WO1999012912A1 - Thiourea derivatives or non-toxic salts thereof for inhibitng ras-transformed cell growth - Google Patents

Abstract

The present invention relates to novel thiourea derivatives of formula (I) which possess an excellent activity for inhibiting ras-transformed cell growth, pharmaceutically acceptable salt or stereoisomer thereof, wherein R1 represents hydrogen; straight-chain or branched C1-C8-alkyl which is optionally substituted by substituents selected from a group consisting of halogen, C1-C6-alkoxy, C1-C6-alkoxycarbonyl and di(C1-C4-alkyl)amino; C2-C6-alkenyl; C1-C4-alkoxycarbonyl; C3-C6-cycloalkyl; phenyl which is optionally mono- to trisubstituted by substituents selected from a group consisting of halogen, C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkylthio, halogeno-C1-C6-alkyl, azido, nitro, amino, phenyl, di(C1-C4-alkyl)amino and hydroxy; phenyl-C1-C4-alkyl; naphthyl which is optionally substituted by di(C1-C4-alkyl)amino; benzoyl; pyridyl which is optinally substituted by substituents selected from a group consisting of halogen and C1-C6-alkoxy; or adamantyl; R2 and R3 independently of one another represent hydrogen, straight-chain or branched C1-C6-alkyl, C3-C6-cycloalkyl or benzyloxybenzyl; R4 represents C1-C4-alkyl substituted by phenyl wherein the phenyl moiety is optionally mono- to trisubstituted by substituents selected from a group consisting of halogen, halogeno-C1-C4-alkyl, C1-C4-alkylenedioxy, C1-C6-alkyl, nitro, C1-C6-alkoxy, carboxyl and C1-C6-alkoxycarbonyl; naphthyl-C1-C4-alkyl; thiophenyl-C1-C4-alkyl; C1-C6-alkyl which is optionally substituted by substituents selected from a group consisting of pyridyl, oxypyridyl, C1-C6-alkoxy and C1-C6-alkylthio; or C2-C6-alkynyl; and X represents nitro or cyano. The present invention also relates to a process for the preparation of the thiourea derivatives and a pharmaceutical composition for inhibition of ras-transformed cell growth comprising the same as an active ingredient.

Description

THIOUREA DERIVATIVES OR NON-TOXIC SALTS THEREOF FOR INHIBITING RAS-TRANSFORMED CELL GROWTH

TECHNICAL FIELD

The present invention relates to novel thiourea derivatives, pharmaceutically acceptable non-toxic salts or stereoisomers thereof which possess an excellent activity for inhibiting ras-transformed cell growth. The present invention also relates to a process for the preparation of the thiourea derivatives and a pharmaceutical composition for inhibition of ras-transformed cell growth comprising the same as an active ingredient.

BACKGROUND ART

A ras protein is famesylated or geranylgeranylated by farnesyltransferases [farnesyl protein transferase (hereinafter referred to as "FPTase") or geranylgeranyl protein transferase (hereinafter referred to as "GGPTase"), respectively] to be translocated into an intracelluar membrane, in which the ras protein is activated or inactivated by GTP or GDP. The activated ras protein forwards the downstream signal transduction pathways to transmit the outside signal into nucleus. And then, the nucleus activates translational factors (e.g., myc, jun, fos etc.) to forward cell growth or nucleus division. (M. Barbacid, Annu. Rev. Biochem., 56, 779, 1987, P J. Casey et al., Natl. Acad. Sci. U.S.A. 86, 8323, 1989).

The transformed ras proteins, e.g., H-Ras, N-Ras, K-RasA, K-RasB etc., translated by the mutated ras gene, in activated state, result in the unregulated cell growth, thereby causing cell tumorization. Especially, the mutated ras genes are found in patients suffered from various cancers, e.g., colon cancer (about 50%), pancreas cancer (about 90%), lung cancer (about 50%), and thyroid gland cancer (about 30%) (S. Rodenhuis, Semin. Cancer Biol. 3, 241, 1992).

Various researches have been carried out to develop ras inhibitors. Most of the researches have been focused on FPTase inhibitors, which may inhibit the translocation of ras proteins into an intracellular membrane. For example, Cys-Val-Phe-Met mimetic derivatives, mimic to C -terminal of ras protein(Cys-Al-A2-Met), are disclosed (J. L. Goldstein et al, J. Biol. Chem., 266, 15575, 1991; A. M. Garcia et al, J. Biol. Chem., 268, 18415, 1993; S. L. Graham et al., J. Med. Chem., 37, 725, 1994).

Various derivatives mimicking Cys-Ile-Phe-Met as a prototype inhibitor, such as for example, alkylamine derivatives wherein Phe-Met moietyl is displaced by aromatic alkylamine (S. J. Desolms et al., J. Med. Chem., 38, 3967, 1995) and carbonylamide derivatives wherein aminomethylnaphthalene is combined with cysteine and trans-3(S)- ethylproline(WO9606609, 1996), were disclosed to have FPTase inhibitory activity. And pseudopeptide derivatives containing substituted imidazolethyl group instead of cysteine were disclosed to have FPTase inhibitory activity (J. H. Hunt et al, J. Med. chem., 39, 353, 1996; WO9610035, 1996; WO9610034, 1996; WO9609836, 1996). And also, WO9639173 disclosed that compounds containing p-cyanobenzyl- imidazolacetate instead of cysteine and N-naphthylmethyl instead of phenylalanine, respectively, in the structure of Cys-Ile-Phe-Met, have FPTase inhibitory activity.

However, it has been pointed out that the FPTase inhibitors described in the above can not effectively inhibit the farnesylation of the K-ras protein, which is the most frequently found ras-protein in human cancer. It is the reason why FPTase inhibitors fail to inhibit the prenylation of the K-ras protein in cells that the K-ras protein suppressed by FPTase inhibitors keeps its activity by using GGPTase instead of FPTase (G. L. James et al., J. Biol. Chem. 270, 6221, 1995).

DISCLOSURE OF INVENTION

Therefore, the present inventors have extensively researched to develop ras-transformed cell growth inhibitors, which can block the prenylation of the K-ras protein; and, as a result, have discovered that novel thiourea derivatives of the following formula (I) exhibit excellent activity for inhibiting K-ras prenylation as well as ras-transformed cell (per se) growth.

Accordingly, it is a primary object of the present invention to provide thiourea derivatives represented by the following formula (I):

pharmaceutically acceptable salt or stereoisomer thereof, wherein Ri represents hydrogen; straight-chain or branched G-Cg-alkyl which is optionally substituted by substituents selected from a group consisting of halogen, G-Cβ-alkoxy, Cι-C6-alkoxycarbonyl and di(Cι-C₄-alkyl)amino; C -C₆-alkenyl; Cι-C₄-alkoxycarbonyl; C₃-Cό- cycloalkyl; phenyl which is optionally mono- to trisubstituted by substituents selected from a group consisting of halogen, Ci-Cό-alkyl, G-Cό-alkoxy, Ci-Cδ-alkylthio, halogeno-G-Cό -alkyl, azido, nitro, amino, phenyl, di(G-C4-alkyl)amino and hydroxy; phenyl-Cι-C₄-alkyl; naphthyl which is optionally substituted by di(Cι-C₄-alkyl)amino; benzoyl; pyridyl which is optionally substituted by substituents selected from a group consisting of halogen and G-Cό-alkoxy; or adamantyl,

R2 and R3 independently of one another represent hydrogen, straight- chain or branched G-Cό-alkyl, C₃-C6-cycloalkyl or benzyloxy- benzyl,

R4 represents Cι-C₄-alkyl substituted by phenyl wherein the phenyl moiety is optionally mono- to trisubstituted by substituents selected from a group consisting of halogen, halogeno-Cι-C₄-alkyl, Cι-C₄-alkylenedioxy, G-Cό-alkyl, nitro, G-Cό-alkoxy, carboxyl and Ci -Cό-alkoxycarbonyl; naphthyl-Ci -C₄-alkyl; thiophenyl-C 1 -C₄-alkyl; Ci-Cβ-alkyl which is optionally substituted by substituents selected from a group consisting of pyridyl, oxypyridyl, G-Ce-alkoxy and Ci-Cβ-alkylthio; or C₂-C6-alkynyl, and

X represents nitro or cyano.

It is another object of the present invention to provide processes for preparing the compound of formula (I).

It is a further object of the present invention to provide a pharmaceutical composition comprising the compound of formula (I) as an active ingredient together with a pharmaceutically acceptable carrier.

BEST MODE FOR CARRYING OUT THE INVENTION

The thiourea derivatives of the present invention may be pharmaceutically acceptable non-toxic salt forms. The non-toxic salts may include conventional acid addition salts used in the field of anticancer agents, e.g., salts originated from inorganic acid such as hydrochloric acid, hydrobromic acid, sulfonic acid, sulfamic acid, phosphoric acid, or nitric acid, and organic acid such as acetic acid, propionic acid, succinic acid, glycolic acid, stearic acid, malic acid, hydroxymalic acid, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid, sulfanyl acid, 2-acetoxybenzoic acid, fumaric acid, toluensulfonic acid, methandisulfonic acid, ethandisulfonic acid, oxalic acid, trifluoroacetic acid. Such acid addition salts may be prepared in accordance with any of the conventional methods.

Since the compound of formula (I) according to the present invention may have asymmetric carbon atoms depending on the substituents, they can be present in the form of racemate, diastereomer mixture or the individual stereospecific isomers. Thus, the present invention also includes all of these stereoisomers and their mixtures.

Among the compound of formula (I) according to the present invention, the preferred compounds include those wherein Ri represents phenyl which is optionally mono- to trisubstituted by substituents selected from a group consisting of halogen, Ci-Cβ-alkyl, G-Cό-alkoxy, Ci-Cό-alkylthio, halogeno-G-Cό-alkyl, azido, nitro, amino, phenyl, di(Cι-C₄-alkyl)amino and hydroxy; or pyridyl which is optionally substituted by substituents selected from a group consisting of halogen and G-Cβ-alkoxy, R₂ and R₃ independently of one another represent straight-chain or branched G-Cό-alkyl,

R4 represents G-C4-alkyl substituted by phenyl wherein the phenyl moiety is optionally mono- to trisubstituted by substituents selected from a group consisting of halogen, halogeno-G-C -alkyl, G-G-alkylenedioxy, G-Ce-alkyl, nitro, G-Cδ-alkoxy, carboxyl and Ci-Ce-alkoxycarbonyl; and

X represents nitro or cyano.

The present invention includes, within its scope, processes for the preparation of a thiourea derivative of formula (I) or non-toxic salts thereof. The compound of formula (I) may be prepared in accordance with Scheme 1 or Scheme 2 described below :

Reaction Scheme 1

Reaction Scheme 2

In the above Scheme 1 and 2,

Ri, R , R₃, R4 and X are defined as previously described, and

P and P' independently of one another represent amino-protecting group.

In the present invention, the amino-protecting group may be selected from conventional ones, such as for example, fluorenylmethyl- oxycarbonyl(Fmoc), t-butoxycarbonyl(Boc) and benzyl oxycarbonyl(Cbz).

The processes summarized in the above Reaction Scheme 1 and 2 will be more specifically explained in the following.

Step 1. Reductive Alkylation

The aldehyde derivative protected with an amino-protecting group such as t-butoxycarbonyl may be synthesized in accordance with conventional methods (Org. Syn. Vol. 67, 1988, 69 and Synthesis, 1983, 676). That is, the aldehyde derivative may be reacted with Ri-amine in the presence of sodium cyanoborohydride or other conventional reducing agent to give the compound of formula (III). This reaction can be facilitated by the addition of potassium acetate or acetic acid and 3A molecular seive.

Step 2. Amino Protection

The compound of formula (III) may be protected by a conventional amino-protecting group, e.g. 9-fluorenylmethyloxycarbonyl, to give a compound of formula (IV).

Step 3. Deprotectoin The compound of formula (IV) having two kinds of amino- protecting group may be dissolved in an appropriate organic solvent and then reacted with deprotecting agent, e.g., trifluoroacetic acid, to remove selectively one of the two amino-protecting groups.

Step 4. Amide Bond Formation

The compound of formula (V) may be reacted with 1-substituted- lH-imidazol-5-ylacetic acid hydrochloride in a solvent in the presence of an appropriate coupling agent to give a compound of formula (VI). The coupling agent may be one or more selected from conventional catalysts, e.g., hydroxybenzotriazole, dialkylcarbodimide and triethylamine. The preferable solvent may be dimethylformamide, methylene chloride, or a mixture thereof.

Step 5. Deprotection and Addition

The compound of formula (VI) having an amino-protecting group may be dissolved in an appropriate organic solvent, e.g., dimethylformamide or methylene chloride, and then reacted with deprotecting agent, e.g., piperidine, to remove the amino-protecting group. Then, the resulting deproteced compound may be reacted with a substituted isothiocyanate of formula (VIII) in a solvent such as methylene chloride to give the desired compound of formula (I).

Step 6. Addition

The compound of formula (III) having an amino group may be reacted with substituted isothiocyanate in an appropriate solvent to give a compound of formula (VII). The solvent may be selected from dimethylformamide, methylene chloride and acetonitrile.

Step 7. Deprotection and Amide Bond Formation

The compound of formula (VII) having an amino-protecting group may be dissolved in an organic solvent, such as dimethylformamide, methylene chloride, etc., and reacted with deprotecting agent, such as piperidine, to remove the protecting group. The resulting compound is then reacted with l-substituted-lH-imidazol-5-ylacetic acid hydrochloride of formula (IX) in the presence of an appropriate coupling agent to give the compound of formula (I). The coupling agent may be one or more selected from conventional catalysts, e.g. hydroxybenzotriazole, dialkylcarbodimide and triethylamine. And as the solvent, dimethylformamide, methylene chloride, or a mixture thereof can be mentioned.

The non-toxic pharmaceutically acceptable salts of the compound (I) may be prepared according to the conventional methods known per se in the art from the compound (I). Generally, they are prepared by reacting the organic bases in an appropriate solvent or solvent mixture with a salt-forming inorganic or organic acid in a stoichiometric amount or in excess.

The present invention also includes within its scope a pharmaceutical composition for inhibition of ras-transformed cell growth comprising a therapeutically effective amount of the novel compound of formula (I), as defined above, or a pharmaceutically acceptable salt thereof as an active ingredient together with a pharmaceutically acceptable carrier. The composition of the present invention may include additives such as lactose or corn starch, lubricant such as magnesium stearate, or conventional emulsifier, suspending agent, stabilizer, isotonic agent. If necessary, sweetner and/or flavoring agent may be added.

The composition of the present invention may be administered orally or parenterally, including intravenous, intraperitoneal, subcutaneous, rectal and topical routes of administration. Therefore, the composition of the present invention may be formulated into various forms such as tablets, capsules, aqueous solutions or suspensions. In case of tablets for oral use, carriers such as lactose, com starch, and lubricating agents, e.g. magnesium stearate, are commonly added. For oral administration in capsule form, lactose and/or dried corn starch can be used as a diluent. When an aqueous suspension are required for oral use, the active ingredient may be combined with emulsifying and/or suspending agents. If desired, certain sweeteners and/or flavoring agents may be added. For intramuscular, intraperitoneal, subcutaneous and intravenous use, sterile solutions of the active ingredient are usually prepared, and the pH of the solutions should be suitably adjusted and buffered. For intravenous use, the total concentration of solutes should be controlled in order to render the preparation isotonic. The composition of the present invention may be in the form of aqueous solution containing pharmaceutically acceptable carriers, e.g., saline, at a pH level of 7.4. The solutions may be introduced into a patient's intramuscular blood-stream by local bolus injection.

The compounds of the present invention may be administered in an effective amount ranging from about O. lmg/kg to about 20mg/kg, preferably from about 0.5mg/kg to about lOmg/kg, per day into a subject patient suffered from various cancers, e.g., colorectal carcinoma, exocrine pancreatic carcinoma, and myeloid leukemias. Of course, the dosage may be changed according to patient's age, weight, susceptibility, or symptom.

The following Examples are given for the purpose of illustration only, and are not intended to limit the scope of the invention.

Preparative Example 1 l-(4-Nitrobenzyl)-lH-imidazol-5-ylacetic acid HC1

<Step 1> lH-Imidazol-4-ylacetic acid methyl ester HC1

Hydrogen chloride gas was bubbled through a solution of lH-imidazol-4-ylacetic acid hydrochloride (10.0 g, 61.5 mmol) in methanol (200 ml) until saturated. The solution was allowed to stand for 18h at room temperature and then concentrated in vacuo to give the title compound (11.6 g, 100%) as a white solid.

1H-NMR (DMSO-d₆) : $ 9.05(s, 1H), 7.50(s, 1H), 3.90(s, 2H), 3.60(s, 3H).

<Step 2> l-(Triphenylm ethyl)- lH-imidazol-4-ylacetic acid methyl ester

To a suspension of lH-imidazol-4-ylacetic acid methyl ester HC1 (11.6 g, 65.6 mmol) in dichloromethane (350 ml) and DMF (50 ml) were added triethylamine (27.4 ml, 196.6 mmol) and triphenylm ethyl chloride (21.9 g, 78.6 mmol). The mixture was stirred for 15hr. The reaction mixture was washed with water and brine. The organic layer was concentrated in vacuo and purified by silica gel column chromatography(eluent: EtOAc/n-hexane=2/l, v/v) to provide a white solid of the title compound (7.44 g, 74 % in 2 steps). TLC : R_f = 0.20 (EtOAc / n-hexane = 1 / 1)

1H-NMR (CDCI3) : δ 7.45(s, 1H), 7.05-7.45(m, 15H), 6.75(s, 1H),

3.70(s, 2H)

<Steρ 3> l-(4-Nitrobenzyl)-lH-imidazol-5-ylacetic acid methyl ester

To a solution of l-triphenylmethyl-lH-imidazol-4-ylacetic acid methyl ester (4.96 g, 13.0 mmol) in acetonitrile (100 ml) was added 4-nitrobenzylbromide (2.80 g, 13.0 mmol) and the mixture was heated to 65°C for 24hr. The reaction mixture was concentrated to diyness, dissolved in methanol (150 ml) and heated to reflux temperature for lhr. The solution was concentrated in vacuo to the volume of 50 ml. Crystallization from methanol gave the title compound (3.27 g, 92 %) as a white solid.

TLC : Rr = 0.50 (CH₂C1₂ / MeOH = 9 / 1)

1H-NMR (DMSO-de) : 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)

<Steρ 4> l-(4-Nitrobenzyl)-lH-imidazol-5-ylacetic acid HCl

A solution of l-(4-nitrobenzyl)-lH-imidazol-5-ylacetic acid methyl ester (3.30 g, 11.9 mmol) in IN HCl (25 ml) was heated at 60°C for 4hr and concentrated in vacuo to dryness. Crystallization from methanol gave the title compound (1.64 g, 53 %) as a white solid

1H-NMR (DMSO-de) : 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)

Preparative Example 2. l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetic acid HCl <Step 1> l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetic acid methyl ester

The title compound (0.89 g, 93 %) was prepared from l-(triphenylmethyl)-lH-imidazol-4-ylacetic acid methyl ester (1.43 g, 3.74 mmol) and 4-cyanobenzylbromide (0.81 g, 4.11 mmol) according to the same reaction as described in <Step 3> of Preparative Example 1.

1H-NMR (DMSO-dό) : 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> l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetic acid HCl

The title compound (0.76 g, 90 %) as a white solid was prepared from l-(4-cyanobenzyl)-lH-imidazol-5-ylacetic acid methyl ester (0.86 g, 3.37 mmol) and 1.0 N HCl (50 ml) according to the same reaction as described in <Step 4> of Preparative Example 1.

-H-NMR (DMSO-dό) : 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)

Preparative Example 3 N-t-Butoxycarbonyl-L-isoleucine aldehyde

<Steρ 1> N-t-Butoxycarbonyl-L-isoleucine-N'-methoxy-N'-methylamide

To a suspension of N,O-dimethylhydroxylamine HCl (6.1 g, 62.5 mmol) in methylene chloride (60 ml) was added N-methyl morpholine (7.6 ml, 69.1 mmol) dropwise at -10°C, and this solution was stored at the same temperature. A solution of N-t-butoxycarbonyl-L-isoleucine (15 g, 62.4 mmol), N-methylmorpholine (7.6 ml, 69.1 mmol) and isobutylchloroformate (8.1 ml, 62.4 mmol) in methylene chloride (300 ml) was added dropwise to the solution of N,O-dimethylhydroxylamine prepared above, and stirred overnight at room temperature. After the addition of water (100 ml), the mixture was extracted with ethylacetate (100 ml X 3). The organic phase was washed with water (100 ml x 2) and brine (100 ml), dried over MgSO , and concentrated in vacuo. The residue was purified by silica gel column chromatography(eluent: ethylacetate/n-hexane=l/4, v/v), to give an oil of the title compound (15.1 g, 89%).

TLC : R_f = 0.25 (EtOAc /n-hexane / EtOH = 25 / 100 / 2)

1H-NMR (CDC1₃) : 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

To a suspension of LiAlH₄ (2.4 g, 54.7 mmol) in dry THF (300 ml) was added dropwise a solution of N-t-butoxycarbonyl-L-isoleucine -N'-methoxy-N'-methylamide (15 g, 54.7 mmol) in dry THF (30 ml) while mamtaining a temperature at -45°C or less. After the addition, the aqueous potassium bisulfate solution (12.7 g / 35 mL) was added dropwise while maintaning a temperature of -35°C, and then the reaction mixture was warmed to room temperature. The reaction mixture was mixed with an adequete amount of celite, and stirred for 1 hr. After the removal of celite by filtration, the organic phase was washed with water, dried over MgSO₄, and concentrated in vacuo to give an oil of the title compound (8.2 g, 69%). TLC : R_f = 0.55 (EtOAc / n-hexane / EtOH = 25 / 100 / 2)

1H-NMR (CDCfe) : 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)

Preparative Example 4

N-(2,3-Dichlorobenzyl)-2(S)-{[l-(4-nitrobenzyl)-lH-imidazol-5-yl]acetyl}ami no-3 (S)-methylpentylamine

<Step 1> N-(2,3-Dichlorobenz T)-2(S)-(t-butoxycarbonyl)amino-3(S)-methylpentylamin

To a solution of N-t-butoxycarbonyl-L-isoleucine aldehyde (4.52 g, 21.0 mmol) prepared from Preparative Example 3 in methanol (50 ml) were added 2,3-dichlorobenzylamine (4.07 g, 23.1 mmol), acetic acid (0.5 ml), and molecular sieve (3A, 5 g), and followed by sodium cyanoborohydride (1.45 g, 21.0 mmol). The mixture was stirred for overnight at room temperature. After the removal of insoluble material by filtration, the filtrate was concentrated in vacuo. The residue was poured into water (100 ml), extracted with ethylacetate (100 ml). The organic layer was dried over MgS0₄, and concentrated in vacuo. The residue was purified by silica gel column chromatography(eluent: ethylacetate/n-hexane=l/3, v/v), to give a light yellow oil of the title compound (5.0 g, 63%).

TLC : R_f = 0.49 (CH₂C1₂ / MeOH = 10 / 1)

1H-NMR (CDC1₃) : 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-butoxycarb onyl)amino-3(S)-methylpentylamine

To a solution of N-(2,3-dichlorobenzyl)-2(S)-(t-butoxycarbonyl) amino-3(S)-methylpentylamine (2.79 g, 7.39 mmol) in dichloromethane (30 ml) was added triethylamine (1.54 ml, 11.08 mmol) dropwise. After cooling to 0°C, the solution of 9-fluorenylmethylchloroformate (2.29 g, 8.87 mmol) in dichloromethane (20 ml) was added, and the mixture was stirred for overnight at room temperature. The reaction mixture was diluted with dichloromethane (100 ml), and washed with 5% HCl, saturated sodium bicarbonate solution, and brine several times. The ogranic phase was dried over MgSO , and concentrated in vacuo. The residue was purified by silica gel column chromatography(eluent: ethylacetate/n-hexane=l/5, v/v), to give a white solid of the title compound (2.42 g, 55%).

TLC : R_f = 0.29 (EtOAc / n-hexane = 1 / 4)

1H-NMR (CDCb) : 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)-m ethylpentylamine trifluoroacetic acid salt

To a solution of N-(2,3-dichlorobenzyl)-N-(9-fluorenylmethyloxy carbonyl)-2(S)-(t-butoxycarbonyl)amino-3(S)-methylpentylamine (2.42 g) in methylene chloride (30 ml) was added trifluoroacetic acid (10 ml) dropwise, and the mixture was stirred for 2 hr at room temperature. The reaction mixture was concentrated in vacuo to give an oil of the title compound, which was used for next steps without further purification.

<Step 4>

N-(2,3-Dichlorobenzyl)-N-(9-fluorenylmethyloxycarbonyl)-2(S)-{[l-(4-nitrobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

To a solution of l-(4-nitrobenzyl)-lH-imidazol-5-ylacetic acid HCl ( 1.05 g, 3.54 mmol) prepared from Preparative Example 1 in methylene chloride (50 ml) were added 1-hydroxybenzotriazole (0.82 g, 5.31 mmol), l-ethyl-3-(3-dimethylaminopropyl)carbodiimide (1.0 g, 4.60 mmol), and triethylamine (1.69 ml, 10.6 mmol) while stirring. After stirring for lhr, N-(2,3-dichlorobenzyl)-N-(9-fluorenylmethyloxycarbonyl)-2(S)-amino-3(S)-m ethylpentylamine trifluoroacetic acid salt (2.46 g, 4.03 mmol) was added to the reaction mixture and stirred for overnight at room temperature. The reaction mixture was poured into water, the organic phase was separated, dried over MgSO₄, and concentrated in vacuo to give the title compound.

<Step 5>

N-(2,3-Dichlorobenzyl)-2(S)-{ [ l-(4-nitrobenzyl)- lH-imidazol-5-yl]acetyl}ami no-3 (S)-methylpentylamine

N-(2,3-Dichlorobenzyl)-N-(9-fluorenylmethyloxycarbonyl)-2(S)-{[l- (4-nitrobenzyl)- 1 H-imidazol-5 -y l]acetyl } amino-3 (S )-methylpentylamine(prepa red in step 4) was dissolved in dimethylformamide (14 ml), and then piperidine (6 ml) was added. The reaction mixture was stirred for 4 hr at room temperature, and then the solvent was distilled off in vacuo. The residue was purified by silca gel column chromatography(eluent: methylene chloride/methanol=9/l, v/v), to give a white solid of the title compound (430 mg).

TLC : R_f = 0.20 (CH₂C1₂ / MeOH = 10 / 1)

Η-NMR (CDC1₃) : δ 8.20(d, 2H), 7.58(s, IH), 7.40(m, IH),

7.12-7.36(m, 4H), 7.05(s, IH), 5.70-6.00(m, IH), 5.33(s, 2H), 3.75-4.10(m, 3H), 3.38(s, 2H), 2.62(d, 2H), 1.78(bs, IH), 1.42-1.65(m, IH), 1.22-1.42(m, IH), 0.96-1.22(m, IH), 0.75-0.95(m, 6H)

Preparative Example 5

N-(2,3-Dichlorobenzyl)-2(S)-{[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}am ino-3 (S )-methy lpentylamine

l-(4-Cyanobenzyl)-lH-imidazol-5-ylacetic acid HCl was reacted according to the same procedure as Steps 4 and 5 of Preparative Example 4 to give the title compound.

TLC : R_f = 0.35 (CH₂C1₂ / MeOH = 10 / 1)

1H-NMR (CDCI3) : δ 7.62(d, 2H), 7.53(s, IH), 7.40(m, 3H), 7.00-7.35(m, 5H), 5.92(d, IH), 5.22(s, 2H), 3.75-4.05(m, 3H), 3.38(s, 2H), 2.62(m, 2H), 1.82(bs, IH), 1.42-1.65(m, 2H), 1.22-1.42(m, IH), 0.96-1.22(m, IH), 0.75-0.95(m, 6H)

Preparative Example 6

N-(l-Naphmylmemyl)-2(S)-{[l-(4-nitrobenzyl)-lH-imidazol-5-yl]acetyl}amin o-3 (S)-methylpentylamine

<Step 1>

N-( 1 -Naphthylmethyl)-2(S)-(/-butoxycarbonyl)amino-3 (S)-methy lpentylamine A solution of 1-naphthylmethylamine (0.90 g, 5.71 mmol) in methanol (10 ml) was adjusted to pH 6 by the addition of triethylamine. Then, sodium cyanoborohydride (8.60 ml, 1M solution in tetrahydro- furan), potassium acetate (562 mg, 5.71 mmol), and molecular sieves (2.00 g) were added thereto at 0°C under nitrogen. N-/-Butoxycarbonyl- L-isoleucine aldehyde (1.23 g, 5.71 mmol) in methanol was added dropwise to above solution. The reaction mixture was stirred at 20°C under nitrogen for 2hr. After concentration m vacuo, the residue was partitioned between water and ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried over MgSO₄ and concentrated in vacuo. The residue was purified by silica gel column chromatography(eluent: EtOAc /n-hexane=l/3, v/v) to give the title compound (740 mg, 36 %) as a white solid.

TLC : R_f = 0.20 (EtOAc / n-hexane = 1 / 2)

1H-NMR (CDC1₃) : δ 7.40-8.25(m, 7H), 4.65(d, IH), 4.15-4.40(m, 2H),

3.60-3.80(m, IH), 2.70-2.90(m, 2H), 1.40-1.70(m, 13H), 0.80-1.00(m, 6H)

<Step 2>

N-(l-Naphthylmethyl)-N-(9-fluorenylmethyloxycarbonyl)-2(S)-(/-butoxycarbo nyl)amino-3(S)-methylpentylamine

To a solution of N-(l-naphthylmethyl)-2(S)-(t-butoxycarbonyl)amino -3(S)-methylpentylamine (1.00 g, 2.81 mmol) in dichloromethane (10 ml) was added triethylamine (0.47 ml, 3.37 mmol) dropwise. 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 thereto. The reaction mixture was stirred at room temperature for 2hr. After concentration in vacuo, the residue was partitioned between 5% HCl and ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried over MgSO₄ and concentrated in vacuo. The residue was purified by silica gel column chromatography(eluent: EtOAc/n-hexane=l/5, v/v) to give the title compound (1.39 g, 86 %) as a white solid.

TLC : R_f = 0.36 (EtOAc / n-hexane = 1 / 5)

1H-NMR (CDC1₃) : δ 7.00-8.20(m, 15H), 5.33(m, IH), 4.62-5.05(m, 2H), 4.40-4.60(m, IH), 4.10-4.38(m, IH), 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-(l-Naphthylmethyl)-N-(9-fluorenylmethyloxycarbonyl)-2(S)-amino-3(S)-me thylpentylamine trifluoroacetic acid salt

N-( 1 -Naphthylmethyl)-N-(9-fluorenylmethyloxycarbonyl)-2(S)-ft- butoxycarbonyl)amino-3(S)-methylpentylamine (827 mg, 1.43 mmol) was dissolved in dichloromethane (30 ml) and trifluoroacetic acid (10 ml) was added thereto. The reaction mixture was stirred for 2hr at room temperature and then concentrated to dryness to give the title compound.

<Step 4>

N-( 1 -Naphthylmethyl)-N-(9-fluorenylmethyloxycarbonyl)-2(S)- { [ 1 -(4-nitroben zyl)- 1 H-imidazol-5 -yl]acetyl } amino-3 (S)-methylpentylamine

To a solution of l-(4-nitrobenzyl)- 1 H-imidazol-5 -ylacetic acid HCl (140 mg, 0.54 mmol) from Preparative Example 1 in dry dichloromethane / dry dimethylformamide (10 ml / 3 ml) were added l-hydroxybenzotriazole(HOBt) (109 mg, 0.80 mmol), l-ethyl-3 -(3 -dimethyl -aminopropyl)carbodiimde(EDC) (154 mg, 0.80 mmol) and triethylamine (0.19 ml, 1.34 mmol). The reaction mixture was stirred for 30 min. N-(l-naphthylmethyl)-N-(9-fluorenylmethyloxycarbonyl)-2(S)-amino-3(S)-met hylpentylamine trifluoroacetic acid salt (318 mg, 0.54 mmol) was added to this solution. After concentration in vacuo, the residue was partitioned between water and ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried over MgSO₄ and concentrated in vacuo. The residue was purified by silica gel column chromatography(eluent:

v/v) to give the title compound (249 mg, 63 %) as a white solid.

TLC : R_f = 0.50 (CH₂C1₂ / MeOH = 10 / 1)

1H-NMR (CDC1₃) : δ 6.90-8.25(m, 21H), 6.28(d, IH), 5.3 l(s, 2H), 5.20(dd, 2H), 4.02(bs, IH), 4.08-4.97(m, 3H), 3.78(t, IH), 2.93(d, 2H), 1.48(m, IH), 1.26(m, IH), 0.68-1.16(m, 7H)

<Step 5>

N-(l-Naphthylmethyl)-2(S)-{[l-(4-nitrobenzyl)-lH-imidazol-5-yl]acetyl}amin o-3(S)-methylpentylamine

N-(l-Naphthylmethyl)-N-(9-fluorenylmethyloxycarbonyl)-2(S)-{[l-(4- nitrobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine(249 mg, 0.34 mmol) was dissolved in dimethylformamide (8 ml) and piperidine (2 ml). The reaction solution was stirred at room temperature for 2hr. The solvents were removed by distillation in vacuo. The residue was purified by silica gel column chromatography(eluent: CH₂Cl₂/MeOH=10/l, v/v) to give the title compound (116 mg, 68 %) as a white solid.

TLC : R_f = 0.40 (CH2CI2 / MeOH = 10 / 1)

1H-NMR (CDCI3) : δ 6.90-8.20(m, 13H), 5.80(d, IH), 5.04(dd, 2H),

4.22(s, 2H), 3.90(bs, IH), 3.18(dd, 2H), 2.78(d, 2H), 1.48(m, IH), 1.26(m, IH), 1.04(m, IH), 0.87(m, 6H)

Example 1

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

To a solution of N-(2,3-dichlorobenzyl)-2(S)-{[l-(4-nitrobenzyl)-lH- imidazol-5-yl]acetyl}-amino-3(S)-methylpentylamine in methyenechloride (0.02M, 1ml, 0.02mmol) was added benzylisothiocyanate (0.1M in CH2CI2, 0.2ml, 0.02mmol). The reaction mixture was agitated for 5hr at room temperature. The mixture was purified by silica gel column chromatography(eluent: methylene chloride/methanol=9/l, v/v) to give the title compounds as a white solid.

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

Examples 2-26.

N-(2,3 -Dichlorobenzyl)-2(S)- { [ 1 -(4-nitrobenzyl)- 1 H-imidazol-5-yl] acetyl}amino-3(S)-methylpentylamine was reacted with the corresponding isothiocyanates under the same condition as described in Example 1 to give the title compounds.

Example 2

N-(2,3-Dichlorobenzyl)-N-(2-bromophenyl)thiocarbamoyl-2(S)-{[l-(4-nitrobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 3

N-(2,3-Dichlorobenzyl)-N-(3-bromophenyl)thiocarbamoyl-2(S)-{[l-(4-nitrobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDC1 ) : δ 7.05-8.20(m, 13H), 5.35(s, 2H), 4.82(m, 2H), 4.65(dd, IH), 4.18(m, IH), 3.35(s, 2H), 3.10(dd, IH), 1.65(m, IH), 1.42(m, IH), 1.05(m, IH), 0.92(m, 6H)

Example 4

N-(2,3-Dichlorobenzyl)-N-(4-chlorophenylthiocarbamoyl)-2(S)-{ [ 1 -(4-nitroben zyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 5

N-(2,3-Dichlorobenzyl)-N-(ethylthiocarbamoyl)-2(S)-{ [ 1 -(4-nitrobenzyl)- lH-i midazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 6

N-(2,3-Dichlorobenzyl)-N-(2-fluorophenylthiocarbamoyl)-2(S)-{ [ 1 -(4-nitroben zyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-mefhylpentylamine Η-NMR (CDCb) : δ 7.02-8.20(m, 13H), 5.38(s, 2H), 5.10(m, 2H), 4.72(dd, IH), 4.22(m, IH), 3.38(s, 2H), 3.10(dd, IH), 1.62(m, IH), 1.43(m, IH), 1.10(m, IH), 0.90(m, 6H)

Example 7

N-(2,3-Dichlorobenzyl)-N-(3-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-nitroben zyl)- 1 H-imidazol-5 -yljacetyl } amino-3 (S)-methylpentylamine

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

Example 8

N-(2,3-Dichlorobenzyl)-N-(4-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-nitroben zyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methy lpentylamine

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

Example 9

N-(2,3-Dichlorobenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrob enzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 10 N-(2,3-dichlorobenzyl)-N-(methylthiocarbamoyl)-2(S)-{ [ l-(4-nitrobenzyl)- 1H- imidazol-5-yl] acetyl } amino-3 (S)-methy lpentylamine

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

Example 11

N-(2,3-Dichlorobenzyl)-N-(3-trifluoiOmethylphenylthiocarbamoyl)-2(S)-{[l-(4

-nitrobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 12

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

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

Example 13

N-(2,3-Dichlorobenzyl)-N-( l-naphthylthiocarbamoyl)-2(S)-{ [ 1 -(4-nitrobenzyl)

- 1 H-imidazol-5-yl] acetyl } amino-3 (S )-methylpentylamine

1H-NMR (CDCb) : δ 6.85-8.18(m, 16H), 5.38(d, 2H), 5.05(bs, IH), 4.40(d, 2H), 4.05(m, IH), 3.28(s, 2H), 2.95(dd, IH), 1.60(m, IH), 1.40(m, IH), 1.05(m, IH), 0.88(m, 6H) Example 14

N-(2,3-DichloiObenzyl)-N-(phenylethylthiocarbamoyl)-2(S)-{[l-(4-nitrobenzyl

)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 15

N-(2,3-Dichlorobenzyl)-N-(n-butylthiocarbamoyl)-2(S)-{[l-(4-nitrobenzyl)-lH

-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 16

N-(2,3-Dichlorobenzyl)-N-(2-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-nitrob enzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 17

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

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

Example 18

N-(2,3-Dichlorobenzyl)-N-(cyclohexylthiocarbamoyl)-2(S)-{[l-(4-nitiObenzyl)

-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 19

N-(2,3-Dichlorobenzyl)-N-[(4-dimethylamino)-l-naphthylthiocarbamoyl]-2(S)- { [ 1 -(4-nitrobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methy lpentylamine

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

Example 20

N-(2,3-Dichlorobenzyl)-N-(phenylthiocarbamoyl)-2(S)-{[l-(4-nitrobenzyl)-lH -imidazol-5-yl] acetyl } amino-3 (S )-methylpentylamine

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

Example 21

N-(2,3-Dichlorobenzyl)-N-(n-propylthiocarbamoyl)-2(S)-{[l-(4-nitrobenzyl)-l

H-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine 1H-NMR (CDCb) : δ 7.10-8.22(m, 9H), 5.90(bs, IH), 5.60(d, 2H), 4.85-5.40(m, 2H), 4.75(dd, IH), 4.30(m, IH), 3.64-3.85(m, 2H), 3.55(s, 2H), 3.20(dd, IH), 1.42-1.85(m, 4H), 1.22(m, IH), 1.05(m, 6H), 1.00(q, 3H)

Example 22

N-(2,3-Dichlorobenzyl)-N-(4-azidophenylthiocarbamoyl)-2(S)-{[l-(4-nitroben zyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 23

N-(2,3-Dichlorobenzyl)-N-(4-bromophenylthiocarbamoyl)-2(S)-{[l-(4-nitrobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 24

N-(2,3-Dichlorobenzyl)-N-(2-chlorophenylthiocarbamoyl)-2(S)-{[l -(4-nitroben zyl)- 1 H-imidazol-5 -yl] acetyl} amino-3 (S)-methylpentylamine

1H-NMR (CDCb) : r5 6.90-8.20(m, 13H), 5.80(m, IH), 5.38(m, 2H), 4.65-5.04(m, 2H), 4.50(dd, IH), 4.05-4.38(m, 2H), 3.28(s, 2H), 3.00(dd, IH), 1.65(m, IH), 1.38(m, IH), 1.05(m, IH), 0.88(m, 6H) Example 25

N-(2,3-Dichlorobenzyl)-N-(3-chlorophenylthiocarbamoyl)-2(S)-{ [ 1 -(4-nitroben zyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 26

N-(2,3-Dichlorobenzyl)-N-(2,4-dichlorophenylthiocarbamoyl)-2(S)-{[l-(4-nitr obenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 27

N-(2,3-Dichlorobenzyl)-N-(benzylthiocarbamoyl)-2(S)-{ [ l-(4-cyanobenzyl)- 1

H-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

To a solution of N-(2,3-dichlorobenzyl)-2(S)-{[l-(4-cyanobenzyl)- 1 H-imidazol-5 -yl] acetyl} amino-3 (S)-methylpentylamine prepared from Preparative Example 5 in methylene chloride (0.02M, 1ml, 0.02mmol) was added benzylisothiocyanate (0.1M in CH2C1₂, 0.2ml, 0.02mmol). The reaction mixture was agitated for 2hr at room temperature. The mixture was purified by silica gel column chromatography(eluent: methylene chloride/ methanol=9/l, v/v) to give the title compound as a white solid.

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

Examples 28-67

N-(2,3-Dichlorobenzyl)-2(S)-{[l-(4-cyanobenzyl)-lH-imidazol-5-yl] acetyl} amino-3 (S)-methylpentylamine was reacted with the corresponding isothiocyanates under the same condition as described in Example 27 to give the title compounds.

Example 28

N-(2,3-Dichlorobenzyl)-N-(2-bromophenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methy lpentylamine

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

Example 29

N-(2,3-Dichlorobenzyl)-N-(3-bromophenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 30

N-(2,3 -Dichlorobenzyl)-N-(4-chlorophenylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine 1H-NMR (CDCb) : δ 6.90-8.00(m, 13H), 4.60-5.28(m, 5H), 4.08(m, IH), 3.25(s, 2H), 3.05(dd, IH), 1.60(m, IH), 1.38(m, IH), 0.85-1.05(m, 7H)

Example 31

N-(2,3-Dichlorobenzyl)-N-(ethylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-lH- imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 32

N-(2,3-Dichlorobenzyl)-N-(2-fluorophenylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanobe nzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methy lpentylamine

Η-NMR (CDCb) : 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, IH), 1.60(m, IH), 1.38(m, IH), 0.85-1.05(m, 7H)

Example 33

N-(2,3-Dichlorobenzyl)-N-(3-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5 -yl]acetyl } amino-3 (S )-methy lpentylamine

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

Example 34 N-(2,3-Dichlorobenzyl)-N-(4-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe oo

nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 35

N-(2,3-Dichlorobenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyano benzyl)- 1 H-imidazol-5 -yl] acetyl} amino-3 (S)-methy lpentylamine

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

Example 36

N-(2,3-Dichlorobenzyl)-N-(methylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-l

H-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

Η-NMR (CDCb) : r5 6.90-7.65(m, 9H), 6.05(bs, IH), 5.30(dd, IH), 5.05(t, IH), 4.40-4.80(dd, 2H), 4.10(m, IH), 3.32(s, 2H), 3.10(d, 3H), 3.00(dd, IH), 1.60(m, IH), 1.45(m, IH), 0.85-1.10(m, 7H)

Example 37

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

1H-NMR (CDCb) : δ 6.95-8.20(m, 13H), 4.55-5.38(m, 5H), 4.08(m, IH), 3.28(s, 2H), 3.05(dd, IH), 1.60(m, IH), 1.40(m, IH), 0.85-1.10(m, 7H) Example 38

N-(2,3-Dichlorobenzyl)-N-(allylthiocarbamoyl)-2(S)-{ [ l-(4-cyanobenzyl)- IH-i midazol-5 -yl] acetyl } amino-3 (S)-methylpentylamine

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

Example 39

N-(2,3-DichloiObenzyl)-N-(pyridine-4-ylthiocarbamoyl)-2(S)-{[l-(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 ( S )-methy lpentylamine

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

Example 40

N-(2,3-DicUorobenzyl)-N-(isobutylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-l

H-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.00-7.65(m, 9H), 6.91(d, IH), 5.74(bs, IH),

5.30(m, 2H), 5.05-5.20(m, IH), 4.62(dd, 2H), 4.05-4.13(m, IH),

3.45-3.58(m, IH), 3.25(m, 2H), 3.02(m, IH), 1.83(m, IH), 1.62(bs, IH), 1.45(m, IH), 1.05(m, IH), 0.90(m, 6H), 0.75(m, 6H)

Example 41

N-(2,3-Dichlorobenzyl)-N-(n-butylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-l H-imidazol-5 -yl] acetyl } amino-3 (S )-methylpentylamine

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

Example 42

N-(2,3 -Dichlorobenzyl)-N-(ethoxycarbonylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S)-methylpentylamine

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

Example 43

N-(2,3-Dichlorobenzyl)-N-( l-naphthylthiocarbamoyl)-2(S)-{ [ l-(4-cyanobenzyl

)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methy lpentylamine

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

Example 44

N-(2,3-Dichlorobenzyl)-N-(phenethylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl) - 1 H-imidazol-5 -yl]acetyl } amino-3 (S )-methy lpentylamine

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

Example 45

N-(2,3-Dichlorobenzyl)-N-(benzoylthiocarbamoyl)-2(S)-{ [ l-(4-cyanobenzyl)- 1

H-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine 1H-NMR (CDCb) : δ 7.05-7.80(m, 14H), 6.38(bs, IH), 5.35(s, 2H), 4.70-5.20(bs, 3H), 4.30(bs, IH), 3.45(s, 2H), 3.20(bs, IH), 2.00(bs, IH), 1.50(m, IH), 1.00(m, IH), 0.80(m, 6H)

Example 46

N-(2,3-Dichlorobenzyl)-N-(cyclohexylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl

)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 47

N-(2,3-DichloiObenzyl)-N-[(4-dimethylamino)-l-naphthylthiocarbamoyl]-2(S)-

{[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 48

N-(2,3-Dichlorobenzyl)-N-(2-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyano benzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 49 N-(2,3-Dichlorobenzyl)-N-(4-nitrophenylthiocarbamoyl)-2(S)-{[l-(4-cyanoben zyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 50

N-(2,3-Dichlorobenzyl)-N-(phenylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-l

H-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 51

N-(2,3-Dichlorobenzyl)-N-(n-propylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanobenzyl)-

1 H-imidazol-5-yl]acetyl} amino-3 (S)-methylpentylamine

1H-NMR (CDCb) : δ 7.00-7.75(m, 9H), 5.35(d, 2H), 5.10(m, IH),

4.42-4.80(dd, 2H), 4.08(m, IH), 3.68 (t, 2H), 3.32(s, 2H), 3.02(dd, IH),

1.62(m, IH), 1.50(m, 2H), 1.40(m, IH), 1.05(m, IH), 0.94(m, 6H), 0.78 (t, 3H)

Example 52

N-(2,3-Dichlorobenzyl)-N-(3-methylphenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S)-methylpentylamine

Η-NMR (CDCb) : δ 7.00-7.65(m, 13H), 5.30(d, 2H), 5.20(m, IH), 4.70 & 5.04(dd, 2H), 4.20(m, IH), 3.32(s, 2H), 3.12(dd, IH), 2.12(s, 3H), 1.64(bs, IH), 1.42(m, IH), 1.05(m, IH), 0.90(m, 6H) Example 53

N-(2,3-Dichlorobenzyl)-N-(2-methylphenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 54

N-(2,3-Dichlorobenzyl)-N-(4-methylphenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpenxylamine

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

Example 55

N-(2,3-Dichlorobenzyl)-N-(4-azidophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 56

N-(2,3-Dichlorobenzyl)-N-(4-bromophenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 57

N-(2,3-Dichlorobenzyl)-N-(2-chlorophenylthiocarbamoyl)-2(S)-{[l -(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpenxylamine

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

Example 58

N-(2,3-Dichlorobenzyl)-N-(3-chlorophenylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 59

N-(2,3-Dichlorobenzyl)-N-(2,4-dichlorophenylthiocarbamoyl)-2(S)-{[l-(4-cya nobenzyl)-l H-imidazol-5 -yl] acetyl} amino-3 (S)-methy lpentylamine

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

Example 60

N-(2,3-Dichlorobenzyl)-N-(2-methoxypyridine-5-ylthiocarbamoyl)-2(S)-{[l-(4 -cy anobenzyl)- 1 H-imidazol-5-yl]acetyl } amino-3 (S )-methylpentylamine 1H-NMR (CDCb) : δ 7.00-7.84(m, 12H), 6.68(d, IH), 5.28(d, 2H), 4.98-5.20(bs, 2H), 4.68(d, IH), 4.18(m, IH), 3.87(s, 3H), 3.30(s, 2H), 3.12(dd, IH), 1.40-1.62(m, 2H), 1.02(m, IH), 0.90(m, 6H)

Example 61

N-(2,3-Dichlorobenzyl)-N-(3-ethoxypropylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 6.80-7.65(m, 10H), 5.38(d, 2H), 5.20(m, IH),

4.52(d, 2H), 4.05(m, IH), 3.70(m, 2H), 3.40(m, 2H), 3.32(s, 2H),

3.06-3.28(m, 4H), 2.93(dd, IH), 1.75 (t, 3H), 1.60(bs, IH), 1.40(m, IH), 1.04(m, IH), 0.85(m, 6H)

Example 62

N-(2,3-Dichlorobenzyl)-N-(4-aminophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : 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, IH), 4.07(m, IH), 2.80-3.40(m, 3H), 1.95(m, IH), 1.25-1.70(m, 2H), 0.90(m, 6H)

Example 63

N-(2,3-Dichlorobenzyl)-N-(2-methoxyethylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 6.82-7.65(m, 10H), 5.95(bs, IH), 5.38(d, 2H),

5.18(m, IH), 4.60(dd, 2H), 4.10(m, IH), 3.72 (t, 2H), 3.40 (t, 2H),

3.28(s, 2H), 3.15(s, 3H), 3.02(dd, IH), 1.63(bs, IH), 1.42(m, IH), 1.04(m, IH), 0.88(m, 6H) Example 64

N-(2,3-Dichlorobenzyl)-N-(cyclopentylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzy 1)- 1 H-imidazol-5-y 1] acetyl } amino-3 (S )-methy lpentylamine

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

Example 65

N-(2,3-Dichlorobenzyl)-N-(cyclopropylthiocarbamoyl)-2(S)-{[l-(4-cyanobenz yl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

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

Example 66

N-(2,3-Dichlorobenzyl)-N-(ethoxycarbonylmethylthiocarbamoyl)-2(S)- { [ 1 -(4-c y anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methylpentylamine

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

Example 67

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

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

Example 68

N-(2,3-Dichlorobenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyano benzyl)- lH-imidazol-5-yl]acetyl} amino-3 (S)-methy lpentylamine HCl

The compound (500 mg) prepared from Example 35 was dissolved in HCl-ethanol (6N, 5ml), and stirred for 2 hr at room temperature. The reaction mixture was concentrated in vacuo, and the residue was crystallized from methylene chloride/diethylether(l/10, v/v) to give the title compound as a white solid.

1H-NMR (CDCb) : δ 8.83(s, IH), 7.60(d, 2H), 7.48(s, IH), 7.34(m, 3H), 7.20(m, IH), 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)-{[l-(4-cyano benzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpeniylamine methanesulf- onic acid salt

To a solution of the compound (500 mg) prepared from Example 35 in methylene chloride (10ml) were added methanesulfonic acid (3 ml) and water (0.5ml), and the resulting mixture was stirred for 30 min at room temperature. The organic phase was separated, dried over MgSO₄, and concentrated in vacuo. The residue was crystallized from methylene chloride / diethylether(l/10, v/v) to give the title compound as a white solid. 1H-NMR (CDCb) : δ 14.9(s, IH), 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, IH), 3.80(s, 3H), 3.40-3.77(m, 2H), 3.23(m, IH), 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)-{[l-(4-cyanobenzyl )- lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine HCl

The compound prepared from Example 46 was reacted under the same condition as described in Example 68 to give the title compound.

1H-NMR (CDCb) : δ 8.10-8.14(m, IH), 7.70(d, 2H), 7.41-7.49(m, 5H),

7.20 (t, IH), 7.00(d, IH), 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, IH), 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)-{[l-(4-cyan obenzyl)- lH-imidazol-5-yl]acexyl}amino-3(R)-methylpentylamine HCl

N-t-Butoxycarbonyl-D-isoleucine aldehyde was reacted under the same condition as described in Preparative Example 4 to give a compound N-(2,3-dichlorobenzyl)-2(R)-{[l-(4-cyanobenzyl)-lH-imidazol-5- yl] acetyl} amino-3 (R)-methylpentylamine, which was then reacted with 4-methoxyphenylisothiocyanate under the same condition as described in Example 27 and Example 68 to give the title compound.

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

Example 72

N-(2,3-Dichlorobenzyl)-N-(thiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-lH-imid azol-5-yl]acetyl}amino-3(S)-methylpentylamine

<Step 1>

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

-methylpentylamine

To a solution of N-(2,3-dichlorobenzyl)-2(S)-(t-butoxycarbonyl) amino-3(S)-methylpentylamine (2.15 g, 5.7 mmol) in methylene chloride (50 ml) was added benzoylisothiocyanate (0.93 g, 5.7 mmol), and then stirred for 2 hr at room temperature. The reaction mixture was concentrated in vacuo, and then the resulting residue was dissolved in methanol (50 ml) and 2N NaOH (50 ml). The reaction mixture was refluxed for 24 hr, concentrated in vacuo, and the residue was purified by silica gel column chromatography(eluent: methylene chloride/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-cy anobenzyl)- 1 H-imid azol-5-yl]acetyl}amino-3(S)-methylpentylamine

To a solution of N-(2,3-dichlorobenzyl)-N-(thiocarbamoyl)-2(S)- (t-butoxycarbonyl)amino-3(S)-methylpentylamine (90 mg, 0.21 mmol) in dichloromethane (7 ml) was added trifluoroacetic acid (3 ml), and stirred for 1 hr at room temperature. The reaction mixture was washed with saturated sodium bicaibonate, dried over MgSO₄, and concentrated in vacuo. The residue was reacted with l-(4-cyanobenzyl)-lH-imidazol- 5-yl acetic acid HCl (69 mg, 0.25 mmol) under the same condition described in <step 4> of Prepaiative Example 4 to give the title compound (20 mg).

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

Example 73

N-(2,3-Dichlorobenzyl)-N-(allylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-lH-i midazol-5 -yl] acetyl } aminopropylamine

<Step 1>

N-(2,3-dichlorobenzyl)-2(S)-{[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}ami nopropylamine

Using the same method as described in Preparative Example 3, N-t-butoxycarbonyl-L-alanine was converted to N-(t-butoxycarbonyl)-L- alanine aldehyde. And then the reaction was carried out as described in Preparative Example 4, but replacing l-(4-nitrobenzyl)-lH-imidazol-5- ylacetic acid HCl with l-(4-cyanobenzyl)-lH-imidazol-5-ylacetic acid HCl to give the title compound.

1H-NMR (CDCb) : δ 6.99-7.62(m, 9H), 6.17(d, IH), 5.25(s, 2H), 3.98(m, IH), 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)-{[l-(4-cyanobenzyl)-lH-i midazol-5-yl]acetyl}aminopropylamine

To a solution of N-(2,3-dichlorobenzyl)-2(S)-{[l-(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}aminopropylamine in methyenechloride (0.02M, lml, 0.02mmol) was added allylisothiocyanate (0.1M in CH₂C1₂, 0.2ml, 0.02mmol). The reaction mixture was agitated for lhr at room temperature. The mixture was purified by silica gel column chromatography(eluent: methylene chloride/methanol=9/l, v/v) to give the title compound as a white solid.

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

Examples 74-116

N-(2,3-Dichlorobenzyl)-2(S)-{[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}am inopropylamine was reacted with the corresponding isothiocyanates under the same condition as described in <Step 2> of Example 73 to give the title compounds.

Example 74

N-(2,3-Dichlorobenzyl)-N-(benzylthiocarbamoyl)-2(S)-{ [ l-(4-cyanobenzyl)- 1

H-imidazol-5 -yl] acetyl } aminopropylamine

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

Example 75 N-(2,3-Dichlorobenzyl)-N-(2-biphenylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl )- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

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

Example 76

N-(2,3-Dichlorobenzyl)-N-(2-bromophenylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}aminopiOpylamine

Η-NMR (CDCb) : δ 8.04(bs, IH), 6.97-7.67(m, 13H), 5.30(s, 2H), 5.28(d, IH), 4.81(bs, IH), 4.77(d, IH), 4.29(m, IH), 3.36(s, 2H), 3.07(dd, IH), 1.2 l(d, 3H)

Example 77

N-(2,3-Dichlorobenzyl)-N-(3-bromophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanob enzyl)- lH-imidazol-5-yl]acetyl} aminopropylamine

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

Example 78

N-(2,3-Dichlorobenzyl)-N-(4-bromophenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)- lH-imidazol-5-yl]acetyl} aminopropylamine

1H-NMR (CDCb) : δ 8.85(bs, IH), 6.93-7.59(m, 13H), 5.61(d, IH), 5.24(s, 2H), 4.7 l(d, IH), 4.52(m, IH), 4.12(m, IH), 3.33(s, 2H), 2.98(dd, IH), 1.24(d, 3H) Example 79

N-(2,3-Dichlorobenzyl)-N-(n-butylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-l

H-imidazol-5-yl]acetyl}aminopropylamine

1H-NMR (CDCb) : δ 6.93-7.67(m, 9H), 6.38(bs, IH), 5.34(s, 2H), 5.14(d, IH), 4.70(m, IH), 4.59(d, IH), 4.09(m, IH), 3.61(m, 2H), 3.33(s, 2H), 2.94(dd, IH), 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)-{[l-(4-cyanobenzyl)-l H -imidazol- 5 -yl] acetyl } aminopropylamine

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

Example 81

N-(2,3-Dichlorobenzyl)-N-(2-chlorophenylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}aminopropylamine

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

Example 82

N-(2,3-Dichlorobenzyl)-N-(3-chlorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5-yl] acetyl } aminopropylamine

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

Example 83

N-(2,3-Dichlorobenzyl)-N-(4-chlorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5-yl] acetyl } aminopropylamine

1H-NMR (CDCb) : δ 8.81(bs, IH), 6.94-7.59(m, 13H), 5.60(d, IH), 5.24(s, 2H), 4.7 l(d, IH), 4.52(m, IH), 4.13(m, IH), 3.33(s, 2H), 2.99(dd, IH), 1.24(d, 3H)

Example 84

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

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

Example 85

N-(2,3 -Dichlorobenzyl)-N-(cyclohexylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanobenzyl

)-lH-imidazol-5-yl]acetyl}aminopropylamine

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

Example 86

N-(2,3-Dichlorobenzyl)-N-(cyclopentylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzy l)-lH-imidazol-5-yl]acetyl}aminopropylamine 1H-NMR (CDCb) : δ 6.93-7.66(m, 9H), 6.21(bs, IH), 5.33(s, 2H), 5.17(d, IH), 4.68(m, IH), 4.58(d, IH), 4.05(m, IH), 3.32(s, 2H), 2.91(dd, IH), 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)-{[l-(4-cya nobenzyl)-lH-imidazol-5-yl]acetyl}aminopropylamine

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

Example 88

N-(2,3-Dichlorobenzyl)-N-[2-(dimethylamino)ethylthiocarbamoyl]-2(S)-{[l-(4 -cy anobenzyl)- 1 H-imidazol-5 -yl]acetyl } aminopropylamine

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

Example 89

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

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

Example 90 N-(2,3-Dichlorobenzyl)-N-[3-(dimethylamino)propylthiocarbamoyl]-2(S)-{[l-( 4-cyanobenzyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

Η-NMR (CDCb) : δ 8.91(bs, IH), 6.80-7.66(m, 9H), 5.44(d, IH),

5.36(s, 2H), 4.95(m, IH), 4.55(d, 2H), 4.12(m, IH), 3.68(m, 2H),

3.32(dd, 2H), 2.92(dd, IH), 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)-{[l-(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

^'H-NMR (CDCb) : δ 7.75(bs, IH), 6.84-7.67(m, 9H), 5.35(s, 2H), 4.94 (t, IH), 4.66(dd, 2H), 4.12(m, IH), 3.74(bs, 2H), 3.42(m, 2H), 3.32(s, 2H), 3.2 l(m, 2H), 2.94(dd, IH), 1.78(bs, 2H), 1.14(d, 3H), 0.90 (t, 3H)

Example 92

N-(2,3-Dichlorobenzyl)-N-(ethylthiocarbamoyl)-2(S)-{[l -(4-cyanobenzyl)- 1H- imidazol-5-yl]acetyl}am inopropylamine

^'H-NMR (CDCb) : δ 6.92-7.66(m, 9H), 6.45(bs, IH), 5.34(s, 2H), 5.18(d, IH), 4.63(m, IH), 4.58(d, IH), 4.07(m, IH), 3.66(m, 2H), 3.32(s, 2H), 2.91(dd, IH), 1.18(d, 3H), 1.16 (t, 3H)

Example 93

N-(2,3-Dichlorobenzyl)-N-(2-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

1H-NMR (CDCb) : δ 8.28(bs, IH), 6.95-7.60(m, 13H), 5.36(d, IH), 5.25(s, 2H), 4.79(m, IH), 4.75(d, IH), 4.22(m, IH), 3.32(s, 2H), 3.04(dd, IH), 1.21(d, 3H) Example 94

N-(2,3-Dichlorobenzyl)-N-(3-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5 -yl]acetyl } aminopropylamine

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

Example 95

N-(2,3-Dichlorobenzyl)-N-(4-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

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

Example 96

N-(2,3-Dichlorobenzyl)-N-(4-hydroxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyano benzyl)- 1 H-imidazol-5 -yl] acetyl} aminopropylamine

1H-NMR (CD₃OD) : δ 6.69-7.75(m, 13H), 5.37(s, 2H), 5.32(d, IH), 5.00(d, IH), 4.24(m, IH), 4.10(m, IH), 3.43(dd, IH), 3.41(s, 2H), 1.17(d, 3H)

Example 97

N-(2,3-Dichlorobenzyl)-N-(4-isopropylphenylthiocarbamoyl)-2(S)-{[l-(4-cyan obenzyl)- lH-imidazol-5-yl]acetyl} aminopropylamine

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

Example 98

N-(2,3-Dichlorobenzyl)-N-(2-methoxyethylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

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

Example 99

N-(2,3-Dichlorobenzyl)-N-(2-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyano benzyl)- 1 H-imidazol-5 -yl] acetyl} aminopropylamine

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

Example 100

N-(2,3-Dichlorobenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyano benzyl)-lH-imidazol-5-yl]acetyl}aminopropylamine

1H-NMR (CDCb) : δ 8.26(bs, IH), 6.84-7.59(m, 13H), 5.38(d, IH), 5.26(s, 2H), 4.75(m, IH), 4.72(d, IH), 4.16(m, IH), 3.79(s, 3H), 3.3 l(s, 2H), 3.01(dd, IH), 1.21(d, 3H)

Example 101

N-(2,3-Dichlorobenzyl)-N-(3-methoxypropylthiocarbamoyl)-2(S)-{[l-(4-cyano benzyl)- lH-imidazol-5-yl]acetyl} aminopropylamine 1H-NMR (CDCb) : δ 7.82(bs, IH), 6.81-7.67(m, 9H), 5.36(dd, 2H), 4.98 (t, IH), 4.62(dd, 2H), 4.13(m, IH), 3.68(m, 2H), 3.37(m, 2H), 3.3 l(s, 2H), 2.96(dd, IH), 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)-{[l-(4- cyanobenzyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

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

Example 103

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

^'H-NMR (CDCb) : δ 6.92-7.67(m, 9H), 6.56(bs, IH), 5.29(s, 2H), 5.13(d, IH), 4.65(m, IH), 4.58(d, IH), 4.09(m, IH), 3.32(s, 2H), 3.1 l(s, 3H), 2.92(dd, IH), 1.18(d, 3H)

Example 104

N-(2,3-Dichlorobenzyl)-N-(4-methylthiophenylthiocarbamoyl)-2(S)-{[l-(4-cya nob enzyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

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

Example 105 N-(2,3-Dichlorobenzyl)-N-(2-naphthylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl )-lH-imidazol-5-yl]acetyl}aminopropylamine

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

Example 106

N-(2,3-Dichlorobenzyl)-N-(4-nitrophenylthiocarbamoyl)-2(S)-{[l-(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

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

Example 107

N-(2,3-Dichlorobenzyl)-N-(n-pentylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}aminopropylamine

1H-NMR (CDCb) : δ 6.93-7.66(m, 9H), 6.21(bs, IH), 5.33(s, 2H),

5.07(d, IH), 4.77(m, IH), 4.59(d, IH), 4.12(m, IH), 3.63(m, IH), 3.48

(t, 2H), 3.3 l(s, IH), 2.97(dd, IH), 1.68(m, IH), 1.17(d, 3H), 0.74-1.30(m, 8H)

Example 108

N-(2,3 -Dichlorobenzyl)-N-(phenethylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanobenzyl)

- 1 H-imidazol-5-yl]acetyl } aminopropylamine

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

Example 109

N-(2,3-Dichlorobenzyl)-N-(phenylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-l

H-imidazol-5-yl]acetyl}aminopropylamine

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

Example 110

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

¹ H-NMR (CDCb) : δ 6.93-7.67(m, 9H), 6.35(bs, IH), 5.33(s, 2H), 5.14(d, IH), 4.72(m, IH), 4.59(d, IH), 4.09(m, IH), 3.59(m, 2H), 3.33(s, 2H), 2.93(dd, IH), 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)-{[l-(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

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

Example 112

N-(2,3-Dichlorobenzyl)-N-(2-methylphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine ^'H-NMR (CDCb) : δ 7.87(bs, IH), 6.96-7.60(m, 13H), 5.3 l(d, IH), 5.27(s, 2H), 4.8 l(m, IH), 4.75(d, IH), 4.20(m, IH), 3.3 l(s, 2H), 3.06(dd, IH), 2.11(s, 3H), 1.20(d, 3H)

Example 113

N-(2,3-Dichlorobenzyl)-N-(4-methylphenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)- 1 H-imidazol-5-yl] acetyl } aminopropylamine

1H-NMR (CDCb) : δ 8.29(bs, IH), 6.96-7.58(m, 13H), 5.43(d, IH), 5.26(s, 2H), 4.72(d, IH), 4.70(m, IH), 4.17(m, IH), 3.32(s, 2H), 3.00(dd, IH), 2.33(s, 3H), 1.2 l(d, 3H)

Example 114

N-(2,3-Dichlorobenzyl)-N-(3-trifluoiOmethylphenylthiocarbamoyl)-2(S)-{[l-(4 -cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

-H-NMR (CDCb) : δ 9.44(bs, IH), 6.92-7.85(m, 13H), 5.8 l(d, IH), 5.27(s, 2H), 4.71(d, IH), 4.43(m, IH), 4.13(m, IH), 3.33(s, 2H), 3.00(dd, IH), 1.28(d, 3H)

Example 115

N-(2,3-Dichlorobenzyl)-N-(2,4-dimethylphenylthiocarbamoyl)-2(S)-{[l-(4-cya nobenzyl)- lH-imidazol-5-yl]acetyl} aminopropylamine

^'H-NMR (CDCb) : δ 7.85(bs, IH), 6.96-7.60(m, 12H), 5.27(s, 2H), 5.20(d, IH), 4.85(m, IH), 4.74(d, IH), 4.20(m, IH), 3.3 l(s, 2H), 3.05(dd, IH), 2.3 l(s, 3H), 2.07(s, 3H), 1.20(d, 3H)

Example 116 N-(2,3-Dichlorobenzyl)-N-(3,4-dimethylphenylthiocarbamoyl)-2(S)-{[l-(4-cya nobenzyl)-lH-imidazol-5-yl]acetyl}aminopropylamine

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

Example 117

N-(2,3-Dichlorobenzyl)-N-(allylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-lH-i midazol-5-yl]acetyl}amino-3-methylbutylamine

<Step 1>

N-(2,3-dichlorobenzyl)-2(S)-{[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}ami no-3 -methylbutylamine

Using the same method as described in Preparative Example 3, N-t-butoxycarbonyl-L-valine was converted to N-(t-butoxycarbonyl)-L- valine aldehyde. And then the reaction was carried out under the same condition as described in Preparative Example 4, but replacing 1 -(4-nitrobenzyl)- 1 H-imidazol-5 -ylacetic acid HCl with l-(4-cyanobenzyl)- 1 H-imidazol-5 -ylacetic acid HCl to give the title compound.

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

<Step 2>

N-(2,3-Dichlorobenzyl)-N-(allylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-lH-i midazol-5-yl]acetyl}amino-3-methylbuxylamine

To a solution of N-(2,3-dichlorobenzyl)-2(S)-{[l -(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}amino-3-methylbutylamine in methyene chloride (0.02M, 1ml, 0.02mmol) was added allylisothiocyanate (0.1M in CH₂C1₂, 0.2ml, 0.02mmol). The reaction mixture was agitated for lhr at room temperature. The mixture was purified by silica gel column chromatography(eluent: methylene chloride/methanol=9/l, v/v) to give the title compound as a white solid.

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

Examples 118-160

N-(2, 3 -Dichlorobenzyl)-2(S )- { [ 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl] acetyl} amino-3 -methylbutylamine was reacted with the corresponding isothiocyanates under the same condition as described in <Step 2> of Example 117 to give the title compounds.

Example 118

N-(2,3-Dichlorobenzyl)-N-(benzylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanobenzyl)- 1

H-imidazol-5-yl]acetyl}amino-3-methylbutylamine(YHS98- 18-02)

¹H-NMR(CDCb) : δ 6.91-7.64(m, 14H), 6.31(bs, IH), 5.26(d, 2H), 5.07(t, IH), 4.8 l(m, 2H), 4.54(d, IH), 4.06(m, IH), 3.26(s, 2H), 3.05(dd, IH), 1.83(m, IH), 1.90(d, 6H)

Example 119

N-(2,3 -Dichlorobenzyl)-N-(2-biphenylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanobenzyl

)-lH-imidazol-5-yl]acetyl}amino-3-methylbutylamine ^'H-NMR(CDCb) : δ 6.64-7.75(m, 18H), 5.26(s, 2H), 4.84(m, IH), 4.80(d, IH), 4.48(d, IH), 4.03(m, IH), 3.34(s, 2H), 2.98(dd, IH), 1.82(m, IH), 0.87(dd, 6H)

Example 120

N-(2,3-Dichlorobenzyl)-N-(2-bromophenylthiocarbamoyl)-2(S)-{[l -(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

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

Example 121

N-(2,3-Dichlorobenzyl)-N-(3-bromophenylthiocarbamoyl)2(S)-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

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

Example 122

N-(2,3-DichloiObenzyl)-N-(4-biOmophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-3-methylbutylamine

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

Example 123

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

-H-NMR(CDCb) : δ 6.89-7.67(m, 9H), 5.93(bs, IH), 5.35(d, 2H), 5.04(t, IH), 4.65(dd, 2H), 4.04(m, IH), 3.68(m, IH), 3.48(m, IH), 3.33(s, 2H), 3.02(dd, IH), 1.84(m, IH), 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)-{[l-(4-cyanobenzyl)-l H-imidazol-5 -yl] acetyl} amino-3 -methylbutylamine

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

Example 125

N-(2,3-Dichlorobenzyl)-N-(2-chlorophenylthiocarbamoyl)-2(S)-{[l -(4-cyanobe nzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

1H-NMR(CDCb) : δ 6.94-7.69(m, 13H), 5.25(s, 2H), 5.11(d, IH), 5.07(m, IH), 4.72(d, IH), 4.19(m, IH), 3.36(s, 2H), 3.14(dd, IH), 1.85(m, IH), 0.9 l(m, 6H)

Example 126

N-(2,3-Dichlorobenzyl)-N-(3-chlorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3-methylbutylamine

-H-NMR(CDCb) : δ 8.47(bs, IH), 6.89-7.60(m, 13H), 5.34(d, IH), 5.26(s, 2H), 4.58(t, IH), 4.66(d, IH), 4.09(m, IH), 3.33(s, 2H), 3.11(dd, IH), 1.89(m, IH), 0.92(m, 6H) Example 127

N-(2,3-Dichlorobenzyl)-N-(4-chlorophenylthiocarbamoyl)-2(S)-{[l -(4-cyanobe nzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

-H-NMR(CDCb) : δ 8.33(bs, IH), 6.90-7.61(m, 13H), 5.30(d, IH), 5.24(s, 2H), 4.89(t, IH), 4.66(d, IH), 4.08(m, IH), 3.32(s, 2H), 3.11(dd, IH), 1.88(m, IH), 0.9 l(t, 6H)

Example 128

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

-H-NMR(CDCb) : δ 8.33(bs, IH), 6.97-7.60(m, 12H), 5.29(d, IH), 5.26(s, 2H), 4.89(t, IH), 4.65(d, IH), 4.09(m, IH), 3.33(s, 2H), 3.10(dd, IH), 2.32(s, 3H), 1.88(m, IH), 0.9 l(t, 6H)

Example 129

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

1H-NMR(CDC1₃) : δ 6.88-7.66(m, 9H), 5.98(bs, IH), 5.34(d, 2H), 5.06(t, IH), 4.64(dd, IH), 4.25(m, IH), 4.01(m, IH), 3.33(s, 2H), 3.00(dd, IH), 1.84(m, IH), 0.88-1.98(m, 10H), 0.91(t, 6H)

Example 130

N-(2,3-Dichlorobenzyl)-N-(cyclopentylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanobenzy l)-lH-imidazol-5-yl]acetyl}amino-3-methylbutylamine

1H-NMR(CDC1₃) : δ 6.88-7.66(m, 9H), 6.25(d, IH), 5.34(d, 2H), 5.03(t, IH), 4.65(dd, IH), 4.65(dd, IH), 4.02(m, IH), 3.33(s, 2H), 3.01(dd, IH), 1.84(m, IH), 1.18-2.06(m, 8H), 0.90(dd, 6H)

Example 131

N-(2,3-DichloiObenzyl)-N-(2,4-dichlorophenylthiocarbamoyl)-2(S)-{[l-(4-cya nobenzyl)-l H-imidazol-5 -yl] acetyl} amino-3 -methylbutylamine

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

Example 132

N-(2,3-DichloiObenzyl)-N-[2-(dimethylamino)ethylthiocarbamoyl]-2(S)-{[l-(4

-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3-methylbutylamine

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

Example 133

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

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

Example 134

N-(2,3-Dichlorobenzyl)-N-[3-(dimethylamino)propylthiocarbamoyl]-2(S)-{[l-( 4-cyanobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine Η-NMR(CDCb) : δ 8.88(bs, IH), 6.81-7.67(m, 9H), 5.40(dd, 2H),

5.1 l(t, IH), 4.52(s, 2H), 4.05(m, IH), 3.67(m, 2H), 3.33(dd, 2H),

2.93(dd, IH), 2.40(m, 2H), 1.87(s, 6H), 1.83(m, IH), 1.77(m, 2H), 0.90(d, 6H)

Example 135

N-(2,3-Dichlorobenzyl)-N-(3-ethoxypropylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

1H-NMR(CDCb) : δ 6.76-7.67(m. 9H), 5.37(dd, 2H). 5.15(t, IH). 4.54(d, 2H), 4.03(m, IH), 3.72(m, 2H), 3.43(m, 2H), 3.33(s, 2H), 3.18(m, 2H), 2.93(dd, IH), 1.78(m, IH), 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)- 1 H- imidazol-5-yl] acetyl} amino-3 -methylbutylamine

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

Example 137

N-(2,3-Dichlorobenzyl)-N-(2-fluorophenylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanobe nzyl)- 1 H-imidazol-5-yl] acetyl } amino-3 -methylbutylamine

-H-NMR(CDCb) : δ 6.90-7.62(m, 13H), 5.26(s, 2H), 5.11(d, IH), 5.07(t, IH), 4.70(d, IH), 4.15(m, IH), 3.36(s, 2H), 3.11(dd, IH), 1.85(m, IH), 0.91(dd, 6H) Example 138

N-(2,3-Dichlorobenzyl)-N-(3-fluorophenylthiocarbamoyl)-2(S)-{[l -(4-cyanobe nzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

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

Example 139

N-(2,3-Dichlorobenzyl)-N-(4-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5 -yl]acetyl } amino-3 -methylbutylamine

-H-NMR(CDCb) : δ 8.10(bs, IH), 6.97-7.63(m, 13H), 5.3 l(s, 2H), 5.22(d, IH), 4.95(t, IH), 4.68(d, IH), 4.10(m, IH), 3.34(s, 2H), 3.13(dd, IH), 1.89(m, IH), 0.92(dd, 6H)

Example 140

N-(2,3-Dichlorobenzyl)-N-(4-hydiOxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyano benzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

Η-NMR(CD₃OD) : δ 6.67-7.71(m, 13H), 5.39(s, 2H), 5.03(dd, 2H), 4.29(m, IH), 3.87(m, IH), 3.67(d, IH), 3.44(s, 3H), 3.3 l(s, 2H), 2.68(m, IH), 1.77(m, IH), 0.89(t, 6H)

Example 141

N-(2,3-Dichlorobenzyl)-N-(4-isopropylphenylthiocarbamoyl)-2(S)-{[l-(4-cyan obenzyl)- lH-imidazol-5-yl]acetyl} amino-3 -methylbutylamine

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

Example 142

N-(2,3-Dichlorobenzyl)-N-(2-methoxyethylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

Η-NMR CDCb) : δ 6.88-7.66(m, 9H), 6.01(bs, IH), 5.35(d, 2H),

5.16(1, IH), 4.62(dd, IH), 4.07(m, IH), 3.82(m, IH), 3.68(m, IH),

3.41(m, 2H), 3.33(s, 2H), 3.13(s, 3H), 3.06(dd, IH), 1.83(m, IH), 0.91(d, 6H)

Example 143

N-(2,3-Dichlorobenzyl)-N-(2-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyano benzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

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

Example 144

N-(2,3-Dichlorobenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyano benzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

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

Example 145

N-(2,3-Dichlorobenzyl)-N-(3-methoxypropylthiocarbamoyl)-2(S)-{[l-(4-cyano benzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine -H-NMR(CDCb) : δ 6.81-7.67(m, 9H), 5.37(dd, 2H), 5.17(t, IH), 4.52(dd, 2H), 4.04(m, IH), 3.42(m, 2H), 3.32(s, 2H), 3.29(m, 2H), 2.96(dd, IH), 2.88(s, 3H), 1.83(m, IH), 1.75(m, 2H), 0.90(d, 6H)

Example 146

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

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

Example 147

N-(2,3-Dichlorobenzyl)-N-(methylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanobenzyl)- 1

H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

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

Example 148

N-(2,3-Dichlorobenzyl)-N-(4-methylthiophenylthiocarbamoyl)-2(S)-{[l-(4-cya nobenzyl)- 1 H-imidazol-5-yl] acetyl } amino-3 -methylbutylamine

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

Example 149 N-(2,3-Dichlorobenzyl)-N-(2-naphthylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl )- 1 H-imidazol-5-yl] acetyl } amino-3 -methylbutylamine

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

Example 150

N-(2,3-Dichlorobenzyl)-N-(4-nitrophenylthiocarbamoyl)-2(S)-{[l-(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

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

Example 151

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

-H-NMR(CDCb) : δ 6.90-7.66(m, 9H), 5.78(bs, IH), 5.35(dd, 2H),

5.09(t, IH), 4.63(dd, 2H), 4.05(m, IH), 3.32(s, 2H), 3.19-3.74(m, 2H),

3.04(dd, IH), 1.84(m, IH), 1.60(m, IH), 1.16(m, IH), 1.06(m, 2H), 0.91(dd, 6H), 0.81(m, 2H), 0.71(t, 3H)

Example 152

N-(2,3-Dichlorobenzyl)-N-(phenethylthiocarbamoyl)-2(S)-{[l -(4-cyanobenzyl)

- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

-H-NMR(CDCb) : δ 6.68-7.64(m, 14H), 5.60(bs, IH), 5.33(dd, 2H), 5.03(t, IH), 4.44(dd, 2H), 4.00(m, IH), 3.84(m, 2H), 3.3 l(s, 2H), 2.97(dd, IH), 2.80(t, 2H), 1.81(m, IH), 0.89(d, 6H)

Example 153

N-(2,3-Dichlorobenzyl)-N-(phenylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanobenzyl)- 1

H-imidazol-5 -yl]acety 1 } amino-3 -methylbutylamine

-H-NMR(CDCb) : δ 8.32(bs, IH), 6.94-7.58(m, 14H), 5.23(s, IH), 5.20(d, IH), 5.07(t, IH), 4.67(d, IH), 4.10(m, IH), 3.3 l(s, 2H), 3.13(dd, IH), 1.86(m, IH), 0.91(dd, 6H)

Example 154

N-(2,3-Dichlorobenzyl)-N-(n-propylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}amino-3-methylbutylamine

1H-NMR(CDCb) : δ 6.88-7.66(m, 9H), 5.89(bs, IH), 5.35(dd, 2H), 5.04(t, IH), 4.64(dd, 2H), 4.03(m, IH), 3.63(m, IH), 3.47(m, IH), 3.32(s, 2H), 3.01(dd, IH), 1.84(m, IH), 1.51(m, 2H), 0.9 l(m, 6H), 0.79(t, 3H)

Example 155

N-(2,3-Dichlorobenzyl)-N-(3-methylphenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)- 1 H-imidazol-5 -yl]acetyl } amino-3 -methylbutylamine

1H-NMR(CDCb) : δ 7.83(bs, IH), 7.01-7.59(m, 13H), 5.25(s, 2H), 5.14(d, IH), 5.02(t, IH), 4.67(d, IH), 4.10(m, IH), 3.35(s, 2H), 3.10(dd, IH), 2.3 l(s, 3H), 1.87(m, IH), 0.91(dd, 6H)

Example 156

N-(2,3-Dichlorobenzyl)-N-(2-methylphenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine Η-NMR(CDCb) : δ 6.99-7.62(m, 13H), 5.28(s, 2H), 5.13(t, IH), 5.08(d, IH), 4.70(d, IH), 4.13(m, IH), 3.33(s, 2H), 3.13(dd, IH), 2.05(s, 3H), 1.87(m, IH), 0.90(dd, 6H)

Example 157

N-(2,3-Dichlorobenzyl)-N-(4-methylphenylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

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

Example 158

N-(2,3-Dichlorobenzyl)-N-(3-hifluoromethylphenylthiocarbamoyl)-2(S)-{[l-(4

-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3-methylbutylamine

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

Example 159

N-(2,3-Dichlorobenzyl)-N-(2,4-dimethylphenylthiocarbamoyl)-2(S)- {[ 1 -(4-cya nobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

-H-NMR(CDCb) : δ 6.89-7.62(m, 13H), 5.28(s, 2H), 5.1 l(t, IH), 5.06(d, IH), 4.69(d, IH), 4.12(m, IH), 3.34(s, 2H), 3.12(dd, IH), 2.30(s, 3H), 2.0 l(s, 3H), 1.85(m, IH), 0.90(dd, 6H)

Example 160 N-(2,3-Dichlorobenzyl)-N-(3,4-dimethylphenylthiocarbamoyl)-2(S)-{[l-(4-cya nobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

1H-NMR(CDCb) : δ 6.91-7.72(m, 13H), 5.27(s, 2H), 5.1 l(d, IH), 5.06(t, IH), 4.66(d, IH), 4.10(m, IH), 3.35(s, 2H), 3.09(dd, IH), 2.20(s, 6H), 1.86(m, IH), 0.91(dd, 6H)

Example 161

N-(2,3-Dichlorobenzyl)-N-(allylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-lH-i midazol-5-yl]acetyl}amino-4-methylpentylamine

<Step 1>

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

Using the same method as described in Preparative Example 3, N-(t-butoxycarbonyl)-L-leucine was converted to N-(t-butoxycarbonyl)-L- leucine aldehyde. And then the reaction was carried out under the same condition as described in Preparative Example 4, but replacing 1 -(4-nitrobenzyl)- 1 H-imidazol-5 -ylacetic acid HCl with l-(4-cyanobenzyl)- lH-imidazol-5-ylacetic acid HCl to give the title compound.

^'H-NMR (CDCb) : δ 6.99-7.63(m, 9H), 6.17(d, IH), 5.27(s, 2H), 4.08(m, IH), 3.85(s, 2H), 3.35(s, 2H), 2.61(d, 2H), 1.52(m, IH), 1.27(m, 2H), 0.88(d, 6H)

<Step 2>

N-(2,3 -Dichlorobenzy l)-N-(allylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanobenzyl)- IH-i midazol-5-yl]acetyl}amino-4-methylpentylamine

To a solution of N-(2,3-dichlorobenzyl)-2(S)-{[l-(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine in methyene chloride (0.02M, 1ml, 0.02mmol) was added allylisothiocyanate (0.1M in CH₂C1₂, 0.2ml, 0.02mmol). The reaction mixture was agitated for lhr at room temperature. The mixture was purified by silica gel column chromatography(eluent: methylene chloride/methanol=9/l, v/v) to give the title compound as a white solid.

1H-NMR (CDCb) δ : 6.95-7.68(m, 9H), 6.48(bs, IH), 5.82(m, IH), 5.3 l(m, 3H), 5.05(m, 2H), 4.62(m, 2H), 4.26(m, 3H), 3.3 l(s, 2H), 3.01(dd, IH), 1.25-1.53(m, 3H), 0.87(d, 6H)

Examples 162-204

N-(2,3-Dichlorobenzyl)-2(S)-{[l-(4-cyanobenzyl)-lH-imidazol-5-yl] acetyl }amino-4-methylpentylamine was reacted with the corresponding isothiocyanates under the same condition as described in <Step 2> of Example 161 to give the title compounds.

Example 162

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

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

Example 163

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

1H-NMR (CDCb) : δ 6.65-7.72(m, 19H), 5.21(s, 2H), 5.01(d, IH), 4.55(m, 2H), 4.15(m, IH), 3.3 l(s, 2H), 2.94(dd, IH), 1.25- 1.5 l(m, 3H), 0.85(d, 6H)

Example 164

N-(2,3-Dichlorobenzyl)-N-(2-bromophenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } amino-4-methylpentylamine

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

Example 165

N-(2,3-Dichlorobenzyl)-N-(3-bromophenylthiocaιbamoyl)-2(S)-{[l-(4-cyanob enzyl)- lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

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

Example 166

N-(2,3-Dichlorobenzyl)-N-(4-bromophenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

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

Example 167

N-(2,3-Dichlorobenzyl)-N-(n-butylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-l

H-imidazol-5-yl]acetyl}amino-4-methylpentylamine ^'H-NMR (CDCb) : δ 6.84-7.66(m, 9H), 6.24(bs, IH), 5.3 l(q, 2H), 5.02(d, IH), 4.62(m, 2H), 4.16(m, IH), 3.69(m, IH), 3.52(m, IH) 3.32(s, 2H), 2.96(dd, IH), 1.16-1.58(m, 7H), 0.87(m, 9H)

Example 168

N-(2,3-Dichlorobenzyl)-N-(isobutylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-l H-imidazol-5 -yl] acetyl } amino-4-methy lpentylamine

^'H-NMR (CDCb) : δ 6.88-7.67(m, 9H), 6.24(bs, IH), 5.3 l(q, 2H), 5.02(d, IH), 4.69(m, 2H), 4.19(m, IH), 3.55(m, IH), 3.32(m, 3H), 3.01(dd, IH), 1.87(m, IH), 1.27-1.58(m, 3H), 0.83(m, 12H)

Example 169

N-(2,3-Dichlorobenzyl)-N-(2-chlorophenylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

1H-NMR (CDCb) : δ 7.93(bs, IH), 6.63-7.68(m, 13H), 5.22(m, 3H), 4.78(m, 2H), 4.37(m, IH), 3.35(s, 2H), 3.11(dd, IH), 1.25-1.54(m, 3H), 0.9 l(d, 6H)

Example 170

N-(2,3-Dichlorobenzyl)-N-(3-chlorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

1H-NMR (CDCb) : δ 7.93(bs, IH), 6.63-7.68(m, 13H), 5.22(m, 3H), 4.78(m, 2H), 4.37(m, IH), 3.35(s, 2H), 3.11(dd, IH), 1.25-1.54(m, 3H), 0.9 l(d, 6H)

Example 171 N-(2,3-Dichlorobenzyl)-N-(4-chlorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5 -yl] acetyl } amino-4-methylpentylamine

1H-NMR (CDCb) : δ 8.69(bs, IH), 6.72-7.61(m, 13H), 5.48(d, IH), 5.22(s, 2H), 4.76(d, IH), 4.55(m, IH), 4.2 l(m, IH), 3.33(s, 2H), 3.05(dd, IH), 1.25-1.54(m, 3H), 0.88(dd, 6H)

Example 172

N-(2,3-Dichlorobenzyl)-N-(3-chloro-4-methylphenylthiocarbamoyl)-2(S)-{[l-(

4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

1H-NMR (CDCb) : δ 8.69(bs, IH), 6.78-7.61(m, 12H), 5.48(d, IH), 5.26(s, 2H), 4.76(d, IH), 4.55(m, IH), 4.2 l(m, IH), 3.35(s, 2H), 3.05(dd, IH), 2.34(s, 3H), 1.26-1.54(m, 3H), 0.88(dd, 6H

Example 173

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

Η-NMR (CDCb) : δ 6.81-7.67(m, 9H), 5.87(bs, IH), 5.3 l(s, 2H), 5.05(d, IH), 4.62(m, 2H), 4.21(m, 2H), 3.33(s, 2H), 2.96(dd, IH), 1.09-1.97(m, 13H), 0.88(dd, 6H)

Example 174

N-(2,3-DicWorobenzyl)-N-(cyclopentylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzy l)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

^'H-NMR (CDCb) : δ 6.81-7.67(m, 9H), 6.05(bs, IH), 5.31(dd, 2H), 5.11(d, IH), 4.63(m, 3H), 4.15(m, IH), 3.33(s, 2H), 2.96(dd, IH), 1.26-2.05(m, 11H), 0.87(m, 6H) Example 175

N-(2,3-Dichlorobenzyl)-N-(2,4-dichlorophenylthiocarbamoyl)-2(S)-{[l-(4-cya nobenzyl)- 1 H-imidazol-5-yl]acetyl } amino-4-methylpentylamine

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

Example 176

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

1H-NMR (CDCb) : δ 6.87-7.66(m, 9H), 5.32(dd, 2H), 4.56-4.82(m, 3H), 4.29(m, IH), 3.56(m, IH), 3.32(d, 2H), 3.12(dd, IH), 2.77(m, IH), 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)-{[l-( 4-cyanobenzy 1)- 1 H-imidazol-5 -yl] acetyl } amino-4-methylpentylamine

^'H-NMR (CDCb) : δ 7.81(bs, IH), 6.57-7.59(m, 13H), 5.25(m, 3H), 4.77(m, 2H), 4.27(m, IH), 3.33(s, 2H), 3.01(m, 7H), 1.27-1.59(m, 3H), 0.9 l(d, 6H)

Example 178

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

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

Example 179

N-(2,3-Dichlorobenzyl)-N-(3-ethoxypropylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl} amino-4-methylpentylamine

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

Example 180

N-(2,3-Dichlorobenzyl)-N-(ethylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-lH- imidazol-5-yl]acetyl}amino-4-methylpentylamine

1H-NMR (CDCb) : δ 6.88-7.66(m, 9H), 6.39(bs, IH), 5.31(dd, 2H), 5.06(d, IH), 4.58(m, 2H), 4.14(m, IH), 3.68(m, 2H), 3.3 l(s, 2H), 2.96(dd, IH), l. l l-1.54(m, 6H), 0.88(m, 6H)

Example 181

N-(2,3-Dichlorobenzyl)-N-(2-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5 -yl] acetyl } amino-4-methylpentylamine

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

Example 182

N-(2,3-Dichlorobenzyl)-N-(3-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine -H-NMR (CDCb) : δ 8.84(bs, IH), 6.81-7.59(m, 13H), 5.5 l(d, IH), 5.24(s, 2H), 4.75(d, IH), 4.58(m, IH), 4.19(m, IH), 3.34(s, 2H), 3.05(dd, IH), 1.25-1.53(m, 3H), 0.88(m, 6H)

Example 183

N-(2,3-Dichlorobenzyl)-N-(4-fluorophenylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

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

Example 184

N-(2,3-Dichlorobenzyl)-N-(4-hydroxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyano ben2yl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

1H-NMR (CDCb) : δ 6.93-7.66(m, 13H), 5.42(d, 2H), 5.02(dd, 2H), 4.33(m, IH), 3.92(m, IH), 3.46(dd, IH), 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-cyan obenzyl)- 1 H-imidazol-5 -yl]acetyl } amino-4-methy lpentylamine

1H-NMR (CDCb) : δ 8.19(bs, IH), 6.82-7.59(m, 9H), 5.3 l(m, 3H), 4.75(m, 2H), 4.25(m, IH), 3.34(s, 2H), 3.05(dd, IH), 2.89(m, IH), 1.03-1.56(m, 9H), 0.88(d, 6H)

Example 186 N-(2,3-Dichlorobenzyl)-N-(2-methoxyethylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)- lH-imidazol-5-yl]acetyl} amino-4-methylpentylamine

^'H-NMR (CDCb) : δ 6.89-7.66(m, 13H), 6.28(bs, IH), 5.33(dd, 2H), 4.84(m, 2H), 4.39(d, IH), 4.25(m, IH), 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)-{[l-(4-cyano benzyl)-lH-imidazol-5-yl]acexyl}amino-4-methylpentylamine

1H-NMR (CDCb) : δ 8.2 l(d, IH), 6.77-7.64(m, 13H), 5.17(s, 2H), 5.03(m, 2H), 4.73(d, IH), 4.41(m, IH), 3.57(s, 3H), 3.35(s, 2H), 3.12(dd, IH), 1.25-1.61(m, 3H), 0.91(d, 6H)

Example 188

N-(2,3-Dichlorobenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyano benzyl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

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

Example 189

N-(2,3 -Dichlorobenzy l)-N-(3 -methoxypropylthiocarbamoyl)-2(S)- {[ 1 -(4-cyano benzyl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

-H-NMR (CDCb) : δ 6.83-7.66(m, 9H), 5.33(dd, 2H), 4.93(m, IH), 4.59(dd, 2H), 4.24(m, IH), 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)-{[l-(4- cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

Η-NMR (CDCb) : δ 8.81(bs, IH), 6.67-7.94(m, 12H), 5.3 l(m, 3H), 4.69(m, 2H), 4.23(m, IH), 3.87(s, 3H), 3.32(s, 2H), 3.07(dd, IH), 1.25-1.55(m, 3H), 0.87(d, 6H)

Example 191

N-(2,3-Dichlorobenzyl)-N-(methylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-l

H-imidazol-5-yl]acetyl}amino-4-methylpentylamine

1H-NMR (CDCb) : δ 6.93-7.66(m, 9H), 6.71(bs, IH), 5.31(dd, 2H), 5.05(d, IH), 4.58(m, 2H), 4.14(m, IH), 3.3 l(s, 3H), 3.08(d, 2H), 2.93(dd, IH), 1.25-1.58(m, 3H), 0.87(m, 6H)

Example 192

N-(2,3-Dichlorobenzyl)-N-(4-methylthiophenylthiocarbamoyl)-2(S)-{[l-(4-cya nobenzyl)-l H-imidazol-5 -yl] acetyl }amino-4-methy lpentylamine

1H-NMR (CDCb) : δ 8.48(bs, IH), 6.78-7.59(m, 13H), 5.29(m, 3H), 4.7 l(m, 2H), 4.22(m, IH), 3.33(s, 2H), 3.04(dd, IH), 2.45(s, 3H), 1.25-1.55(m, 3H), 0.87(m, 6H)

Example 193

N-(2,3-DicMorobenzyl)-N-(2-naphthylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl

)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

1H-NMR (CDCb) : δ 8.72(bs, IH), 6.78-7.89(m, 16H), 5.3 l(m, 3H), 4.8 l(m, 2H), 4.29(m, IH), 3.36(s, 2H), 3.07(dd, IH), 1.27-1.54(m, 3H), 0.89(d, 6H)

Example 194

N-(2,3 -Dichlorobenzyl)-N-(4-nitrophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanoben zyl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

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

Example 195

N-(2,3-Dichlorobenzyl)-N-(n-pentylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanobenzyl)-

1 H-imidazol-5 -y 1] acetyl } amino-4-methy lpentylamine

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

Example 196

N-(2,3 -Dichlorobenzyl)-N-(phenethylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanobenzyl)

-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

1H-NMR (CDCb) : δ 6.74-7.64(m, 14H), 5.93(bs, IH), 5.29(dd, 2H), 4.69(m, 2H), 4.45(d, IH), 4.17(m, IH), 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)-{[l-(4-cyanobenzyl)-l

H-imidazol-5-yl]acetyl}amino-4-methylpentylamine 1H-NMR (CDCb) : δ 8.38(bs, IH), 6.79-7.57(m, 14H), 5.29(m, 3H), 4.75(m, 2H), 4.26(m, IH), 3.33(s, 2H), 3.05(dd, IH), 1.25-1.55(m, 3H), 0.87(m, 6H)

Example 198

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

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

Example 199

N-(2,3-Dichlorobenzyl)-N-(3-methylphenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

1H-NMR (CDCb) : δ 8.19(bs, IH), 6.76-7.57(m, 13H), 5.29(m, 3H), 4.71(m, 2H), 4.27(m, IH), 3.34(s, 2H), 3.05(dd, IH), 2.3 l(m, 3H), 1.25-1.55(m, 3H), 0.9 l(d, 6H)

Example 200

N-(2,3-Dichlorobenzyl)-N-(2-methylphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanob enzyl)- lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

1H-NMR (CDCb) : δ 7.78(bs, IH), 6.78-7.61(m, 13H), 5.29(m, 3H), 4.81(m, 2H), 4.29(m, IH), 3.33(s, 2H), 3.09(dd, IH), 2.09(s, 3H), 1.25-1.53(m, 3H), 0.9 l(d, 6H)

Example 201 3

N-(2,3-Dichlorobenzyl)-N-(4-methylphenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)- lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

^'H-NMR (CDCb) : δ 8.21(bs, IH), 6.81-7.61(m, 13H), 5.3 l(m, 3H), 4.75(m, 2H), 4.26(m, IH), 3.34(s, 2H), 3.06(dd, IH), 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)-{[l-(4 -cyanobenzyl)- 1 H-imidazol-5-yl]acetyl } amino-4-methylpentylamine

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

Example 203

N-(2,3-Dichlorobenzyl)-N-(2,4-dimethylphenylthiocarbamoyl)-2(S)-{[l-(4-cya nobenzyl)- lH-imidazol-5-yl]acetyl} amino-4-methylpentylamine

¹ H-NMR (CDCb) : δ 6.81-7.6 l(m, 12H), 5.25(m, 3H), 4.79(m, 2H), 4.3 l(m, IH), 3.34(s, 2H), 3.08(dd, IH), 2.3 l(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-cya nobenzyl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

1H-NMR (CDCb) : δ 8.01(bs, IH), 6.79-7.61(m, 12H), 5.29(m, 3H), 4.76(m, 2H), 4.28(m, IH), 3.36(s, 2H), 3.06(dd, IH), 2.23(m, 6H), 1.27-1.53(m, 3H), 0.9 l(d, 6H) Example 205

N-(2,3-Dichlorobenzyl)-N-(allylthiocarbamoyl)-2-{[l-(4-cyanobenzyl)-lH-imi dazol-5-yl]acetyl}amino-2-methylpropylamine

<Step 1>

N-(2,3-Dichlorobenzyl)-2-{[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino -2 -methylpropy lamine

Using the same method as described in Preparative Example 3, 2-(t-butoxycarbonyl)amino-2-methylpropionic acid was converted to 2-(t-butoxycarbonyl)amino-2-methylpropion aldehyde. And then the reaction was carried out under the same condition as described in Preparative Example 4, but replacing l-(4-nitrobenzyl)-lH-imidazol-5- ylacetic acid HCl with 1 -(4-cyanobenzyl)- lH-imidazol-5-ylacetic acid HCl to give the title compound.

-H-NMR(CDCb) : δ 7.61(d, 2H), 7.53(s, IH), 7.22(d, 2H), 7.16(d, 2H), 7.01(s, IH), 6.43(bs, IH), 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-{[l-(4-cyanobenzyl)-lH-imi dazol-5-yl]acetyl}amino-2-methylpropylamine

To a solution of N-(2,3-dichlorobenzyl)-2-{[l-(4-cyanobenzyl)-lH- imidazol-5-yl]acetyl}amino-2-methylpropylamine in methyene chloride (0.02M, 1ml, 0.02mmol) was added allylisothiocyanate (0.1M in CH₂C1₂, 0.2ml, 0.02mmol). The reaction mixture was agitated for lhr at room temperature. The mixture was purified by silica gel column chromatography(eluent: methylene chloride/methanol=9/l, v/v) to give the title compound as a white solid.

-H-NMR(CDCb) : δ 8.20(bs, IH), 7.65(d, 2H), 7.45(m, 2H), 7.20(m, 3H), 7.00(s, IH), 6.95(d, IH), 6.40(bs, IH), 5.80(m, IH), 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)

Examples 206-251

N-(2,3-Dichlorobenzyl)-2-{[l-(4-cyanobenzyl)-lH-imidazol-5-yl] acetyl }amino-2-methylpropylamine was reacted with the corresponding isothiocyanates under the same condition as described in <Step 2> of Example 205 to give the title compounds.

Example 206

N-(2,3 -Dichlorobenzyl)-N-(benzylthiocarbamoyl)-2- {[ 1 -(4-cyanobenzyl)- IH-i midazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : 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 -Dichlorobenzy l)-N-(2 -biphenylthiocarbamoyl)-2- {[ 1 -(4-cyanobenzyl)- 1

H-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : δ 7.60(d, 3H), 7.38(m, 4H), 7.30(s, 7H), 7.10(d, 3H), 6.95(s, IH), 6.70(d, IH), 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-{[l-(4-cyanobenz yl)- 1 H-imidazol-5 -yl] acetyl } amino-2-methylpropylamine

Η-NMR(CDCb) : δ 7.60(m, 4H), 7.45(m, 2H), 7.30(m, 3H), 7.15(m, 4H), 6.95(s, IH), 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-{[l-(4-cyanobenz yl)- 1 H-imidazol-5 -yl] acetyl } amino-2-methylpropylamine

-H-NMR(CDCb) : δ 7.60(d, 2H), 7.45(m, 4H), 7.25(m, 3H), 7.10(d, 3H), 6.95(s, IH), 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-cyanobenz yl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDC1₃) : δ 7.60(d, 2H), 7.43(m, 4H), 7.22(m, 4H), 7.08(d, 3H), 6.95(s, IH), 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-{[l-(4-cyanobenzyl)-lH-i midazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : δ 7.65(d, 2H), 7.45(m, 2H), 7.20(m, 3H), 7.00(s, IH), 6.90(d, IH), 6.06bs, IH), 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, 2H), 0.86(t, 3H)

Example 212

N-(2,3 -Dichlorobenzyl)-N-(isobutylthiocarbamoyl)-2- {[ 1 -(4-cyanobenzyl)- 1H- imidazol-5 -yl] acetyl } am ino-2-methylpropylamine

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

Example 213

N-(2,3 -Dichlorobenzyl)-N-(t-butylthiocarbamoyl)-2- {[ 1 -(4-cyanobenzyl)- IH-i midazol-5-yl]acetyl}amino-2-methylpropylamine

^'H-NMR(CDCb) : δ 7.65(d, 2H), 7.48(m, 2H), 7.20(m, 3H), 7.00(s, IH), 6.95(d, IH), 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-{[l-(4-cyanobenz y 1)- 1 H-imidazol-5 -yl] acetyl } amino-2 -methylpropy lamine

-H-NMR(CDCb) : δ 7.60(d, 3H), 7.20-7.50(m, 7H), 7.12(d, 3H), 6.97(s, IH), 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- { [ l-(4-cyanobenz yl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine -H-NMR(CDCb) : δ 7.60(d, 2H), 7.43(d, 2H), 7.28(m. 5H), 7.10(d, 3H), 6.95(s, IH), 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-cyanobenz yl)- lH-imidazol-5 -yl] acetyl } amino-2-methylpropylamine

1H-NMR(CDCb) : δ 7.60(d, 2H), 7.45(s, 2H), 7.28(s, 5H), 7.08(d, 3H), 6.95(s, IH), 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 -Dichlorobenzy l)-N-(3-chloro-4-methylphenylthiocarbamoyl)-2- { [ 1 -(4-c y anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-2-methylpropylamine

-H-NMR(CDCb) : δ 7.60(d, 2H), 7.45(m, 2H), 7.23(m, 2H), 7.20(s, 2H), 7.10(d, 2H), 6.95(s, IH), 6.40(bs, IH), 5.80(m, IH), 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 -Dichlorobenzy l)-N-(cy clohexy lthiocarbamoy l)-2-{ [ 1 -(4-cyanobenzyl)- 1

H-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : δ 7.65(d, 2H), 7.53(s, IH), 7.45(d, IH), 7.20(t, 3H), 7.00(s, IH), 6.95(d, IH), 5.70(bs, IH), 5.40(s, 2H), 4.90(s, 2H), 4.20(m, IH), 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 -DicWorobenzyl)-N-(cyclopentylthiocarbamoyl)-2- { [ 1 -(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : δ 7.65(d, 2H), 7.52(s, IH), 7.45(d, IH), 7.20(t, 3H), 7.00(s, IH), 6.95(d, IH), 5.90(bs, IH), 5.38(s, 2H), 4.92(s, 2H), 4.62(q, IH), 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-cyanob enzyl)- 1 H-imidazol-5-yl] acetyl } amino-2-methylpropylamine

1H-NMR(CDCb) : δ 7.60(d, 2H), 7.45(t, 2H), 7.40(m, 2H), 7.24(m, 2H), 7.10(d, 3H), 6.95(s, IH), 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-{[l-(4-cy anobenzyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : δ 7.65(d, 2H), 7.5 l(s, IH), 7.45(d, IH), 7.20(d, 3H), 7.00(s, IH), 6.90(d, IH), 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, 6H)

Example 222

N-(2,3-DicMorobenzyl)-N-[4-(dimethylamino)phenylthiocarbamoyl]-2-{[l-(4- cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : δ 7.58(d, 2H), 7.45(m, 2H), 7.27(m, IH), 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-{[l-(4-cya nobenzyl)- 1 H-imidazol-5 -yl]acetyl } amino-2-methylpropylamine

-H-NMR(CDCb) : 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-{[l-(4-cyanobenz yl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : δ 7.65(d, 2H), 7.45(m, 2H), 7.20(t, 3H), 7.00(s, IH), 6.95(s, IH), 6.80(d, IH), 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)- 1 H-imi dazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : δ 7.65(d, 2H), 7.45(m, 2H), 7.20(t, 3H), 7.00(s, IH), 6.95(d, IH), 6.20(bs, IH), 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-Dic orobenzyl)-N-(2-fluorophenylthiocarbamoyl)-2-{[l-(4-cyanobenz y 1)- 1 H-imidazol-5 -yl] acetyl } amino-2 -methylpropylamine

1H-NMR(CDCb) : δ 7.60(d, 2H), 7.40(m, 3H), 7.27(m, 2H), 7.20(m, 5H), 6.95(s, IH), 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-{[l-(4-cyanobenz yl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : 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-{[l-(4-cyanobenz y 1)- 1 H-imidazol-5 -yl] acetyl } amino-2 -methylpropy lamine

-H-NMR(CDCb) : δ 7.60(d, 2H), 7.45(m, 2H), 7.22(m, 3H), 7.10(d, 3H), 7.00(s, IH), 6.95(s, IH), 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-DicWorobenzyl)-N-(4-hyα^oxyphenylthiocarbamoyl)-2-{[l-(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : 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-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5 -yl]acetyl } amino-2-methylpropylamine -H-NMR(CDCb) : <5 7.60(d, 2H), 7.45(s, 2H), 7.25(s, 2H), 7.20(s, 3H), 7.10(d, 3H), 6.95(s, IH), 5.30(s, 2H), 5.10(s, 2H), 4.05(s, 2H), 3.25(s, 2H), 2.90(q, IH), 1.45(s, 6H), 1.12(d, 6H)

Example 231

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

-H-NMR(CDCb) : δ 7.65(d, 2H), 7.45(m, 2H), 7.20(t, 3H), 7.00(s, IH), 6.95(d, IH), 6.25(bs, IH), 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-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5 -yl] acetyl} amino-2-methylpropylamine

1H-NMR(CDCb) : δ 8.10(d, IH), 7.65(s, IH), 7.60(d, 2H), 7.48(s, 2H), 7.25(t, IH), 7.12(d, 3H), 7.00(t, 3H), 6.90(d, IH), 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-{[l-(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : δ 7.60(d, 2H), 7.45(s, 2H), 7.27(m, IH), 7.10(m, 5H), 7.00(s, IH), 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-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5-yl] acetyl } amino-2-methylpropylamine

-H-NMR(CDCb) : δ 7.65(d, 2H), 7.45(m, 2H), 7.20(t, 3H), 7.00(s, 2H), 6.90(d, IH), 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-{[l-(4-cya nobenzyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDC1₃) : δ 7.90(s, IH), 7.60(d, 3H), 7.40(m, 2H), 7.25(t, IH), 7.10(d, 3H), 6.90(s, IH), 6.80(d, IH), 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-{[l-(4-cyanobenzyl)-lH-i midazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : δ 7.65(d, 2H), 7.45(s, 2H), 7.20(t, 3H), 7.00(s, IH), 6.90(d, IH), 6.55(bs, IH), 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-{[l-(4-cyano b enzyl)- 1 H-imidazol-5 -yl] acetyl } amino-2-methylpropylamine

-H-NMR(CDCb) : δ 7.60(d, 2H), 7.45(s, 2H), 7.28(s, IH), 7.20(s, 4H), 7.10(d, 2H), 6.95(s IH), 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 -Dichlorobenzy l)-N-(2-naphthylthiocarbamoyl)-2- { [ 1 -(4-cyanobenzyl)- 1

H-imidazol-5-yl]acetyl}amino-2-methylpropylamine

Η-NMR(CDCb) : δ 7.60-7.85(m, 4H), 7.45(m, 7H), 7.30(t, 2H), 7.15(d, IH), 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-nitiOphenylthiocarbamoyl)-2-{[l-(4-cyanobenzyl

)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : δ 8.18(d, 2H), 7.73(d, 2H), 7.47(t, 3H), 7.42(d, IH), 7.25(m, IH), 7.10(d, 3H), 6.00(s, IH), 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 -Dichlorobenzy l)-N-(n-pentylthiocarbamoyl)-2- {[ 1 -(4-cyanobenzyl)- 1 H- imidazol-5 -yl] acetyl } amino-2-methy lpropylamine

-H-NMR(CDCb) : δ 7.65(d, 2H), 7.45(m, 2H), 7.20(t, 3H), 7.00(s, IH), 6.95(d, IH), 5.95(bs, IH), 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-(phenethylthiocarbamoyl)-2-{[l-(4-cyanobenzyl)-l

H-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : δ 7.65(d, 2H), 7.45(m, 2H), 7.18(d, 6H), 7.00(s, IH), 6.95(m, 2H), 6.72(d, IH), 5.80(bs, IH), 5.40(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)- 1 H-i midazol-5-yl]acetyl}amino-2-methylpropylamine

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

Example 243

N-(2,3-DicWorobenzyl)-N-(n-propylthiocarbamoyl)-2-{[l-(4-cyanobenzyl)-lH

-imidazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : δ 7.65(d, 2H), 7.45(m, 2H), 7.20(t, 3H), 7.00(s, IH), 6.95(d, IH), 6.10(bs, IH), 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 -Dichlorobenzy l)-N-(3 -methylphenylthiocarbamoyl)-2- { [ 1 -(4-cyanobenz yl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

¹H-NMR(CDCb) : δ 7.60(d, 2H), 7.45(d, 2H), 7.25(m, 3H), 7.08(d, 5H), 6.97(s, IH), 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-cyanobenz yl)- 1 H-imidazol-5 -yl]acetyl } amino-2-methylpropylamine -H-NMR(CDCb) : δ 7.60(d, 2H), 7.45(m, 2H), 7.25(m, 4H), 7.10(t, 4H), 6.95(s, IH), 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-{[l-(4-cyanobenz yl)- lH-imidazol-5-yl]acetyl} amino-2-methylpropylamine

¹H-NMR(CDCb) : δ 7.57(d, 2H), 7.45(s, 2H), 7.26(t, 2H), 7.12(m, 6H), 6.95(s, IH), 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-{[l-(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-2-methylpropylamine

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

Example 248

N-(2,3 -Dichlorobenzy l)-N-(2,4-dimethylphenylthiocarbamoyl)-2- { [ 1 -(4-cy ano benzyl)- 1 H-imidazol-5 -yl] acetyl } amino-2-methylpropylamine

-H-NMR(CDCb) : δ 7.60(d, 2H), 7.45(m, 2H), 7.24(d, IH), 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 -Dichlorobenzy l)-N-(3 ,4-dimethylphenylthiocarbamoyl)-2- {[ 1 -(4-cyano benzyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : δ 7.57(d, 2H), 7.45(s, 2H), 7.25(m, IH), 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 -Dichlorobenzy l)-N-(3 -dimethylaminopropylthiocarbamoyl)-2- {[ 1 -(4-cy anobenzyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : r5 9.20(bs, IH), 7.56(d, 2H), 7.42-7.48(m, 2H), 7.16-7.23(m, 3H), 7.00(s, 3H), 6.90(d, 2H), 5.40(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, 6H)

Example 251

N-(2,3-DicUorobenzyl)-N-(ethoxycarbonylthiocarbamoyl)-2-{[l-(4-cyanobenz yl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : δ 7.50-7.75(m, 5H), 7.43-7.46(m, IH), 7.18-7.25(m, 2H), 7.00(s, IH), 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)- IH-i midazol-5 -yl] acetyl } aminobutylamine

<Step 1>

N-(2,3-Dichlorobenzyl)-2(S)-{[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}am inobutylamine The title compound was prepared by using the same procedure as Preparative Example 4, but replacing N-t-butoxycarbonyl-L-isoleucine aldehyde and 1 -(4-nitrobenzyl)- 1 H-imidazol-5 -ylacetic acid HCl with L-2- (t-butoxycarbonyl)aminobutyraldehyde and l-(4-cyanobenzyl)-lH-imidazol- 5 -ylacetic acid, respectively.

-H-NMR(CDCb) δ 7.61(d, 2H), 7.52(s, IH), 7.38(dd, 2H), 7.11-7.21(m, 4H), 7.0 l(s, IH), 6.08(d, IH), 5.26(s, 2H), 3.83-3.92(m, 3H), 3.35(s, 2H), 2.62(d, 2H), 1.33-1.5 l(m,2H), 0.84(t, 3H)

<Step 2>

N-(2,3-Dichlorobenzyl)-N-(allylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-lH-i midazol-5 -yl] acetyl } aminobutylamine

To a solution of N-(2,3-dichlorobenzyl)-2(S)-{[l-(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}aminobutylamine in methyene chloride (0.02M, lml, 0.02mmol) was added allylisothiocyanate (0.1M in CH2CI2, 0.2ml, 0.02mmol). The reaction mixture was agitated for lhr at room temperature. The mixture was purified by silica gel column chromatography(eluent: methylene chloride/methanol=9/l, v/v) to give the title compound as a white solid.

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

Examples 253-297 N-(2,3-Dichlorobenzyl)-2(S)-{ [ 1 -(4-cyanobenzyl)- 1 H-imidazol-5 -yl] acetyl }aminobutylamine was reacted with the corresponding isothiocyanates under the same condition as described in <Step 2> of Example 252 to give the title compounds.

Example 253

N-(2,3-Dichlorobenzyl)-N-(benzylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-l

H-imidazol-5-yl]acetyl}aminobutylamine

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

Example 254

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

1H-NMR(CDCb) : δ 7.68(d, IH), 7.58(d, 2H), 7.41(1, IH), 7.30(m, 8H), 7.12(d, 2H), 7.01(s, IH), 6.98(s, 2H), 6.69(d, IH), 5.21(s, 2H), 5.12(bs, IH), 4.5 l(d, 2H), 3.90(bs, IH), 3.32(s, 2H), 2.95(dd, IH), 1.60(m, IH), 1.40(m, IH), 0.85(t, 3H)

Example 255

N-(2,3-Dichlorobenzyl)-N-(2-bromophenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)- lH-imidazol-5 -yl] acetyl } aminobutylamine

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

Example 256

N-(2,3-Dichlorobenzyl)-N-(3-biOmophenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

Η-NMR (CDCb) : δ : 9.00(bs, IH), 7.60(d, 2H), 7.50(m, IH), 7.41(m, 3H), 7.30(m, IH), 7.20(d, 2H), 7.10(m, 3H), 6.96(s, 2H), 5.63(d, IH), 5.23(s, 2H), 4.68(d, IH), 4.52(m, IH), 4.0 l(m, IH), 3.38(s, 2H), 3.05(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90(t, 3H)

Example 257

N-(2,3-Dichlorobenzyl)-N-(4-bromophenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}aminobutylamine

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

Example 258

N-(2,3-Dichlorobenzyl)-N-(n-butylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-l H-imidazol-5 -yl] acetyl } aminobutylamine

-H-NMR(CDCb) : δ 7.65(d, 2H), 7.50(s, IH), 7.41(d, IH), 7.18(m, 4H), 7.00(s, IH), 6.95(s, IH), 6.22(bs, IH), 5.33(q, 2H), 5.07(d, IH), 4.75(m, IH), 4.58(d, IH), 4.01(m, IH), 3.60(m, 2H), 3.32(s, 2H), 3.00(dd, IH), 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)- 1 H-imidazol-5-yl]acetyl } aminobutylamine

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

Example 260

N-(2,3-Dichlorobenzyl)-N-(t-butylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-l

H-imidazol-5-yl]acetyl}aminobutylamine

1H-NMR(CDCb) : δ 7.65(d, 2H), 7.52(s, IH), 7.41(t, 2H), 7.18(m, 3H), 7.05(s, IH), 6.90(d, 2H), 5.38(q, 2H), 5.07(m, IH), 4.65(q, 2H), 4.0 l(m, IH), 3.32(s, 2H), 3.00(dd, IH), 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-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}aminobutylamine

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

Example 262

N-(2,3-DicMorobenzyl)-N-(3-chlorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}aminobutylamine

-H-NMR(CDCb) : r5 8.95(bs, IH), 7.60(d, 2H), 7.40(m, 4H), 7.25(m, 3H), 7.15(m, 3H), 6.95(m, 2H),5.60(d, IH), 5.25(s, 2H), 4.68(d, IH), 4.50(m, IH), 4.01(m, IH), 3.39(s, 2H), 3.05(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90(t, 3H)

Example 263

N-(2,3 -DicWorobenzyl)-N-(4-chlorophenylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanobe nzyl)- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

1H-NMR (CDCb) : δ 8.70(bs, IH), 7.60(d, 2H), 7.45(m, 2H), 7.30(s, 4H), 7.10(m, 3H), 7.95(m, IH), 6.85(d, IH), 5.55(d, IH), 5.23(s, 2H), 4.70(d, IH), 4.55(m, IH), 4.0 l(m, IH), 3.37(s, 2H), 3.05(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90(t, 3H)

Example 264

N-(2,3-Dichlorobenzyl)-N-(3-chloro-4-methylphenyl)thiocarbamoyl-2(S)-{[l-(

4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}aminobutylamine

1H-NMR(CDCb) : δ 8.80(bs, IH), 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, IH), 5.25(s, 2H), 4.68(d, IH), 4.59(m, IH), 4.01(m, IH), 3.38(s, 2H), 3.04(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.92(t, 3H)

Example 265

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

-H-NMR(CDC1₃) : δ 7.65(d, 2H), 7.53(s, IH), 7.41(d, IH), 7.18(m, 4H), 7.02(d, IH), 6.92(d, 2H), 5.85(bs, IH), 5.33(q, 2H), 5.05(m, IH), 4.80(m, IH), 4.60(d, IH), 4.30(m, IH), 4.00(m, IH), 3.36(s, 2H), 3.00(dd, IH), 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)-{[l -(4-cyanobenzy 1)- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

-H-NMR(CDCb) : δ 7.65(d, 2H), 7.55(s, IH), 7.41(d, IH), 7.18(d, 3H), 7.08(d, IH), 7.05(m, IH), 6.95(d, IH), 6.05(s, IH), 5.35(q, 2H), 5.07(d, IH), 4.70(h, IH), 4.58(d, IH), 4.00(m, IH), 3.36(s, 2H), 3.00(dd, IH), 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)-{[l-(4-cya nobenzyl)- 1 H-imidazol-5-yl] acetyl } aminobutylamine

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

Example 268

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

-H-NMR(CDCb) : δ 7.65(d, 2H), 7.50(s, IH), 7.35(m, 2H), 7.20(d, 2H), 7.05(s, IH), 6.90(d, 2H), 5.38(q, 2H), 4.90(m, 2H), 4.60(d, IH), 4.10(m, IH), 3.55(m, 2H), 3.35(s, 2H), 3.12(dd, IH), 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)-{[l-( 4-cyanobenzyl)- 1 H-imidazol-5 -yl]acetyl } aminobutylamine -H-NMR(CDCb) : δ 7.90(bs, IH), 7.60(d, 2H), 7.45(m, 2H), 7.20(m, IH), 7.10(m, 4H), 7.00(d, 2H), 6.62(d, 2H), 5.28(s, 2H), 5.20(d, IH), 4.90(m, IH), 4.70(d, IH), 4.10(m, IH), 3.38(s, 2H), 3.08(dd, IH), 2.95(s, 6H), 1.55(m, 2H), 0.90(t, 3H)

Example 270

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

-H-NMR(CDCb) : δ 8.95(bs, IH), 7.65(d, 3H), 7.50(s, IH), 7.4 l(d, IH), 7.18(d, 3H), 7.03(s, IH), 6.90(d, IH), 6.42(bs, IH), 5.40(q, 2H), 5.04(m, IH), 4.58(s, 2H), 4.03(m, IH), 3.64(m, 2H), 3.32(q, 2H), 2.96(dd, IH), 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)-{[l-(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

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

Example 272

N-(2,3-Dichlorobenzyl)-N-(3-ethoxypropylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}aminobutylamine

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

Example 273

N-(2,3-Dichlorobenzyl)-N-(ethylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-lH- imidazol-5-yl]acetyl}aminobutylamine

-H-NMR(CDCb) : r5 7.65(d, 2H), 7.50(s, IH), 7.41(d, IH), 7.18(m, 4H), 6.96(m, 2H), 6.40(bs, IH), 5.35(q, 2H), 5.10(d, IH), 4.70(m, IH), 4.55(d, IH), 4.00(m, IH), 3.62(h, 2H), 3.35(s, 2H), 2.98(dd, IH), 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-cyanobe nzyl)- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

1H-NMR(CDCb) : δ 8.18(bs, IH), 7.60(d, 2H), 7.40(m, 3H), 7.22(m, 2H), 7.10(m, 3H), 7.00(s, IH), 5.38(m, IH), 5.24(s, 2H), 4.82(m, IH), 4.71(d, IH), 4.12(m, IH), 3.38(s, 2H), 3.10(dd, IH), 1.55(m, 2H), 0.90(t, 3H)

Example 275

N-(2,3-Dichlorobenzyl)-N-(3-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5-yl] acetyl } aminobutylamine

-H-NMR(CDCb) : δ 8.88(s, IH), 7.60(d, 2H), 7.45(m, 2H), 7.02-7.50(m, 7H), 6.92(m, 3H), 5.60(d, IH), 5.28(q, 2H), 4.70(d, IH), 4.58(m, IH), 4.03(m, IH), 3.40(s, 2H), 3.06(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90(t, 3H) Example 276

N-(2,3-Dichlorobenzyl)-N-(4-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

^'H-NMR(CDCb) : δ 8.58(s, IH), 7.60(d, 2H), 7.45(m, 2H), 7.25(m, 3H), 7.10(m, 4H), 6.98(m, 3H), 5.50(d, IH), 5.25(q, 2H), 4.70(d, IH), 4.60(m, IH), 4.04(m, IH), 3.36(s, 2H), 3.10(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90(t, IH)

Example 277

N-(2,3-Dichlorobenzyl)-N-(4-hydroxyphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyano benzyl)-lH-imidazol-5-yl]acetyl}aminobutylamine

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

Example 278

N-(2,3-Dichlorobenzyl)-N-(4-isopropylphenylthiocarbamoyl)-2(S)-{[l-(4-cyan obenzyl)- 1 H-imidazol-5 -yl]acetyl } aminobutylamine

Η-NMR (CDCb) : δ 8.18(s, IH), 7.60(d, 2H), 7.45(m, 2H), 7.20(m, 5H), 7.10(m, 3H), 7.00(s, 2H), 5.40(d, IH), 5.25(s, 2H), 4.80(m, IH), 4.68(d, IH), 4.08(m, IH), 3.38(s, 2H), 3.08(dd, IH), 2.90(p, IH), 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-cyanob enzyl)- lH-imidazol-5-yfJacetyl} aminobutylamine -H-NMR(CDCb) : δ 7.65(d, 2H), 7.52(s, IH), 7.41(d, IH), 7.18(m, 4H), 7.00(s, IH), 6.92(d, IH), 6.25(bs, IH), 5.35(q, 2H), 4.90(m, 2H), 4.60(d, IH), 4.10(m, IH), 3.78(m, 2H), 3.43(m, 2H), 3.33(s, 2H), 3.20(s, 3H), 3.10(dd, IH), 1.55(m, 2H), 0.90(t, 3H)

Example 280

N-(2,3-Dichlorobenzyl)-N-(2-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyano benzyl)- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

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

Example 281

N-(2,3-Dichlorobenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyano benzyl)- lH-imidazol-5-yl]acetyl}aminobutylamine

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

Example 282

N-(2,3-Dichlorobenzyl)-N-(3-methoxypropylthiocarbamoyl)-2(S)-{[l-(4-cyano benzyl)- 1 H-imidazol-5 -yl] acetyl} aminobutylamine

1H-NMR(CDCb) : δ 7.65(d, 2H), 7.5 l(s, IH), 7.40(d, 2H), 7.20(m, 3H), 7.00(s, IH), 6.92(s, IH), 6.85(d, IH), 5.38(q, 2H), 5.00(t, IH), 4.60(q, 2H), 4.10(m, IH), 3.70(m, 2H), 3.40(m, IH), 3.32(s, 2H), 3.00(dd, IH), 2.92(s, 3H), 1.75(q, 2H), 1.55(m, 2H), 0.90(t, 3H)

Example 283

N-(2,3-Dichlorobenzyl)-N-(2-methoxypridin-5-ylthiocarbamoyl)-2(S)-{[l-(4-c yanobenzyl)-lH-imidazol-5-yl]acetyl}aminobutylamine

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

Example 284

N-(2,3 -Dichlorobenzyl)-N-(methylthiocarbamoyl)-2(S )-{[ 1 -(4-cyanobenzyl)- 1

H-imidazol-5 -yl] acetyl } aminobutylamine

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

Example 285

N-(2,3 -Dichlorobenzyl)-N-(4-methylthiophenylthiocarbamoyl)-2(S)- {[ 1 -(4-cya nobenzyl)- 1 H-imidazol-5-yl] acetyl } aminobutylamine

1H-NMR(CDCb) : δ 8.50(s, IH), 7.60(d, 2H), 7.43(m, 2H), 7.2 l(m, 4H), 7.10(m, 3H), 6.98(s, 2H), 5.45(d, IH), 5.2(s, 2H), 4.70(d, 2H), 4.05(m, IH), 3.38(s, 2H), 3.07(dd, IH), 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

)-l H-imidazol-5 -yl] acetyl} aminobutylamine

-H-NMR(CDCb) : δ 8.78(s, IH), 7.60-7.85(m, 4H), 7.35-7.55(m, 7H), 7.20(m, 2H), 6.97(m, 4H), 5.5 l(d, IH), 5.20(q, 2H), 4.72(d, 2H), 4.10(m, IH), 3.39(s, 2H), 3.10(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90(t, 3H)

Example 287

N-(2,3-Dichlorobenzyl)-N-(4-nitrophenylthiocarbamoyl)-2(S)-{[l-(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

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

Example 288

N-(2,3-Dichlorobenzyl)-N-(n-pentylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}aminobutylamine

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

Example 289

N-(2,3 -Dichlorobenzyl)-N-(phenethylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanobenzyl)

- 1 H-imidazol-5 -y 1] acetyl } aminobutylamine -H-NMR(CDCb) : δ 7.65(d, 2H), 7.48(s, IH), 7.39(d, IH), 7.18(m, 6H), 7.00(m, 4H), 6.95(d, IH), 5.97(bs, IH), 5.3 l(q, 2H), 4.78(m, 2H), 4.45(d, IH), 3.98(m, IH), 3.78(m, 2H), 3.32(s, 2H), 3.00(dd, IH), 2.85(t, 2H), 1.55(m, 2H), 0.90(t, 3H)

Example 290

N-(2,3-Dichlorobenzyl)-N-(phenylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-l

H-imidazol-5-yl]acetyl}aminobutylamine

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

Example 291

N-(2,3 -Dichlorobenzyl)-N-(n-propylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanobenzyl)-

1 H-imidazol-5 -y 1] acetyl } aminobutylamine

^'H-NMR(CDCb) : δ 7.65(d, 2H), 7.50(s, IH), 7.41(d, IH), 7.18(m, 4H),

6.97(m, 2H), 6.32(bs, IH), 5.33(q, 2H), 5.008(d, IH), 4.75(m, IH),

4.59(d, IH), 4.01(m, IH), 3.59(m, 2H), 3.38(s, 2H), 3.00(dd, IH), 1.57(m, 4H), 0.90(p, 6H)

Example 292

N-(2,3-Dichlorobenzyl)-N-(3-methylphenylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}aminobutylamine

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

Example 293

N-(2,3-Dichlorobenzyl)-N-(2-methylphenylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

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

Example 294

N-(2,3-Dichlorobenzyl)-N-(4-methylphenylthiocarbamoyl-2(S)-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5-yl] acetyl } aminobutylamine

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

Example 295

N-(2,3-Dichlorobenzyl)-N-(3-tτifluoromethylphenylthiocarbamoyl)-2(S)- { [ 1 -(4 -cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

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

Example 296 N-(2,3-Dichlorobenzyl)-N-(2,4-dimethylphenylthiocarbamoyl)-2(S)-{[l-(4-cya nobenzyl)- 1 H-imidazol-5-yl] acetyl } aminobutylamine

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

Example 297

N-(2,3-DichloiObenzyl)-N-(3,4-dimethylphenylthiocarbamoyl)-2(S)-{[l-(4-cya nobenzyl)- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

^-NMR CDCb) : δ 8.10(s, IH), 7.58(d, 2H), 7.45(m, 2H), 7.4 l(d, IH), 7.18(m, 5H), 7.00(s, 4H), 5.27(m, 3H), 4.72(m, 2H), 4.10(m, IH), 3.39(s, 2H), 3.06(dd, IH), 2.25(s, 6H), 1.60(m, 2H), 0.90(t, 3H)

Example 298

N-(2,3-Dichlorobenzyl)-N-(allylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-lH-i midazol-5-yl] acetyl } amino-3 -(4-benzyloxy)phenylpropylamine

<Step 1>

N-(2,3-Dichlorobenzyl)-2(S)-{ [ 1 -(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}am ino-3 -(4-benzyloxy)phenylpropylamine

Using the same method as described in Preparative Example 3, N-boc-O-benzyl-L-tyrosine was converted to N-boc-O-benzyl-L-tyrosine aldehyde. And then the reaction was carried out under the same condition as described in Preparative Example 4, but replacing 1 -(4-nitrobenzyl)- 1 H-imidazol-5 -ylacetic acid HCl with 1 -(4-cyanobenzy 1)- 1 H-imidazol-5 -ylacetic acid HCl to give the title compound. -H-NMR(CDCb) : δ 7.57(d, IH), 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, IH), 5.04(s, 2H), 4.87(d, IH), 4.16-4.23(m, IH), 3.82(d, 2H), 3.27(t, 2H), 2.57-2.73(m, 4H)

<Step 2>

N-(2,3-Dichlorobenzyl)-N-(allylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-lH-i midazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

To a solution of N-(2,3-Dichlorobenzyl)-2(S)-{[l-(4-cyano benzyl)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine in methyene chloride (0.02M, 1ml, 0.02mmol) was added allylisothiocyanate (0.1M in CH2CI2, 0.2ml, 0.02mmol). The reaction mixture was agitated for lhr at room temperature. The mixture was purified by silica gel column chromatography(eluent: methylene chloride/methanol=9/l, v/v) to give the title compound as a white solid.

^'H-NMR(CDCb) : δ 7.60(d, 2H), 7.25-7.45(m, 7H), 7.17(t, 2H),

6.85-7.05(m, 7H), 6.75(d, IH), 6.40(s, IH), 5.85(m, IH), 5.15(s, 2H),

5.05(s, 3H), 4.52-4.85(m, 4H), 4.25(t, 3H), 3.50(t, IH), 3.35(m, IH), 3.10(m, IH), 2.85(m, IH), 2.65(m, IH)

Examples 299-343

N-(2, 3 -Dichlorobenzyl)-2(S )- { [ 1 -(4-cyanobenzyl)- 1 H-imidazol-5 -yl] acetyl}amino-3-(4-benzyloxy)phenylpropylamine was reacted with the corresponding isothiocyanates under the same condition as described in <Step 2> of Example 298 to give the title compounds.

Example 299 N-(2,3-Dichlorobenzyl)-N-(benzylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-l H-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

Η-NMR(CDCb) : 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, IH), 3.48(t, IH), 3.30(m, IH), 3.10(m, IH), 2.85(m, IH), 2.65(m, IH)

Example 300

N-(2,3-Dichlorobenzyl)-N-(2-biphenylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl

)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

1H-NMR(CDCb) : δ 7.70(d, IH), 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, IH), 3.48(t, IH), 3.32(m, IH), 3.05(m, IH), 2.85(m, IH), 2.60(m, IH)

Example 301

N-(2,3-Dichlorobenzyl)-N-(2-bromophenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)- 1 H-imidazol-5-yl] acetyl } amino-3 -(4-benzyloxy)phenylpropylamine

-H-NMR(CDCb) : δ 7.65(d, IH), 7.58(d, 3H), 7.25-7.45(m, 8H),

7.20(m, 4H), 6.85-7.05(m, 7H), 6.65(d, IH), 5.35(d, IH), 5.05(s, 2H),

4.65-4.90(m, 4H), 4.50(m, IH), 3.48(t, IH), 3.30(m, IH), 3.18(m, IH), 2.85(m, IH), 2.65(m, IH)

Example 302

N-(2,3-Dichlorobenzyl)-N-(3-bromophenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

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

Example 303

N-(2,3-Dichlorobenzyl)-N-(4-bromophenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

-H-NMR(CDCb) : δ 8.60(bs, IH), 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, IH), 5.55(d, IH), 5.05(s, 2H), 4.50-4.80(m, 4H), 4.25(m, IH), 3.48(t, IH), 3.30(m, IH), 3.18(m, IH), 2.95(m, IH), 2.65(m, IH)

Example 304

N-(2,3-Dichlorobenzyl)-N-(n-butylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanobenzyl)- 1

H-imidazol-5-yl]acetyl } amino-3 -(4-benzyloxy)phenylpropylamine

-H-NMR(CDCb) : δ 7.60(d, 2H), 7.25-7.45(m, 7H), 7.18(t, IH),

6.85-7.05(m, 8H), 6.78(d, IH), 6.22(bs, IH), 5.50(s, IH), 5.05(s, 2H),

4.50-4.85(m, 4H), 4.20(m, 3H), 3.65(m, 2H), 3.48(t, IH), 3.30(m, IH), 3.05(m, IH), 2.85(m, IH), 2.65(m, IH), 1.30(m, 4H), 0.85(t, 3H)

Example 305

N-(2,3-Dichlorobenzyl)-N-isobutylthiocarbamoyl-2(S)-{[l-(4-cyanobenzyl)-l

H-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

1H-NMR (CDCb) : 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, IH), 5.08(s, 2H), 5.00(d, IH),

4.80(m, 3H), 4.55(m, IH), 4.25(m, IH), 3.50(t, 2H), 3.35(m, 2H), 3.10(m, IH), 2.85(m, IH), 2.65(m, lH)1.90(m, IH), 0.80(m, 6H)

Example 306 N-(2,3-Dichlorobenzyl)-N-(t-butylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl]acetyl } amino-3 -(4-benzyloxy)phenylpropylamine

Η-NMR (CDCb) : 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, IH), 5.05(s, 2H), 4.95(d, 2H), 4.60(q, 2H), 4.30(m, IH), 3.50(t, IH), 3.33(m, IH), 3.05(m, IH), 2.75(d, 2H), 1.40(s, 9H)

Example 307

N-(2,3-Dichlorobenzyl)-N-(2-chlorophenylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanobe nzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -(4-benzyloxy)phenylpiOpylamine

-H-NMR(CDCb) : δ 7.95(bs, IH), 7.65(d, IH), 7.58(d, 2H),

7.10-7.50(m, 12H), 6.95(m, 7H), 6.62(d, IH), 5.30(d, IH), 5.05(s, 2H),

4.65-4.85(m, 4H), 4.45(m, IH), 3.48(t, IH), 3.30(m, IH), 3.18(m, IH), 2.90(m, IH), 2.65(m, IH)

Example 308

N-(2,3-Dichlorobenzyl)-N-(3-chlorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

1H-NMR(CDCb) : δ 8.70(bs, IH), 7.58(d, 2H), 7.45(m, 5H), 7.38(m, 5H), 7.18(m, 3H), 6.95(m, 7H), 6.40(d, IH), 5.60(d, IH), 5.07(s, 2H), 4.50-4.85(m, 4H), 4.28(m, IH), 3.48(t, IH), 3.33(m, IH), 3.18(m, IH), 2.95(m, IH), 2.65(m, IH)

Example 309

N-(2,3-Dichlorobenzyl)-N-(4-chlorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine -H-NMR(CDCb) : δ 8.60(bs, IH), 7.58(d, 2H), 7.10-7.45(m, 13H), 6.95(m, 7H), 6.42(d, IH), 5.56(d, IH), 5.05(s, 2H), 4.50-4.82(m, 4H), 4.25(m, IH), 3.48(t, IH), 3.30(m, IH), 3.18(m, IH), 2.95(m, IH), 2.65(m, IH)

Example 310

N-(2,3-Dichlorobenzyl)-N-(3-chloro-4-methylphenylthiocarbamoyl)-2(S)-{[l-( 4-cyanobenzyl)- 1 H-imidazol-5 -yl]acetyl } amino-3 -(4-benzyloxy)phenylpropyla mine

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

Example 311

N-(2,3 -Dichlorobenzyl)-N-(cyclohexylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanobenzyl

)- 1 H-imidazol-5-yl]acetyl } amino-3 -(4-benzyloxy)phenylpropylamine

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

Example 312

N-(2,3 -Dichlorobenzy l)-N-(cy clopentylthiocarbamoy 1)-2(S)- { [ 1 -(4-cyanobenzy

1)- 1 H-imidazol-5-y 1] acetyl } amino-3 -(4-benzyloxy)phenylpropylamine

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

Example 313

N-(2,3-Dichlorobenzyl)-N-(2,4-dichlorophenylthiocarbamoyl)-2(S)-{[l-(4-cya nobenzyl)- lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

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

Example 314

N-(2,3-Dichlorobenzyl)-N-[(2-dimethylamino)ethylthiocarbamoyl]-2(S)-{[l-(4 -cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropyla mine

-H-NMR(CDCb) : δ 7.62(d, 3H), 7.38(m, 7H), 7.08(m, 6H), 6.90(d, 3H), 6.78(s, IH), 4.90-5.10(m, 2H), 4.60(q, 2H), 4.38(m, IH), 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)-{[l-( 4-cyanobenzy 1)- 1 H-imidazol-5 -yl] acetyl } amino-3 -(4-benzyloxy)phenylpropyla mine

-H-NMR(CDCb) : δ 7.80(bs, IH), 7.58(d, 2H), 7.30-7.45(m, 7H), 7.00-7.22(m, 9H), 6.8 l(m, 3H), 6.65(d, 2H), 5.20(d, IH), 5.07(s, 2H), 4.85(m, 3H), 4.72(d, IH), 4.35(m, IH), 3.48(t, IH), 3.35(m, IH), 3.15(m, IH), 2.95(s, 3H), 2.80(m, 2H) Example 316

N-(2,3-Dichlorobenzyl)-N-[(3-dimethylamino)propylthiocarbamoyl]-2(S)-{[l-( 4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropyla mine

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

Example 317

N-(2,3-Dichlorobenzyl)-N-(ethoxycarbonylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -(4-benzyloxy)phenylpropylamine

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

Example 318

N-(2,3 -Dichlorobenzyl)-N-(3 -ethoxypropylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

1H-NMR(CDCb) : 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, IH), 3.759d, 2H), 3.44(m, 4H), 3.25(m, 4H), 3.05(m, IH), 2.75(d, 2H), 1.80(m, 2H), 0.92(t, 3H)

Example 319 N-(2,3-Dichlorobenzyl)-N-(ethylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-lH- imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

1H-NMR(CDCb) : δ 7.60(d, 2H), 7.25-7.45(m, 7H), 7.17(t, IH),

6.87-7.05(m, 8H), 6.75(d, IH), 6.35(s, IH), 5.20(d, IH), 5.05(s, 2H),

4.80(q, 2H), 4.60(d, 2H), 4.25(t, 3H), 4.67(p, 2H), 3.50(t, IH), 3.35(m, IH), 3.05(m, IH), 2.85(m, IH), 2.65(m, IH), 1.18(t, 3H)

Example 320

N-(2,3-Dichlorobenzyl)-N-(2-fluoiOphenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

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

Example 321

N-(2,3-Dichlorobenzyl)-N-(3-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5-yl] acetyl } amino-3 -(4-benzyloxy)phenylpropylamine

Η-NMR(CDCb) : δ 8.65(bs, IH), 7.58(d, 2H), 7.42(m, 3H), 7.30(m, 6H), 7.19(m, 3H), 6.95(m, 8H), 6.42(d, IH), 5.60(d, IH), 5.07(s, 2H), 4.78(m, 3H), 4.60(m, IH), 4.30(m, IH), 3.48(t, IH), 3.33(m, IH), 3.18(m, IH), 2.95(m, IH), 2.65(m, IH)

Example 322

N-(2,3 -Dichlorobenzyl)-N-(4-fluorophenylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine -H-NMR(CDCb) : δ 8.42(bs, IH), 7.58(d, 2H), 7.42(m, 4H), 7.30(m, 5H), 7.10(m, 4H), 6.95(m, 7H), 6.50(d, IH), 5.50(d, IH), 5.07(s, 2H), 4.70(m, 4H), 4.30(m, IH), 3.48(t, IH), 3.33(m, IH), 3.18(m, IH), 2.95(m, IH), 2.65(m, IH)

Example 323

N-(2,3-Dichlorobenzyl)-N-(4-hydroxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyano benzyl)- lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

1H-NMR(CDCb) : δ 8.10(bs, IH), 7.58(d, 2H), 7.38(m, 7H), 7.18(t, 2H), 6.95(m, 10H), 6.68(d, 2H), 5.16(d, IH), 5.05(s, 2H), 4.90(m, 3H), 4.62(d, IH), 4.38(bs, IH), 3.48(t, IH), 3.33(t, IH), 3.1 l(m, IH), 2.77(d, 2H)

Example 324

N-(2,3-Dichlorobenzyl)-N-(4-isopropylphenylthiocarbamoyl)-2(S)-{[l-(4-cyan obenzyl)- 1 H-imidazol-5-yl] acetyl } amino-3 -(4-benzyloxy)phenylpropylamine

-H-NMR(CDCb) : δ 8.13(bs, IH), 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, IH), 5.38(d, IH), 5.07(s, 2H), 4.78(m, 4H), 4.30(m, IH), 3.48(t, IH), 3.33(m, IH), 3.18(m, IH), 2.90(m, IH), 2.65(m, IH)

Example 325

N-(2,3-Dichlorobenzyl)-N-(2-methoxyethylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

1H-NMR(CDCb) : δ 8.14(bs, IH), 7.7.60(m, 2H), 7.38(m, 5H), 7.20(m, 3H), 6.95(m, 7H), 6.70(d, IH), 6.28(s, IH), 5.36(d, IH), 5.07(d, 2H), 4.85(m, 3H), 4.60(m, IH), 4.30(m, IH), 3.80(m, IH), 3.48(m, 2H), 3.33(m, IH), 3.18(m, 3H), 2.90(m, IH), 2.70(m, IH), 1.12(d, 3H)

Example 326

N-(2,3-Dichlorobenzyl)-N-(2-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyano benzyl)- 1 H-imidazol-5 -yl]acetyl } amino-3 -(4-benzyloxy)phenylpropylamine

^'H-NMR(CDCb) : δ 8.20(d, IH), 7.60(m, 3H), 7.38(m, 7H), 7.18(m, 2H), 7.00(m, 7H), 6.90(m, 4H), 5.15(d, IH), 5.05(s, 2H), 4.92(m, 3H), 4.70(d, IH), 4.45(m, IH), 3.60(s, 3H), 3.48(t, IH), 3.33(m, IH), 3.18(m, IH), 2.80(d, 2H)

Example 327

N-(2,3-Dichlorobenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyano benzyl)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

1H-NMR(CDCb) : δ 8.10(bs, IH), 7.58(d, 3H), 7.40(m, 7H), 7.20(m, 4H), 6.95(m, 8H), 6.75(d, IH), 5.36(d, IH), 5.07(s, 2H), 4.78(m, 4H), 4.32(m, IH), 3.80(s, 3H), 3.48(t, IH), 3.33(m, IH), 3.18(m, IH), 2.90(m, IH), 2.65(m, IH)

Example 328

N-(2,3-Dichlorobenzyl)-N-(3-methoxypropylthiocarbamoyl)-2(S)-{[l-(4-cyano benzyl)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

1H-NMR(CDCb) : 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, IH), 3.70(m, 2H), 3.48(t, IH), 3.38(m, 3H), 3.08(m, IH), 2.92(s, 3H), 2.75(d, 2H)

Example 329

N-(2,3 -Dichlorobenzyl)-N-(2-methoxvpyτidm-5-ylthiocarbamoyl)-2(S)- { [ 1 -(4- 12,

cyanobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -(4-benzyloxy)phenylpropylam ine

-H-NMR(CDCb) : δ 8.60(bs, IH), 8.00(s, IH), 7.63(m, IH), 7.58(d,

2H), 7.40(m, 3H), 7.07-7.37(m, 7H), 6.95(m, 6H), 6.72(d, IH), 6.58(d,

IH), 5.52(d, IH), 5.07(s, 2H), 4.78(m, 4H), 4.3 l(m, IH), 3.90(s, 3H),

3.48(t, IH), 3.33(m, IH), 3.18(m, IH), 2.95(m, IH), 2.65(m, IH)

Example 330

N-(2,3-Dichlorobenzyl)-N-(methylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-l

H-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

1H-NMR(CDCb) : δ 7.61(d, 2H), 7.40(m, 8H), 7.15(t, IH), 6.95(m, 8H), 6.70(d, IH), 5.20(d, IH), 5.07(s, 2H), 4.80(q, 2H), 4.60(m, 2H), 4.21(m, IH), 3.48(t, IH), 3.33(m, IH), 3.13(d, 3H), 3.05(m, IH), 2.90(m, IH), 2.65(m, IH)

Example 331

N-(2,3-Dichlorobenzyl)-N-(4-methylthiophenylthiocarbamoyl)-2(S)-{[l-(4-cya nobenzyl)- 1 H-imidazol-5-yl] acetyl } amino-3 -(4-benzyloxy)phenylpropylamine

1H-NMR(CDCb) : δ 8.40(bs, IH), 7.58(d, 2H), 7.42(m, 4H), 7.25(m, 8H), 7.18(m, 2H), 6.95(m, 6H), 6.60(d, IH), 5.42(d, IH), 5.07(s, 2H), 4.70(m, 4H), 4.30(m, IH), 3.48(t, IH), 3.33(m, IH), 3.18(m, IH), 2.92(m, IH), 2.70(m, IH), 2.45(s, 3H)

Example 332

N-(2,3 -Dichlorobenzyl)-N-(2-naphthylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanobenzyl

)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine -H-NMR(CDCb) : δ 8.60(bs, IH), 7.78(m, 4H), 7.15-7.55(m, 15H), 6.95(m, 6H), 6.60(d, IH), 5.50(d, IH), 5.07(s, 2H), 4.78(m, 4H), 4.40(m, IH), 3.48(t, IH), 3.33(m, IH), 3.18(m, IH), 2.90(m, IH), 2.65(m, IH)

Example 333

N-(2,3-Dichlorobenzyl)-N-(4-nitrophenylthiocarbamoyl)-2(S)-{[l-(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl} amino-3 -(4-benzyloxy)phenylpropylamine

-H-NMR(CDCb) : δ 9.40(s, IH), 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, IH), 5.80(d, IH), 5.07(s, 2H), 4.80(d, IH), 4.62(q, 2H), 4.40(m, IH), 4.20(m, IH), 3.48(t, IH), 3.33(m, IH), 3.11(m, IH), 3.00(m, IH), 2.65(m, IH)

Example 334

N-(2,3-Dichlorobenzyl)-N-(n-pentylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

1H-NMR(CDCb) : δ 7.60(d, 2H), 7.40(m, 8H), 7.15(t, IH), 7.00(m, 5H), 6.88(m, 3H), 6.12(s, IH), 5.07(s, 2H), 4.99(d, IH), 4.80(m, 3H), 4.59(d, IH), 4.30(m, IH), 3.65(m, IH), 3.48(t, IH), 3.33(m, 2H), 3.1 l(m, IH), 2.85(m, IH), 2.65(m, IH), 1.70(m,2H), 1.10(m, 2H), 0.80(m, 5H)

Example 335

N-(2,3-Dichlorobenzyl)-N-(phenethylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)

-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

1H-NMR(CDCb) : δ 7.60(d, 2H), 7.40(m, 7H), 7.18(m, 3H), 6.85-7.10(m, 11H), 6.76(d, IH), 5.95(s, IH), 5.07(s, 2H), 4.80(m, 4H), 4.42(d, IH), 4.24(m, IH), 3.85(m, 2H), 3.48(t, IH), 3.33(m, IH), 3.03(m, IH), 2.82(t, 2H), 2.70(m, 2H) Example 336

N-(2,3-Dichlorobenzyl)-N-(phenylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)-l H-imidazol-5-yl]acetyl} amino-3 -(4-benzyloxy)phenylpropylamine

-H-NMR(CDCb) : δ 8.30(bs, IH), 7.58(d, 2H), 7.20-7.45(m, 13H), 7.18(m, 2H), 6.95(m, 6H), 6.62(d, IH), 5.41(d, IH), 5.07(s, 2H), 4.73(m, 4H), 4.32(m, IH), 3.48(t, IH), 3.33(m, IH), 3.18(m, IH), 2.90(m, IH), 2.65(m, IH)

Example 337

N-(2,3-Dichlorobenzyl)-N-(n-propylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzyl)- 1 H-imidazol-5-yl]acetyl } amino-3 -(4-benzyloxy)phenylpropylamine

^'H-NMR(CDCb) : δ 7.62(d, 2H), 7.42(m, 4H), 7.32(m, 3H), 7.18(t, IH), 7.00(m, 6H), 6.90(m, 2H), 6.79(d, IH), 6.30(s, IH), 5.15(d, IH), 5.07(s, 2H), 4.80(q, 2H), 4.58(d, 2H), 4.25(m, IH), 3.5 l(m, 3H), 3.33(m, IH), 3.08(m, IH), 2.90(m, IH), 2.65(m, IH), 1.55(q, 2H), 0.85(t, 3H)

Example 338

N-(2,3-Dichlorobenzyl)-N-(3-methylphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

-H-NMR(CDCb) : δ 8.12(bs, IH), 7.58(d, 2H), 7.42(m, 3H), 7.32(m, 4H), 7.18(m, 6H), 6.95(m, 7H), 6.65(d, IH), 5.40(d, IH), 5.07(s, 2H), 4.78(m, 4H), 4.35(m, IH), 3.48(t, IH), 3.33(m, IH), 3.18(m, IH), 2.90(m, IH), 2.65(m, IH), 2.32(s, 3H)

Example 339 N-(2,3-Dichlorobenzyl)-N-(2-methylphenylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanob enzyl)- 1 H-imidazol-5-yl]acetyl } amino-3 -(4-benzyloxy)phenylpropylamine

1H-NMR (CDCb) : δ 7.68(bs, IH), 7.58(d, 2H), 7.42(m, 3H), 7.30(m, 4H), 7.19(m, 5H), 6.95(m, 9H), 5.25(d, IH), 5.07(s, 2H), 4.79(m, 4H), 4.40(m, IH), 3.48(t, IH), 3.33(m, IH), 3.18(m, IH), 2.85(m, IH), 2.75(m, IH), 2.12(s, 3H)

Example 340

N-(2,3-Dichlorobenzyl)-N-(4-methylphenylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanob enzyl)- lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

-H-NMR(CDCb) : δ 8.15(bs, IH), 7.58(d, 2H), 7.38(m, 7H), 7.18(s, 6H), 6.95(m, 7H), 6.70(d, IH), 5.36(d, IH), 5.07(s, 2H), 4.79(m, 4H), 4.36(m, IH), 3.48(t, 1H)„ 3.33(m, IH), 3.18(m, IH), 2.85(m, IH), 2.70(m,lH), 2.34(s, 3H)

Example 341

N-(2,3-DicMorobenzyl)-N-(3-trifluoromethylphenylthiocarbamoyl)-2(S)-{[l-(4 -cy anobenzyl)- 1 H-imidazol-5-y 1] acetyl } amino-3 -(4-benzyloxy)phenylpropyla mine

^'H-NMR (CDCb) : δ 9.02(bs, IH), 7.72(m, 2H), 7.40-7.55(m, 7H),

7.11-7.38(m, 6H), 6.95(m, 7H), 6.40(d, IH), 5.70(d, IH), 5.07(s, 2H),

4.71(m, 3H), 4.52(m, IH), 4.28(m, IH), 3.48(t, 1H)„ 3.33(m, IH), 3.20(m, IH), 3.00(m, IH), 2.65(m, IH)

Example 342

N-(2,3-Dichlorobenzyl)-N-(2,4-dimethylphenylthiocarbamoyl)-2(S)-{[l-(4-cya nobenzyl)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine 1H-NMR(CDCb) : 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, IH), 5.07(s, 2H), 4.79(m, 4H), 4.40(m, IH), 3.48(t, 1H)„ 3.33(m, IH), 3.18(m, IH), 2.85(m, IH), 2.75(m, IH), 2.3 l(s, 3H), 2.10(s, 3H)

Example 343

N-(2,3-Dichlorobenzyl)-N-(3,4-dimethylphenylthiocarbamoyl)-2(S)-{[l-(4-cya nobenzyl)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

Η-NMR (CDCb) : δ 8.00(bs, IH), 7.58(d, 2H), 7.42(m, 3H), 7.32(m, 4H), 7.15(m, 3H), 6.95(m, 9H), 6.72(d, IH), 5.32(d, IH), 5.07(s, 2H), 4.79(m, 4H), 4.37(m, IH), 3.48(t, IH), 3.33(m, IH), 3.18(m, IH), 2.85(m, IH), 2.75(m, IH), 2.25(s, 6H)

Example 344

N-(2,3-Dichlorobenzyl)-N-(allylthiocarbamoyl)-2-{ [ 1 -(4-cyanobenzyl)- lH-imi dazol-5 -yl]acetyl } aminoethylamine

<Step 1>

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

Using the same method as described in Preparative Example 3, N-boc-glycine was converted to N-boc-glycine aldehyde. And then the reaction was carried out under the same condition as described in Preparative Example 4, but replacing 1 -(4-nitrobenzyl)- 1 H-imi dazol- 5-ylacetic acid HCl with l-(4-cyanobenzyl)-lH-imidazol-5-ylacetic acid HCl to give the title compound.

-H-NMR(CDCb) : δ 7.60(d, 2H), 7.53(s, IH), 7.38(dd,lH), 7.13-7.21(m, 4H), 6.98(s, IH), 6.61(bs, IH), 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)- lH-imi dazol-5 -yl] acetyl } aminoethylamine

To a solution of N-(2,3-dichlorobenzyl)-2-{[l-(4-cyanobenzyl)-lH- imidazol-5-yl]acetyl}aminoethylamine in methyene chloride (0.02M, 1ml, 0.02mmol) was added allylisothiocyanate (0.1M in CH₂C1₂, 0.2ml, 0.02mmol). The reaction mixture was agitated for lhr at room temperature. The mixture was purified by silica gel column chromatography(eluent: methylene chloride/methanol=9/l, v/v) to give the title compound as a white solid.

Η-NMR(CDCb) : δ 7.63(d, 2H), 7.5 l(s, IH), 7.42(d, IH), 7.25(d, IH), 7.16(d, 2H), 7.04(d, IH), 6.96(s, IH), 6.66(bs, IH), 5.80-5.96(m, IH), 5.27(s, 2H), 5.12(dd, 2H), 4.94(d, 2H), 4.30(t, 2H), 3.29-3.39(m, 4H)

Examples 345-387

N-(2,3-Dichlorobenzyl)-2-{ [ 1 -(4-cyanobenzyl)- lH-imidazol-5-yl] acetyl} aminoethylamine was reacted with the corresponding isothiocyanates under the same condition as described in <Step 2> of Example 344 to give the title compounds.

Example 345

N-(2,3 -Dichlorobenzyl)-N-(benzylthiocarbamoyl)-2- { [ 1 -(4-cyanobenzyl)- 1 H-i midazol-5-yl]acetyl}aminoethylamine -H-NMR(CDCb) : δ 7.58(d, 2H), 7.45(s, IH), 7.40(d, IH), 7.03-7.32(m, 9H), 6.9 l(s, IH), 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-{[l -(4-cyanobenzyl)- 1

H-imidazol-5-yl]acetyl}aminoethylamine

1H-NMR(CDCb) : δ 7.99(bs, IH), 7.62(d, IH), 7.57(d, 2H), 7.46(s, IH), 7.29-7.42(m, 8H), 7.16(d, 2H), 7.04(d, 2H), 6.91(s, IH), 5.77(d, IH), 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-{[l-(4-cyanobenz y 1)- 1 H-imidazol-5 -yl] acetyl } aminoethylamine

-H-NMR(CDCb) : δ 8.17(bs, IH), 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, IH), 5.2 l(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-dicWorobenzyl)-N-(3-bromophenylthiocarbamoyl)-2-{[l-(4-cyanobenz yl)- lH-imidazol-5-yl]acetyl} aminoethylamine

-H-NMR(CDCb) : δ 9.11(bs, IH), 7.40-7.59(m, 6H), 7.15-7.32(m, 4H), 7.09(d, 2H), 6.92(s, IH), 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-cyanobenz yl)-lH-imidazol-5-yl]acetyl}aminoethylamine

¹H-NMR(CDCb) : δ 8.91(bs, IH), 7.57(d, 2H), 7.40-7.46(m, 4H), 7.34(s, IH), 7.19-7.30(m, 3H), 7.07(d, 2H), 6.92(s, IH), 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)- IH-i midazol-5-yl]acetyl}aminoethylamine

1H-NMR(CDCb) : δ 7.64(d, 2H), 7.52(s, IH), 7.41(d, IH), 7.13-7.23(m,

3H), 7.04(d, IH), 6.98(s, IH), 6.50(bs, IH), 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)- 1 H- imidazol-5 -yl] acetyl } aminoethylamine

-H-NMR(CDCb) : δ 7.64(d, 2H), 7.52(s, IH), 7.42(d, IH), 7.14-7.24(m, 3H), 7.05(d, IH), 6.98(s, IH), 6.45(bs, IH), 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, IH), 0.84(d, 6H)

Example 352

N-(2,3-Dichlorobenzyl)-N-(t-butylthiocarbamoyl)-2-{[l-(4-cyanobenzyl)-lH-i midazol-5 -y 1] acetyl } aminoethylamine

-H-NMR(CDCb) : δ 7.64(d, 2H), 7.55(s, IH), 7.44(d, IH), 7.15-7.32(m, 3H), 7.03(s, IH), 6.97(d, IH), 5.55(bs, IH), 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-{[l-(4-cyanobenz yl)- 1 H-imidazol-5 -yl]acetyl } aminoethylamine

1H-NMR(CDCb) : δ 8.20(bs, IH), 7.56-7.67(m, 3H), 7.40-7.46(m, 3H), 7.08-7.37(m, 6H), 6.95(s, IH), 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-cyanobenz y 1)- 1 H-imidazol-5 -yl] acetyl } aminoethylamine

Η-NMR(CDCb) : δ 7.60(d, 2H), 7.47(s, IH), 7.37-7.45(m, 3H), 7.12-7.29(m, 6H), 6.95(s, IH), 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-{[l -(4-cyanobenz y 1)- 1 H-imidazol-5 -yl] acetyl } aminoethylamine

-H-NMR(CDCb) : δ 8.85(bs, IH), 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, IH), 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-{[l-(4-c yanobenzyl)- 1 H-imidazol-5 -yl] acetyl } aminoethylamine -H-NMR(CDCb) : δ 8.89(bs, IH), 7.57(d, 2H), 7.46(s, IH), 7.37-7.43(m, 2H), 7.20-7.27(m, 3H), 7.08-7.15(m, 3H), 6.93(s, IH), 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-{[l -(4-cyanobenzyl)- 1

H -imidazol-5 -y 1] acetyl } aminoethylamine

-H-NMR(CDCb) : δ 7.64(d, 2H), 7.55(s, IH), 7.42(d, IH), 7.01-7.23(m, 5H), 6.14(bs, IH), 5.29(s, 2H), 4.91(s, 2H), 4.25-4.33(m, IH), 3.81(t, 2H), 3.37(s, 2H), 3.26-3.3 l(m, 2H), 1.96-2.02(m, 2H), 1.63(bs, 2H), 1.05-1.35(m, 6H)

Example 358

N-(2,3 -Dichlorobenzy l)-N-(cyclopentylthiocarbamoyl)-2-{[l-(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}aminoethylamine

-H-NMR(CDCb) : δ 7.64(d, 2H), 7.54(s, IH), 7.42(d, IH), 6.99-7.23(m, 5H), 6.37(bs, IH), 5.29(s, 2H), 4.95(s, 2H), 4.70(q, IH), 3.77(t, 2H), 3.37(s, 2H), 3.25-3.3 l(m, 2H), 1.98-2.1 l(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-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } amino ethylamine

-H-NMR(CDCb) : δ 8.30(bs, IH), 7.55-7.62(m, 3H), 7.47(s, IH), 7.41(dd, IH), 7.16-7.30(m, 3H), 7.12(d, 2H), 6.98(bs, IH), 6.94(s, IH), 5.21(s, 2H), 5.09(s, 2H), 3.3 l(t, 2H), 3.44(q, 2H), 3.36(s, 2H) Example 360

N-(2,3 -Dichlorobenzyl)-N-(4-dimethylaminophenylthiocarbamoyl)-2- { [ 1 -(4-cy anobenzyl)- 1 H-imidazol-5 -yl]acetyl } aminoethylamine

-H-NMR(CDCb) : δ 8.11(bs, IH), 7.56(d, 2H), 7.46(s, IH), 7.43(d, IH), 7.25(d, 2H), 7.10(d, 3H), 6.96(s, IH), 6.25(d, IH), 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-{[l-(4-cya nobenzyl)- lH-imidazol-5-yl]acetyl}aminoethylamine

1H-NMR(CDCb) : δ 7.64(d, 2H), 7.50(s, IH), 7.41(dd, IH), 7.05-7.24(m, 4H), 6.97(s, IH), 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-{[l-(4-cyanobenz y 1)- 1 H-imidazol-5 -yl] acetyl } aminoethylamine

-H-NMR(CDCb) : δ 7.64(d, 2H), 7.54(s, IH), 7.42(d, 2H), 7.15-7.23(m,

2H), 7.02(s, IH), 6.03(d, IH), 5.3 l(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)- IH-imi dazol-5 -yl]acetyl } aminoethylamine

-H-NMR(CDCb) : δ 7.64(d, 2H), 7.53(s, IH), 7.4 l(d, IH), 7.03-7.24(m, 4H), 6.98(s, IH), 6.56(bs, IH), 5.28(s, 2H), 4.94(s, 2H), 3.78(t, 2H), 3.65(q, 2H), 3.37(s, 2H), 3.3 l(q, 2H), 1.9 l(t, 3H)

Example 364

N-(2,3-Dichlorobenzyl)-N-(2-fluorophenylthiocarbamoyl)-2-{[l-(4-cyanobenz y 1)- 1 H-imidazol-5 -yl] acetyl } aminoethylamine

-H-NMR(CDCb) : δ 8.30(bs, IH), 7.58(d, 2H), 7.41-7.5 l(m, 3H), 7.03-7.29(m, 8H), 6.94(s, IH), 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-{[l-(4-cyanobenz yl)- 1 H-imidazol-5 -yl]acetyl } aminoethylamine

1H-NMR(CDCb) : δ 8.98(bs, IH), 7.57(d, 2H), 7.47(s, IH), 7.40-7.45(m, IH), 7.22-7.30(m, 6H), 7.09(d, 2H), 6.93(s, IH), 6.85- 6.91(m, IH), 5.22(s, 2H), 5.20(s, 2H), 3.78(t, 2H), 3.30-3.36(m, 2H), 3.38(s, 2H)

Example 366

N-(2,3 -Dichlorobenzyl)-N-(4-fluorophenylthiocarbamoyl)-2- { [ 1 -(4-cyanobenz yl)- 1 H-imidazol-5 -yl] acetyl } aminoethylamine

-H-NMR(CDCb) : δ 8.68(bs, IH), 7.58(d, 2H), 7.41-7.47(m, IH), 7.19-7.37(m, 6H), 7.08(d, 2H), 7.02(s, IH), 6.94(s, IH), 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 -Dichlorobenzy l)-N-(4-hydroxyphenylthiocarbamoyl)-2- { [ 1 -(4-cyanobe nzyl)- 1 H-imidazol-5 -yl]acetyl } aminoethylamine

-H-NMR(CD₃OD) δ : 7.74(s, IH), 7.64(d, 2H), 7.48(d, IH), 7.32(t, IH), 7.22(d, 2H), 7.14(d, IH), 7.08(d, 2H), 6.95(s, IH), 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-{[l-(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}aminoethylamine

-H-NMR(CDCb) : δ 8.39(bs, IH), 7.56(d, 2H), 7.47(s, IH), 7.39-7.46(m, IH), 7.11-7.3 l(m, 5H), 7.03(d, 2H), 6.96(s, IH), 5.21(s, 2H), 5.12(s, 2H), 3.84(t, 2H), 3.36(bs, 4H), 2.83-2.96(m, IH), 1.23(d, 6H)

Example 369

N-(2,3-Dichlorobenzyl)-N-(2-methoxyethylthiocarbamoyl)-2-{[l-(4-cyanobenz yl)- 1 H-imidazol-5 -yl] acetyl} aminoethylamine

1H-NMR(CDCb) : δ 7.64(d, 2H), 7.54(s, IH), 7.43(d, IH), 7.16-7.23(m, 3H), 7.01(s, IH), 6.98(d, IH), 6.41(bs, IH), 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-cyanobe nzyl)- 1 H-imidazol-5 -yl] acetyl } amino ethylamine

-H-NMR(CDCb) : δ 8.14(d, IH), 7.45-7.61(m, 5H), 7.20-7.28(m, 2H), 7.09-7.16(m, 3H), 7.01(s, IH), 6.81(d, IH), 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-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5 -yl] acetyl } aminoethylamine

-H-NMR(CDCb) : δ 8.38(bs, IH), 7.57(d, 2H), 7.46(s, IH), 7.41-7.45(m, IH), 7.16-7.14(m, 4H), 7.09(d, 2H), 6.95(s, IH), 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-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5-yl]acetyl } aminoethylamine

-H-NMR(CDCb) : δ 7.64(d, 2H), 7.54(s, IH), 7.43(d, IH), 7.16-7.23(m, 3H), 7.03(s, IH), 6.91(bs, IH), 6.89(d, IH), 5.3 l(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-{[l-(4-cya nobenzyl)- 1 H-imidazol-5 -yl] acetyl } aminoethylamine

-H-NMR(CDCb) : δ 8.86(bs, IH), 8.01(d, IH), 7.71(dd, IH), 7.59(d, 2H), 7.45(s, IH), 7.41-7.44(m, IH), 7.19-7.28(m, 2H), 7.10(d, 2H), 6.93(s, IH), 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)- IH-i midazol-5 -yl] acetyl } aminoethylamine

-H-NMR(CDCb) : δ 7.64(d, 2H), 7.5 l(s, IH), 7.41(d, IH), 7.15-7.23(m, 3H), 7.04(d, IH), 6.97(d, IH), 6.78(bs, IH), 5.27(s, 2H), 4.93(s, 2H), 3.79(t, 2H), 3.37(s, 2H), 3.27-3.37(m, 2H), 3.1 l(d, 2H)

Example 375

N-(2,3-Dichlorobenzyl)-N-(4-methylthiophenylthiocarbamoyl)-2-{[l-(4-cyano benzyl)- 1 H-imidazol-5 -yl] acetyl } aminoethylamine

-H-NMR(CDCb) : r5 8.67(bs, IH), 7.56(d, 2H), 7.46(s, IH), 7.41-7.45(m, IH), 7.18-7.49(m, 5H), 7.08(d, 2H), 6.94(s, IH), 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)- 1

H-imidazol-5-yl]acetyl}aminoethylamine

¹H-NMR(CDCb) : δ 8.93(bs, IH), 7.69-7.80(m, 3H), 7.58(dd, IH), 7.41-7.48(m, 5H), 7.23-7.30(m, 2H), 7.06-7.12(m, IH), 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-{[l-(4-cyanobenzyl )- 1 H-imidazol-5 -yl] acetyl } aminoethylamine

-H-NMR(CDCb) : δ 9.52(bs, IH), 8.17(d, 2H), 7.83(d, 2H),

7.53-7.59(m, 3H), 7.42-7.46(m, IH), 7.24-7.27(m, 2H), 7.09(d, 2H),

6.97(s, IH), 6.82-6.89(m, IH), 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

'H-NMR^DCb) : δ 7.64(d, 2H), 7.53(s, IH), 7.42(d, IH), 7.02-7.23(m,

4H), 6.99(s, IH), 6.29(bs, IH), 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, IH), 1.04-1.29(m, 2H), 0.78-0.89(m, 5H)

Example 379

N-(2,3 -Dichlorobenzyl)-N-(phenethylthiocarbamoyl)-2- { [ 1 -(4-cyanobenzyl)- 1

H-imidazol-5-yl]acetyl } aminoethylamine

-H-NMR(CDCb) : δ 7.62(d, 2H), 7.50(s, IH), 7.38(d, IH), 7.11-7.17(m, 6H), 6.99-7.07(m, 3H), 6.84(d, IH), 6.07(bs, IH), 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-{[l-(4-cyanobenzyl)-lH-i midazol-5-yl]acetyl}aminoethylamine

1H-NMR(CDCb) : δ 8.57(bs, IH), 7.55(d, 2H), 7.47(s, IH), 7.33-7.45(m, 5H), 7.17-7.29(m, 3H), 7.08(d, 2H), 6.95(s, IH), 5.20(s, 2H), 5.14(s, 2H), 3.82(t, 2H), 3.37(bs, 4H)

Example 381

N-(2,3-Dic orobenzyl)-N-(n-propylthiocarbamoyl)-2-{[l-(4-cyanobenzyl)-lH

-imidazol-5-yl]acetyl}aminoethylamine -H-NMR(CDCb) : δ 7.64(d, 2H), 7.53(s, IH), 7.42(d, IH), 7.02-7.23(m,

4H), 6.99(s, IH), 6.46(bs, IH), 5.28(s, 2H), 4.92(s, 2H), 3.8 l(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-{[l-(4-cyanobenz yl)- 1 H-imidazol-5 -yl]acetyl } aminoethylamine

1H-NMR(CDCb) : δ 8.43(bs, IH), 7.56(d, 2H), 7.47(s, IH), 7.41-7.45(m, IH), 7.01-7.29(m, 8H), 6.96(s, IH), 5.2 l(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-cyanobenz yl)- 1 H-imidazol-5 -yl] acetyl } aminoethylamine

-H-NMR(CDCb) : δ 8.02(bs, IH), 7.57(d, 2H), 7.47(s, IH), 7.43-7.46(m, IH), 7.20-7.30(m, 6H), 7.10(d, 2H), 6.94(s, IH), 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, 3H)

Example 384

N-(2,3 -Dichlorobenzyl)-N-(4-methylphenythiocarbamoyl)-2- { [ 1 -(4-cyanobenz yl)- lH-imidazol-5-yl]acetyl} aminoethylamine

-H-NMR(CDCb) : δ 8.44(bs, IH), 7.56(d, 2H), 7.46(s, IH), 7.41-7.44(m, IH), 7.07-7.28(m, 8H), 6.95(s, IH), 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-{[l-(4-cy anobenzyl)-lH-imidazol-5-yl]acetyl}aminoethylamine

1H-NMR(CDCb) : δ 9.33(bs, IH), 7.85-7.89(m, IH), 7.69(s, IH), 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, IH), 5.24(s, 4H), 3.72(t, 2H), 3.37(bs, 4H)

Example 386

N-(2,3-Dichlorobenzyl)-N-(2,4-dimethylphenylthiocarbamoyl)-2-{[l-(4-cyano benzyl)- lH-imidazol-5-yl]acetyl}aminoethylamine

-H-NMR(CDCb) : δ 7.91(bs, IH), 7.57(d, 2H), 7.47(s, IH), 7.42-7.46(m, IH), 7.20-7.30(m, 3H), 7.15(d, 2H), 7.01(s, 2H), 6.94(s, IH), 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 -Dichlorobenzy l)-N-(3 ,4-dimethylphenylthiocarbamoyl)-2- { [ 1 -(4-cy ano benzyl)-lH-imidazol-5-yl]acetyl}aminoethylamine

1H-NMR(CDCb) : δ 8.33(bs, IH), 7.56(d, 2H), 7.47(s, IH), 7.41-7.45(m, IH), 7.08-7.29(m, 7H), 6.96(s, IH), 5.2 l(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 -Naphthyhnethyl)-N-allylthiocarbamoyl-2(S)- { [ 1 -(4-nitrobenzyl)- 1 H-imid azol-5-yl]acetyl}amino-3(S)-methylpentylamine

To a solution of N-(l-naphthylmethyl)-2(S)-{[l-(4-nitrobenzyl)-lH- imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine in dichloromethane (0.02M, 1ml, 0.02mmol) was added allylisothiocyanate (0.1M in CH₂C , 0.2ml, 0.02mmol). The reaction mixture was agitated overnight at room temperature. The mixture was purified by silica gel column chromatography(eluent: CH2CI2 /MeOH=9/l, v/v) to give the title compound as a white solid.

^"H-NMR (CDCb) : 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, IH), 1.60(m, IH), 1.42(bs, IH), 0.85-1.15(m, 7H)

Examples 389-417

N-( 1 -Naphthylmethyl)-2(S)- { [ 1 -(4-nitrobenzyl)- lH-imidazol-5-yl] acetyl}amino-3(S)-methylpentylamine was reacted with the corresponding isothiocyanates under the same condition as described in Example 388 to give the title compounds.

Example 389

N-( 1 -Naphthylmethyl)-N-benzylthiocarbamoyl-2(S)- { [ 1 -(4-nitrobenzyl)- lH-im idazol-5-yl]acetyl}amino-3(S)-methylpentylamine

Η-NMR (CDCb) : δ 7.02-8.20(m, 18H), 5.95(t, IH), 5.30(m, 3H), 5.02(m, 2H), 4.80(d, 2H), 4.22(bs, IH), 3.28(s, 2H), 3.15(dd, IH), 1.60(m, IH), 1.42(bs, IH), 0.85-1.15(m, 7H)

Example 390

N-(l-Naphthylmethyl)-N-(2-bromophenylthiocarbamoyl)-2(S)-{[l-(4-nitrobenz yl)- 1 H-imidazol-5 -yl]acetyl } amino-3 (S)-methylpentylamine

1H-NMR (CDCb) : δ 7.02-8.18(m, 17H), 5.10-5.45(m, 5H), 4.35(m, IH), 3.40(d, 2H), 3.22(dd, 2H), 1.60(m, IH), 1.42(bs, IH), 0.85-1.15(m, 7H)

Example 391

N-(l-Naphthylmethyl)-N-(3-bromophenylthiocarbamoyl)-2(S)-{[l-(4-nitrobenz yl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.02-8.18(m, 17H), 5.10-5.40(m, 5H), 4.25(m, IH), 3.38(s, 2H), 3.20(dd, 2H), 1.60(m, IH), 1.40(bs, IH), 0.80-1.10(m, 7H)

Example 392

N-( 1 -Naphthylmethyl)-N-(n-butylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrobenzyl)- 1 H-i midazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.05-8.20(m, 13H), 5.25-5.62(dd, 2H), 4.95(d, IH), 4.20(m, IH), 3.64(m, IH), 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-(l-Naphthylmethyl)-N-(4-chlorophenylthiocarbamoyl)-2(S)-{[l-(4-nitrobenz yl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.00-8.20(m, 17H), 5.10-5.42(m, 5H), 4.25(m, IH), 3.40(s, 2H), 3.20(dd, 2H), 1.60(m, IH), 1.40(m, IH), 1.05(m, IH), 0.90(t, 6H)

Example 394

N-( l-Naphthylmethyl)-N-ethoxycarbonylthiocarbamoyl-2(S)-{ [ l-(4-nitrobenzy

1)- 1 H-imidazol-5-yl] acetyl } amino-3 (S )-methylpentylamine ^'H-NMR (CDCb) : δ 7.10-8.22(m, 13H), 6.30(d, IH), 5.35(m, 3H), 5.00(d, 2H), 4.25(m, IH), 4.15(q, 2H), 3.40(s, 2H), 3.05(dd, 2H), 1.60(m, IH), 1.20-1.40(m, 5H), 0.80(m, 6H)

Example 395

N-( 1 -Naphthylmethyl)-N-ethylthiocarbamoyl-2(S)- { [ 1 -(4-nitrobenzyl)- lH-imid azol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.05-8.20(m, 13H), 5.55(t, IH), 5.20-5.40(m, 3H), 4.95(d, 2H), 4.20(m, IH), 3.60(q, 2H), 3.40(s, 2H), 3.05(dd, 2H), 1.60(m, IH), 1.40(m, IH), 1.20(m, IH), 1.02(t, 3H), 0.85(t, 6H)

Example 396

N-( 1 -Naphthylmethyl)-N-(2-fluorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrobenz y 1)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S)-methylpentylamine

1H-NMR (CDCb) : δ 7.05-8.20(m, 17H), 5.20-5.40(m, 5H), 4.35(m, IH), 3.42(s, 2H), 3.20(dd, 2H), 1.65(m, 2H), 1.40(m, IH), 1.15(m, IH), 0.90(m, 6H)

Example 397

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

-H-NMR(CDCb) : £ 7.05-8.20(m, 17H), 5.20-5.40(m, 5H), 4.30(m, IH), 3.38(s, 2H), 3.20(dd, 2H), 1.60(m, 2H), 1.40(m, IH), 1.15(m, IH), 0.90(m, 6H)

Example 398 N-( 1 -Naphthylmethyl)-N-(4-fluorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrobenz yl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.00-8.20(m, 17H), 5.20-5.40(m, 5H), 4.25(m, IH), 3.38(s, 2H), 3.20(dd, 2H), 1.60(m, 2H), 1.40(m, IH), 1.15(m, IH), 0.90(m, 6H)

Example 399

N-( 1 -Naphthylmethyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrobe nzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methylpentylamine

Η-NMR (CDCb) : δ 6.80-8.18(m, 17H), 5.20-5.40(m, 5H), 4.23(m, IH), 3.78(s, 3H), 3.40(s, 2H), 3.20(dd, 2H), 1.60(m, 2H), 1.40(m, IH), 1.15(m, IH), 0.90(m, 6H)

Example 400

N-( 1 -Naphthylmethyl)-N-methylthiocarbamoyl-2(S)- { [ 1 -(4-nitrobenzyl)- lH-im idazol-5-yl]acetyl } amino-3 (S)-methylpentylamine

1H-NMR (CDCb) : δ 7.00-8.22(m, 13H), 5.20-5.45(m, 3H), 5.00(d, 2H), 4.20(m, IH), 3.38(s, 2H), 3.15(dd, 2H), 3.10(d, 3H), 1.60(m, 2H), 1.40(m, IH), 1.15(m, IH), 0.90(m, 6H)

Example 401

N-( 1 -Naphthy lmethyl)-N-( 1 -naphthylthiocarbamoyl)-2(S )- { [ 1 -(4-nitrobenzyl)-

1 H-imidazol-5-y 1] acetyl } amino-3 (S )-methylpentylamine

-H-NMR (CDCb) : δ 7.00-8.15(m, 20H), 5.20-5.60(m, 5H), 4.40(m, IH), 3.42(s, 2H), 3.15(dd, 2H), 3.10(d, 3H), 1.60(m, 2H), 1.40(m, IH), 1.15(m, IH), 0.90(m, 6H) Example 402

N-( 1 -Naphthy lmethyl)-N-phenylethylthiocarbamoyl-2(S )- { [ 1 -(4-nitrobenzyl)- 1

H-imidazol-5-yl]acetyl } amino-3 (S)-methylpentylamine

1H-NMR (CDCb) : δ 6.75-8.20(m, 18H), 5.20-5.60(m, 3H), 4.80(s, 2H), 4.20(m, IH), 3.90(m, IH), 3.70(m, IH), 3.38(s, 2H), 3.05(dd, 2H), 2.70(t, 2H), 1.60(m, 2H), 1.40(m, IH), 1.15(m, IH), 0.90(m, 6H)

Example 403

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

1H-NMR (CDCb) : δ 7.00-8.20(m, 17H), 5.20-5.60(m, 5H), 4.25(m, IH), 3.38(s, 2H), 3.20(dd, 2H), 1.60(m, 2H), 1.40(m, IH), 1.15(m, IH), 0.90(m, 6H)

Example 404

N-( 1 -Naphthy lmethyl)-N-benzoylthiocarbamoyl-2(S )- { [ 1 -(4-nitrobenzyl)- 1 H-i midazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.10-8.20(m, 18H), 6.20(bs, IH), 5.20-5.55(m, 3H), 5.00(d, 2H), 4.45(m, IH), 3.50(s, 2H), 3.15(dd, IH), 1.80(m, 2H), 1.45(m, IH), 0.85-1.12(m, 7H)

Example 405

N-( 1 -Naphthy lmethyl)-N-cyclohexylthiocarbamoyl-2(S)- { [ 1 -(4-nitrobenzyl)- 1

H-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

^'H-NMR (CDCb) : 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, IH), 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)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S)-methy lpentylamine

1H-NMR (CDCb) : δ 7.00-8.20(m, 19H), 5.20-5.55(m, 5H), 4.38(m, IH), 3.45(s, 2H), 3.25(dd, IH), 2.80(ss, 6H), 1.80(m, IH), 1.40(bs, IH), 1.10(m, IH), 0.85(m, 6H)

Example 407

N-(l-Naphthylmethyl)-N-(2-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-nitrobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 6.90-8.18(m, 17H), 6.80(s, IH), 5.20-5.40(m, 3H), 5.10(d, 2H), 4.35(m, IH), 3.40(s, 2H), 3.20(dd, IH), 3.20(s, 3H), 1.80(m, IH), 1.40(bs, IH), 1.10(m, IH), 0.85(m, 6H)

Example 408

N-( 1 -Naphthylmethyl)-N-(4-nitrophenylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrobenzy l)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.00-8.20(m, 17H), 5.60(m, IH), 5.38(d, 2H), 5.10(d, 2H), 4.25(m, IH), 3.40(s, 2H), 3.20(dd, IH), 1.80(m, IH), 1.40(bs, IH), 1.10(m, IH), 0.85(m, 6H)

Example 409

N-( 1 -Naphthylmethyl)-N-n-propylthiocarbamoyl-2(S)- { [ 1 -(4-nitrobenzyl)- 1 H-i midazol-5-yl]acetyl}amino-3(S)-methylpentylamine ^'H-NMR (CDCb) : δ 7.00-8.20(m, 13H), 5.60(m, IH), 5.40(d, 2H), 5.25(m, IH), 4.98(d, 2H), 4.20(m, IH), 3.60(m, IH), 3.42(m, IH), 3.40(s, 2H), 3.10(dd, IH), 1.80(m, IH), 1.60(bs, IH), 1.40(m, 2H), 1.10(m, IH), 0.85(m, 6H), 0.70(t, 3H)

Example 410

N-( l-Naphthylmethyl)-N-(2-methylphenylthiocarbamoyl)-2(S)-{ [ l-(4-nitroben zyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S)-methylpentylamine

1H-NMR (CDCb) : δ 7.00-8.20(m, 17H), 5.25-5.42(m, 3H), 5.10(d, 2H), 4.30(m, IH), 3.40(s, 2H), 3.22(dd, IH), 2.00(s, 3H), 1.80(m, IH), 1.40(m, IH), 1.10(m, IH), 0.90(m, 6H)

Example 411

N-( l-Naphthylmethyl)-N-(3-methylphenylthiocarbamoyl)-2(S)-{ [ l-(4-nitroben zyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 6.96-8.20(m, 17H), 5.40(d, IH), 5.20(m, IH), 5.10(d, 2H), 4.25(m, IH), 3.40(s, 2H), 3.18(dd, IH), 2.30(s, 3H), 2.00(m, IH), 1.40(m, IH), 1.10(m, IH), 0.90(m, 6H)

Example 412

N-(l-Naphthylmethyl)-N-(4-methylphenylthiocarbamoyl)-2(S)-{[l-(4-nitroben zyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S)-methylpentylamine

-H-NMR (CDCb) : δ 7.00-8.20(m, 17H), 5.40(d, IH), 5.20(m, IH), 5.10(d, 2H), 4.30(m, IH), 3.38(s, 2H), 3.20(dd, IH), 2.30(s, 3H), 2.00(m, IH), 1.40(m, IH), 1.10(m, IH), 0.90(m, 6H) Example 413

N-(l-Naphthylmethyl)-N-(4-azidophenylthiocarbamoyl)-2(S)-{[l-(4-nitrobenz yl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 6.80-8.10(m, 17H), 4.95-5.38(m, 5H), 4.20(m, IH), 3.27(s, 2H), 3.08(dd, IH), 1.58(bs, IH), 1.32(m, IH), 1.00(m, IH), 0.92(m, 6H)

Example 414

N-(l-Naphthylmethyl)-N-(4-bromophenylthiocarbamoyl)-2(S)-{[l-(4-nitrobenz y 1)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S)-methy lpentylamine

^"H-NMR (CDCb) : δ 7.00-8.10(m, 17H), 4.92-5.40(m, 5H), 4.20(m, IH), 3.25(s, 2H), 3.05(dd, IH), 1.57(bs, IH), 1.34(m, IH), 0.98(m, IH), 0.82(m, 6H)

Example 415

N-( 1 -Naphthylmethyl)-N-(2-chlorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrobenz y 1)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S)-methy lpentylamine

1H-NMR (CDCb) : δ 7.00-8.15(m, 17H), 5.00-5.38(m, 5H), 4.24(m, IH), 3.32(s, 2H), 3.13(dd, IH), 1.58(bs, IH), 1.36(m, IH), 1.00(m, IH), 0.80(m, 6H)

Example 416

N-( 1 -Naphthylmethyl)-N-(3 -chloι^*ophenylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrobenz yl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.00-8.10(m, 17H), 4.98-5.22(m, 5H), 4.20(m, IH), 3.28(s, 2H), 3.10(dd, IH), 1.56(bs, IH), 1.35(m, IH), 1.00(m, IH), 0.80(m, 6H)

Example 417

N-( 1 -Naphthylmethyl)-N-(2,4-dichlorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-nitro benzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.00-8.15(m, 16H), 5.00-5.18(m, 5H), 4.25(m, IH), 3.30(s, 2H), 3.14(dd, IH), 1.60(bs, IH), 1.34(m, IH), 1.00(m, IH), 0.82(m, 6H)

Example 418

N-( 1 -Naphthylmethyl)-N-(2-bromophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

<Step 1>

N-( l-Naphthylmethyl)-2(S)-{ [ 1 -(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}ami no-3(S)-methylpentylamine

Using the same method as described in Preparative Example 3 N-t-butoxycarbonyl-L-isoleucine was converted to N-(t-butoxycarbonyl)-L- isoleucine aldehyde. And then the reaction was carried out under the same condition as described in Preparative Example 4, but replacing 1 -(4-nitrobenzyl)- lH-imidazol-5 -ylacetic acid hydrochloride with l-(4- cyanobenzyl)-l H-imidazol-5 -ylacetic acid hydrochloride to give the title compound.

-H-NMR (CDCb) : δ 6.80-8.20(m, 13H), 5.95(d, IH), 4.80-5.12(dd, 2H), 4.15-4.20(m, 2H), 3.80-4.00(m, IH), 3.15(m, 2H), 2.60-2.80(m, 2H), 2.24(bs, IH), 1.20-1.60(m, 2H), 0.92-1.20(m, IH), 0.60-0.92(m, 6H) <Step 2>

N-(l-Naphthylmethyl)-N-(2-bromophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)- 1 H-imidazol-5-yl] acetyl } amino-3 (S )-methylpentylamine

To a solution of N-(l-naphthylmethyl)-2(S)-{[l-(4-cyanobenzyl)-lH- imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine in dichloromethane (0.02M, 1ml, 0.02mmol) was added 2-bromophenylisothiocyanate (0.1M in CH2CI2, 0.2ml, 0.02mmol). The reaction mixture was agitated for 4hr at room temperature. The mixture was purified by silica gel column chromatography(eluent:

v/v) to give the title compound as a white solid.

¹ H-NMR (CDCb) : δ 7.10-8.00(m, 17H), 5.40(m, 2H), 5.20(d, 4H), 4.40(m, 2H), 4.05(bs, IH), 3.40(s, 2H), 3.25(dd, IH), 1.80(m, IH), 1.42(bs, IH), 0.80-1.10(m, 7H)

Examples 419-447

N-( 1 -Naphthylmethyl)-2(S)- { [ 1 -(4-cyanobenzyl)- 1 H-imidazol-5 -yl] acetyl}amino-3(S)-methylpentylamine was reacted with the corresponding isothiocyanates under the same condition as described in <Step 2> of Example 418 to give the title compounds.

Example 419

N-( 1 -Naphthylmethyl)-N-(4-chlorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanoben zyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

^"H-NMR (CDCb) : δ 7.10-8.00(m, 17H), 5.00-5.40(m, 4H), 4.25(m, IH), 4.05(bs, IH), 3.36(s, 2H), 3.20(dd, IH), 1.80(m, IH), 1.42(bs, IH), 0.80-1.10(m, 7H) Example 420

N-( 1 -Naphthylmethyl)-N-(2-fluorophenylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanoben zyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

^"H-NMR (CDCb) : δ 7.05-7.95(m, 17H), 5.05-5.40(m, 4H), 4.35(m, IH), 4.10(bs, IH), 3.40(s, 2H), 3.20(dd, IH), 1.80(m, IH), 1.42(bs, IH), 0.80-1.10(m, 7H)

Example 421

N-(l-Naphthylmethyl)-N-(3-fluoiOphenylthiocaι^*bamoyl)-2(S)-{[l-(4-cyanoben zyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 6.90-7.95(m, 17H), 5.05-5.50(m, 5H), 4.25(m, IH), 3.38(s, 2H), 3.18(dd, IH), 1.60(m, IH), 1.40(bs, IH), 1.05(m, IH), 0.80(t, 6H)

Example 422

N-( 1 -Naphthylmethyl)-N-(4-fluorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl} amino-3 (S)-methylpentylamine

^'H-NMR (CDCb) : _c 7.00-7.95(m, 17H), 5.30(d, 2H), 5.20-5.42(m, IH), 5.15(m, 2H), 4.20(m, IH), 3.40(s, 2H), 3.20(dd, IH), 1.80(m, IH), 1.40(m, IH), 1.04(m, IH), 0.85(t, 6H)

Example 423

N-( 1 -Naphthylmethyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 6.80-7.95(m, 17H), 5.25-5.40(m, 3H), 5.10(m, 2H), 4.25(m, IH), 3.75(s, 3H), 3.40(s, 2H), 3.20(dd, IH), 1.80(m, IH), 1.40(m, IH), 1.04(m, IH), 0.85(m, 6H)

Example 424

N-( 1 -Naphthylmethyl)-N-(3 -trifluoromethylphenylthiocarbamoyl)-2(S)- { [ 1 -(4- cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.00-7.90(m, 17H), 5.05-5.50(m, 5H), 4.30(m, IH), 3.35(s, 2H), 3.20(dd, IH), 1.80(m, IH), 1.40(m, IH), 1.04(m, IH), 0.85(m, 6H)

Example 425

N-( 1 -Naphthylmethyl)-N-(2-methoxyphenylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 6.88-8.20(m, 17H), 4.85-5.35(m, 5H), 4.30(m, IH), 3.40(s, 2H), 3.22(s, 3H), 3.20(dd, IH), 1.75(m, IH), 1.40(m, IH), 1.05(m, IH), 0.90(m, 6H)

Example 426

N-( 1 -Naphthylmethyl)-N-(4-nitrophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanobenz yl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.05-8.15(m, 17H), 5.55(m, IH), 5.30(d, 2H), 5.05(d, 2H), 4.24(m, IH), 3.38(s, 2H), 3.20(dd, IH), 1.75(m, IH), 1.40(m, IH), 1.05(m, IH), 0.90(m, 6H)

Example 427

N-( 1 -Naphthy lmethyl)-N-(2-methylpheny lthiocarbamoyl)-2(S )- { [ 1 -(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine -H-NMR (CDCb) : 7.05-8.20(m, 17H), 5.30(m, 3H), 5.10(dd, 2H), 3.40(s, 2H), 3.20(dd, IH), 1.98(s, 3H), 1.60(m, IH), 1.40(m, IH), 1.10(m, IH), 0.95(m, 6H)

Example 428

N-(l-Naphthylmethyl)-N-(3-methylphenylthiocarbamoyl)-2(S)-{[l-(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 6.90-7.90(m, 17H), 5.35(m, 3H), 5.10(d, 2H), 3.38(s, 2H), 3.20(dd, IH), 2.25(s, 3H), 1.60(m, IH), 1.40(m, IH), 1.10(m, IH), 0.95(m, 6H)

Example 429

N-( 1 -Naphthylmethyl)-N-(4-methylphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.05-7.95(m, 17H), 5.30(m, 3H), 5.10(dd, 2H), 3.40(s, 2H), 3.18(dd, IH), 2.30(s, 3H), 1.55(m, IH), 1.42(m, IH), 1.05(m, IH), 0.85(m, 6H)

Example 430

N-(l-Naphthylmethyl)-N-allylthiocarbamoyl-2(S)-{[l-(4-cyanobenzyl)-lH-imi dazol-5-yl]acetyl } amino-3 (S)-methylpentylamine

^'H-NMR (CDCb) : δ 7.05-7.95(m, 13H), 5.60(t, IH), 5.35(m, 3H), 4.98(d, 2H), 4.20(m, IH), 3.65(m, IH), 3.42(m, IH), 3.38(s, 2H), 3.10(dd, IH), 1.65(m, IH), 1.40(m, IH), 1.10(m, IH), 0.85(m, 6H)

Example 431 N-( 1 -Naphthy lmethyl)-N-benzylthiocarbamoyl-2(S)- { [ 1 -(4-cyanobenzyl)- 1 H-i midazol-5 -yl] acetyl } amino-3 (S)-methylpentylamine

1H-NMR (CDCb) : δ 7.05-7.90(m, 18H), 6.00(t, IH), 5.30(s, 2H), 5.20(m, IH), 5.05(dd, 2H), 4.80(d, 2H), 4.24(m, IH), 3.28(s, 2H), 3.15(dd, IH), 1.58(m, IH), 1.40(m, IH), 1.05(m, IH), 0.85(t, 6H)

Example 432

N-( 1 -Naphthylmethyl)-N-(3 -bromophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.10-7.95(m, 17H), 5.60(m, IH), 5.30(s, 2H), 5.10(m, 2H), 4.30(m, IH), 3.38(s, 2H), 3.20(dd, IH), 1.60(m, IH), 1.40(m, IH), 1.05(m, IH), 0.85(t, 6H)

Example 433

N-( 1 -Naphthylmethyl)-N-(n-butylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanobenzyl)- IH

-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : 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, IH), 1.60(m, IH), 1.42-1.55(m, 3H), 1.05-2.22(m, 3H), 0.85(m, 9H)

Example 434

N-( 1 -Naphthy lmethyl)-N-ethylthiocarbamoyl-2(S)- {[ 1 -(4-cy anobenzyl)- 1 H-imi dazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.05-7.95(m, 13H), 5.62(m, IH), 5.35(m, 2H), 5.00(m, 2H), 4.20(m, IH), 3.60(m, 2H), 3.35(s, 2H), 3.10(dd, IH), 1.60(m, IH), 1.40(m, IH), 1.10(m, IH), 1.04(t, 3H), 0.85(m, 6H) Example 435

N-( 1 -Naphthylmethyl)-N-(4-azidophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl} amino-3 (S)-methylpentylamine

^'H-NMR (CDCb) : δ 6.95-7.95(m, 17H), 5.04-5.42(m, 5H), 4.25(m, IH), 3.36(s, 2H), 3.18(dd, IH), 1.60(m, IH), 1.40(m, IH), 1.08(m, IH), 0.85(t, 6H)

Example 436

N-( 1 -Naphthylmethyl)-N-(4-bromophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobe nzyl)- 1 H-imidazol-5-yl]acetyl } amino-3 (S)-methylpentylamine

Η-NMR (CDCb) : δ 7.02-7.90(m, 17H), 5.04-5.48(m, 5H), 4.28(m, IH), 3.38(s, 2H), 3.20(tt, IH), 1.60(m, IH), 1.40(m, IH), 1.05(m, IH), 0.86(t, 6H)

Example 437

N-( 1 -Naphthylmethyl)-N-(2-chlorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanoben zyl)- 1 H-imidazol-5 -yl]acetyl} amino-3 (S)-methylpentylamine

^"H-NMR (CDCb) : δ 7.05-7.90(m, 17H), 5.08-5.46(m, 5H), 4.40(m, IH), 3.40(s, 2H), 3.22(tt, IH), 1.62(m, IH), 1.41(m, IH), 1.07(m, IH), 0.85(m, 6H)

Example 438

N-( 1 -Naphthy lmethyl)-N-methylthiocarbamoyl-2(S)- { [ 1 -(4-cyanobenzyl)- 1 H-i midazol-5 -yl]acetyl } amino-3 (S )-methy lpentylamine

-H-NMR (CDCb) : δ 7.00-7.95(m, 13H), 5.78(m, IH), 5.20-5.40(m, 2H), 5.00(m, 2H), 4.20(m, IH), 3.60(m, 2H), 3.34(s, 2H), 3.10(dd, IH), 3.00(d, 3H), 1.60(m, IH), 1.40(m, IH), 1.10(m, IH), 0.85(m, 6H)

Example 439

N-( 1 -Naphthylmethyl)-N-( 1 -naphthylthiocarbamoyl)-2(S )- { [ 1 -(4-cyanobenzyl)

- 1 H-imidazol-5-yl] acetyl } amino-3 (S )-methy lpentylamine

1H-NMR (CDCb) : δ 7.00-8.00(m, 20H), 5.55(dd, IH), 5.25(d, 2H), 5.20(d, 2H), 4.40(m, IH), 3.40(s, 2H), 3.25(dd, IH), 3.00(d, 3H), 1.60(m, IH), 1.40(m, IH), 1.10(m, IH), 0.85(t, 6H)

Example 440

N-( 1 -Naphthy lmethyl)-N-phenylethylthiocarbamoyl-2(S )- { [ 1 -(4-cy anobenzyl)- lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 6.80-7.95(m, 18H), 5.50(m, IH), 5.35(d, 2H), 4.80(d, 2H), 4.20(m, IH), 3.90(m, IH), 3.70(m, IH), 3.35(s, 2H), 3.05(dd, 3H), 2.70(m, 2H), 1.40(m, IH), 1.10(m, IH), 0.85(t, 6H)

Example 441

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

-H-NMR (CDCb) : δ 7.05-7.90(m, 18H), 6.20(m, IH), 5.40(d, 2H), 5.00(dd, 2H), 4.40(m, IH), 3.52(d, 2H), 3.05(m, 3H), 1.60(m, IH), 1.40(m, IH), 1.10(m, IH), 0.80(m, 6H)

Example 442

N-( 1 -Naphthylmethyl)-N-cyclohexylthiocarbamoyl-2(S)- { [ 1 -(4-cyanobenzyl)- 1

H-imidazol-5-yl] acetyl } amino-3 (S )-methylpentylamine Η-NMR (CDCb) : 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)- { [ l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.00-8.20(m, 19H), 5.20-5.60(m, 5H), 4.42(m, IH), 3.40(s, 2H), 3.25(dd, IH), 2.85(s, 6H), 1.60(m, IH), 1.40(m, IH), 1.05(m, IH), 0.84(t, 6H)

Example 444

N-( 1 -Naphthy lmethyl)-N-phenylthiocarbamoyl-2(S )-{[ 1 -(4-cyanobenzy 1)- 1 H-i midazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.05-7.95(m, 18H), 5.22-5.44(m, 3H), 5.10(dd, 2H), 4.30(m, IH), 3.38(s, 2H), 3.18(dd, IH), 1.60(m, IH), 1.40(m, IH), 1.10(m, IH), 0.85(t, 6H)

Example 445

N-( 1 -Naphthylmethyl)-N-(n-propylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanobenzyl)- 1

H-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.05-7.95(m, 13H), 5.60(t, IH), 5.20-5.38(m, 3H), 4.98(d, 2H), 4.25(m, IH), 3.60(m, IH), 3.42(m, IH), 3.38(s, 2H), 3.10(tt, IH), 1.60(m, IH), 1.42(q, 2H), 1.40(m, IH), 1.10(m, IH), 0.85(t, 6H). 0.70(t, 3H) Example 446

N-( 1 -Naphthylmethyl)-N-(3 -chlorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S)-methylpentylamine

^'H-NMR (CDCb) : δ 7.05-7.92(m, 17H), 5.00-5.55(m, 5H), 4.32(m, IH), 3.38(s, 2H), 3.18(tt, IH), 1.60(m, IH), 1.40(m, IH), 1.08(m, IH), 0.88(m, 6H)

Example 447

N-(l-Naphthylmethyl)-N-(2,4-dichlorophenylthiocarbamoyl)-2(S)-{[l-(4-cyan obenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR(CDCb) : δ 7.05-7.90(m, 16H), 5.05-5.45(m, 5H), 4.38(m, IH), 3.38(s, 2H), 3.20(tt, IH), 1.65(m, IH), 1.42(m, IH), 1.08(m, IH), 0.86(t, 6H)

Example 448

N-( 1 -Naphthylmethyl)-N-allylthiocarbamoyl-2(S)- { [ 1 -(4-nitrobenzyl)- 1 H-imid azol-5 -yl]acetyl } amino-3 -methylbutylamine

<Step 1>

N-(l-Naphmyhτ emyl)-2(S)-{[l-(4-mtrobenzyl)-lH-imidazol-5-yl]acetyl}amin o-3 -methylbutylamine

Using the same method as described in Preparative Example 3, N-t-butoxycarbonyl-L-valine was converted to N-(t-butoxycarbonyl)-L- valine aldehyde. And then the reaction was carried out under the same condition as described in Preparative Example 4 to give the title compound. TLC : R_f = 0.31 (CH₂C1₂ / MeOH = 10 / 1)

1H-NMR (CDCb) : 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, IH), 5.10(d, IH), 4.20(s, 2H), 3.70-3.90(m, IH), 3.00-3.30(dd, 2H), 2.85-3.00(m, IH), 2.65-2.83(m, 2H), 2.00(b, IH), 1.60-1.80(m, IH), 0.75-1.00(m, 6H)

<Step 2>

N-( 1 -Naphthylmethyl)-N-allylthiocarbamoyl-2(S)-{ [ l-(4-nitrobenzyl)- lH-imid azol-5-yl] acetyl } amino-3 -methylbutylamine

To a solution of N-(l-naphthylmethyl)-2(S)-{[l-(4-nitrobenzyl)-lH- imidazol-5-yl]acetyl}amino-3-methylbutylamine in dichloromethane (0.02M, lml, 0.02mmol) was added allylisothiocyanate (0.1M in CH2CI2, 0.2ml, 0.02mmol). The reaction mixture was agitated for 4hr at room temperature. The mixture was purified by silica gel column chromatography(eluent: CH2Cl2/MeOH=9/l, v/v) to give the title compound as a white solid.

^'H-NMR (CDCb) : δ 7.05-8.20(m, 13H), 5.70(m, 2H), 5.40(d, 2H), 5.20(m, IH), 4.22(m, 3H), 3.38(s, 2H), 3.10(dd, IH), 1.80(m, IH), 0.90(d, 6H)

Examples 449-463

N-( 1 -Naρhthylmethyl)-2(S)- { [ 1 -(4-nitrobenzyl)- lH-imidazol-5-yl]ace- tyl} amino-3 -methylbutylamine was reacted with the corresponding isothiocyanates under the same condition as described in <Step 2> of Example 448 to give the title compounds.

Example 449 N-( 1 -Naphthy lmethyl)-N-benzylthiocarbamoyl-2(S)- { [ 1 -(4-nitrobenzyl)- 1 H-im idazol-5 -yl] acetyl } amino-3 -methylbutylamine

^'H-NMR (CDCb) : δ 7.05-8.20(m, 18H), 6.00(t, IH), 5.20-5.38(m, 3H), 5.05(d, 2H), 4.82(d, 2H), 4.18(m, IH), 3.35(s, 2H), 3.17(dd, IH), 1.80(m, IH), 0.85(d, 6H)

Example 450

N-( 1 -Naphthylmethyl)-N-(2-bromophenylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrobenz yl)-lH-imidazol-5-yl]acetyl}amino-3-methylbutylamine

Η-NMR (CDCb) : δ 7.10-8.20(m, 17H), 5.05-5.45(m, 5H), 4.30(m, IH), 3.42(s, 2H), 3.20(dd, IH), 1.82(m, IH), 0.90(dd, 6H)

Example 451

N-( l-Naphthylmethyl)-N-(3-bromophenylthiocarbamoyl)-2(S)-{ [ 1 -(4-nitrobenz yl)- 1 H-imidazol-5 -yl]acetyl } amino-3 -methylbutylamine

^'H-NMR (CDCb) : δ 7.10-8.20(m, 17H), 5.25-5.42(m, 3H), 5.15(m, 2H), 4.20(m, IH), 3.40(s, 2H), 3.20(dd, IH), 1.85(m, IH), 0.90(dd, 6H)

Example 452

N-( 1 -Naphthylmethyl)-N-(n-butylthiocarbamoyl)-2(S)-{ [ 1 -(4-nitrobenzyl)- 1 H-i midazol-5 -yl] acetyl } amino-3 -methylbutylamine

1H-NMR (CDCb) : δ 7.05-8.20(m, 13H), 5.45(d, 2H), 5.22(m, IH), 4.96(d, 2H), 4.18(m, IH), 3.65(m, IH), 3.42(s, 2H), 3.40(s, 2H), 3.15(dd, IH), 1.80(m, IH), 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-nitrobenz y 1)- 1 H-imidazol-5 -yl]acetyl } amino-3 -methylbutylamine

-H-NMR(CDCb) : δ 7.05-8.20(m, 17H), 5.22-5.45(m, 3H), 5.10(d, 2H), 4.20(m, IH), 3.65(m, IH), 3.38(s, 2H), 1.82(m, IH), 0.85(dd, 6H)

Example 454

N-( 1 -Naphthylmethyl)-N-ethoxycarbonylthiocarbamoyl-2(S)- { [ 1 -(4-nitrobenzy

1)- 1 H-imidazol-5-yl] acetyl } amino-3 -methylbutylamine

^'H-NMR (CDCb) : δ 7.10-8.22(m, 13H), 6.20(d, IH), 5.18-5.45(m, 3H), 4.95(d, IH), 4.22(m, IH), 4.15(q, 2H), 3.70(s, 2H), 3.42(s, 2H), 3.08(dd, IH), 1.65(m, IH), 1.22(t, 2H), 0.75(t, 6H)

Example 455

N-( 1 -Naphthy lmethyl)-N-ethy lthiocarbamoyl-2(S)- { [ 1 -(4-nitrobenzyl)- 1 H-imid azol-5-yl] acetyl } amino-3 -methylbutylamine

-H-NMR (CDCb) : δ 7.05-7.95(m, 13H), 5.43(d, 2H), 5.20(m, IH), 4.97(d, 2H), 4.15(m, IH), 3.60(m, 2H), 3.40(s, 2H), 3.10(dd, IH), 1.78(m, IH), 1.00(t, 2H), 0.87(t, 6H)

Example 456

N-( 1 -Naphthylmethyl)-N-(2-fluorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrobenz yl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

1H-NMR (CDCb) : δ 6.98-8.18(m, 17H), 5.05-5.42(m, 5H), 4.25(m, IH), 3.43(s, 2H), 3.20(dd, IH), 1.80(m, IH), 0.90(t, 6H)

Example 457 N-( 1 -Naphthylmethyl)-N-(3 -fluorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrobenz yl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

¹ H-NMR (CDCb) : δ 6.85-8.18(m, 17H), 5.05-5.45(m, 5H), 4.20(m, IH), 3.40(s, 2H), 3.20(dd, IH), 1.85(m, IH), 0.90(d, 6H)

Example 458

N-( 1 -Naphthylmethyl)-N-(4-fluorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrobenz yl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

1H-NMR (CDCb) : δ 6.90-8.20(m, 17H), 5.20-5.42(m, 3H), 5.05(d, 2H), 4.20(m, IH), 3.38(s, 2H), 3.20(dd, IH), 1.82(m, IH), 0.87(m, 6H)

Example 459

N-( 1 -Naphthylmethyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrobe nzyl)- 1 H-imidazol-5-yl] acetylamino } -3 -methylbutylamine

-H-NMR (CDCb) : δ 6.80-8.20(m, 17H), 5.20-5.45(m, 3H), 5.05(d, 2H), 4.22(m, IH), 3.78(s, 3H), 3.40(s, 2H), 3.20(dd, IH), 1.82(m, IH), 0.87(d, 6H)

Example 460

N-( 1 -Naph11 ylmethyl)-N-methylthiocarbamoyl-2(S)- { [ 1 -(4-nitrobenzyl)- 1 H-im ida2:ol-5-yl]acetyl}amino-3-methylbutylamine

1H-NMR (CDCb) : δ 7.05-8.22(m, 13H), 5.15-5.45(m, 3H), 4.98(d, 2H), 4.18(m, IH), 3.44(s, 2H), 3.15(dd, IH), 3.08(s, d), 1.82(m, IH), 0.87(d, 6H)

Example 461 N-( 1 -Naphthy lmethyl)-N-( 1 -naphthy lthiocarbamoyl)-2(S )- { [ 1 -(4-nitrobenzyl)- 1 H-imidazol-5 -yl]acetyl } amino-3 -methylbutylamine

1H-NMR (CDCb) : δ 7.04-8.15(m, 20H), 5.18-5.60(m, 5H), 4.30(m, IH), 3.40(s, 2H), 3.22(dd, IH), 1.80(m, IH), 0.85(m, 6H)

Example 462

N-( 1 -Naphthy lmethyl)-N-phenylethylthiocarbamoyl-2(S)- { [ 1 -(4-nitrobenzyl)- 1

H-imidazol-5-yl]acetyl}amino-3-methylbutylamine

Η-NMR (CDCb) : δ 6.78-8.20(m, 18H), 5.45(m, IH), 5.40(d, 2H), 5.25(dd, 2H), 4.10(m, IH), 3.92(m, IH), 3.70(m, IH), 3.38(s, 2H), 3.10(dd, IH), 2.72(m, 2H), 1.80(m, IH), 0.90(d, 6H)

Example 463

N-( 1 -Naphthy lmethyl)-N-(3 -trifluoromethylphenylthiocarbamoyl)-2(S )- { [ 1 -(4- nitrobenzyl)- 1 H-imidazol-5-yl] acetyl } amino-3 -methylbutylamine

1H-NMR (CDCb) : δ 6.92-8.18(m, 17H), 5.55(d, IH), 5.30(d, 2H), 5.15(m, 2H), 4.22(m, IH), 3.40(s, 2H), 3.20(dd, IH), 1.84(m, IH), 0.95(t, 6H)

Example 464

N-( 1 -Naphthy lmethyl)-N-(3 -bromophenylthiocarbamoyl)-2- { [ 1 -(4-nitrobenzyl)

- 1 H-imidazol-5 -yl] acetyl } aminoethylamine

<Step 1>

N-( 1 -Naphthy lmethyl)-2- { [ 1 -(4-nitrobenzyl)- 1 H-imidazol-5 -yl]acetyl } aminoet hylamine Using the same method as described in Preparative Example 3, N-t-butoxycarbonyl-L-glycine was converted to N-(t-butoxycarbonyl)- L-glycine aldehyde. And then the reaction was carried out under the same condition as described in Preparative Example 4 to give the title compound.

TLC : R_f = 0.15 (CH₂C1₂ / MeOH = 5 / 1)

Η-NMR (CDCb) : δ 8.10(d, 3H), 7.65-7.95(m, 2H), 7.40-7.43(m, 5H), 7.08(d, 2H), 6.95(s, IH), 6.23(b, IH), 5.18(s, 2H), 4.23(s, 2H), 3.20-3.30(m, 4H), 2.80(t, 2H), 1.97-2.20(b, IH)

<Step 2>

N-( 1 -Naphthy lmethyl)-N-(3 -bromophenylthiocarbamoyl)-2- { [ 1 -(4-nitrobenzyl)

- 1 H-imidazol-5 -y 1] acetyl } aminoethylamine

To a solution of N-(l-naphthylmethyl)-2-{[l -(4-nitrobenzyl)- 1H- imidazol-5-yl]acetyl}aminoethylamine in dichloromethane (0.02M, 1ml, 0.02mmol) was added 3-bromophenylisothiocyanate (0.1M in CH2CI2, 0.2ml, 0.02mmol). The reaction mixture was agitated for 3hr at room temperature. The mixture was purified by silica gel column chromatography(eluent:

v/v) to give the title compound as a white solid.

Η-NMR (CDCb) : δ 7.00-8.20(m, 17H), 6.48(bs, IH), 5.50(s, 2H), 5.25(s, 2H), 3.80(t, 2H), 3.32(s, 2H), 3.00(t, 2H)

Examples 465-469

N-( l-Naphthylmethyl)-2(S)-{ [ 1 -(4-nitrobenzyl)- lH-imidazol-5-yl] acetyl} aminoethylamine was reacted with the corresponding isothiocyanates under the same condition as described in <Step 2> of Example 464 to give the title compounds.

Example 465

N-( 1 -Naphthylmethyl)-N-(4-chlorophenylthiocarbamoyl)-2- { [ 1 -(4-nitrobenzyl)

- 1 H-imidazol-5 -y 1] acetyl } aminoethylamine

^'H-NMR (CDCb) : δ 7.00-8.18(m, 17H), 6.60(bs, IH), 5.45(s, 2H), 5.23(s, 2H), 3.82(t, 2H), 3.35(s, 2H), 3.02(t, 2H)

Example 466

N-(l-Naphι ylmemyl)-N-(3-fluorophenylthiocarbamoyl)-2-{[l-(4-nitrobenzyl) - 1 H-imidazol-5-yl]acetyl} aminoethylamine

^'H-NMR (CDCb) : δ 6.85-8.40(m, 17H), 6.58(bs, IH), 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)

- 1 H-imidazol-5 -yl]acetyl } aminoethylamine

^'H-NMR (CDCb) : δ 7.00-8.15(m, 17H), 6.64(bs, IH), 5.42(s, 2H), 5.24(s, 2H), 3.85(t, 2H), 3.34(s, 2H), 3.10(t, 2H)

Example 468

N-( 1 -Naphthy lmethyl)-N-(4-methoxyphenylthiocarbamoyl)-2- { [ 1 -(4-nitrobenz yl)- lH-imidazol-5-yl]acetyl} aminoethylamine

-H-NMR (CDCb) : 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 -Naphthy lmethyl)-N-(3 -trifluoromethylphenylthiocarbamoyl)-2- { [ 1 -(4-nitr obenzyl)- 1 H-imidazol-5 -yl]acetyl } aminoethylamine

1H-NMR (CDCb) : δ 6.92-8.15(m, 17H), 6.42(bs, IH), 5.55(s, 2H), 5.28(s, 2H), 3.75(s, 2H), 2.98(t, 2H)

Example 470

N-( 1 -Naphthy lmethyl)-N-(3-bromophenylthiocarbamoyl)-2-{ [ 1 -(4-nitrobenzyl)

-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

<Step 1> 2-(t-Butoxycarbonyl)amino-2-methylpropionic acid

To a solution of 2-amino-2-methylpropionic acid (15.0 g, 146 mmol) in dioxane (290 ml) and water (145 ml) was added IN NaOH (146 ml) and then di-t-butyl pyrocarbonate (36.8 ml, 160 mmol) was added dropwise thereto at 0°C. The reaction mixture was stirred at room temperature for 30 min. The solution was concentrated in vacuo to the volume of about 200ml and cooled in an ice-water bath. After addition of ethyl acetate (300 ml), the mixture was acidified with an aqueous solution of potassium bisulfate to pH=2~3. The organic layer was washed with water, saturated sodium bicarbonate solution and brine, dried over MgSO₄ and concentrated in vacuo to give the title compound (25.1 g, 85 %) as a white solid.

1H-NMR (CDCb) : δ 9.40-10.60(bs, IH), 5.00-5.40(bs, IH), 1.58(s, 6H), 1.43(s, 9H) <Steρ 2> 2-(/-Butoxycarbonyl)amino-2-methylpropanol

To a solution of 2-(t-butoxycarbonyl)amino-2-methylpropionic acid (9.54 g, 47 mmol) in dry tetrahydrofuran (250ml) was added triethylamine (6.54 ml 47 mmol), and then ethylchloroformate (5.38 ml, 564 mmol) was added dropwise thereto while maintaining the temperature at 5°C. The reaction mixture was stirred at 5°C for 30min. The precipitate was filtered off. To the filtrate was added dropwise sodium borohydride (3.55 g, 94.0 mmol) in water (50 ml) at 0°C. The reaction mixture was stirred for lhr at room temperature and concentrated in vacuo. The residue was partitioned between 2N HCl (100 ml) and ethyl acetate (150 ml). The organic layer was washed with water, saturated sodium bicarbonate solution and brine, dried over MgSO₄ and concentrated in vacuo. The residue was purified by silica gel column chromatography(eluent: EtOAc/n-hexane=l/2, v/v) to give the title compound (7.10 g, 80 %) as a white solid.

TLC : Rf=0.38 (EtOAc / n-hexane = 1 / 2)

1H-NMR (CDCb) : δ 4.60-4.80(b, IH), 3.58(s, 2H), 1.43(s, 9H), 1.25(s,

6H)

<Step 3> 2-(t-Butoxycarbonyl)amino-2-methylpropione aldehyde

To a solution of oxalylchloride (4.39 ml, 50.3 mmol) in dichloromethane (90ml) was added a solution of dimethylsulfoxide (7.14 ml, 101 mmol) in dichloromethane (20 ml) dropwise for 5min at -60°C ~ -70°C. The reaction mixture was stirred for 30min. To the above solution was added a solution of 2-(t-butoxycarbonyl)amino-2-methyl- propanol (8.65 g, 457 mmol) in dichloromethane (40 ml) dropwise. The reaction mixture was stirred for lhr while maintaining the temperature at -60°C. To the reaction mixture was added triethylamine (31.9 ml, 229 mmol) dropwise. The mixture was stirred for lhr at room temperature. After the addition of dichloromethane (100 ml), the reaction mixture was washed with 5% HCl and saturated sodium bicarbonate solution, dried over MgSO₄ and concentrated in vacuo. The residue was purified by silica gel column chromatography(eluent: EtOAc/n-hexane=l/2, v/v) to give the title compound (7.96 g, 93 %) as a white solid.

^"H-NMR (CDCb) : δ 9.44(s, IH), 5.03(b, IH), 1.44(s, 9H), 1.33(s, 6H)

<Step 4>

N-( 1 -Naphthy lmethyl)-2- {[ 1 -(4-nitrobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-2

-methylpropylamine

The reaction was carried out under the same condition as described in Preparative Example 4, but replacing N-(t-butoxycarbonyl)- L-isoleucine aldehyde and 2,3-dichlorobenzylamine with 2-(t-butoxy- carbonyl)amino-2-methylpropion aldehyde and 1-naphthylmethylamine, respectively, to give the title compound.

TLC : R_f = 0.31 (CH₂C1₂ / MeOH = 9 / 1)

-H-NMR (CDCb) : 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, IH), 6.23(s, IH), 5.20(s, 2H), 4.20(s, 2H), 3.02(s, 2H), 2.62(s, 2H), 2.18(b, IH), 1.23(s, 6H)

<Steρ 5>

N-( 1 -Naphthy lmethyl)-N-(3 -bromophenylthiocarbamoyl)-2- { [ 1 -(4-nitrobenzyl)

- 1 H-imidazol-5 -yl]acetyl } amino-2-methylpropylamine To a solution of N-(l-naphthylmethyl)-2-{[l-(4-nitrobenzyl)-lH- imidazol-5-yl] acetyl }amino-2-methylpropylamine in dichloromethane (0.02M, 1ml, 0.02mmol) was added 3-bromophenylisothiocyanate (0.1M in CH2CI2, 0.2ml, 0.02mmol). The reaction mixture was agitated for 4hr at room temperature. The mixture was purified by silica gel column chromatography(eluent:

v/v) to give the title compound as a white solid.

'H-NMR (CDCb) : 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)

Examples 471-475

N-( 1 -Naphthylmethyl)-2- { [ 1 -(4-nitrobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-2-methylpropylamine was reacted with the corresponding isothiocyanates under the same condition as described in <Step 5> of Example 470 to give the title compounds.

Example 471

N-( 1 -Naphthy lmethyl)-N-(4-chlorophenylthiocarbamoyl)-2- { [ 1 -(4-nitrobenzyl)

-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR (CDCb) : 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)

- 1 H-imidazol-5 -yl]acetyl } amino-2-methylpropylamine 1H-NMR (CDCb) : 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 -fluorophenylthiocarbamoy l)-2- { [ 1 -(4-nitrobenzyl)

-1 H-imidazol-5 -yl] acetyl }amino-2-methylpropylamine

1H-NMR (CDCb) : 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-(l-Naphthylmethyl)-N-(4-fluoiOphenylthiocarbamoyl)-2-{ [l-(4-nitrobenzyl) - 1 H-imidazol-5 -yl] acetyl } amino-2-methylpropylamine

1H-NMR (CDCb) : 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-(l-Naphthylmethyl)-N-(4-methoxyphenylthiocaιbamoyl)-2-{[l-(4-nitrobenz yl)- 1 H-imidazol-5 -yl] acetyl} amino-2-methylpropylamine

1H-NMR (CDCb) : 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)- IH-im idazol-5-yl]acetyl}aminopentylamine

<Step 1> N-(l-Naphthylmethyl)-2(S)-{[l-(4-nitiObenzyl)-lH-imidazol-5-yl]acetyl}amin opentylamine

Using the same method as described in Preparative Example 3, N-t-butoxycarbonyl-L-norvaline was converted to N-t-butoxycarbonyl- L-norvaline aldehyde. And then the reaction was carried out under the same condition as described in Preparative Example 4 to give the title compound.

TLC : R_f = 0.39 (CH₂C1₂ / MeOH = 10 / 1)

^'H-NMR (CDCb) : a 8.14(m, 3H), 7.70-8.00(m, 2H), 7.37-7.62(m, 5H), 7.03(d, 2H), 6.92(s, IH), 5.8 l(d, IH), 5.10(dd, 2H), 4.20(s, 2H), 3.90-4.10(m, IH), 3.17(dd, 2H), 2.72(m, 2H), 1.82(s, IH), 1.30-1.50(m, 4H), 0.80-1.00(m, 3H)

<Step 2>

N-( 1 -Naphthylmethyl)-N-benzylthiocarbamoyl-2(S)- { [ 1 -(4-nitrobenzyl)- 1 H-im idazol-5-yl] acetyl } aminopentylamine

To a solution of N-(l-naphthylmethyl)-2(S)-{[l-(4-nitrobenzyl)-lH- imidazol-5-yl]acetyl}aminopentylamine in dichloromethane (0.02M, 1ml, 0.02mmol) was added benzylisothiocyanate (0.1M in CH2CI2, 0.2ml, 0.02mmol). The reaction mixture was agitated for 4hr at room temperature. The mixture was purified by silica gel column chromatography(eluent:

v/v) to give the title compound as a white solid.

1H-NMR (CDCb) : δ 7.00-8.20(m, 18H), 5.35(d, 2H), 5.20(m, IH), 5.02(m, 2H), 4.82(d, 2H), 4.24(m, IH), 3.25(s, 2H), 3.12(dd, IH), 1.40(m, 4H), 0.85 (t, 3H) Example 477-487

N-( l-Naphthylmethyl)-2(S)-{ [ 1 -(4-nitrobenzyl)- lH-imidazol-5-yl] acetyl }aminopentylamine was reacted with the corresponding isothiocyanates under the same condition as described in <Step 2> of Example 476 to give the title compounds.

Example 477

N-(l-Naphthylmethyl)-N-(2-bromophenylthiocarbamoyl)-2(S)-{[l-(4-nitrobenz y 1)- 1 H-imidazol-5 -yl] acetyl } aminop entylamine

1H-NMR (CDCb) : δ 7.05-8.18(m, 17H), 5.50(d, 2H), 5.35(s, 2H), 5.18(m, 2H), 4.40(m, IH), 3.40(s, 2H), 3.22(dd, IH), 1.44(m, 4H), 0.85 (t, 3H)

Example 478

N-(l-Naphthylmethyl)-N-(3-biOmophenylthiocarbamoyl)-2(S)-{[l-(4-nitrobenz yl)-lH-imidazol-5-yl]acetyl}aminopentylamine

Η-NMR (CDCb) : δ 7.05-8.20(m, 17H), 5.60(d, IH), 5.32(s, 2H), 5.08(d, IH), 4.82 (bs, IH), 4.25(m, IH), 3.38(s, 2H), 3.16(dd, IH), 1.42(m, 4H), 0.85 (t, 3H)

Example 479

N-( 1 -Naphthylmethyl)-N-(4-chlorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrobenz yl)-lH-imidazol-5-yl]acetyl}aminopentylamine

1H-NMR (CDCb) : δ 7.05-8.20(m, 17H), 5.34(d, 2H), 5.05-5.60(dd, 2H), 4.90 (bs, IH), 4.25(m, IH), 3.38(s, 2H), 3.20(dd, IH), 1.40(m, 4H), 0.84 (t, 3H) Example 480

N-( 1 -Naphthy lmethyl)-N-ethy lthiocarbamoy 1-2(S)- { [ 1 -(4-nitrobenzyl)- 1 H-imid azol-5 -yl] acetyl } aminopentylamine

^"H-NMR (CDCb) : δ 7.05-8.20(m, 13H), 5.40(d, 2H), 4.90-5.30(m, 3H), 4.20(m, IH), 3.58(m, 2H), 3.35(s, 2H), 3.05(dd, IH), 1.40(m, 4H), 1.05 (t, 3H), 0.84 (t, 3H)

Example 481

N-( 1 -Naphthylmethyl)-N-(2-fluorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrobenz yl)-lH-imidazol-5-yl]acetyl}aminopentylamine

1H-NMR (CDCb) : δ 7.00-8.18(m, 17H), 5.32(s, 2H), 5.00-5.52(m, 3H), 4.35 (bs, IH), 3.40(s, 2H), 3.20(dd, IH), 1.42(m, 4H), 0.86 (t, 3H)

Example 482

N-( 1 -Naphthylmethyl)-N-(3-fluorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrobenz yl)- 1 H-imidazol-5 -yl] acetyl } aminop entylamine

1H-NMR (CDCb) : δ 6.85-8.20(m, 17H), 5.58(d, 2H), 5.35(s, 2H), 5.10(d, IH), 4.90 (bs, IH), 4.25(m, IH), 3.38(s, 2H), 3.18(dd, IH), 1.42(m, 4H), 0.85 (t, 3H)

Example 483

N-( 1 -Naphthylmethyl)-N-(4-fluorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrobenz yl)- lH-imidazol-5-yl]acetyl} aminopentylamine

1H-NMR (CDCb) : δ 6.98-8.20(m, 17H), 5.35(s, 2H), 5.02-5.58(m, 2H), 4.95 (bs, IH), 4.25 (bs, IH), 3.35(s, 2H), 3.20(dd, IH), 1.42(m, 4H), 0.85 (t, 3H)

Example 484

N-( 1 -Naphthylmethyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrobe nzyl)-lH-imidazol-5-yl]acetyl}aminopentylamine

1H-NMR (CDCb) : δ 6.80-8.20(m, 17H), 5.45(m, IH), 5.38(d, 2H), 5.10(d, 2H), 4.30 (bs, IH), 3.38(s, 2H), 3.18(dd, IH), 1.40(m, 4H), 0.85 (t, 3H)

Example 485

N-( 1 -Naphthylmethyl)-N-methylthiocarbamoyl-2(S)- { [ 1 -(4-nitrobenzyl)- 1 H-im idazol-5-yl]acetyl}aminopentylamine

1H-NMR (CDCb) : δ 7.00-8.20(m, 13H), 5.40(d, 2H), 4.90-5.30(m, 3H), 4.20 (bs, IH), 3.35(s, 2H), 3.10(dd, IH), 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)-lH-imidazol-5-yl]acetyl}aminopentylamine

1H-NMR (CDCb) : δ 7.02-8.18(m, 17H), 5.72(d, IH), 5.30(s, 2H), 5.10(d, IH), 4.75 (bs, IH), 4.22 (bs, IH), 3.38(s, 2H), 3.16(dd, IH), 1.30-1.50(m, 4H), 0.88 (t, 3H)

Example 487

N-( l-Naphthylmethyl)-N-allylthiocarbamoyl-2(S)-{ [ 1 -(4-nitrobenzyl)- lH-imid azol-5 -yl]acetyl } aminopentylamine Η-NMR (CDCb) : δ 7.02-8.20(m, 13H), 5.78(m, IH), 5.40(d, 2H), 4.90-5.30(m, 5H), 4.22(m, 3H), 3.35(s, 2H), 3.10(dd, IH), 1.30-1.50(m, 4H), 0.88 (t, 3H)

Example 488

N-( 1 -Naphthylmethyl)-N-(2-bromophenylthiocarbamoyl)-2-{ [ 1 -(4-nitrobenzyl)

- 1 H-imidazol-5-yl]acetyl } amino-2-cyclohexylethylamine

<Step 1>

N-(l-Naphthylmethyl)-2-{[l-(4-nitiObenzyl)-lH-imidazol-5-yl]acetyl}amino-2

-cyclohexylethylamine

Using the same method as described in Preparative Example 3, N-t-butoxycarbonyl-2-amino-2-cyclohexylacetic acid was converted to N-(t-butoxycarbonyl)-2-amino-2-cyclohexylacetaldehyde. And then the reaction was carried out under the same condition as described in Preparative Example 4 to give the title compound.

<Step 2>

N-( 1 -Naphthylmethyl)-N-(2-bromophenylthiocarbamoyl)-2- { [ 1 -(4-nitrobenzyl)

-lH-imidazol-5-yl]acetyl}amino-2-cyclohexylethylamine

To a solution of N-(l-naphthylmethyl)-2-{[l-(4-nitrobenzyl)-lH- imidazol-5-yl]acetyl}amino-2-cyclohexylethylamine in dichloromethane (0.02M, 1ml, 0.02mmol) was added 2-bromophenylisothiocyanate (0.1M in CH₂CI₂, 0.2ml, 0.02mmol). The reaction mixture was agitated for 4hr at room temperature. The mixture was purified by silica gel column chromatography(eluent: CH2Cl2/MeOH=9/l, v/v) to give the title compound as a white solid. 1H-NMR (CDCb) : 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)- 1 H-imidazol-5-yl]acetyl } amino-2-cyclohexylethylamine was reacted with the conesponding isothiocyanates under the same condition as described in <Step 2> of Example 488 to give the title compounds.

Example 489

N-( 1 -Naphthy lmethyl)-N-(4-fluoropheny lthiocarbamoy l)-2- { [ 1 -(4-nitrob enzyl)

-lH-imidazol-5-yl]acetyl}amino-2-cyclohexylethylamine

^'H-NMR (CDCb) : 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-nitrobenz y 1)- 1 H-imidazol-5 -yl]acetyl } amino-2-cy clohexylethylamine

1H-NMR (CDCb) : 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)- IH-imida zol-5-yl]acetyl}amino-2-cyclohexylethylamine

^'H-NMR (CDCb) : 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)- 1 H-imidazol-5 -yl] a cetyl}amino-3(S)-methylpentylamine

<Step 1>

N-Benzyl-2(S)-{[l-(4-nitiObenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methy lpentylamine

Using the same method as described in Preparative Example 3, N-t-butoxycarbonyl-L-isoleucine was converted to N-(t-butoxycarbonyl)-L- isoleucine aldehyde. And then the reaction was ca ied out under the same condition as described in Preparative Example 4, but replacing 2,3-dichlorobenzylamine with benzylamine to give the title compound.

TLC : R_f = 0.20 (CH₂C1₂ / MeOH = 9/1)

Η-NMR (CDCb) : δ 7.00-8.20(m, 11H), 6.08(d, IH), 5.06(dd, 2H), 3.90(m, IH), 3.76(dd, 2H), 3.38(dd, 2H), 2.78(m, 3H), 1.48(m, IH), 1.26(m, IH), 1.04(m, IH), 0.85(m, 6H)

<Step 2>

N-Benzyl-N-benzylthiocarbamoyl-2(S)-{[l-(4-nitrobenzyl)-lH-imidazol-5-yl]a cetyl } amino-3 (S)-methylpentylamine

To a solution of N-benzyl-2(S)-{[l-(4-nitrobenzyl)-lH-imidazol- 5 -yl] acetyl} amino-3 (S)-methylpentylamine in dichloromethane (0.02M, 1ml, 0.02mmol) was added benzylisothiocyanate (0.1M in CH2CI2, 0.2ml, 0.02mmol). The reaction mixture was agitated for 3hr at room temperature. The mixture was purified by silica gel column chromatography(eluent:

v/v) to give the title compound as a white solid.

-H-NMR(CDCb) : δ 7.00-8.20(m, 16H), 5.80(t, IH), 5.20-5.40(m, 3H), 4.78(t, 2H), 4.55(s, 2H), 4.15(m, IH), 3.25(s, 2H), 3.18(dd, 2H), 1.62(m, IH), 1.45(m, IH), 1.05(m, IH), 0.90(t, 6H)

Example 493-508

N-Benzyl-2(S)-{[l-(4-nitiObenzyl)-lH-imidazol-5-yl]acetyl}amino- 3 (S)-methy lpentylamine was reacted with the conesponding isothiocyanates under the same condition as described in <Step 2> of Example 492 to give the title compounds.

Example 493

N-Benzyl-N-(2-bromophenylthiocarbamoyl)-2(S)-{ [ 1 -(4-nitrobenzyl)- 1 H-imid azol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.05-8.20(m, 15H), 5.30(m, 3H), 4.65-4.92(dd, 2H), 4.25(m, IH), 3.38(s, 2H), 3.22(dd, 2H), 1.65(m, IH), 1.45(m, IH), 1.05(m, IH), 0.90(t, 6H)

Example 494

N-Benzyl-N-(3-bromophenylthiocarbamoyl)-2(S)-{[l-(4-nitrobenzyl)-lH-imid azol-5-yl]acetyl}amino-3(S)-methylpentylamine

Η-NMR (CDCb) : δ 7.00-8.20(m, 15H), 5.35(d, 2H), 4.95-5.22(m, 2H), 4.60(d, IH), 4.20(m, IH), 3.35(s, 2H), 3.20(dd, 2H), 1.64(m, IH), 1.45(m, IH), 1.05(m, IH), 0.90(m, 6H)

Example 495 N-Benzyl-N-(4-chlorophenylthiocarbamoyl)-2(S)-{ [ 1 -(4-nitrobenzyl)- lH-imid azol-5-yl] acetyl } amino-3 (S )-methylp entylamine

1H-NMR (CDCb) : δ 7.05-8.18(m, 15H), 5.34(d, 2H), 5.20(m, IH), 4.60-4.95(dd, 2H), 4.18(m, IH), 3.34(s, 2H), 3.22(dd, 2H), 1.65(m, IH), 1.45(m, IH), 1.08(m, IH), 0.92(m, 6H)

Example 496

N-Benzyl-N-ethylthiocarbamoyl-2(S)-{[l-(4-nitrobenzyl)-lH-imidazol-5-yl]ac etyl } amino-3 (S)-methylpentylamine

1H-NMR (CDCb) : δ 7.02-8.20(m, 11H), 5.40(d, 2H), 5.20(m, IH), 4.52(s, 2H), 4.10(m, IH), 3.58(m, 2H), 3.32(s, 2H), 3.10(dd, 2H), 1.65(m, IH), 1.42(m, IH), 1.08(m, IH), 1.05(t, 3H), 0.95(m, 6H)

Example 497

N-Benzyl-N-(2-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-nitrobenzyl)-lH-imida zol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.05-8.20(m, 15H), 5.35(d, 2H), 5.20(m, IH), 4.62-4.95(dd, 2H), 4.22(m, IH), 3.35(s, 2H), 3.20(dd, 2H), 1.62(m, IH), 1.45(m, IH), 1.10(m, IH), 0.90(t, 6H)

Example 498

N-Benzyl-N-(3 -fluorophenylthiocarbamoy 1)-2(S )- { [ 1 -(4-nitrobenzyl)- 1 H-imida zol-5-yl]acetyl } amino-3 (S)-methylpentylamine

'H-NMR (CDCb) : δ 6.85-8.18(m, 15H), 5.38(d, 2H), 5.17(m, IH), 4.58-4.98(dd, 2H), 4.20(m, IH), 3.34(s, 2H), 3.22(dd, 2H), 1.60(m, IH), 1.43(m, IH), 1.08(m, IH), 0.90(m, 6H) Example 499

N-Benzyl-N-(4-fluorophenylthiocarbamoyl)-2(S)-{ [ 1 -(4-nitrobenzyl)- IH-imida zol-5-yl]acetyl}amino-3(S)-methylpentylamine

^"H-NMR (CDCb) : δ 6.95-8.20(m, 15H), 5.35(d, 2H), 5.20(t, IH), 4.60-4.95(dd, 2H), 4.20(m, IH), 3.35(s, 2H), 3.20(dd, 2H), 1.60(m, IH), 1.44(m, IH), 1.06(m, IH), 0.92(m, 6H)

Example 500

N-Benzyl-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l -(4-nitrobenzyl)- IH-im idazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 6.84-8.20(m, 15H), 5.36(d, 2H), 5.22(m, IH), 4.60-4.88(dd, 2H), 4.18(m, IH), 3.80(s, 3H), 3.38(s, 2H), 3.20(dd, 2H), 1.62(m, IH), 1.45(m, IH), 1.06(m, IH), 0.92(t, 6H)

Example 501

N-Benzyl-N-methylthiocarbamoyl-2(S)-{ [ 1 -(4-nitrobenzyl)- lH-imidazol-5-yl]a cetyl}amino-3(S)-methylpentylamine

Η-NMR (CDCb) : δ 7.00-8.20(m, 11H), 5.72(t, IH), 5.40(d, 2H), 5.18(t, IH), 4.52(d, 2H), 4.15(m, IH), 3.32(s, 2H), 3.12(dd, IH), 3.08(d, 3H), 1.62(m, IH), 1.44(m, IH), 1.04(m, IH), 0.95(t, 6H)

Example 502

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

1H-NMR (CDCb) : δ 6.90-8.18(m, 15H), 5.35(d, 2H), 5.08(m, IH), 4.60-5.12(dd, 2H), 4.20(m, IH), 3.35(s, 2H), 3.24(dd, IH), 1.65(m, IH), 1.45(m, IH), 1.02(m, IH), 0.95(m, 6H)

Example 503

N-Benzyl-N-allythiocarbamoyl-2(S)-{[l -(4-nitrobenzyl)- lH-imidazol-5-yl]acet yl } amino-3 (S)-methylpentylamine

1H-NMR (CDCb) : δ 7.00-8.20(m, 11H), 5.60(m, IH), 5.05-5.42(m, 2H), 4.95(m, IH), 4.52(s, 2H), 4.18(m, 2H), 3.27(s, 2H), 3.08(dd, IH), 1.38-1.65(m, 2H), 1.05(m, IH), 0.82(m, 6H)

Example 504

N-Benzyl-N-( 1 -naphthylthiocarbamoyl)-2(S)-{ [ 1 -(4-nitrobenzyl)- lH-imidazol-

5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.00-8.15(m, 18H), 5.28(m, 4H), 4.85(q, IH), 4.24(m, IH), 3.35(s, 2H), 3.10(dd, IH), 1.35-1.60(m, 2H), 1.05(m, IH), 0.88(m, 6H)

Example 505

N-Benzyl-N-phenylethylthiocarbamoyl-2(S)-{ [ 1 -(4-nitrobenzyl)- lH-imidazol-

5 -yl] acetyl } amino-3 (S)-methylpentylamine

Η-NMR CDCb) : δ 6.90-8.20(m, 16H), 5.04-5.55(m, 5H), 4.38(s, 2H), 4.12(m, IH), 3.90(m, IH), 3.72(m, IH), 3.25(s, 2H), 3.04(dd, IH), 2.72(t, 2H), 1.38-1.62(m, 2H), 1.02(m, IH), 0.84(m, 6H)

Example 506

N-Benzyl-N-(n-butylthiocarbamoyl)-2(S)-{[l -(4-nitrobenzyl)- lH-imidazol-5-yl

] acetyl } amino-3 (S )-methylpentylamine 1H-NMR (CDCb) : δ 7.02-8.20(m, 11H), 5.18-5.52(m, 5H), 4.46(s, 2H), 4.08(m, IH), 3.62(m, IH), 3.42(m, IH), 3.35(s, 2H), 3.10(dd, IH), 1.38-1.62(m, 2H), 1.35(m, 2H), 1.05(m, 2H), 0.90(m, 6H), 0.82(t, 3H)

Example 507

N-Benzyl-N-cyclohexylthiocaιbamoyl-2(S)-{ [ 1 -(4-nitiObenzyl)- lH-imidazol-5

-yl] acetyl } amino-3 (S )-methy lpentylamine

Η-NMR (CDCb) : 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, IH), 0.92-1.73(m, 13H), 0.85(m, 6H)

Example 508

N-Benzyl-N-phenylthiocarbamoyl-2(S)-{[l-(4-nitiObenzyl)-lH-imidazol-5-yl]a cetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : 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, IH), 0.35-0.60(m, 2H), 1.03(m, IH), 0.92(m, 6H)

Example 509

N-(Thiophen-2-ylmethyl)-N-benzylthiocarbamoyl-2(S)-{[l-(4-nitrobenzyl)-lH

-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

<Step 1>

N-(Thiophen-2-ylmethyl)-2(S)- {[ 1 -(4-nitrobenzyl)- 1 H-imidazol-5 -yl] acetyl} a mino-3 (S)-methylpentylamine

Using the same method as described in Preparative Example 3, N-t-butoxycarbonyl-L-isoleucine was converted to N-(t-butoxycarbonyl)-L- isoleucine aldehyde. And then the reaction was canied out under the same condition as described in Preparative Example 4, but replacing 2,3-dichlorobenzylamine with thiophen-2-ylmethylamine to give the title compound.

TLC : Rf = 0.20 (CH₂C1₂ / MeOH = 10 / 1)

Η-NMR (CDCb) : δ 8.20(d, 2H), 7.59(s, IH), 7.15-7.40(m, 3H), 7.08(s, IH), 6.84-7.00(m, 2H), 5.70-6.03(m, IH), 5.34(s, 2H), 3.80-4.15(m, 3H), 3.38(s, 2H), 2.60-2.80(m, 2H), 1.82(bs, IH), 1.22-1.65(m, 2H), 0.97-1.22(m, IH), 0.75-0.95(m, 6H)

<Step 2>

N-(Thiophen-2-ylmethyl)-N-benzylthiocarbamoyl-2(S)- { [ 1 -(4-nitrobenzyl)- IH

-imidazol-5-yl]acetyl } amino-3 (S)-methylpentylamine

To a solution of N-(thiophen-2-ylmethyl)-2(S)-{[l-(4-nitrobenzyl)- lH-imidazol- 5-yl]acetyl}amino-3(S)-methylpentylamine in dichloromethane (0.02M, 1ml, 0.02mmol) was added benzylisothiocyanate (0.1M in CH₂C1₂, 0.2ml, 0.02mmol). The reaction mixture was agitated for 4hr at room temperature. The mixture was purified by silica gel column chromatography(eluent: CH₂Cl2/MeOH=9/l, v/v) to give the title compound as a white solid.

1H-NMR (CDCb) : δ 6.84-8.20(m, 14H), 6.18-6.35(tt, IH), 5.35(d, 2H), 5.00(m, IH), 4.60-4.82(m, 4H), 4.18(m, IH), 3.25(s, 2H), 3.20(dd, IH), 1.38-1.62(m, 2H), 1.05(m, IH), 0.95(d, 6H)

Examples 510-520

N-(Thiophen-2-ylmethyl)-2(S)-{[l-(4-nitrobenzyl)-lH-imidazol-5-yl] acetyl} amino-3 (S)-methylpentylamine was reacted with the conesponding isothiocyanates under the same condition as described in <Step 2> of Example 509 to give the title compounds.

Example 510

N-(Thiophen-2-ylmethyl)-N-(2-bromophenylthiocarbamoyl)-2(S)-{ [ 1 -(4-nitrob enzyl)- 1 H-imidazol-5-yl]acetyl } amino-3 (S)-methy lpentylamine

1H-NMR (CDCb) : δ 7.00-8.18(m, 13H), 5.35(d, 2H), 5.02-5.20(m, 2H), 4.80(d, IH), 4.32(m, IH), 3.38(s, 2H), 3.32(dd, IH), 1.40-1.62(m, 2H), 1.10(m, IH), 0.97(d, 6H)

Example 511

N-(Thiophen-2-ylmethyl)-N-(3-bromophenylthiocarbamoyl)-2(S)-{ [ 1 -(4-nitrob enzyl)- lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

-H-NMR (CDCb) : δ 7.05-8.18(m, 13H), 6.58,6.82(dd, IH), 5.35(s, 2H), 4.63-4.88(m, 3H), 4.18(m, IH), 3.36(s, 2H), 3.25(dd, IH), 1.35-1.60(m, 2H), 1.12(m, IH), 0.98(m, 6H)

Example 512

N-(Thiophen-2-ylmethyl)-N-(4-chlorophenylthiocarbamoyl)-2(S)-{[l -(4-nitrob enzyl)- lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

Η-NMR (CDCb) : δ 7.02-8.20(m, 13H), 5.18-5.42(m, 3H), 4.75(m, 2H), 4.20(m, IH), 3.38(s, 2H), 3.28(dd, IH), 1.35-1.60(m, 2H), 1.10(m, IH), 0.98(m, 6H)

Example 513

N-(Thiophen-2-ylmethyl)-N-ethylthiocarbamoyl-2(S)- { [ 1 -(4-nitrobenzyl)- 1 H-i midazol-5-yl]acetyl}amino-3(S)-methylpentylamine

-H-NMR (CDCb) : δ 6.90-8.22(m, 9H), 5.86-6.05(tt, IH), 5.40(m, 2H), 4.58-5.00(m, 3H), 4.16(m, IH), 3.65(m, 2H), 3.34(s, 2H), 3.20(dd, IH), 1.42-1.65(m, 2H), 1.16(m, 3H), 1.14(m, IH), 0.97(m, 6H)

Example 514

N-(Thiophen-2-ylmethyl)-N-(2-fluorophenylthiocarbamoyl)-2(S)- {[ 1 -(4-nitrob enzyl)- 1 H-imidazol-5-yl]acetyl } amino-3 (S)-methylpentylamine

-H-NMR (CDCb) : δ 7.02-8.20(m, 13H), 5.36(d, 2H), 5.00-5.22(m, 2H), 4.80(d, IH), 4.28(m, IH), 3.40(s, 2H), 3.32(dd, IH), 1.35-1.64(m, 2H), 1.14(m, IH), 0.97(d, 6H)

Example 515

N-(Thiophen-2-ylmethyl)-N-(3-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-nitrob enzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

Η-NMR (CDCb) : δ 7.00-8.20(m, 13H), 5.35(d, 2H), 4.84-5.22(m, 2H), 4.70(d, IH), 4.20(m, IH), 3.38(s, 2H), 3.26(dd, IH), 1.32-1.65(m, 2H), 1.12(m, IH), 0.98(m, 6H)

Example 516

N-(Thiophen-2-ylmethyl)-N-(4-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-nitrob enzyl)- 1 H-imidazol-5-yl]acetyl } amino-3 (S)-methylpentylamine

1H-NMR (CDCb) : δ 7.00-8.20(m, 13H), 5.36(m, 2H), 4.90-5.22(m, 2H), 4.72(d, IH), 4.20(m, IH), 3.38(s, 2H), 3.24(dd, IH), 1.32-1.65(m, 2H), 1.12(m, IH), 0.98(m, 6H) Example 517

N-(Thiophen-2-ylmethyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-nitr obenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 6.85-8.20(m, 13H), 5.38(m, 2H), 4.85-5.25(m, 2H), 4.75(d, IH), 4.20(m, IH), 3.80(s, 3H), 3.38(s, 2H), 3.26(dd, IH), 1.40-1.65(m, 2H), 1.15(m, IH), 0.98(d, 6H)

Example 518

N-(Thiophen-2-ylmethyl)-N-methylthiocarbamoyl-2(S)-{[l-(4-nitrobenzyl)-lH

-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 6.90-8.20(m, 9H), 6.06-6.30(tt, IH), 5.40(m, 2H), 4.85(m, 2H), 4.58(dd, IH), 4.10(m, IH), 3.32(s, 2H), 3.22(dd, IH), 3.08(d, 3H), 1.38-1.65(m, 2H), 1.12(m, IH), 0.94(d, 6H)

Example 519

N-(Thiophen-2-ylmethyl)-N-(3-trifluoromethylphenylthiocarbamoyl)-2(S)-{[l-

(4-nitrobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

-H-NMR (CDCb) : δ 7.02-8.18(m, 13H), 5.20-5.58(m, 3H), 4.70(d, 2H), 4.18(m, IH), 3.38(s, 2H), 3.28(d, IH), 1.35-1.60(m, 2H), 1.10(m, IH), 0.96(m, 6H)

Example 520

N-(Thiophen-2-ylmethyl)-N-allylthiocarbamoyl-2(S)-{[l-(4-nitrobenzyl)-lH-i midazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 6.85-8.22(m, 9H), 5.88-6.15(tt, IH), 5.38(d, 2H), 4.85-5.10(m, 2H), 4.62(t, IH), 4.20(m, 2H), 3.35(s, 2H), 3.22(dd, IH), 1.35-1.60(m, 2H), 1.10(m, IH), 0.95(d, 6H)

Example 521

N-[2-(Thiophen-2-yl)ethyl]-N-benzylthiocarbamoyl-2(S)-{[l-(4-nitrobenzyl)-l H-imidazol-5 -yl] acetyl} amino-3 (S)-methylpentylamine

<Step 1>

N-[2-(Thiophen-2-yl)ethyl]-2(S)-{[l-(4-nitrobenzyl)-lH-imidazol-5-yl]acetyl} amino-3 (S)-methylpentylamine

Using the same method as described in Preparative Example 3, N-t-butoxycarbonyl-L-isoleucine was converted to N-(/-butoxycarbonyl)-L- isoleucine aldehyde. And then the reaction was canied out under the same condition as described in Preparative Example 4, but replacing 2,3-dichlorobenzylamine with 2-(thiophen-2-yl)ethylamine to give the title compound.

TLC : Rf = 0.20 (CH₂C1₂ / MeOH = 10 / 1)

-H-NMR (CDCB) : δ 8.20(d, 2H), 7.59(s, IH), 7.15-7.40(m, 3H), 7.08(s, IH), 6.84-7.00(m, 2H), 5.70-6.03(m, IH), 5.34(s, 2H), 3.80-4.15(m, 3H), 3.38(s, 2H), 2.60-2.80(m, 2H), 1.82 (bs, IH), 1.22-1.65(m, 2H), 0.97-1.22(m, IH), 0.75-0.95(m, 6H)

<Step 2>

N-[2-(Thiophen-2-yl)ethyl]-N-benzylthiocarbamoyl-2(S)-{[l-(4-nitrobenzyl)-l

H-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

To a solution of N-[2-(Thiophen-2-yl)ethyl]-2(S)-{[l-(4-nitrobenzyl) -lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine in dichloromethane (0.02M, 1ml, 0.02mmol) was added benzylisothiocyanate (0.1M in CH2CI2, 0.2ml, 0.02mmol). The reaction mixture was agitated for 4hr at room temperature. The mixture was purified by silica gel column chromatography(eluent: CH₂Cl2/MeOH=9/l, v/v) to give the title compound as a white solid.

1H-NMR (CDCb) : δ 6.75-8.20(m, 14H), 5.25(d, 2H), 4.95 (bs, IH), 4.20(m, IH), 4.05(m, IH), 3.64 (bs, IH), 3.25-3.34 (bs, 4H), 3.20(dd, IH), 1.30-1.70(m, 2H), 1.10(m, IH), 0.90(m, 6H)

Examples 522-525

N-[2-(Thiophen-2-yl)ethyl]-2(S)-{[l-(4-nitrobenzyl)-lH-imidazol-5-yl] acetyl} amino-3 (S)-methylpentylamine was reacted with the conesponding isothiocyanates under the same condition as described in <Step 2> of Example 521 to give the title compounds.

Example 522

N-[2-(Thiophen-2-yl)efhyl]-N-(4-chlorophenylthiocarbamoyl)-2(S)-{[l-(4-nitro b enzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methy lpentylamine

-H-NMR (CDCb) : δ 6.85-8.15(m, 13H), 5.30(dd, 2H), 4.86 (bs, IH), 4.16(m, IH), 3.95 (bs, IH), 3.60(m, IH), 3.28(s, 2H), 3.18(m, 2H), 3.05(dd, IH), 1.30-1.70(m, 2H), 1.10(m, IH), 0.90(m, 6H)

Example 523

N-[2-(Thiophen-2-yl)ethyl]-N-ethylthiocarbamoyl-2(S)-{ [ 1 -(4-nitrobenzyl)- IH

-imidazol-5 -yl]acetyl } amino-3 (S)-methylpentylamine

1H-NMR (CDCb) : δ 6.80-8.20(m, 9H), 5.40(m, 2H), 4.95 (bs, IH), 4.08(m, IH), 3.35-3.80(m, 4H), 3.26(s, 2H), 2.98(m, 2H), 2.86(dd, IH), 1.30-1.70(m, 2H), 1.10(m, IH), 0.90(m, 6H)

Example 524

N-[2-(Thiophen-2-yl)ethyl]-N-(3-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-nitro benzyl)- lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

Η-NMR (CDCb) : δ 6.85-8.10(m, 13H), 5.30(d, 2H), 5.22 (bs, IH), 4.80 (bs, IH), 4.18(m, 2H), 4.02(m, IH), 3.55(m, IH), 3.30(s, 2H), 3.18(m, 2H), 3.05(dd, IH), 1.30-1.70(m, 2H), 1.05(m, IH), 0.92(m, 6H)

Example 525

N-[2-(Thiophen-2-yl)ethyl]-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-ni tiObenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 6.85-8.20(m, 13H), 5.35(m, 2H), 5.00 (bs, IH), 4.15(m, IH), 3.95(m, IH), 3.65(m, IH), 3.28(s, 2H), 3.18(m, 2H), 3.02(dd, IH), 1.30-1.70(m, 2H), 1.05(m, IH), 0.92(m, 6H)

Example 526

N-(2-Trifluoromethylbenzyl)-N-benzylthiocarbamoyl-2(S)- { [ 1 -(4-cyanobenzyl

)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methy lpentylamine

<Step 1>

N-(2-Trifluoromethylbenzyl)-2(S)-{[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acety 1 } amino-3 (S)-methylpentylamine

Using the same method as described in Preparative Example 3, N-t-butoxycarbonyl-L-isoleucine was converted to N-t-butoxycarbonyl-L- isoleucine aldehyde. And then the reaction was canied out under the same condition as described in Preparative Example 4, but replacing 2,3-dichlorobenzylamine and l-(4-nitrobenzyl)-lH-imidazol-5-ylacetic acid hydrochloride with 2-trifluoromethylbenzylamine and l-(4-cyanobenzyl)-lH -imidazol-5 -ylacetic acid hydrochloride, respectively, to give the title compound.

TLC : R_f = 0.40 (CH₂C1₂ / MeOH = 10 / 1)

1H-NMR (CDCb) : δ 7.6(m, 3H), 7.5(m, 3H), 7.4(m, IH), 7.1(d, 2H), 7.0(s, IH), 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

)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

To a solution of N-(2-trifluoromethylbenzyl)-2(S)-{ [1 -(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine in dichloro methane (0.02M, 1ml, 0.02mmol) was added benzylisothiocyanate (0.1M in CH2CI2, 0.2ml, 0.02mmol). The reaction mixture was agitated for 4hr at room temperature. The mixture was purified by silica gel column chromatography(eluent: CH2Cb/MeOH=9/l, v/v) to give the title compound as a white solid.

1H-NMR (CDCb) : δ 7.00-7.68(m, 15H), 5.28(d, 2H), 4.62-5.18(m, 5H), 4.12(m, IH), 3.24(s, 2H), 3.05(dd, IH), 1.38-1.70 (bs, 2H), 1.06(m, IH), 0.88(m, 6H)

Examples 527-580

N-(2-Trifluoromethylbenzyl)-2(S)-{[l-(4-cyanobenzyl)-lH-imidazol-5- yl] acetyl} amino-3 (S)-methylpentylamine was reacted with the conesponding isothiocyanates under the same condition as described in <Step 2> of Example 526 to give the title compounds.

Example 527

N-(2-Trifluoromethylbenzyl)-N-(2-biOmophenylthiocarbamoyl)-2(S)-{ [ 1 -(4-cy anobenzyl)- lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

^'H-NMR (CDCb) : δ 7.00-7.75(m, 14H), 5.25(d, 2H), 4.98-5.35 (bs, 2H), 4.86(d, IH), 4.23(m, IH), 3.35(d, 2H), 3.16(dd, IH), 1.35-1.65 (bs, 2H), 1.04(m, IH), 0.90(m, 6H)

Example 528

N-(2-Trifluoromethylbenzyl)-N-(3-bromophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 6.88-7.70(m, 14H), 5.52 (bs, IH), 5.22(s, 2H), 4.78(dd, 2H), 4.15(m, IH), 3.35(s, 2H), 3.10(dd, IH), 1.35-1.65 (bs, 2H), 1.04(m, IH), 0.92(m, 6H)

Example 529

N-(2-Trifluoromethylbenzyl)-N-(4-chlorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- 1 H-imidazol-5-yl]acetyl } amino-3 (S)-methylpentylamine

1H-NMR (CDCb) : δ 6.88-7.70(m, 14H), 5.45 (bs, IH), 5.25(d, 2H), 4.80(dd, 2H), 4.18(m, IH), 3.32(s, 2H), 3.13(dd, IH), 1.30-1.68 (bs, 2H), 1.02(m, IH), 0.86(m, 6H)

Example 530

N-(2-Trifluoromethylbenzyl)-N-ethylthiocarbamoyl-2(S)-{[l-(4-cyanobenzyl)- 1 H-imidazol-5-yl]acetyl } amino-3 (S )-methylpenty lamine Η-NMR (CDCb) : δ 6.95-7.78(m, 10H), 5.45 (bs, IH), 5.84-6.02 (bs,

IH), 5.36(dd, 2H), 5.02 (bs, IH), 4.64-4.95(dd, 2H), 4.08(m, IH),

3.60(m, 2H), 3.35(s, 2H), 3.04(dd, IH), 1.30-1.70 (bs, 2H), 1.03(m, 2H), 0.85(m, 6H)

Example 531

N-(2-Trifluoromethylbenzyl)-N-(2-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 6.88-7.75(m, 14H), 5.25(d, 2H), 4.98-5.24 (bs, 2H), 4.64(d, IH), 4.20(m, IH), 3.35(s, 2H), 3.12(dd, IH), 1.30-1.70 (bs, 2H), 1.05(m, IH), 0.85(m, 6H)

Example 532

N-(2-Trifluoromethylbenzyl)-N-(3-fluorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

^'H-NMR (CDCb) : δ 6.80-7.80(m, 14H), 5.44 (bs, IH), 5.24(s, 2H), 4.83(dd, 2H), 4.17(m, IH), 3.37(s, 2H), 3.14(dd, IH), 1.30-1.70 (bs, 2H), 1.05(m, IH), 0.85(m, 6H)

Example 533

N-(2-Trifluoromethylbenzyl)-N-(4-fluoiOphenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

^'H-NMR (CDCb) : δ 7.00-7.75(m, 14H), 5.38 (bs, IH), 5.25(m, 2H), 4.75-5.02 (bs, 2H), 4.15(m, IH), 3.35(s, 2H), 3.12(dd, IH), 1.30-1.75 (bs, 2H), 1.05(m, IH), 0.90(m, 6H) Example 534

N-(2-Trifluoromethylbenzyl)-N-methylthiocarbamoyl-2(S)- { [ 1 -(4-cyanobenzyl

)- 1 H-imidazol-5-yl] acetyl } amino-3 (S )-methy lpentylamine

^'H-NMR (CDCb) : £ 6.85-7.75(m, 10H), 6.25-6.44 (bs, IH), 5.35(d, 2H), 4.80-5.10 (bs, 2H), 4.63(dd, IH), 4.08(m, IH), 3.32(s, 2H), 3.08(s, 3H), 3.00(dd, IH), 1.30-1.75 (bs, 2H), 1.05(m, IH), 0.88(m, 6H)

Example 535

N-(2-Trifluoromethylbenzyl)-N-(3-trifluoromethylphenylthiocarbamoyl)-2(S)-{

[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

^'H-NMR (CDCb) : δ 6.90-7.75(m, 14H), 5.62 (bs, IH), 5.25(s, 2H), 4.78(dd, 2H), 4.13(m, IH), 3.32(s, 2H), 3.14(dd, IH), 1.30-1.75 (bs, 2H), 1.05(m, IH), 0.90(m, 6H)

Example 536

N-(2-Trifluoromethylbenzyl)-N-allylthiocarbamoyl-2(S)-{ [ 1 -(4-cyanobenzyl)- 1

H-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : δ 7.00-7.75(m, 10H), 6.00-6.20 (bs, IH), 5.78(m,

IH), 5.35(dd, 2H), 5.05(d, 2H), 4.62-4.95(dd, 2H), 4.24(m, IH), 4.15(m,

IH), 3.30(s, 2H), 3.08(dd, IH), 1.30-1.70(m, 2H), 1.05(m, IH), 0.86(m, 6H)

Example 537

N-(2-Trifluoromethylbenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4- cy anobenzyl)- 1 H-imidazol-5-yl] acetyl } amino-3 (S )-methylpentylamine

Η-NMR (CDCb) : δ 7.8(d, IH), 7.6(d, 2H), 7.5(m, 2H), 7.3(m, 2H), 7.1(s, IH), 6.9(d, 2H), 5.3(m, 2H), 4.9(d, 2H), 4.2(m, IH), 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-(t-butylthiocarbamoyl-2(S)- {[ 1 -(4-cyanobenzy

1)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methy lpentylamine

^'H-NMR (CDCb) : δ 7.00-7.78(m, 10H), 5.32(m, 3H), 4.68 (bs, 2H), 4.10(m, IH), 3.35(s, 2H), 3.02(dd, IH), 1.30-1.70(m, 2H), 1.05(m, IH), 0.88(m, 6H)

Example 539

N-(2-Trifluoromethylbenzyl)-N-(l-adamantylthiocarbamoyl)-2(S)-{[l-(4-cyan obenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

^'H-NMR(CDCb) : 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, IH), 5.12(d, IH), 4.70(s, 2H), 4.10(m, IH), 3.35(s, 2H)2.95(dd, IH), 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-cya nobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR(CDCb) : δ 7.73(d, IH), 7.60(d, 4H), 7.45(d, IH), 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, IH), 3.40(s, 2H), 3.12(dd, IH), 1.65(m, IH), 1.00-1.50(m, 2H), 0.90(t, 6H)

Example 541 N-(2-Trifluoromethylbenzyl)-N-(2-biphenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)- 1 H-imidazol-5-yl]acetyl } amino-3 (S)-methylpentylamine

^'H-NMR(CDCb) : δ 7.50-7.65(m, 5H), 7.20-7.40(m, 9H), 7.15(m, 3H), 7.05(s, IH), 6.85(m, IH), 6.00(s, IH), 5.25(s, 2H), 4.65(m, 2H), 4.10(m, IH), 3.38(s, 2H), 3.00(dd, IH), 1.60(m, IH), 0.95-1.45(m, 2H), 0.85(m, 6H)

Example 542

N-(2-Trifluoromethylbenzyl)-N-(n-butylthiocarbamoyl)-2(S)-{[l-(4-cyanobenz yl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

^'H-NMR(CDCb) : δ 7.75(s, IH), 7.65(d, 3H), 7.40-7.55(m, 2H), 7.20(d, 3H), 7.05(s, IH), 5.90-6.20(m, 2H), 5.40(m,2H), 4.90-5.10(m, 2H), 4.65(m, IH), 4.10(m, IH), 3.40-3.70(m, 2H), 3.20(s, 2H), 3.05(dd, IH), 1.62(m, IH), 1.45(m, 3H), 1.30(m, IH), 1.15(m, 3H), 0.85(m, 6H), 0.80(m, 3H)

Example 543

N-(2-Trifluoromethylbenzyl)-N-(t-butylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanobenz yl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

^'H-NMR(CDCb) : δ 7.75(s, IH), 7.65(d, 2H), 7.54(s, IH), 7.40-7.50(m, 3H), 7.20(d, 2H), 7.05(s, IH), 5.20-5.40(m, 4H), 4.70(m, 2H), 4.65(m, IH), 4.10(m, IH), 3.35(s, 2H), 3.00(dd, IH), 1.40-1.62(m, 2H), 1.35(s, 9H), 1.10(m, IH), 0.85(m, 6H)

Example 544

N-(2-Trifluoromethylbenzyl)-N-(2-chloroethylthiocarbamoyl)-2(S)-{[l-(4-cyan obenzyl)- 1 H-imidazol-5 -yl]acetyl } amino-3 (S )-methylpentylamine 1H-NMR(CDCb) : δ 7.70(s, IH), 7.65(d, 2H), 7.54(s, IH),

7.25-7.52(m, 3H), 7.20(d, 2H), 7.05(s, IH), 5.38(s, 2H), 4.70(s, 2H),

4.00(m, 3H), 3.40(m, IH), 3.35(s, 2H), 2.95(dd, IH), 1.62(m, IH), 1.35(m, 3H), 1.10(m, IH), 0.85(m, 6H)

Example 545

N-(2-Trifluoromethylbenzyl)-N-(3-chloiO-4-methylphenylthiocarbamoyl)-2(S)-

{[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

¹H-NMR(CDCb) : δ 7.70(d, IH), 7.60(m, 3H), 7.25-7.50(m, 4H),

7.18(m, 4H), 7.05(s, IH), 5.20-5.40(m, 3H), 4.80(m, 2H), 4.20(m, IH),

3.40(s, 2H), 3.15(dd, IH), 2.30(s, 3H), 1.65(m, IH), 1.10-1.55(m, 2H), 0.85(m, 6H)

Example 546

N-(2-Trifluoromethylbenzyl)-N-cyclohexylthiocarbamoyl-2(S)- {[ 1 -(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

¹H-NMR(CDCb) : δ 7.80(s, IH), 7.70(s, IH), 7.65(d, 2H), 7.40-7.60(m, 2H), 7.10-7.30(m, 4H), 5.60(m, IH), 5.40(s, 2H), 5.00(m, 2H), 4.65(m, IH), 4.15(m, 2H), 3.40(s, 2H), 3.15(dd, IH), 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)-{[l-(4 -cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methylpentylamine

-H-NMR(CDCb) : δ 7.75(d, IH), 7.60(d, 2H), 7.50(m, IH), 7.20-7.40(m, 3H), 7.15(d, 2H), 7.00(s, IH), 6.90(d, IH), 5.30(s, 2H), 4.90(m, 2H), 4.30(m, IH), 3.38(s, 2H), 3.20(dd, IH), 1.64(m, IH), 1.10-1.40(m, 2H), 0.85(t, 6H)

Example 548

N-(2-Trifluoromethylbenzyl)-N-(4-isopiOpylphenylthiocarbamoyl)-2(S)-{[l-(4- cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

^-NMR^DCb) : δ 7.65(m, 2H), 7.60(m, 3H), 7.30-7.50(m, 3H),

7.00-7.20(m, 6H), 5.70(bs, IH), 5.35(m, 2H), 4.80(m, 2H), 4.20(m, IH),

3.40(s, 2H), 3.10(dd, IH), 2.90(m, IH), 1.65(m, IH), 1.40(m, IH), 1.20(d, 6H), 1.15(m, IH), 0.85(t, 6H)

Example 549

N-(2-Trifluoromethylbenzyl)-N-(3-methoxypropylthiocarbamoyl)-2(S)-{[l-(4- cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl} amino-3 (S)-methy lpentylamine

-H-NMR(CDCb) : δ 7.75(s, IH), 7.70(d, 2H), 7.45(m, 2H), 7.25(d, 2H), 7.10(s, 2H), 6.90(d, IH), 5.75(bs, IH), 5.45(d, 2H), 5.10(m, IH), 4.70(m, 2H), 4.10(m, IH), 3.70(m, 2H), 3.50(t, IH), 3.40(s, 3H), 3.34(m, IH), 2.95(dd, IH), 2.80(d, 2H), 1.80(m, 2H), 1.64(m, IH), 1.10-1.40(m, 2H), 0.90(d, 6H)

Example 550

N-(2-Trifluoromethylbenzyl)-N-(2-naphthylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methylpentylamine

-H-NMR(CDCb) : δ 7.60-7.80(m, 5H), 7.25-7.60(m, 9H), 7.00(m, 3H), 5.60(m, IH), 5.20(s, 2H), 4.90(m, 2H), 4.20(m, IH), 3.38(s, 2H), 3.15(dd, IH), 1.64(m, IH), 1.00-1.40(m, 2H), 0.85(t, 6H)

Example 551 N-(2-Trifluoromethylbenzyl)-N-ethoxycaι^*bonylmethylthiocarbamoyl-2(S)- { [ 1 - (4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

-H-NMR(CDCb) : δ 7.65(m, 3H), 7.45(m, 3H), 7.20(m, 3H), 7.00(s, IH), 5.35(s, 5H), 4.70(m, IH), 4.35(m, 2H), 4.16(q, 2H), 3.38(s, 2H), 3.05(dd, IH), 1.36-1.64(m, 2H), 1.25(t, 3H), 1.10(m, IH), 0.85(t, 6H)

Example 552

N-(2-Trifluoromethylbenzyl)-N-(4-methylthiophenylthiocarbamoyl)-2(S )- { [ 1 -( 4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

-H-NMR(CDCb) : δ 7.75(d, IH), 7.60(d, 2H), 7.50(m, 3H),

7.15-7.38(m, 5H), 7.10(d, 2H), 7.00(s, IH), 5.42(m, IH), 5.30(s, 2H),

4.80(m, 2H), 3.90-4.20(m, 2H), 3.38(s, 2H), 3.15(dd, IH), 2.45(s, 3H), 1.64(m, IH), 1.00-1.40(m, 2H), 0.85(t, 6H)

Example 553

N-(2-Trifluoromethylbenzyl)-N-isopropylthiocarbamoyl-2(S)- { [ 1 -(4-cyanoben zyl)- 1 H-imidazol-5 -yl]acetyl } amino-3 (S)-methylpentylamine

-H-NMR(CDCb) : δ 7.75(s, 2H), 7.65(d, 2H), 7.50(m, 2H), 7.22(d, 3H), 7.05(s, IH), 5.90(bs, IH), 5.40(m, 2H), 5.00(m, 2H), 4.65(m, IH), 4.15(m, IH), 3.50(m, IH), 3.38(s, 2H), 3.25(m, IH), 3.10(dd, IH), 1.52-1.80(m, 2H), 1.40(m, IH), 1.10(m, IH), 0.90(m, 6H), 0.75(p, 6H)

Example 554

N-(2-Trifluoromethylbenzyl)-N-(2-methoxyethylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

-H-NMR(CDCb) : δ 7.75(s, IH), 7.65(d, 3H), 7.45(m, 2H), 7.15-7.30(m, 3H), 7.10(s, IH), 6.15(bd, IH), 5.80(bs, IH), 5.30(m, 2H), 4.80-5.10(m, 2H), 4.65(m, IH), 4.20(m, IH), 3.74(m, 2H), 3.40(s, 4H), 3.20(d, 3H), 1.40-1.64(m, 2H), 1.10(m, IH), 0.87(d, 6H)

Example 555

N-(2-Trifluoromethylbenzyl)-N-cyclopiOpylthiocarbamoyl-2(S)- { [ 1 -(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR(CDCb) : δ 7.75(s, IH), 7.65(d, 3H), 7.45(m, 2H), 7.10-7.25(m, 4H), 6.55(bd, IH), 5.80(bs, IH), 5.40(s, 2H), 5.15(m, IH), 4.80(m, IH), 4.65(m, 2H), 4.05(m, IH), 3.40(s, 2H), 3.05(m, 2H), 1.60(m, IH), 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)-{

[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR(CDCb) : δ 7.75(s, IH), 7.65(d, 2H), 7.55(s, IH), 7.45(t, 2H), 7.20(d, 3H), 7.00(s, IH), 5.40(d, 2H), 4.70-5.10(m, 3H), 4.20(m, IH), 3.64(m, 2H), 3.40(m, 2H), 3.15(dd, IH), 2.65(m, 2H), 2.20(bs, 4H), 1.35-1.65(m, 2H), 1.28(s, IH), 1.10(m, IH), 0.87(t, 6H)

Example 557

N-(2-Trifluoromethylbenzyl)-N-(3-ethoxypropylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl} amino-3 (S)-methy lpentylamine

-H-NMR(CDCb) : δ 7.80(s, IH), 7.65(d, 2H), 7.45(m, 2H), 7.25(d, 2H), 7.10(s, 2H), 6.85(m, IH), 5.80(bs, IH), 5.45(d, 2H), 5.10(m, IH), 4.60-4.90(m, 2H), 4.10(m, IH), 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)

-{[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

-H-NMR(CDCb) : a 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, IH), 5.30(m, 2H), 4.80(m, IH), 4.20(m, IH), 3.40(s, 2H), 3.10(dd, IH), 2.90(s, 6H), 1.60(m, IH), 1.10-1.44(m, 2H), 0.87(t, 6H)

Example 559

N-(2-Trifluoromethylbenzyl)-N-(n-pentylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S)-methy lpentylamine

-H-NMR(CDCb) : 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, IH), 4.10(m, IH), 3.64(m, IH), 3.40(s, 4H), 3.10(dd, IH), 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)-{[l-(4-cyan obenzyl)-lH-imidazol-5-yl]ace1yl}amino-3(S)-methylpentylamine

¹H-NMR(CDCb) : δ 8.10(m, 2H), 7.52-7.75(m, 6H), 7.28-7.50(m, 2H),

7.12(d, 2H), 7.00(s, IH), 6.85(d, IH), 5.70-5.90(m, IH), 5.30(s, 2H),

4.80(m, IH), 4.55(bs, IH), 4.10(m, 2H), 3.40(s, 2H), 3.10(dd, IH), 1.64(m, IH), 1.10-1.50(m, 2H), 0.87(m, 6H)

Example 561

N-(2-Trifluoromethylbenzyl)-N-(t-octylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanobenz yl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S)-methylpentylamine

-H-NMR(CDCb) : δ 7.70(m, 2H), 7.65(d, 2H), 7.50(s, IH), 7.45(t, 2H), 7.20(d, 2H), 7.05(s, IH), 5.40(d, 2H), 5.25(s, IH), 4.70(m, 2H), 4.10(m, IH), 3.34(q, 2H), 3.00(m, IH), 2.10(m, 2H), 1.60(m, IH), 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)-{[l-(4-cyanobenzyl

)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR(CDCb) : δ 7.70(d, IH), 7.57(m, 4H), 7.20-7.50(m, 7H), 7.10(d, 2H), 7.00(s, IH), 5.40-5.60(m, 2H), 5.24(s, IH), 4.80-5.00(m, 2H), 4.20(m, IH), 3.40(s, 2H), 3.10(dd, IH), 1.64(m, IH), 1.00-1.50(m, 2H), 0.87(m, 6H)

Example 563

N-(2-Trifluoromethylbenzyl)-N-(n-propylthiocarbamoyl)-2(S)-{[l-(4-cyanoben zyl)- 1 H-imidazol-5 -yl]acetyl } amino-3 (S)-methylpentylamine

1H-NMR(CDCb) : δ 7.65(m, 3H), 7.45(m, 2H), 7.22(d, 3H), 7.05(s, 2H), 6.10(m, IH), 5.40(m, 2H), 4.80-5.10(m, 2H), 4.65(m, IH), 4.10(m, IH), 3.54(m, 2H), 3.40(s, 2H), 3.10(dd, IH), 1.40-1.64(m, 3H), 1.00-1.30(m, 2H), 0.87(t, 6H), 0.75(m, 3H)

Example 564

N-(2-Trifluorome11ιylbenzyl)-N-(2-methylphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methylpentylamine

1H-NMR(CDCb) : a 7.75(d, IH), 7.60(m, 4H), 7.45(m, 3H), 7.15(m, 6H), 7.00(s, IH), 5.30(m, 3H), 4.85(m, 2H), 4.20(m, IH), 3.40(s, 2H), 3.20(dd, IH), 2.05(d, 3H), 1.64(m, IH), 1.00-1.50(m, 2H), 0.87(t, 6H)

Example 565

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

^'H-NMR(CDCb) : δ 7.75(m, 2H), 7.60(m, 3H), 7.40(m, 2H), 7.15(d, 2H), 7.05(s, IH), 6.95(m, 3H), 5.95(bs, IH), 5.30(m, 2H), 4.85(m, 2H), 4.20(m, IH), 3.40(s, 2H), 3.20(dd, IH), 2.30(s, 3H), 2.00(d, 3H), 1.64(m, IH), 1.00-1.50(m, 2H), 0.87(t, 6H)

Example 566

N-(2-Trifluoromeι ylbenzyl)-N-(3,4-dimethylphenylthiocarbamoyl)-2(S)-{[l-(

4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR(CDCb) : δ 7.75(d, IH), 7.60(m, 3H), 7.40(m, 2H), 7.15(d, 3H), 7.05(s, IH), 6.95(d, 2H), 5.40(m, 3H), 4.80(m, 2H), 4.20(m, IH), 3.40(s, 2H), 3.15(dd, IH), 2.20(d, 6H), 1.64(m, IH), 1.00-1.50(m, 2H), 0.87(t, 6H)

Example 567

N-(2-Trifluoromethylbenzyl)-N-(3 -methylphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methylpentylamine

-H-NMR(CDCb) : δ 7.70(m, 2H), 7.55(m, 4H), 7.35(m, IH),

6.95-7.20(m, 7H), 6.20(s, IH), 5.30(m, 2H), 4.80(m, 2H), 4.20(m, IH),

3.40(s, 2H), 3.15(dd, IH), 2.30(s, 3H), 1.64(m, IH), 1.00-1.50(m, 2H), 0.87(t, 6H) Example 568

N-(2-Trifluoromethylbenzyl)-N-(4-bromophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

-H-NMR(CDCb) : δ 7.70(d, IH), 7.60(m, 4H), 7.45(m, 3H), 7.30(m, 3H), 7.10(d, 3H), 7.00(s, IH), 5.60(m, IH), 5.20(m, 2H), 4.80(m, 2H), 4.20(m, IH), 3.40(s, 2H), 3.15(dd, IH), 1.64(m, IH), 1.00-1.50(m, 2H), 0.87(t, 6H)

Example 569

N-(2-Trifluoromethylbenzyl)-N-(2-chlorophenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

¹H-NMR(CDCb) : δ 7.75(m, 2H), 7.60(m, 4H), 7.40(m, 4H), 7.15(m, 4H), 7.00(s, IH), 5.80(bs, IH), 5.30(m, 2H), 4.85(m, 2H), 4.20(m, IH), 3.40(s, 2H), 3.20(dd, IH), 1.64(m, IH), 1.00-1.50(m, 2H), 0.87(t, 6H)

Example 570

N-(2-Trifluoromethylbenzyl)-N-(3-chlorophenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

-H-NMR(CDCb) : δ 7.75(d, IH), 7.60(m, 4H), 7.20-7.50(m, 5H),

7.15(m, 4H), 7.00(s, IH), 5.65(m, IH), 5.30(m, 2H), 4.80(m, 2H),

4.20(m, IH), 3.40(s, 2H), 3.15(dd, IH), 1.64(m, IH), 1.00-1.50(m, 2H), 0.87(t, 6H)

Example 571

N-(2-Trifluoromethylbenzyl)-N-(4-dimethylamino-l-naphthylthiocarbamoyl)-2 (S )-{[ 1 -(4-cyanobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methylpentylami ne 1H-NMR(CDCb) : δ 8.20(d, IH), 7.75(d, IH), 7.20-7.60(m, 9H), 7.00(m, 4H), 5.85(s, IH), 5.30(m, 2H), 5.20(d, 2H), 4.95(m, IH), 4.30(m, IH), 3.40(s, 2H), 3.20(dd, IH), 2.90(s, 6H), 1.64(m, IH), 1.00-1.50(m, 2H), 0.87(t, 6H)

Example 572

N-(2-Trifluoromethylbenzyl)-N-(2-methoxyphenylthiocarbamoyl)-2(S )- { [ 1 -(4- cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methy lpentylamine

^'H-NMR(CDCb) : δ 8.25(d, IH), 7.80(d, IH), 7.60(m, 6H), 7.30(m, IH), 7.10(m, 4H), 6.95(t, IH), 6.80(d, IH), 5.30(m, 3H), 4.85(m, 2H), 4.30(m, IH), 3.55(s, 3H), 3.40(s, 2H), 3.20(dd, IH), 2.05(d, 3H), 1.64(m, IH), 1.00-1.50(m, 2H), 0.92(d, 6H)

Example 573

N-(2-Trifluoromethylbenzyl)-N-(4-methylphenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

¹H-NMR(CDCb) : δ 7.75(d, IH), 7.60(d, 3H), 7.40(m, 3H), 7.15(m, 5H), 7.00(s, IH), 5.30(m, 3H), 4.75-5.10(m, 3H), 4.20(m, IH), 3.40(s, 2H), 3.10(dd, IH), 2.35(s, 3H), 1.64(m, IH), 1.00-1.50(m, 2H), 0.87(t, 6H)

Example 574

N-(2-Trifluoromethylbenzyl)-N-phenethylthiocarbamoyl-2(S)- { [ 1 -(4-cyanoben zyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR(CDCb) : δ 7.65(d, 2H), 7.60(s, IH), 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, IH), 4.10(m, IH), 3.80(m, 2H), 3.40(s, 2H), 3.05(m, IH), 2.80(m, 2H), 1.64(m, IH), 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)- lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR(CDC1₃) : δ 7.95(m, IH), 7.75(m, 2H), 7.60(d, 3H), 7.45(m,

IH), 7.30(m, 2H), 7.15(d, 2H), 7.00(s, IH), 6.70(d, IH), 6.00(bs, IH),

5.30(m, 2H), 4.80(m, 2H), 4.20(m, IH), 3.85(s, 3H), 3.40(s, 2H), 3.20(dd, IH), 1.64(m, IH), 1.00-1.50(m, 2H), 0.87(t, 6H)

Example 576

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

-H-NMR(CDCb) : δ 7.75(m, IH), 7.65(d, 2H), 7.45(m, 3H), 7.20(d, 2H), 7.10(m, IH), 7.00(s, IH), 5.40(d, 2H), 4.80(m, 3H), 4.20(m, IH), 3.70(m, 3H), 3.35(m, 2H), 2.95(m, IH), 2.55(m, 2H), 2.00(m, 6H), 1.64(m,lH), 1.00-1.50(m, 5H), 0.87(m, 6H)

Example 577

N-(2-Trifluoromethylbenzyl)-N-(2-hydroxyphenylthiocarbamoyl)-2(S)- { [ 1 -(4-c y anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methylpentylamine

Η-NMR(CDCb) : δ 7.65(s, IH), 7.60(d, 3H), 7.55(m, 4H), 7.40(d, 2H), 7.15(d, 3H), 7.00(s, IH), 6.85(m, IH), 6.00(bs, IH), 5.25(s, 2H), 3.95(m, IH), 3.90(s, 2H), 3.40(s, 2H), 2.65(m, 2H), 1.85(bs, 2H), 1.64(m, IH), 1.00-1.50(m, 2H), 0.87(m, 6H) Example 578

N-(2-Trifluoromethylbenzyl)-N-(4-hydroxyphenylthiocarbamoyl)-2(S)-{[l-(4-c yanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

^'H-NMR(CDCb) : 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, IH), 3.40(m, 2H), 3.10(d, IH), 1.64(m, IH), 1.00-1.50(m, 3H), 0.87(t, 6H)

Example 579

N-(2-Trifluoromethylbenzyl)-N-(2-chloropyridin-5-ylthiocarbamoyl)-2(S)-{[l-

(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

¹H-NMR(CDCb) : δ 8.30(d, IH), 8.00(t, IH), 7.75(d, IH), 7.60(d, 2H), 7.45(m, 2H), 7.30(m, 2H), 7.10(d, 2H), 7.00(s, IH), 6.60(m, IH), 5.75(m, IH), 5.25(m, 2H), 4.80(m, IH), 4.10(m, IH), 3.40(s, 2H), 3.20(dd, IH), 1.64(m, IH), 1.00-1.50(m, 2H), 0.87(t, 6H)

Example 580

N-(2-Trifluoromethylbenzyl)-N-cyclopentylthiocarbamoyl-2(S)-{[l-(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

^'H-NMR(CDCb) : δ 7.80(s, IH), 7.65(d, 3H), 7.45(m, 2H), 7.20(d, 3H),

7.10(s, IH), 5.90(bs, IH), 5.40(s, 2H), 5.00(m, 2H), 4.60(m, 2H),

4.10(m, IH), 3.40(s, 2H), 3.10(dd, IH), 1.95(m, 2H), 1.00-1.80(m, 9H), 0.87(t, 6H)

Example 581

N-(2-Trifluoromethylbenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4- cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl} amino-3 (S)-methylpentylamine hydrochloride Hydrogen chloride gas was bubbled through a solution of Example 537 in ethyl acetate while stπring until a white slurry appeared. It was crystallized from diethylether to produce a solid, which was then filtered and recrystallized from ethanol to give the title compound as a white solid.

1H-NMR (CD3OD) : δ 9.18(s, IH), 7.85(m, 4H), 7.80(s, IH), 7.64(m, 4H), 7.39(d, 2H), 7.02(d, 2H), 5.80(s, 2H), 5.35(dd, 2H), 4.30(m, IH), 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-cy anobenzyl)- 1

H-imidazol-5 -yl] acetyl} aminopropylamine

<Step 1>

N-(2-Trifluoromethylbenzyl)-2(S)-{[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acety 1 } aminopropylamine

Using the same method as described in Preparative Example 3, N-t-butoxycarbonyl-L-alanine was converted to N-(t-butoxycarbonyl)-L- alanine aldehyde. And then the reaction was carried out under the same condition as described in Preparative Example 4, but replacing 2,3-dichlorobenzylamine and 1 -(4-nitrobenzyl)- 1 H-imidazol-5- ylacetic acid hydrochloride with 2-trifluoromethylbenzylamine and 1 -(4-cyanobenzy 1)- lH-imidazol-5-ylacetic acid hydrochloride, respectively, to give the title compound.

^'H-NMR (CDCb) : δ 7.00-7.66(m, 10H), 6.29(d, IH), 5.27(s, 2H), 4.00(m, IH), 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)- 1

H-imidazol-5 -yl] acetyl } aminopropylamine

To a solution of N-(2-trifluoromethylbenzyl)-2(S)-{[l-(4-cyano- benzyl)-lH-imidazol-5-yl]acetyl} aminopropylamine in dichloromethane (0.02M, 1ml, 0.02mmol) was added allylisothiocyanate (0.1M in CH₂C1₂, 0.2ml, 0.02mmol). The reaction mixture was agitated for 2hr at room temperature. The mixture was purified by silica gel column chromatography(eluent: CH2Cb/MeOH=9/l, v/v) to give the title compound as a white solid.

^'H-NMR (CDCb) : δ 6.99-7.71(m, 9H), 6.51 (bs, IH), 5.84(m, IH), 5.30(s, 2H), 5.15(d, IH), 5.06(m, 2H), 4.70(d, IH), 4.50(d, IH), 4.29 (bs, 2H), 4.09(m, IH), 3.32(s, 2H), 2.96(dd, IH), 1.17(d, 3H)

Examples 583-625

N-(2-trifluoromethylbenzyl)-2(S)- {[ 1 -(4-cyanobenzyl)- lH-imidazol-5 - yl] acetyl} aminopropylamine was reacted with the conesponding isothiocyanates under the same condition as described in <Step 2> of Example 582 to give the title compounds.

Example 583

N-(2-Trifluoromethylbenzyl)-N-benzylthiocarbamoyl-2(S)- { [ 1 -(4-cyanobenzyl

)- 1 H-imidazol-5-yl] acetyl } aminopropylamine

^"H-NMR (CDCb) : δ 6.95-7.67(m, 14H), 5.36(d, IH), 5.22(s, IH), 4.86(d, 2H), 4.72(d, IH), 4.68(s, IH), 4.08(m, IH), 3.26(s, 2H), 2.98(dd, IH), 1.16(d, 3H)

Example 584

N-(2-Trifluoromethylbenzyl)-N-(2-biphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

1H-NMR (CDCb) : δ 6.95-7.62(m, 18H), 5.25(d, IH), 5.21(s, 2H), 4.63(d, IH), 4.43(s, IH), 3.94 (bs, IH), 3.27(s, 2H), 2.83(dd, IH), 1.1 l(d, 3H)

Example 585

N-(2-Trifluoromethylbenzyl)-N-(2-bromophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

1H-NMR (CDCb) : δ 6.99-7.73(m, 13H), 5.57 (bs, IH), 5.28(d, IH), 5.24(s, 2H), 4.83(d, IH), 4.72(bs, IH), 4.28(m, IH), 3.34(s, 2H), 3.08(dd, IH), 1.21(d, 3H)

Example 586

N-(2-Trifluoromethylbenzyl)-N-(3-bromophenylthiocarbamoyl)-2(S)-{ [ 1 -(4-cy anobenzyl)-lH-imidazol-5-yl]acetyl}aminopropylamine

-H-NMR (CDCb) : r5 9.17 (bs, IH), 6.94-7.70(m, 13H), 5.95(d, IH), 5.29(s, 2H), 4.77(d, IH), 4.32(m, IH), 4.09(m, IH), 3.33(s, 2H), 2.96(dd, IH), 1.24(d, 3H)

Example 587

N-(2-Trifluoromethylbenzyl)-N-(4-bromophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- 1 H-imidazol-5-yl] acetyl } aminopropylamine 1H-NMR (CDCb) : δ 8.95 (bs, IH), 6.95-7.7 l(m, 13H), 5.87(d, IH), 5.24(s, 2H), 4.79(d, IH), 4.36(m, IH), 4.10(m, IH), 3.34(s, 2H), 2.97(dd, IH), 1.23(d, 3H)

Example 588

N-(2-Trifluoromethylbenzyl)-N-(n-butylthiocarbamoyl)-2(S)-{[l-(4-cyanobenz yl)-lH-imidazol-5-yl]acetyl}aminopropylamine

Η-NMR (CDCb) : δ 7.00-7.71(m, 9H), 6.27 (bs, IH), 5.33(s, 2H), 5.21(d, IH), 4.69(d, IH), 4.62(m, IH), 4.08(m, IH), 3.60(m, 2H), 3.33(s, 2H), 2.97(dd, IH), 1.49(m, 2H), 1.26(m, 2H), 1.18(d, 3H), 0.85 (t, 3H)

Example 589

N-(2-Trifluoromeι ylbenzyl)-N-isobutylthiocarbamoyl-2(S)-{[l-(4-cyanobenzy l)-lH-imidazol-5-yl]acetyl}aminopropylamine

Η-NMR (CDCb) : δ 7.00-7.72(m, 9H), 6.18 (bs, IH), 5.34(s, 2H), 5.22(d, IH), 4.76(m, IH), 4.71(d, IH), 4.10(m, IH), 3.44(m, 2H), 3.33(s, 2H), 3.02(dd, IH), 1.84(m, IH), 1.18(d, 3H), 0.76(d, 6H)

Example 590

N-(2-Trifluoromethylbenzyl)-N-(2-chlorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- lH-imidazol-5-yl]acetyl} aminopropylamine

^"H-NMR (CDCb) : δ 6.99-7.73(m, 13H), 5.53(d, IH), 5.24(s, 2H), 4.88(d, IH), 4.72(m, IH), 4.26(m, IH), 3.34(s, 2H), 3.08(dd, IH), 1.21(d, 3H)

Example 591 N-(2-Trifluoromethylbenzyl)-N-(3-chlorophenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

^'H-NMR (CDCb) - $ 9.18 (bs, IH), 6.94-7.70(m, 13H), 5.94(d, IH), 5.28(s, 2H), 4.77(d, IH), 4.33(m, IH), 4.09(m, IH), 3.33(s, 2H), 2.96(dd, IH), 1.23(d, 3H)

Example 592

N-(2-Trifluoromethylbenzyl)-N-(4-chlorophenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

Η-NMR (CDCb) : a 8.68 (bs, IH), 7.00-7.72(m, 13H), 5.82(d, IH), 5.24(s, 2H), 4.80(d, IH), 4.38(m, IH), 4.1 l(m, IH), 3.35(s, 2H), 2.99(dd, IH), 1.22(d, 3H)

Example 593

N-(2-Trifluoromethylbenzyl)-N-(3-chloro-4-methylphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanobenzyl)- lH-imidazol-5-yl] acetyl} aminopropylamine

^"H-NMR (CDCb) : δ 7.01-7.72(m, 12H), 5.85(d, IH), 5.29(s, 2H), 4.80(d, IH), 4.42(m, IH), 4.13(m, IH), 3.36(s, 2H), 2.99(dd, IH), 2.36(s, 3H), 1.24(d, 3H)

Example 594

N-(2-Trifluoromethylbenzyl)-N-cyclohexylthiocarbamoyl-2(S)- { [ 1 -(4-cyanobe nzyl)- 1 H-imidazol-5 -y 1] acetyl } aminopropylamine

-H-NMR (CDCb) : δ 7.03-7.72(m, 9H), 5.94 (bs, IH), 5.30(s, 2H), 5.18(d, IH), 4.88(m, IH), 4.68(d, IH), 4.22(m, IH), 4.07(m, IH), 3.33(s, 2H), 2.98(dd, IH), 0.85-1.90(m, 10H), 1.16(d, 3H) Example 595

N-(2-Trifluoromethylbenzyl)-N-cyclopentylthiocarbamoyl-2(S)-{[l -(4-cyanobe nzyl)- 1 H-imidazol-5-yl] acetyl } aminopropylamine

Η-NMR (CDCb) : δ 7.03-7.71(m, 9H), 5.98 (bs, IH), 5.34(s, 2H), 5.23(d, IH), 4.67(d, IH), 4.55(m, IH), 4.07(m, IH), 3.33(s, 2H), 2.98(dd, IH), 1.25-1.96(m, 6H), 1.20(d, 3H)

Example 596

N-(2-Trifluoromethylbenzyl)-N-(2,4-dichlorophenylthiocarbamoyl)-2(S)-{[l-(4

-cyanobenzyl)-lH-imidazol-5-yl]acetyl}aminopropylamine

1H-NMR (CDCb) : δ 7.02-7.92(m, 12H), 5.25(s, 2H), 5.20(d, IH), 4.86(d, IH), 4.75(m, IH), 4.24(m, IH), 3.32(s, 2H), 3.08(dd, IH), 1.22(d, 3H)

Example 597

N-(2-Trifluoromethylbenzyl)-N-[2-(dimethylamino)ethylthiocarbamoyl]-2(S)-{ [ 1 -(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl} aminopropylamine

Η-NMR (CDCb) : δ 7.00-7.72(m, 9H), 5.40(d, IH), 5.36(s, 2H), 4.97(m, IH), 4.78(d, IH), 4.21(m, IH), 3.59(m, 2H), 3.35(d, 2H), 3.12(dd, IH), 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)- 1 H-imidazol-5 -yl]acetyl } aminopropylamine

^'H-NMR (CDCb) : δ 6.58-7.73(m, 13H), 5.29(s, 2H), 5.40(d, IH), 4.86(m, IH), 4.84(d, IH), 4.18(m, IH), 3.35(s, 2H), 3.04(dd, IH), 2.96(d, 6H), 1.30(d, 3H)

Example 599

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

Η-NMR (CDCb) : δ 7.03-7.70(m, 9H), 5.39(d, IH), 5.24(s, 2H), 4.85(m, IH), 4.79(d, IH), 4.14(m, IH), 3.74(m, 2H), 3.33 (bs, 2H), 2.95(dd, IH), 2.63(m, 2H), 2.18(m, 2H), 1.89(s, 6H), 1.1 l(m, 3H)

Example 600

N-(2-Trifluoromethylbenzyl)-N-(3-ethoxypropylthiocarbamoyl)-2(S)-{ [ 1 -(4-cy anobenzyl)- lH-imidazol-5-yl]acetyl} aminopropylamine

^"H-NMR (CDCb) : δ 6.86-7.7 l(m, 9H), 5.35(s, 2H), 4.89(m, IH), 4.80(dd, 2H), 4.09(m, IH), 3.74 (bs, 2H), 3.41(m, 2H), 3.32(s, 2H), 3.15(m, 2H), 2.92(dd, IH), 1.77 (bs, 2H), 1.12(d, 3H), 0.82 (t, 3H)

Example 601

N-(2-Trifluoromethylbenzyl)-N-ethylthiocarbamoyl-2(S)- { [ 1 -(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}aminopropylamine

Η-NMR (CDCb) : δ 7.02-7.71(m, 9H), 6.24 (bs, IH), 5.30(s, 2H), 5.14(d, IH), 4.68(d, IH), 4.58(m, IH), 4.08(m, IH), 3.65(m, 2H), 3.33(s, 2H), 2.94(dd, IH), 1.27(m, 2H), 1.18(m, 3H), 1.16(d, 3H)

Example 602

N-(2-Trifluoromethylbenzyl)-N-(2-fluorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

^'H-NMR (CDCb) : δ 6.93-7.83(m, 13H), 5.36(d, IH), 5.25(s, 2H), 4.86(d, IH), 4.71(m, IH), 4.21(m, IH), 3.37(s, 2H), 3.05(dd, IH), 1.21(d, 3H)

Example 603

N-(2-Trifluoromethylbenzyl)-N-(3-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- lH-imidazol-5-yl]acetyl}aminopropylamine

Η-NMR (CDCb) : δ 8.85 (bs, IH), 6.73-7.94(m, 13H), 5.87(d, IH), 5.27(s, 2H), 4.80(d, IH), 4.43(m, IH), 4.12(m, IH), 3.36(s, 2H), 2.99(dd, IH), 1.24(d, 3H)

Example 604

N-(2-Trifluoromethylbenzyl)-N-(4-fluorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- 1 H-imidazol-5 -yl]acetyl } aminopropylamine

1H-NMR (CDCb) : δ 8.66 (bs, IH), 6.97-7.72(m, 13H), 5.79(d, IH), 5.25(s, 2H), 4.8 l(d, IH), 4.45(m, IH), 4.12(m, IH), 3.34(s, 2H), 2.99(dd, IH), 1.22(d, 3H)

Example 605

N-(2-Trifluoromethylbenzyl)-N-(4-hydroxyphenylthiocarbamoyl)-2(S)- { [ 1 -(4-c yanobenzyl)- 1 H-imidazol-5-yl]acetyl} aminopropylamine

-H-NMR (CD₃OD) : δ 6.72-7.73(m, 13H), 5.70(d, 2H), 5.35(s, 2H), 5.05(d, IH), 4.19(m, IH), 3.99(m, IH), 3.41(s, 2H), 3.25(dd, IH), 1.18(d, 3H) Example 606

N-(2-Trifluoromethylbenzyl)-N-(4-isopropylphenylthiocarbamoyl)-2(S)-{[l-(4- cyanobenzyl)-lH-imidazol-5-yl]acetyl}aminopiOpylamine

1H-NMR (CDCb) : a 8.33 (bs, IH), 6.98-7.7 l(m, 13H), 5.64(d, IH), 5.25(s, 2H), 4.8 l(d, IH), 4.65(m, IH), 4.15(m, IH), 3.33(s, 2H), 3.01(dd, IH), 2.90(m, IH), 1.23(m, 9H)

Example 607

N-(2-Trifluoromethylbenzyl)-N-(2-methoxyethylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

1H-NMR (CDCb) : δ 7.02-7.72(m, 9H), 6.25 (bs, IH), 5.33(s, 2H), 5.06(d, IH), 4,.86(m, IH), 4.72(d, IH), 4.13(m, IH), 3.74(m, 2H), 3.42(m, 2H), 3.33(s, 2H), 3.11(s, 3H), 3.04(dd, IH), 1.16(d, 3H)

Example 608

N-(2-Trifluoromethylbenzyl)-N-(2-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4- cyanobenzyl)-lH-imidazol-5-yl]acetyl}aminopropylamine

1H-NMR (CDCb) : δ 8.2 l(d, IH), 6.78-7.78(m, 13H), 5.23(s, 2H), 5.15(m, IH), 5.09(m, IH), 4.91(d, IH), 4.30(m, IH), 3.54(s, 3H), 3.35(s, 2H), 3.14(dd, IH), 1.20(d, 3H)

Example 609

N-(2-Trifluoromethylbenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4- cyanobenzyl)-lH-imidazol-5-yl]acetyl}aminopropylamine

1H-NMR (CDCb) : δ 8.30 (bs, IH), 6.83-7.7 l(m, 13H), 5.63(d, IH), 5.28(s, 2H), 4.82(d, IH), 4.60(m, IH), 4.14(m, IH), 3.80(s, 3H), 3.33(s, 2H), 3.01(dd, IH), 1.21(d, 3H)

Example 610

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

^"H-NMR (CDCb) : δ 7.82 (bs, IH), 6.96-7.73(m, 9H), 5.35(d, 2H), 4.93(d, IH), 4.70(d, IH), 4.1 l(m, IH), 3.70(m, 2H), 3.40(m, 2H), 3.32(s, 2H), 2.95(dd, IH), 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)- 1 H-imidazol-5 -yl] acetyl} aminopropylamine

Η-NMR (CDCb) : δ 6.72-8.1 l(m, 12H), 5.87(d, IH), 5.25(s, 2H), 4.81(d, IH), 4.43(m, IH), 4.13(m, IH), 3.92(s, 3H), 3.33(s, 2H), 2.99(dd, IH), 1.23(d, 3H)

Example 612

N-(2-Trifluoromethylbenzyl)-N-methylthiocarbamoyl-2(S)- { [ 1 -(4-cyanobenzyl

)-lH-imidazol-5-yl]acetyl}aminopropylamine

¹ H-NMR (CDCb) : δ 6.98-7.70(m, 9H), 6.74(bs, IH), 5.29(s, 2H), 5.21(d, IH), 4.68(d, IH), 4.51(m, IH), 4.05(m, IH), 3.33(s, 2H), 3.12(s, 3H), 2.91(dd, IH), 1.16(d, 3H)

Example 613

N-(2-Trifluoromethylbenzyl)-N-(4-methylthiophenylthiocarbamoyl)-2(S)-{[l-( 4-cyanobenzyl)- 1 H-imidazol-5 -yl]acetyl } aminopropylamine ^'H-NMR (CDCb) : δ 8.66 (bs, IH), 6.95-7.7 l(m, 13H), 5.78(d, IH), 5.24(s, 2H), 4.801(d, IH), 4.46(m, IH), 4.12(m, IH), 3.3 l(s, 2H), 2.98(dd, IH), 2.47(s, 3H), 1.21(d, 3H)

Example 614

N-(2-Trifluoromethylbenzyl)-N-(2-naphthylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

¹ H-NMR (CDCb) : δ 8.99 (bs, IH), 6.87-7.8 l(m, 16H), 5.84(d, IH), 5.18(s, 2H), 4.83(d, IH), 4.49(m, IH), 4.16(m, IH), 3.33(s, 2H), 2.99(dd, IH), 1.22(d, 3H)

Example 615

N-(2-Trifluoromethylbenzyl)-N-(4-nitrophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyan obenzyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

1H-NMR (CDCb) : r5 .66 (bs, IH), 6.66-8.19(m, 13H), 6.09(d, IH), 5.25(s, 2H), 4.78(d, IH), 4.17(m, H), 4.10(m, IH), 3.39(s, 2H), 2.99(dd, IH), 1.27(d, 3H)

Example 616

N-(2-Trifluoromethylbenzyl)-N-(n-pentylthiocarbamoyl)-2(S)-{[l-(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

^'H-NMR (CDCb) : δ 7.70-7.72(m, 9H), 6.081 (bs, IH), 5.33(s, 2H), 5.21(d, IH), 4.78(m, IH), 4.70(d, IH), 4.10(m, IH), 3.57(m, IH), 3.48(s, IH), 3.32(s, 2H), 3.02(dd, IH), 1.60(m, IH), 1.17(d, 3H), 0.69-1.25(m, 8H)

Example 617 N-(2-Trifluoromethylbenzyl)-N-phenethylthiocarbamoyl-2(S)-{[l -(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

^'H-NMR (CDCb) : δ 6.99-7.64(m, 14H), 6.22 (bs, IH), 5.30(s, 2H), 5.12(d, IH), 4.63(m, IH), 4.61(d, IH), 4.02(m, IH), 3.89(m, 2H), 3.3 l(s, 2H), 2.91(dd, IH), 2.86 (t, 2H), 1.13(d, 3H)

Example 618

N-(2-TrifluoiOmethylbenzyl)-N-phenylthiocarbamoyl-2(S)-{[l-(4-cyanobenzyl )- 1 H-imidazol-5 -yl]acetyl } aminopropylamine

-H-NMR (CDCb) : δ 8.62 (bs, IH), 6.96-7.71(m, 14H), 5.74(d, IH), 5.24(s, 2H), 4.8 l(d, IH), 4.55(m, IH), 4.14(m, IH), 3.33(s, 2H), 3.00(dd, IH), 1.21(d, 3H)

Example 619

N-(2-Trifluorome. ylberιzyl)-N-(n-propylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

^'H-NMR (CDCb) : δ 6.99-7.71(m, 9H), 6.30 (bs, IH), 5.32(s, 2H), 5.27(d, IH), 4.69(d, IH), 4.64(m, IH), 4.08(m, IH), 3.57(m, 2H), 3.33(s, 2H), 2.96(dd, IH), 1.53(dd, IH), 1.17(d, 3H), 0.79 (t, 3H)

Example 620

N-(2-Trifluoromethylbenzyl)-N-(2-methylphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- 1 H-imidazol-5-yl] acetyl } aminopropylamine

1H-NMR (CDCb) : δ 8.42 (bs, IH), 6.97-7.7 l(m, 13H), 5.69(d, IH), 5.25(s, 2H), 4.8 l(d, IH), 4.62(m, IH), 4.15(m, IH), 3.34(s, 2H), 3.01(dd, IH), 2.33(s, 3H), 1.21(d, 3H) Example 621

N-(2-Trifluoromethylbenzyl)-N-(3-methylphenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- lH-imidazol-5-yl]acetyl} aminopropylamine

Η-NMR (CDCb) : δ 7.82 (bs, IH), 6.97-7.73(m, 13H), 5.5 l(d, IH), 5.26(s, 2H), 4.86(d, IH), 4.75(m, IH), 4.20(m, IH), 3.32(s, 2H), 3.07(dd, IH), 2.09(s, 3H), 1.21(d, 3H)

Example 622

N-(2-Trifluoromethylbenzyl)-N-(4-methylphenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } aminopropylamine

Η-NMR (CDCb) : δ 8.39 (bs, IH), 6.97-7.7 l(m, 13H), 5.66(d, IH), 5.25(s, 2H), 4.8 l(d, IH), 4.63(m, IH), 4.15(m, IH), 3.33(s, 2H), 3.00(dd, IH), 2.34(s, 3H), 1.21(d, 3H)

Example 623

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

-H-NMR (CDCb) : δ 9.51 (bs, IH), 6.92-7.89(m, 13H), 6.06(d, IH), 5.27(s, 2H), 4.78(d, IH), 4.30(m, IH), 4.12(m, IH), 3.33(s, 2H), 2.97(dd, IH), 1.25(d, 3H)

Example 624

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

1H-NMR (CDCb) : δ 6.97-7.72(m, 12H), 5.46(d, IH), 5.27(s, 2H), 4.85(d, IH), 4.75(m, IH), 4.19(m, IH), 3.32(s, 2H), 3.07(dd, IH), 2.3 l(s, 3H), 2.05(s, 3H), 1.20(d, 3H)

Example 625

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

1H-NMR (CDCb) : δ 8.30 (bs, IH), 6.98-7.71(m, 12H), 5.64(d, IH), 5.26(s, 2H), 4.8 l(d, IH), 4.62(m, IH), 4.15(m, IH), 3.33(s, 2H), 3.01(dd, IH), 2.23(s, 6H), 1.20(d, 3H)

Example 626

N-(2-Trifluoromethylbenzyl)-N-allylthiocarbamoyl-2(S)-{[l-(4-cyanobenzyl)-l

H-imidazol-5-yl]acetyl}amino-3-methylbutylamine

<Step 1>

N-(2-Trifluoromethylbenzyl)-2(S)-{[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acety 1 } amino-3 -methylbutylamine

Using the same method as described in Preparative Example 3, N-t-butoxycarbonyl-L-valine was converted to N-t-butoxycarbonyl-L- valine aldehyde. And then the reaction was carried out under the same condition as described in Preparative Example 4, but replacing 2,3-dichlorobenzylamine and 1 -(4-nitrobenzyl)- 1 H-imidazol-5 -ylacetic acid hydrochloride with 2-trifluoromethylbenzylamine and l-(4-cyanobenzyl)- lH-imidazol-5-ylacetic acid hydrochloride, respectively, to give the title compound.

-H-NMR (CDCb) : δ 7.00 - 7.65(m, 10H), 6.23(d, IH), 5.27(s, 2H), 3.88(s, 2H), 3.81(m, IH), 3.37(s, 2H), 2.68(d, 2H), 1.76(m, IH), 0.84 (t, 6H)

<Step 2>

N-(2-Trifluoromethylbenzyl)-N-allylthiocarbamoyl-2(S)- { [ 1 -(4-cyanobenzyl)- 1

H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

To a solution of N-(2-trifluoromethylbenzyl)-2(S)-{ [1 -(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}amino-3-methylbutylamine in dichloromethane (0.02M, 1ml, 0.02mmol) was added allylisothiocyanate (O. IM in CH2CI2, 0.2ml, 0.02mmol). The reaction mixture was agitated for 3hr at room temperature. The mixture was purified by silica gel column chromatography(eluent: CH2Cl2/MeOH=9/l, v/v) to give the title compound as a white solid.

Η-NMR (CDCb) : δ 7.00-7.73(m, 9H), 5.96 (bs, IH), 5.81(m, IH), 5.35(d, 2H), 5.02(m, 2H), 4.97(d, IH), 4.65(d, IH), 4.26(m, IH), 4.04(m, IH), 3.33(s, 2H), 3.08(dd, IH), 1.87(m, IH), 0.91 (t, 6H)

Examples 627-669

N-(2-Trifluoromethylbenzyl)-2(S)-{[l-(4-cyanobenzyl)-lH-imidazol-5- yl]acetyl}amino-3-methylbutylamine was reacted with the conesponding isothiocyanates under the same condition as described in <Step 2> of Example 626 to give the title compounds.

Example 627

N-(2-Trifluoromethylbenzyl)-N-benzylthiocarbamoyl-2(S)- { [ 1 -(4-cyanobenzyl

)- 1 H-imidazol-5-yl] acetyl } amino-3 -methylbutylamine

'H-NMR (CDCb) : δ 6.99-7.68(m, 14H), 6.21 (bs, IH), 5.27(d, 2H), 5.05 (t, IH), 4.96(d, IH), 4.81(dd, 2H), 4.67(d, IH), 4.05(m, IH), 3.28(s, 2H), 3.10(dd, IH), 1.83(m, IH), 1.90(dd, 6H)

Example 628

N-(2-Trifluoromethylbenzyl)-N-(2-biphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

^•H-NMR (CDCb) : δ 6.89-7.71(m, 18H), 5.25(s, 2H), 5.20(m, IH), 4.76(m, IH), 4.62(d, IH), 3.97(m, IH), 3.33(s, 2H), 2.99(dd, IH), 1.84(m, IH), 0.85(dd, 6H)

Example 629

N-(2-Trifluoromethylbenzyl)-N-(2-bromophenylthiocarbamoyl)-2(S)-{ [ 1 -(4-cy anobenzyl)- 1 H-imidazol-5-yl] acetyl } amino-3 -methylbutylamine

Η-NMR (CDCb) : δ 7.02-7.76(m, 13H), 5.26(s, 2H), 5.20(d, IH), 5.17(m, IH), 4.88(d, IH), 4.39(m, IH), 3.38(s, 2H), 3.20(dd, IH), 1.88(m, IH), 0.91(dd, 6H)

Example 630

N-(2-Trifluoromethylbenzyl)-N-(3-bromophenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5 -yl]acety 1 } amino-3 -methylbutylamine

1H-NMR (CDCb) : δ 8.47 (bs, IH), 6.795-7.72(m, 13H), 5.54(d, IH), 5.27(s, 2H), 4.76(d, IH), 4.72(m, IH), 4.05(m, IH), 3.35(s, 2H), 3.14(dd, IH), 1.90(m, IH), 0.90 (t, 6H)

Example 631

N-(2-Trifluoromethylbenzyl)-N-(4-bromophenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine 1H-NMR (CDCb) : δ 8.28 (bs, IH), 6.80-7.74(m, 13H), 5.47(d, IH), 5.28(d, 2H), 4.79(m, IH), 4.78(d, IH), 4.07(m, IH), 3.36(s, 2H), 3.16(dd, IH), 1.91(m, IH), 0.9 l(m, 6H)

Example 632

N-(2-TrifluoiOmethylbenzyl)-N-(n-butylthiocarbamoyl)-2(S)-{[l-(4-cyanobenz yl)- 1 H-imidazol-5 -yl]acetyl } amino-3 -methylbutylamine

Η-NMR (CDCb) : δ 7.01-7.73(m, 9H), 5.71 (bs, IH), 5.35(d, 2H),

5.05 (t, IH), 4.75(dd, 2H), 4.02(m, IH), 3.53(m, 2H), 3.33(s, 2H),

3.07(dd, IH), 1.87(m, IH), 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-cyanobenzy

1)- 1 H-imidazol-5-yl]acetyl} amino-3 -methylbutylamine

^'H-NMR (CDCb) : δ 7.02-7.74(m, 9H), 5.69 (bs, IH), 5.37(d, 2H),

5.14 (t, IH), 4.76(dd, 2H), 4.05(m, IH), 3.48(m, IH), 3.34(s, 2H),

3.28(m, IH), 3.12(dd, IH), 1.87(m, IH), 1.76(m, IH), 0.93(dd, 6H), 0.70(m, 6H)

Example 634

N-(2-Trifluoromethylbenzyl)-N-(2-chlorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- lH-imidazol-5-yl]acetyl} amino-3 -methylbutylamine

Η-NMR (CDCb) : δ 6.96-7.76(m, 13H), 5.28(d, 2H), 5.17(d, IH), 5.09(m, IH), 4.87(d, IH), 4.19(m, IH), 3.38(d, 2H), 3.19(dd, IH), 1.90(m, IH), 0.92 (t, 6H) Example 635

N-(2-Trifluoromethylbenzyl)-N-(3 -chlorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

Η-NMR (CDCb) : a 8.45 (bs, IH), 6.82-7.74(m, 13H), 5.55(d, IH), 5.29(d, 2H), 4.78 (d IH), 4.74(m, IH), 4.07(m, IH), 3.37(s, 2H), 3.16(dd, IH), 1.92(m, IH), 0.92 (t, 6H)

Example 636

N-(2-Trifluoromethylbenzyl)-N-(4-chlorophenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5-yl] acetyl } amino-3 -methylbutylamine

Η-NMR (CDCb) : a 8.26 (bs, IH), 6.81-7.73(m, 13H), 5.46(d, IH), 5.25(d, 2H), 4.80(m, IH), 4.77(d, IH), 4.05(m, IH), 3.35(s, 2H), 3.14(dd, IH), 1.90(m, IH), 0.90 (t, 6H)

Example 637

N-(2-Trifluoromethylbenzyl)-N-(3-chloiO-4-methylphenylthiocarbamoyl)-2(S)-

{[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3-methylbutylamine

1H-NMR (CDCb) : a 8.29 (bs, IH), 6.87-7.73(m, 12H), 5.49(d, IH), 5.28(s, 2H), 4.79(m, IH), 4.77(d, IH), 4.07(m, IH), 3.36(s, 2H), 3.14(dd, IH), 2.34(s, 3H), 1.91(m, IH), 0.91 (t, 6H)

Example 638

N-(2-Trifluoromethylbenzyl)-N-cyclohexylthiocarbamoyl-2(S)- { [ 1 -(4-cyanobe nzyl)- lH-imidazol-5-yl]acetyl} amino-3 -methylbutylamine

^"H-NMR (CDCb) : a 7.04-7.74(m, 9H), 5.98 (bs, IH), 5.36(s, 2H), 5.12 (t, IH), 4.75(dd, IH), 4.18(m, IH), 4.0 l(m, IH), 3.34(s, 2H), 3.08(dd, IH), 1.84(m, IH), 0.83-1.98(m, 10H), 0.90 (t, 6H)

Example 639

N-(2-Trifluoromethylbenzyl)-N-cyclopentylthiocarbamoyl-2(S)- {[ 1 -(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3-methylbutylamine

^'H-NMR (CDCb) : a 7.03-7.73(m, 9H), 5.54 (bs, IH), 5.35(d, 2H), 5.03 (t, IH), 4.75(dd, 2H), 4.61(m, IH), 4.01(m, IH), 3.34(s, 2H), 3.08(dd, IH), 1.85(m, IH), 1.09-2.06(m, 8H), 0.91(dd, 6H)

Example 640

N-(2-Trifluoromethylbenzyl)-N-(2,4-dichlorophenylthiocarbamoyl)-2(S)- { [ 1 -(4 -cy anobenzyl)- 1 H-imidazol-5 -yl]acetyl } amino-3 -methylbutylamine

-H-NMR(CDCb) : a 6.82-7.75(m, 12H), 5.28(d, IH), 5.26(s, 2H), 4.92(m, IH), 4.85(d, IH), 4.16(m, IH), 3.35(s, 2H), 3.19(dd, IH), 1.87(m, IH), 0.90(t, 6H)

Example 641

N-(2-Trifluoromethylbenzyl)-N-[2-(dimethylamino)ethylthiocarbamoyl]-2(S)-{

[l-(4-cyanobenzyl)-lH-imidazol-5-yl]ace1yl}ammo-3-methylbutylamine

1H-NMR(CDCb) : r5 7.02-7.71(m, 9H), 6.82(bs, IH), 5.36(dd, 2H), 4.79(m, 3H), 4.28(m, IH), 3.56(m, 2H), 3.33(d, 2H), 3.14(dd, IH), 2.44(m, 2H), 1.97(s, 6H), 1.88(m, IH), 0.89(d, 6H)

Example 642

N-(2-Trifluoromethylbenzyl)-N-[4-(dimethylamino)phenylthiocarbamoyl]-2(S) - { [ 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl] acetyl } amino-3 -methylbutylamine -H-NMR(CDCb) : a 6.61-7.73(m, 13H), 5.29(s, 2H), 5.18(d, IH), 5.14(m, IH), 4.79(d, IH), 4.08(m, IH), 3.35(s, 2H), 3.12(dd, IH), 2.93(s, 6H), 1.88(m, IH), 0.90(dd, 6H)

Example 643

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

-H-NMR(CDCb) : a 8.87(bs, IH), 7.04-7.72(m, 13H), 5.41(dd, 2H),

4.92(m, IH), 4.74(s, 2H), 4.01(m, IH), 3.73(m, 2H), 3.35(d, 2H),

2.92(dd, IH), 2.44(m, 2H), 1.89(s, 6H), 1.83(m, IH), 1.80(m, 2H), 0.88(dd, 6H)

Example 644

N-(2-Trifluoromethylbenzyl)-N-(3-ethoxypropylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

-H-NMR(CDCb) : a 7.04-7.72(m, 9H), 6.75(bs, IH), 5.38(dd, 2H), 5.09(t, IH), 4.70(dd, 2H), 4.0 l(m, IH), 3.75(m, 2H), 3.39(m, 2H), 3.36(s, 2H), 3.14(m, 2H), 2.95(dd, IH), 1.85(m, IH), 1.8 l(m, 2H), 0.88(dd, 6H), 0.80(t, 3H)

Example 645

N-(2-Trifluoromethylbenzyl)-N-ethylthiocarbamoyl-2(S)- { [ 1 -(4-cyanobenzy 1)-

1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

-H-NMR(CDCb) : a 7.00-7.72(m, 9H), 5.80(bs, IH), 5.35(dd, 2H), 4.98(t, IH), 4.93(d, IH), 4.62(d, IH), 4.02(m, IH), 3.60(m, 2H), 3.33(s, 2H), 3.05(dd, IH), 1.87(m, IH), 1.06(t, 3H), 0.90(m, 6H) Example 646

N-(2-Trifluoromethylbenzyl)-N-(2-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl} amino-3 -methylbutylamine

-H-NMR(CDCb) : a 6.93-7.75(m, 13H), 5.29(d, IH), 5.27(s, 2H), 5.0 l(t, IH), 4.83(d, IH), 4.13(m, IH), 3.37(s, 2H), 3.151(dd, IH), 1.88(m, IH), 0.90(t, 6H)

Example 647

N-(2-Trifluoromethylbenzyl)-N-(3-fluoiOphenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- lH-imidazol-5-yl]acetyl}amino-3-methylbutylamine

-H-NMR(CDCb) : a 8.35(bs, IH), 6.82-7.73(m, 13H), 5.50(d, IH), 5.27(s, 2H), 4.80(m, IH), 4.77(d, IH), 4.06(m, IH), 3.36(s, 2H), 3.15(dd, IH), 1.89(m, IH), 0.9 l(t, 6H)

Example 648

N-(2-Trifluoromethylbenzyl)-N-(4-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- lH-imidazol-5-yl]acetyl} amino-3 -methylbutylamine

Η-NMR(CDCb) : a 8.05(bs, IH), 6.87-7.73(m, 13H), 5.38(d, IH), 5.27(s, 2H), 4.82(m, IH), 4.78(d, IH), 4.06(m, IH), 3.34(s, 2H), 3.15(dd, IH), 1.88(m, IH), 0.90(t, 6H)

Example 649

N-(2-Trifluoromethylbenzyl)-N-(4-hydroxyphenylthiocarbamoyl)-2(S)- { [ 1 -(4-c yanobenzyl)- 1 H-imidazol-5-yl]acetyl } amino-3 -methylbutylamine

-H-NMR(CD₃OD) : a 6.69-7.75(m, 13H), 5.43(d, IH), 5.37(s, 2H), 5.05(d, IH), 4.25(m, 2H), 3.49(dd, 2H), 2.68(m, IH), 1.77(m, IH), 0.90(d, 6H)

Example 650

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

-H-NMR(CDCb) : a 7.02-7.73(m, 13H), 5.27(s, 2H), 5.18(d, IH), 5.04(t, IH), 4.79(d, IH), 4.08(m, IH), 3.35(s, 2H), 3.14(dd, IH), 2.89(m, IH), 1.87(m, IH), 1.22(d, 6H), 0.91(t, 6H)

Example 651

N-(2-Trifluoromethylbenzyl)-N-(2-methoxyethylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

-H-NMR(CDCb) : a 7.03-7.73(m, 9H), 5.96(bs, IH), 5.36(dd, 2H), 5.11(t, IH), 4.73(dd, IH), 4.13(m, IH), 3.70(m, 2H), 3.37(m, 2H), 3.34(s, 2H), 3.09(dd, IH), 3.07(s, 3H), 1.86(m, IH), 0.91(d, 6H)

Example 652

N-(2-Trifluoromethylbenzyl)-N-(2-methoxyphenylthiocarbamoyl)-2(S )- { [ 1 -(4- cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

1H-NMR(CDCb) : a 8.28(d, IH), 6.76-7.78(m, 13H), 5.20(s, 2H), 5.19(t, IH), 5.01(dd, 2H), 4.18(m, IH), 3.52(s, 3H), 3.37(s, 2H), 3.15(dd, IH), 1.87(m, IH), 0.94(d, 6H)

Example 653

N-(2-Trifluoromethylberιzyl)-N-(4-methoxyphenylthiocaιbamoyl)-2(S)-{[l-(4- cy anobenzyl)- 1 H-imidazol-5-yl] acetyl } amino-3 -methylbutylamine 1H-NMR(CDCb) : a 6.82-7.73(m, 13H), 5.30(s, 2H), 5.25(d, IH), 4.99(s, IH), 4.79(d, IH), 4.07(m, IH), 3.78(s, 3H), 3.35(s, 2H), 3.13(dd, IH), 1.88(m, IH), 0.90(t, 6H)

Example 654

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

-H-NMR(CDCb) : a 6.81-7.73(m, 9H), 5.38(dd, 2H), 5.11(t, IH), 4.68(s, 2H), 4.02(m, IH), 3.70(m, 2H), 3.39(m, 2H), 3.33(s, 2H), 2.97(dd, IH), 2.80(s, 3H), 1.83(m, IH), 1.77(m, 2H), 0.89(d, 6H)

Example 655

N-(2-Trifluoromethylbenzyl)-N-(2-methoxypyridin-5-ylthiocarbamoyl)2(S)-{[l -(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

-H-NMR(CDCb) : a 8.28(bs, IH), 6.69-7.9 l(m, 12H), 5.45(d, IH), 5.27(d, 2H), 4.81(m, IH), 4.78(d, IH), 4.07(m, IH), 3.90(s, 3H), 3.33(s, 2H), 3.14(dd, IH), 1.91(m, IH), 0.90(t, 6H)

Example 656

N-(2-Trifluoromethylbenzyl)-N-methylthiocarbamoyl-2(S)- { [ 1 -(4-cyanobenzyl

)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

-H-NMR(CDCb) : a 6.97-7.7 l(m, 9H), 6.20(bs, IH), 5.35(dd, 2H), 4.96(d, IH), 4.91(t, IH), 4.61(d, IH), 4.00(m, IH), 3.33(s, 2H), 3.08(s, 3H), 3.04(dd, IH), 1.86(m, IH), 0.90(t, 6H)

Example 657 N-(2-Trifluoromethylbenzyl)-N-(4-methylthiophenylthiocarbamoyl)-2(S)-{[l-( 4-cyanobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

-H-NMR(CDCb) : a 7.94(bs, IH), 6.88-7.73(m, 13H), 5.36(d, IH), 5.26(d, 2H), 4.92(t, IH), 4.78(d, IH), 4.06(m, IH), 3.35(s, 2H), 3.14(dd, IH), 2.46(s, 3H), 1.88(m, IH), 0.90(t, 6H)

Example 658

N-(2-Trifluoromethylbenzyl)-N-(2-naphthylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-3-methylbutylamine

1H-NMR(CDCb) : a 8.21(bs, IH), 6.85-7.82(m, 16H), 5.44(d, IH), 5.20(d, 2H), 4.97(m, IH), 4.83(d, IH), 4.11(m, IH), 3.37(s, 2H), 3.16(dd, IH), 1.89(m, IH), 0.9 l(t, 6H)

Example 659

N-(2-Trifluoromethylbenzyl)-N-(4-nitrophenylthiocarbamoyl)-2(S)-{[l -(4-cyan obenzyl)- 1 H-imidazol-5 -yl]acetyl } amino-3 -methylbutylamine

-H-NMR(CDCb) : a 9.13(bs, IH), 6.62-8.17(m, 13H), 5.73(d, IH), 5.26(s, 2H), 4.76(d, IH), 4.56(m, IH), 4.03(m, IH), 3.38(s, 2H), 3.19(dd, IH), 1.96(m, IH), 0.91(dd, 6H)

Example 660

N-(2-Trifluoromethylbenzyl)-N-(n-pentylthiocarbamoyl)-2(S)-{[l-(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

-H-NMR(CDCb) : a 7.02-7.74(m, 9H), 5.59(bs, IH), 5.36(dd, 2H), 5.17(t, IH), 4.74(dd, 2H), 4.04(m, IH), 3.33(s, 2H), 3.19-3.74(m, 2H), 3.11(dd, IH), 1.87(m, IH), 1.51(m, IH), 1.14(m, IH), 1.06(m, 2H), 0.92(dd, 6H), 0.87(m, 2H), 0.64(t, 3H)

Example 661

N-(2-Trifluoromethylbenzyl)-N-phenethylthiocarbamoyl-2(S)- { [ 1 -(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl} amino-3 -methylbutylamine

^'H-NMR(CDCb) : a 6.97-7.68(m, 14H), 5.70(bs, IH), 5.34(dd, 2H), 4.99(t, IH), 4.64(dd, 2H), 3.99(m, IH), 3.86(m, 2H), 3.32(s, 2H), 3.01(dd, IH), 2.80(t, 2H), 1.83(m, IH), 0.89(dd, 6H)

Example 662

N-(2-Trifluoromethylbenzyl)-N-phenylthiocarbamoyl-2(S)-{[l-(4-cyanobenzyl

)-lH-imidazol-5-yl]acetyl}amino-3-methylbutylamine

1H-NMR(CDCb) : a 7.94(bs, IH), 6.94-7.73(m, 14H), 5.36(d, IH), 5.26(s, 2H), 4.98(t, IH), 4.80(d, IH), 4.08(m, IH), 3.35(s, 2H), 3.14(dd, IH), 1.87(m, IH), 0.90(dd, 6H)

Example 663

N-(2-Trifluoromethylbenzyl)-N-(n-propylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

-H-NMR(CDCb) : a 7.00-7.72(m, 9H), 5.74(bs, IH), 5.35(dd, 2H), 5.05(t, IH), 4.76(dd, 2H), 4.02(m, IH), 3.58(m, IH), 3.48(m, IH), 3.33(s, 2H), 3.07(dd, IH), 1.85(m, IH), 1.45(m, 2H), 0.91(dd, 6H), 0.72(t, 3H)

Example 664

N-(2-Trifluoromethylbenzyl)-N-(2-methylphenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5-yl] acetyl } amino-3 -methylbutylamine -H-NMR(CDCb) : a 6.94-7.75(m, 13H), 5.35(d, IH), 5.28(s, 2H), 5.00(t, IH), 5.02(t, IH), 4.81(d, IH), 4.10(m, IH), 3.37(s, 2H), 3.15(dd, IH), 2.33(s, 3H), 1.89(m, IH), 0.92(dd, 6H)

Example 665

N-(2-Trifluoromethylbenzyl)-N-(3-methylphenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

-H-NMR(CDCb) : a 7.01-7.75(m, 13H), 5.30(s, 2H), 5.23(d, IH), 5.10(t, IH), 4.84(d, IH), 4.14(m, IH), 3.36(s, 2H), 3.18(dd, IH), 2.01(s, 3H), 1.91(m, IH), 0.91(t, 6H)

Example 666

N-(2-Trifluoromethylbenzyl)-N-(4-methylphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- 1 H-imidazol-5 -yl]acety 1 } amino-3 -methylbutylamine

-H-NMR(CDCb) : a 7.76(bs, IH), 7.00-7.73(m, 13H), 5.27(s, 2H), 5.23(d, IH), 5.00(t, IH), 4.79(d, IH), 4.08(m, IH), 3.35(s, 2H), 3.13(dd, IH), 2.32(s, 3H), 1.87(m, IH), 0.90(t, 6H)

Example 667

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

-H-NMR(CDCb) : a 8.82(bs, IH), 6.75-7.73(m, 13H), 5.67(d, IH), 5.26(s, 2H), 4.77(d, IH), 4.62(m, IH), 4.06(m, IH), 3.36(s, 2H), 3.17(dd, IH), 1.92(m, IH), 0.91(t, 6H)

Example 668 N-(2-Trifluoromethylbenzyl)-N-(2,4-dimethylphenylthiocarbamoyl)-2(S)-{[l-( 4-cyanobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -methylbutylamine

-H-NMR(CDCb) : a 6.92-7.75(m, 13H), 5.29(s, 2H), 5.21(d, IH), 5.15(m, IH), 4.83(d, IH), 4.12(m, IH), 3.35(s, 2H), 3.17(dd, IH), 2.30(s, 3H), 1.96(s, 3H), 1.90(m, IH), 0.90(t, 6H)

Example 669

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

-H-NMR(CDCb) : a 6.93-7.73(m, 13H), 5.28(s, 2H), 5.22(d, IH), 5.02(t, IH), 4.79(d, IH), 4.10(m, IH), 3.36(s, 2H), 3.13(dd, IH), 2.21(s, 6H), 1.86(m, IH), 0.90(t, 6H)

Example 670

N-(2-Trifluoromethylbenzyl)-N-allylthiocarbamoyl-2(S)-{[l-(4-cyanobenzyl)-l

H-imidazol-5-yl]acetyl}amino-4-methylpentylamine

<Step 1>

N-(2-Trifluoromethylbenzyl)-2(S)- {[ 1 -(4-cyanobenzyl)- lH-imidazol-5-yl]acety

1 } amino-4-methy lpentylamine

Using the same method as described in Preparative Example 3, N-t-butoxycarbonyl-L-leucine was converted to N-t-butoxycarbonyl-L- leucine aldehyde. And then the reaction was carried out under the same condition as described in Preparative Example 4, but replacing 2,3-dichlorobenzylamine and 1 -(4-nitrobenzyl)- 1 H-imidazol-5 -ylacetic acid hydrochloride with 2-trifluoromethylbenzylamine and l-(4-cyanobenzyl)- 1 H-imidazol-5 -ylacetic acid hydrochloride, respectively, to give the title compound. ^'H-NMR(CDCb) : a 7.00-7.66(m, 10H), 6.14(d, IH), 5.27(s, 2H), 4.08(m, IH), 3.90(s, 2H), 3.35(s, 2H), 2.65(d, 2H), 1.52(m, IH), 1.27(m, 2H), 0.88(d, 6H)

<Step 2>

N-(2-Trifluoromethylbenzyl)-N-allylthiocarbamoyl-2(S)-{ [ 1 -(4-cyanobenzyl)- 1

H-imidazol-5-yl]acetyl}amino-4-methylpentylamine

To a solution of N-(2-trifluoromethylbenzyl)-2(S)-{ [1 -(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine in dichloromethane (0.02M, 1ml, 0.02mmol) was added allylisothiocyanate (O. IM in CH2CI2, 0.2ml, 0.02mmol). The reaction mixture was agitated for 3hr at room temperature. The mixture was purified by silica gel column chromatography(eluent: CH2Cl2/MeOH=9/l, v/v) to give the title compound as a white solid.

1H-NMR(CDCb) : a 6.78-7.71(m, 11H), 6.40(bs, IH), 5.85(m, 2H), 5.33(d, 2H), 4.69-5.07(dd, 2H), 4.69(bs, IH), 4.33(d, 2H), 4.15(m, IH), 3.3 l(s, 2H), 3.05(dd, IH), 1.25-1.52(m, 3H), 0.85(d, 6H)

Examples 671-713

N-(2-Trifluoromethylbenzyl)-2(S)- { [ 1 -(4-cyanobenzyl)- 1 H-imidazol-5 - yl] acetyl }amino-4-methylpentylamine was reacted with the conesponding isothiocyanates under the same condition as described in <Step 2> of Example 670 to give the title compounds.

Example 671

N-(2-Trifluoromethylbenzyl)-N-benzylthiocarbamoyl-2(S)- { [ 1 -(4-cyanobenzyl )-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

-H-NMR(CDCb) : a 6.72-7.67(m, 14H), 6.75(bs, IH), 5.22(d, 2H), 4.63-4.98(m, 3H), 4.17(m, IH), 3.25(s, 2H), 3.05(dd, IH), 1.25-1.62(m, 3H), 0.85(d, 6H)

Example 672

N-(2-Trifluoromethylbenzyl)-N-(2-biphenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)- lH-imidazol-5-yl]acetyl} amino-4-methylpentylamine

^'H-NMR(CDCb) : a 6.93-7.71(m, 19H), 6.66(bs, IH), 5.12-5.21(m, 3H), 4.67-4.76(d, IH), 4.09(m, IH), 3.29(s, 2H), 2.92(dd, IH), 1.10-1.62(m, 3H), 0.83(d, 6H)

Example 673

N-(2-Trifluoromethylbenzyl)-N-(2-biOmophenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-4-methylpentylamine

¹H-NMR(CDCb) : a 6.99-7.82(m, 13H), 6.65(bs, IH), 5.48(m, IH), 5.29(s, IH), 5.22(s, 2H), 4.87-4.96(d, IH), 4.71(m, IH), 4.36(m, IH), 3.35(s, 2H), 3.14(dd, IH), 1.25-1.62(m, 3H), 0.89(d, 6H)

Example 674

N-(2-Trifluoromethylbenzyl)-N-(3-bromophenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl} amino-4-methylpentylamine

1H-NMR(CDCb) : a 8.95(bs, IH), 6.96-7.71(m, 13H), 6.66(d, IH), 5.75(bd, IH), 5.26(s, 2H), 4.86(d, IH), 4.40(m, IH), 4.13(m, IH), 3.34(s, 2H), 3.03(dd, IH), 1.26-1.70(m, 3H), 0.86(d, 6H) Example 675

N-(2-Trifluoromethylbenzyl)-N-(4-bromophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl }amino-4-methylpentylamine

-H-NMR(CDCb) : a 8.73(bs, IH), 6.95-7.71(13H), 6.63(d, lH), 5.70(d, IH), 5.21(s, 2H), 4.85(d, IH), 4.47(m, IH), 4.14(m. IH), 3.34(s, 2H), 3.03(dd, IH), 1.26-1.70(m, 3H), 0.86(d, 6H)

Example 676

N-(2-Trifluoromethylbenzyl)-N-(n-butylthiocarbamoyl)-2(S)-{[l-(4-cyanobenz yl)- 1 H-imidazol-5 -yl] acetyl} amino-4-methylpentylamine

1H-NMR(CDCb) : a 6.98-7.82(m, 9H), 6.86(d, IH), 6.22(bs, IH), 5.00-5.42(m, 3H), 4.70(d, lH), 4.14(m, IH), 3.40-3.78(m, 2H), 3.32(s, 2H), 2.99(dd, IH), l. l l-1.70(m, 8H), 0.88(m, 10H)

Example 677

N-(2-Trifluoromethylbenzyl)-N-isobutylthiocarbamoyl-2(S )-{[ 1 -(4-cyanobenzy

1)- 1 H-imidazol-5 -yl]acetyl } amino-4-methylpentylamine

^'H-NMR(CDCb) : a 6.86-7.82(m, 10H), 6.11(bs, IH), 4.98-5.52(m, 3H), 4.66-4.75(d, 2H), 4.18(bs, IH), 3.47-3.80(m, IH), 3.3 l(s, 2H), 3.03(dd, IH), 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-cy anobenzyl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

1H-NMR(CDC1₃) : a 6.98-7.74(m, 13H), 6.66(bs, IH), 5.38-5.60(bs, IH), 5.22(s, 2H), 4.90(d, IH), 4.70(m, IH), 4.35(m, IH), 3.35(s, 2H), 3.12(dd, IH), 1.25-1.60(m, 3H), 0.89(d, 6H)

Example 679

N-(2-Trifluoromethylbenzyl)-N-(3-chlorophenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5-yl] acetyl } amino-4-methylpentylamine

-H-NMR(CDCb) : a 8.93(bs, IH), 6.95-7.71(13H), 6.70(d, IH), 5.75(bd, IH), 5.25(s, 2H), 4.90(d,lH), 4.39 9m, IH), 4.15(m, IH), 3.34(s, 2H), 3.02(dd, IH), 1.25-1.68(m, 3H), 0.86(d, 6H)

Example 680

N-(2-Trifluoromethylbenzyl)-N-(4-chlorophenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-4-methy lpentylamine

Η-NMR(CDCb) : a 8.71(1H, br), 6.95-7.71(m, 13H), 6.63(d, IH), 5.70(bd, IH), 5.22(s, 2H), 4.46(m, IH), 4.16(m, IH), 3.34(s, 2H), 3.04(dd, IH), 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)- 1 H-imidazol-5 -yl] acetyl } amino-4-methy lpentylamine

^•H-NMR(CDCb) : a 8.71(bs, IH), 6.96-7.7 l(m, 2H), 6.70(d, IH), 5.70(bd, IH), 5.25(s, 2H), 4.88(d, IH), 4.30(m, IH), 4.15(m, IH), 3.34(s, 2H), 3.03(dd, IH), 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-cyanobe nzyl)- 1 H-imidazol-5-yl] acetyl } amino-4-methylpentylamine 1H-NMR(CDCb) : a 6.96-7.72(m, 9H), 6.86(bd, IH), 5,86(bs, IH), 5.10-5.30(m, 3H), 4.70(d, 2H), 4.20(m, 2H), 3.32(s, 2H), 3.03(dd, IH), 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-cyanobe nzyl)- lH-imidazol-5-yl]acetyl} amino-4-methylpentylamine

-H-NMR(CDCb) : a 6.96-7.72(m, 9H), 6.85(bd, IH), 5.95(bs, IH), 5.10-5.42(m, 3H), 4.66(m, 2H), 4.15(m, IH), 3.32(s, 2H), 3.03(dd, IH), 1.80-2.10(m, 3H), 1.10-1.72(m, 9H), 0.86(d, 6H)

Example 684

N-(2-Trifluoromethylbenzyl)-N-(2,4-dichloiOphenylthiocarbamoyl)-2(S)- { [ 1 -(4 -cy anobenzyl)- 1 H-imidazol-5-y 1] acetyl } amino-4-methylpentylamine

-H-NMR(CDCb) : a 6.98-7.73(m, 12H), 6.55(bd, IH), 5.52(m, IH), 5.22(s, 2H), 4.90(d, IH), 4.59(m, IH), 4.32(m, IH), 3.34(s, 2H), 3.10(dd, IH), 1.25-1.62(m, 3H), 0.87(d, 6H)

Example 685

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

-H-NMR(CDCb) : a 7.03-7.72(m, 10H), 6.72(bs, IH), 5.39(dd, 2H), 5.07(m, IH), 4.74(m, 2H), 4.08(m, IH), 3.52(bs, 2H), 3.36(s, 2H), 3.13(dd, IH), 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)- lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

-H-NMR(CDCb) : a 7.83(bs, IH), 6.58-7.72(m, 14H), 5.38(d, IH), 5.26(s, 2H), 4.86(d, IH), 4.74(m, IH), 4.24(m, IH), 3.34(s, 2H), 3.07(dd, IH), 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)- 1 H-imidazol-5 -yl] acetyl } amino-4-methylpentylamine

1H-NMR(CDCb) : a 8.75(bs, IH), 7.02-7.71(m, 10H), 5.38(dd, 2H), 4.82(m, 3H), 4.24(m, IH), 3.71(m, 2H), 3.32(dd, 2H), 2.94(dd, IH), 2.55(m, 4H), 2.02(bs, 6H), 1.49(m, 2H), 1.19(m, IH), 0.86(d, 6H)

Example 688

N-(2-Trifluoromethylbenzyl)-N-(3-ethoxypropylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-4-methylpentylamine

-H-NMR(CDCb) : a 7.03-7.71(m, 10H), 6.87(bs, IH), 5.35(dd, 2H), 4.80(m, 3H), 4.20(m, IH), 3.75(m, 2H), 3.41(m, 2H), 3.3 l(s, 2H), 3.16(m, 2H), 2.95(dd, IH), 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-cyanobenzy 1)- lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

1H-NMR(CDCb) : a 6.78-7.71(m, 10H), 6.28(bs, IH), 5.32(d, 2H), 5.22(d, IH), 4.70(d, IH), 4.60(m, IH), 3.64(m, 2H), 3.32(s, 2H), 2.99(dd, IH), 2.94(s, 6H), 1.26-1.57(m, 3H), 1.1 l(t, 3H), 0.87(m, 6H) Example 690

N-(2-Trifluoromethylbenzyl)-N-(2-fluorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

-H-NMR(CDCb) : a 8.12(bs, IH), 6.69-7.72(m, 14H), 5.52(d, IH), 5.23(s, 2H), 4.90(d, IH), 4.66(m, IH), 4.30(m, IH), 3.08(dd, IH), 1.26-1.58(m, 3H), 0.88(d, 6H)

Example 691

N-(2-Trifluoromethylbenzyl)-N-(3-fluoiOphenylthiocarbamoyl)-2(S)- { [ l-(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl }amino-4-methylpentylamine

1H-NMR(CDCb) : a 8.85(bs, IH), 6.69-7.71(m, 14H), 5.81(q, IH), 5.24(s, 2H), 4.88(d, IH), 4.49(m, IH), 4.07(m, IH), 3.34(d, 2H), 3.04(dd, IH), 1.21-1.60(m, 3H), 0.88(d, 6H)

Example 692

N-(2-Trifluoromethylbenzyl)-N-(4-fluorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- 1 H-imidazol-5-yl] acetyl } amino-4-methylpentylamine

1H-NMR(CDCb) : a 8.52(bs, IH), 6.65-7.71(m, 14H), 5.62(d, IH), 5.23(s, 2H), 4.88(d, IH), 4.51(m, IH), 4.17(m, IH), 3.34(d, 2H), 3.05(dd, IH), 1.26-1.58(m, 3H), 0.87(dd, 6H)

Example 693

N-(2-Trifluoromethylbenzyl)-N-(4-hydiOxyphenylthiocarbamoyl)-2(S)- { [ 1 -(4-c yanobenzyl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

1H-NMR(CDCb) : a 8.18(bs, IH), 6.69-7.70(m, 14H), 5.38(d, IH), 5.23(d, 2H), 4.86(d, IH), 4.78(m, IH), 4.23(m, IH), 3.33(s, 2H), 3.04(dd, IH), 1.26-1.58(m, 3H), 0.87(d, 6H)

Example 694

N-(2-Trifluoromethylbenzyl)-N-(4-isopropylphenylthiocarbamoyl)-2(S)-{[l-(4- cyanobenzyl)- 1 H-imidazol-5-yl]acetyl } amino-4-methylpentylamine

1H-NMR(CDCb) : a 8.20(bs, IH), 6.74-7.71(m, 14H), 5.5 l(d, IH), 5.23(s, 2H), 4.87(d, IH), 4.69(m, IH), 4.20(m, IH), 3.34(s, 2H), 3.07(dd, IH), 2.90(m, IH), 1.23(d, 6H), 1.14-1.58(m, 3H), 0.89(m, 6H)

Example 695

N-(2-Trifluoromethylbenzyl)-N-(2-methoxy ethylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

^•H-NMR(CDCb) : a 6.92-7.72(m, 10H), 6.24(bs, IH), 5.33(dd, 2H), 4.86(dd, 2H), 4.78(m, IH), 4.23(m, IH), 3.73(m, 2H), 3.39(m, 2H), 3.32(s, 2H), 3.10(s, 3H), 3.08(dd, IH), 1.26-1.58(m, 3H), 0.89(d, 6H)

Example 696

N-(2-Trifluoromethylbenzyl)-N-(2-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4- cy anobenzyl)- 1 H-imidazol-5-yl] acetyl } amino-4-methylpentylamine

1H-NMR(CDCb) : a 6.77-8.26(m, 14H), 5.19(s, 2H), 5.06(m, IH), 5.03(dd, 2H), 4.39(m, IH), 3.54(s, 3H), 3.36(s, 2H), 3.16(dd, IH), 1.26-1.62(m, 3H), 0.92(d, 6H)

Example 697

N-(2-Trifluoromethylbenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S )- { [ 1 -(4- cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine -H-NMR(CDCb) : a 8.20(bs, IH), 6.78-7.72(m, 14H), 5.5 l(d, IH), 5.24(m, IH), 4.87(d, IH), 4.65(m, IH), 4.23(m, IH), 3.79(s, 3H), 3.33(s, 2H), 3.06(dd, IH), 1.26-1.58(m, 3H), 0.87(d, 6H)

Example 698

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

Η-NMR(CDCb) : a 7.02-7.73(m, 10H), 6.91(bs, IH), 5.35(d, 2H),

4.85(m, IH), 4.78(dd, 2H), 4.21(m, IH), 3.70(m, 2H), 3.39(m, 2H),

3.40(m, 2H), 3.3 l(s, 2H), 2.98(dd, IH), 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)-{[ l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

1H-NMR(CDCb) : a 8.75(bs, IH), 6.69-7.99(m, 13H), 5.69(d, IH), 5.24(s, 2H), 4.88(d, IH), 4.49(m, IH), 4.18(m, IH), 3.91(s, 3H), 3.33(s, 2H), 3.05(dd, IH), 1.26-1.58(m, 3H), 0.87(dd, 6H)

Example 700

N-(2-Trifluoromethylbenzyl)-N-methylthiocarbamoyl-2(S)-{ [ 1 -(4-cyanobenzyl

)- 1 H-imidazol-5-yl] acetyl } amino-4-methylpentylamine

1H-NMR(CDCb) : a 8.21(bs, IH), 6.69-7.72(m, 10H), 5.53(d, IH), 5.23(s, 2H), 4.87(d, IH), 4.66(m, IH), 4.24(m, IH), 3.35(s, 2H), 3.06(dd, IH), 2.32(s, 3H), 1.26-1.58(m, 3H), 0.88(d, 6H)

Example 701 N-(2-Trifluoromethylbenzyl)-N-(4-methylthiophenylthiocarbamoyl)-2(S)-{[l-( 4-cyanobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-4-methylpentylamine

¹H-NMR(CDCb) : 8 8.51(bs, IH), 6.72-7.71(m, 14H), 5.62(d, IH), 5.22(s, 2H), 4.87(d, IH), 4.56(m, IH), 4.20(m, IH), 3.34(s, 2H), 3.05(dd, IH), 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-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } amino-4-methy lpentylamine

-H-NMR(CDCb) : a 8.73(bs, IH), 6.72-7.80(m, 17H), 5.69(d, IH), 5.16(s, 2H), 4.91(d, IH), 4.61(m, IH), 4.24(m, IH), 3.35(s, 2H), 3.07(dd, IH), 1.26-1.58(m, 3H), 0.88(dd, 6H)

Example 703

N-(2-Trifluoromethylbenzyl)-N-(4-nitrophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy an obenzyl)- lH-imidazol-5-yl]acetyl} amino-4-methylpentylamine

-H-NMR(CDCb) : a 9.51(bs, IH), 6.64-8.18(m, 14H), 5.89(d, IH), 5.23(s, 2H), 4.90(d, IH), 4.26(m, IH), 4.11(m, IH), 3.39(s, 2H), 3.07(dd, IH), 1.26-1.53(m, 3H), 0.86(t, 6H)

Example 704

N-(2-Trifluoromethylbenzyl)-N-(n-pentylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanoben zyl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

-H-NMR(CDCb) : a 6.88-7.72(m, 10H), 6.01(bs, IH), 5.24(m, 3H), 4.78(m, IH), 4.7 l(d, IH), 4.20(m, IH), 3.61(m, IH), 3.48(m, IH), 3.32(s, 2H), 3.06(dd, IH), 0.68-1.60(m, 12H), 0.90(d, 6H) Example 705

N-(2-Trifluoromethylbenzyl)-N-phenethylthiocarbamoyl-2(S)-{[l-(4-cyanoben zyl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

^•H-NMR(CDCb) : a 6.99-7.67(m, 14H), 6.88(bs, IH), 5.30(d, 2H), 4.98(d, IH), 4.63(d, IH), 4.62(m, IH), 4.14(m, IH), 3.88(m, 2H), 3.30(s, 2H), 2.97(dd, IH), 2.84(t, 2H), 1.22-1.54(m, 3H), 0.86(dd, 6H)

Example 706

N-(2-Trifluoromethylbenzyl)-N-phenylthiocarbamoyl-2(S)-{[l-(4-cyanobenzyl )- 1 H-imidazol-5-yl]acetyl } amino-4-methylpeniylamine

^•H-NMR(CDCb) : a 8.27(bs, IH), 6.64-7.72(m, 15H), 5.54(d, IH), 5.23(s, 2H), 4.88(d, IH), 4.66(m, IH), 4.23(m, IH), 3.34(s, 2H), 3.07(dd, IH), 2.84(t, 2H), 1.26-1.59(m, 3H), 0.87(dd, 6H)

Example 707

N-(2-Trifluoromethylbenzyl)-N-(n-propylthiocarbamoyl)-2(S)-{[l-(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl } amino-4-methylpentylamine

-H-NMR(CDCb) : a 6.82-7.71(m, 10H), 6.23(bs, IH), 5.32(d, 2H), 5.17(d, IH), 4.70(d, IH), 4.64(m, IH), 4.16(m, IH), 3.58(m, 2H), 3.32(s, 2H), 3.01(dd, IH), 1.5 l(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)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-4-methylpentylamine 1H-NMR(CDCb) : a 8.21(bs, IH), 6.69-7.72(m, 14H), 5.53(d, IH), 5.23(s, 2H), 4.87(d, IH), 4.66(m, IH), 4.24(m, IH), 3.35(s, 2H), 3.06(dd, IH), 2.32(s, 3H), 1.26-1.58(m, 3H), 0.88(d, 6H)

Example 709

N-(2-Trifluoromethylbenzyl)-N-(3-methylphenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl }amino-4-methylpentylamine

-H-NMR(CDCb) : a 6.69-7.72(m, 10H), 5.47(d, IH), 5.24(s, 2H), 4.89(d, IH), 4.73(m, IH), 4.28(m, IH), 3.34(s, 2H), 3.11(dd, IH), 2.08(s, 3H), 1.26-1.60(m, 3H), 0.89(d, 6H)

Example 710

N-(2-Trifluoromethylbenzyl)-N-(4-methylphenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5-yl] acetyl } amino-4-methylpentylamine

¹H-NMR(CDCb) : a 8.24(bs, IH), 6.74-7.72(m, 14H), 5.53(d, IH), 5.24(s, 2H), 4.88(d, IH), 4.68(m, IH), 4.24(m, IH), 3.34(s, 2H), 3.07(dd, IH), 2.34(s, 3H), 1.26-1.58(m, 3H), 0.88(d, 6H)

Example 711

N-(2-Trifluoromethylbenzyl)-N-(3-trifluoromethylphenylthiocarbamoyl)-2(S)-{

[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

1H-NMR(CDCb) : a 9.26(bs, IH), 6.64-7.83(m, 14H), 5.85(d, IH), 5.24(s, 2H), 4.90(d, IH), 4.34(m, IH), 4.13(m, IH), 3.34(s, 2H), 3.04(dd, IH), 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)- 1 H-imidazol-5 -yl] acetyl } amino-4-methy lpentylamine

^•H-NMR(CDCb) : a 6.82-7.73(m, 13H), 5.37(d, IH), 5.25(s, 2H), 4.88(d, IH), 4.72(m, IH), 4.28(m, IH), 3.34(s, 2H), 3.10(dd, IH), 2.3 l(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)-{[l-( 4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}amino-4-methylpentylamine

-H-NMR(CDCb) : a 8.11(bs, IH), 6.75-7.72(m, 13H), 5.49(d, IH), 5.24(s, 2H), 4.87(d, IH), 4.67(m, IH), 4.24(m, IH), 3.35(s, 2H), 3.06(dd, IH), 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-methylpropylamine

<Step 1>

N-(2-Trifluoromethylbenzyl)-2-{[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}a mino-2-methylpropylamine

Using the same methods as described in Preparative Example 3, 2-(N-t-butoxycarbonylamino)-2-methylpropionic acid was converted to 2-(N-t-butoxycarbonylamino)-2-methylpropion aldehyde. And then the reaction was carried out under the same condition as described in Preparative Example 4, but replacing 2,3-dichlorobenzylamine and 1 -(4-nitrobenzyl)- 1 H-imidazol-5 -ylacetic acid hydrochloride with 2-trifluor- omethylbenzyl amine and 1 -(4-cyanobenzyl)- 1 H-imidazol-5 -ylacetic acid hydrochloride, respectively, to give the title compound. ^•H-NMR(CDC13) : a 7.38-7.68(m, 7H), 7.17(d, 2H), 6.98(s, IH), 6.42(bs, IH), 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)- 1 H- imidazol-5-yl]acetyl}amino-2-methylpropylamine

To a solution of N-(2-trifluoromethylbenzyl)-2-{[l-(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine in dichloromethane (0.02M, 1ml, 0.02mmol) was added allylisothiocyanate (O. IM in CH₂C1 , 0.2ml, 0.02mmol). The reaction mixture was agitated for 3hr at room temperature. The mixture was purified by silica gel column chromatography(eluent:

v/v) to give the title compound as a white solid.

^■H-NMR(CDCb) : a 7.73(d, IH), 7.65(d, 2H), 7.55(m, 3H), 7.17(d, 3H), 7.00(s, IH), 5.80(m, IH), 5.35(s, 2H), 5.07(m, 4H), 4.20(t, 2H), 4.00(s, 2H), 3.25(s, 2H), 1.40(s, 6H)

Examples 715-760

N-(2-Trifluoromethylbenzyl)-2-{ [ 1 -(4-cyanobenzyl)- 1 H-imidazol-5 -yl] acetyl} amino-2-methylpropylamine was reacted with the conesponding isothiocyanates under the same condition as described in <Step 2> of Example 714 to give the title compounds.

Example 715

N-(2-TrifluoromethylberLzyl)-N-benzylthiocarbamoyl-2- { [ 1 -(4-cyanobenzyl)- 1 H-imidazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.63(m, 5H), 7.45(m, 2H), 7.20(m, 6H), 7.05(bs, IH), 7.00(s, IH), 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-cyanoben zyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : a 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-biOmophenylthiocarbamoyl)-2- {[ 1 -(4-cyano benzyl)- lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.75(d, IH), 7.45-7.70(m, 6H), 7.37(m, 3H), 7.12(d, 3H), 7.00(s, IH), 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-{[l-(4-cyano benzyl)- lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : a 7.73(d, IH), 7.40-7.65(m, 6H), 7.20-7.37(m, 4H), 7.10(d, 2H), 6.95(s, IH), 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-cyano benzyl)- lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.73(d, IH), 7.60(d, 3H), 7.42(d, 4H), 7.27(m, 3H), 7.07(d, 2H), 6.95(s, IH), 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)

- 1 H-imidazol-5 -yl] acetyl } amino-2-methylpropy lamine

-H-NMR(CDCb) : £ 7.73(d, IH), 7.60(d, 2H), 7.55(m, 3H), 7.17(d, 3H), 7.00(s, IH), 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)-

1 H-imidazol-5 -yl] acetyl} amino-2-methylpropylamine

1H-NMR(CDCb) : a 7.40-7.68(m, 5H), 7.15(m, 3H), 7.00(s, IH), 5.38(s, 2H), 5.00(s, 2H), 4.08(s, 2H), 3.38(m, 2H), 3.25(s, 2H), 1.75(m, IH), 1.42(s, 6H), 0.66(d, 6H)

Example 722

N-(2-Trifluoromethylbenzyl)-N-(/-butylthiocarbamoyl)-2- { [ 1 -(4-cyanobenzy 1)- lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDC1₃) : a 8.90(s, IH), 7.73(d, IH), 7.65(d, 2H), 7.55(m, 3H), 7.20(m, 3H), 7.02(s, IH), 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-chlorophenylthiocaι^*bamoyl)-2- { [ 1 -(4-cyano benzyl)- lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : a 7.73(d, IH), 7.60(d, 2H), 7.45(m, 2H), 7.20-7.40(m, 4H), 7.15(d, 2H), 7.00(s, IH), 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-{[l -(4-cyano benzyl)- lH-imidazol-5-yl]acetyl } amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.73(d, IH), 7.58(d, 3H), 7.25-7.50(m, 6H), 7.17(m, IH), 7.05(d, 2H), 6.95(s, IH), 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-cyano benzyl)- 1 H-imidazol-5 -yl] acetyl } amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.73(d, IH), 7.58(d, 3H), 7.45(m, 2H), 7.22(m, 5H), 7.05(d, 2H), 6.95(s, IH), 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)- lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine -H-NMR(CDCb) : a 7.73(d, IH), 7.58(d, 3H), 7.43(m, 2H), 7.28(m, 2H), 7.20(m, 2H), 7.07(d, 2H), 6.95(s, IH), 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-cyanobenzy

1)- 1 H-imidazol-5 -yl] acetyl} amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.73 (d, IH), 7.40-7.65(m, 5H), 7.17(m, 3H), 7.00(s, IH), 5.40(s, IH), 5.25(s, IH), 5.00(s, IH), 4.10(m, 2H), 3.90(s, IH), 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-cyanobenz yl)-l H-imidazol-5 -yl] acetyl }amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.73(d, IH), 7.20-7.50(m, 5H), 7.17(m, 3H), 7.00(s, IH), 5.40(s, 2H), 4.95(s, 2H), 4.58(m, IH), 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-c y anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.73(d, IH), 7.60(d, 4H), 7.45(m, 2H), 7.30(m, 3H), 7.12(d, 3H), 7.00(s, IH), 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)- lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : a 8.90(bs, IH), 7.73(d, IH), 7.62(d, 2H), 7.45(m, 3H), 7.17(d, 3H), 7.05(s, IH), 5.92(bs, IH), 5.40(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-{[ l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : a 7.73(d, IH), 7.60(m, 4H), 7.45(m, 2H), 7.35(d, IH), 7.12(d, 2H), 7.00(s, IH), 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-{[ l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

Η-NMR(CDCb) : a 9.12(bs, IH), 7.73(d, IH), 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, 2H), 1.40(s, 6H)

Example 733

N-(2-Trifluoromethylbenzyl)-N-ethoxycarbonylthiocaι^*bamoyl-2- { [ 1 -(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : a 7.50-7.70(m, 6H), 7.40(m, IH), 7.17(d, 2H), 7.00(m, IH), 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)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.73(d, IH), 7.62(d, 2H), 7.40-7.58(m, 3H), 7.18(d, 3H), 7.00(s, IH), 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-{[l-(4-cyano benzyl)- 1 H-imidazol-5 -yl] acetyl } amino-2-methylpropylamine

1H-NMR(CDCb) : a 8.90(bs, IH), 7.73(d, IH), 7.65(d, 2H), 7.55(m, 3H), 7.20(d, 2H), 7.05(m, 2H), 5.82(s, IH), 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)- 1 H

-imidazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.73(d, IH), 7.65(d, 2H), 7.45(m, 3H), 7.17(d, 3H), 7.00(s, IH), 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-cy ano benzyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine 1H-NMR(CDCb) : a 7.73(d, IH), 7.60(m, 3H), 7.45(m, 3H), 7.20(m, IH), 7.12(d, 4H), 6.95(s, IH), 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-{[l-(4-cyano benzyl)- lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.73(d, IH), 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-cyano benzyl)- 1 H-imidazol-5 -yl]acetyl } amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.73(d, IH), 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-cya nobenzyl)- lH-imidazol-5-yl]acetyl} amino-2-methylpropylamine

(CDCB, CD3-OD) 7.73(d, IH), 7.60(d, 3H), 7.43(m, 2H), 7.30(d, IH), 7.10(m, 4H), 6.95(s, IH), 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-cy anobenzyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.73(d, IH), 7.58(m, 3H), 7.45(m, 2H), 7.30(m, 2H), 7.20(s, 3H), 7.10(d, 2H), 7.00(s, IH), 5.30(s, 4H), 4.00(s, 2H), 3.25(s, 2H), 2.90(q, IH), 1.43(s, 6H), 1.12(d, 6H)

Example 742

N-(2-Trifluoromethylbenzyl)-N-(2-methoxy ethylthiocarbamoyl)-2- { [ 1 -(4-cyan obenzyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : a 8.60(bs, IH), 7.73(d, IH), 7.60(d, 2H), 7.50(m, 3H), 7.17(d, 3H), 7.00(s, IH), 6.20(bs, IH), 5.40(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-cya nobenzyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : a 8.70(s, IH), 8.12(d, IH), 7.76(d, IH), 7.63(m, IH), 7.57(d, 2H), 7.50(m, 2H), 7.30(d, IH), 7.17(d, 3H), 7.00(m, 2H), 6.80(d, IH), 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-cya nobenzyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : a 7.73(d, IH), 7.60(m, 3H), 7.45(m, 2H), 7.30(d, IH), 7.12(d, 4H), 7.00(s, IH), 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-cya nobenzyl)- lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : a 9.00(bs, IH), 7.73(d, IH), 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)- 1 H-imidazol-5 -yl] acetyl } amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.90(bs, IH), 7.73(d, IH), 7.60(d, 4H), 7.45(m, 2H), 7.30(d, IH), 7.10(d, 2H), 6.95(s, IH), 6.75(d, IH), 5.80(m, IH), 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)- 1 H-imidazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.73(d, IH), 7.65(d, 2H), 7.45(m, 4H), 7.17(d, 2H), 7.12(s, IH), 7.00(s, IH), 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-{[l-(4-c yanobenzyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.73(d, IH), 7.58(d, 3H), 7.45(m, 3H), 7.30(d, IH), 7.20(s, 3H), 7.10(d, 2H), 6.95(s, IH), 5.80(m, IH), 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-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl } amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.60-7.82(m, 6H), 7.45(m, 7H), 7.12(d, IH), 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-cyanob enzyl)- 1 H-imidazol-5 -yl] acetyl } amino-2-methylpropylamine

-H-NMR(CDCb) : a 8.18(d, 2H), 7.72(4 2H), 7.55(m, 4H), 7.45(q, 2H), 7.30(s, IH), 7.10(d, 2H), 6.95(s, IH), 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

)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : a 8.70(bs, IH), 7.73(d, IH), 7.65(d, 2H), 7.50(m, 3H), 7.19(d, 3H), 7.00(s, IH), 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-phenethylthiocarbamoyl-2-{[l-(4-cyanobenzyl

)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.69(s,lH), 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)- 1

H-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : a 7.73(d, IH), 7.58(m, 3H), 7.45(m, 2H), 7.25(m, 6H), 7.07(d, 2H), 7.00(s, IH), 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

)- 1 H-imidazol-5-yl]acetyl } amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.73(d, IH), 7.65(d, 2H), 7.50(m, 3H), 7.17(d, 3H), 7.00(s, IH), 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-{[l-(4-cyan obenzyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine ^•H-NMR(CDCb) : a 7.73(d, IH), 7.65(m, IH), 7.58(d, 2H), 7.45(m, 2H), 7.32(d, IH), 7.20(d, IH), 7.10(m, 5H), 7.00(s, IH), 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-cy an obenzyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : a 7.73(d, IH), 7.65(m, IH), 7.55(d, 2H), 7.40(m, 3H), 7.20(s, 3H), 7.12(d, 3H), 6.95(s, IH), 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-cyan obenzyl)-lH-imidazol-5-yl]acetyl}amino-2-methylpropylamine

1H-NMR(CDCb) : a 7.73(d, IH), 7.65(m, IH), 7.57(d, 2H), 7.45(m, 2H), 7.36(d, IH), 7.17(s, 6H), 7.00(s, IH), 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)- lH-imidazol-5-yl]acetyl} amino-2-methylpropylamine

^'H-NMR(CDCb) : a 7.73(d, IH), 7.62(d, IH), 7.55(d, 3H), 7.45(m, 4H), 7.36(d, IH), 7.07(d, 3H), 6.94(s, IH), 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-c yanobenzyl)- 1 H-imidazol-5-yl]acetyl } amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.75(d, 2H), 7.65(4 IH), 7.60(4 2H), 7.50(s, 2H), 7.39(d, IH), 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-c yanobenzyl)- 1 H-imidazol-5 -yl] acetyl }amino-2-methylpropylamine

-H-NMR(CDCb) : a 7.75(4 IH), 7.65(d, IH), 7.58(d, 2H), 7.45(s, 2H), 7.35(d, IH), 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)- 1

H-imidazol-5-yl]acetyl} amino butylamine

<Step 1>

N-(2-Trifluoromethylbenzyl)-2(S)-{[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acety 1 } aminobutylamine

Using the same methods as described in Preparative Example 3, 2(S)-(N-t-butoxycarbonyl)aminobutyric acid was converted to 2(S)-(N-t-butoxycarbonyl)aminobutyraldehyde. And then the reaction was carried out under the same condition as described in Preparative Example 4, but replacing 2,3-dichlorobenzylamine and 1 -(4-nitrobenzyl)- 1H- imidazol-5 -ylacetic acid hydrochloride with 2-trifluoromethylbenzylamine and l-(4-cyanobenzyl)-lH-imidazol-5-ylacetic acid hydrochloride, respectively, to give the title compound. -H-NMR(CDCB) : a 7.64(4 IH), 7.59(4 2H), 7.5 l(s, 3H), 7.13(4 2H), 7.00(s, IH), 6.23(d, IH), 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)- 1

H-imidazol-5-yl]acetyl}amino butylamine

To a solution of N-(2-trifluoromethylbenzyl)-2(S)-{[l-(4- cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl} aminobutylamine in dichloromethane (0.02M, 1ml, 0.02 mmol) was added allylisothiocyanate (O. IM in CH₂C1₂, 0.2ml, 0.02mmol). The reaction mixture was agitated for 3hr at room temperature. The mixture was purified by silica gel column chromatography (eluent: CH2Cl2/MeOH=9/l, v/v) to give the title compound as a white solid.

-H-NMR(CDCb) : a 7.65(m, 3H), 7.47(m, 3H), 7.18(m, 3H), 7.00(s,

2H), 6.41(bs, IH), 5.85(m, IH), 5.35(q, 3H), 5.05(m, 2H), 4.70(d, 2H),

4.30(t, 2H), 4.00(q, IH), 3.35(s, 2H), 3.03(dd, IH), 1.65(m, IH), 1.45(m, IH), 0.90(t, 3H)

Examples 762-806

N-(2-Trifluoromethylbenzyl)-2(S)-{[l -(4-cyanobenzy 1)- 1 H-imidazol-5 - yl] acetyl} aminobutylamine was reacted with the conesponding isothiocyanates under the same condition as described in <Step 2> of Example 761 to give the title compounds.

Example 762 N-(2-Trifluoromethylbenzyl)-N-benzylthiocarbamoyl-2(S)- { [ 1 -(4-cyanobenzyl )- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

-H-NMR(CDCb) : a 7.70(s, IH), 7.60(4 2H), 7.45(m, 3H), 7.23(m, 4H), 7.15(m, 4H), 7.00(m, 2H), 6.70(bs, IH), 5.25(m, 3H), 4.85(d, 2H), 4.70(d, 2H), 4.00(q, IH), 3.25(s, 2H), 3.05(dd, IH), 1.58(m, 2H), 0.88(t, 3H)

Example 763

N-(2-Trifluoromethylbenzyl)-N-(2-biphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanob enzyl)- lH-imidazol-5-yl]acetyl}aminobutylamine

-H-NMR(CDCb) : a 7.60(m, 4H), 7.45(s, IH), 7.30(m, 10H), 7.12(d, 2H), 6.98(m, 2H), 5.45(bs, IH), 5.20(s, 2H), 4.62(bs, IH), 3.80(s, IH), 3.30(s, 2H), 2.90(dd, IH), 1.60(m, IH), 0.85(t, 3H)

Example 764

N-(2-Trifluoromethylbenzyl)-N-(2-bromophenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)-lH-imidazol-5-yl]acetyl}aminobutylamine

1H-NMR(CDCb) : a 7.72(t, 3H), 7.55(m, 4H), 7.40(m, 3H), 7.32(m, IH), 7.12(m, 3H), 7.00(s, 2H), 5.45(bs, IH), 5.25(s, 2H), 4.85(d, 2H), 4.20(m, IH), 3.40(s, 2H), 3.15(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90(t, 3H)

Example 765

N-(2-Trifluoromethylbenzyl)-N-(3-bromophenyltbiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)-lH-imidazol-5-yl]acetyl}aminobutylamine

1H-NMR(CDC1₃) : a 9.10(s, IH), 7.70(4 IH), 7.55(m, 4H), 7.45(s, 2H), 7.20-7.40(m, 4H), 7.10(d, 2H), 6.95(s, IH), 6.85(d, IH), 5.90(d, IH), 5.29(s, 2H), 4.74(d, IH), 4.40(s, IH), 4.00(s, IH), 3.40(s, 2H), 3.02(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90((t, 3H)

Example 766

N-(2-Trifluoromethylbenzyl)-N-(4-bromophenylthiocarbamoyl)-2(S)-{ [ 1 -(4-cy anobenzyl)-lH-imidazol-5-yl]acetyl}aminobutylamine

1H-NMR(CDCb) : a 8.80(s, IH), 7.70(d, IH), 7.56(d, 2H), 7.45(d, 4H), 7.35(m, 3H), 7.08(d, 2H), 6.95(s, IH), 6.80(d, IH), 5.80(d, IH), 5.22(s, 2H), 4.76(d, IH), 4.41(s, IH), 4.00(m, IH), 3.39(s, 2H), 3.04(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90(t, 3H)

Example 767

N-(2-Trifluoromethylbenzyl)-N-n-butylthiocarbamoyl-2(S)-{[l-(4-cyanobenzyl )- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

^'H-NMR(CDCb) : 8 7.66(m, 3H), 7.45(m, 3H), 7.20(m, 3H), 7.10(m, 3H), 7.00(s, IH), 6.20(bs, IH), 5.35(m, 3H), 4.70(d, 2H), 4.00(m, IH), 3.60(m, 2H), 3.34(s, 2H), 3.02(dd, IH), 1.60(m, IH), 1.50(m, 3H), 1.18(m, 2H), 0.88(m, 6H)

Example 768

N-(2-Trifluoromethylbenzyl)-N-isobutylthiocarbamoyl-2(S)-{[l-(4-cyanobenzy l)-lH-imidazol-5-yl]acetyl}aminobutylamine

1H-NMR(CDCb) : a 7.65(m, 3H), 7.52(m, 2H), 7.40(m, 2H), 7.18(m, 3H), 7.00(s, IH), 6.00(s, IH), 5.34(q, 2H), 5.12(m, IH), 4.85(m, IH), 4.70(d, IH), 4.02(s, IH), 3.50(m, IH), 3.34(s, 3H), 3.05(dd, IH), 1.80(m, IH), 1.50(m, 2H), 0.90((t, 3H), 0.75(m, 6H) Example 769

N-(2-Trifluoromethylbenzyl)-N-(/-butylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanobenz yl)-lH-imidazol-5-yl]acetyl}aminobutylamine

-H-NMR(CDCb) : a 7.71(m, IH), 7.65(d, 2H), 7.55(m, 2H), 7.45(m, 2H), 7.18(d, 2H), 7.05(s, IH), 5.36(q, 2H), 5.15(m, IH), 4.75(q, 2H), 4.00(m, IH), 3.35(s, 2H), 3.05(dd, IH), 1.55(m, 2H), 1.3 l(s, 9H), 0.90((t, 3H)

Example 770

N-(2-Trifluoromethylbenzyl)-N-(2-chlorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- 1 H-imidazol-5-yl] acetyl } aminobutylamine

-H-NMR(CDCb) : a 7.90(bs, IH), 7.72(t, 2H), 7.60(m, 3H), 7.42(m, 4H), 7.25(m, 2H), 7.10(d, 2H), 7.00(s, IH), 6.95(bs, IH), 5.46(bs, IH), 5.25(s, 2H), 4.85(d, IH), 4.80(s, IH), 4.20(m, IH), 3.40(s, 2H), 3.12(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90((t, 3H)

Example 771

N-(2-Trifluoromethylbenzyl)-N-(3-chlorophenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)-lH-imidazol-5-yl]acetyl}aminobutylamine

1H-NMR(CDCb) : a 9.05(bs, IH), 7.70(d, IH), 7.60(d, 3H), 7.42(m, 5H), 7.20(m, 2H), 7.10(d, 2H), 6.95(s, IH), 6.85(ds, IH), 5.90(d, IH), 5.28(s, 2H), 4.80(d, IH), 4.40(s, IH), 4.00(m, IH), 3.40(s, 2H), 3.05(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90((t, 3H)

Example 772 N-(2-Trifluoromethylbenzyl)-N-(4-chlorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)-lH-imidazol-5-yl]acetyl}aminobutylamine

Η-NMR(CDCb) : a 8.80(bs, IH), 7.70(4 IH), 7.60(d, 3H), 7.40(s,

2H), 7.30(m, 5H), 7.10(4 2H), 6.95(s, IH), 6.80(s, IH), 5.80(d, IH),

5.23(s, 2H), 4.80(d, IH), 4.42(s, IH), 4.00(m, IH), 3.38(s, 2H), 3.05(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90((t, 3H)

Example 773

N-(2-Trifluoromethylbenzyl)-N-(3-chloro-4-methylphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanobenzyl)- lH-imidazol-5-yl] acetyl} aminobutylamine

-H-NMR(CDCb) : a 8.85(bs, IH), 7.70(d, IH), 7.56(d, 3H), 7.45(s, IH), 7.38(m, 3H), 7.25(m, 2H), 7.10(d, 2H), 6.95(s, IH), 6.88(d, IH), 5.80(d, IH), 5.27(s, 2H), 4.80(d, IH), 4.42(s, IH), 4.00(m, IH), 3.38(s, 2H), 3.05(dd, lH),2.30(s, 3H), 1.70(m, IH), 1.50(m, IH), 0.90((t, 3H)

Example 774

N-(2-Trifluoromethylbenzyl)-N-cyclohexylthiocarbamoyl-2(S)- {[ 1 -(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}aminobutylamine

Η-NMR(CDCb) : a 7.65(m, 3H), 7.52(s, IH), 7.43(m, 2H), 7.18(m, 3H), 7.00(s, 2H), 5.80(bs, IH), 5.35(s, 3H), 5.1 l(m, IH), 4.82(m, IH), 4.75(d, IH), 4.22(m, IH), 4.00(m, IH), 3.38(s, 2H), 3.02(dd, IH), 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-cyanobe nzyl)- 1 H-imidazol-5-yl] acetyl } aminobutylamine

-H-NMR(CDCb) : a 7.65(m, 3H), 7.52(s, IH), 7.43(m, 2H), 7.18(m, 3H), 7.00(s, IH), 5.95(m, IH), 5.35(q, 2H), 5.20(m, IH), 4.80(m, IH), 4.64(m, 2H), 4.01(m, IH), 3.35(s, 2H), 3.05(dd, IH), 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)-{[l-(4 -cy anobenzyl)- lH-imidazol-5-yl]acetyl}aminobutylamine

1H-NMR(CDCb) : a 8.20(bs, IH), 7.75(4 2H), 7.60(m, 3H), 7.40(m,

4H), 7.28(m, IH), 7.15(m, 2H), 7.00(s, IH), 6.8 l(s, IH), 5.55(bs, IH),

5.25(s, 2H), 4.83(d, IH), 4.70(bs, IH), 4.18(m, IH), 3.40(s, 2H), 3.16(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.95(t, 3H)

Example 777

N-(2-Trifluoromeι ylbenzyl)-N-[2-(dimethylamino)ethylthiocarbamoyl]-2(S)-{ [ 1 -(4-cyanobenzyl)- 1 H-imidazol-5 -yl] acetyl} aminobutylamine

-H-NMR(CDCb) : a 7.65(m, 3H), 7.42(m, 4H), 7.18(m, 3H), 7.05(s, IH), 6.78(bs, IH), 4.65-5.05(m, 2H), 4.10(m, IH), 3.50(s, 2H), 3.38(s, 2H), 3.14(dd, IH), 2.40(m, 2H), 1.90(s, 6H), 1.50(m, 2H), 0.90(t, 3H)

Example 778

N-(2-Trifluoromeι ylbenzyl)-N-[4-(dimethylamino)phenylthiocarbamoyl]-2(S) - { [ 1 -(4-cyanobenzyl)- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

-H-NMR(CDCb) : a 7.90(bs, IH), 7.70(d, IH), 7.58(d, 3H), 7.48(m, 2H), 7.40(t, 2H), 7.10(t, 3H), 7.00(s, IH), 6.65(d, 2H), 5.45(d, IH), 5.28(s, 2H), 4.80(d, 2H), 4.08(m, IH), 3.38(s, 2H), 3.10(dd, IH), 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)- 1 H-imidazol-5 -yl] acetyl} aminobutylamine

-H-NMR(CDCb) : a 9.90(bs, IH), 7.72(s, IH), 7.65(4 2H), 7.42(m, 3H), 7.20(d, 2H), 7.05(d, IH), 7.00(s, IH), 5.40(q, 2H), 5.00(m, IH), 4.70(s, 2H), 4.0 l(m, IH), 3.70(m, 2H), 3.32(q, 2H), 2.90(dd, IH), 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-cya nobenzyl)- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

-H-NMR(CDCb) : a 7.65(m, 3H), 7.50(m, 2H), 7.42(d, IH), 7.30(s,

IH), 7.18(d, 2H), 7.02(d, IH), 6.25(m, IH), 5.32(m, 3H), 4.90(d, IH),

4.65(d, IH), 4.18(q, 2H), 4.05(bs, IH), 3.38(s, 2H), 3.00(m, IH), 1.70(m, 2H), 1.25(m, 2H), 0.88(m, 4H)

Example 781

N-(2-Trifluoromethylbenzyl)-N-(3-ethoxypropylthiocarbamoyl)-2(S)-{ [ 1 -(4-cy anobenzyl)- lH-imidazol-5 -yl] acetyl } aminobutylamine

-H-NMR(CDCb) : a 7.65(m, 3H), 7.42(m, 4H), 7.18(m, 3H), 7.00(s, IH), 6.82(bs, IH), 5.38(q 2H), 4.90(m, 2H), 4.68(d, IH), 4.00(m, IH), 3.75(q, 2H), 3.42(m, 2H), 3.38(s, 2H), 3.18(m, 2H), 2.98(dd, IH), 1.80(p, 2H), 1.50(m, 2H), 0.85(q, 6H)

Example 782

N-(2-Trifluoromethylbenzyl)-N-ethylthiocarbamoyl-2(S)- { [ 1 -(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}aminobutylamine -H-NMR(CDCb) : a 7.65(m, 3H), 7.45(m, 3H), 7.18(m, 3H), 7.00(s, 2H), 6.30(bs, IH), 5.33(q 3H), 4.65(d, 2H), 4.00(m, IH), 3.65(m, 2H), 3.38(s, 2H), 3.00(dd, IH), 1.70(m, IH), 1.50(m, IH), 1.12(t, 3H), 0.90(t, 3H)

Example 783

N-(2-Trifluoromethylbenzyl)-N-(2-flurophenylthiocarbamoyl)-2(S)-{[l-(4-cya nobenzyl)- lH-imidazol-5-yl]acetyl}aminobutylamine

'H-NMR^DCb) : a 8.20(bs, IH), 7.71(d, 2H), 7.58(m, 3H), 7.43(m, 3H), 7.18(m, 5H), 7.00(m, 2H), 5.60(d, IH), 5.26(q 3H), 4.85(d, IH), 4.52(s, IH), 4.10(m, IH), 3.39(s, 2H), 3.10(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90(t, 3H)

Example 784

N-(2-Trifluoromethylbenzyl)-N-(3 -fluorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

-H-NMR(CDCb) : a 8.95(s, IH), 7.70(d, IH), 7.57(m, 3H), 7.45(s, IH), 7.40(m, 2H), 7.25(m, 3H), 7.10(d, 2H), 6.97(s, IH), 6.85(m, 2H), 5.85(d, IH), 5.28(s, 3H), 4.75(d, 2H), 4.45(m, IH), 4.00(m, IH), 3.38(s, 2H), 3.08(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90(t, 3H)

Example 785

N-(2-Trifluoromethylbenzyl)-N-(4-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)-lH-imidazol-5-yl]acetyl}aminobutylamine

1H-NMR(CDCb) : a 8.60(s, IH), 7.72(d, IH), 7.58(m, 4H), 7.35(m, 4H), 7.10(t, 3H), 7.00(s, 2H), 6.83(d, IH), 5.73(d, IH), 5.28(s, 2H), 4.80(d, IH), 4.50(bs, IH), 4.00(m, IH), 3.38(s, 2H), 3.08(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90(t, 3H)

Example 786

N-(2-Trifluoromethylbenzyl)-N-(4-hydroxyphenylthiocarbamoyl)-2(S)- { [ 1 -(4-c yanobenzyl)- 1 H-imidazol-5-yl]acetyl} aminobutylamine

-H-NMR(CD₃OD) : a 7.75(m, 2H), 7.62(m, 3H), 7.40(m, 2H), 7.23(d, 2H), 7.10(d, 2H), 6.95(s, IH), 6.75(d, 2H), 5.60(d, IH), 5.38(s, 2H), 5.10(d, IH), 4.03(m, 2H), 3.43(q, 2H), 3.30(m, IH), 3.08(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90(t, 3H)

Example 787

N-(2-Trifluoromethylbenzyl)-N-(4-isopiOpylphenylthiocarbamoyl)-2(S)-{[l-(4- cy anobenzyl)- 1 H-imidazol-5 -yl]acetyl } aminobutylamine

-H-NMR(CDCb) : a 8.20(bs, IH), 7.70(d, IH), 7.57(d, 3H), 7.50(m, IH), 7.40(t, 2H), 7.23(m, 4H), 7.20(d, 2H), 7.00(s, 2H), 5.60(d, IH), 5.26(s, 2H), 4.80(d, IH), 4.70(bs, IH), 4.05(m, IH), 3.38(s, 2H), 3.08(dd, IH), 2.90(m, IH), 1.70(m, IH), 1.50(m, IH), 1.12(4 6H), 0.90(t, 3H)

Example 788

N-(2-Trifluoromethylbenzyl)-N-(2-methoxy ethylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)-lH-imidazol-5-yl]acetyl}aminobutylamine

Η-NMR(CDCb) : a 7.65(m, 3H), 7.52(s, IH), 7.42(t, 2H), 7.20(d, 4H),

7.00(s, IH), 6.20(s, IH), 5.35(q, 2H), 4.98(m, 2H), 4.70(d, IH),

4.08(m, IH), 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)-{[l-(4- cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

^'H-NMR(CDCb) : a 8.22(d, IH), 7.77(d, IH), 7.65(s, IH), 7.50(m, 5H), 7.25(m, 2H), 7.07(m, 5H), 6.90(d, IH), 5.28(s, 2H), 5.10(s, 2H), 4.90(d, IH), 4.20(m, IH), 3.58(s, 3H), 3.38(s, 2H), 3.18(dd, IH), 1.60(m, 2H), 0.90(t, 3H)

Example 790

N-(2-Trifluoromethylbenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4- cyanobenzyl)- IH-imi dazol-5-yl]acetyl} aminobutylamine

Η-NMR(CDCb) : a 8.22(bs, IH), 7.70(d, IH), 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, IH), 5.28(s, 2H), 4.80(d, IH), 4.65(m, IH), 4.02(m, IH), 3.80(s, 3H), 3.38(s, 2H), 3.08(dd, IH), 1.60(m, 2H), 0.90(t, 3H)

Example 791

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

1H-NMR(CDCb) : a 7.72(d, IH), 7.65(d, 2H), 7.45(m, 4H), 7.20(d, 2H), 7.10(d, IH), 7.00(s, IH), 6.90(s, IH), 5.38(q, 2H), 4.90(m, 2H), 4.70(d, IH), 4.02(m, IH), 3.72(m, 2H), 3.40(m, 2H), 3.58(s, 3H), 3.33(s, 2H), 3.00(dd, IH), 2.85(s, 3H), 1.80(m, 2H), 1.50(m, 2H), 0.90(t, 3H)

Example 792

N-(2-Trifluoromeι ylbenzyl)-N-(2-methoxypyridin-5-ylthiocarbamoyl)-2(S)-{[ l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}aminobutylamine -H-NMR(CDCb) : a 8.80(bs, IH), 8.00(4 IH), 7.77(d, 2H), 7.58(4 3H), 7.40(m, 3H), 7.10(4 2H), 6.90(m, 2H), 6.75(4 IH), 5.80(d, IH), 5.28(s, 2H), 4.70(d, IH), 4.50(s, IH), 4.02(m, IH), 3.90(s, 3H), 3.38(s, 2H), 3.06(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90(t, 3H)

Example 793

N-(2-Trifluoromethylbenzyl)-N-methylthiocarbamoyl-2(S)-{[l-(4-cyanobenzyl

)-lH-imidazol-5-yl]acetyl}aminobutylamine

1H-NMR(CDC1₃) : a 7.65(m, 3H), 7.45(m, 3H), 7.20(m, 3H), 7.00(m, 2H), 6.70(s, IH), 5.32(m, 3H), 4.65(d, IH), 4.55(s, IH), 4.00(m, IH), 3.38(s, 2H), 3.12(d, 3H), 2.96(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90(t, 3H)

Example 794

N-(2-Trifluoromethylbenzyl)-N-(4-methylthiophenylthiocarbamoyl)-2(S)-{[l-( 4-cyanobenzyl)- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

^•H-NMR(CDCb) : a 8.50(bs, IH), 7.70(d, IH), 7.58(d, 3H), 7.32-7.46(m, 4H), 7.25(d, 3H), 7.10(d, 2H), 7.00(s, IH), 6.90(s, IH), 5.70(d, IH), 5.25(s, 2H), 4.80(d, IH), 4.55(s, IH), 4.01(m, IH), 3.38(s, 2H), 3.06(dd, IH), 2.45(s, 3H), 1.70(m, IH), 1.50(m, IH), 0.90(t, 3H)

Example 795

N-(2-Trifluoromethylbenzyl)-N-(2-naphthylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanob enzyl)- 1 H-imidazol-5-yl] acetyl } aminobutylamine

-H-NMR(CDCb) : a 8.80(bs, IH), 7.68-7.83(m, 5H), 7.58(d, 2H), 7.22(m, 7H), 7.00(m, 3H), 6.88(d, IH), 5.80(d, IH), 5.20(s, 2H), 4.82(d, IH), 4.60(s, IH), 4.05(m, IH), 3.38(s, 2H), 3.09(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90(t, 3H)

Example 796

N-(2-Trifluoromethylbenzyl)-N-(4-nitrophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyan obenzyl)- 1 H-imidazol-5 -yl]acetyl } aminobutylamine

-H-NMR(CDCb) : a 9.60(bs, IH), 8.20(d, 2H), 7.80(d, 2H), 7.70(d, IH), 7.55(m, 4H), 7.40(m, 2H), 7.10(d, 2H), 7.00(d, 2H), 6.75(d, IH), 6.02(d, IH), 5.23(s, 2H), 4.80(d, IH), 4.25(m, IH), 3.98(s, IH), 3.40(s, 2H), 3.09(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90(t, 3H)

Example 797

N-(2-Trifluoromethylbenzyl)-N-(n-pentylthiocarbamoyl)-2(S)-{[l-(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

-H-NMR(CDCb) : a 7.70(m, 3H), 7.48(m, 3H), 7.20(m, 4H), 7.00(s, IH), 5.90(s, IH), 5.38(q, 2H), 5.00(m, 2H), 4.70(d, IH), 4.02(m, IH), 3.60(m, IH), 3.45(m, IH), 3.35(s, 2H), 3.06(dd, IH), 1.68(m, 4H), 1.10(m, 2H), 0.90(t, 3H), 0.75(m, 5H)

Example 798

N-(2-Trifluoromethylbenzyl)-N-phenethylthiocarbamoyl-2(S)- { [ 1 -(4-cyanoben zyl)-lH-imidazol-5-yl]acetyl}aminobutylamine

1H-NMR(CDCb) : a 7.62(m, 3H), 7.50(s, IH), 7.40(m, 2H), 7.15(m, 5H), 7.00(m, 4H), 6.10(bs, IH), 5.32(q, 2H), 5.05(m, IH), 4.70(m, IH), 4.60(d, IH), 3.90(m, 3H), 3.36(s, 2H), 3.00(dd, IH), 2.85(t, 2H), 1.57(m, 2H), 0.90(t, 3H) Example 799

N-(2-Trifluoromethylbenzyl)-N-phenylthiocarbamoyl-2(S)-{[l-(4-cyanobenzyl )- 1 H-imidazol-5 -yl] acetyl } aminobutylamine

-H-NMR(CDCb) : a 8.50(bs, IH), 7.72(4 IH), 7.58(d, 3H), 7.40(s,

2H), 7.18-7.40(m, 6H), 7.10(4 2H), 7.00(s, IH), 6.95(s, IH), 5.70(d,

IH), 5.28(s, 2H), 4.80(d, IH), 4.62(s, IH), 4.02(m, IH), 3.38(s, 2H), 3.09(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90(t, 3H)

Example 800

N-(2-Trifluoromethylbenzyl)-N-(n-propylthiocarbamoyl)-2(S)-{[l-(4-cyanoben zyl)- 1 H-imidazol-5 -yl]acetyl } aminobutylamine

-H-NMR(CDCb) : a 7.65(m, 3H), 7.46(m, 3H), 7.20(m, 3H), 7.05(m, 2H), 6.20(s, IH), 5.30(s, 3H), 4.70(d, 2H), 4.00(m, IH), 3.58(m, 2H), 3.38(s, 2H), 3.03(dd, IH), 1.50(m, 4H), 0.90(t, 3H), 0.80(t, 3H)

Example 801

N-(2-Trifluoromethylbenzyl)-N-(3-methylphenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- lH-imidazol-5-yl]acetyl}aminobutylamine

-H-NMR(CDCb) : a 8.30(bs, IH), 7.72(d, IH), 7.55(d, 3H), 7.50(s, IH), 7.40(t, 2H), 7.02-7.24(m, 5H), 7.00(m, 2H), 5.60(d, IH), 5.25(s, 2H), 4.80(d, IH), 4.65(m, IH), 4.02(m, IH), 3.38(s, 2H), 3.06(dd, IH), 2.32(s, 3H), 1.70(m, IH), 1.50(m, IH), 0.90(t,3H)

Example 802

N-(2-Trifluoromethylbenzyl)-N-(2-methylphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } aminobutylamine 1H-NMR(CDCb) : a 7.72(4 IH), 7.55(m, 3H), 7.42(m, 4H), 7.18(m,

7H), 7.00(s, IH), 5.50(d, IH), 5.26(s, 2H), 4.88(d, 2H), 4.12(m, IH),

3.38(s, 2H), 3.12(dd, IH), 2.10(s, 3H), 1.70(m, IH), 1.50(m, IH), 0.90(t,3H)

Example 803

N-(2-Trifluoromethylbenzyl)-N-(4-methylphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)-lH-imidazol-5-yl]acetyl}aminobutylamine

1H-NMR(CDCb) : a 8.30(bs, IH), 7.72(d, IH), 7.55(d, 3H), 7.40(m, 3H), 7.18(m, 5H), 7.00(m, 2H), 5.60(d, IH), 5.25(s, 2H), 4.80(d, IH), 4.65(m, IH), 4.02(m, IH), 3.38(s, 2H), 3.06(dd, IH), 2.32(s, 3H), 1.70(m, IH), 1.50(m, IH), 0.90(t,3H)

Example 804

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

Η-NMR(CDCb) : a 9.40(bs, IH), 7.90(s, IH), 7.70(m, 2H), 7.55(d, 3H), 7.40(m, 5H), 7.05(d, 2H), 6.95(s, IH), 6.85(d, IH), 6.00(d, IH), 5.25(s, 2H), 4.80(d, IH), 4.30(m, IH), 4.00(m, IH), 3.38(s, 2H), 3.03(dd, IH), 1.70(m, IH), 1.50(m, IH), 0.90(t,3H)

Example 805

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

-H-NMR(CDCb) : a 7.72(d, IH), 7.60(d, 3H), 7.4 l(m, 4H), 7.10(d, 3H), 7.00(s, 4H), 5.45(m, IH), 5.26(s, 2H), 4.80(d, 2H), 4.12(m, IH), 3.38(s, 2H), 3.12(dd, IH), 2.35(s, 3H), 2.05(s, 3H), 1.70(m, IH), 1.50(m, IH), 0.90(t, 3H)

Example 806

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

-H-NMR(CDCb) : a 7.72(d, IH), 7.60(4 3H), 7.4 l(m, 4H), 7.10(4 3H), 7.00(s, 4H), 5.45(m, IH), 5.26(s, 2H), 4.80(4 2H), 4.12(m, IH), 3.38(s, 2H), 3.12(dd, IH), 2.35(s, 3H), 2.05(s, 3H), 1.70(m, IH), 1.50(m, IH), 0.90(t, 3H)

Example 807

N-(2-Chlorobenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyanoben zyl)- 1 H-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 according to the same procedure as Preparative Example 4 <Stepl>, but replacing 2,3-dichlorobenzylamine with 2-chlorobenzylamine.

1H-NMR (CDCb) : _<5 7.4(m, 2H), 7.2(m, 2H), 4.6 (bs, IH), 3.9(m, 2H), 3.6 (bs, IH), 2.6 (t, 2H), 1.4(s, 9H), l. l-1.6(m, 3H), 0.8(m, 6H)

<Step 2>

N-(2-Chlorobenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)-(t-butoxycarbon yl)amino-3(S)-methylpentylamine

To a solution of N-(2-chlorobenzyl)-2(S)-(t-butoxycarbonyl)amino- 3(S)-methylpentylamine (0.50 g, 1.48 mmol) in dichloromethane (10 ml) was added 4-methoxyphenylisothiocyanate (0.20 ml, 1.48 mmol). The reaction mixture was stined at room temperature for 3hr and concentrated in vacuo. The residue was purified by silica gel column chromatography(eluent: n-hexane/CH2Cb=2/l, v/v) to give the title compound.

1H-NMR (CDCb) : a 7.2-7.4(m, 6H), 6.9(d, 2H), 5.5(m, IH), 5.1(m, IH), 4.7(m, 2H), 3.9(m, IH), 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)-met hylpentylamine

A solution of N-(2-chlorobenzyl)-N-(4-methoxyphenylthiocarb- amoyl)-2(S)-(t-butoxycarbonyl)amino-3(S)-methylpentylamine (0.30 g) and trifluoro acetic acid (2 ml) in dichloromethane (10 ml) was stined at room temperature for 2.5hr and concentrated in vαcuo. The residue was dissolved in dichloromethane, washed with saturated sodium bicarbonate solution and dried over magnesium sulfate. The solution was concentrated in vαcuo to give the title compound.

<Step 4>

N-(2-Chlorobenzyl)-N-(4-methoxyphenyltirιiocarbamoyl)-2(S)- {[ 1 -(4-cyanoben zyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

To a solution of 1 -(4-cyanobenzyl)- 1 H-imidazol-5 -ylacetic acid HCl (0.16 g, 0.57 mmol), 1-hydroxybenzotriazole hydrate (0.11 g, 0.85 mmol), and l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.16 g, 0.85 mmol) in dichloromethane (30 ml) was added triethylamine (0.12 ml, 1.13 mmol). The reaction mixture was stined at room temperature for 30min. Then, N-(2-chlorobenzyl)-N-(4-methoxy- phenylthiocarbamoyl)-2(S)-amino-3(S)-methylpentylamine (0.23 g, 0.57 mmol) was added thereto. The reaction mixture was stined overnight at room temperature and cencentrated in vacuo. The residue was dissolved in ethyl acetate, washed with 10% citric acid and saturated sodium bicarbonate solution, and then dried over magnesium sulfate. This solution was concentrated in vacuo and the residue was purified by silica gel column chromatography(eluent:

v/v) to give the title compound (0.15 g).

-H-NMR (CDCb) : a 7.6(4 2H), 7.4 (m&s, 2H), 7.2(m, 3H), 7.0-7. l(m, 4H), 7.0(s, IH), 6.8(4 2H), 5.2(4 2H), 4.8(dd, 2H), 4.1(m, IH), 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)-{[l-(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl} amino-3 (S)-methylpentylamine

<Step 1>

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

3 (S)-methylpentylamine

The title compound was prepared according to the same procedure as Preparative Example 4, but replacing 2,3-dichlorobenzylamine and 1 -(4-nitrobenzyl)- lH-imidazol-5-yl]acetic acid hydrochloride with 3-chlorobenzylamine and l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetic acid hydrochloride, respectively. TLC : R_f = 0.3 (CH₂C1₂ / MeOH = 10 / 1)

-H-NMR (CDCb) : a 7.6(4 2H), 7.5(s, IH), 7.2-7.3(m, 3H), 7.1(m, 3H), 7.0(s, IH), 5.3(s, 2H), 3.9(m, IH), 3.7(d, 2H), 3.4(s, 2H), 2.7(d, 2H), 1.0-1.5(m, 3H), 0.8-1.0(m, 6H)

<Steρ 2>

N-(3-Chlorobenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methylpentylamine

To a solution of N-(3-chlorobenzyl)-2(S)-{[l-(4-cyanobenzyl)-lH- imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine (0.50 g, 1.48 mmol) in dichloromethane (10 ml) was added 4-methoxyphenylisothiocyanate (0.20 ml, 1.48 mmol). The reaction mixture was stined at room temperature for 3hr and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluent:

v/v) to give the title compound.

^'H-NMR (CDCb) : 8 7.7(4 2H), 7.5(s, IH), 7.3 (m&s, 3H), 7.2(s, IH), 7.1-7.2(m, 4H), 7.0(s, IH), 6.8(d, 2H), 5.2(m, 2H), 4.8(dd, 2H), 4.2(m, IH), 3.8(s, 3H), 3.4(s, 2H), 3.2(dd, 2H), 1.0-1.6(m, 3H), 0.9(m, 6H)

Examples 809-819

N-(3-Chlorobenzyl)-2(S)-{[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl } amino-3 (S)-methylpentylamine was reacted with the conesponding isothiocyanates under the same condition as described in <Step 2> of Example 808 to give the title compounds.

Example 809 N-(3-Chlorobeι 2yl)-N-benzylthiocarbamoyl-2(S)-{[l-(4-cyanobenzyl)-lH-imi dazol-5-yl]acetyl } amino-3 (S)-methy lpentylamine

^'H-NMR (CDCb) : 8 6.90-7.62(m, 15H), 6.20 (t, IH), 5.28(4 2H), 4.42-5.20(m, 5H), 4.15(m, IH), 3.25(s, 2H), 3.12(dd, IH), 1.30-1.65(m, 2H), 1.05(m, IH), 0.88(m, 6H)

Example 810

N-(3 -Chlorobenzyl)-N-(2-bromopheny Ithiocarbamoy 1)-2(S)- { [ 1 -(4-cyanobenzy

1)- 1 H-imidazol-5 -yl]acetyl } amino-3 (S )-methylpentylamine

^'H-NMR (CDCb) : 8 7.00-7.70(m, 14H), 5.35(s, 2H), 5.18(m, IH), 4.65-5.02(dd, 2H), 4.24(m, IH), 3.35(s, 2H), 3.20(dd, IH), 1.35-1.70(m, 2H), 1.05(m, IH), 0.90(m, 6H)

Example 811

N-(3-Chlorobenzyl)-N-(3-bromophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzy 1)- 1 H-imidazol-5-yl] acetyl } amino-3 (S )-methylpentylamine

^'H-NMR (CDCb) : 8 6.90-7.58(m, 14H), 5.22(s, 2H), 4.90 (t, IH), 4.30 & 5.22(dd, 2H), 4.15(m, IH), 3.32(s, 2H), 3.16(dd, IH), 1.35-1.70(m, 2H), 1.05(m, IH), 0.90(m, 6H)

Example 812

N-(3-Chlorobenzyl)-N-(4-chlorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzy 1)- 1 H-imidazol-5 -yl]acetyl } amino-3 (S )-methylpentylamine

1H-NMR (CDCb) : 8 6.95-7.60(m, 14H), 5.22(d, 2H), 4.95 (t, IH), 4.52 & 5.18(dd, 2H), 4.16(m, IH), 3.30(s, 2H), 3.18(dd, IH), 1.35-1.70(m, 2H), 1.05(m, IH), 0.92(m, 6H) Example 813

N-(3 -Chlorobenzyl)-N-ethylthiocarbamoyl-2(S)- {[ 1 -(4-cyanobenzyl)- 1 H-imida zol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : 8 7.00-7.65(m, 10H), 5.85 (t, IH), 5.35(4 2H), 5.04 (t, IH), 4.42 & 4.68(dd, 2H), 4.10(m, IH), 3.55(m, 2H), 3.28(s, 2H), 3.08(dd, IH), 1.35-1.70(m, 2H), 1.05(m, IH), 1.04 (t, 3H), 0.88(m, 6H)

Example 814

N-(3-Chlorobenzyl)-N-(2-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzy l)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : 8 7.00-7.78(m, 14H), 5.25(s, 2H), 4.15(m, IH), 4.60 & 5.10(dd, 2H), 4.20(m, IH), 3.35(s, 2H), 3.16(dd, IH), 1.35-1.70(m, 2H), 1.05(m, IH), 0.90(m, 6H)

Example 815

N-(3 -Chlorobenzyl)-N-(3 -fluorophenylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanobenzy

1)-1 H-imidazol-5 -yl] acetyl} amino-3 (S)-methylpentylamine

^"H-NMR (CDCb) : 8 6.90-7.60(m, 14H), 5.25(s, 2H), 4.95 (bs, IH), 4.50 & 5.20(dd, 2H), 4.18(m, IH), 3.35(s, 2H), 3.18(dd, IH), 1.35-1.70(m, 2H), 1.05(m, IH), 0.90(m, 6H)

Example 816

N-(3 -Chlorobenzyl)-N-(4-fluorophenylthiocarbamoyl)-2(S)- {[ 1 -(4-cyanobenzy l)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR (CDCb) : 8 7.00-7.60(m, 14H), 5.25(d, 2H), 4.95-5.18(m, 2H), 4.55(d, IH), 4.15(m, IH), 3.32(s, 2H), 3.16(dd, IH), 1.30-1.70(m, 2H), 1.05(m, IH), 0.90(m, 6H)

Example 817

N-(3 -Chlorobenzyl)-N-methylthiocarbamoyl-2(S)- {[ 1 -(4-cyanobenzyl)- 1 H-imi dazol-5-yl]acetyl } amino-3 (S)-methylpentylamine

Η-NMR (CDCb) : 8 6.88-7.68(m, 10H), 6.25 (bs, IH), 5.35(dd, 2H), 5.02(m, IH), 4.40 & 4.72(dd, 2H), 4.10(m, IH), 3.30(s, 2H), 3.05(m, 4H), 1.30-1.70(m, 2H), 1.05(m, IH), 0.92(m, 6H)

Example 818

N-(3-Chlorobenzyl)-N-(3-trifluoromethylphenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S)-methylpentylamine

^"H-NMR (CDCb) : 8 6.95-7.60(m, 14H), 5.22(s, 2H), 4.82 (bs, IH), 4.50 & 5.38(dd, 2H), 4.18(m, IH), 3.35(s, 2H), 3.20(dd, IH), 1.30-1.70(m, 2H), 1.05(m, IH), 0.90(m, 6H)

Example 819

N-(3-Chlorobenzyl)-N-allylthiocarbamoyl-2(S)-{ [ 1 -(4-cyanobenzyl)- IH-imida zol-5-yl]acetyl } amino-3 (S)-methylpentylamine

¹ H-NMR (CDCb) : 8 6.95-7.65(m, 10H), 5.95 (t, IH), 5.78(m, IH), 5.20(m, IH), 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, IH), 0.88(m, 6H)

Example 820

N-(2,6-Dichlorobenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)- {[ 1 -(4-cyano benzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 2,6-dichloro- benzylamine.

-H-NMR (CDCb) : 8 7.7(4 2H), 7.4-7.5 (m&s, 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, IH), 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)-{[l -(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 2-fluoro benzylamine.

1H-NMR (CDCb) : 8 7.7(d, 2H), 7.5 (m&s, 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, IH), 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)-{[l-(4-cyano benzyl)-lH-imidazol-5-yl]acetyl}ammo-3(S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 2,3-difluoro- benzylamine.

1H-NMR (CDCb) : 8 7.6(d, 2H), 7.5(s, 2H), 7.4(m, IH), 7.3(s, IH), 7.0-7.2(m, 6H), 6.8(4 2H), 5.3(4 2H), 4.8(dd, 2H), 4.2(m, IH), 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)-{[l-(4-cyano benzyl)- 1 H-rmidazol-5-yl] acetyl } amino-3 (S)-methy lpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 2,6-difluoro- benzylamine.

^'H-NMR (CDCb) : 8 7.7(4 2H), 7.5(s, 2H), 7.3-7.4 (m&s, IH), 7.1-7.3(m, 5H), 7.1(s, IH), 6.8(4 2H), 5.3(d, 2H), 4.9(dd, 2H), 4.3(m, IH), 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-cyanoben zyl)- lH-imidazol-5-yl]acetyl} amino-3 (S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 4-t-butyl- benzylamine.

Η-NMR (CDCb) : 8 7.6(d, 2H), 7.5(s, IH), 7.4(m, 2H), 7.3(s, IH), 7.3(m, 4H), 7.1(m, 2H), 6.9(d, 2H), 5.3(d, 2H), 4.8(dd, 2H), 4.3(m, IH), 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-cyanoben zyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 2-ethoxy- benzylamine.

Example 826

N-(Pyridin-3 -yl)methyl-N-(4-methoxyphenylthiocarbamoyl)-2(S)- {[ 1 -(4-cyano b enzyl)- 1 H-imidazol-5 -y 1] acetyl } amino-3 (S )-methy lpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 3-amino- methylpyridine.

1H-NMR (CDCb) : 8 8.6(4 IH), 8.5(s, IH), 8.1(m, IH), 7.6(d, 2H), 7.5(s, IH), 7.3(m, 2H), 7.1-7.2(m, 3H), 7.0(s, IH), 6.9(d, 2H), 5.3(d, 2H), 4.6(d, 2H), 4.2(m, IH), 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)- lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 3,4-dimethoxy- phenylethylamine.

^'H-NMR (CDCb) : 8 7.6(d, 2H), 7.5(s, IH), 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, IH), 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-cyanoben zyl)- 1 H-imidazol-5 -yl]acetyl } amino-3 (S )-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with l-amino-2- phenylpropane.

Η-NMR (CDCb) : 8 7.6(4 2H), 7.5(s, IH), 7.2-7.4(m, 5H), 7.1-7.2(m, 3H), 7.0(s, IH), 6.9(m, IH), 6.8(d, 2H), 5.3(m, 2H), 4.6(m, IH), 4.2(m, IH), 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 -cy anobenzyl)- 1 H-imidazol-5-yl] acetyl } amino-3 (S )-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 2-(2-methoxy- phenyl)ethylamine.

^'H-NMR (CDCb) : 8 7.6(d, 2H), 7.5(m, 2H), 7.2-7.3(m, 3H), 7.2(d, IH), 7.1(d, 2H), 6.9-7.0(m, 4H), 5.3(m, 2H), 4.2(m, IH), 3.9(s, 3H), 3.7(s, 3H), 3.6 (q, 2H), 3.3(s, 2H), 3.2(d, 2H), 2.9(m, 2H), l. l-1.7(m, 3H), 0.9(m, 6H)

Example 830

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

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 4-nitro- benzylamine.

1H-NMR (CDCb) : 8 8.16-8.2 l(m, 2H), 7.96 (bs, IH), 7.55-7.60(m,

2H), 7.47(s, IH), 7.36-7.43(m, 2H), 7.00-7.17(m, 5H), 6.82-6.88(m, 3H),

6.57-6.03(m, IH), 5.20-5.38(m, 3H), 4.84-5.03(m, IH), 4.59-4.71(m, IH),

4.04-4.16(m, IH), 3.79(s, 3H), 3.35(m, 2H), 3.12(m, IH), 1.54-1.63(m, IH), 1.35(m, IH), 1.12(m, IH), 0.90(m, 6H)

Example 831

N-[2-(2-Fluorophenyl)]ethyl-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-c yanobenzyl)- lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 2-(2-fluoro- phenyl)ethylamine.

^"H-NMR (CDCb) : 8 7.60(m, 3H), 7.43(s, IH), 7.14-7.2 l(m, 5H), 7.08(m, 4H), 6.99(m, IH), 5.26(m, 2H), 5.00(m, IH), 4.14(m, IH), 3.81(s, 3H), 3.42-3.58(m, IH), 3.28(s, 2H), 3.02-3.15(m, IH), 2.94 (bs, 2H), 1.65(m, IH), 1.45(m, IH), 1.10(m, IH), 0.93(m, 6H)

Example 832

N-(4-methoxybenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanob enzyl)- lH-imidazol-5-yl]acetyl } amino-3 (S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 4-methoxy- benzylamine.

-H-NMR (CDCb) : a 7.60(4 2H), 7.47(s, IH), 7.29-7.35(m, 2H), 7.09-7.17(m, 4H), 7.02(m, 3H), 7.00(s, IH), 6.85(m, 3H), 5.14-5.38(m, 3H), 4.52-4.82(m, 2H), 4.15(m, IH), 3.80(s, 3H), 3.78(s, 3H), 3.32(s, 2H), 3.11-3.22(m, IH), 1.59-1.63(m, IH), 1.43-1.5 l(m, IH), 1.12(m, IH), 0.90(m, 6H)

Example 833

N-(3 ,4-Methylenedioxybenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)- { [ 1 -(

4-cyanobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with piperonylamine.

^'H-NMR (CDCb) : 8 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, IH), 3.80(s, 3H), 3.32(s, 2H), 3.11-3.22(m, IH), 2.02(m, IH), 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-cyanoben zyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 2-methyl- benzylamine.

-H-NMR (CDCb) : 8 7.6(d, 2H), 7.4(s, IH), 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, IH), 3.8(s, 3H), 3.3(s, 2H), 3.1(dd, 2H), 2.3(s, 3H), l. l-1.5(m, 3H), 0.9(m, 6H)

Example 835

N-(2-Methylbenzyl)-N-(3-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobenzy 1)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methy lpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate with 2-methylbenzylamine and 3-fluorophenylisothio- cyanate, respectively.

^'H-NMR (CDCb) : 8 7.6(d, 2H), 7.4(s, IH), 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, IH), 3.4(s, 2H), 3.1(d, 2H), 2.3(s, 3H), l.l-1.6(m, 3H), 0.9-1.0(m, 6H)

Example 836

N-(2-Methylbenzyl)-N-(2-methoxypyridm-5-yl)thiocarbamoyl-2(S)-{[l-(4-cya nobenzyl)- lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate with 2-methylbenzylamine and 2-methoxypyridin-5- ylisothiocyanate, respectively.

-H-NMR (CDCb) : 8 7.8(s, IH), 7.6(d, 2H), 7.4(m, IH), 7.3(s, IH), 7.2(m, 3H), 7.1 (s+d, 3H), 7.0(s, IH), 6.7(d, IH), 5.3(d, 2H), 4.5 & 5.0(dd, 2H), 4.2(m, IH), 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)-{[l-(4-cyanoben zyl)- lH-imidazol-5-yl]acetyl} amino-3 (S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 4-fluoro- benzylamine.

^'H-NMR (CDCb) : 8 7.6(4 2H), 7.4(s, IH), 7.3(m, IH), 7.2(m, 2H),

7.0-7. l(m, 5H), 7.0(s, IH), 6.8(4 2H), 5.3(m, 2H), 4.5-4.8(dd, 2H),

4.1-4.2(m, IH), 3.8(s, 3H), 3.3(s, 2H), 3.1(dd, 2H), l. l-1.5(m, 3H), 0.9(m, 6H)

Example 838

N-(Pyridin-4-ylmethyl)-N-(4-meι oxyphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyano benzyl)- 1 H-imidazol-5 -yl]acetyl } amino-3 (S)-methy lpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 4-aminomethyl- pyridine.

-H-NMR (CDCb) : 8 8.5(d, 2H), 7.6(d, 2H), 7.6(s, IH), 7.5(m, IH),

7.0-7. l(m, 5H), 6.9(s, IH), 6.8(d, 2H), 5.2(s, 2H), 4.5-4.8(dd, 2H),

4.1-4.2(m, IH), 3.8(s, 3H), 3.3(s, 2H), 3.1(dd, 2H), l. l-1.5(m, 3H), 0.9(m, 6H)

Example 839

N-(Pyridin-2-ylmethyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyano benzyl)- 1 H-imidazol-5 -yl]acetyl } amino-3 (S)-methy lpentylamine The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 2-aminomethyl- pyridine.

-H-NMR (CDCb) : 8 8.6(4 2H), 7.8(m, 2H), 7.6(s, IH), 7.5(s, IH), 7.3-7.4(m, 3H), 7.1(d, 2H), 7.0(s, IH), 6.9(d, 2H), 5.3(d, 2H), 4.4-4.8(dd, 2H), 4.2(m, IH), 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-y lmethyl)-N-(3 -fluoropheny Ithiocarbamoy 1)-2(S)- { [ 1 -(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate with 2-aminomethylpyridine and 3-fluorophenylisothio- cyanate, respectively.

Η-NMR (CDCb) : 8 8.6(d, IH), 7.8 (t, IH), 7.6(d, 2H), 7.5 (m+s, 2H), 7.2-7.4(m, 4H), 7.2(d, 2H), 7.0(s, IH), 6.9 (t, IH), 5.3(s, 2H), 4.4 & 4.9(dd, 2H), 4.3(m, IH), 3.3(m, 2H), 3.1(dd, 2H), l. l-1.6(m, 3H), 0.9(m, 6H)

Example 841

N-(3-Fluorobenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyanoben zyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 3-fluorobenzyl- amine. 1H-NMR (CDCb) : 8 7.7(d, 2H), 7.5(s, 2H), 7.4(m, IH), 7.3(d, IH), 7.1-7.2(m, 7H), 6.9(d, 2H), 5.4(s, 2H), 4.9(dd, 2H), 4.3(m, IH), 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)-{[l-(4-cyanobenzyl )- 1 H-imidazol-5-yl] acetyl } amino-3 (S )-methy lpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate with 3-fluorobenzylamine and 3-fluorophenylisothiocyanate, respectively.

^"H-NMR (CDCb) : 8 7.6(d, 2H), 7.4(s, IH), 7.2-7.3(m, 2H), 6.8-7. l(m, 9H), 5.2(s, 2H), 4.5 & 5.1(dd, 2H), 4.1(m, IH), 3.3(s, 2H), 3.2(dd, 2H), l. l-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 according to the same procedure as Example 807, but replacing 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate with 3-fluorobenzylamine and cyclohexylisothiocyanate, respectively.

-H-NMR (CDCb) : 8 7.7(4 2H), 7.4-7.5(m, 3H), 7.3-7.4(m, 2H), 7.2(d, 2H), 7.0(s, IH), 5.3(d, 2H), 5.1-5.2(m, IH), 4.5-4.8(m, 2H), 4.2(m, IH), 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-cyan obenzyl)- 1 H-imidazol-5-yl] acetyl } amino-3 (S)-methy lpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate with 3-fluorobenzylamine and 2-methoxypyridin-5-ylisothio- cyanate, respectively.

^"H-NMR (CDCb) : 8 7.8(4 IH), 7.5-7.6(m, 7H), 7.4(s, IH), 7.1(4 2H), 7.0(s, IH), 6.7(m, IH), 4.6 & 5.2(s, 2H), 4.2(m, IH), 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- cy anobenzyl)- 1 H-imidazol-5-y 1] acetyl } amino-3 (S )-methylpenty lamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 3-trifluoromethyl benzy lamine.

^"H-NMR (CDCb) : 8 7.7(d, 2H), 7.6(m, 2H), 7.5(s, IH), 7.3(d, IH), 7.1-7.2(m, 5H), 7.1(s, IH), 6.9(d, 2H), 5.3(s, 2H), 5.0(dd, 2H), 4.3(m, IH), 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-cy anobenzyl)- 1 H-imidazol-5-yl] acetyl } amino-3 (S)-methylpentylamine The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate with 3-trifluoromethylbenzylamine and 3-fluorophenylisothiocyanate, respectively.

1H-NMR (CDCb) : 8 7.5-7.7(m, 5H), 7.5(s, IH), 7.3(m, IH), 6.8-7.2(m, 7H), 5.3(s, 2H), 4.6 & 5.1(dd, 2H), 4.2(m, IH), 3.4(s, 2H), 3.2(dd, 2H), l. l-1.6(m, 3H), 0.9-1.0(m, 6H)

Example 847

N-(3 -Trifluoromethylbenzyl)-N-cyclohexylthiocarbamoyl-2(S)- {[ 1 -(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate with 3-trifluoromethylbenzylamine and cyclohexylisothio- cyanate, respectively.

-H-NMR (CDCb) : 8 7.7(d, 2H), 7.5(s, IH), 7.2-7.3(m, 2H), 7.2(d, 2H),

6.8-7.0(m, 3H), 5.3(s, 2H), 5.2(m, IH), 4.5 & 4.8(m, 2H), 4.1(m, IH),

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-meι oxypyridin-5-ylthiocarbamoyl)-2(S)-{[ l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine and 4-methoxyphenyl- isothiocyanate with 3-trifluoromethylbenzylamine and 2-methoxypyridin-5- ylisothiocyanate, respectively.

-H-NMR (CDCb) : 8 7.8(4 IH), 7.6(4 2H), 7.5(4 IH), 7.3 (m+s, 2H), 6.9-7.1 (d+m, 4H), 6.7(4 IH), 5.2(4 2H), 4.5 & 5.2(dd, 2H), 4.2(m, IH), 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)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 3-methoxy- carbonylbenzylamine .

1H-NMR (CDCb) : 8 7.99(d, IH), 7.89(s, IH), 7.58(4 2H), 7.44(m, 3H), 7.02-7. l l(m, 5H), 6.82(4 2H), 5.27(m, 2H), 5.16(m, 2H), 4.63(d, IH), 4.06-4.23(m, IH), 3.92(s, 3H), 3.78(s, 3H), 3.40(s, 2H), 3.13-3.21(m, IH), 1.52-1.65(m, IH), 1.38(m, IH), 1.02(m, IH), 0.90(m, 6H)

Example 850

N-(3-Methoxycarbonylbenzyl)-N-(3-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-c yanobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate with 3-methoxycarbonylbenzylamine and 3-fluorophenylisothiocyanate, respectively.

-H-NMR (CDCb) : 8 8.01(d, IH), 7.90(s, IH), 7.59(d, 2H), 7.46(m, 3H), 7.19-7.26(m, IH), 6.86-7.1 l(m, 7H), 5.18-5.30(m, 3H), 4.95(m, IH), 4.60(d, IH), 4.10-4.23(m, IH), 3.93(s, 3H), 3.35(s, 2H), 3.24(m, IH), 1.70(m, IH), 1.43-1.60(m, IH), 1.06(m, IH), 0.90(m, 6H)

Example 851

N-(3 -Carboxybenzyl)-N-(3 -fluorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanobenz yl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine hydrochloride

To a solution of the compound of Example 850 (110 mg) in ethanol(1.5 ml) was added lithium hydroxide solution (1M, 2 ml). The reaction mixture was stined at room temperature for 3hr. After the addition of IN HCl solution (2.5 ml), the mixture was extracted with dichloromethane. The organic phase was dried over magnesium sulfate and concentrated in vacuo to give a white solid of the title compound (57 mg, 53%).

^'H-NMR (CDCb) : 8 9.54(d, IH), 8.94(s, IH), 8.30-8.47(m, IH), 7.93(m, 4H), 7.42-7.85(m, 4H), 7.15-7.38(m, 3H), 7.00 (t, IH), 5.60(s, 2H), 5.13-5.40(m, 2H), 4.40(m, IH), 4.05(m, IH), 3.39-3.76(m, 3H), 1.40-1.52(m, 2H), 1.19-1.30(m, IH), 0.86(m, 6H)

Example 852

N-(4-Methoxy carbonylbenzyl)-N-(4-methoxyphenylthiocarbamoy 1)-2(S)- { [ 1 -(

4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 4-methoxy- carb onylbenzy lamine .

^'H-NMR (CDCb) : 8 8.02(d, 2H), 7.59(d, 2H), 7.49(s, IH), 7.30(m, 2H), 7.06-7.12(m, 4H), 7.02(s, IH), 6.83(d, 2H), 5.30(m, 2H), 5.16(m, 2H), 4.65(d, IH), 4.03-4.27(m, IH), 3.92(s, 3H), 3.78(s, 3H), 3.33(s, 2H), 3.12(m, IH), 1.63(m, IH), 1.40(m, IH), 1.05(m, IH), 0.90(m, 6H)

Example 853

N-(4-Methoxycarbonylbenzyl)-N-(3-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-c yanobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine and 4-methoxyphenylisothiocyanate with 4-methoxycarbonylbenzylamine and 3 -fluorophenylisothiocyanate, respectively.

1H-NMR (CDCb) : 8 9.25(s, 2H), 8.50(m, IH), 8.00(m, 4H), 7.69(s,

IH), 7.53(d, 2H), 7.40(d, 2H), 7.16(d, 2H), 6.90(m, 2H), 5.64(s, 2H),

5.20(m, 2H), 4.23-5.54(m, IH), 4.05(m, IH), 3.81(s, 3H), 3.40-3.73(m, 2H), 1.51 (bs, 2H), 1.25(m, IH), 0.90(m, 6H)

Example 854

N-(4-Carboxybenzyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanob enzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine hydrochloride

The title compound was prepared according to the same procedure as Example 851, but replacing the compound of Example 850 with the compound of Example 852.

-H-NMR (CDCb) : 8 9.25(s, IH), 8.41-8.6 l(m, IH), 7.95(m, 4H), 7.69(s, IH), 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, IH), 3.98(m, IH), 3.81(m, 3H), 3.43-3.69(m, 3H), 1.50-1.58(m, 2H), 1.12(m, IH), 0.88(m, 6H) Example 855

N-(4-Carboxybenzyl)-N-(3-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cyanobenz yl)-l H-imidazol-5 -yl] acetyl} amino-3 (S)-methylpentylamine hydrochloride

The title compound was prepared according to the same procedure as Example 851, but replacing the compound of Example 850 with the compound of Example 853.

^'H-NMR (CDCb) : 8 9.57 (bs, IH), 9.26(s, IH), 8.43-8.63(m, IH), 8.00(m, 4H), 7.71(s, IH), 7.53(4 2H), 7.42(d, 2H), 7.17-7.34(m, 3H), 7.02(m, IH), 5.66(s, 2H), 5.18-5.42(m, 2H), 4.26-4.50(m, IH), 4.08(m, IH), 3.40-3.71(m, 3H), 1.50-1.62(m, 2H), 1.15(m, IH), 0.87(m, 6H)

Example 856

N-( l-Oxypyridin-2-ylmethyl)-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{ [ l-(4- cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

To a solution of the compound of Example 839 (62 mg) in dichloromethane (5 ml) was added -chloroperbenzoic acid (0.04 g). The reaction mixture was stined for 2hr at room temperature. After concentration in vacuo, the residue was purified by column chromatography(eluent: methylene chloride/methanol=9/l, v/v) to give a solid of the title compound.

1H-NMR (DMSO-Q6 + TFA-di) : 8 8.7(s, IH), 8.2(m, IH), 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, IH), 3.4-3.7 (m & s, 7H), 1.4(m, 2H), 1.0(m, IH), 0.8(m, 6H) Example 857

N-Methyl-N-(4-methoxyphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanobenzyl)- 1 H-i midazol-5 -yl] acetyl } amino-3 (S)-methy lpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with methylamine.

Η-NMR (CDCb) : 8 7.40-7.70(m, 3H), 7.30(s, IH), 7.00-7.25(m, 5H), 6.80-6.95(m, 2H), 5.00-5.40(m, 3H), 4.00-4.30(m, IH), 3.80(m, 4H), 3.30(m, 2H), 3.18(s, 3H), 3.07(dd, IH), 1.37-1.80(m, 2H), 1.00-1.30(m, IH), 0.92(m, 6H)

Example 858

N-Isobutyl-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{ [ 1 -(4-cyanobenzyl)- 1 H-i midazol-5-yl]acetyl}amino-3(S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with isobutylamine.

-H-NMR (CDCb) : 8 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, IH), 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

N-n-Butyl-N-(4-meι oxyphenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanobenzyl)- IH-i midazol-5-yl]acetyl}amino-3(S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with n-butylamine. 1H-NMR (CDCb) : 8 7.6(4 2H), 7.5(s, IH), 7.2(4 2H), 7.1(d, 2H), 7.0(s, IH), 6.9(d, 2H), 5.2-5.3(m, 2H), 4.1(m, IH), 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), l . l-1.4(m, 5H), 0.9(m, 6H)

Example 860

N-[2-(Ethylthio)ethyl]-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyanob enzyl)- lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 2-(ethylthio) ethylamine.

-H-NMR (CDCb) : 8 7.6(d, 2H), 7.4(s, IH), 7.2(d, 2H), 7.1(d, 2H), 7.0(s, IH), 6.8(d, 2H), 5.3(s, 2H), 4.1(m, IH), 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), l.l(m, IH), 0.9-1.0(m, 6H)

Example 861

N-(3-Ethoxy)propyl-N-(4-methoxyphenylthiocarbamoyl)-2(S)-{[l-(4-cyanoben zyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with 3-ethoxypropyl- amine.

1H-NMR (CDCb) : 8 7.6(m, 3H), 7.5(d, 2H), 7.1-7.2(m, 3H), 7.0(s, IH), 6.9(d, IH), 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)-{[l-(4-cyanobenzyl)- 1 H-imidazol-5-yl] acetyl } amino-3 (S )-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine with propargylamine.

H-NMR (CDCb) : a 7.57(d, 2H), 7.46(s, IH), 7.08(d, 2H), 6.92(s, IH),

6.78(m, IH), 5.21(s, 2H), 5.05(s, IH), 4.45(m, IH), 4.00-4.30(m, 3H),

3.78(s, 3H), 3.35-3.70(m, IH), 3.29(s, 2H), 2.90-3.25(m, IH), 1.00-1.90(m, 3H), 0.88(m, 6H)

Example 863

N-(2-Propynyl)-N-(3 -fluorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cyanobenzyl)- 1

H-imidazol-5 -yl] acetyl } amino-3 (S)-methylpentylamine

The title compound was prepared according to the same procedure as Example 807, but replacing 2-chlorobenzylamine and 4-methoxyphenyl- isothiocyanate4 with propargylamine and 3-fluorophenylisothiocyanate, respectively.

-H-NMR (CDCb) : 8 7.58(d, 2H), 7.48(s, IH), 7.00-7.30(m, 3H), 6.93(s, IH), 6.67-6.87(m, IH), 6.40-6.66(m, 3H), 5.20(s, 2H), 5.09(s, IH), 4.50(m, IH), 4.00-4.30(m, 3H), 3.35-3.80(m, IH), 3.29(s, 2H), 2.95-3.25(m, IH), 1.00-1.90(m, 3H), 0.90(m, 6H)

Example 864

N-(2-Trifluoromethylbenzyl)-N-(allylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrobenzyl)-

1 H-imidazol-5 -yl] acetyl } amino-3 (S )-methylpentylamine <Step 1>

N-(2-Trifluoromethylbenzyl)-2(S)-{[l-(4-nitrobenzyl)-lH-imidazol-5-yl]acetyl } amino-3 (S)-methylpentylamine

Using the same method as described in Preparative Example 3, N-/-butoxycarbonyl-L-isoleucine was converted to N-(t-butoxycarbonyl)-L- isoleucine aldehyde. And then the reaction was carried out under the same condition as described in Preparative Example 4, but replacing 2,3-dichlorobenzylamine with 2-trifluoromethylbenzylamine to give the title compound.

-H-NMR(CDCb) : 8 8.17(d, 2H), 7.65(d, IH), 7.52(d, 2H), 7.5 l(s, IH), 7.33-7.41(m, IH), 7.17(d, 2H), 7.04(s, IH), 5.93(d, IH), 5.30(s, 2H), 3.89(s, 2H), 3.80-3.87(m, IH), 3.36(s, 2H), 2.69(d, 2H), 1.44-1.54(m, IH), 1.33-1.40(m, IH), 0.95-1.01(m, IH), 0.80-0.92(m, 6H)

<Step 2>

N-(2-Trifluoromethylbenzyl)-N-(allylthiocarbamoyl)-2(S)- { [ 1 -(4-nitrobenzyl)-

1 H-imidazol-5-yl] acetyl } amino-3 (S )-methylpenty lamine

To a solution of N-(2-Trifluoromethylbenzyl)-2(S)-{[l-(4-nitro- benzyl)-lH-imidazol-5-yl]acetyl}ammo-3(S)-methylpentylamine in dichloro methane (0.02M, 1ml, 0.02mmol) was added allylisothiocyanate (O.IM in CH₂C1₂, 0.2ml, 0.02mmol). The reaction mixture was agitated for 2hr at room temperature. The mixture was purified by silica gel column chromatography(eluent:

v/v) to give the title compound as a white solid.

^'H-NMR(CDCb) : 8 8.21(d, 2H), 7.72(4 IH), 7.39-7.53(m, 3H), 7.15-7.28(m, 3H), 7.02(s, IH), 5.87(bs, IH), 5.71-5.85(m, IH), 5.30-5.52(m, 2H), 4.70-5.08(m, 2H), 4.65(d, IH), 4.21-4.29(m, 2H), 4.05-4.14(m, IH), 3.33(s, 2H), 3.06(dd, IH), 1.65(bs, IH), 1.26-1.44(m, IH), 0.97-1.05(m, IH), 0.86-0.92(m, 6H)

Examples 865-868

N-(2-Trifluoromethylbenzyl)-2(S)- { [ 1 -(4-nitrobenzyl)- 1 H-imidazol-5 - yl] acetyl} amino-3 (S)-methylpentylamine was reacted with the conesponding isothiocyanates under the same condition as described in <Step 2> of Example 864 to give the title compounds.

Example 865

N-(2-Trifluoromethylbenzyl)-N-(4-chlorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-nit robenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

-H-NMR(CDCb) : 8 8.15(d, 2H), 7.70(d, IH), 7.40-7.58(m, 3H), 7.19-7.30(m, 5H), 7.14(d, 2H), 6.97(s, IH), 5.22-5.4 l(m, IH), 5.3 l(d, 2H), 4.82-4.95(m, IH), 4.77(d, IH), 3.34(s, 2H), 3.13(dd, IH), 1.64-1.70(m, IH), 1.40-1.48(m, IH), 0.98-1.06(m, IH), 0.86-0.93(m, 6H)

Example 866

N-(2-Trifluoromethylbenzyl)-N-cyclohexylthiocarbamoyl-2(S)- { [ 1 -(4-nitroben zyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR(CDCb) : 8 8.20(d, 2H), 7.70-7.74(m, IH), 7.55(s, IH), 7.42-7.46(m, 2H), 7.13-7.26(m, 3H), 7.04(s, IH), 5.42(d, 2H), 5.17(bs, IH), 4.73(dd, 2H), 4.17-4.22(m, IH), 4.05-4. l l(m, IH), 3.34(s, 2H), 3.04(dd, IH), 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-nit robenzyl)-lH-imidazol-5-yl]acetyl}amino-3(S)-methylpentylamine

1H-NMR(CDCb) : 8 8.28(bs, IH), 8.14(4 2H), 7.72(4 IH),

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, IH), 5.32(s, 2H), 4.82-4,95(m, IH), 4.77(4 IH),

4.08-4.16(m, IH), 3.35(s, 2H), 3.18(dd, IH), 1.62-1.70(m, IH), 1.38-1.46(m, IH), 0.98-1.06(m, IH), 0.86-0.92(m, 6H)

Example 868

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

-H-NMR(CDCb) : 8 8.15(d, 2H), 7.72(d, IH), 7.66(bs, IH), 7.41-7.57(m, 3H), 7.24-7.29(m, 2H), 7.07-7.18(m, 3H), 7.0 l(s, IH), 6.84(d. 2H), 5.35(d, 2H), 5.08-5.26(m, 2H), 4.79(d, IH), 4.06-4.18(m, IH), 3.78(s. 3H), 3.34(s, 2H), 3.11(dd, IH), 1.62-1.73(m, IH), 1.32-1.48(m, IH), 0.96-1.09(m, IH), 0.86-0.92(m, 6H)

Example 869

N-(2-Trifluoromethylbenzyl)-N-allylthiocarbamoyl-2-{[l-(4-cyanobenzyl)-lH- imidazol-5 -yl] acetyl } aminoethylamine

<Step 1>

N-(2-Trifluoromethylbenzyl)-2-{[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acetyl}a minoethylamine

Using the same method as described in Preparative Example 3, N-t-butoxycarbonyl-L-glycine was converted to N-(t-butoxycarbonyl)-L- glycine aldehyde. And then the reaction was carried out under the same condition as described in Preparative Example 4, but replacing 2,3-dichlorobenzylamine and 1 -(4-nitrobenzyl)- 1 H-imidazol-5 -ylacetic acid hydrochloride with 2-trifluoromethylbenzylamine and 1 -(4-cyanobenzy 1)- 1 H-imidazol-5 -ylacetic acid hydrochloride, respectively, to give the title compound.

-H-NMR(CDCb) : a 7.32-7.63(m, 7H), 7.14(4 2H), 7.01(s, IH), 6.53(bs, IH), 5.26(s, 2H), 3.89(s, 2H), 3.36(s, 2H), 3.27(q, 2H), 2.73(t, 2H)

<Step 2>

N-(2-Trifluorometτιylbenzyl)-N-(allylthiocarbamoyl)-2- { [ 1 -(4-cyanobenzyl)- 1

H-imidazol-5-yl]acetyl}aminoethylamine

To a solution of N-(2-Trifluoromethylbenzyl)-2-{[l-(4-cyanobenzyl)- lH-imidazol-5-yl]acetyl}aminoethylamine in dichloromethane (0.02M, 1ml, 0.02mmol) was added allylisothiocyanate (O. IM in CH2CI2, 0.2ml, 0.02mmol). The reaction mixture was agitated for 2hr at room temperature. The mixture was purified by silica gel column chromatography(eluent:

v/v) to give the title compound as a white solid.

-H-NMR(CDCb) : 8 7.64(d, 2H), 7.53(s, IH), 7.25-7.46(m, 2H),

7.31-7.44(m, 2H), 7.16(d, 2H), 7.06(bs, IH), 6.98(s, IH), 6.61(bs, IH),

5.79-5.99(m, IH), 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)

Examples 870-873 N-(2-Trifluoromethylbenzy l)-2- { [ 1 -(4-cyanobenzyl)- 1 H-imidazol-5 -yl] acetyl} aminoethylamine was reacted with the conesponding isothiocyanates under the same condition as described in <Step 2> of Example 869 to give the title compounds.

Example 870

N-(2-Trifluoromethylbenzyl)-N-(4-chlorophenylthiocarbamoyl)-2- { [ 1 -(4-cyano benzyl)- lH-imidazol-5-yl]acetyl}aminoethylamine

-H-NMR(CDCb) : δ 8.90(bs, IH), 7.68(4 IH), 7.51-7.61(m, 4H), 7.40-7.47(m, 3H), 7.29(d, 2H), 7.06(4 2H), 6.99(bs, IH), 6.93(s, IH), 5.3 l(s, 2H), 5.18(s, 2H), 3.68(t, 2H), 3.37(s, 2H), 3.29-3.34(m, 2H)

Example 871

N-(2-Trifluoromethylbenzyl)-N-cyclohexylthiocarbamoyl-2- { [ 1 -(4-cyanobenzy l)-lH-imidazol-5-yl]acetyl}aminoethylamine

-H-NMR(CDCb) : δ 7.69(d, IH), 7.63(4 2H), 7.53(s, IH), 7.40-7.49(m, 2H), 7.29(d, IH), 7.16(d, 2H), 7.00(s, IH), 6.06(bs, IH), 5.29(s, 2H), 5.01(s, 2H), 4.23-4.30(m, IH), 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-cy ano benzyl)- lH-imidazol-5-yl]acetyl}aminoethylamine

-H-NMR(CDCb) : δ 8.82(bs, IH), 7.69(d, IH), 7.59(s, IH), 7.54(s, 2H),

7.38-7.49(m, 2H), 7.23-7.33(m, 3H), 7.09(d, 2H), 6.99(s, IH),

6.86-6.96(m, IH), 6.66(bs, IH), 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-cya nobenzyl)- 1 H-imidazol-5-yl] acetyl } aminoethylamine

-H-NMR(CDCb) : a 8.42(bs, IH), 7.68(4 IH), 7.56(4 2H), 7.38-7.50(m, 3H), 7.26(4 2H), 6.97(4 2H), 6.95(s, IH), 6.87(4 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)- 1

H-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylamine

<Step 1>

N-(2-Trifluoromethylbenzyl)-2(S)-{[l-(4-cyanobenzyl)-lH-imidazol-5-yl]acety 1 } amino-3 -(4-benzyloxy)phenylpropy lamine

Using the same method as described in Preparative Example 3, N-t-butoxycarbonyl-L-(O-benzyl)tyrosine was converted to N-t-butoxy- carbonyl-L-(O-benzyl)tyrosine aldehyde. And then the reaction was carried out under the same condition as described in Preparative Example 4, but replacing 2,3-dichlorobenzylamine and 1 -(4-nitrobenzyl)- 1H- imidazol-5 -ylacetic acid hydrochloride with 2-trifluoromethylbenzylamine and l-(4-cyanobenzyl)-lH-imidazol-5-ylacetic acid hydrochloride, respectively, to give the title compound.

-H-NMR(CDCb) : 8 7.62(4 IH), 7.58(4 2H), 7.51-7.54(m, 2H), 7.30-7.45(m, 7H), 6.96-7.03(m, 5H), 6.84(4 2H), 6.12(4 IH), 5.03(s, 2H), 4.86(d, IH), 4.17-4.22(m, IH), 3.86(s, 2H), 3.26(t, 2H), 2.62-2.71(m, 4H) <Steρ 2>

N-(2-Trifluoromethylbenzyl)-N-allylthiocarbamoyl-2(S)- { [ 1 -(4-cyanobenzyl)- 1

H-imidazol-5 -yl] acetyl } amino-3 -(4-benzyloxy)phenylpropylamine

To a solution of N-(2-trifluoromethylbenzyl)-2(S)-{[l-(4- cyanobenzyl)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxy)phenylpropylam ine in dichloromethane (0.02M, 1ml, 0.02mmol) was added allylisothiocyanate (O.IM in CH2CI2, 0.2ml, 0.02mmol). The reaction mixture was agitated for 2hr at room temperature. The mixture was purified by silica gel column chromatography(eluent:

v/v) to give the title compound as a white solid.

-H-NMR(CDCb) : 8 7.70(d, IH), 7.60(d, 2H), 7.42(m, 5H), 7.32(m, 5H), 7.00(m, 7H), 6.68(s, IH), 5.82(m, IH), 5.32(d, IH), 5.07(m, 4H), 4.73(m, 4H), 4.3 l(m, 3H), 3.50(t, IH), 3.33(m, IH), 3.12(m, IH), 2.85(m, IH), 2.65(m, IH)

Examples 875-878

N-(2-Trifluoromethylbenzyl)-2(S)- {[ 1 -(4-cyanobenzyl)- 1 H-imidazol- 5 -yl] acetyl} amino-3 -(4-benzyloxy)phenylpropylamine was reacted with the conesponding isothiocyanates under the same condition as described in <Step 2> of Example 874 to give the title compounds.

Example 875

N-(2-Trifluoromethylbenzyl)-N-(4-chlorophenylthiocarbamoyl)-2(S)- { [ 1 -(4-cy anobenzyl)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxyphenyl)propylamin e -H-NMR(CDCb) : a 8.70(bs, IH), 7.71(4 2H), 7.55(4 3H), 7.35(m, 12H), 6.95(m, 6H), 6.30(bs, IH), 5.80(4 IH), 5.07(s, 2H), 4.85(4 IH), 4.65(q, 2H), 4.47(m, IH), 4.20(m, IH), 3.48(t, IH), 3.33(m, IH), 3.16(m, IH), 2.95(m, IH), 2.60(m, IH)

Example 876

N-(2-Trifluoromethylbenzyl)-N-cyclohexylthiocarbamoyl-2(S)- {[ 1 -(4-cyanobe nzyl)-lH-imidazol-5-yl]acetyl}amino-3-(4-benzyloxyphenyl)propylamine

1H-NMR(CDCb) : 8 7.70(d, IH), 7.58(4 3H), 7.40(m, 7H), 7.18(4 2H), 7.00(m, 5H), 6.85(m, 3H), 5.82(bs, IH), 5.07(s, 2H), 4.80(m, 3H), 4.65(d, IH), 4.20(m, 2H), 3.48(t, IH), 3.33(m, IH), 3.10(m, IH), 2.75(m, 2H), 1.90(m, 2H), 1.55(m, 4H), 1.00(m, 4H)

Example 877

N-(2-Trifluoromeι ylbenzyl)-N-(3-fluorophenylthiocarbamoyl)-2(S)-{[l-(4-cy anobenzyl)- 1 H-imidazol-5 -yl] acetyl } amino-3 -(4-benzyloxyphenyl)propylamin

-H-NMR(CDCb) : 8 8.80(bs, IH), 7.70(d, IH), 7.55(d, 3H), 7.37(m, 4H), 7.28(m, 7H), 6.96(m, 8H), 6.30(bs, IH), 5.80(d, IH), 5.07(s, 2H), 4.85(d, IH), 4.65(q, 2H), 4.50(m, IH), 4.20(m, IH), 3.48(t, IH), 3.30(m, IH), 3.16(m, IH), 2.95(m, IH), 2.60(m, IH)

Example 878

N-(2-Trifluoromethylbenzyl)-N-(4-methoxyphenyltbiocarbamoyl)-2(S )- { [ 1 -(4- cy anobenzyl)- 1 H-imidazol-5-yl]acetyl } amino-3 -(4-benzyloxyphenyl)propylam ine

1H-NMR(CDCb) : 8 8.10(bs, IH), 7.70(d, IH), 7.55(d, 3H), 7.40(m, 6H), 7.30(m, 2H), 7.20(4 2H), 6.96(m, 9H), 6.60(bs, IH), 5.60(d, IH), 5.07(s, 2H), 4.74(m, 4H), 4.30(m, IH), 3.80(s, 3H), 3.48(t, IH), 3.34(m, IH), 3.16(m, IH), 2.90(m, IH), 2.60(m, IH)

Experimental Example 1

In Vitro Cell Growth Inhibition Assay

The viability of K-ras transformed cells was measured by using MTT colorimetric assay which is based on the conversion of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) to MTT- formazan by mitochondrial enzyme. In brief, cells were dispensed within 96-well culture plate in 100 μ l culture medium at a density of 200 cells/well. Following 24 hours incubation at 37°C, 5% CO , 100% relative humidity, 100 μ 1 of culture medium containing compound or culture medium containing compound vehicle was dispensed within appropriate wells. Culture plates were then incubated for 4 days prior to addition of MTT reagent. MTT solution (5 mg/ml PBS) was added to the well in a concentration of 0.5 mg/ml. After incubation for 4 hours, mixed culture medium and MTT solution were carefully removed, then 100 μ l DMSO was added to the well to solubilize formazan. The absorbance of each well was measured using microculture plate reader at 570 nm. Measurements were performed in triplicate. Growth inhibition of 50% (IC50) is calculated in terms of %T/C [(absorbance of treated cells/absorbance of control cells) X 100]. The results of effective compounds shown in Table 1 reflects their ability to inhibit K-ras transformed cell growth in vitro. Table 1. Inhibition of K-ras transformed cell growth

Table 1. (continued)

Table 1. (continued)

Table 1. (continued)

Table 1. (continued)

Table 1. (continued)

From results of Table 1, the compound of formula (I) according to the present invention were identified as having a potent inhibitory activity against K-ras transformed cell growth.

Experimental Example 2

In vitro inhibition of FPTase Bovine brain cytosol was fractionated with ammonium sulfate and subjected the active fraction to ion exchange chromatography on a Mono Q column followed by gel filtration on sephacryl S-200. The Ras protein substrate, K-ras4B, is expressed in Escherichia coli. The donor of farnesyl residues to ras protein is [³H] farnesyl pyrophosphate (FPP). The standard reaction mixture contained the following concentrations of components in a final volume of 50 μl ; 50 mM HEPES pH7.5, 5 mM MgCb, 5mM dithiothreitol (DTT), 10 μM ZnCb, 0.2% n-Octyl-β -D-glucopyranoside and 300 nM K-ras4B. The mixture also contained 200 nM of [³H]FPP (16.0 Ci/mmol; Amersham Life Science) and 1.5 μg of partially purified farnesyl-protein transferase.

Test compounds were dissolved in 99.9% ethyl alcohol (EtOH). After incubation for 1 hr at 37°C in 1.5 ml effendorf tubes, the reaction was stopped by the addition of 90 μi of 4% sodium dodecyl sulfate (SDS) and then 90 μi of 30% trichloroacetic acid (TCA). The tubes were left on ice for 45-60 min and then the precipitates were transfened to Millipore multiscreen filtration 96-well plate with glass fiber C membrane (Millipore Corp.).

Following filtration using the multiscreen vacuum manifold, the wells were washed once with 200 μi of 4%SDS/6%TCA and five times with 200 μi of 6% TCA. Following removal of the bottom seal, excess washing fluid was blotted and the plates were allowed to dry before the filters were punched into 6 ml vials using the multiscreen punch. After punching, 5 ml of scintillation fluid (Packard) was added and radioactivity was determined by scintillation counting (Beckman LS5801). Dose-response curves for inhibitors used were duplicated at each drug concentration, and the IC50 estimations were made from Litchfield- Wilcoxon method. The data presented below in Table 2 reflects the ability of the test compound to inhibit ras famesylation.

Table 2. In vitro inhibition of FPTase

From results of Table 2, the formula (I) of this invention were identified as having an ability to inhibit FPTase effectively.

Experimental Example 3 Inhibition of K-ras4B processing

NIH3T3 cells transfected with oncogenic human K-ras4B were plated in 6-well plate and cultured until 10 per well. The cells were treated for 48 hours with either vehicle or the test compounds (each 10 μ M). Cells were washed and lysed in 1 ml of lysis buffer (1 X PBS(phosphate buffer saline), 1% Triton X-100, 1 mM phenylmethyl- sulfonyl fluoride, 25/ig/ml leupeptin, 16 g/ml benzamidine HCl, 1 mg/ml Sigma- 104 phosphate substrate) at 4°C for 1 hour. Lysates were cleared (10,000 rpm, 4°C, 15 min), and equal amounts of protein were immunoprecipitated with the anti-ras antibody-agarose beads (OP01A, Oncogene Science) at 4°C for 2 hours. The immunoprecipitated proteins were separated on a 15% SDS-PAGE, transfened to Hybond-ECL (Amersham Corp.), and immunoblotted using an anti-K-ras antibody (OP24, Oncogene Science). Antibody reactions were visualized using peroxidase-conjugated goat anti-mouse IgG and an enhanced chemiluminescence detection system (ECL, Amersham Corp.).

Posttranslational modifications have different effects on electro- phoretic mobility. Unprocessed ras protein migrate slightly faster than their prenylated counterparts. Therefore, the intensities of the bands conesponding to prenylated and nonprenylated K-ras proteins were compared to determine the inhibition of prenyl transfer to protein. The results of effective compounds presented in Table 3 reflects the ability to inhibit K-ras4B processing. Table 3. Inhibition of K-ras4B processing by compounds of this invention.

The sign '-' indicates no effect; and '+' to '+++' indicates increasing inhibition of K-ras4B processing. Inhibitory effect; '+++': 80-100%, '++': 40-80%, '+': 10-40%, '-': < 10%.

From the results of Table 3, the compound of formula (I) according to the present invention were identified as having an ability to inhibit K-ras4B processing effectively.

Claims

WHAT IS CLAIMED IS:

1. A thiourea derivative represented by the following formula (I):

pharmaceutically acceptable salt or stereoisomer thereof, wherein Ri represents hydrogen; straight-chain or branched G-Cg-alkyl which is optionally substituted by substituents selected from a group consisting of halogen, G-C╧î-alkoxy, G-C╧î-alkoxycarbonyl and di(C:╬╣-C₄-alkyl)amino; C2-C╧î-alkenyl; C╬╣-C₄-alkoxycarbonyl; C₃-C₆- cycloalkyl; phenyl which is optionally mono- to trisubstituted by substituents selected from a group consisting of halogen, Ci-C╧î-alkyl, C╬╣-C₆-alkoxy, Ci-C╬▓-alkylthio, halogeno-Ci-C╧î -alkyl, azido, nitro, amino, phenyl, di(C╬╣-C₄-alkyl)amino and hydroxy; phenyl-C╬╣-C -alkyl; naphthyl which is optionally substituted by di(C╬╣-C₄-alkyl)amino; benzoyl; pyridyl which is optionally substituted by substituents selected from a group consisting of halogen and G-C╬┤-alkoxy; or adamantyl, R2 and R₃ independently of one another represent hydrogen, straight- chain or branched Ci-C╧î-alkyl, C3-C╧î-cycloalkyl or benzyloxy- benzyl, R4 represents d-O-alkyl substituted by phenyl wherein the phenyl moiety is optionally mono- to trisubstituted by substituents selected from a group consisting of halogen, halogeno-C╬╣-C -alkyl, C╬╣-C₄-alkylenedioxy, C╬╣-C₆-alkyl, nitro, Ci-C╧î-alkoxy, carboxyl and Ci -C╧î-alkoxycarbonyl; naphthyl-C 1 -C -alkyl; thiophenyl-C 1 -C₄-alkyl; Ci-C╬┤-alkyl which is optionally substituted by substituents selected from a group consisting of pyridyl, oxypyridyl, G-C╧î-alkoxy and C╬╣-C₆-alkylthio; or C2-C₆-alkynyl, and

X represents nitro or cyano.

2. The compound of claim 1, wherein

Ri represents phenyl which is optionally mono- to trisubstituted by substituents selected from a group consisting of halogen, Ci-Cβ-alkyl, Ci-Cό-alkoxy, G-Cό-alkylthio, halogeno-G-Cό-alkyl, azido, nitro, amino, phenyl, di(G-C -alkyl)amino and hydroxy; or pyridyl which is optionally substituted by substituents selected from a group consisting of halogen and Ci-Cό-alkoxy,

R₂ and R3 independently of one another represent straight-chain or branched Ci-C╧î-alkyl,

R4 represents C╬╣-C -alkyl substituted by phenyl wherein the phenyl moiety is optionally mono- to trisubstituted by substituents selected from a group consisting of halogen, halogeno-C╬╣-C₄-alkyl, C╬╣-C -alkylenedioxy, Ci-C╬┤-alkyl, nitro, G-C╧î-alkoxy, carboxyl and d -C╧î-alkoxycarbonyl; and

X represents nitro or cyano.

3. A process for preparing a thiourea derivative of formula (I) as defined in claim 1, characterized in that a compound represented by the following formula (VI):

wherein R2, R3, R4 and X are defined in claim 1 and P' represents an amino-protecting group, is deprotected and then reacted with a substituted isothiocyanate represented by the following formula (VIII):

R,NCS (Vffl)

wherein Ri is defined in claim 1, if appropriate, in an organic solvent.

4. A process for preparing a thiourea derivative of formula (I) as defined in claim 1, characterized in that a compound represented by the following formula (VII):

wherein Ri, R₂, R₃ and R are defined in claim 1 and P represents an amino-protecting group, is deprotected and then reacted with a 1 -substituted- lH-imidazol-5ylacetic acid hydrochloride represented by the following formula (IX):

wherein X is defined in claim 1, if appropriate, in the presence of a coupling agent.

5. A pharmaceutical composition for inhibition of ras-transformed cell growth comprising a therapeutically effective amount of the compound of formula (I), as defined in claim 1, or a pharmaceutically acceptable salt thereof as an active ingredient together with a pharmaceutically acceptable carrier.