, 3H), 7.42 (m, 5H), 7.20 (m, 2H), 7.10 (d, 2H ), 6.95 (s, 1H), 6.85 (ds, 1H), 5.90 (d, 1H), 5.28 (s, 2H), 4.80 (d, 1H), 4.40 (s, 1H), 4.00 (m, 1H) , 3.40 (s, 2H), 3.05 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 ((t, 3H)

Example 772

N- (2-trifluoromethylbenzyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.80 (bs, 1H), 7.70 (d, 1H), 7.60 (d, 3H), 7.40 (s, 2H), 7.30 (m, 5H), 7.10 (d, 2H ), 6.95 (s, 1H), 6.80 (s, 1H), 5.80 (d, 1H), 5.23 (s, 2H), 4.80 (d, 1H), 4.42 (s, 1H), 4.00 (m, 1H) , 3.38 (s, 2H), 3.05 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 ((t, 3H)

Example 773

N- (2-trifluoromethylbenzyl) -N- (3-chloro-4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.85 (bs, 1H), 7.70 (d, 1H), 7.56 (d, 3H), 7.45 (s, 1H), 7.38 (m, 3H), 7.25 (m, 2H ), 7.10 (d, 2H), 6.95 (s, 1H), 6.88 (d, 1H), 5.80 (d, 1H), 5.27 (s, 2H), 4.80 (d, 1H), 4.42 (s, 1H) , 4.00 (m, 1H), 3.38 (s, 2H), 3.05 (dd, 1H), 2.30 (s, 3H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 ((t, 3H)

Example 774

N- (2-trifluoromethylbenzyl) -N-cyclohexylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutyl Amine

¹ H-NMR (CDCl ₃ ): δ 7.65 (m, 3H), 7.52 (s, 1H), 7.43 (m, 2H), 7.18 (m, 3H), 7.00 (s, 2H), 5.80 (bs, 1H ), 5.35 (s, 3H), 5.11 (m, 1H), 4.82 (m, 1H), 4.75 (d, 1H), 4.22 (m, 1H), 4.00 (m, 1H), 3.38 (s, 2H) , 3.02 (dd, 1H), 1.90 (m, 2H), 1.20-1.65 (m, 8H), 1.10 (m, 2H), 0.90 (t, 3H)

Example 775

N- (2-trifluoromethylbenzyl) -N-cyclopentylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutyl Amine

¹ H-NMR (CDCl ₃ ): δ 7.65 (m, 3H), 7.52 (s, 1H), 7.43 (m, 2H), 7.18 (m, 3H), 7.00 (s, 1H), 5.95 (m, 1H ), 5.35 (q, 2H), 5.20 (m, 1H), 4.80 (m, 1H), 4.64 (m, 2H), 4.01 (m, 1H), 3.35 (s, 2H), 3.05 (dd, 1H) , 2.00 (m, 2H), 1.20-1.70 (m, 8H), 0.87 (t, 3H)

Example 776

N- (2-trifluoromethylbenzyl) -N- (2,4-dichlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.20 (bs, 1H), 7.75 (d, 2H), 7.60 (m, 3H), 7.40 (m, 4H), 7.28 (m, 1H), 7.15 (m, 2H ), 7.00 (s, 1H), 6.81 (s, 1H), 5.55 (bs, 1H), 5.25 (s, 2H), 4.83 (d, 1H), 4.70 (bs, 1H), 4.18 (m, 1H) , 3.40 (s, 2H), 3.16 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.95 (t, 3H)

Example 777

N- (2-trifluoromethylbenzyl) -N- [2- (dimethylamino) ethylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (m, 3H), 7.42 (m, 4H), 7.18 (m, 3H), 7.05 (s, 1H), 6.78 (bs, 1H), 4.65-5.05 (m , 2H), 4.10 (m, 1H), 3.50 (s, 2H), 3.38 (s, 2H), 3.14 (dd, 1H), 2.40 (m, 2H), 1.90 (s, 6H), 1.50 (m, 2H), 0.90 (t, 3H)

Example 778

N- (2-trifluoromethylbenzyl) -N- [4- (dimethylamino) phenylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.90 (bs, 1H), 7.70 (d, 1H), 7.58 (d, 3H), 7.48 (m, 2H), 7.40 (t, 2H), 7.10 (t, 3H ), 7.00 (s, 1H), 6.65 (d, 2H), 5.45 (d, 1H), 5.28 (s, 2H), 4.80 (d, 2H), 4.08 (m, 1H), 3.38 (s, 2H) , 3.10 (dd, 1H), 2.95 (s, 6H), 1.60 (m, 2H), 0.90 (t, 3H)

Example 779

N- (2-trifluoromethylbenzyl) -N- [3- (dimethylamino) propylthiocarbamoyl] -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 9.90 (bs, 1H), 7.72 (s, 1H), 7.65 (d, 2H), 7.42 (m, 3H), 7.20 (d, 2H), 7.05 (d, 1H ), 7.00 (s, 1H), 5.40 (q, 2H), 5.00 (m, 1H), 4.70 (s, 2H), 4.01 (m, 1H), 3.70 (m, 2H), 3.32 (q, 2H) , 2.90 (dd, 1H), 2.38 (m, 2H), 1.79 (s, 8H), 1.50 (p, 2H), 0.87 (t, 3H)

Example 780

N- (2-trifluoromethylbenzyl) -N-ethoxycarbonylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (m, 3H), 7.50 (m, 2H), 7.42 (d, 1H), 7.30 (s, 1H), 7.18 (d, 2H), 7.02 (d, 1H ), 6.25 (m, 1H), 5.32 (m, 3H), 4.90 (d, 1H), 4.65 (d, 1H), 4.18 (q, 2H), 4.05 (bs, 1H), 3.38 (s, 2H) , 3.00 (m, 1H), 1.70 (m, 2H), 1.25 (m, 2H), 0.88 (m, 4H)

Example 781

N- (2-trifluoromethylbenzyl) -N- (3-ethoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (m, 3H), 7.42 (m, 4H), 7.18 (m, 3H), 7.00 (s, 1H), 6.82 (bs, 1H), 5.38 (q 2H) , 4.90 (m, 2H), 4.68 (d, 1H), 4.00 (m, 1H), 3.75 (q, 2H), 3.42 (m, 2H), 3.38 (s, 2H), 3.18 (m, 2H), 2.98 (dd, 1H), 1.80 (p, 2H), 1.50 (m, 2H), 0.85 (q, 6H)

Example 782

N- (2-trifluoromethylbenzyl) -N-ethylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (m, 3H), 7.45 (m, 3H), 7.18 (m, 3H), 7.00 (s, 2H), 6.30 (bs, 1H), 5.33 (q 3H) , 4.65 (d, 2H), 4.00 (m, 1H), 3.65 (m, 2H), 3.38 (s, 2H), 3.00 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 1.12 (t, 3 H), 0.90 (t, 3 H)

Example 783

N- (2-trifluoromethylbenzyl) -N- (2-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.20 (bs, 1H), 7.71 (d, 2H), 7.58 (m, 3H), 7.43 (m, 3H), 7.18 (m, 5H), 7.00 (m, 2H ), 5.60 (d, 1H), 5.26 (q 3H), 4.85 (d, 1H), 4.52 (s, 1H), 4.10 (m, 1H), 3.39 (s, 2H), 3.10 (dd, 1H), 1.70 (m, 1 H), 1.50 (m, 1 H), 0.90 (t, 3 H)

Example 784

N- (2-trifluoromethylbenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.95 (s, 1H), 7.70 (d, 1H), 7.57 (m, 3H), 7.45 (s, 1H), 7.40 (m, 2H), 7.25 (m, 3H ), 7.10 (d, 2H), 6.97 (s, 1H), 6.85 (m, 2H), 5.85 (d, 1H), 5.28 (s, 3H), 4.75 (d, 2H), 4.45 (m, 1H) , 4.00 (m, 1H), 3.38 (s, 2H), 3.08 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 (t, 3H)

Example 785

N- (2-trifluoromethylbenzyl) -N- (4-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.60 (s, 1H), 7.72 (d, 1H), 7.58 (m, 4H), 7.35 (m, 4H), 7.10 (t, 3H), 7.00 (s, 2H ), 6.83 (d, 1H), 5.73 (d, 1H), 5.28 (s, 2H), 4.80 (d, 1H), 4.50 (bs, 1H), 4.00 (m, 1H), 3.38 (s, 2H) , 3.08 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 (t, 3H)

Example 786

N- (2-trifluoromethylbenzyl) -N- (4-hydroxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminobutylamine

¹ H-NMR (CD ₃ OD): δ 7.75 (m, 2H), 7.62 (m, 3H), 7.40 (m, 2H), 7.23 (d, 2H), 7.10 (d, 2H), 6.95 (s, 1H), 6.75 (d, 2H), 5.50 (d, 1H), 5.38 (s, 2H), 5.10 (d, 1H), 4.03 (m, 2H), 3.43 (q, 2H), 3.30 (m, 1H) ), 3.08 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 (t, 3H)

Example 787

N- (2-trifluoromethylbenzyl) -N- (4-isopropylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.20 (bs, 1H), 7.70 (d, 1H), 7.57 (d, 3H), 7.50 (m, 1H), 7.40 (t, 2H), 7.23 (m, 4H ), 7.20 (d, 2H), 7.00 (s, 2H), 5.60 (d, 1H), 5.26 (s, 2H), 4.80 (d, 1H), 4.70 (bs, 1H), 4.05 (m, 1H) , 3.38 (s, 2H), 3.08 (dd, 1H), 2.90 (m, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 1.12 (d, 6H), 0.90 (t, 3H)

Example 788

N- (2-trifluoromethylbenzyl) -N- (2-methoxyethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (m, 3H), 7.52 (s, 1H), 7.42 (t, 2H), 7.20 (d, 4H), 7.00 (s, 1H), 6.20 (s, 1H ), 5.35 (q, 2H), 4.98 (m, 2H), 4.70 (d, 1H), 4.08 (m, 1H), 3.75 (m, 2H), 3.40 (m, 2H), 3.33 (s, 2H) , 3.10 (s, 4H), 1.65 (m, 2H), 0.90 (t, 3H)

Example 789

N- (2-trifluoromethylbenzyl) -N- (2-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.22 (d, 1H), 7.77 (d, 1H), 7.65 (s, 1H), 7.50 (m, 5H), 7.25 (m, 2H), 7.07 (m, 5H ), 6.90 (d, 1H), 5.28 (s, 2H), 5.10 (s, 2H), 4.90 (d, 1H), 4.20 (m, 1H), 3.58 (s, 3H), 3.38 (s, 2H) , 3.18 (dd, 1H), 1.60 (m, 2H), 0.90 (t, 3H)

Example 790

N- (2-trifluoromethylbenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.22 (bs, 1H), 7.70 (d, 1H), 7.58 (d, 2H), 7.45 (m, 2H), 7.40 (t, 2H), 7.20 (d, 2H ), 7.10 (d, 2H), 7.00 (s, 2H), 6.85 (d, 2H), 5.60 (d, 1H), 5.28 (s, 2H), 4.80 (d, 1H), 4.65 (m, 1H) , 4.02 (m, 1H), 3.80 (s, 3H), 3.38 (s, 2H), 3.08 (dd, 1H), 1.60 (m, 2H), 0.90 (t, 3H)

Example 791

N- (2-trifluoromethylbenzyl) -N- (3-methoxypropylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.72 (d, 1H), 7.65 (d, 2H), 7.45 (m, 4H), 7.20 (d, 2H), 7.10 (d, 1H), 7.00 (s, 1H ), 6.90 (s, 1H), 5.38 (q, 2H), 4.90 (m, 2H), 4.70 (d, 1H), 4.02 (m, 1H), 3.72 (m, 2H), 3.40 (m, 2H) , 3.58 (s, 3H), 3.33 (s, 2H), 3.00 (dd, 1H), 2.85 (s, 3H), 1.80 (m, 2H), 1.50 (m, 2H), 0.90 (t, 3H)

Example 792

N- (2-trifluoromethylbenzyl) -N- (2-methoxypyridin-5-ylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole -5-yl] acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.80 (bs, 1H), 8.00 (d, 1H), 7.77 (d, 2H), 7.58 (d, 3H), 7.40 (m, 3H), 7.10 (d, 2H ), 6.90 (m, 2H), 6.75 (d, 1H), 5.80 (d, 1H), 5.28 (s, 2H), 4.70 (d, 1H), 4.50 (s, 1H), 4.02 (m, 1H) , 3.90 (s, 3H), 3.38 (s, 2H), 3.06 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 (t, 3H)

Example 793

N- (2-trifluoromethylbenzyl) -N-methylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (m, 3H), 7.45 (m, 3H), 7.20 (m, 3H), 7.00 (m, 2H), 6.70 (s, 1H), 5.32 (m, 3H ), 4.65 (d, 1H), 4.55 (s, 1H), 4.00 (m, 1H), 3.38 (s, 2H), 3.12 (d, 3H), 2.96 (dd, 1H), 1.70 (m, 1H) , 1.50 (m, 1 H), 0.90 (t, 3 H)

Example 794

N- (2-trifluoromethylbenzyl) -N- (4-methylthiophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.50 (bs, 1H), 7.70 (d, 1H), 7.58 (d, 3H), 7.32-7.46 (m, 4H), 7.25 (d, 3H), 7.10 (d , 2H), 7.00 (s, 1H), 6.90 (s, 1H), 5.70 (d, 1H), 5.25 (s, 2H), 4.80 (d, 1H), 4.55 (s, 1H), 4.01 (m, 1H), 3.38 (s, 2H), 3.06 (dd, 1H), 2.45 (s, 3H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 (t, 3H)

Example 795

N- (2-trifluoromethylbenzyl) -N- (2-naphthylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.80 (bs, 1H), 7.68-7.83 (m, 5H), 7.58 (d, 2H), 7.22 (m, 7H), 7.00 (m, 3H), 6.88 (d , 1H), 5.80 (d, 1H), 5.20 (s, 2H), 4.82 (d, 1H), 4.60 (s, 1H), 4.05 (m, 1H), 3.38 (s, 2H), 3.09 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 (t, 3H)

Example 796

N- (2-trifluoromethylbenzyl) -N- (4-nitrophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 9.60 (bs, 1H), 8.20 (d, 2H), 7.80 (d, 2H), 7.70 (d, 1H), 7.55 (m, 4H), 7.40 (m, 2H ), 7.10 (d, 2H), 7.00 (d, 2H), 6.75 (d, 1H), 6.02 (d, 1H), 5.23 (s, 2H), 4.80 (d, 1H), 4.25 (m, 1H) , 3.98 (s, 1H), 3.40 (s, 2H), 3.09 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 (t, 3H)

Example 797

N- (2-trifluoromethylbenzyl) -N- (n-pentylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.70 (m, 3H), 7.48 (m, 3H), 7.20 (m, 4H), 7.00 (s, 1H), 5.90 (s, 1H), 5.38 (q, 2H ), 5.00 (m, 2H), 4.70 (d, 1H), 4.02 (m, 1H), 3.60 (m, 1H), 3.45 (m, 1H), 3.35 (s, 2H), 3.06 (dd, 1H) , 1.68 (m, 4H), 1.10 (m, 2H), 0.90 (t, 3H), 0.75 (m, 5H)

Example 798

N- (2-trifluoromethylbenzyl) -N- (2-phenylethylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.62 (m, 3H), 7.50 (s, 1H), 7.40 (m, 2H), 7.15 (m, 5H), 7.00 (m, 4H), 6.10 (bs, 1H ), 5.32 (q, 2H), 5.05 (m, 1H), 4.70 (m, 1H), 4.60 (d, 1H), 3.90 (m, 3H), 3.36 (s, 2H), 3.00 (dd, 1H) , 2.85 (t, 2H), 1.57 (m, 2H), 0.90 (t, 3H)

Example 799

N- (2-trifluoromethylbenzyl) -N-phenylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.50 (bs, 1H), 7.72 (d, 1H), 7.58 (d, 3H), 7.40 (s, 2H), 7.18-7.40 (m, 6H), 7.10 (d , 2H), 7.00 (s, 1H), 6.95 (s, 1H), 5.70 (d, 1H), 5.28 (s, 2H), 4.80 (d, 1H), 4.62 (s, 1H), 4.02 (m, 1H), 3.38 (s, 2H), 3.09 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 (t, 3H)

Example 800

N- (2-trifluoromethylbenzyl) -N- (n-propylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.65 (m, 3H), 7.46 (m, 3H), 7.20 (m, 3H), 7.05 (m, 2H), 6.20 (s, 1H), 5.30 (s, 3H ), 4.70 (d, 2H), 4.00 (m, 1H), 3.58 (m, 2H), 3.38 (s, 2H), 3.03 (dd, 1H), 1.50 (m, 4H), 0.90 (t, 3H) , 0.80 (t, 3H)

Example 801

N- (2-trifluoromethylbenzyl) -N- (3-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.30 (bs, 1H), 7.72 (d, 1H), 7.55 (d, 3H), 7.50 (s, 1H), 7.40 (t, 2H), 7.02-7.24 (m , 5H), 7.00 (m, 2H), 5.60 (d, 1H), 5.25 (s, 2H), 4.80 (d, 1H), 4.65 (m, 1H), 4.02 (m, 1H), 3.38 (s, 2H), 3.06 (dd, 1H), 2.32 (s, 3H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 (t, 3H)

Example 802

N- (2-trifluoromethylbenzyl) -N- (2-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.72 (d, 1H), 7.55 (m, 3H), 7.42 (m, 4H), 7.18 (m, 7H), 7.00 (s, 1H), 5.50 (d, 1H ), 5.26 (s, 2H), 4.88 (d, 2H), 4.12 (m, 1H), 3.38 (s, 2H), 3.12 (dd, 1H), 2.10 (s, 3H), 1.70 (m, 1H) , 1.50 (m, 1 H), 0.90 (t, 3 H)

Example 803

N- (2-trifluoromethylbenzyl) -N- (4-methylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 8.30 (bs, 1H), 7.72 (d, 1H), 7.55 (d, 3H), 7.40 (m, 3H), 7.18 (m, 5H), 7.00 (m, 2H ), 5.60 (d, 1H), 5.25 (s, 2H), 4.80 (d, 1H), 4.65 (m, 1H), 4.02 (m, 1H), 3.38 (s, 2H), 3.06 (dd, 1H) , 2.32 (s, 3H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 (t, 3H)

Example 804

N- (2-trifluoromethylbenzyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 9.40 (bs, 1H), 7.90 (s, 1H), 7.70 (m, 2H), 7.55 (d, 3H), 7.40 (m, 5H), 7.05 (d, 2H ), 6.95 (s, 1H), 6.85 (d, 1H), 6.00 (d, 1H), 5.25 (s, 2H), 4.80 (d, 1H), 4.30 (m, 1H), 4.00 (m, 1H) , 3.38 (s, 2H), 3.03 (dd, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 0.90 (t, 3H)

Example 805

N- (2-trifluoromethylbenzyl) -N- (2,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.72 (d, 1H), 7.60 (d, 3H), 7.41 (m, 4H), 7.10 (d, 3H), 7.00 (s, 4H), 5.45 (m, 1H ), 5.26 (s, 2H), 4.80 (d, 2H), 4.12 (m, 1H), 3.38 (s, 2H), 3.12 (dd, 1H), 2.35 (s, 3H), 2.05 (s, 3H) , 1.70 (m, 1 H), 1.50 (m, 1 H), 0.90 (t, 3 H)

Example 806

N- (2-trifluoromethylbenzyl) -N- (3,4-dimethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} aminobutylamine

¹ H-NMR (CDCl ₃ ): δ 7.72 (d, 1H), 7.60 (d, 3H), 7.41 (m, 4H), 7.10 (d, 3H), 7.00 (s, 4H), 5.45 (m, 1H ), 5.26 (s, 2H), 4.80 (d, 2H), 4.12 (m, 1H), 3.38 (s, 2H), 3.12 (dd, 1H), 2.35 (s, 3H), 2.05 (s, 3H) , 1.70 (m, 1 H), 1.50 (m, 1 H), 0.90 (t, 3 H)

Example 807

N- (2-chlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

[Step 1]

N- (2-chlorobenzyl) -2 (S)-(t-butoxycarbonyl) amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Step 1 of Reference Example 4, using 2-chlorobenzylamine instead of 2,3-dichlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.4 (m, 2H), 7.2 (m, 2H), 4.6 (bs, 1H), 3.9 (m, 2H), 3.6 (bs, 1H), 2.6 (t, 2H), 1.4 (s, 9H), 1.1-1.6 (m, 3H), 0.8 (m, 6H)

[Step 2]

N- (2-chlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-(t-butoxycarbonyl) amino-3 (S) -methylpentylamine

N- (2-chlorobenzyl) -2 (S)-(t-butoxycarbonyl) amino-3 (S) -methylpentylamine (0.50 g, 1.48 mmol) was dissolved in dichloromethane (10 ml) and 4- Methoxyphenylisothiocyanate (0.20 ml, 1.48 mmol) was added and stirred at room temperature for 3 hours. The solvent was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (hexane / dichloromethane = 2/1, v / v) to give the title compound as a solid.

¹ H-NMR (CDCl ₃ ): δ 7.2-7.4 (m, 6H), 6.9 (d, 2H), 5.5 (m, 1H), 5.1 (m, 1H), 4.7 (m, 2H), 3.9 (m , 1H), 3.8 (s, 3H), 3.3 (m, 2H), 1.4 (s, 9H), 1.2-1.6 (m, 3H), 0.9 (m, 6H)

[Step 3]

N- (2-chlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S) -amino-3 (S) -methylpentylamine

N- (2-chlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-(t-butoxycarbonyl) amino-3 (S) -methylpentylamine (0.3 g), Trifluoroacetic acid (2 ml) and dichloromethane (10 ml) solution were stirred at room temperature for 2.5 hours. The reaction solution was concentrated under reduced pressure, the residue was dissolved in dichloromethane, washed with saturated sodium bicarbonate solution, the organic layer was dehydrated with anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to prepare an oily title compound.

[Step 4]

N- (2-chlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride (0.16 g, 0.57 mmol), 1-hydroxybenzotriazole hydrate (0.11 g, 0.85 mmol) and 1- (3-dimethyl Aminopropyl) -3-ethylcarbodiimide hydrochloride (0.16 g, 0.85 mmol) was dissolved in dichloromethane (30 ml) and triethylamine (0.12 ml, 1.13 mmol) was added dropwise and stirred at room temperature for 30 minutes. N- (2-chlorobenzyl) -N- (4-methoxyphenyl) thiocarbamoyl-2 (S) -amino-3 (S) -methylpentylamine (0.23 g, 0.57 mmol) was added to the reaction solution. The reaction solution was diluted with dichloromethane (50 ml), washed with saturated aqueous sodium bicarbonate solution, the organic layer was dehydrated with anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure. The concentrated residue was purified by silica gel column chromatography (dichloromethane / methanol = 40/1) to give the title compound (0.15 g) in the foam.

¹ H-NMR (CDCl ₃ ): δ 7.6 (d, 2H), 7.4 (ms, 2H), 7.2 (m, 3H), 7.0-7.1 (m, 4H), 7.0 (s, 1H), 6.8 (d , 2H), 5.2 (d, 2H), 4.8 (dd, 2H), 4.1 (m, 1H), 3.7 (s, 3H), 3.3 (s, 2H), 3.1 (dd, 2H), 1.0-1.6 ( m, 3H), 0.9 (m, 6H)

Example 808

N- (3-chlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

[Step 1]

N- (3-chlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

3-chlorobenzylamine and 1- (4-cyanobenzyl) -1H-imidazole-5 instead of 2,3-dichlorobenzylamine and 1- (4-nitrobenzyl) -1H-imidazol-5-monoacetic acid hydrochloride The title compound was prepared in the same manner as in Reference Example 4 using monoacetic acid hydrochloride.

TLC: R _f = 0.3 (dichloromethane / methanol = 10/1)

¹ H-NMR (CDCl ₃ ): δ 7.6 (d, 2H), 7.5 (s, 1H), 7.2-7.3 (m, 3H), 7.1 (m, 3H), 7.0 (s, 1H), 5.3 (s , 2H), 3.9 (m, 1H), 3.7 (d, 2H), 3.4 (s, 2H), 2.7 (d, 2H), 1.0-1.5 (m, 3H), 0.8-1.0 (m, 6H)

[Step 2]

N- (3-chlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

N- (3-Chlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine (0.50 g , 1.48 mmol) was dissolved in dichloromethane (10 ml) and 4-methoxyphenyl isothiocyanate (0.20 ml, 1.48 mmol) was added dropwise. After the reaction mixture was stirred at room temperature for 3 hours, the solvent was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane / dichloromethane = 2/1, v / v) to give the title compound in the solid phase.

¹ H-NMR (CDCl ₃ ): δ 7.7 (d, 2H), 7.5 (s, 1H), 7.3 (ms, 3H), 7.2 (s, 1H), 7.1-7.2 (m, 4H), 7.0 (s , 1H), 6.8 (d, 2H), 5.2 (m, 2H), 4.8 (dd, 2H), 4.2 (m, 1H), 3.8 (s, 3H), 3.4 (s, 2H), 3.2 (dd, 2H), 1.0-1.6 (m, 3H), 0.9 (m, 6H)

Example 809-819

Corresponding to N- (3-chlorobenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine The title compound was prepared in the same manner as Step 2 of Example 808 using isothiocyanate.

Example 809

N- (3-chlorobenzyl) -N-benzylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-7.62 (m, 15H), 6.20 (t, 1H), 5.28 (d, 2H), 4.42-5.20 (m, 5H), 4.15 (m, 1H), 3.25 (s, 2H), 3.12 (dd, 1H), 1.30-1.65 (m, 2H), 1.05 (m, 1H), 0.88 (m, 6H)

Example 810

N- (3-chlorobenzyl) -N- (2-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.70 (m, 14H), 5.35 (s, 2H), 5.18 (m, 1H), 4.65-5.02 (dd, 2H), 4.24 (m, 1H), 3.35 (s, 2H), 3.20 (dd, 1H), 1.35-1.70 (m, 2H), 1.05 (m, 1H), 0.90 (m, 6H)

Example 811

N- (3-chlorobenzyl) -N- (3-bromophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-7.58 (m, 14H), 5.22 (s, 2H), 4.90 (t, 1H), 4.30 5.22 (dd, 2H), 4.15 (m, 1H), 3.32 ( s, 2H), 3.16 (dd, 1H), 1.35-1.70 (m, 2H), 1.05 (m, 1H), 0.90 (m, 6H)

Example 812

N- (3-chlorobenzyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino -3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.95-7.60 (m, 14H), 5.22 (d, 2H), 4.95 (t, 1H), 4.52 5.18 (dd, 2H), 4.16 (m, 1H), 3.30 ( s, 2H), 3.18 (dd, 1H), 1.35-1.70 (m, 2H), 1.05 (m, 1H), 0.92 (m, 6H)

Example 813

N- (3-chlorobenzyl) -N-ethylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.65 (m, 10H), 5.85 (t, 1H), 5.35 (d, 2H), 5.04 (t, 1H), 4.42 4.68 (dd, 2H), 4.10 ( m, 1H), 3.55 (m, 2H), 3.28 (s, 2H), 3.08 (dd, 1H), 1.35-1.70 (m, 2H), 1.05 (m, 1H), 1.04 (t, 3H), 0.88 (m, 6H)

Example 814

N- (3-chlorobenzyl) -N- (2-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.78 (m, 14H), 5.25 (s, 2H), 4.15 (m, 1H), 4.60 5.10 (dd, 2H), 4.20 (m, 1H), 3.35 ( s, 2H), 3.16 (dd, 1H), 1.35-1.70 (m, 2H), 1.05 (m, 1H), 0.90 (m, 6H)

Example 815

N- (3-chlorobenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.90-7.60 (m, 14H), 5.25 (s, 2H), 4.95 (bs, 1H), 4.50 5.20 (dd, 2H), 4.18 (m, 1H), 3.35 ( s, 2H), 3.18 (dd, 1H), 1.35-1.70 (m, 2H), 1.05 (m, 1H), 0.90 (m, 6H)

Example 816

N- (3-chlorobenzyl) -N- (4-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 7.00-7.60 (m, 14H), 5.25 (d, 2H), 4.95-5.18 (m, 2H), 4.55 (d, 1H), 4.15 (m, 1H), 3.32 (s, 2H), 3.16 (dd, 1H), 1.30-1.70 (m, 2H), 1.05 (m, 1H), 0.90 (m, 6H)

Example 817

N- (3-chlorobenzyl) -N-methylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.88-7.68 (m, 10H), 6.25 (bs, 1H), 5.35 (dd, 2H), 5.02 (m, 1H), 4.40 4.72 (dd, 2H), 4.10 ( m, 1H), 3.30 (s, 2H), 3.05 (m, 4H), 1.30-1.70 (m, 2H), 1.05 (m, 1H), 0.92 (m, 6H)

Example 818

N- (3-chlorobenzyl) -N- (3-trifluoromethylphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.95-7.60 (m, 14H), 5.22 (s, 2H), 4.82 (bs, 1H), 4.50 5.38 (dd, 2H), 4.18 (m, 1H), 3.35 ( s, 2H), 3.20 (dd, 1H), 1.30-1.70 (m, 2H), 1.05 (m, 1H), 0.90 (m, 6H)

Example 819

N- (3-chlorobenzyl) -N-allylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) Methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 6.95-7.65 (m, 10H), 5.95 (t, 1H), 5.78 (m, 1H), 5.20 (m, 1H), 5.05 (d, 2H), 4.40-4.75 (dd, 2H), 4.02-3.35 (m, 3H), 1.30-1.70 (m, 2H), 1.05 (m, 1H), 0.88 (m, 6H)

Example 820

N- (2,6-dichlorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 2,6-dichlorobenzylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.7 (d, 2H), 7.4-7.5 (ms, 2H), 7.3 (m, 3H), 7.1-7.2 (m, 4H), 6.8 (d, 2H), 5.4 (m, 2H), 4.9 (dd, 2H), 4.3 (m, 1H), 3.8 (s, 3H), 3.4 (s, 2H), 3.2 (dd, 2H), 1.0-1.8 (m, 3H), 0.9 (m, 6H)

Example 821

N- (2-fluorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 2-fluorobenzylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.7 (d, 2H), 7.5 (ms, 2H), 7.1-7.4 (m, 8H), 7.1 (s, 4H), 6.9 (d, 2H), 5.4 (d , 2H), 4.8 (dd, 2H), 4.2 (m, 1H), 3.8 (s, 3H), 3.4 (s, 2H), 3.2 (dd, 2H), 1.0-1.8 (m, 3H), 0.9 ( m, 6H)

Example 822

N- (2,3-difluorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 2,3-difluorobenzylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.6 (d, 2H), 7.5 (s, 2H), 7.4 (m, 1H), 7.3 (s, 1H), 7.0-7.2 (m, 6H), 6.8 (d , 2H), 5.3 (d, 2H), 4.8 (dd, 2H), 4.2 (m, 1H), 3.8 (s, 3H), 3.4 (s, 2H), 3.2 (dd, 2H), 1.0-1.8 ( m, 3H), 0.8 (m, 6H)

Example 823

N- (2,6-difluorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 2,6-difluorobenzylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.7 (d, 2H), 7.5 (s, 2H), 7.3-7.4 (ms, 1H), 7.1-7.3 (m, 5H), 7.1 (s, 1H), 6.8 (d, 2H), 5.3 (d, 2H), 4.9 (dd, 2H), 4.3 (m, 1H), 3.8 (s, 3H), 3.5 (s, 2H), 3.3 (dd, 2H), 1.0- 1.7 (m, 3H), 0.9 (m, 6H)

Example 824

N- (4-t-butylbenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 4-t-butylbenzylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.6 (d, 2H), 7.5 (s, 1H), 7.4 (m, 2H), 7.3 (s, 1H), 7.3 (m, 4H), 7.1 (m, 2H ), 6.9 (d, 2H), 5.3 (d, 2H), 4.8 (dd, 2H), 4.3 (m, 1H), 3.8 (s, 3H), 3.4 (s, 2H), 3.2 (dd, 2H) , 1.4 (s, 9H), 1.0-1.7 (m, 3H), 0.9 (m, 6H)

Example 825

N- (2-ethoxybenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 2-ethoxybenzylamine instead of 2-chlorobenzylamine.

Example 826

N- (pyridin-3-yl) methyl-N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 3-amino-methylpyridine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 8.6 (d, 1H), 8.5 (s, 1H), 8.1 (m, 1H), 7.6 (d, 2H), 7.5 (s, 1H), 7.3 (m, 2H ), 7.1-7.2 (m, 3H), 7.0 (s, 1H), 6.9 (d, 2H), 5.3 (d, 2H), 4.6 (d, 2H), 4.2 (m, 1H), 3.8 (s, 3H), 3.4 (s, 2H), 3.2 (dd, 2H), 1.0-1.9 (m, 3H), 0.9-1.0 (m, 6H)

Example 827

N- [2- (3,4-dimethoxyphenyl)] ethyl-N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imid Dazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 3,4-dimethoxy-phenylethylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.6 (d, 2H), 7.5 (s, 1H), 7.3 (m, 2H), 7.1 (d, 2H), 7.0 (m, 2H), 6.8 (d, 2H ), 6.7 (d, 2H), 5.3 (d, 2H), 5.1 (m, 2H), 4.2 (m, 1H), 3.9 (s, 6H), 3.8 (s, 3H), 3.6 (m, 2H) , 3.3 (s, 2H), 2.9 (m, 2H), 1.0-1.7 (m, 3H), 0.9-1.0 (m, 6H)

Example 828

N- (2-phenylpropyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 1-amino-2-phenylpropane instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.6 (d, 2H), 7.5 (s, 1H), 7.2-7.4 (m, 5H), 7.1-7.2 (m, 3H), 7.0 (s, 1H), 6.9 (m, 1H), 6.8 (d, 2H), 5.3 (m, 2H), 4.6 (m, 1H), 4.2 (m, 1H), 3.9 (s, 3H), 3.8 (s, 2H), 3.3 ( m, 4H), 2.0-2.7 (m, 3H), 2.4 (m, 3H), 1.0 (m, 6H), 0.8 (d, 3H)

Example 829

N- [2- (2-methoxyphenyl) ethyl] -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole- 5-yl] acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 2- (2-methoxy-phenyl) ethylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.6 (d, 2H), 7.5 (m, 2H), 7.2-7.3 (m, 3H), 7.2 (d, 1H), 7.1 (d, 2H), 6.9-7.0 (m, 4H), 5.3 (m, 2H), 4.2 (m, 1H), 3.9 (s, 3H), 3.7 (s, 3H), 3.6 (q, 2H), 3.3 (s, 2H), 3.2 ( d, 2H), 2.9 (m, 2H), 1.1-1.7 (m, 3H), 0.9 (m, 6H)

Example 830

N- (4-nitrobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 4-nitrobenzylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 8.16-8.21 (m, 2H), 7.96 (bs, 1H), 7.55-7.60 (m, 2H), 7.47 (s, 1H), 7.36-7.43 (m, 2H) , 7.00-7.17 (m, 5H), 6.82-6.88 (m, 3H), 6.57-6.03 (m, 1H), 5.20-5.38 (m, 3H), 4.84-5.03 (m, 1H), 4.59-4.71 ( m, 1H), 4.04-4.16 (m, 1H), 3.79 (s, 3H), 3.35 (m, 2H), 3.12 (m, 1H), 1.54-1.63 (m, 1H), 1.35 (m, 1H) , 1.12 (m, 1 H), 0.90 (m, 6 H)

Example 831

N- [2- (2-fluorophenyl)] ethyl-N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole- 5-yl] acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 2- (2-fluorophenyl) ethylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.60 (m, 3H), 7.43 (s, 1H), 7.14-7.21 (m, 5H), 7.08 (m, 4H), 6.99 (m, 1H), 5.26 (m , 2H), 5.00 (m, 1H), 4.14 (m, 1H), 3.81 (s, 3H), 3.42-3.58 (m, 1H), 3.28 (s, 2H), 3.02-3.15 (m, 1H), 2.94 (bs, 2H), 1.65 (m, 1H), 1.45 (m, 1H), 1.10 (m, 1H), 0.93 (m, 6H)

Example 832

N- (4-methoxybenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 4-methoxybenzylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.47 (s, 1H), 7.29-7.35 (m, 2H), 7.09-7.17 (m, 4H), 7.02 (m, 3H), 7.00 (s, 1H), 6.85 (m, 3H), 5.14-5.38 (m, 3H), 4.52-4.82 (m, 2H), 4.15 (m, 1H), 3.80 (s, 3H), 3.78 (s, 3H ), 3.32 (s, 2H), 3.11-3.22 (m, 1H), 1.59-1.63 (m, 1H), 1.43-1.51 (m, 1H), 1.12 (m, 1H), 0.90 (m, 6H)

Example 833

N- (3,4-methylenedioxybenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using piperonylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.20-7.50 (m, 3H), 7.00-7.18 (m, 4H), 6.60-6.90 (m, 4H), 6.04 (s, 2H) , 5.10-5.35 (m, 3H), 4.52-4.82 (m, 2H), 4.11-4.21 (m, 1H), 3.80 (s, 3H), 3.32 (s, 2H), 3.11-3.22 (m, 1H) , 2.02 (m, 1H), 1.40-1.63 (m, 2H), 1.02-1.15 (m, 2H), 0.92 (m, 6H)

Example 834

N- (2-methylbenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 2-methylbenzylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.6 (d, 2H), 7.4 (s, 1H), 7.2 (m, 2H), 7.1 (m, 3H), 7.0 (s, 2H), 6.8 (d, 2H ), 5.3 (m, 2H), 4.5-4.8 (dd, 2H), 4.2 (m, 1H), 3.8 (s, 3H), 3.3 (s, 2H), 3.1 (dd, 2H), 2.3 (s, 3H), 1.1-1.5 (m, 3H), 0.9 (m, 6H)

Example 835

N- (2-methylbenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 2-methylbenzylamine and 3-fluorophenylisothiocyanate instead of 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate.

¹ H-NMR (CDCl ₃ ): δ 7.6 (d, 2H), 7.4 (s, 1H), 7.2-7.3 (m, 3H), 7.1 (m, 3H), 7.0 (s, 2H), 6.9 (d , 2H), 5.3 (m, 2H), 4.8 (dd, 2H), 4.2 (m, 1H), 3.4 (s, 2H), 3.1 (d, 2H), 2.3 (s, 3H), 1.1-1.6 ( m, 3H), 0.9-1.0 (m, 6H)

Example 836

N- (2-methylbenzyl) -N- (2-methoxypyridin-5-yl) thiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5- Acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 2-methylbenzylamine and 2-methoxypyridin-5-ylisothiocyanate instead of 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate. .

¹ H-NMR (CDCl ₃ ): δ 7.8 (s, 1H), 7.6 (d, 2H), 7.4 (m, 1H), 7.3 (s, 1H), 7.2 (m, 3H), 7.1 (s + d , 3H), 7.0 (s, 1H), 6.7 (d, 1H), 5.3 (d, 2H), 4.5 5.0 (dd, 2H), 4.2 (m, 1H), 3.8 (s, 3H), 3.3 (s , 2H), 3.1 (d, 2H), 2.4 (s, 3H), 1.0-1.6 (m, 3H), 0.8-0.9 (m, 6H)

Example 837

N- (4-fluorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 4-fluorobenzylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.6 (d, 2H), 7.4 (s, 1H), 7.3 (m, 1H), 7.2 (m, 2H), 7.0-7.1 (m, 5H), 7.0 (s , 1H), 6.8 (d, 2H), 5.3 (m, 2H), 4.5-4.8 (dd, 2H), 4.1-4.2 (m, 1H), 3.8 (s, 3H), 3.3 (s, 2H), 3.1 (dd, 2H), 1.1-1.5 (m, 3H), 0.9 (m, 6H)

Example 838

N- (pyridin-4-ylmethyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 4-aminomethylpyridine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 8.5 (d, 2H), 7.6 (d, 2H), 7.6 (s, 1H), 7.5 (m, 1H), 7.0-7.1 (m, 5H), 6.9 (s , 1H), 6.8 (d, 2H), 5.2 (s, 2H), 4.5-4.8 (dd, 2H), 4.1-4.2 (m, 1H), 3.8 (s, 3H), 3.3 (s, 2H), 3.1 (dd, 2H), 1.1-1.5 (m, 3H), 0.9 (m, 6H)

Example 839

N- (pyridin-2-ylmethyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 2-aminomethylpyridine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 8.6 (d, 2H), 7.8 (m, 2H), 7.6 (s, 1H), 7.5 (s, 1H), 7.3-7.4 (m, 3H), 7.1 (d , 2H), 7.0 (s, 1H), 6.9 (d, 2H), 5.3 (d, 2H), 4.4-4.8 (dd, 2H), 4.2 (m, 1H), 3.8 (s, 3H), 3.3 ( s, 2H), 3.1 (dd, 2H), 1.0-1.6 (m, 3H), 0.9 (m, 6H)

Example 840

N- (pyridin-2-ylmethyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 2-aminomethylpyridine and 3-fluorophenylisothiocyanate instead of 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate.

¹ H-NMR (CDCl ₃ ): δ 8.6 (d, 1H), 7.8 (t, 1H), 7.6 (d, 2H), 7.5 (m + s, 2H), 7.2-7.4 (m, 4H), 7.2 (d, 2H), 7.0 (s, 1H), 6.9 (t, 1H), 5.3 (s, 2H), 4.4 4.9 (dd, 2H), 4.3 (m, 1H), 3.3 (m, 2H), 3.1 (dd, 2H), 1.1-1.6 (m, 3H), 0.9 (m, 6H)

Example 841

N- (3-fluorobenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 3-fluorobenzylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.7 (d, 2H), 7.5 (s, 2H), 7.4 (m, 1H), 7.3 (d, 1H), 7.1-7.2 (m, 7H), 6.9 (d , 2H), 5.4 (s, 2H), 4.9 (dd, 2H), 4.3 (m, 1H), 3.9 (s, 3H), 3.4 (s, 2H), 3.3 (dd, 2H), 1.2-1.7 ( m, 3H), 1.0 (m, 6H)

Example 842

N- (3-fluorobenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 3-fluorobenzylamine and 3-fluorophenylisothiocyanate instead of 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate.

¹ H-NMR (CDCl ₃ ): δ 7.6 (d, 2H), 7.4 (s, 1H), 7.2-7.3 (m, 2H), 6.8-7.1 (m, 9H), 5.2 (s, 2H), 4.5 5.1 (dd, 2H), 4.1 (m, 1H), 3.3 (s, 2H), 3.2 (dd, 2H), 1.1-1.6 (m, 3H), 0.9 (m, 6H)

Example 843

N- (3-fluorobenzyl) -N-cyclohexylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 ( S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 3-fluorobenzylamine and cyclohexylisothiocyanate instead of 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate.

¹ H-NMR (CDCl ₃ ): δ 7.7 (d, 2H), 7.4-7.5 (m, 3H), 7.3-7.4 (m, 2H), 7.2 (d, 2H), 7.0 (s, 1H), 5.3 (d, 2H), 5.1-5.2 (m, 1H), 4.5-4.8 (m, 2H), 4.2 (m, 1H), 3.3 (s, 2H), 3.1 (dd, 2H), 1.8-2.0 (m , 2H), 1.3-1.6 (m, 6H), 1.0-1.2 (m, 3H), 0.8-1.0 (m, 8H)

Example 844

N- (3-fluorobenzyl) -N- (2-methoxypyridin-5-yl) thiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 3-fluorobenzylamine and 2-methoxypyridin-5-ylisothiocyanate instead of 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate It was.

¹ H-NMR (CDCl ₃ ): δ 7.8 (d, 1H), 7.5-7.6 (m, 7H), 7.4 (s, 1H), 7.1 (d, 2H), 7.0 (s, 1H), 6.7 (m , 1H), 4.6 5.2 (s, 2H), 4.2 (m, 1H), 3.9 (s, 3H), 3.3 (s, 2H), 3.2 (dd, 2H), 1.0-1.6 (m, 3H), 0.8 -0.9 (m, 6H)

Example 845

N- (3-trifluoromethylbenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 3-trifluoromethylbenzylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.7 (d, 2H), 7.6 (m, 2H), 7.5 (s, 1H), 7.3 (d, 1H), 7.1-7.2 (m, 5H), 7.1 (s , 1H), 6.9 (d, 2H), 5.3 (s, 2H), 5.0 (dd, 2H), 4.3 (m, 1H), 3.9 (s, 3H), 3.4 (s, 2H), 3.3 (dd, 2H), 1.2-1.7 (m, 3H), 0.9 (m, 6H)

Example 846

N- (3-trifluoromethylbenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 3-trifluoromethylbenzylamine and 3-fluorophenylisothiocyanate instead of 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate.

¹ H-NMR (CDCl ₃ ): δ 7.5-7.7 (m, 5H), 7.5 (s, 1H), 7.3 (m, 1H), 6.8-7.2 (m, 7H), 5.3 (s, 2H), 4.6 5.1 (dd, 2H), 4.2 (m, 1H), 3.4 (s, 2H), 3.2 (dd, 2H), 1.1-1.6 (m, 3H), 0.9-1.0 (m, 6H)

Example 847

N- (3-trifluoromethylbenzyl) -N-cyclohexylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 3-trifluoromethylbenzylamine and cyclohexylisothiocyanate instead of 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate.

¹ H-NMR (CDCl ₃ ): δ 7.7 (d, 2H), 7.5 (s, 1H), 7.2-7.3 (m, 2H), 7.2 (d, 2H), 6.8-7.0 (m, 3H), 5.3 (s, 2H), 5.2 (m, 1H), 4.5 4.8 (m, 2H), 4.1 (m, 1H), 3.3 (s, 2H), 3.1 (dd, 2H), 1.8-2.0 (m, 2H) , 1.3-1.6 (m, 6H), 1.0-1.2 (m, 3H), 0.8-0.9 (m, 6H)

Example 848

N- (3-trifluoromethylbenzyl) -N- (2-methoxypyridin-5-ylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole -5-yl] acetyl} amino-3 (S) -methylpentylamine

The title compound in the same manner as in Example 807 using 3-trifluoromethylbenzylamine and 2-methoxypyridin-5-ylisothiocyanate instead of 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate Was prepared.

¹ H-NMR (CDCl ₃ ): δ 7.8 (d, 1H), 7.6 (d, 2H), 7.5 (d, 1H), 7.3 (m + s, 2H), 6.9-7.1 (d + m, 4H) , 6.7 (d, 1H), 5.2 (d, 2H), 4.5 5.2 (dd, 2H), 4.2 (m, 1H), 3.8 (s, 3H), 3.3 (s, 2H), 3.2 (dd, 2H) , 1.0-1.6 (m, 3H), 0.8-0.9 (m, 6H)

Example 849

N- (3-methoxycarbonylbenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 3-methoxycarbonylbenzylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.99 (d, 1H), 7.89 (s, 1H), 7.58 (d, 2H), 7.44 (m, 3H), 7.02-7.11 (m, 5H), 6.82 (d , 2H), 5.27 (m, 2H), 5.16 (m, 2H), 4.63 (d, 1H), 4.06-4.23 (m, 1H), 3.92 (s, 3H), 3.78 (s, 3H), 3.40 ( s, 2H), 3.13-3.21 (m, 1H), 1.52-1.65 (m, 1H), 1.38 (m, 1H), 1.02 (m, 1H), 0.90 (m, 6H)

Example 850

N- (3-methoxycarbonylbenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 3-methoxycarbonylbenzylamine and 3-fluorophenylisothiocyanate instead of 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate.

¹ H-NMR (CDCl ₃ ): δ 8.01 (d, 1H), 7.90 (s, 1H), 7.59 (d, 2H), 7.46 (m, 3H), 7.19-7.26 (m, 1H), 6.86-7.11 (m, 7H), 5.18-5.30 (m, 3H), 4.95 (m, 1H), 4.60 (d, 1H), 4.10-4.23 (m, 1H), 3.93 (s, 3H), 3.35 (s, 2H ), 3.24 (m, 1H), 1.70 (m, 1H), 1.43-1.60 (m, 1H), 1.06 (m, 1H), 0.90 (m, 6H)

Example 851

N- (3-carboxybenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -Methylpentylamine Hydrochloride

Example 850 Compound (110 mg) was dissolved in ethanol (1.5 ml) and the lithium hydroxide solution (1M, 2 ml) was slowly added dropwise, and the reaction mixture was stirred at room temperature for 3 hours. After adding 1N hydrochloric acid solution (2.5 ml), the reaction solution was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give the title compound (57 mg, 53%) as a white solid.

¹ H-NMR (CDCl ₃ ): δ 9.54 (d, 1H), 8.94 (s, 1H), 8.30-8.47 (m, 1H), 7.93 (m, 4H), 7.42-7.85 (m, 4H), 7.15 -7.38 (m, 3H), 7.00 (t, 1H), 5.60 (s, 2H), 5.13-5.40 (m, 2H), 4.40 (m, 1H), 4.05 (m, 1H), 3.39-3.76 (m , 3H), 1.40-1.52 (m, 2H), 1.19-1.30 (m, 1H), 0.86 (m, 6H)

Example 852

N- (4-methoxycarbonylbenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 4-methoxycarbonylbenzylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 8.02 (d, 2H), 7.59 (d, 2H), 7.49 (s, 1H), 7.30 (m, 2H), 7.06-7.12 (m, 4H), 7.02 (s , 1H), 6.83 (d, 2H), 5.30 (m, 2H), 5.16 (m, 2H), 4.65 (d, 1H), 4.03-4.27 (m, 1H), 3.92 (s, 3H), 3.78 ( s, 3H), 3.33 (s, 2H), 3.12 (m, 1H), 1.63 (m, 1H), 1.40 (m, 1H), 1.05 (m, 1H), 0.90 (m, 6H)

Example 853

N- (4-methoxycarbonylbenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 4-methoxycarbonylbenzylamine and 3-fluorophenylisothiocyanate instead of 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate.

¹ H-NMR (CDCl ₃ ): δ 9.25 (s, 2H), 8.50 (m, 1H), 8.00 (m, 4H), 7.69 (s, 1H), 7.53 (d, 2H), 7.40 (d, 2H ), 7.16 (d, 2H), 6.50 (m, 2H), 5.64 (s, 2H), 5.20 (m, 2H), 4.23-5.54 (m, 1H), 4.05 (m, 1H), 3.81 (s, 3H), 3.40-3.73 (m, 2H), 1.51 (bs, 2H), 1.25 (m, 1H), 0.90 (m, 6H)

Example 854

N- (4-carboxybenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -Methylpentylamine Hydrochloride

The title compound was prepared in the same manner as in Example 851 using the compound prepared in Example 852.

¹ H-NMR (CDCl ₃ ): δ 9.25 (s, 1H), 8.41-8.61 (m, 1H), 7.95 (m, 4H), 7.69 (s, 1H), 7.53 (m, 4H), 7.15 (d , 2H), 6.90 (d, 2H), 5.64 (s, 2H), 5.16-5.29 (m, 2H), 4.37 (m, 1H), 3.98 (m, 1H), 3.81 (m, 3H), 3.43- 3.69 (m, 3H), 1.50-1.58 (m, 2H), 1.12 (m, 1H), 0.88 (m, 6H)

Example 855

N- (4-carboxybenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -Methylpentylamine Hydrochloride

Using the compound prepared in Example 853, the title compound was prepared in the same manner as in Example 851.

¹ H-NMR (CDCl ₃ ): δ 9.57 (bs, 1H), 9.26 (s, 1H), 8.43-8.63 (m, 1H), 8.00 (m, 4H), 7.71 (s, 1H), 7.53 (d , 2H), 7.42 (d, 2H), 7.17-7.34 (m, 3H), 7.02 (m, 1H), 5.66 (s, 2H), 5.18-5.42 (m, 2H), 4.26-4.50 (m, 1H ), 4.08 (m, 1H), 3.40-3.71 (m, 3H), 1.50-1.62 (m, 2H), 1.15 (m, 1H), 0.87 (m, 6H)

Example 856

N- (1-oxypyridin-2-ylmethyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazole-5 -Yl] acetyl} amino-3 (S) -methylpentylamine

Example 839 After dissolving compound (62 mg) in dichloromethane (5 ml), -chloroperbenzoic acid (0.04 g) was slowly added dropwise and the reaction mixture was stirred at room temperature for 2 hours. The reaction solvent was concentrated under reduced pressure, and the residue was then purified by silica gel column chromatography (dichloromethane / methanol = 9/1, v / v) to prepare the title compound as a solid.

¹ H-NMR (DMSO-d ₆ + TFA-d ₁ ): δ 8.7 (s, 1H), 8.2 (m, 1H), 7.8 (m, 2H), 7.6-7.8 (m, 3H), 7.4 (d , 2H), 7.2-7.3 (m, 3H), 6.9 (d, 2H), 5.4 (s, 2H), 5.1 (m, 2H), 4.1 (m, 1H), 3.4-3.7 (ms, 7H), 1.4 (m, 2H), 1.0 (m, 1H), 0.8 (m, 6H)

Example 857

N-methyl-N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S ) -Methylpentylamine

The title compound was prepared in the same manner as in Example 807, using methylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.40-7.70 (m, 3H), 7.30 (s, 1H), 7.00-7.25 (m, 5H), 6.80-6.95 (m, 2H), 5.00-5.40 (m, 3H), 4.00-4.30 (m, 1H), 3.80 (m, 4H), 3.30 (m, 2H), 3.18 (s, 3H), 3.07 (dd, 1H), 1.37-1.80 (m, 2H), 1.00 -1.30 (m, 1H), 0.92 (m, 6H)

Example 858

N-isobutyl-N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 ( S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using isobutylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.60 (d, 2H), 7.35-7.53 (m, 2H), 7.00-7.25 (m, 5H), 6.80-6.93 (m, 2H), 5.10-5.40 (m, 3H), 4.00-4.30 (m, 1H), 3.80 (m, 3H), 3.40-3.70 (m, 2H), 3.27 (s, 3H), 2.95-3.20 (m, 2H), 1.30-2.40 (m, 3H), 0.80-1.30 (m, 13H)

Example 859

Nn-butyl-N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S ) -Methylpentylamine

The title compound was prepared in the same manner as in Example 807, using n-butylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.6 (d, 2H), 7.5 (s, 1H), 7.2 (d, 2H), 7.1 (d, 2H), 7.0 (s, 1H), 6.9 (d, 2H ), 5.2-5.3 (m, 2H), 4.1 (m, 1H), 3.8 (s, 3H), 3.4-3.7 (m, 2H), 3.3 (s, 2H), 3.0-3.2 (m, 2H), 1.5-1.7 (m, 5H), 1.1-1.4 (m, 5H), 0.9 (m, 6H)

Example 860

N- [2- (ethylthio) ethyl] -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 2- (ethylthio) ethylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.6 (d, 2H), 7.4 (s, 1H), 7.2 (d, 2H), 7.1 (d, 2H), 7.0 (s, 1H), 6.8 (d, 2H ), 5.3 (s, 2H), 4.1 (m, 1H), 3.8 (s, 3H), 3.4-3.6 (m, 2H), 3.3 (s, 2H), 3.2 (dd, 2H), 2.8 (t, 2H), 2.6 (q, 2H), 1.5-1.6 (m, 2H), 1.3 (t, 3H), 1.1 (m, 1H), 0.9-1.0 (m, 6H)

Example 861

N- (3-ethoxy) propyl-N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using 3-ethoxypropylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.6 (m, 3H), 7.5 (d, 2H), 7.1-7.2 (m, 3H), 7.0 (s, 1H), 6.9 (d, 1H), 5.3 (s , 2H), 4.1-4.2 (m, 3H), 3.8 (s, 3H), 3.4-3.6 (m, 4H), 3.3 (s, 2H), 3.1 (dd, 2H), 1.4-1.8 (m, 3H ), 1.2 (t, 3H), 0.9-1.0 (m, 6H)

Example 862

N- (2-propynyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using propazylamine instead of 2-chlorobenzylamine.

¹ H-NMR (CDCl ₃ ): δ 7.57 (d, 2H), 7.46 (s, 1H), 7.08 (d, 2H), 6.92 (s, 1H), 6.78 (m, 1H), 5.21 (s, 2H ), 5.05 (s, 1H), 4.45 (m, 1H), 4.00-4.30 (m, 3H), 3.78 (s, 3H), 3.35-3.70 (m, 1H), 3.29 (s, 2H), 2.90- 3.25 (m, 1 H), 1.00-1.90 (m, 3 H), 0.88 (m, 6 H)

Example 863

N- (2-propynyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3 (S) -methylpentylamine

The title compound was prepared in the same manner as in Example 807, using propazylamine and 3-fluorophenylisothiocyanate instead of 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate.

¹ H-NMR (CDCl ₃ ): δ 7.58 (d, 2H), 7.48 (s, 1H), 7.00-7.30 (m, 3H), 6.93 (s, 1H), 6.67-6.87 (m, 1H), 6.40 -6.66 (m, 3H), 5.20 (s, 2H), 5.09 (s, 1H), 4.50 (m, 1H), 4.00-4.30 (m, 3H), 3.35-3.80 (m, 1H), 3.29 (s , 2H), 2.95-3.25 (m, 1H), 1.00-1.90 (m, 3H), 0.90 (m, 6H)

Example 864

N- (2-trifluoromethylbenzyl) -N- (allylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

[Step 1]

N- (2-Trifluoromethylbenzyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

N- (t-butoxycarbonyl) -L-isorucin aldehyde was prepared in the same manner as in Reference Example 3 using Nt-butoxycarbonyl-L-isoleucine, and then 2,3-dichlorobenzylamine Instead, the title compound was prepared in the same manner as in Reference Example 4 using 2-trifluoromethylbenzylamine.

¹ H-NMR (CDCl ₃ ): δ 8.17 (d, 2H), 7.65 (d, 1H), 7.52 (d, 2H), 7.51 (s, 1H), 7.33-7.41 (m, 1H), 7.17 (d , 2H), 7.04 (s, 1H), 5.93 (d, 1H), 5.30 (s, 2H), 3.89 (s, 2H), 3.80-3.87 (m, 1H), 3.36 (s, 2H), 2.69 ( d, 2H), 1.44-1.54 (m, 1H), 1.33-1.40 (m, 1H), 0.95-1.01 (m, 1H), 0.80-0.92 (m, 6H)

[Step 2]

N- (2-trifluoromethylbenzyl) -N- (allylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino- 3 (S) -methylpentylamine

N- (2-trifluoromethylbenzyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine A solution diluted with dichloromethane (0.02M, 1ml, 0.02mmol) and a solution of allyl isothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) were reacted at room temperature for 2 hours, and then the reaction solution was briefly reacted. Purification by silica gel column chromatography (dichloromethane / methanol = 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 8.21 (d, 2H), 7.72 (d, 1H), 7.39-7.53 (m, 3H), 7.15-7.28 (m, 3H), 7.02 (s, 1H), 5.87 (bs, 1H), 5.71-5.85 (m, 1H), 5.30-5.52 (m, 2H), 4.70-5.08 (m, 2H), 4.65 (d, 1H), 4.21-4.29 (m, 2H), 4.05 -4.14 (m, 1H), 3.33 (s, 2H), 3.06 (dd, 1H), 1.65 (bs, 1H), 1.26-1.44 (m, 1H), 0.97-1.05 (m, 1H), 0.86-0.92 (m, 6H)

Example 865-868

N- (2-trifluoromethylbenzyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine The title compound was prepared in the same manner as in Step 2 of Example 864, using the corresponding isothiocyanate.

Example 865

N- (2-trifluoromethylbenzyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl } Amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.15 (d, 2H), 7.70 (d, 1H), 7.40-7.58 (m, 3H), 7.19-7.30 (m, 5H), 7.14 (d, 2H), 6.97 (s, 1H), 5.22-5.41 (m, 1H), 5.31 (d, 2H), 4.82-4.95 (m, 1H), 4.77 (d, 1H), 3.34 (s, 2H), 3.13 (dd, 1H) ), 1.64-1.70 (m, 1H), 1.40-1.48 (m, 1H), 0.98-1.06 (m, 1H), 0.86-0.93 (m, 6H)

Example 866

N- (2-trifluoromethylbenzyl) -N-cyclohexylthiocarbamoyl-2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.20 (d, 2H), 7.70-7.74 (m, 1H), 7.55 (s, 1H), 7.42-7.46 (m, 2H), 7.13-7.26 (m, 3H) , 7.04 (s, 1H), 5.42 (d, 2H), 5.17 (bs, 1H), 4.73 (dd, 2H), 4.17-4.22 (m, 1H), 4.05-4.11 (m, 1H), 3.34 (s , 2H), 3.04 (dd, 1H), 1.63-1.90 (m, 4H), 1.26-1.50 (m, 6H), 0.82-1.20 (m, 6H)

Example 867

N- (2-trifluoromethylbenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.28 (bs, 1H), 8.14 (d, 2H), 7.72 (d, 1H), 7.40-7.60 (m, 3H), 7.23-7.28 (m, 2H), 7.03 -7.20 (m, 3H), 6.84-7.16 (m, 3H), 5.38-5.48 (m, 1H), 5.32 (s, 2H), 4.82-4,95 (m, 1H), 4.77 (d, 1H) , 4.08-4.16 (m, 1H), 3.35 (s, 2H), 3.18 (dd, 1H), 1.62-1.70 (m, 1H), 1.38-1.46 (m, 1H), 0.98-1.06 (m, 1H) , 0.86-0.92 (m, 6H)

Example 868

N- (2-trifluoromethylbenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-nitrobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3 (S) -methylpentylamine

¹ H-NMR (CDCl ₃ ): δ 8.15 (d, 2H), 7.72 (d, 1H), 7.66 (bs, 1H), 7.41-7.57 (m, 3H), 7.24-7.29 (m, 2H), 7.07 -7.18 (m, 3H), 7.01 (s, 1H), 6.84 (d. 2H), 5.35 (d, 2H), 5.08-5.26 (m, 2H), 4.79 (d, 1H), 4.06-4.18 (m , 1H), 3.78 (s. 3H), 3.34 (s, 2H), 3.11 (dd, 1H), 1.62-1.73 (m, 1H), 1.32-1.48 (m, 1H), 0.96-1.09 (m, 1H ), 0.86-0.92 (m, 6H)

Example 869

N- (2-trifluoromethylbenzyl) -N-allylthiocarbamoyl-2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

[Step 1]

N- (2-trifluoromethylbenzyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

N- (t-butoxycarbonyl) -L-glycine aldehyde was prepared in the same manner as in Reference Example 3 using Nt-butoxycarbonyl-L-glycine, and then 2,3-dichlorobenzylamine and 1- 2-trifluoromethylbenzylamine and 1- (4-cyanobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride instead of (4-nitrobenzyl) -1H-imidazol-5-ylacetic acid hydrochloride The title compound was prepared in the same manner as in Reference Example 4.

¹ H-NMR (CDCl ₃ ): δ 7.32-7.63 (m, 7H), 7.14 (d, 2H), 7.01 (s, 1H), 6.53 (bs, 1H), 5.26 (s, 2H), 3.89 (s , 2H), 3.36 (s, 2H), 3.27 (q, 2H), 2.73 (t, 2H)

[Step 2]

N- (2-trifluoromethylbenzyl) -N- (allylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

A solution obtained by diluting N- (2-trifluoromethylbenzyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine with dichloromethanedichloromethane ( 0.02M, 1ml, 0.02mmol) and a solution of allyl isothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) were reacted at room temperature for 2 hours, and then the reaction solution was subjected to a short silica gel column chromatography (dichloromethane). / Methanol = 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 7.64 (d, 2H), 7.53 (s, 1H), 7.25-7.46 (m, 2H), 7.31-7.44 (m, 2H), 7.16 (d, 2H), 7.06 (bs, 1H), 6.98 (s, 1H), 6.61 (bs, 1H), 5.79-5.99 (m, 1H), 5.26 (s, 2H), 5.14 (s, 2H), 5.08 (s, 2H), 4.28-4.33 (m, 2H), 3.80 (t, 2H), 3.36 (s, 2H), 3.27-3.33 (m, 2H)

Example 870-873

N- (2-trifluoromethylbenzyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine with the corresponding isothiocyanate The title compound was prepared in the same manner as Step 2 of Example 869.

Example 870

N- (2-trifluoromethylbenzyl) -N- (4-chlorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino Ethylamine

¹ H-NMR (CDCl ₃ ): δ 8.90 (bs, 1H), 7.68 (d, 1H), 7.51-7.61 (m, 4H), 7.40-7.47 (m, 3H), 7.29 (d, 2H), 7.06 (d, 2H), 6.99 (bs, 1H), 6.93 (s, 1H), 5.31 (s, 2H), 5.18 (s, 2H), 3.68 (t, 2H), 3.37 (s, 2H), 3.29- 3.34 (m, 2 H)

Example 871

N- (2-trifluoromethylbenzyl) -N-cyclohexylthiocarbamoyl-2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 7.69 (d, 1H), 7.63 (d, 2H), 7.53 (s, 1H), 7.40-7.49 (m, 2H), 7.29 (d, 1H), 7.16 (d , 2H), 7.00 (s, 1H), 6.06 (bs, 1H), 5.29 (s, 2H), 5.01 (s, 2H), 4.23-4.30 (m, 1H), 3.85 (t, 2H), 3.37 ( s, 2H), 3.27-3.33 (m, 2H), 1.90-1.97 (m, 2H), 1.44-1.62 (m, 2H), 0.99-1.39 (m, 6H)

Example 872

N- (2-trifluoromethylbenzyl) -N- (3-fluorophenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 8.82 (bs, 1H), 7.69 (d, 1H), 7.59 (s, 1H), 7.54 (s, 2H), 7.38-7.49 (m, 2H), 7.23-7.33 (m, 3H), 7.09 (d, 2H), 6.99 (s, 1H), 6.86-6.96 (m, 1H), 6.66 (bs, 1H), 5.32 (s, 2H), 5.21 (s, 2H), 3.72 (t, 2H), 3.39 (s, 2H), 3.27-3.34 (m, 2H)

Example 873

N- (2-trifluoromethylbenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Aminoethylamine

¹ H-NMR (CDCl ₃ ): δ 8.42 (bs, 1H), 7.68 (d, 1H), 7.56 (d, 2H), 7.38-7.50 (m, 3H), 7.26 (d, 2H), 6.97 (d , 2H), 6.95 (s, 1H), 6.87 (d, 2H), 5.25 (s, 2H), 5.20 (s, 2H), 3.80- (bs, 5H), 3.36 (bs, 2H)

Example 874

N- (2-trifluoromethylbenzyl) -N-allylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 -(4-benzyloxy) phenylpropylamine

[Step 1]

N- (2-trifluoromethylbenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3- (4-benzyloxy) Phenylpropylamine

Nt-butoxycarbonyl-L- (O-benzyl) tyrosine aldehyde was prepared in the same manner as in Reference Example 3 using Nt-butoxycarbonyl-L- (O-benzyl) tyrosine, and then 2,3- 2-trifluoromethylbenzylamine and 1- (4-cyanobenzyl) -1H-imidazole-5- instead of dichlorobenzylamine and 1- (4-nitrobenzyl) -1H-imidazol-5-monoacetic acid hydrochloride The title compound was prepared in the same manner as in Reference Example 4 using monoacetic acid hydrochloride.

¹ H-NMR (CDCl ₃ ): δ 7.62 (d, 1H), 7.58 (d, 2H), 7.51-7.54 (m, 2H), 7.30-7.45 (m, 7H), 6.96-7.03 (m, 5H) , 6.84 (d, 2H), 6.12 (d, 1H), 5.03 (s, 2H), 4.86 (d, 1H), 4.17-4.22 (m, 1H), 3.86 (s, 2H), 3.26 (t, 2H ), 2.62-2.71 (m, 4H)

[Step 2]

N- (2-trifluoromethylbenzyl) -N-allylthiocarbamoyl-2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3 -(4-benzyloxy) phenylpropylamine

N- (2-trifluoromethylbenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3- (4-benzyloxy) After diluting phenylpropylamine with dichloromethane (0.02M, 1ml, 0.02mmol) and allyl isothiocyanate diluted with dichloromethane (0.1M, 0.2ml, 0.02mmol) at room temperature for 2 hours The reaction solution was purified by short silica gel column chromatography (dichloromethane / methanol = 9/1, v / v) to give the title compound as a white solid.

¹ H-NMR (CDCl ₃ ): δ 7.70 (d, 1H), 7.60 (d, 2H), 7.42 (m, 5H), 7.32 (m, 5H), 7.00 (m, 7H), 6.68 (s, 1H ), 5.82 (m, 1H), 5.32 (d, 1H), 5.07 (m, 4H), 4.73 (m, 4H), 4.31 (m, 3H), 3.50 (t, 1H), 3.33 (m, 1H) , 3.12 (m, 1 H), 2.85 (m, 1 H), 2.65 (m, 1 H)

Example 875-878

N- (2-trifluoromethylbenzyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} amino-3- (4-benzyloxy) The title compound was prepared in the same manner as Step 2 of Example 874, using an isothiocyanate corresponding to phenylpropylamine.

Example 875

N- (2-trifluoromethylbenzyl) -N- (4-chlorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] Acetyl} amino-3- (4-benzyloxyphenyl) propylamine

¹ H-NMR (CDCl ₃ ): δ 8.70 (bs, 1H), 7.71 (d, 2H), 7.55 (d, 3H), 7.35 (m, 12H), 6.95 (m, 6H), 6.30 (bs, 1H ), 5.80 (d, 1H), 5.07 (s, 2H), 4.85 (d, 1H), 4.65 (q, 2H), 4.47 (m, 1H), 4.20 (m, 1H), 3.48 (t, 1H) , 3.33 (m, 1H), 3.16 (m, 1H), 2.95 (m, 1H), 2.60 (m, 1H)

Example 876

N- (2-trifluoromethylbenzyl) -N- (cyclohexylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl] acetyl} Amino-3- (4-benzyloxyphenyl) propylamine

¹ H-NMR (CDCl ₃ ): δ 7.70 (d, 1H), 7.58 (d, 3H), 7.40 (m, 7H), 7.18 (d, 2H), 7.00 (m, 5H), 6.85 (m, 3H ), 5.82 (bs, 1H), 5.07 (s, 2H), 4.80 (m, 3H), 4.65 (d, 1H), 4.20 (m, 2H), 3.48 (t, 1H), 3.33 (m, 1H) , 3.10 (m, 1H), 2.75 (m, 2H), 1.90 (m, 2H), 1.55 (m, 4H), 1.00 (m, 4H)

Example 877

N- (2-trifluoromethylbenzyl) -N- (3-fluorophenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3- (4-benzyloxyphenyl) propylamine

¹ H-NMR (CDCl ₃ ): δ 8.80 (bs, 1H), 7.70 (d, 1H), 7.55 (d, 3H), 7.37 (m, 4H), 7.28 (m, 7H), 6.96 (m, 8H ), 6.30 (bs, 1H), 5.80 (d, 1H), 5.07 (s, 2H), 4.85 (d, 1H), 4.65 (q, 2H), 4.50 (m, 1H), 4.20 (m, 1H) , 3.48 (t, 1H), 3.30 (m, 1H), 3.16 (m, 1H), 2.95 (m, 1H), 2.60 (m, 1H)

Example 878

N- (2-trifluoromethylbenzyl) -N- (4-methoxyphenylthiocarbamoyl) -2 (S)-{[1- (4-cyanobenzyl) -1H-imidazol-5-yl ] Acetyl} amino-3- (4-benzyloxyphenyl) propylamine

¹ H-NMR (CDCl ₃ ): δ 8.10 (bs, 1H), 7.70 (d, 1H), 7.55 (d, 3H), 7.40 (m, 6H), 7.30 (m, 2H), 7.20 (d, 2H ), 6.96 (m, 9H), 6.60 (bs, 1H), 5.60 (d, 1H), 5.07 (s, 2H), 4.74 (m, 4H), 4.30 (m, 1H), 3.80 (s, 3H) , 3.48 (t, 1 H), 3.34 (m, 1 H), 3.16 (m, 1 H), 2.90 (m, 1 H), 2.60 (m, 1 H).

[Effects of the Invention]

Test Example 1 Proliferation Inhibition Test on K-Lass Transformed Cell Line

MTT [3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide] colorimetric assay was used to measure the viability of K-Las transformed cells. Based on the principle that MTT is converted to MTT-formazan by mitochondrial enzymes. The cells are suspended in 100 μl of medium in 200 wells of each well in 96 well culture plates, and then divided at 24 ° C. under 37 ° C. and 5% CO ₂ . Incubated for hours. Samples of the appropriate concentrations were prepared by dissolving the compound prepared in Example, and then 100 μl of these samples were added to wells containing cells and incubated for 96 hours at 37 ° C. and 5% CO ₂ . After incubation, all the wells were added to 5 mg / ml in PBS (phosphatebuffered saline) solution and incubated for another 4 hours. The medium containing MTT was completely removed and 100 μl of DMSO was added to each well to dissolve MTT-formazan. Absorbance was measured at 570 nm with a microplate reader (DL1000, Dynatech Laboratories Co.), and based on this, a concentration (IC ₅₀ ) that inhibits cell growth by 50% was determined. Results for more preferred compounds among the compounds according to the invention are shown in Table 1.

It can be seen from the results of Table 1 that the compound of formula (I) according to the present invention has a very good antiproliferative effect on Ras mutant cells.

Test Example 2 Inhibition Test for FPTase Enzyme

Farnesylated protein transferase was partially purified from bovine brain using FPLC and gel filtration. Human recombinant K-ras4B (His6) protein expressed and purified in E. coli was used as a substrate, and farnesyl pyrophosphate (FPP) labeled with ³ H was used as a prenyl residue donor. The reaction solution is 50 mM N- (2-hydroxyethyl) piperazine-N '-(2-ethanesulphonic acid) (HEPES), 5 mM-MgCl ₂ , 10 μM ZnCl ₂ , 5 mM dithiothreitol ), 0.2% n-octyl-beta-D-glucopyranoside composition, mixed with 0.6 μg of K-Ras4B (His6) protein and 0.15 μCi [ ³ H] FPP, and then the compound of Example It was dissolved in 99.9% ethanol and added. 1.5 μg of FPTase was added thereto and prepared to have a volume of 50 μl with sterile distilled water. The reaction was carried out at 37 ° C. for 1 hour and terminated by adding 90 μl of 4% sodium dodecyl sulfate (SDS) and 90 μl of 30% trichloroacetic acid (TCA) in this order. The reaction solution was left on ice for 60 minutes, and the precipitated protein was collected by filtration and washed with an aqueous solution containing 4% SDS and 6% TCA. 5 ml of the liquid mixture for the liquid scintillation counter was respectively added, and the radiation dose of the reaction product was measured with a liquid scintillation counter (Beckman 5801). After setting the radiation dose of the control group to 100%, the inhibitory degree was calculated by converting the relative radiation dose of the compound treated group into a percentage (%), and the IC ₅₀ value was calculated by the Litchfield-Wilcoxon method. Results for more preferred compounds among the compounds according to the invention are shown in Table 2.

From the results of Table 2, the compounds of the general formula (I) according to the present invention can be confirmed that the inhibitory effect on the FPTase enzyme.

Test Example 3 Ras-Processing Suppression Test

Incubate 10 ⁵ human K-Ras4B transformed cell lines in a 6-well dish, then add compounds to a concentration of 10 μM and continue incubating for 48 hours. Cultured cells were lysed buffer [Lysis buffer, 1 × PBS (phosphate buffer saline), 1% Triton X-100, 1 mM phenylmethylsulfonyl fluoride, 25 μg / ml leupeptin, 16 μg / ml Benzamidine hydrochloride, 1 mg / ml Sigma-104 phosphate substrate] in 1 ml and lyse cells at 4 ° C. 10 [mu] l of Pan-Las antibody-bound agarose (Y13, 259) is added and reacted again while rotating at 4 ° C for 2 hours. Immunoprecipitated proteins are separated by 15% SDS-acrylamide electrophoresis and fixed to Hybond-ECL membrane (Amersham Corp.). The protein-fixed membrane is bound to the anti-K-ras antibody as the primary antibody and immunodetected using the ECL kit (Amersham Corp.). In 15% SDS-acrylamide electrophoresis, unprocessed K-Ras moves slower than prenylated K-Ras protein, so we can observe the degree of inhibition of FPTase by inhibitors treated in cells. Results for more preferred compounds among the compounds according to the invention are shown in Table 3.

From the results of Table 3, it can be seen that the compound of formula (I) according to the present invention has an excellent lath-processing inhibitory effect on K-Ras4B.

Claims (5)

Thiourea derivatives represented by the following general formula (I), pharmaceutically acceptable salts containing them, or stereoisomers thereof. R ₁ is hydrogen; Straight or branched C ₁ -C ₈ -alkyl; C ₁ -C ₅ -alkyl substituted with dimethylamino or C ₁ -C ₅ -alkoxy; C ₂ -C ₆ -alkenyl; C ₁ -C ₄ -alkoxycarbonyl; C ₃ -C ₆ -cycloalkyl; Phenyl; Halogen, hydroxy, nitro, azido, C ₁ -C ₅ -alkyl, amino, dimethylamino, C ₁ -C ₃ -alkoxy, phenyl, C ₁ -C ₃ -alkylthio, and trifluoro-C _1- Phenyl substituted with 1 to 3 substituents selected from the group consisting of C ₃ -alkyl; Phenyl-C ₁ -C ₄ -alkyl; Naphthyl; Naphthyl substituted with di (C ₁ -C ₄ -alkyl) amino; Benzoyl; Pyridyl; Pyridyl substituted with halogen or C ₁ -C ₆ -alkoxy; Or adamantyl, R ₂ and R ₃ are each independently hydrogen; Straight or branched C ₁ -C ₆ -alkyl; C ₃ -C ₆ -cycloalkyl; Or benzyloxybenzyl, R ₄ is C ₁ -C ₆ -alkyl; Phenyl-C ₁ -C ₄ -alkyl; With a substituent selected from the group consisting of halogen, nitro, C ₁ -C ₅ -alkyl, C ₁ -C ₃ -alkoxy, carboxy, methoxycarbonyl, methylenedioxy, and trifluoro-C ₁ -C ₃ -alkyl C ₁ -C ₄ -alkyl substituted with 1 to 3 substituted phenyl; Naphthyl-C ₁ -C ₄ -alkyl; Thiophenyl-C ₁ -C ₄ -alkyl; Pyridyl-C ₁ -C ₆ -alkyl; Oxypyridyl-C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy-C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkylthio-C ₁ -C ₆ -alkyl; Or C ₂ -C ₆ -alkynyl, X represents nitro or cyano. The compound of claim 1, wherein R ₁ is phenyl; Halogen, hydroxy, nitro, azido, C ₁ -C ₅ -alkyl, amino, dimethylamino, C ₁ -C ₃ -alkoxy, phenyl, C ₁ -C ₃ -alkylthio, and trifluoro-C _1- Phenyl substituted with 1 to 3 substituents selected from the group consisting of C ₃ -alkyl; Pyridyl; Or pyridyl substituted with halogen or C ₁ -C ₆ -alkoxy, R ₂ and R ₃ are each independently hydrogen; Or straight or branched C ₁ -C ₆ -alkyl, R ₄ is phenyl-C ₁ -C ₄ -alkyl; Or a substituent selected from the group consisting of halogen, nitro, C ₁ -C ₅ -alkyl, C ₁ -C ₃ -alkoxy, carboxy, methoxycarbonyl, methylenedioxy, and trifluoro-C ₁ -C ₃ -alkyl C ₁ -C ₄ -alkyl substituted with 1 to 3 substituted phenyl, X is a nitro or cyano, thiourea derivative, a pharmaceutically acceptable salt containing them, or stereoisomers thereof. After removing the amino protecting group of the compound represented by the following general formula (VI), the substituted isothiocyanate represented by the following general formula (VII) is reacted to contain a thiourea derivative represented by the following general formula (I), and these Pharmaceutically acceptable salts, or methods for producing stereoisomers thereof. Wherein R ₁ , R ₂ , R ₃ , R ₄ and X are the same as defined in claim 1, and P ′ is an aminoprotecting group. The amino protecting group of the compound represented by the following general formula (VII) was removed, and then 1-substituted-1H-imidazol-5ylacetic acid hydrochloride represented by the following general formula (VII) was reacted to represent the following general formula (I). A thiourea derivative, a pharmaceutically acceptable salt containing them, or a stereoisomer thereof. Wherein R ₁ , R ₂ , R ₃ , R ₄ and X are the same as defined in claim 1 and P is an aminoprotecting group. A lath mutant cell growth inhibitory composition comprising a thiourea derivative represented by the following general formula (I), a pharmaceutically acceptable salt containing them, or a stereoisomer thereof as an active ingredient and a pharmaceutically acceptable carrier. In the above, R ₁ , R ₂ , R ₃ , R ₄ and X are the same as defined in claim 1.