WO1992013828A1 - Novel benzanilide derivative or salt thereof - Google Patents

Abstract

A benzanilide derivative represented by general formula (I), which has a testosterone 5α reductase inhibitory activity, a pharmaceutically acceptable salt thereof, a pharmaceutical composition thereof, and a process for producing the same.

Description

 Specification

 New benzanilide derivatives or their salts

 The present invention relates to a novel benzanilide derivative having a testosterone 5-reductase inhibitory action, a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the same, and a method for producing them. Background art

 Testosterone (TS) secreted by the testis and adrenal gland is taken up by the target cells of the orchid diyun, and then reduced to dihydrotestosterone (DHT) by the action of intracellular 5-reductase. It is. DHT generated in this way is thought to be closely related to the development of prostatic hyperplasia and prostate cancer. In addition, the onset and exacerbation of androgenetic alopecia and acne seborrhea are also thought to be one of the causes of excess DHT and TS.

 Therefore, suppressing the reduction of TS to DHT, which has higher androgenic activity, is considered to be extremely effective for diseases such as prostatic hypertrophy. Various attempts have been made to synthesize compounds having such compounds.

As a conventionally known non-steroid type compound having a testosterone 5 α-reductase inhibitory activity, for example, a benzoylaminophenoloxybutanoic acid derivative represented by the following formula is known (European Patent Publication No. 294,035). ).

(For the definitions of R ¹ , R ² and A groups in the formula, see the above publication)

In addition, European Patent Publication Nos. 218 and 728 describe the following general formula:

(For the meanings of the symbols in the general formula, see the above publication). The compounds of the general formula include the same benzanilide derivatives as in the present invention. However, the publication only describes the SRS-Α antagonistic activity of these compounds, but does not report any testosterone 5-reductase inhibitory activity. Disclosure of the invention

The present inventors have created various compounds and proceeded with screening, and as a result, the benzanilide derivative represented by the following general formula (I) or a salt thereof has been shown to inhibit testosterone 5-reductase in comparison with the above-mentioned known compounds. The present inventors have found that they have an excellent antiprostatic hypertrophy action based on the action, and have completed the present invention.

(I)

(Wherein, R ¹ is a hydrogen atom, a lower alkyl group, a lower alkoxy group or a halogen atom, R ² is a hydrogen atom or a lower alkyl group, R ³ is a lower alkyl group or a halogen atom, and (R ³ ) n represents that the benzene ring is substituted with 0 to 4 R ³ groups which may be the same or different, X, represents a lower alkylene group, X ₂ represents 10—, and formula 1—0—. (Wherein Y! Is a linear or branched alkylene group having 1 to 10 carbon atoms), a group represented by the formula: CH—NR ⁵ — (wherein R ⁴ ′ is a lower alkyl group) Represents a phenyl group which may be replaced by, and R ⁵ represents a hydrogen atom or a lower alkyl group, respectively.), A group represented by the formula: NR ⁵ — Y ₂ — or a formula: 一₂ — NR ⁵ — (wherein, R ⁵ have the same meanings as defined above, Upsilon ₂ denotes respectively a lower alkylene group.) the and location R ⁴ is a lower alkyl group, The purpose of the present invention is to provide a benzanilide derivative represented by the above general formula (I) or a pharmaceutically acceptable salt thereof. Another object of the present invention is to provide a pharmaceutical composition comprising the above derivative or a salt thereof and a pharmaceutically acceptable carrier.

 Still another object of the present invention is to provide a method for producing the above derivative or a salt thereof.

 Hereinafter, the general formula (I) will be described in detail.

In the definition of the general formula in this specification, unless otherwise specified, the term “lower” means a straight or branched carbon chain having 1 to 6 carbon atoms. I do.

 Therefore, the “lower alkyl group” specifically includes, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl (amyl) Group, isopentyl group, neopentyl group, tert-pentyl group, 1-methylbutyl group, 2-methylbutyl group, 1,2-dimethylpropyl group, hexyl group, isohexyl group, 1-methylpentyl group, 2-methylpentyl group, 3-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl Butyl group, 1-ethylbutyl group, 2-ethylbutyl ¾, 1, 1, 2-trimethylpropyl group, 1, 2, 2-trimethylpropyl group, 1-ethyl-1-methyl Propyl group, 1-ethyl-2-methylpropyl group and the like.

 The “lower alkoxy group” includes methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group, pentyloxy (amyloxy) group, isopentyl group. Examples include a xy group, a tert-pentyloxy group, a neopentyloxy group, a 2-methylbutoxy group, a 1,2-dimethylpropoxy group, an 11-ethylpropoxy group, and a hexyloxyl group.

Further, the “lower alkylene group” includes a methylene group, an ethylene group, a methylmethylene group, a trimethylene group, a 1-methylethylene group, a 2-methylmethylene group, a tetramethylene group, a 1-methyltrimethylene group, and a 2-methyltrimethylene group. Group, 1-ethylethylene group, 2-ethylethylene group, pentamethylene group, 1-methyltetramethylene group, 2-methyltetramethylene group, 3-methyltetramethylene group, 4-methyltetramethylene group, hexamethylene group, ethylmethylene group, Propylmethylene group, isopropylmethylene group, butylmethylene group, Sobutylmethylene group, sec-butylmethylene group, tert-butylmethylene group, pentylmethylene group, isopentylmethylene group, (2-methylbutyl) methylene group, 1-propylethylene group, 2-propylethylene group, 1-isopropyl Ethylene group, 2-isopropylethylene group, 1-butylethylene group, 2-butylethylene group, 1-isobutylethylene group, 2-isobutylethylene group, 1-propyl trimethylene group, 2-propyl trimethylene group, 3-propyl Lethylene group, 1-isopropyl trimethylene group, 2-isopropyl trimethylene group, 3-isopropyl trimethylene group, 1-ethyltetramethylene group, 1,1-dimethylethylene group, 2,2-dimethylethylene group. Dimethyl trimethylene group, 2, 2-dimethyl trimethylene group, 3,3-dimethyltrimethylene group, 1,2-dimethylethylene group, 1,2-dimethyltrimethylene group, getylmethylene group, 1,1-dimethylethyl group, 1-methyl-1-propylethylene group, 1,2 —Getylethylene group, 1,2,3-dimethyltrimethylene group, etc. Examples of the “alkylene group having 1 to 10 carbon atoms” include hexyl methylene in addition to the above “lower alkylene group”. Group, isohexylmethylene group, (2-methylpentyl) methylene group, (3-methylpentyl) methylene group, (2,3-dimethylpentyl) methylene group, (2-methylhexyl) methylene group, (3 -Methylhexyl) methylene group, (4-methylhexylmethylene group, (2-ethylpentyl) methylene group, (3-ethylpentyl) methylene group, (2-methyl-3 —Ethylpentyl) methylene group, heptylenemethylene group, octylmethylene group, (3-methylheptyl) methylene group, nonanylmethylene group, (5-methyloctyl) methylene group, 1-pentylethylene group, 2-pentylethylene group, 1 Monoisopentylethylene group, 2-isopentylethylene group, (2-methylhexyl) ethylene group, (3-methylhexyl) ethylene group, etc. The “halogen atom” includes a fluorine atom, Chlorine atom, And a bromine atom.

 The compound (I) of the present invention may form an acid addition salt. Also, depending on the type of the substituent, a salt with a base may be formed. Specific examples of such salts include mineral acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, and phosphoric acid, formic acid, drunk acid, propionic acid, oxalic acid, malonic acid, and succinic acid. , Fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, methanesulfonic acid, ethanesulfonic acid, and other organic acids, aspartic acid, glutamic acid, and other acidic amino acids, and acid addition salts, sodium, potassium, Examples include inorganic bases such as magnesium, calcium, and aluminum; organic bases such as methylamine, ethylamine, and ethanolamine; salts with basic amino acids such as lysine and ordithine; and ammonium salts.

 Furthermore, the present invention also includes various solvates and polymorphs of the compound (I) of the present invention.

Manufacturing method

The compound of the present invention can be produced by applying various synthetic methods utilizing characteristics based on the basic skeleton or the type of substituent. The typical production method is shown below.

(R ³ )

 0— X, — COOR '

R ⁴ — X,

(r)

 (I)

(Wherein, R ¹ , R ² , R ³ , (R ³ ) n, and ¾ have the above-mentioned meaning, and R ⁷ represents a carboxylic acid protecting group.)

 The compound (I) of the present invention can be produced by removing an ester residue from the corresponding ester represented by the general formula (II).

 In this reaction, conventional methods such as hydrolysis in the presence of a base such as sodium carbonate or sodium hydroxide, or treatment with an acid such as trifluoroacetic acid or hydrochloric acid can be applied.

The compound represented by the following general formula (1 '), which is a starting compound of the compound of the present invention, comprises a substituted aniline represented by the general formula (II) and a carboxylic acid represented by the general formula (III) or a reactive derivative thereof. It is produced by reacting

 ()

(Wherein, R ¹ , R ² , R ^3. (R ³ ) n, R ⁴ , R ⁷ , X, and X ₂ have the preceding meanings, and Z ¹ is a group represented by the formula X ₂ — (Wherein, X ₂ and R ⁴ have the meanings described above.) Or 可能 な which can be substituted with a group represented by the formula X ₂ —R <(wherein, X ₂ and R have the meanings described above.) the, Z ² is wherein one; groups (. wherein, R ⁷ are each as defined above) represented by Xi -COOR ⁷ or formula

-Xi -COOR ^7- substitutable group (wherein, X,

R ⁷ has the meaning described above. ) Means respectively. ]

 Reactive derivatives of compound (III) include acid halides such as acid chloride and acid bromide; acid azide; N-hydroxybenzotriazole ト リ active ester with N-hydroxysuccinimide; symmetry Acid anhydrides; mixed acid anhydrides with alkyl carbonic acid; mixed acid anhydrides such as P-toluenesulfonic acid mixed acid anhydride; and the like.

In the reaction, compound (II) and compound (II) or a reactive derivative thereof are used in an approximately equimolar amount or one of them in an excess amount, and an organic solvent inert to the reaction, for example, pyridine, tetrahydrofuran.dioxane, ether, benzene, Toluene, xylene, methylene chloride, dichloroethane, chloroform, N, N-dimethylformamide, ethyl acetate, The reaction is performed in a solvent such as acetonitrile.

 Depending on the type of reactive derivative, the addition of a base such as triethylamine, pyridine, picoline, lutidine, N, N-dimethylaniline, potassium carbonate, or sodium hydroxide during the reaction facilitates the reaction. May be advantageous. Pyridine can also serve as a solvent.

 The reaction temperature depends on the type of the reactive derivative and is not particularly limited.

In the above general formula (Π), when Z ¹ is a group that can be substituted for a group represented by the formula X ₂ —, specifically, for example, a group represented by (li b) or (li e) in the following reaction scheme The method further comprises the step of substituting Z ¹ with a group represented by the formula X ₂ -R ⁴ . This reaction can be performed by a known 0-alkylation, 0-allylation or N-alkylation reaction. For example, the reaction can be carried out by reacting a substituted phenol, a substituted aniline, or a substituted alkylamine with a halogenated compound. The reaction is carried out in a solvent inert to the reaction, for example, dimethylformamide, dimethylsulfoxide, alcohols, or, in the case of alkylation of a substituted phenol, in addition to the above solvent, methyl ethyl ketone, acetone, etc. Performed in a solvent. Depending on the type of reaction, it may be advantageous to add a base such as sodium hydroxide, potassium carbonate, or sodium hydride during the reaction to make the reaction proceed smoothly.

In the above general formula (DI), when Z ² is a group that can be substituted for a group represented by the formula (11) COOR ⁷ , specifically, for example, a group represented by the following reaction formula (H b) or (mc) the further substitution of Z ² based on the Ru shown in equation one ¾ one COOR ^7, comprising the step. This reaction can be carried out by a usual 0-alkylation reaction.

In addition, if necessary, an N-alkylation step of R ² and Z or R ^{5 in} the above formula can be included. This reaction can be carried out using a conventional N-alkylation reaction. These reactions can be performed in any order, and include the steps of introducing a protecting group and removing the protecting group as necessary.

 Hereinafter, the details of the method for producing the starting compound of the compound of the present invention are shown by the following reaction step formulas (i) to (V).

Each reaction in the reaction scheme is known.

 (V) (r)

(VI) (r)

 (He) (Dlb)

(上式中， A¹は水酸基， 二トロ基又は式— Y₂— N0₂で示される基を (式中， Y₂は前記の意味を有する。）. Α²は水酸基， アミノ基， 又は式 - Υ₂— ΝΗ₂で示される基を （式中， Υ₂は前記の意味を有する。）， Α³ は保護基を有する水酸基， 二トロ基， 式一 Υ₂— Ν0₂で示される基を (式中， Υ₂は前記の意味を有する。）， A ま保護基を有する水酸基を 夫々意味する。 また， その他の基は前記と同じ意味を有する。） 上記反応工程式中においては， 必要により R², R⁵のアルキル化反 応を任意の段階で含んでいてもよい。

(In the above formulas, A ¹ is hydroxyl group, the two Toro group or the formula - Y ₂ -.. N0 based (formula represented by _2, Y ₂ are each as defined above) Alpha ² is a hydroxyl group, an amino group, or A group represented by the formula-Υ ₂ — ΝΗ ₂ (wherein Υ ₂ has the above-mentioned meaning), Α ³ is a hydroxyl group having a protecting group, a dinitro group, and a group represented by the formula Υ ₂ — Ν 0 ₂ In the above reaction scheme, the groups (wherein Υ ₂ has the above-mentioned meaning), A and a hydroxyl group having a protecting group, respectively, have the same meanings as above. If necessary, the alkylation reaction of R ² and R ⁵ may be included at any stage.

 The reaction products obtained by the above processes are isolated and purified as free compounds, their salts or various solvates. The salt can be produced by subjecting it to a conventional salt-forming reaction.

 Isolation and purification are carried out by applying ordinary chemical operations such as extraction, concentration, distillation, crystallization, filtration, recrystallization, and various types of chromatography. Industrial applicability

 The compounds of the present invention have testosterone 5α-reductase inhibitory activity and are useful for various diseases caused by the effects of benign prostatic hyperplasia and other male hormones, such as prostate cancer, seborrhea, acne, and male pattern baldness. Useful for treatment.

 As described above, the inhibitory effect of the compound of the present invention on 5-reductase is evident from the test of 5-reductase inhibitory activity (in vitro) using human vulvar skin fibroblasts (HS27).

 The test method and test results are described below.

 (1) Preparation of testosterone-5 α-reductase

 Human fibroblasts (HS27) collected by subculture were homogenized by adding lOmM Tris-HCl buffer (PH7.0), and then subjected to sonication for 15 seconds X 3 times with a Sonifia. The solution was further centrifuged (3000 rpm for 10 minutes), and the resulting supernatant was used as the enzyme solution.

(2) Measurement of testosterone-5 α-reductase inhibitory activity Add 50 mM Tris-HCl buffer (pH 5.0), dithiothreitol (final concentration ImM), NADPH (final concentration 5 mM), [4-1 "C] one testosterone (final concentration 0.04 fi Ci) and several concentrations of the compound of the present invention were added to a total volume of 500 ^ 1. After incubating this mixture at 37 ° C for 60 minutes, the enzyme reaction was stopped by adding 2.0 ml of ethyl ethylate, and further used as a carrier. Testosterone, dihydrotestosterone, 4-androstene-3,17-dione, and 5 "-androstan-13-α, 17 ^ 3-diol were added. Then, centrifugation was performed, and the resulting supernatant (1.0 ml) was concentrated and spotted on a silica gel thin layer plate. The mixture was separated using a mixture of ethyl acetate and cyclohexane (1: 1). The spots of androsten-13, 17-dione, dihydrotestosterone and 5α-androstan-13 and 17β-diol were cut out from the plate, and their radioactivity was measured using a liquid scintillation counter. The inhibition rate was calculated by the following equation. The 50% inhibitory concentration was determined from the results and shown in Table 1.

ΒΖΑ — Β '/ Α'

 Inhibition rate (%) = X 100

 ΒΖΑ

Α: Total radioactivity spotted on TLC

 (When the compound of the present invention is not added)

B: Total radioactivity of dihydrotestosterone and 5-androstane-13, 17β-diol

 (When the compound of the present invention is not added)

Α ': Total radioactivity spotted on TLC

 (When the compound of the present invention is added)

B ': Total radioactivity of dihydrotestosterone and 5-androstan-13, V7 β-diol

 (When the compound of the present invention is added)

Test results . The table below shows the inhibitory activity of the compound of the present invention on 5α-reductase measured using human HS27.

表より明らかな様に,本発明化合物はヒ ト HS27を用いた 5 —リ ダクターゼ阻害活性の試験において高い活性を示すものであり，臨床 上の高い有用性が期待できる。 対照化合物は,欧州公開特許公報 294, 035号に記載された化合物であり， 治験 Να ΟΝΟ— 3805として医薬 品としての開発が進められている化合物であるがそれと比較しても， 本発明化合物は数倍効果が強く，又,毒性も非常に低いことより，医薬 としての有用性の高い薬剤を提供し得ると考えられる。

As is clear from the table, the compound of the present invention shows high activity in the test for 5-reductase inhibitory activity using human HS27, and high clinical utility is expected. The control compound is a compound described in European Patent Publication No. 294,035 and is a compound that is being developed as a pharmaceutical product in clinical trial ΝαΟΝΟ-3805. Because the effect is several times stronger and the toxicity is very low, it is considered that a drug with high utility as a medicine can be provided.

 Furthermore, some of the compounds of the present invention have persistence.

In addition, since the compound of the present invention has a non-steroid skeleton, it does not have side effects as seen in anti-androgen drugs comprising steroid hormone derivatives. Pharmaceutical compositions containing one or more of the compounds represented by the general formula (I) or a salt thereof as an active ingredient can be prepared by using a carrier, an excipient, and other additives that are usually used in formulation. It is prepared by

 Pharmaceutical carriers and excipients include solid or liquid non-toxic pharmaceutical substances. Examples of these include lactose, magnesium sul- arate, starch, talc, gelatin, agar, pentine, acacia, olive oil, sesame oil, cocoa butter, ethylene glycol and the like and other commonly used ones.

 Administration may be oral, such as tablets, pills, capsules, granules, or liquids, or parenteral, such as injections, suppositories, or transdermals, such as intravenous or intramuscular injections. . The dose is determined as appropriate for each individual case, taking into account the symptoms, age of the subject, and gender.

 In the case of oral administration, it is usually 0.1 to 500 mg, preferably 1 to 200 mg per day for an adult, and is administered once to several times a day. In addition, depending on the symptom, in the case of transdermal administration, it is usually administered once to several times a day in the range of 0.01 to 500 mg at a time. However, the dose is not limited to these.

Prescription example

 Next, examples of the formulation of the compound of the present invention as a medicine will be described.

Prescription example 1

 Tablets

 20 mg of the compound of Example 24

 Lactose 57mg

 Cornstarch 38mg

 Hydroxypropyl cellulose 4mg

 Magnesium stearate lmg

 Total amount I 20mg

20 g of the compound of Example 24, lactose 57 g, and corn starch 38 g are uniformly mixed. Then add 40 g of 10% hydroxypropylcellulose solution And wet granulation. After sieving, dry. Magnesium stearate (lg) is added to the obtained granules and mixed. Compress into tablets using a 7mZm5.6R mortar and punch.

Prescription example 2

 Capsule

15 _mg of the compound of Example 24

 40mg crystalline cellulose

Crystal lactose 144m _g

 Magnesium stearate lmg

 Total amount 200mg

 15 g of the compound of Example 24, 40 g of crystalline cellulose, i44 g of crystalline lactose and lg magnesium stearate lg are mixed uniformly, and filled into a No. 3 capsule with a capsule filling machine to obtain a capsule.

 (Example)

Next, the compound of the present invention and the method for producing the same will be described specifically with reference to examples. As a reference example, a production example of the raw material compounds used in the examples will be described.

Reference example 1

N, N-dimethylform of 2,3-dimethyl-412-trophenol (482 mg, 2.89 mmo 1) and 1- (p-isobutylphenyl) ethyl bromide 380 mg (1.58 mmo 1) in an argon stream § Mi de solutions carbonate force potassium 32 Omg added 50 ^e C to warm during and stirred for 4 hours. Ether was added, water was added and the layers were separated. The organic layer was further washed with saturated saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and eluted with a 16: 1 mixture of hexane and ethyl acetate. mg of 4- [1- (p-isobutylphenyl) ethoxy) 1, 2-dimethylnitrobenzene was obtained as a pale yellow oil.

Physicochemical properties Mass spectrometry value (mZ z): 3 26 (M-1) ⁺

Nuclear magnetic resonance spectra (CD C 1 _3, TMS internal standard)

 δ: 0.8 9 (6 Η, d), 1 6 7 (3 H, d)

 1.8.4 (1 H, m), 2 3 2 (3 H, s)

 2.44 (3H, s), 244 (2H, d)

 5. 3 7 (1 H, q), 6 6 1 (1 H, d)

 7.1 2 (2 H, d), 7 2 4 (2 H, d)

 7.62 (1 H, d)

Reference example 2

 In the same manner as in Reference Example 1, p- (3-methyl-3-phenylbutoxy) 2-token benzene was obtained.

Starting compound: 3-methyl-3-phenylbutyl bromide, p-

 Nitrophenol

Physicochemical properties

Mass spectrometry value (mZz): 285 (M ⁺ )

Nuclear magnetic resonance spectra (CD C 1 _3, TMS internal standard)

 6: 1.40 (6 H, s), 2.17 (2 H, t),

 3.84 (2 H, t), 6.73 (2 H, d), 7.16 to 7.39 (5 H, m), 8.08 (2 H, d) Reference example 3

 In the same manner as in Reference Example 1, ethyl 4-[(0-benzyloxycarbonyl) phenoxy] -1,2,2-dimethylbutyrate was obtained.

Starting compound: benzyl 2-hydroxybenzoate

Physicochemical properties

 Mass spec (mZz): 37 1 (M + 1) ''

Nuclear magnetic resonance spectra (CD C 1 _3, TMS internal standard)

δ: 1.1 to: I.4 (9Η, m), 2.04 (2 H, t), 3.9 to 4.2 (4Η, m) .5.52 (2Η, m) s), 6.8-7.1 (2Η, m), 7.2-7.6 (6Η, m), 7. 7 8 (1 H, dd)

Reference example 4

 Under an argon stream, add 10 Omg of platinum oxide to 1.2 Og of ethanol (10 mL) in 4- [11- (p-isobutylphenyl) ethoxy]-2,3-dimethylnitrobenzene. , Replaced with hydrogen, and stirred for 1 hour. The platinum was filtered off, and the filtrate was distilled off under reduced pressure to obtain 1.09 g of oily 4- [1- (p-isobutylphenyl) ethoxy] -1,2,3-dimethylaniline.

Physicochemical properties

Mass spec (m / z): 298 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 6: 0.86 (6 Η, d), 1.55 (3 H, d),

 1.68-: I. 96 (1H, m), 2.06 (3H, s), 2.19 (3H, s), 2.42 (2H, d), 3.34 (2 H, br), 5.06 (1 H, q),

6.37 (1 H, d), 6.48 (1 H, d),

7.06 (2 H, d), 7.26 (2 H. d)

Reference example 5

 In an argon stream, p- (3-methyl-3-phenyl) butoxynitrobenzene 32 Omg of ethanol 5 Oml of 10% palladium carbon 5 Omg was added, and the mixture was purged with hydrogen and stirred until hydrogen absorption ceased. . The catalyst was filtered, and the base solution was distilled off under reduced pressure to obtain 28 mg of p- (3-methyl-3-phenyl) butoxydiline.

Physicochemical properties

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 5: 1.39 (6 H, s), 2.11 (2 H, t),

3.32 (2H, br), 3.71 (2H, t), 6.59 (2H, s), 7.21 to 7.37 (5H, m) Reference example 6 In the same manner as in Reference Example 5, p- (4-hydroxy) butylylaniline was obtained.

 Starting compound: p- (4-hydroxy) butyl ditrobenzene Physicochemical properties

Mass spec (MZz): 16.5 (M ⁺ )

Nuclear magnetic resonance spectra (CD C 1 _3, TMS internal standard)

 δ: 1.5-1 to 1.67 (4 Η, m),

 2.44 to 2.59 (2H, m), 3.62 (2 H, t), 6.60 (2 Η, d), 6.96 (2 Η d)

Reference Example 7

 To a solution of 200 mg of ρ- (ρ-isobutylbenzyloxy) aniline in 5 ml of methylene chloride was added dropwise 2 ml of trifluoroacetic anhydride under ice-cooling, and the mixture was warmed to room temperature and stirred for 20 minutes. The reaction solution was concentrated under reduced pressure, and the residue was dissolved in 8 ml of acetone. To this solution, 40 Omg of methyl iodide and 20 Omg of lithium carbonate were added, and the mixture was heated and passed for 2 hours. The reaction solution was concentrated under reduced pressure, and the residue was dissolved in a mixture of 3 ml of methanol and a 5N aqueous solution of sodium hydroxide, heated to 50 and stirred for 12 hours. The reaction solution was concentrated under reduced pressure and extracted with ethyl acetate. The extract was washed successively with water and saturated saline, and dried over anhydrous sodium sulfate. The residue obtained by concentration under reduced pressure was subjected to silica gel column chromatography, eluted with a mixture of hexane: ethyl acetate (8: 1), and p- (p-isobutylbenzyloxy) -N-methylaniline 13 Omg I got

Physicochemical properties

Mass spec (mZz): 26 9 (M ⁺ )

Nuclear magnetic resonance spectrum (CDCI ₃ , TMS internal standard)

 δ: 0.90 (6 H, d), 1.85 (1 H, m),

2.46 (2 H, d), 2.78 (3 H, s), 2.92 (1 H, m), 4.8 2 (2 H, s), 6.5 4 (2 H, m), 6.85 (2 H, m), 6. 9 to 7.4 (4H, m)

Reference Example 8

 To a solution of 12-mg of 5-methylsalicylic acid in 3 ml of methylene chloride was added 0.1 ml of N, N-dimethylformamide and 36 mg of oxalyl chloride, and the mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure, and the obtained crystalline residue was dissolved in 2 ml of methylene chloride. This was added to a solution of 20-mg of 4- (p-isobutylbenzyloxy) aniline, 1 ml of pyridine and 1 ml of methylene chloride under ice-cooling, the temperature was raised to room temperature, and the mixture was stirred for 40 minutes. The reaction solution was concentrated under reduced pressure and extracted with ethyl acetate. The extract was washed successively with 1N hydrochloric acid and saturated saline, and dried over anhydrous sodium sulfate. The residue obtained by concentration under reduced pressure was subjected to silica gel column chromatography, and eluted with a mixture of hexane: ethyl ethyl ester (7: 1) to give 2-hydroxy-4 '-(p-isobutylbenzyloxy) -one. 11-Omg of 5-methylbenzanilide was obtained. Physicochemical properties

Mass spec (mZ z): 390 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ 0 90 (6 H, d), 1.87 (1 Η, m)

 2 34 (3 H, s), 2.48 (2 H, d)

 5 05 (2 H, s), 6.94 (1 H, d)

 7 02 (2 H, d), 7.28 (2 H, d)

7 2 to 7.3 (2H, m) ₍ 7.36 (2Hd), 7.48 (2H, d), 7.83 (1H, s)

 1 1.8 (1 H, s)

Reference Example 9

 In the same manner as in Reference Example 8, 5-chloro-2-hydroxy-4- (p-isobutylbenzyloxy) benzanilide was obtained.

Raw material compound: 5-mouth salicylic acid

Physicochemical properties Mass spec (mZz): 410 (M + 1) +

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.91 (6 H, d), 1.87 (1 H, m),

 2.49 (2 H, d), 5.05 (2 H, s), 6.9 to 7.1 (3 H, m), 7.14 (2 H, d)

7.3 to 7.5 (6H, m), 7.78 (1H, s) 12.0 (1H, s)

 Reference example 10

P- (p-isobutylbenzyloxy) aniline 200 mg, triethylamine 100 mg, 5-methoxysalicylic acid 160 mg, 1-hydroxybenzotriazole 160 mg dimethylformamide 9 m 1 solution 1 Echiru 3- (3-dimethylaminopropyl § amino propyl) raised the Karubojiimi de hydrochloride 1 8 O mg up to 5 O ^e C was added under room temperature and stirred for 1 3 hours. The reaction was stopped by adding water, the reaction solution was diluted with ethyl acetate, washed sequentially with 1N hydrochloric acid, water, and saturated saline, and dried over anhydrous sodium sulfate. The residue obtained by concentration under reduced pressure was subjected to silica gel column chromatography, eluted with a mixture of hexane and ethyl acetate (5: 1) to give 2-hydroxy-4- (p-isobutylbenzyloxy) -1.5. —200 mg of methoxybenzanilide was obtained.

Physicochemical properties

Mass spec (mZz): 406 (M + 1) ⁺

 Nuclear magnetic resonance spectrum (CDC1, TMS internal standard)

 δ: 0.90 (6 H, d), 1.86 (1 H, m),

 2.46 (2 Η, d), 3.7 to 3.9 (4 Η, m), 5.0 (2 Η, s), 6.8 to 7.5 (1 1 Η, m),

7.80 (1Η, s)

Reference example 1 1

In the same manner as in Reference Example 10, 5-fluoro mouth-2-hydroxy-4 ′-(Ρ-isobutylbenzyloxy) benzanilide was obtained. Starting compound: 5-Fluorosalicylic acid

Physicochemical properties

Mass spec (mZz): 394 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.92 (6Η, d), 0.97 (1H, m),

 2.49 (2 H, d), 5.05 (2 H, s),

6. 9 to 7.1 (3H, m)

 7.Table 7.3 (4H, m)

 7.35 (2H, d), 7.76 (1H, s) 11.73 (1H, s)

Reference example 1 2

 In the same manner as in Reference Example 10, 3-hydroxy-1- 4 ′ ′ (p-isobutylbenzyloxy) benzanilide was obtained.

Raw material compound: m-hydroxybenzoic acid

Physicochemical properties

 Mass spec (mZz '): 376 (M + 1) +

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.91 (6Η, d) 1.87 (1H, m),

 2.48 (2 H, d) 5.0 2 (2 H, s),

6.96 (2 H, d) 7.01 (1 H, d d)

7.15 (2 H, d) 7.27 (1 H, t),

7.34 (3 H, m) 7.40 (1 H, d),

7 6 1 (2 H, d) 8.77 (1 H, s), 90 3 (1 H, s)

Reference Example 1 3

 In the same manner as in Reference Example 10, 4-hydroxy-4 (P-isobutylpentyloxy) benzanilide was obtained.

Raw material compound: p-hydroxybenzoic acid

Physicochemical properties Mass spec (mZ z): 3 76 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 6: 0.90 (6 Η, d), 1.87 (1H, m),

 2.49 (2 H, d), 5, 0 4 (2 H, s),

6. 9 to 7.0 (4 H, m), 7.18 (2 H, d),

7.3 to 7.4 (2 H, d d), 7.70 (2 H, d),

8.05 (2 H, d d), 9.70 (1 H, s),

 9.8 to 10.0 (1H, m)

 Reference example 1 4

 In the same manner as in Reference Example 10, ethyl 41- [o- [N- [p- (p-isobutylbenzyloxy) phenyl] -capsulebamoyl] phenyloxy] 1-2,2-dimethylbutyrate was obtained.

Starting compound: 0— (3—ethoxycarbonyl 3-methylbutoxy) benzoic acid

Physicochemical properties

 Mass spec (mZz): 5 17 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.91 (6 Η, d), 1.18 (3 H, t),

 1.32 (6 H, s), 1.87 (1Η, m),

2.2 2 (2 Η, t), 2.48 (2 Η, d),

4.09 (2Η, q), 4.27 (2Η, t),

5.05 (2 Η, s), 7.0 2 (3 Η, d d),

 7. 1 to 7.2 (3Η, m), 7.36 (2Η, d), 7.47 (1Η, t), 7.64 (2Η, d),

8.29 (1 Η, d d), 9.7 4 (1 Η, s) Reference example 1 5

In the same manner as in Reference Example 10, ethyl 4- [o- [N- [p- (p-isobutylbenzyloxy) phenyl] -1-N-methylcarbamoyl] phenoxy] butylate was obtained. Starting compound: o- (3-ethoxycarbonylpropoxy) benzoic acid

Physicochemical properties

 Mass spec (mZz): 504 (M + 1) +

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.90 (6Η, d), 1.1 to 1.3 (3H, m),

 1.7 to 2.3 (3 H, m),

 2.4 to 2.6 (4 H, m),

 3.17, 3.44 (total 3H, each s),

 3.7 to 4.4 (4 H, m),

 4.92, 5.05 (total 2H, each s),

 6. 6-7. 7,

 8. 1 to 8.2 (12H in total, m each)

Reference Example 1 6

2- (3-Ethoxycarbonylpropoxy) benzoic acid To a solution of 1.2 g of methylene chloride (12 ml) was added 1 drop of N, N-dimethylformamide under a stream of argon, followed by oxalyl chloride. Lml was added dropwise. The reaction solution was returned to room temperature, stirred for 2.5 hours, and concentrated under reduced pressure to obtain 1.10 g of 0- (3-ethoxycarbonylpropoxy) benzoyl chloride. This was dissolved in methylene chloride (2 ml), and 4- [1-1 (p-isobutylphenyl) ethoxy] -1,2,3-dimethylaniline 1.09 g, pyridine 0.5 ml, The solution was added at room temperature to 1 Oml of methylene chloride and stirred for 2 hours. The reaction mixture was poured into ice-1 hydrochloric acid and extracted with ether. The extract was washed with water and saturated saline, dried over anhydrous sodium sulfate, and evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, eluted with a mixture of hexane: ethyl acetate (14: 1 to 7: 1), and ethyl 4- [o- [N- [2,3-dimethyl-4-1 ( p-Isobutyl-1-methylbenzyloxy) phenyl] rubamoyl] phenoxy] butyrate 1. Obtain 75 g Was.

 Physicochemical properties

Mass spec (m / z): 5 3 2 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.89 (6Η, d), 1.21 (3H, t),

 1. 6 2 (3Η, d), 1.76 7: I. 89 (1Η, m),

2 1 5-2. 2 5 (2 Η, m), 2.23 (3 Η, s), 2 3 3 (3 Η, s), 2.44 to 2.5 2 (4 H, m ), 4 1 1 (2 Η, q) 4.27 (2 H, t), 5 2 7 (1 H, q) 6.65 (1 H, d),

7, 0 3 (1H, d) 7.10 to 7.32 (5H, m), 7.35 (1H, m) 7.43 to 7.51 (1H, m ), 8, 2 7 (1 H, dd), 9.28 (1 H, s) Reference example 1 7

 In the same manner as in Reference Example 16, ethyl 41- [0— [N— [p- (3-methyl-3-phenylbutoxy) phenyl] carbamoyl] phenoxy] butylate was obtained.

Starting compound: P — (3-Methyl-3 — phenylbutoxy) aniline, o — (3 — Ethoxycarbonylpropoxy)

Physicochemical properties

Mass spec (m / z): 4 8 9 (M ⁺ )

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ 2 3 (3 Η, t) 1.42 (6 H, s),

 2 16 (2 H, t) 2.28 (2 H, quint), 25 6 (2 H, t) 3.78 (2 H, t), 4 1 4 (2 H, q) 4 . 2 6 (2 H, t), 6 7 7 (2 H, d) 7.0 1 (1 H, d),

7.13 (1H, t) 7.18 to 7.50 (6H, m), 7.54 (2H, d), 8.27 (1H, dd), 9.71 (1H, s)

Reference Example 1 8

 2-Hydroxy-4 '-(p-isobutylbenzyloxy) -15-Methylbenzanilide In a solution of 1 OO mg of 2-butanone in 1 O ml, 60 mg of ethyl 4-bromobutyrate, 60 mg of tetrabutylammonium bromide 10 mg and 40 mg of potassium carbonate were added, and the mixture was refluxed for 1.5 hours. The reaction solution was concentrated under reduced pressure, and extracted with ethyl acetate. The extract was washed successively with water and saturated saline and dried over anhydrous sodium sulfate. The residue obtained by concentration under reduced pressure was subjected to silica gel column chromatography, and eluted with a mixture of hexane: ethyl acetate (5: 1).

4- [2— [N— [p— (p-isobutylbenzyloxy) phenyl] lubamoyl] -1-methylphenoxy] butyrate lOmg was obtained.

Physicochemical properties

Mass spec (mZ z): 504 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.91 (6 Η, d) 1 2 4 3 H, t)

 1.87 (1 H, m) 2 27 2 H, t)

 2.36 (3 H, s) 2 49 2 H, d)

 2.56 (2 H, t) 4 1 4 2 H, q)

 4.2 4 (2 H, t) 5 0 4 2 H, s)

 6.91 (1H, d) 6982H, d)

 7.18 (2 H, d) 7 2 6 1 H, d)

 7.36 (2 H, d) 7 62 2 H, d)

 8 0 8 (1 H, s) 9 7 8 1 H, s)

Reference Example 1 9

Ethyl o— [N— [p— [p— (isobutylbenzyloxy) phenyl] dirubamoyl] phenoxy] Got a set.

Starting compound: 2-hydroxy 4 '-(p-isobutylbenzyloxy) benzanilide

Physicochemical properties

Mass spec (mZ z): 4 62 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.92 (6 Η, d), 1 3 3 (3 H, t),

 1.87 (1 H, m), 2 49 (2 H, d),

4.3 7 (2 H, q), 4 7 9 (2 H, s),

5.05 (2 H, s), 690 (1 H, d), 7.00 (2 H, d), 7 1 to 7.2 (3 H, m), 7.37 ( 2 H, d), 7 4 7 (1 H, t), 7.85 (2 H, d), 8 35 (1 H, d),

1 0.3 (1 H, s)

Reference Example 20

 In the same manner as in Reference Example 18, ethyl m- [N- [p- [p- (isobutylbenzyloxy) phenyl] -lubamoyl] phenyloxy] acetate was obtained.

Starting compound: 3-hydroxy 411 (p-isobutylbenzyloxy) benzanilide

Physicochemical properties

Mass spec (mZ z): 4 62 (M + 1) ⁺

Nuclear magnetic resonance spectra (CD C 1 _3, TMS internal standard)

 6: 0.91 (6 Η, d) 1.30 (3 H, t)

 1.87 (1 H, m) 2.49 (2 H, d)

 4.29 (2 H, q) 4.70 (2 H, s)

 5.05 (2 H, s) 7.0 1 (2 H, d)

 7.11 (1 H, d) 7.18 (2 H, d)

7. 3-7. 5 (5 Hm), 7.55 (2 Hd), 7.73 (1 H, s)

Reference Example 2 1

 In the same manner as in Reference Example 18, ethyl 4- [m- [N- [p- (p-isobutylbenzyloxy) phenyl] -caprolvamoyl] phenoxy] butyrate was obtained.

Raw material compound: 3-hydroxy-4-1- (p-butylpentyloxy) benzanilide

Physicochemical properties

Mass spec (z): 490 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.91 (6 Η, d), 1.25 (3 H, t),

 1.86 (1 H, m), 2.13 (2 H, m),

2.4 to 2.6 (4 H, m), 4.08 (2 H, t),

4.17 (2 H, q), 5.04 (2 H, s),

6.98 (2 H, d), 7.06 (1 H, d),

7.18 (2 H, d), 7.3 to 7.5 (5 H, m),

7 57 (2 H, d), 7.84 (1 H, s)

Reference Example 22

 In the same manner as in Reference Example 18, ethyl 4- [4-chloro-2- [N- [P- (p-isobutylbenzyloxy) phenyl] -caprolvamoyl] phenoxy] petitate was obtained.

Starting compound: 5-chloro-2-hydroxy-4 '-(p-isobutylbenzyloxy) benzanilide Physicochemical properties

 Mass spec (mZz): 524 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.91 (6 Η, d), 1.24 (3 H, t),

1.87 (1H, m), 2.29 (2H, m), 2.49 (2H, d), 2.57 (2H, t), 4.15 (2 H, q), 425 (2 H, t),

 5.04 (2 H, s), 6 98 (3 H, m), 7.18 (2 H, d), 73-7.5 (3 H, m) 7.59 (2 H, d) , 8 25 (2 H, d), 9.67 (1 H, s)

 Reference Example 23

 In the same manner as in Reference Example 18, ethyl 4- [2- [N- [p- (p-isobutylbenzyloxy) phenyl] -l-bamoyl] -14-methoxyphenoxy] petitate was obtained.

Starting compound: 2-hydroxy-5-methoxy4 '-(p-isobutylbenzyloxy) benzanilide

Physicochemical properties

Mass spec (mZ z): 520 (M + 1) ^τ

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.91 (6 Η, d), 1.23 (3 H, t),

 I. 87 (1 H, m), 2.26 (2 H, m),

2.49 (2 H, d), 2.56 (2 H, t),

3.84 (3 H, s), 4.15 (2 H, q),

4.22 (2 H, t), 5.04 (2 H, s),

6. 9 to 7.1 (4 H, m), 7.18 (2 H, d)

7.36 (2 H, d), 7.6 1 (2 H, d),

7 84 (1H, d), 9.89 (1H, s)

Reference Example 24

 In the same manner as in Reference Example 18, ethyl 4- [4-fluoro-2- [N- [P- (p-isobutylbenzyloxy) phenyl] -caproluvyl] phenyloxy] petite was obtained.

Starting compound: 5-Fluoro-2-hydroxy-4 '-(p-isobutylbenzyloxy) benzanilide Physicochemical properties Mass spec (z): 508 (M + 1) ⁺

 Nuclear magnetic resonance spectrum (CDC1, TMS internal standard)

 δ: 0.91 (6Η, d) 1.23 (3H, t)

 1.87 (1 H, m) 2.28 (2 H, m)

 2.49 (2 H, d) 2.56 (2 H, t)

 4.15 (2 H, q) 4.24 (2 H, t)

 5.04 (2 H, s) 6.9 to 7.0 (3 H m), 7.1 to 7.2 (3 H m), 7.36 (2 H d),

7.59 (2 H, d) 8.00 (1 H, d d)

9.78 (1 H, s)

Reference Example 25

 To a solution of o- (3-ethoxycarbonylpropoxy) benzoic acid (25 Omg) and methylene chloride (2 ml) was added 4 ml of thionyl chloride and heated under reflux for 2 hours. The reaction solution was concentrated under reduced pressure to obtain 27 mg of o- (3-ethoxycarbonylpropoxy) benzoyl chloride. This was dissolved in 2 ml of methylene chloride, added to a solution of 25 mg of p- (p-isobutylbenzyloxy) aniline, 0.5 ml of pyridine and 2 ml of methylene chloride at room temperature, and stirred for 20 minutes. The reaction solution was poured into a mixture of ice-1N hydrochloric acid and extracted with ethyl acetate. The extract was washed with water and saturated saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and eluted with a mixture of hexane: ethyl acetate (12: 1 to 5: 1). ) 430 mg of phenyl, carbamoyl, phenoxy] butyrate were obtained.

Physicochemical properties

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 <5: 0.92 (6 H, d), 1.24 (3 H, t),

1.80 to 1.96 (1H, m), 2.25 to 2. 35 (2 H, m), 2.50 (1 H, d),

 2.58 (2 H, t) 4.15 (2 H, q), 4.28 (2 H, t), 5.04 (2H, s), 7.00 (2 H, AB q),

 7.00 to 7.04 (l H, m),

 7.12 to 7.17 (1H, m), 7, 19 (2H, ABq), 7.37 (2H, ABq),

 7.45 to 7.52 (1H, m),

 7.62 (2H, AB q), 8.29 (1 H, d d), 9.76 (1 H, s)

Reference Example 26

 To a solution of 890 mg of 2,3-dimethyl-412-tropanol, 1.72 g of 1,4- (4-isobutylphenyl) butyl bromide, 5 Omg of tetrabutylammonium bromide and 30 ml of 2-butanone Then, 1.1 g of potassium carbonate was added, and the mixture was refluxed for 3.5 hours. The reaction solution was concentrated under reduced pressure, and the obtained residue was extracted with ethyl acetate. The extract was washed with a saturated sodium hydrogen carbonate solution and saturated saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and eluted with a mixture of hexane: toluene (4: 1) to give 2,3-dimethyl-41- [1- (4-isobutylphenyl) butoxy] nitrobenzene. 1, 16 g were obtained.

Physicochemical properties

 Mass spectrometry value (mZz): FAB 356 (M + 1) +

 1 89 (base peak)

Nuclear magnetic resonance spectra _{(27 OMH z, CD C.1 3} , TMS internal standard)

 5: 0.87 (6 H, d), 0.95 (3 H, t),

 1. 32 ~: I. 6 1 (2Η, m),

1.76〜: I. 90 (2H, m), 1.96 to 2.08 (1 H, m), 2.36 (3H, s), 2.44 (3 H, s), 2.44 (2 H, d), 5.17 (1 H, dd), 6.57 (1 H, d), 7.1 1 (2 H, d), 7.20 (2 H, d), 7.59 (1 H, d)

Reference Example 27

 In the same manner as in Reference Example 26, 4-isobutyl benzyloxy 2-methylnitrobenzene was obtained.

Starting compounds: 3-methyl-412-tropanol, 4-isobutylbenzyl bromide

Physicochemical properties

 Mass spectrometry value (m / z): G C-MS 299 (M +)

 1 47 (base peak)

 Nuclear magnetic resonance spectrum (9 OMHz, CDC13, TMS internal standard)

 δ: 00..99 11 ((66 ΗΗ ,, dd)), 1.66 to 2.04 (1 Η, m), 2.50 (2 Η, d) 2.62 (3 Η, s ), 5.09 (22, s) 6.79 to 6.93 (2Η, m), 7.17 (2Η, d), 7.33 (2Η, d), 8.07 (1 Η, dd)

Reference Example 2 8

 In the same manner as in Reference Example 26, 2,3-dimethyl-41- (4-isobutyl) benzyloxynitrobenzene was obtained.

Raw material compound: 4-isobutyl pendirubide, 2,3-dimethyl-4,2-trophenenole

Physicochemical properties

 Mass spectrometry value (mZz): GC-MS 3 13 (M +)

 1 47 (base peak)

Nuclear magnetic resonance spectrum (90MHz, CDC 10, TMS internal standard) δ 0.91 (6 Η, d) L. 64 ~ 2.06 (1 H, m), 2.27 (3 H, s) 2.45 (3 H, s), 2.49 (2 H, d) 5.1 1 (2 H, s), 6.79 (1 H, s) 7.16 (2 H, d), 7.33 (2 H, d) 7.75 (1 H, d) Reference Example 29

 In the same manner as in Reference Example 26, 4- (4-isobutyl-α-methyl) benzyloxy ditrobenzene was obtained.

Starting compounds: 4-Isobutyl-methylbenzylbutamate, 412-Trophenanol

Physicochemical properties

 Mass spectrometry value (m / z): FAB (P 0 s.)

300 (M + 1) ⁺ 16 1 (base peak) Nuclear magnetic resonance spectrum (27 OMHz, CDC3, TMS internal standard)

 δ: 00.87 (6 H, d), 1.66 (3 H, d),

 1.75 ~: I. 91 (1 H, m), 2.45 (2H, d), 5.39 (1 H, q). 6.92 (2 H, d), 7.14 (2 H , d), 7.26 (2 H, d), 8.12 (2 H, d)

Reference Example 30

 In the same manner as in Reference Example 26, 41 (naethyl-41-isobutyl) benzyloxynitrobenzene was obtained.

Starting compounds: naethyl-4-isobutylbenzylbutane

 4 12 Troponol

Physicochemical properties

 Mass spectrometry value (mZz): FAB (P 0 s.)

3 14 (M + 1) ⁺ 175 (base peak) Nuclear magnetic spectrum (27 OMH z, CD C 13, TMS internal standard)

 δ 0.90 (6 Η, d), 1.20 (3 H, t),

 1.75 to 2.10 (3H, m), 2.44 (2 H, d), 5.10 (1 H, t), 6.91 (2 H, d),

7.17 (2 H, d), 7.22 (2 H, d),

8.10 (2 H, d)

Reference example 3 1

 In the same manner as in Reference Example 26, 4- (4-isobutyl-methyl) benzyloxy-2-methylnitrate benzene was obtained.

Starting compound: 4-isobutyl-α-methylbenzylbutane amide,

 3—Methyl-4—Nitrophenol

Physicochemical properties

 Mass spectrometry value (mZz): FAB (Pos.)

3 1 4 (M + 1) ⁺ 16 1 (base peak) Nuclear magnetic resonance spectrum (90 MHz, CDC 13, TMS internal standard) δ 086 (6 H, d), 1.65 (3 H, d),

 1 75 to 1.90 (1H, m), 2.45 (2H, d), 255 (3H, s), 5.37 (1H, q), 673 (1H, dd) , 6.78 (1 H, d), 7 14 (2 H, d), 7.26 (2 H, d), 7.99 (1 H, d)

Reference Example 32

 In the same manner as in Reference Example 26, forty-one (α-ethyl-41-isobutyl) benzyloxy-2-methylnitrobenzene was obtained.

Raw material compound: α-ethyl 4-isobutyl pendirubide, 3

 -Mechinore 412 Trof Enore

Physicochemical properties

 Mass spectrometry value (mZz): FAB (Pos.)

328 (M + 1) ⁺ 1 75 (base peak) Nuclear magnetic resonance spectrum (27 OMH II, CDC13, TMS internal standard)

 δ 0 8 9 (6 H, d), 0.99 (3 H, t),

 1 80 0-: I. 95 (2 H, m),

 1 96 to 2.09 (1H, m), 2.45 (2H, d), 256 (3H, s), 5.09 (1H, t), 673 (1H , Dd), 6.79 (1 H, d), 7.14 (2 H, d), 7, 23 (2 H, d), 7.99 (1 H, d)

 Reference example 3 3

 In the same manner as in Reference Example 26, 4- (4-isobutyl-isopropyl) benzyloxynitrobenzene was obtained.

Starting compounds: 4-isobutyl-2-isopropylbenzyl bromide, 412 trophenol

Physicochemical properties

 Mass spectrometry value (mZz): FAB (Pos.)

^{3 28 (M + 1) +} 1 8 9 (base peak) Nuclear magnetic resonance spectrum _{(9 OMHz, CDC 1 3,} TMS internal standard)

 6: 0.87 (6 Η, d), 0.90 (3 H, d),

 1.05 (3Η, d), 1.68 ~: L. 99 (1Η, m), 2.00 to 2.28 (1H, m), 2.44 (2H, d), 4. 8 6 (1 H, d), 6.88 (2 H, d),

7.00 66 ((22 HH ,, dd)),, 77.2 1 (2 H, d),

8.0077 ((22 HH ,, dd)) ,, 33..1 0 to 3.60 (2 H, br) Reference example 3 4

 In the same manner as in Reference Example 26, 41- (4-isobutyl-1-isopropyl) benzyloxy-2-methylnitrobenzene was obtained.

Starting compounds: 4-Isobutyl-I-isopropylbenzyl

, 3-Methyl-1-412trophenol Physicochemical properties

Mass spectrometry value (mZz): (. P o s) FAB 342 (M +) Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.86 (6 H, d), 0 89 (3 H, d),

 1.04 (3 H, d), 1.70 to 2.18 (2 H, m),

2.44 (2 H, d), 2 54 (3 H, s),

4.84 (1H, d), 6.64 to 6.74 (2H, m),

7.08 (2 H, d), 723 (2 H, d),

7.94 (1 H, d)

Reference Example 35

 In the same manner as in Reference Example 26, 3-chloro-41- [1- (4-isobutylyl) ethoxy] nitrobenzene was obtained.

Starting compound: 2-chloro-412-tropanol

Physicochemical properties

 Mass spec (m / z): 332 (M-1) +

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ 0.80 (6 Η, d), 1.65 (3 H, d),

 1.5 to 2.0 (1H, m), 2.37 (2H, d), 5.37 (1H, q), 6.76 (1H, d), 6.9 to 7. 3 (4 H, m), 7.89 (1 H, dd) 8.1 9 (1 H, d)

Reference Example 36

 In the same manner as in Reference Example 26, 4- (4-isobutyl) -benzyloxy-2-methylnitrate benzene was obtained.

Starting compounds: 1-promo 1- (4-isobutyl) phenylbutane,

 3-Methyl-412 tropanol

Physicochemical properties

Nuclear magnetic resonance spectrum (9 OMHz, CDC 10, TMS internal standard) 5: 0.87 (6H, d), 0.95 (3H, t), 1.26 to 1.56 (2 H, m),

 1.68 to 2.09 (3H, m), 2.44 (2H, d), 2.54 (3H, s), 5.14 (1H, dd), 6.63 to 6. 75 (1H, m), 6.75 (1H, s), 5.14 (1H, dd), 6.63 to 6.75 (1H, m),

6.75 (1H, s), 7.08 (2H, d),

7.20 (2 H, d), 7.95 (1 H, d) Reference example 37

 In the same manner as in Reference Example 26, 4- (4-isobutyl-α-propyl) benzyloxynitrobenzene was obtained.

Starting compound: 1-bromo-11- (4-isobutyl) phenylbutane, 412-tropanol

Physicochemical properties

Nuclear magnetic resonance spectrum _{(90 MHz, CDC 1 3,} TMS internal standard) δ: 0. 87 (6 Η , d), 0. 95 (3 H, t),

 1.26 ~: I.64 (2 H, m),

 1.67 to 2.11 (3H, m), 2.44 (2H, d), 5.16 (1H, dd), 6.89 (2H, d),

 7.09 (2 H, d), 7.2 1 (2 H, d), 8.08 (2 H, d)

Reference Example 38

 In the same manner as in Reference Example 26, 4- (α, 4-diisobutyl) benzyloxy-2-methylditrobenzene was obtained.

Starting compounds: na, 4-diisobutylbenzyl bromide, 3-methyl-4-nitrophenol

Physicochemical properties

 Mass spectrometry value (ιηΖ ζ): FAB (Pos.) 356 (M + 1 +

 1 7 (base peak)

Nuclear magnetic resonance spectrum (10 OMH z, CDC lg, TMS internal standard) Associate)

 δ: 0.86 (6Η, d), 0.87 (3Η, d),

 0.98 (3Η, d), 1.52 to 2.12 (4Η, m), 2.42 (2H, d), 2.53 (3H, s), 5 18 (1H, dd), 6.70 (1Hdd), 6.74 (1H, s), 7.08 (2H, d), 7.20 (2H, d), 7.95 (1 H, d)

Reference Example 3 9

 In the same manner as in Reference Example 26, 41- (a, 4-diisobutyl) benzyloxynitrite-opened benzene was obtained.

Starting compounds: 2,4-diisobutylbenzyl bromide, 4-nitrophenol

Physicochemical properties

Mass spectrometry value (mZ z): FAB340 (M-1) ⁺

 1 7 (base peaK

 Nuclear magnetic resonance spectrum (10 OMHz, CDC13. TMS internal standard)

 δ 0.86 (6 Η, d) 0 8 8 (3 H, d),

 0.97 (3 H, d) 1.4 1 to 2.0 9 (4 H, m), 2.42 (2 H, d) 52 0 (1 H, d d)

6. 8 7 (2 H, d) 7 0 8 (2 H, d),

7.2 1 (2 H, d) 8 0 7 (2 H, d)

Reference example 4 0

 In the same manner as in Reference Example 26, 2,3-dimethyl-41- (α-ethyl-4-isobutyl) benzyloxynitrophenol was obtained.

Starting compounds: α-ethyl-4-isobutylbenzyl bromide, 2,

 3-Dimethyl 412 trophenol

Physicochemical properties

Mass spectrometry value (m / z): FAB (P 0 s.) 3 4 2 (M + 1) ⁺ 1 7 5 (base peak)

 Nuclear magnetic resonance spectrum (27 OMHz, CDC13, TMS internal standard)

 δ 0 8 6 (6 H, d), 1.000 (3 H, t),

 17 5 to 2.0 9 (3 H, m), 2.37 (3 H, s), 24 3 (2 H, d), 24 4 (3 H, s), 5 10 ( 1 H, t), 6 56 (1 H, d), 7 1 1 (2 H, d), 7 2 0 (2 H, d),

5 9 (1 H, d)

Reference example 4 1

 In the same manner as in Reference Example 26, 2,3-dimethyl-41- (4-isobutyl-2-isopropyl) benzylbenzene-opened benzene was obtained. Starting compounds: 4-Isobutyl-2-isopropylbenzylbutamide, 2,3-dimethyl-4-212 trophenol Physical and chemical properties

 Mass spectrometry (m / z): m / e (FAB)

3 2 8 (M + 1) + 1 8 9 (base peak) Nuclear magnetic resonance spectrum _{(9 OMH z, CDC 1 3} , TMS internal standard) δ: 0. 8 7 (6 H, d), 0. 9 0 (3 H, d),

 1.05 (3H, d), 1.68-: I.99 (1H, m),

2.00 to 2.28 (1H, m), 2.44 (2H, d), 4.86 (1H, d), 6.88 (2H, d),

7.06 (2 H, d), 7.2 1 (2 H, d),

8.07 (2 H, d)

Reference example 4 2

In the same manner as in Reference Example 26, 5-promo 2,3-dimethyl-41- (4-isobutyl-α-methyl) benzyloxynitrobenzene was obtained. Starting compounds: 4-Isobutyl-α-methylbenzylbutamate, 6-bromo-2.3-dimethyl-412-trophenol Reference example 4 3

 In the same manner as in Reference Example 26, 3,5-dimethyl-41- (4-isobutyl-methyl) benzyloxynitrite benzene was obtained.

Starting compound: 4-Isoptyl-α-methylbenzylbutane amide, 2,

 6-dimethyl-412 tropanol physicochemical properties

 Mass spectrometry value (mZz): F A B (P os.)

 3 26 (M-1) + 16 1 (base peak) Nuclear magnetic resonance spectrum (40 OMHz, CDC13, TMS internal standard)

 δ: 00.90 (6Η, d), 1.69 (3Η, d),

 1 8 0 to 1.92 (1 Η, m), 2.17 (6 Η, s), 2 4 7 (2 Η, d), 4.99 (1 Η, q), 7 1 1 (2 Η, d), 7 2 3 (2 Η, d), 7 8 6 (2 Η, s)

Reference example 4 4

 In the same manner as in Reference Example 26, 41- (2,4-diisobutyl) benzyloxy-1,2,3-dimethylnitrobenzene was obtained.

Starting compound: 4- (a, 4-diisobutyl) benzyl bromide,

 2,3-Dimethyl 412 trophenol

Physicochemical properties

 Mass spectrometry value (mZz): F A B (P os.)

3 7 0 (M + 1) + 1 4 7 (base peak) Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.86 (6 Η, d), 0.93 (3 H, d),

 0.99 (3 Η, d), 1.5 2 to 1.67 (1 H, m), 1.77 to 1, 90 (2 H, m),

1.98 to 2.09 (1H.m), 2.31 (3H, s), 2.44 (3H, s), 2.44 (2H, d), 5.22 (1 H, dd), 6.57 (1 H, d), 7.1 1 (2 H, d), 7.21 (2 H, d), 7.59 (1 H, d)

 Reference example 45

 In the same manner as in Reference Example 26, 4- (4-isobutyl-methylbenzyloxy) -1,2,6-dimethylnitrobenzene was obtained.

 Raw material compound: 4,12-trough 3,5-dimethylphenol

Physicochemical properties

 Mass spectrum (mZz): 327 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.89 (6 Η, d), 1.62 (3 H, d),

 1.72 ~ 2.00 (1 H, m), 2.24 (6 H, s), 2.47 (2 Η, d), 5.31 (1 Η, q),

6.57 (2 Η, s), 7.08 to 7.3 1 (4 Η, m) Reference example 46

 In the same manner as in Reference Example 26, 4- (1-isobutyl-2-methylbenzyloxy) -1,2,3,5-trimethylnitrobenzene was obtained. Starting compound: 412 trow 2, 3, 6-trimethylphenol Physicochemical properties

Mass spec (mZz): 340 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.90 (6Η, d), 1.65 (3 H, d),

 1.86 (1 H, m), 2.09 (3H, s),

 2.13 (3H, s), 2.33 (3 H, s), 2.47 (2 H, m), 4.89 (1 H, m),

7.1 1 7.12 (2H, m),

 7.22 to 7: 26 (2 H, m), 7.49 (1 H, s) Reference example 47

1- (4-isobutylphenyl) ethanol 1.12 g, 3— A solution of 0.87 g of chilled 4-nitrophenol, 1.64 g of triphenylphosphine and THF 2 Om1 under ice-cooling, 1.7 N-diisopropyrazodicarboxylate THF solution 3.7 ml was added, and the mixture was stirred at room temperature for 3 hours.

 The solvent of the reaction solution was distilled off under reduced pressure, and the obtained oil was subjected to silica gel column chromatography (using 100 g of silica gel), and eluted with a mixture of hexane: ethyl acetate: t9: 1. 0.83 g of 3-ethyl 4- [1- (4-isobutylphenyl) ethoxy] benzene was obtained.

Physicochemical properties

 Mass spec (mZz): 3 27 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ 0.91 (6 Η, d), 1 1 9 (3 H, t),

 1, 65 1 88 (1 H, m), 2.44 (3 H, d), 280 (2 H, q), 5.35 (1 H, g), 67 7 (2 H, m ), 7.20 (m, 4H), 790 (1H, d)

Reference Example 4 8

 N-Propyl-1-isobutylaniline 7 8 Omg,

To a solution of 970 mg of 4-nitroben jilbide, 50 ms of potassium iodide and 50 ml of 2-butanone was added 850 IT. G of lithium carbonate, and the mixture was heated and refluxed for 10 hours. The reaction solution was concentrated under reduced pressure, and the obtained residue was extracted with ethyl acetate. The extract was washed with water and saturated saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and eluted with a mixture of hexane: ethyl acetate (95: 5) to give N- (4-ditrobenzyl) -l-N-propyl-l-isobutyranyline 1.45. g was obtained.

Physicochemical properties, mass spectrometry (mZz): 326 (M +) Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

5: 0.8 ~ 1.0 (9 H, m),

 16-: I.8 (3 H, m), 2.36 (2 H, s), 3 34 (2 H, s), 4.59 (2 H, s), 65 6 (2 H, s), 6.97 (2H, s), 741 (2H, s), 8.17 (2H, s) Reference example 4 9

 In the same manner as in Reference Example 48, N- (4-nitrobenzyl) -N, 4-disobutylaniline was obtained.

Starting compound: N, 4-diisobutylaniline

Physicochemical properties

 Mass spec (mZz): 340 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.87 (6Η, d) 0.96 (6H, d)

 1. 7 7 (1 H, m) 2. 1 2 (1 H, m)

2. 3 4 (2 H, d) 3.2 1 (2 H, d)

4.63 (2 H, s) 6.5 4 (2 H, d)

6.94 (2 H, d) 7.35 (2 H, d)

8. 1 4 (2 H, d)

Reference example 5 0

 In the same manner as in Reference Example 48, N-ethyl-N- (412-trobenzyl) -14-isobutylaniline was obtained.

Starting compound: N-ethyl 4-isobutylaniline

Physicochemical properties

Mass spec (mZz): 3 1 2 (M ⁺ )

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 6: 0.85 (6 H, d), 1.19 (3 H, t),

1.6 to 2.0 (1H, m), 1.14 (2H, d), 3.46 (2H, q), 4.54 (2H, s), 6.5 6 (2 H, dt), 6.96 (2 H, dt), 7.4 1 (2H, dt), 8.16 (2H, dt) Reference example 5 1

 In the same manner as in Reference Example 48, 4-isobutyl-N-methyl-N- (3-methyl-4-12-trobenzyl) aniline was obtained.

Raw material compound: 4-isobutyl-N-methylaniline

Physicochemical properties

 Mass spec (m / z): 3 1 2 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 <5: 0.88 (6 H, d), 1.80 (1 H, m),

 2.18 (2H, d), 2.58 (3H, s),

2.99 (3 H, s), 4, 50 (2 H, s),

6.6 to 6.8 (2H, m)

 6. 9 to 7.1 (2H, m)

 7.1 to 7.3 (2H, m) 95 (1H, d) Reference example 52

 In the same manner as in Reference Example 48, 4-isobutyl-N-methyl-N- (2-methyl-3-nitrobenzyl) aniline was obtained.

Starting compound: 4-Isobutyl-N-methylaniline

Physicochemical properties

 Mass spec (mZz): 3 12 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 6 0.89 (6 H, d), 1.80 (1 H, m),

 2.38 (2H, d), 2.42 (3H, s),

4.47 (2 H, s), 6.5 to 6.7 (2 H, m),

3.0 1 (3H, s), 6.9 to 7.1 (2H, m), 7.2 to 7.5 (2H, m) 7.6 to 7.8 (1H, m ) Reference Example 53

To a solution of 890 mg of monoisobutylbenzoic acid and 15 ml of methylene chloride was added 0.1 ml of N, N-dimethylformamide and o-chloride under ice-cooling. 1.5 ml of Xalil was added. The mixture was heated to room temperature, stirred for 2 hours, and concentrated under reduced pressure. The residue obtained was dissolved in 3 ml of methylene chloride, and the solution was added to a mixture of 69 mg of 412 troaline phosphorus, 3 ml of pyridin and 3 ml of methylene chloride under ice-cooling. After the dropwise addition, the mixture was heated to room temperature and stirred for 3.5 hours. The reaction solution was concentrated under reduced pressure, and the obtained residue was extracted with ethyl acetate. The extract was washed successively with water and saturated saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained crystalline residue was recrystallized from isopropanol to obtain 79 Omg of 4-isobutyl-N- (412-trophenyl) benzamide. Physicochemical properties

 Mass spec (mZz): 298 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.92 (6 Η, d), 1.91 (I H, m),

 2.56 (2 H, d), 7.2 to 7.4 (2 Η, m),

7. 7 to 8.0 (4 Η, m),

 8. u 8.3 (3 Η, m)

Reference Example 5 4

 In the same manner as in Reference Example 53, 41-isobutyl-N (412-trophenyl-2-acetyl) anilide was obtained.

Starting compound: 4-isobutylaniline

Physicochemical properties

 Mass spec (mZz): 3 1 2 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 5: 0.83 (6 H, d), 1 78 (1 H, m)

 2.38 (2 H, d), 38 2 (2 H, s), 7.07 (2 H, d), 748 (2 H, d), 7.61 (2 H, d) d), 8 20 (2 H, d), 10 .1 9 (1 H, s)

Reference Example 5 5 Under a stream of argon, in a solution of 62 mg of N- (4-isobutylphenyl) -14-phenylphenylacetamide and 6 ml of tetrahydrofuran, 1 M-borane-tetrahydrofuran complex tetrahydrofuran solution 6 m 1 Was added dropwise and stirred at room temperature for 1 hour. The reaction was stopped by adding methanol and concentrated hydrochloric acid sequentially under ice cooling, neutralized with a 5N aqueous sodium hydroxide solution, and concentrated under reduced pressure. The obtained residue was extracted with ethyl acetate. The extract was washed with water and saturated saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and eluted with a mixture of hexane: ethyl acetate (6: 1) to obtain N- (412-trophenethyl) -14-isobutylaniline (520 mg). Was. Physicochemical properties

 Mass spec (mZ z): 298 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 «5: 0.88 (6 H, d), 1.79 (1 H, m),

 2.37 (2 H, d), 3.04 (2 H, t),

3.45 (3 H, m), 6.5 to 6.6 (2 H, m),

6. 9 to 7.1 (2 H, m)

 7.3 to 7.5 (2H, m)

 8. 1 to 8.3 (2 H, m)

Reference Example 5 6

 In the same manner as in Reference Example 55, N (4-isobutylbenzyl) -14-nitroaniline was obtained.

Starting compound: 4-Isoptyl-N— (412-trophenyl) benzamide

Physicochemical properties

Mass spec (m / z): 285 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.90 (6 Η, d), 1.85 (1 H, m),

2.47 (2 H, d), 4.37 (2 H, d), 4.84 (1H, m), 6.5 to 6.7 (2H, m), 7.0 to 7.4 (4H, m),

 8.0 to 8.2 (2 H, m)

 Reference Example 5 7

 3 ml of a 35% formaldehyde solution was added to a solution of N- (4-nitrobenzyl) 14-isobutylaniline (34 Omg) and formic acid (3 ml), and the mixture was heated to 100 ° C and stirred for 45 minutes. The reaction solution was poured into iced water, neutralized with lime carbonate, and extracted with black-mouthed form. The extract was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and eluted with a mixture of hexane and ethyl acetate (9: 1) to give N-methyl-N- (412-trobenzyl) -14-isobutylaniline. 90 mg was obtained. Physicochemical properties

Mass spec (mZz): 298 (M ⁺ )

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ 0.89 (6 Η, d), 16 to 2.0 (1 H, m), 2.37 (2 Η, d), 30 1 (3 H, s), 4.56 (2 Η, s), 6 6 9 (2 H, dt),

 7. 00 (2 Η, d t) 7.40 (2 H, d),

 8.1 6 (2 Η, d t)

Reference Example 5 8

 In the same manner as in Reference Example 57, N- (4-isobutylbenzyl) -N-methyl-412nitroaniline was obtained.

Starting compound: N— (4-isobutylbenzyl) 1-412 nitroaniline

Physicochemical properties

Mass spec (m / z): 299 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

6: 0.88 (6 H, d), 1.84 (1 H, m). 2.45 (2H, d), 3.16 (3H, s),

 4.63 (2H, s), 6.6 to 6.8 (2H, m),

7.0 to 7.2 (4 H, m),

 8.0 to 8.2 (2 H, m)

Reference example 59

 In the same manner as in Reference Example 57, 4-isobutyl-N-methyl-N- (412-trophenethyl) aniline was obtained.

Starting compound: 4-isobutyl-N- (4-nitrophenyl) aniline

Physicochemical properties

 Mass spec (mZz): 3 1 2 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ 0 88 (6 H, d), 1.80 (1 Η, m),

 2 38 (2 H, d), 2.85 (3 H, s), 2 98 (2 H, d), 3.58 (2 H, t), 66 to 6.8 (2 H, m) ,

 6 9-7 1 (2 H, m),

 7 1 ~ 7 3 (2 H, m),

 8 1 ~ 8 3 (2 H, m)

Reference Example 60

Under a stream of argon, a mixture of 1.52 g of 2-methyl-4,2,2,2,2,2,2-pyridine, 6 ml of pyridine and 6 ml of methylene chloride was mixed with 2- (3-ethoxycarbonylpropoxy) benzoylcyl under ice-cooling. A solution of 2.4 g of mouth light and 6 ml of methylene chloride was added dropwise, and the mixture was stirred at room temperature for 16 hours. The reaction solution was concentrated under reduced pressure, and the obtained residue was extracted with ethyl acetate. The extract is washed with 1N hydrochloric acid and saturated saline, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the obtained crystalline residue is recrystallized from ethanol to give ethyl 4- [2- [N- (2-methyl 412 trophanyl) rubamoyl] phenoxy] butyrate 2.92 g were obtained.

 Physicochemical properties

Mass spec (m / z): 387 (M + 1) ⁺

 Nuclear magnetic resonance spectrum (CDC13, TMS internal standard)

 δ: I.23 (3Η, t), 2.1 to 2.7 (7H, m).

 4 1 2 (2 H, q), 4.39 (2 H, t), 70 to 7.3 (2 H, m)

 7 4 7 7 (1H, m)

 8 0 8 4 (3 H, m)

 8 5 8 7 (1 H, m) 9.89 (1 H, s) Reference example 6 1

 2,3-Dimethyl 4- [1- (4-isobutylphenyl) butoxy] nitrobenzene under an argon stream 1.23 g of ethanol

To the (5 Oml) solution was added 15 Omg of platinum oxide, and the mixture was purged with hydrogen and stirred at room temperature for 3 hours. The catalyst was removed, and the solution was concentrated under reduced pressure to obtain 1.1 g of 2,3-dimethyl-41- [111- (4-isobutylphenyl) butoxy] aniline I.11 g.

Physicochemical properties

 Mass spectrometry value (mZz): FAB (Pos.)

326 (M + 1) + 1 37 (base peak) Nuclear magnetic resonance spectrum (90 MHz, CDC 1 ₃ TMS internal standard.) Δ: 0. 8 8 ( 6 Η, d), 0. 9 1 (3 H, ),

 1.24 to 2.10 (5 H, m),

 1.70 to 2.50 (2 H, b r),

 2.08 (3 H, s), 2 2 3 (3 H, s),

2.43 (2 H, d), 491 (1 H, d d),

 6. 3 7 (3 H, s), 7 0 5 (2 H, d),

 7.2 2 (2 H, d)

Reference example 6 2 In the same manner as in Reference Example 61, 4-isobutylbenzyloxy-2-methylaniline was obtained.

Raw material compound: 4-isobutyl pendoxy 2-methylnitrobenzene

Physicochemical properties

 Mass spec (mZz): FAB 269 (M +)

 1 54 (base peak)

 Nuclear magnetic resonance spectrum (27 OMHz, CDC13, TMS internal marker

 Associate)

 δ: 00..89 (6Η, d), 1.77-: I. 91 (1H, m),

 2 05 (3 H, s), 2.48 (2 H, d), 3 32 to 3.52 (2H, br),

 4 98 (2 H, s), 6.68 to 6.84 (3H, m),

7.16 (2 H, d), 7.32 (2 H, d)

Reference Example 63

 In the same manner as in Reference Example 61, 2,3-dimethyl-41- (4-isobutyl) benzyloxyazirin was obtained.

Starting compound: 2,3-Dimethyl-41- (4-isobutyl) benzyl benzyl

Physicochemical properties

 Mass spectrometry (mZz): FAB 283 (M +)

 1 36 (base peak)

 Nuclear magnetic resonance spectrum (27 OMHz, CDC13, TMS internal marker

 Associate)

δ: 0.91 (6Η, d) 78 ~: I.94 (1H, m), 2.12 (3H, s) 223 (3H, s), 2.48 (2H, d) 3 37 (2 H, brs), 4.95 (2 H, s) 653 (1 H, d), 6.70 (1 H.d) 7 16 (2 H, d), 7. 3 6 (2 H, d)

 Reference example 6 4

 In the same manner as in Reference Example 61, 4- (4-isobutyl-methyl) benzyloxyaniline was obtained.

 Raw material compound: 4- (4-isobutyl-α-methyl) benzyloxy nitro benzene

 Physicochemical properties

 Mass spectrometry value (mZz): E I 269 (M +)

 1 0 9 (base peak)

Nuclear magnetic resonance spectra (1 0 OMH z, CD C 1 3. TMS internal standard)

 δ: 0.86 (6 Η, d), 1.55 (3 H, d),

 1.64 to 2.03 (1H, m),

 2 2 0 to 2.5 2 (2 H, b r),

 2 4 3 (2 H, d), 5.1 2 (1 H, q), 65 2 (2 H, d), 6.70 (2 H, d), 7 0 7 (2 H, d ), 7.25 (2 H, d)

Reference example 6 5

 In the same manner as in Reference Example 61, 41- (ethyl-41-isobutyl) benzyloxyaniline was obtained.

Starting compound: 4- (N-ethyl-41-isobutyl) benzyloxy

Physicochemical properties

 Mass spectrometry value (mZz): E I 2 8 3 (M +)

 1 0 9 (base peak)

Nuclear magnetic resonance spectra (1 0 OMH z, CDC 1 3, TMS internal standard)

 δ: 0.86 (6Η, d), 0.95 (3 H, t),

1.64 to 2.05 (3 H, m), 2.42 (2 H, d), 3.00 to 3.60 (2H, br),

 4.83 (1 H, t), 6.5 1 (2 H, d),

6.68 (2 H, d), 7.06 (2 H, d),

7.2 1 (2 H, d)

Reference Example 6 6

 In the same manner as in Reference Example 61, 41- (4-isobutyl-α-methyl) benzyloxy-2-methylalanine was obtained.

Raw material compound: 4- (4-isobutyl-α-methyl) benzyloxy 2-methylnitrobenzene

Physicochemical properties

 Mass spectrometry value (mZz): E I 2 8 3 (M +)

 1 2 3 (base peak)

 Nuclear magnetic resonance spectrum (10 OMHz, CDC13, TMS internal standard)

 δ: 0.87 (6 Η, d), 1.55 (3 H, d),

 1.64 to 2.00 (1 H, m), 2.07 (3 H, s), 2.42 (2H, d), 3.96 to 4.64 (2H, br), 5.1 2 (1 H, q), 6.5 u 6.54 (2 H, m), 6.62 to 6.64 (1 H, m), 7.07 (2H, d), 7.26 ( 2 H, d)

Reference example 6 7

 In the same manner as in Reference Example 61, 41- (ethyl-41-isobutyl) benzyloxy-2-methylaniline was obtained.

Starting compound: 4-1 (naethyl-41-isobutyl) benzyloxy-2-methylnitrobenzene

Physicochemical properties

Mass spectrometry value (m / z): EI297 (M ⁺ )

 1 2 3 (base peak)

Nuclear magnetic resonance spectrum (10 OMHz, CDC 1 Q, TMS internal marker Associate)

 6: 0.86 (6H, d), 0.95 (3H, t),

 1.71 to: I. 99 (1H, m), 2.06 (3H, s), 2.43 (2H, d), 3.08 to 3.60 (2H, br), 4. 83 (1 H, t), 6.49 to 65 1 (2 H, m),

6.60 to 6.66 (1 H, m), 7 06 (2 H, d),

7.2 2 (2 H, d)

 Reference Example 6 8

 In the same manner as in Reference Example 61, forty-one (4-isobutyl-isopropyl) benzyloxydirin was obtained.

 Raw material compound: 4- (4-isobutyl-iso-isopropyl) benzene

Physicochemical properties

Mass spectrometry value (m Roh z): FAB 29 7 (M +) (base peak) Nuclear magnetic resonance spectrum _{(9 OMHz, CDC 1 3,} TMS internal standard) δ: 0 8 6 (3 Η, d), 0 8 7 (6 Η, d),

 04 (3 H, d), 1.6 0 to 2.20 (2Η, m),

2.43 (2 H, d), 60 (1 Η, d), 6.5 1 (2 Η, d), 66 7 (2 Η, d), 7.05 (2 Η, d) ), 7, 2 0 (2 Η, d)

Reference Example 6 9

 In the same manner as in Reference Example 61, 4- (4-isobutyl-α-isopropyl) benzyloxy-2-methylaniline was obtained.

Starting compound: 4- (4-isobutyl-isopropyl) benzyloxy-2-methylnitrobenzene

Physicochemical properties

Mass spectrometry value (mZz): FAB 3 12 (M + 1) ⁺

 1 8 9 (base peak)

Nuclear magnetic resonance spectrum (27 OMHz, CDC13, TMS internal marker Associate)

 5: 0.83 (3 H, d), 0.84 (6 H, d),

 1.01 (3H, d), 1.68 to 2.16 (2H, m), 2.04 (3H, s), 2.41 (2H, d), 3. 1 0 to 3.3 0 (2 H, br),

 4.59 (1 H, d), 6.46 to 6.48 (2 H, m),

6.57 to 6.63 (1H, m),

 7.03 (2 H, d), 7.18 (2 H, d) Reference example 70

 In the same manner as in Reference Example 61, 41- (4-isobutyl-l-propyl) benzyloxy-2-methylaniline was obtained. -Raw material compound: 4- (4-isobutyl-1-propyl) benzyloxy 2-methyl benzene

Physicochemical properties

Mass spectrometry value (mZz): EI 311 (M ⁺ )

 1 2 3 (base peak)

 Nuclear magnetic resonance spectrum (9 OMH z, CDC 13, TMS internal standard) (5: 0.88 (6 H, d), 0.92 (3 H, t),

 1.13-2.04 (5 H, m),

 2.00 to 2.80 (2 H, b r),

 2.08 (3 H, S), 2.43 (2 H, d), 4.91 (1 H, dd), 6.50 to 6.61 (3 H, m), 7.06 (2 H, d), 7.22 (2 H, d)

Reference example 7 1

 In the same manner as in Reference Example 61, 4- (1-isobutyl-propyl) benzyloxyaniline was obtained.

Starting compound: 4- (4-isobutyl-propyl) benzyloxynitrobenzene

Physicochemical properties Mass spectrometry value (mZz): EI297 (M +)

 1 0 9 (base peak)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0 8 8 (6 H, d), 0.92 (3 Η, t),

 1 2 7 to 2.0 8 (7Η, m), 2.42 (2Η, d), 48 9 (1Η, d d), 6.52 (2Η, d),

 6 6 8 (2 Η, d), 7.06 (2 Η, d),

 2 2 (2 Η, d)

Reference example 7 2

 In the same manner as in Reference Example 61, 41- (α, 4-diisobutyl) benzyloxy-2-methylaniline was obtained.

Starting compound: 4- (, 4-diisobutyl) benzyloxy-2-methylbenzene

Physicochemical properties

 Mass spectrometry value (mZz): FAB (Pos.)

3 2 6 (M + 1) ⁺¹ 2 3 (base peak) Nuclear magnetic resonance spectrum (9 OMHz, CDC 1 o, TMS internal standard) 6: 0.84 to: I. 00 (12 H, m),

 1. 0— 2.10 (4H, m), 2.07 (3 H, s), 2.43 (2 H, d), 2.90 to 3.3 0 (2 H, br )

4.97 (1 H, d d), 6.49 (1 H, d),

6.50 (1 H, s), 6.60 (1 H, d),

7.06 (2 H, d), 7.2 3 (2 H, d)

Reference Example 7 3

 Reference Example 61 In the same manner as in 1, 41 (na, 4-diisobutyl) benzyloxyaniline was obtained.

Starting compound: 4- (α, 4-diisobutyl) benzyloxynitrobenzene

Physicochemical properties Mass spectrometry value (m / z): FAB (P os.)

 3 1 2 (M + 1) + 1 47 (base peak) Nuclear magnetic resonance spectrum (27 OMHz, CDC13, TMS internal standard)

 δ: 00.86 (6Η, d), 0.92 (3Η, d),

 0 9 5 (3 Η, d), 1.46 ~: I.57 (1 H, m), 1 78 ~ 1.99 (3 H, m), 2.42 (2 H, d),

3, 00 to 3.60 (2H, br), 4.98 (1 H, dd), 664 (2 H, d), 6.88 (2H, d), 709 (2 H , d), 7.2 4 (2 H, d) Reference example 7 4

 In the same manner as in Reference Example 61, 2,3-dimethyl-41- (α-ethyl-4-isobutylbenzyloxydirin) was obtained.

Starting compound: 2,3-dimethyl-41- (1-ethyl-4-isobutyl) benzyloxynitrobenzene

Physicochemical properties

 Mass spectrometry value (mZz): FA B (Pos.)

 3 1 2 (M + 1) + 1 3 7 (base peak) Nuclear magnetic resonance spectrum (27 OMH z, CDC I 3, TMS internal standard)

 6: 0.87 (6 H, d), 0.95 (3 H, t),

 1.69 to 2.10 (3H, m), 2.07 (3H, s), 2.23 (3H, s), 2.43 (2H, d), 4 . 8 4 (1 H, t), 6.37 (2 H, s), 7.06 (2 H, d), 7.22 (2 H, d),

2 6 0 to 3.2 0 (2 H, b r)

Reference example 7 5

In the same manner as in Reference Example 61, 2,3-dimethyl-41- (4-isobutyl-isopropyl) benzyloxydirin was obtained. Starting compound: 2,3-dimethyl-4-1 (4-isobutyl-iso-propyl) benzyloxynitrobenzene

 Physicochemical properties

 Mass spectrometry value (mZ z): FAB (P os.)

3 26 (M + 1) ⁺ 18 9 (base peak) Nuclear magnetic resonance spectrum (270 MHz, CD C 1 _q , TMS internal standard)

 δ: 0.87 (6 Η, d), 0.91 (3 H, d),

 1. 0 2 (3 H, d), 1.75 to 1, 89 (1 H, m),

205 to 2.18 (lH, m), 2.08 (3H, s), 2.26 (3H, s), 3.24 (2H, br),

 4.71 (1H, d), 6.35 (2H, s), 7.07 (2H, d), 7.18 (2H, d) Reference example 7 6

 In the same manner as in Reference Example 61, 3,5-dimethyl-4 (4-isobutylmethyl) benzyloxydirin was obtained.

Starting compound: 3,5-dimethyl-4-1 (4-isobutyl-methyl) benzyloxynitrobenzene

Physicochemical properties

 Mass spectrometry value (mZz): FAB (Pos.)

2 9 8 (M + 1) ⁺ 16 1 (base peak) Nuclear magnetic resonance spectrum (40 OMHz, CDC 13. TMS internal standard)

 5: 0.90 (6 H, d), 1.59 (3 H, d),

 1.81 to: 1.91 (1H, m), 2.0.2 (6H, s), 2.46 (2H, d), 3.38 (2H, br) , 4.77 (1H, q), 6.31 (2H, s), 7.10 (2H, d), 7.27 (2H, q)

Reference Example 7 In the same manner as in Reference Example 61, 41-(, 4-diisobutyl) benzyloxy-2,3-dimethylaniline was obtained.

Starting compound: 4- (a, 4-diisobutyl) benzyloxy-2,3-dimethylnitrobenzene

Physicochemical properties

 Mass spectrometry value (mZz): FA B (Pos.)

340 (M + 1) ⁺ 147 (base peak) Nuclear magnetic resonance spectrum (CDC 1, TMS internal standard)

 5: 0.84 to 0.99 (12H, m),

 1 3 3 to 2.10 (4 H, m),

 2 0 0 to 2.40 (2 H, b r),

 2 0 7 (3 H, s) 2 2 2 (3 H, s), 2 42 (2 H, d) 4 9 6 (1 H, dd), 6 3 6 (2 H, s) 0 5 ( 2 H, d), 7 2 1 (2 H, d)

Reference Example 7 8

 In the same manner as in Reference Example 61, 4 [(4-isobutyl-N-methylarilino) methyl] aniline was obtained.

Starting compound: N-methyl-N- (4-nitrobenzyl) 4-isobutylaniline

Physicochemical properties

 Mass spec (mZz): 2 6 8 (M +)

 Nuclear magnetic resonance spectrum (CDC1, TMS internal standard)

 δ: 0.97 (6 Η, d), 1.6 to 2.0 (1 H, m), 2.35 (2 H, d), 2.88 (3 H, s),

4.3.4 (2 H, s), 6.5 to 6.8 (4 H, m), 6.9 to 7.1 (4 H, m)

Reference Example 7 9

Reference Example 6 In the same manner as in Example 1, 41 [(N-ethyl-41 isoptyla Nirino) Methyl] aniline was obtained.

 Starting compound: N-methyl-N- (4-nitrobenzyl)-4-iso

 Petilaniline

 Physicochemical properties

 Mass spec (mZz): 28 2 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.87 (6Η, d), 1.13 (3 H, t),

 1.6 to 2.0 (1H, m), 1.33 (2H, d), 3.38 (2H, q), 3.2 to 3.8 (2H, m), 4.35 (2H, s), 6.5 to 6.7 (4H, m),

6. 9 to 7.2 (4 H, m)

Reference Example 8 0

 Reference Example 61 In the same manner as in 1, 41-[(N, 4-diisobutylanilino) methyl] aniline was obtained.

Starting compound: N— (4-12-trobenzyl) -1-N, 4-diisobutyl

 Luaniline

Physicochemical properties

 Mass spec (mZz): 310 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 6: 0.86 (6 H, d), 0.94 (6 H, d),

 1. 7 7 (1 H, m), 2.10 (1 H, m),

2.3.3 (2 H, d), 3.14 (2 H, d),

3.4 to 3.7 (2 H, m), 4.45 (2 H, s), 6.5 to 6.7 (4 H, m), 6.8 to 7.1 (4 H, m) m) Reference example 8 1

 Reference Example 61 In the same manner as in 1, 41-[(4-isobutyl-N-propylanilino) methyl] aniline was obtained.

Starting compound: 4-Isoptyl-N— (412-trobenzyl) 1-N-propylaniline Physicochemical properties

 Mass spec (mZz): 296 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ 0.8-1.0 (9H, m), 1.5-2.0 (3 Η, m),

2.34 (2 H, d), 3.27 (2 H, d d),

 3.56 (2H, m), 4.39 (2H, s), 6.5 to 6.6 (4H, m) 6.8 to 7.1 (4H, m) Reference example 82

 Reference Example 61 In the same manner as in 1, 41-((4-isobutyl-N-methylarilino) methyl] -12-methylaniline was obtained.

Starting compound: 4-Isobutyl-N-methyl-N— (3-methyl-4-12-trobenzyl) aniline

Physicochemical properties

 Mass spectrometry value (mZz): 282 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ 0 88 (6 H, d), 1.80 (1 Η, m),

 2 1 4 (3 H, s), 2.37 (2 H, d), 29 1 (3 H, s), 3.54 (2 H, m), 435 (2 H, s), 6 5 to 6.8 (3 H, m), 68 to 7.1 (4 H, m)

Reference Example 83

 Reference Example 61 In the same manner as in 1, 3-[(4-Isobutyl-N-methylarilino) methyl] 1-2-methylaniline was obtained.

Starting compound: 4-Isobutyl-N-methyl-N- (2-methyl-3-12-benzyl) aniline

Physicochemical properties

 Mass spectrometry value (mZz): 282 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

5: 0.88 (6 H, d), 1.79 (1 H, m), 2.09 (3H, s), 336 (2H, d),

2. 93 (3 H, s) , 3 60 (2 H, m), 4. 4 1 (2 H f s), 6 5~ 6. 7 (4 H, m),

6. 8 7 (3 H, m)

 Reference Example 84

 In the same manner as in Reference Example 61, N- (4-aminophenethyl) -14-Vbutyl-N-methylaniline was obtained.

Raw material compound: 4-Isoptyl-N-methyl-N (412-trophenethyl) aniline

Physicochemical properties

 Mass spectrometry value (mZz): 282 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ 0.89 (6 H, d), 1.81 (1 Η, m),

 2.38 (2 H, d), 2.75 (2 H, d d),

 2.89 (3 H, s), 3.46 (2 H, d d),

 3.8 to 4.2 (2H, m), 6.6 to 6.9 (4H, m), 6.9 to 7.2 (4 H, m)

Reference Example 85

 Reference Example 61 In the same manner as in 1, 41- [N- (4-isobutylbenzyl) -1-N-methylamino] aniline was obtained.

Starting compound: N- (4-isobutylbenzyl) -N-methyl-4_

 Nitroairin,

Physicochemical properties

 Mass spec (mZz): 268 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.89 (6 Η, d), 1.85 (1 H, m),

 2.45 (2 Η, d), 2.3 to 2.7 (2 Η, m),

2.83 (3Η, s), 4.34 (2Η, s),

6.67 (4 Η, s), 7.0 to 7.3 (4 Η, m) Reference Example 86

 Reference Example 61 In the same manner as in Example 1, ethyl 4- [2- [N- (4-amino-12-methylphenyl) pothamamoyl] phenoxy] butyrate was obtained.

Raw material compound: Ethyl 4- [2- [N- (2-methyl-412-to-phenyl) -caproluvamoyl] phenyloxy] butylate Physicochemical properties

 Mass spectrum (mZz): 356 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ 1 22 (3 Η, t), 2.0 to 2.6 (7 H, m), 356 (2 H, m), 4.1 1 (2 H, q), 4 28 (2 H, t), 6.5 to 6.7 (2 H, m), 69 to 7.7 (4 H, m), 8.27 (1 H, dd), 924 (1 H, s)

Reference Example 8

 3-Chloro-4-1 [4- (4-isobutylphenyl) ethoxy] nitrobenzene 320 mg, 3 ml of methanol and 3 ml of 1N hydrochloric acid, add lO Omg of iron powder and heat to 50 ° C And stirred for 1 hour. The reaction solution was neutralized with a 1N aqueous solution of sodium hydroxide, the insolubles were removed by filtration, and the aqueous solution was extracted with ethyl acetate. The extract was washed with water and saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and eluted with a mixture of hexane: ethyl ethyl ester (5: 1) to give 3-chloro-4- [1- (4-isobutylphenyl) ethoxyquin] aniline. 60 mg were obtained. Physicochemical properties

Mass spec (mZz): 303 (M ⁺ )

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.88 (6 Η, d), 1.6 1 (3 H, d),

1.70 ~ 2.0 (1 H, m), 2.44 (2 H, d), 3.25 (2 H, s), 5.12 (1 H, q),

 6.34 (1 H, d d), 6.59 (1 H, d), 6.69 (1 H, d), 7.0 to 7.4 (4 H, m) Reference example 88

 In the same manner as in Reference Example 87, 5-promo 2,3-dimethyl-4- (4-isobutyl-methyl) benzyloxydiline was obtained.

 Starting compound: 5-Promo-2,3-dimethyl-4-1 (4-isobutyl methyl) benzyloxybenzene

 Physicochemical properties

 Mass spectrometry (mZz): FAB (P 0 s.) 378 (M + 1),

 1 D 1 (base peak)

Nuclear magnetic resonance spectra (27 OMH z, CDC 1 ₃ internal standard) δ 0 88 (6 H, d), 1. 62 (3 H, d),

 1.79 to 1.96 (1H, m), 1.88 (3H, s), 193 (3H, s), 2.46 (2H, d), 343 (2H, brs ) 5.09 (1 H, q), 680 (1 H, s), 7 10 (2 H, d), 7 3 1 (2 H, d)

Reference example 89

4-Amino-o-cresol 37 Omg, 2- (3-ethoxycalponylpropoxy) 760 mg of benzoic acid, 360 mg of triethylamine and 600 mg of 1-hydroxybenzotriazole and N, N-dimethylformamide 10 m 1 To the solution of (1), 690 mg of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride was added, and the mixture was stirred at room temperature for 3.5 hours. Water was added to the reaction solution and extracted with ethyl acetate. The extract was washed successively with water and saturated saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained crystalline residue was recrystallized from ethanol to give ethyl 4- [2- [N- (4-hydroxy-3-methylphenyl) potumbamoyl] phenoxy] butyrate 560 mg I got

Physicochemical properties

 Mass spec (m / z): 358 (M + 1) +

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ 1.23 (3 Η, t), 2.1 to 2.7 (7 Η, m), 4.14 (2 H, q), 4.25 (2 Η, t), 6.29 ( 1 H, s), 6.72 (1 Η, d), 6.9 to 7.6 (5 Η, m), 8.27 (1 Η, dd), 9.67 (1 Η, s)

Reference Example 90

 In the same manner as in Reference Example 89, ethyl 4- [2- [N-([2,3-dimethyl-4-hydroxyphenyl)]] lubamoyl] phenoxy] petitate was obtained.

Starting compound: 4-amino-2,3-dimethylphenol

Physicochemical properties

 Mass spec (mZz): 372 (M +)

 Nuclear magnetic resonance spectrum (CDC 1, TMS internal standard)

 5: 1.22 (3H, t), 2 1 3 (3 H, s)

 2.20 (3 H, s), 2 24 (2 H, m)

 2.5 1 (2 H, t), 4 1 1 (2 H, q)

 4.28 (2 H, t), 6 25 (1 H, s)

 6.5 1 (1H, s), 704 (1H, d)

 7.Table 7.2 (2 H, m), 77 .. 4488 ((11 HH, d t),

8.3 1 (1H, dd), 934 (1H, s) Reference example 9 1

 In the same manner as in Reference Example 89, ethyl 4- [2- (N- (4-hydroxy2,5-dimethylphenyl) -lubamoyl] phenoxy] butylene was obtained.

Starting compound: 4-amino-2,5-dimethylphenol Physicochemical properties

 Mass spec (m / z): 37 1 (M +)

 Nuclear magnetic resonance spectrum (CD C1, TMS internal standard)

 6: 1.21 (3 H, t), 2.13 (3 H, s),

 2.16 (3 H, s), 2.2 1 to 2.60 (4 H, m),

4.11 (2H, q), 4.27 (2H, t), 6.45 (1H, s), 6.84 (1H, s), 6.99-9 . 5 9 (4 H, m),

 8.32 (1H, dd), 9.31 (1H, s) Reference example 9 2

 In the same manner as in Reference Example 89, ethyl 4- [2- [N- (3-hydroxyphenyl) -rubamoyl] phenyloxy] butylate was obtained. Starting compound: 3-aminophenol

Physicochemical properties

Mass spectrum (mZz): 343 (M ⁺ )

Nuclear magnetic resonance spectra (CD C 1 _3, TMS internal standard)

 δ: 1.24 (3Η, t), 2.2 to 2.7 (4 H, m), 4.15 (2 H, q), 4.26 (2 H, t), 6. 6 to 7.6 (7 H, m), 7.91 (1 H, t), 8.24 (1 H, dd), 9.92 (1 H, s) Reference example 9 3

 In the same manner as in Reference Example 89, ethyl 4- [2- [N- (3-hydroxy2-methylphenyl) -lubamoyl] phenyloxy] butyrate was obtained.

Starting compound: 3-amino-2-methylphenol

Physicochemical properties

 Mass spec (mZ z): 358 (M + 1 +)

Nuclear magnetic resonance spectra (CD C 1 _3, TMS internal standard)

5: 1.22 (3 H, t), 2.17 (3 H, s),

--1 o

 2.2 to 2.6 (4Η, m), 4.11 (2H, q), 4.30 (2Η, t), 6.04 (1H, s),

 6.5 9 (1Η, d), 6.9 to 7.3 (3Η, m), 7.3 to 7.6 (2Η, m), 8.32 (1Η, dd) 9 . 5 2 (1Η, s)

 Reference example 9 4

 In the same manner as in Reference Example 89, ethyl 4- [2- (Ν- (3-hydroxy-4-methylphenyl) -lubamoyl] phenoxy] butyrate was obtained.

 Starting compound: 3-amino-6-methylphenol

 Physicochemical properties

Mass spec (mZ z): 358 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard) 6:. 1 2 4 ( 3 H, t), 2. 2 1 (3 H, s),

 15 2 3 to 2.5 (2 H, m), 2.5 to 2.7 (2 Η, m),

 4 1 6 (2 Η, q), 4.26 (2 Η, t),

 6 8 2 (1Η., Dd), 6 9 to 7.3 (4Η, m) 7 4 8 (1Η, dt), 8 2 8 (1Η, dd), 9 8 8 (1Η, s)

 0 Reference example 9 5

Ethyl 4- [2 [Ν- (4-hydroxy-3-methylmethyl) -rubamoyl] phenyloxy] butylate 340 mg, 1- (4-isobutylphenyl) ethyl bromide 25 Omg and tetrab To a solution 5 of 3O mg of thiammonium ester and 8 ml of 2-butanone was added 16 O mg of potassium carbonate, and the mixture was heated under reflux for 20 hours. After allowing to cool to room temperature, water was added, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and eluted with a mixed solution of hexane: ethyl acetate (4: 1) to give a residue. 37-Omg of ethyl 4- [2- [N- [4- (isobutyl-α-methylbenzyloxy) -3-methylphenyl] potumbamoyl] phenyloxy] butyrate was obtained.

 Physicochemical properties

 Mass spec (m / z): 5 18 (M + 1) +

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 6: 1.90 (6 H, d), 1.2 2 (3 H, t)

 1. 6 2 (3 H, d), 1 8 5 (1 H, m)

2.27 (2 H, m), 2 32 (3 H, s)

2.45 (2 H, d), 2 56 (2 H, t)

 4.1 5 (2 H, q), 4 2 5 (2 H, t)

 5.28 (1 H. q), 6 7 0 (1 H, d)

 7.0 1 (1 H, d), 7 1 to 7.2 (3 H m),

7.2 to 7.4 (3H, m), 7.4 to 7.5 (2H, m).

8.28 (1H, dd), 9.64 (1H, s) Reference example 9 6

 In the same manner as in Reference Example 95, ethyl 4- [2- [N- [4-1- (4-isobutyl-methylbenzyloxy) -1,2,5-dimethylphenyl] potumbamoyl] phenoxy] butylate was obtained.

Raw material compound: ethyl 4- [2— [N— [4— (4-hydroxyloxy)

 2,5-Dimethylphenyl] lvamoyl] phenyl] butylate

Physicochemical properties

Mass spec (mZ z): 5 3 2 (M + 1) ⁺

 Nuclear magnetic resonance spectrum (CD C 13, TMS 'internal standard)

 6: 0.89 (6 H, d), 1.20 (3 H, t),

1.61 (3H, d), 1.85 (1H, m), 2.17 (3H, s), 2.19 to 2.22 (2H, m), 2.28 (3 H, s) .2.46 (2 H, q) 4.06 to 4.13 (2 H, m), 4.26 (2 H, t),

5.25 (1 H, q), 6.56 (1 H, s),

7.01 (1H, d), 7.09 to 7.12 (3H, m), 7.25 to 7.29 (2H, m),

 7.42 to 7.47 (1H, m), 7.62 (1H, s),

8.2 8 (1 H, d d) .9.2 4 (1 H, s) Reference example 9 7

 In the same manner as in Reference Example 95, ethyl 4- [2— [N— [3— (4-1-isobutylbenzyloxy) phenyl] -lubamoyl] phenoxy] petitate was obtained.

Starting compound: ethyl 4- [2- [N- (3-hydroxyphenyl) dirubamoyl] phenoxy] butylate Physicochemical properties

 Mass spec (mZ z): 490 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.91 (6 Η, d) 1.22 (3 H, t),

 1.87 (1 H, m) 2.30 (2 H, m),

2.48 (2 H, d) 2.57 (2 H, t),

4. 1 2 (2 H, q) 4. 2 7 (2 H, t),

5.07 (2 H, s) 6.75 (1 H, d d),

 7.0 1 (1 H, d) 7.0 to 7.2 (4 H, m),

7.2 to 7.3 (1 Hm), 7.36 (2H, d), 7.47 (1H, dt), 7.63 (1H, s),

 8.27 (1H, dd), 9.86 (1H, s) Reference example 9 8

 In the same manner as in Reference Example 95, ethyl 4- [2— [N— [3 -— (4-isobutyl-α-methylbenzyloxy) -12-methylphenyl] potumbamoyl] phenyloxy] butylate was obtained.

Starting compound: ethyl 4- [2— [Ν- (3-hydroxy-1-2-me Tylphenyl) rubamoyl; 1 phenyl) butylene h

 Physicochemical properties

 Mass spec (mZz): 5 18 (M + 1) +

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ 0 89 (6 Η, d), 1 23 (3 Η, t

 1 62 (3 H, d), 1 84 (1 Η, m

 2 24 (2 Η, m), 2 30 (3 Η, s

 2 44 (2 Η, d), 2 5 1 (2 Η, t

 4 12 (2 Η, q), 4 32 (2 Η, t

 5 29 (1 Η, q), 6 58 (1 Η, d

 7, 0 to 7.2 (5Η, m), 7.27 (2Ηd), 7.48 (1 (, dt), 7.58 (1Η, d), 8.30 (1Η, dd), 9.5 1 (1 Η, s) Reference example 99

 In the same manner as in Reference Example 95, ethyl 4- [2- [N- [3- (4-isobutyl-methylbenzyloxy) -14-methylphenyl] potumbamoyl] phenyloxy] butylate was obtained.

Raw material compound: ethyl 4- [2— [N— (3-hydroxy-4

 Methylphenyl) rubamoyl] phenoxy] petitate

Physicochemical properties

Mass spec (mZ z): 518 (M + 1) ⁺

Nuclear magnetic resonance scan Bae-vector (CDC 1 _3, TMS internal standard)

 δ: 0.88 (6 Η, d) 1.23 (3 H, t)

 1.63 (3 H, d) 1.84 (1 H, m)

 2.23 (2 H, m) 2.26 (3 H, s)

 2.43 (2 H, d) 2.52 (2 H, t)

4.13 (2H, q) 4.23 (2H, t) 5.43 (1 H, q), 693 (1 Η, d),

 6.98 (1 H, d), 70-7.2 (4 Η, m),

7.33 (2 Η, d), 7 4 5 (2 Η, m),

8.25 (1 Η, d), 9 6 8 (1 Η, s)

Reference example 1 0 0

 In the same manner as in Reference Example 95, ethyl 4- [2— [Ν— [2,3-dimethyl-2- (4, -dimethylbenzyloxy) phenyl] carbamoyl] phenoxy] butylate was obtained.

 Starting compound: ethyl 4- [2— [Ν — [(2,3-dimethyl-

 4-Hydroxyphenyl)] Lubamoyl] Phenoxy] Petrate, 1 — (4-Methylphenyl) ethyl

 Physicochemical properties

Mass spec (mZ z): 490 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

6: 1.21 (3 H, t), 1.62 (3 H, d),

 2.17 to 2.22 (2 H, m), 2.22 (3 H, s), 2.28 (3Η, s), 2.32 (3Η, s), 2 . 4 9 (2 H, t), 4.09 (2 H, q), 4.26 (2 H, t), 5.25 (1 H, q),

6.62 (1H, d), 7.01 to 7.47 (8H, m), 8.26 (1H, dd), 9.24 (1H, s) Reference example 1 0 1

 In the same manner as in Reference Example 95, ethyl 4- [2— [N— [2,3-dimethyl-41- (4-propyl-1-α-methylbenzyloxy) phenyl] -lubamoyl] phenoxy] Obtained.

Starting compound: Ethyl 4- [2— [Ν— (2,3-dimethyl-41-hydroxyphenyl) -rubamoyl] phenyloxy] butylate, 1-1- (4-propylphenyl) ethyl bromide Mid

 Physicochemical properties

 Melting point 85 to 86 ° C

Elemental analysis (C ₃₂ H ₃₉ NO: as j)

 C (%) H (%) N (%) Theoretical value 7 4.2.5 5.7.5 9 2.71 1 Experimental value 7 4. 2 4 7. 3 7 2. 7 4 Reference example 10 2

 In the same manner as in Reference Example 95, ethyl 4- [2- [N- [2,3-dimethyl-41- (4-ethyl-methylbenzyloxy) phenyl] pyruvamoyl] phenyloxy] butyrate was obtained.

 Raw material compound: Ethyl 4- [2- [N- (2,3-dimethyl-4-hydroxyphenyl) dirubamoyl] phenyloxy] butyrate, I- (4-ethylphenyl) ethyl bromide

Physicochemical properties

 Mass spec (mZ z): 504 (M + 1) +

 Nuclear magnetic resonance spectrum (CDC13, TMS internal standard)

 δ: 1.2 1 (3 Η, t) 1.2 7 (3 H, t),

 1. 6 2 (3 H, d) 2.17 to 2.24 (2 H, m),

2.2 2 (3 H, s) 2.28 (3 H, s),

2.49 (2 H, t) 2.62 (2 H, q),

4.10 (2 H, q) 4.26 (2 H, t),

5.26 (1 H, q) 6.62 (1 H, d),

7. 0 7. 4. 8 (8 H, m),

 8.26 (1H, dd), 9.25 (1H, s) Reference example 10 3

Ethyl 4- [2 -— [N- (4-benzhydrylamino-2-methylphenyl) caprolbumoyl] phenoxy] as in Reference Example 9-5 I got a petit rate.

Starting compound: ethyl 4- [2- [N- (4-amino-2-methyl

 [Phenyl] lervamoyl] phenoxy] butyrate physicochemical properties

 Mass spec (m / z): 522 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 1 2 1 (3 Η, t) 2.19 (5 H, m)

 2 48 (2 H, t) 4.10 (2 H, q) 4 20 (1 H, m) 4.25 (2 H, t) 5 49 (1 H, s) 6.42 (2 H, t) m) 7 0 1 (1H, d) 7.10 (1H, t) 7.2 to 7.4 (10H, m), 7.44 (1H, dt), 7.52 (1 H, d), 8.26 (1 H, dd), 9.20 (1 H, s)

Reference Example 1 04

 In the same manner as in Reference Example 95, ethyl 4- [2- [N- [4- [bis (4-propylphenyl) methylamino] -12-methylphenyl] lubamoyl] phenyloxy] butylate was obtained.

Raw material compound: Ethyl 4- [2- [N- (4-amino-2-methyl) caprubamoyl] phenyloxy] butylate Physicochemical properties

 Mass spec (m / z): 606 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 «5: 0.93 (6 H, t) 1.2 1 (3 H, t)

 1.6 1 (4 H, m) 2.19 (5 H, m)

2.48 (2 H, t) 2.56 (4 H, t)

 4.10 (2 H, q) 4.17 (1 H, s)

 4.25 (2 H, t) 5.43 (1 H, s)

6. 4 1 (2 H, m) 7.0 1 (1 H, d) 1

 74

7.09 to 7.13 (5 H, m), 7.24 (4 H, d),

7.44 (1 H, d t), 7.5 1 (1 H, d),

 8.26 (1 H, d d), 9.18 (1 H, s) Reference example 10 5

 Ethyl 4- [2- [N- (2,3-Dimethyl-4-hydroxyphenyl) caproluvyl] phenoxy] butylate 37 Omg and 10 ml of tetrahydrofuran in 40 ml of a solution of 60% sodium hydride were added at room temperature. For 1 hour. The solvent of the reaction solution was removed under reduced pressure, and the obtained residue was dissolved in 5 ml of N, N-dimethylformamide. This solution was added to a solution of 25 Omg of 11- (4-isopropylphenyl) ethyl bromide and 5 ml of N, N-dimethylformamide under ice-cooling, and the mixture was stirred at room temperature for 4 hours. To the reaction wave was added 100 ml of ethyl group, washed with water, washed with saturated saline, and concentrated under reduced pressure. The resulting oil was subjected to silica gel column chromatography (using 50 g of silica gel) to obtain toluene. Elution with a mixture of ethyl acetate = 9: 1, and ethyl 4- [2-[N- [2,3-dimethyl-4-1 (4-isopropyl-1-methyl-benzyloxy) phenyl] -pyrvamoyl] phenoxy] butylate 15 Omg I got

Physicochemical properties

Mass spec (m / z): 5 18 (M + 1) ⁺

Nuclear magnetic resonance spectra (CD C 1 _3, TMS internal standard)

 δ: I.20 (3Η, t), 1.23 (6H, d),

 1.62 (3 H, d), 2.20 (2 H, t), 2.22 (3 H, s), 2.28 (3 H, s), 2.49 (2 H , t), 2.88 (1 H, quint),

4.09 (2 H, q), 4.26 (2 H, t),

5.27 (1 H, q), 6.64 (1 H, d),

7. 0 1 to 7.47 (8 H, m),

8.26 (1H, dd), 9.26 (1H, s) Reference Example 1 06

 4- (4-Isobutyl-methyl-methylbenzyloxy)-1,2,6-dimethylnitrobenzene To a solution of 51 mg of Omg in 25 ml of ethanol, 45 mg of platinum oxide was added, and the mixture was stirred under a hydrogen atmosphere at normal pressure and room temperature for 7 hours. The insoluble material was removed by filtration, the solvent of the filtrate was distilled off under reduced pressure, the residue was dissolved in toluene (25 ml), and the solvent was again distilled off under reduced pressure to obtain crude 4- (4-isobutyl-methylbenzyl). 1) 6,6-dimethylaniline was obtained. To a solution of 0.33 ml of this compound and 0.31 ml of methylene chloride in 10 ml of methylene chloride, crude 2-((3-ethoxycarbonylpropane) prepared from 47-mg of 2- (3-ethoxyquincarbonylpropoxy) benzoic acid was added. Xy) A benzoylc mouth ride was added under ice-cooling, and the mixture was stirred at room temperature overnight. To the reaction mixture was added 5 Oml of ethyl ethyl acetate, washed successively with water, 1 N hydrochloric acid, saturated saline, saturated aqueous sodium hydrogen carbonate, and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography, and eluted with a mixture of hexane: ethyl ethyl ester (4: 1), and ethyl 4- [2-—N— [4 -— (4-isobutyl-methylbenzolo). Xy) 1,2,6-Dimethylphenyl] lubamoyl] phenoxy] petitate 360 mg was obtained.

Physicochemical properties

Mass spec (m / z): 532 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 5: 0.89 (6H, d), 1.20 (3H, t),

 1.57-1.61 (5Η, m), 1.85 (l H, m), 2.20 (6 H, s), 2.44-2.49 (4 H, m),

4.08 (2 H, q), 4.24 (2 H, t),

5.26 (1 H, q), 6.64 (1 H, s),

7.02 (1 H, d), 7.09 to 7.12 (3 H, m), 7.26 to 7.29 (2 H, m), 7.44: ~ 7.48 (1 H, m),

 8.24 (1 H, d d), 8.85 (1 H, s) Reference example 107

 In the same manner as in Reference Example 106, ethyl 4- [2- [N- [4- (4-isobutyl-methylbenzyloxy)]-1,2,3,5-trimethylphenyl] pyruvamoyl] phenyloxy] butyrate was obtained. . Starting compound: 4-1 (4-isobutyl-1-methylbenzyloxy) -1,2,3,5-trimethylnitrobenzene

 Physicochemical properties

 Mass spec (mZ z): 546 (M + 1) +

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 5: 0.91 (6 Η, d), 1.22 (3 H, t),

 1.59-: I. 62 (3 H, m), 1.87 (1 H, m), 2.09 (3 H, s), 2.16 (3 H, s), 2.17 ( 3 H, s), 2.20 to 2.26 (2H, m),

2.47 to 2.52 (4H, m), 4.11 (2H, q), 4.29 (2H, t), 4.85 (1H, q), 7.04 (1H , d), 7.1 1 to 7.14 (3H, m), 7.31 (2H, d), 7.45 to 49. (2H, m), 8.30 (1 H, dd), 9.35 (1 H, s) Reference example 1 08

 In the same manner as in Reference Example 106, ethyl 4- [2- [N- [2-ethyl (4-isobutyl-methylbenzyloxy) phenyl]]-rubumoyl] phenoxy] petitate was obtained.

Starting compound: 3-ethyl-4,12-trough [1- (4-isobutylphenyl) ethoxy] benzene

Physicochemical properties

Mass spec (mZ z): 532 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard) δ o 88 6 H, d), 1.20 (6 H, m)

 1 62 3 H, d), 1.85 (1 H, m) 2 202 H, m), 2.45 (4 H, m)

 2 60 2 H, q), 4.10 (2 H, q)

 4 27 2 H, t), 5.27 (1 H, q)

 6 72 1 H, d d), 6.79 (1 H, d),

 7 0 1 1 H, d), 7.10 (3 H, m)

 27 2 H, m), 7.45 (1 H, m)

 7 64 1 H, d), 8.27 (1 H, d)

 99. 2266 (1 H, s)

Reference Example 1 09

 A solution of 4- (4-isobutylbenzyloxy) -12-methylaniline (214 mg 0.79 mmo1), triethylamine 5001, methylene chloride (or tetrahydrofuran) in a 2 ml solution at room temperature was added with 2- (3- (Ethoxycarbonylpropoxy)) A 500/1 solution of benzoyl chloride (2,15 mg, 0.79 mmol) in methylene chloride (or tetrahydrofuran) was added, and the mixture was stirred for 20 minutes. The reaction solution was poured into ice-1N hydrochloric acid and extracted with ethyl acetate. The extract was washed with water and saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography, eluting with a mixture of hexane: ethyl acetate (6: 1). The desired ethyl was obtained in an amount of 255 mg of 4- [2- [N- [4- (4-isobutylbenzyloxy) -12-methylphenyl] -lubamoyl] phenyloxy] butylate.

Physicochemical properties

Mass spectrometry value (mZz): 504 (M + 1) ⁺ 147 (base peak) Nuclear magnetic resonance spectrum (27 OMHz, CDC13, TMS internal standard)

δ: 0.90 (6 Η, d), 1.2 1 (3 H, t), 1 7 8〜: I. 9 3 (1 H, m),

 2 2 3 (2 H, q u int), 2.31 (&, 3 H),

4 1 1 (2 H, q), 4.29 (2 H, t), 2 48 (2 H, d), 2.49 (2 H, t),

5, 0 3 (2 H, s), 6.85 to 6.89 (2 H, m), 06 (1 H, d), 7.14 (1 H, t),

 7 11 88 ((22 HH ,, dd)), 7.36 (2 H, d), 745 to 7.5 2 (1 H, m), 7.82 (1 H, d), 8 3 1 (1 H, dd), 9.36 (1 H, s) Reference example 1 1 0

 In the same manner as in Reference Example 100, ethyl 4- [2— [N— [2,3—dimethyl- (4-isobutylbenzyl) oxyphenyl] carbamoyl] phenoxy] butylate was obtained.

Starting compound: 2,3-Dimethyl-41- (4-isobutylbenzyloxy) aniline, 2- (3-ethoxycarbonyl) propyloxybenzoyl compound

 Mass spectrometry value (mZz): 518 (M + 1) + 115 (base peak) Nuclear magnetic resonance spectrum (27 OMHz, CDC13, TMS internal standard)

 δ: 00.90 (6Η, d), 1.2 1 (3 H, t),

 1 79-; I.92 (1H, m),

 2 2 2 (2 H, q u int), 2.25 (3 H, s),

2 2 6 (3 H, s), 2.49 (2 H, d)

 2 5 0 (2 H, t) 4 1 2 (2 H, q)

 4 2 9 (2 H, t) 5 0 5 (2 H, s)

 6 8 6 (1 H, d) 7 0 6 (1 H, d)

 7, 1 4 (1 H, t) 7 1 9 (2 H, d)

7.37 (2H, d) 7.46 to 7.52 (1H, m), 7.53 (1 H, d), 8.31 (1 H, dd), 9.34 (1 H, s)

Reference example 1 1 1

 In the same manner as in Reference Example 109, ethyl 4- [2- [N- [4-[(4-isobutyl-methyl) benzylbenzyloxyphenyl] pothambamoyl] phenyloxy] petite

Starting compounds: 4- (4-isobutyl-methyl-benzyloxy) aniline, 2- (3-ethoxycarbonyl) propyloxybenzoyl

Physicochemical properties

 Mass spectrometry value (m / z): FAB (P 0 s.)

5 0 4 (M + 1) ⁺ 16 1 (base peak) δ: 00.89 (6H, d), 1.22 (3H, t),

 1 62 (3H, d), 1.79 to 1.90 (1 H, m), 2 27 (2 H, quint), 2.45 (2 H, d), 25 6 (2 H , T) 4 1 4 (2 H, q), 4 2 6 (2 H, t) 5 2 9 (1 H, q), 6 8 9 (2 H, d) 7 0 2 (1 H, d) , 7 1 1 (2 H, d) 7 1 2 (1 H, t), 7 26 (2H, d) 7 44 to 7.5 1 (1 H, m), 7 5 3 (2 H, d) 8 2 9 (1 H, dd),

 9 7 0 (1 H, s)

Reference example 1 1 2

 In the same manner as in Reference Example 109, ethyl 4- [2- [N- [4 (a-ethyl-41-isobutylbenzyloxy) phenyl] pyrvamoyl] phenoxy] petitate was obtained.

Starting compound: 41- (Naethyl-41-isobutylbenzyloxy) aniline, 2- (3-ethoxycarbonyl) propyloxybenzoyl compound Physicochemical properties

 Mass spectrometry value (mZz): FAB (Pos.)

5 1 9 (M + D) + 3 4 3 (base peak) Nuclear magnetic resonance spectra (2 7 OMH z, CDC 1 3, TMS internal standard)

 δ: 0.87 (6 Η, d), 0.99 (3 H, t),

 1.20 (3Η, t), 1.78 to 1.92 (2H, m), 1.91 1−2.0.8 (1Η, m),

 2.26 (2Η, quint), 2.44 (2Η, d), 2.55 (2Η, t), 4.13 (2Η, q), 4.22 55 (( 22 ΗΗ ,, tt)), 4 98 (1 Η, t), 6.88 77 ((22 ΗΗ ,, dd)), 700 ((1 Η, d),

7.1 1 (2 Η, d) 1 2 (1 Η, t),

7.2 2 (2 Η, d) 7 4 3 to 7.5 2 (1 Η, m),

7.5 0 (2 Η, d) 8 2 7 (1 Η, d d),

9.6 7 (1 Η, s)

Reference example 1 1 3

 In the same manner as in Reference Example 109, ethyl 4- [2 -— [Ν- [4-1- (4-isobutyl-methylbenzyloxy) -12-methylphenyl] potumbamoyl] phenyloxy] butylate was obtained.

Starting compound: 4- (4-Isobutyl-I-methylbenzyloxy)

 2-Methylaniline, 2- (3-ethoxycarbonyl)

Physicochemical properties

Mass spectrometry value (mZ z): FAB 518 (M + 1) ⁺ ,

 1 6 1 (base peak)

Nuclear magnetic resonance spectra (2 7 OMH z, CD C 1 3, TMS internal standard)

δ: 0.89 (6 Η, d), 1.22 (3 H, t), 1 6 3 (3 H, d), 1.7 7 to 1.92 (1 H, m), 2 20 (2 H, quint), 2.25 (3 H, s), 2 4 6 (2 H, d) 2.48 (2 H, t), 4 10 (2 H, q) 4.28 (2 H, t), 52 9 (1 H, q) 6.74 ~ 6.80 (2 H, m), 7 0 5 (1 H, d) 7.1 4 (2 H, d),

1 4 (1 H, t) 7.27 (2 H, d),

 7.4 4 to 7.5 1 (1 H, m), 7.73 (1 H, d),

8.30 (1 H, d d), 9.32 (1 H, s) Reference example 1 1 4

 In the same manner as in Reference Example 109, ethyl 4- [2- (N- [4- (a-ethyl-41-isobutylbenzyloxy) -12-methylphenyl] potumbamoyl] phenyloxy] butylate was obtained.

Starting compounds: 4- (ethyl-41-isobutylbenzyloxy) -12-methylaniline, 2- (3-ethoxycarbonyl) propyloxybenzoyl compound

Physicochemical properties

 Mass spectrometry value (mZz): FA B (Pos.)

5 3 2 (M + 1) ⁺ 17 5 (base peak) Nuclear magnetic resonance spectrum (27 OMHz, CDC 1 o, TMS internal standard)

 6: 0.88 (6 H, d), 0.99 (3 H, t),

 1.20 (3 H, t), 1.7 7 to 1.90 (2 Η, m), 1.92 to 2.0 7 (1 Η, m),

 2.20 (2Η, q u int), 2..24 (3Η, s),

2.46 (2Η, t), 4.11 (2Η, q), 4.28 (2Η, t), 4.99 (1Η, t),

6.73 (1Η, d d), 6.79 (1 9, d),

7.05 (1Η, d), 7.12 (2Η, d), 7.14 (1 H, t), 7.27 (2 H, d),

 7.45 to 7.5 1 (1 H, m), 7.68 (1 H, d),

8.29 (1 H, d d), 9.29 (1 H, s) Reference example 1 1 5

 In the same manner as in Reference Example 109, ethyl 4- [2- [N- [4-isobutyl-iso-isopropylbenzyloxy) phenyl] carbamoyl] phenoxy] butylate was obtained.

 Starting compounds: 4- (4-isobutyl-α-isopropylbenzyloxy) aniline, 2- (3-ethoxycarbonyl) propyloxybenzoyl compound

 Physicochemical properties

 Mass spectrometry value (mZz): FAB (Pos.)

5 3 2 (M + 1) ⁺ 18 9 (base peak) Nuclear magnetic resonance spectrum (27 OMHz, CDC13, TMS internal standard)

 δ: 0.87 (6Η, d), 0.88 (3 H, d),

 1.06 (3 H, d), 1.22 (3 H, t), 1.79 ~: 1.90 (1 H, m),

 2 0 5 to 2.2 1 (1 H, m),

 2 2 6 (2 H, q u int), 2.45 (2 H, d), 2 56 (2 H, t), 4 1 4 (2 H, q),

4 2 6 (2 H, t), 4 6 7 (1 H, d), 6 8 6 (2 H, d), 7 0 2 (1 H, d),

7, 1 1 (2 H, d), 7 1 4 (1 H, t),

 2 4 (2 H, d), 7.4 4 to 7.5 2 (1 H, m),

7 4 9 (2 H, d), 8 29 (1 H, d d), 9 6 7 (1 H, s)

Reference example 1 1 6

In the same manner as in Reference Example 109, etil 4-1 [2 — [N— [4-(4 —Isobutyl-α-isopropylbenzyloxy) -12-methylphenyl] lubamoyl] phenoxy] petitate was obtained.

Starting compound: 4- (4-isobutyl-1-isopropylbenzyloxy) -12-methylanilin, 2- (3-ethoxycalponyl) propyloxybenzoyl compound

 Mass spectrometry value (mZ z): F A B (P os.)

 5 4 6 (M + 1) + 18 9 (base peak) Nuclear magnetic resonance spectrum (27 OMHz, CDC13, TMS internal standard)

 δ: 00.87 (6Η, d), 0.87 (3Η, d),

 1 0 5 (3 Η, d), 1.20 (3 Η, t), 178-: I. 90 (1 H, m),

 2 0 4 to 2.1 1 (1 H, m),

 2 2 0 (2 H, quint), 2.23 (3 H, s), 24 4 (2 H, d), 2.49 (2 H, t), 4 1 1 (2 H, q ) 4 2 8 (2 H, t), 4 7 7 (1 H, d) 6 7 1 (1 H, dd), 6 7 7 (1 H, d) 7 0 5 (1 H, d), 7 1 1 (2 H, d) 7 1 3 (1 H, t), 7 2 4 (2 H, d) 7 4 5 to 7.5 2 (1 H, m), 7 6 6 (1 H, d ) 8 3 0 (1 H, dd), 9 2 8 (1 H, s)

Reference Example 1 1 7

 In the same manner as in Example 109, ethyl 4- [2— [N— [3-chloro-1- (4-isobutyl-methylbenzyloxy) phenyl] potumbamoyl] phenyloxy] butylate was obtained.

Starting compound: 3-chloro-4-1 [1- (1-isobutylphenyl) ethoxy] aniline Physicochemical properties

 Mass spectrum (mZz): 538 (M +)

Nuclear magnetic resonance spectrum (CDCI _3, TMS internal standard)

 δ: 0.87 (6 Η, d), 1.2 1 (3 Η, t),

 1 66 (3 H, d), 1.6 to 2.0 (1 Η, m), 16 to 2.6 (6 Η, m) 4.1 2 (2 Η, q), 423 (2 T, t), 528 (1Η, q), 676 (1Η, d), 69-7.6 (8Η, m), 778 (1Η, d), 822 (1Η) , Dd), 9 66 (1 Η, s)

Reference example 1 1 8

 In the same manner as in Reference Example 109, ethyl 4- [2- [Ν- [4- (4-isobutyl-1-propylbenzyloxy) -12-methylphenyl] potumbamoyl] phenoxy] butylate was obtained.

Starting compound: 4-1 (4-isobutyl-one-propylbenzyloxy)

 1-Methylaniline, 2- (3-ethoxycarbonyl) propyloxybenzoyl alcohol

Physicochemical properties

Mass spec (mZz): FAB 546 (M + 1) ⁺ ,

 93 (base peak)

Nuclear magnetic resonance spectra _{(27 OMH z, CDC 1 3} , TMS internal standard)

 δ 0 88 (6H, d), 0.94 (3 H, t),

 1 20 (3H, t), 1.36 ~: L. 58 (2 H, m), 1 69 ~: I. 89 (2 H, m),

 1 90-2.04 (1 H, m),

2 20 (2 H, qu int), 2.23 (3 H, s), 245 (2 H, t), 4.10 (2 H, q), 4 27 (2H, t), 5. 06 (1 H, dd), 6 72 (1 H, dd), 6.77 (1 H, d), 704 (1 H, d), 7.11 (2H, d), 7 1 2 (1 H, t), 7 24 (2H, d), 677 02247111 44 to 7.52 (1H, m), 7.67 (1H, d), 829 (1H, dd), 9.28 (1H, s ) Reference example 1 1 9

 In the same manner as in Reference Example 109, ethyl 4- [2- [N- [4- [4- (4-isopropylbenzyloxy) phenyl] carbamoyl] carboxy] petitate was obtained.

Starting compounds: 4- (4-isobutyl-α-propylbenzyloxy) aniline, 2- (3-ethoxycarbonyl) propyloxybenzoyl compound

Physicochemical properties

Mass spectrometry value (mZz): FAB 532 (M + 1) ⁺

 1 47 (base peak)

Nuclear magnetic resonance spectra _{(27 OMH z, CDC 1 3} , TMS internal standard

 Associate)

 δ: o87 (6H, d), 0.94 (3H, t),

 21 (3H, t), 1.33 ~: I. 55 (2H, m), 70 ~: I. 89 (2 H, m),

 90〜2.05 (1 H, m),

 26 (2 H, qu int), 2.43 (2 H, d), 55 (2H, t), 4.13 (2 H, q),

 25 (2 H, t) 5 05 (1 H, d d),

6. 8866 ((22 HH ,, dd)) 7 0 1 (1 H, d), 1 1 (2 H, d) 7 1 3 (1 H, t),

 26 (2 H, d) 7.43 to 7.51 (1 H, m), 49 (2 H, d) 8 27 (1 H, d d),

9 67 (1 H, s) Reference example 1 2 0

 In the same manner as in Reference Example 109, ethyl 4- [2- [N- [4- [a-, 4-diisobutylbenzyloxy] -l-methylphenyl] -potamoyl] phenyloxy] butylate was obtained.

 Starting compounds: 4- (α, 4-diisobutylbenzyloxy) -12-methylaniline, 2- (3-ethoxycarbonyl)

 Physicochemical properties

Mass spec (m / z): FAB (p 0 s.) CD _Q OD added

 56 1 (M + D) + 1 47 (base peak) Nuclear magnetic resonance spectrum (27 OMHz, CDC13, TMS internal standard)

 δ: 0.86 (6 Η, d), 0.93 (3 Η, d),

 0.97 (3Η, d), 1.18 (3Η, t), 1.48: I.59 (1Η, m),

 1 7 8 to 2.0 1 (3 Η, m),

 2 1 8 (2 Η, quint), 2.22 (3 Η, s), 2 42 (2 Η, d), 2.46 (2 Η, t), 4 0 9 (2 Η, q) , 4.26 (2Η, t), 5, 11 (1 1, dd), 6.71 (1Η, dd), 6, 76 (1Η, d), 7.03 (1Η) , d), 7.10 (2 Η, d), 7 1 2 (1 Η, t), 7.26 (2 Η, d), 7.42 to 7.50 (1 Η, m), 7. 6 6 (1Η, d), 8 2 8 (1Η, dd), 9.28 (1Η, s)

Reference example 1 2 1

In the same manner as in Reference Example 109, ethyl 4- [2- [N- [4- (, (diisobutylbenzyloxy) phenyl] potumbamoyl] phenoxy] butylate was obtained. Starting compounds: 4- (α, 4-diisobutylbenzyloxy) aniline, 2- (3-ethoxycarbonyl) propyloxy benzoyl chloride

Physicochemical properties

 Mass spectrometry value (m / z): FAB (P 0 s.)

5 4 6 (M + 1) ⁺ , 1 4 7 (base peak) Nuclear magnetic resonance spectrum (27 OMH z, CDC 13, TMS internal standard)

 δ 0 8 7 (6 H, d), 0.94 (3 H, d),

 0 9 8 (3 H, d), 1.2 1 (3 H, t), 15 1 to 1.60 (1 H, m),

 1 7 8 ~ 2.0 2 (3 H, m),

 2 25 (2 H, quint), 2.43 (2 H, d), 25 4 (2 H, t), 4 13 (2 H, q), 4 25 (2 H, t), 5 1 3 (1 H, dd),

 6 8 6 (2 H, d), 700 (1 H, d), 7 1 1 (2 H, d), 7 1 3 (1 H, t), 26 (2 H, d), 7. 42 ~ 7.5 1 (1 H, m),

7 4 9 (2 H, d), 8 2 7 (1 H, d d),

 9 6 7 (1 H, s)

Reference example 1 2 2

 In the same manner as in Reference Example 109, ethyl 4- [2- [N- [2,3-dimethyl-41- (naethyl-41-isobutylbenzyloxy) phenyl] -levamoyl] phenyloxy] petite was obtained.

Starting compounds: 2,3-Dimethyl-41- (naethyl-4-isobutylbenzyloxy) aniline, 2- (3-ethoxycalponyl) propyloxybenzoyl compound

Mass spectrometry value (mZz): FAB (pos.) C D3 OD added 547 (M + D) ⁺ 1 75 (base peak) Nuclear magnetic resonance spectrum (27 OMHz, CDC13, TMS internal standard)

 δ: 0 8 8 (6 H, d), 1. 00 (3 H, t),

 1 20 (3 H, t), 1.79 to 2.09 (3 H, m), 2 20 (2 H, quint), 2.23 (3 H, s), 2 3 1 ( 3 H, s), 2.44 (2 H, d), 249 (2 H, t), 1 1 (2 H, q) 4, 2 7 (2 H, t), 50 2 (1 H, t) 6.5 9 (1 H, d) 04 (1 H, d) 7.1 1 (2H, d) 7 1 2 (1 H, t)

 2 6 (2 H, d) 7 3 0 (1 H, d)

 7. 4 3 to 7.5 1 (1 H, m),

 8.28 (1H, dd), 9.26 (1H, s) Reference Example 1 23

 In the same manner as in Reference Example 109, ethyl 4- [2- [N- [2,3-dimethyl-41- (4-isobutyl-1-isopropylbenzyloxy) phenyl] potumbamoyl] phenyloxy] butylate was obtained. Starting compounds: 2,3-dimethyl-4- (4-isobutyl-iso-propylbenzyloxy) aniline, 2- (3-ethoxycarbonyl) propyloxybenzoyl compound,

Physicochemical properties

Mass spectrometry (πιΖz): FAB (P os.) CD ₃ OD added

56 1 (M + D) + 1 89 (base peak) Nuclear magnetic resonance spectrum _{(27 OMH z, CDC 1 3} , TMS internal standard)

 δ: 0.87 (6 Η, d), 0.94 (3 Η, d),

1.04 (3Η, d), 1.20 (3 (, t), 1 76-: I. 89 (1 H, m),

 2 07 ~ 2.23 (1 H, m),

 2 20 (2H, qu int), 2.22 (3H, s), 236 (3H, s), 2.43 (2H, d) 2 48 (2H, t) 4 1 0 (2 H, q) 4 26 (2 H, t) 4 84 (1 H, d) 6 53 (1 H, d) 7 03 (1 H, d) 7 09 (2 H, d) 7 1 7 (1 H , t) 7 2 1 (2 H, d) 7 26 (1 H, d) 77.44 to 7.5 1 (1 H, m),

 8 27 (1 H, d d), 9.23 (1 H, s) Reference example 1 24

 In the same manner as in Reference Example 109, ethyl 4- [2- [N- [5-promo 2,3-dimethyl-41- (4-isobutyl-methyl-benzyloxy) phenyl] -pyrvamoyl] phenoxy] butyrate was obtained. .

Starting compound: 5-promo 2,3-dimethyl-41- (4-isobutyl-1-methylbenzyloxy) aniline, 2- (3-ethoxycarbonyl) propyloxybenzoyl alcohol

Reference Example 1 25

 In the same manner as in Reference Example 109, ethyl 41- [2- [N- [3,5-dimethyl-41- (4-isobutyl-α-methylbenzyloxy) phenyl] potumbamoyl] phenyloxy] butylate was obtained.

Starting compounds: 3,5-Dimethyl-41- (4-isobutyl-methylbenzyloxy) aniline, 2- (3-ethoxycalponyl) propyloxybenzoyl compound Physicochemical properties

Mass spectrometry value (mZz): FAB (P 0 s.) 5 3 2 (Μ + 1) +, 16 1 (base peak) Nuclear magnetic resonance spectrum (40 O MH ζ, TMS internal standard)

 6: 0.90 (6 Η, d), 1.24 (3 H, t),

 1.63 (3H, d), 1.81 to: L. 91 (1H, m), 2.13 (6H, s), 230 (2H, quint),

2.47 (2 H, d), 25 8 (2 H, t) 4.14 (2 H, q), 42 7 (2 H, t) 4.87 (1 H, q) , 7 0 1 (1 H, d) 7.12 (2 H, d), 7 1 3 (1 H, t) 7.29 (2 H, d), 7 2 9 (2 H, s)

7. 4 4 to 7.4.8 (1 H, m),

 8.27 (1 H, d d), 9.6 7 (1 H, s) Reference example 1 2 6

 In the same manner as in Reference Example 109, ethyl 4- [2- [N- [4-(a, 4-diisobutylbenzyloxy) -12,3-dimethylphenyl] potumbamoyl] phenoxy] butylate was obtained.

Starting compounds: 4-(, 4-diisobutylbenzyloxy) -1,2,3-dimethylaniline, 2- (3-ethoxyquincarbonyl) propyloxybenzoyl compound

Physicochemical properties

Mass spectrometry value (mZz): FAB (P os.) CD ₃ CD added

547 (M + D) +, 1 47 (base peak) Nuclear magnetic resonance spectra (2 7 OMH z, CDC 1 3, TMS internal standard)

 δ: 0.89 (6 Η, d), 0.95 (3 H, d),

 0.99 (3 H, d), 1.2 1 (3 H, t), 1.55 to: I. 64 (1 H, m),

 1.80-: I. 95 (2 H, m),

1.95 to 2.12 (1 H, m), 2.23 (2H, qunt), 2.25 (3H, s)

2.33 (3 H, s) 2.47 (2 H, d),

2.53 (2 H, t). 1 2 (2 H, q),

4.27 (2 H, t) 5.15 (1 H, d d),

6.6 1 (1 H, d) 7.04 (1 H, d), 7.12 (2 H, d) 7.13 (1 H, t),

7.25 (2 H, d) 7.32 (1 H, d),

7.45 to 7.52 (1 H, m),

 8.33 (1 H, dd), 9.3 1 (1 H, s) Reference example 1 27

 In the same manner as in Reference Example 1 09, ethyl 4- [2- [N- [2-methyl-2- (α, 4-diisobutylbenzyloxy) -1,3,5-dimethylphenyl] -lvamoyl] phenyloxy] Obtained. Starting compound: 2-methyl-4-1 [1-1 (4-isobutylphenyl) -1-3-methylbutoxy] nitrobenzene Physicochemical properties

Mass spec (m / z): 560 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.88 (6Η, d), 0.96 (6 H, q),

 1.20 (3 H, t), 1.52-: 1.61 (1Η, m),

1.8 1 to 1.89 (1 H, m),

 1.92 ~ 2.00 (1 H, m),

 2.17 to 2.26 (2 H, m), 223 (3 H, s), 2.42 to 2.49 (4 H, m), 409 (2 H, q), 4.25 ( 2 H, q), 5.10 (1 H, q),

6.68 to 6.75 (2 H, m),

 7. 0 1 to 7.29 (6H, m),

 7.43 to 7.47 (1 H, m), 7.64 (1 H, d),

8.26 (1 H, dd), 9.26 (1 H, s) Reference example 1 2 8

 2,3-dimethyl-41- [1- (4-isobutyl) phenyl] butoxyaniline 1.1 g, 2- (3-ethoxycarbonylpropoxy) benzoic acid 94 O mg, triethylamine 41 O mg, 1 To a solution of 680 mg of hydroxybenzotriazole and 4 Om1 of N, N-dimethylformamide was added 780 mg of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimid hydrochloride, and the solution was added. The mixture was heated to 0 ° C and stirred for 12 hours. Water was added to the reaction mixture to stop the reaction, ethyl acetate was added, and the mixture was washed with water and saturated saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography, and eluted with a mixture of hexane: ethyl acetate (4: 1), and ethyl 4- [2- [N- [2,3-dimethyl-4-1 ( There was obtained 1.68 g of 4-isobutyl-α-propylbenzyloxy) phenyl] lvamoyl] phenoxy] butyrate.

Physicochemical properties

 Nuclear magnetic resonance spectrum (27 OMHz, CDC 13. TMS internal standard)

 δ: 0.89 (6Η, d), 0.95 (3 H, t),

1. 2 1 (3 H _f t), 1.35 to 1.5 1 (2H, m), 1.74 to: I. 9 1 (2 H, m),

 1 9 6 to 2.10 (1 H, m),

2 2 2 (2 H, quint), 2.25 (3 H, s), 2 32 (3 H, s), 2.46 (2 H, d), 25 2 (2 H,) , 4.15 (2 H, q), 4 3 1 (2 H, t), 5 14 (1 H, dd), 666 (1 H, d), 709 (1 H, d) ), 7.16 (2 H, d), 7 17 (1 H, t), 7.24 (2 H, d), 7, 30 (1 H, d), 7.48 ~ 7.5 3 (1 H, m), 8.33 (1 H, m), 9.3 1 (1 H, s)

Reference Example 1 2 9

 In the same manner as in Reference Example 109, ethyl 4- [2- [N- [4-[(4-isobutyl-N-methylanilino) methyl] phenyl] carbamoyl] phenyloxy] petite was obtained.

Starting compound: 4-1 [4- (4-isobutyl-N-methylanilino)] methyl] aniline

Physicochemical properties

 Mass spec (mZz): 502 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TM S internal standard)

 δ: 0.88 (6 Η, d) 1.20 (3 H, t)

 1.77 (1 H, m) 2.27 (2 H.m)

 2.35 (2 H, t)

 2.96 (3 H, s) 4.12 (2 H, q)

 4.26 (2 H, t) 4.47 (2 H, s)

 6.71 (2 H, d) 7.01 (3 H, d)

 7.13 (1H, t) 7.24 (2H, d)

 7.47 (1 H, d t), 7.63 (2 H, d),

 8.28 (1 H, d d), 9.84 (1 H, s) Reference example 1 30

 In the same manner as in Reference Example 109, ethyl 4- [2- [N- [4-1-((N-ethyl-41-isobutylanilino) methyl] phenyl] carbamoyl] phenoxy] petitate was obtained.

Starting compound: 4-1 [4- (N-ethyl-41-butylbutylarino) methyl] aniline

Physicochemical properties

 Mass spec (mZz): 5 16 (M + 1) +

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

6: 0.86 (6 H, d), 1. 1.3 (6 H, m), 1.76 (1H, m), 227 (2H, t)

 2.33 (2 H. d), 2 56 (2 H, t)

2.43 (2 H, q), 4 1 2 (2 H, q)

4.25 (2 H, t), 4 46 (2 H, s)

6.65 (2 H, d), 6 9 7 (2 H, d)

7.01 (1H, d), 7.13 (1H, t) 7.25 (2H, d), 7.47 (1H, dt), 7.62 (2H, d) , 8.28 (1 H, dt), 9.84 (1 H. s)

Reference example 1 3 1

 In the same manner as in Reference Example 109, ethyl 4- [2- [N- [4-[(N, 4-diisobutylanilino) methyl] phenyl] pyruvamoyl] phenyloxy] butylate was obtained.

Starting compound: 4- [4- (N, 4-diisobutylanilino) methyl] aniline

Physicochemical properties

 Mass spectrometry (mZz): 544 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.87 (6 Η, d), 0 95 (6 H, d)

 1.2 1 (3 H, t), 1 77 (1 H, m)

 2.1 2 (1 H, m), 2 28 (2 H, m)

 2.3 3 (2 H, d), 2 56 (2 H, d)

 3.18 (2 H, d), 4 1 1 (2 H, q)

 4.26 (2 H, t), 4 55 (2 H, s)

 6.60 (2 H, d), 6, 93 (2 H, d)

 7.00 (1 H, d), 7.1 2 (1 H, t)

7.18 (2 H, d), 7, 46 (1 H, dt), 7.59 (2 H, d), 8.27 (1 H, dd), 9.8 1 (1 H, s ) Reference Example 1 32

 In the same manner as in Reference Example 109, ethyl 4- [2- [N- [4-[[(4-isobutyl-N-propylanilino) methyl] phenyl] phenylbamoyl] phenoxy] petitate was obtained.

Raw material compound: 4-[(4-isobutyl-N-propylanilino) methyl] aniline

Physicochemical properties

 Mass spec (m / z): 530 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ 0 88 6 Η, d) 0.92 (3 H, t)

 1 2 1 3 H, t) 1.66 (1 H, m)

 1 77 1 H, m) 2.28 (2 H, m)

 2 35 2 H, d) 2.56 (2 H, t)

 3 32 2 H, t) 4.12 (2 H, q)

 4 26 2 H, t) 4.50 (2 H, s)

 6 6 1 2 H, d) 6.95 (2 H, d)

 00 1 H, d) 7.1 2 (1 H, t)

 7 22 2H, d) 7.46 (1 H, d t), 7 6 12 H, d) 8.27 (1 H, d d) Reference example 1 33

 In the same manner as in Reference Example 109, ethyl 4- [2- [N- [4-1-((4-isobutyl-N-methylanilino) methyl] -12-methylphenyl] pyruvamoyl] phenoxy] butylate was obtained.

Starting compound: 4-[(4-isobutyl-N-methylanilino) methyl] -12-methylaniline

Physicochemical properties

Mass spec (m / z): 5 16 (M ⁺ )

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

δ: 0.89 (6Η, d), 1.2 1 (3H, t), 1.80 (1H, m), 2 2 (2H, m)

 2.3 1 (3 H, s), 2 3 7 (2 H, d)

249 (2 H, t), 2 96 (3 H, s)

4.10 (2 H, q), 4 3 1 (2 H, t)

4.44 (2 H, s), 67 I (2 H, d)

7.00 (2 H, d), 7 0 5 (1 H, d)

7.13 (3H, m), 748 (1H, t)

7.96 (i n, d), 8 3 0 (1 H, d)

9.4 7 (1 H, s)

 Reference example 1 3 4

 In the same manner as in Reference Example 109, ethyl 4- [2- [N- [3-[(4-isobutyl-N-methylanilino) methyl] -12-methylphenyl] lubamoyl] phenoxy] butylate was obtained.

Starting compound: 3-[(4-isobutyl-N-methylanilino) methyl] 1-2-methylaniline

Physicochemical properties

 Mass spec (mZz): 5 16 (M +)

Nuclear magnetic resonance spectra (CD C 1 _3, TMS internal standard)

 6: 0.89 (6 H, d), 1.22 (3 H, t)

 1.79 (1H, m), 2.24 (2H, m)

2.27 (3 H, s), 3.37 (2 H, d)

 2.52 (2 H, t), 2.98 (3 H, s)

 4.1 1 (2 H, q), 4.3 1 (2 H, t)

 4.46 (2 H, s), 6.65 (2 H, d)

 7.00 (2 H, d), 7.06 (1 H, m)

 7.Table 7.3 (3 H, m), 7.49 (1 H d t),

7.7 2 (1 H, d), 8.3 1 (1 H, d d)

9.5 1 (1 H, s)

Reference example 1 3 5 In the same manner as in Reference Example 109, ethyl 4- [2- [N- [4-[2- (4-isobutyl-N-methylanilino) ethyl] phenyl] -force rubamoyl] phenoxy] petitate was obtained.

Raw material compound: N— (4-aminophenethyl) 1-41-isobutyl—N-methylaniline

Physicochemical properties

 Mass spec (m / z): 5 16 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.90 (6Η, d), 1.24 (3H, t),

 1.81 (1 Η, m), 2.31 (2 H, m),

2.38 (2 Η, d), 2.58 (2 H, m),

2.83 (2Η, t), 2.89 (3H, s),

3.5.3 (2 Η, t), 4.15 (2 H, q),

4.28 (2 Η, t), 6.68 (2 H, d),

7.02 (3 Η, m), 7.14 (1 H, t),

7.20 (2 Η, d), 7.47 (1 H, d t),

 7.61 (2 Η, d), 8.28 (1 H, d d),

 9.8.2 (1 Η, s)

Reference Example 1 3 6

 In the same manner as in Reference Example 109, ethyl 4- [2- [N- [4- (4-isobutylbenzyl) -1-N-methylamino] phenyl] carbamoyl] pentinoquine] butylate was obtained.

Starting compound: 4- [N- (4-isobutylbenzyl) -1-N-methyl; amino] aniline

Physicochemical properties

 Mass spectrometry value (mZz): 502 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 6: 0.89 (6 H, d), 1.23 (3 H, t),

1.84 (1H, m), 2.28 (2H, m), 2.44 (2 H, d), 2.56 (2 H, m),

 3.00 (3 H, s), 4.12 (2 H, q),

4.25 (2 H, t), 4.49 (2 H, s),

6.77 (2H, m), 6.99 (1H, d),

7. 0 to 7.2 (5 H, m), 7.44 (1 H, d t), 7.52 (2 H, d), 8.28 (1 H, d d),

9 6 6 (1 H, s)

Reference Example 1 3 7

 Hydrogenation of ethyl 4- [2- [N- (4-amino-2-methylphenyl) pothamamoyl] phenoxy] butyrate 37 Omg and 4-isobutylbenzaldehyde in dichloroethane 7 ml in a stream of argon 33 Omg of sodium triacetoxyborohydride and 6 Omg of acetic acid were added sequentially, and the mixture was stirred at room temperature for 5 hours. Water was added to the reaction solution, which was concentrated under reduced pressure, and the obtained residue was extracted with ethyl acetate. The extract was washed with saturated saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and eluted with a mixture of hexane: ethyl (3: 1) to give ethyl 4- [2- [N— [4- (4-isobutylbenzyl) amino] -ethyl. 2-Methylphenyl] lvamoyl] phenoxy] butylate 51 Omg was obtained.

Physicochemical properties

 Mass spectrometry value (πιΖζ): 5 0 2 (M +)

Nuclear magnetic resonance spectra (CD C 1 _3, TMS internal standard)

 6: 0.90 (6 H, d) 1.2 2 (3 H, t),

 1.85 (1 H, m) 2.21 (2 H, m), 2.25 (3 H, s) 2.45 to 2.5 1 (4 H, m), 4.11 ( 2 H, q) 4.27 (4 H, m),

6.5 5 (2 H, m) 7.0 2 (1 H, d),

7.09 to 7.13 (3H, m),

7, 2 6〜7.2 9 (2 H, m), 7.45 (1 H, dt), 7.63 (1 H, d),

8.28 (1H, dd), 9.25 (1H, s) Reference Example 1 38

 In the same manner as in Reference Example 57, ethyl 4- [2- [N- [4-1- [N- (4-isobutylbenzyl) -1-N-methylamino] -12-methylphenyl] potumbamoyl] phenoxy] petitate was obtained. .

Starting compound: ethyl 4- [2- [N- [4-1- [N- (4-isobutylbenzyl) amino] -12-methylphenyl] -lvamoyl] ethoxy] petitate

 Physicochemical properties

 Mass spec (mZz): 5 16 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ 0 89 (6 Η, d), 1.22 (3 H, t),

 1 84 (1H, m), 2.22 (2H, m), 228 (3H, s), 2.44 to 2.51 (4H, m), 299 (3H, s), 4 1 1 (2 H, q), 428 (2 H, t), 4.49 (2 H, s), 666 (2 H, m) 7.03 (1 H, d),

 08 to 7.16 (5H, m), 7.46 (1 H, t),

7 68 (1 H, m), 8.29 (1 H, d d), 9 28 (1 H, s)

Reference Example 1 39

 In the same manner as in Reference Example 26, 4- (4-isopropylphenol) 2-token benzene was obtained.

Starting compounds: 4-isopropylphenol, 4-fluoronitrobenzene

Physicochemical properties

Mass spectrometry (mZ z): 258 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard) 5: 1.27 (6H, d), 2.95 (1H, m),

 6. 9 to 7.4 (6 H, m), 8.1 to 8.3 (2 H, m) Reference example 1 40

 In the same manner as in Reference Example 26, 4- (4-butylphenoxy) nitrobenzene was obtained.

 Starting compound: 4-butylphenol, 4-fluoronitrobenzene Physicochemical properties

 Mass spectrometry (mZz): 27 1 (M +)

Nuclear magnetic resonance scan Bae-vector (CD C 1 _3, TMS internal standard)

 δ: 0.95 (3Η, m), 1.1 to: I.8 (4H, m),

 2.64 (2 H, t), 6.8 to 7.3 (6 H, m), 8.0 to 8.3 (2 H, m)

Reference example 1 4 1

 In the same manner as in Reference Example 61, 4- (4-isopropylphenoxy) aniline was obtained.

Raw material compound: 4- (4-isopropylphenol) nitrobenzene Physicochemical properties

Mass Spectrometry (mZz): 2 27 (M ⁺ )

Nuclear magnetic resonance scan Bae-vector (CD C 1 _3, TMS internal standard)

 <5: 1.22 (6 H, d), 2.87 (1 H, m),

 3.37 (2 H, m), 6.6 to 7, 3 (8 H.m) Reference Example i 42

 In the same manner as in Reference Example 61, 4- (4-butylphenoxy) aniline was obtained.

Raw material compound: 4- (4-butylphenol) nitrobenzene Physicochemical properties

 Mass analysis mass (mZz): 2 4 1 (M +)

Nuclear magnetic resonance scan Bae-vector (CD C 1 _3, TMS internal standard)

δ: 0.92 (3Η, m), 1.1 to: I. 8 (4 H, m), 2.56 (2H, t), 3.0 to 3.6 (2H, m), 6.5 to 7.2 (8H, m)

Reference Example 1 43

 In the same manner as in Reference Example 128, ethyl 4- [2- [N- [4- (4-isopropylphenoxy) phenyl] -lubamoyl] phenoxy] petitate was obtained.

Raw material compound: 4- (4-isopropylphenol) aniline Physicochemical properties

 Mass spec (mZz): 46 1 (M +)

Nuclear magnetic resonance scan Bae-vector (CDC 1 _3, TMS internal standard)

 5: 1.2 to 1.3 (9 H, m), 2.30 (2 H, m),

2 57 (2H, t), 2.90 (1H, m), 413 (2H, q), 4.28 (2H, t), 693 (2H, dd), 7. 0 1 (3 H, m),

 7 1 3 (1 H, t), 7.18 (2 H, d), 7 47 (1 H, d t), 7.64 (2 H, d),

 8 28 (1 H, dd), 9.80 (1 H, s) Reference example 1 44

 In the same manner as in Reference Example 128, ethyl 4- [2- [N- [4 (4-butylphenyloxy) phenyl] -lubamoyl] phenyloxy] petitate was obtained.

Physicochemical properties

Mass spectrum (mZz): 475 (M ⁺ )

Nuclear magnetic resonance scan Bae-vector (CDC 1 _3, TMS internal standard)

 δ: 0.93 (3Η, t), 123 (3H, t)

 1.36 (2 H, m) 1.60 (2 H, m)

 2.30 (2 H, m) 2.58 (4 H, m)

 4.13 (2 H, q) 4.27 (2 H, t)

6.9 1 (2 H, m) 7.0 1 (3 H, m) 7.14 (3H, m), 7.47 (1H, dt),

 7.64 (2 H, m), 8.28 (1 H, d d), 9.8 1 (1 H, s)

 Reference Example 1 45

 In the same manner as in Reference Example 16, ethyl 41- [0— [N— (p-phenoxyphenyl) -lubamoyl] phenoxy] butylate was obtained. Starting compound: P-Phoxynoxyline, 0— (3-Ethoxycarbonylpropoxy) benzoyl chloride Physicochemical properties

Mass spec (m / z): 19 (M ⁺ )

Nuclear magnetic resonance scan Bae-vector (CDC 1 _3, TMS internal standard)

 6: 1.24 (3 H, t), 2.24 ~ 2.35 (3 H, m), 2.5 1 ~ 2.6 1 (2 H, m), 4 1 3 (2 H, q ), 4.28 (2H, t), 7.00-7, 05 (5 H, m), 7.0 9-7.17 (2 H, m),

 7.3 1 to 7.37 (2 H, m),

 7. 4 5 to 7.5 2 (1 H, m),

 7.6 4 to 7.7 0 (2 H, m),

 8.30 (1 H, d d), 9.84 (1 H, s) Reference example 1 46

 In the same manner as in Reference Example 26, 41- (3-isopropylphenoxy) ditrobenzene was obtained. )

Starting compound: 3-isopropylphenol

Physicochemical properties

 Mass spec (mZz): 25.7 (M +)

Nuclear magnetic resonance spectra (CD C 1 _3, TMS internal standard)

 δ: I.26 (6Η, d), 2.93 (1H, m),

 6. 8 to 7.5 (6 H, m),

8. 1 to 8.3 (2 H, m) Reference example 1 4 7

 In the same manner as in Reference Example 26, 4- (5-isopropyl-12-methylphenoxy) nitrobenzene was obtained.

Raw material compound: 5-Isopropyl-2-methylphenol

Physicochemical properties

 Mass spec (mZz): 27 1 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 6: 1.24 (6 H, d), 2.12 (3 H, s),

 2.89 (1 H, m), 6.8 to 7.3 (5 H, m), 8.0 to 8.3 (2 H, m)

Reference example 1 4 8

 In the same manner as in Example 61, 41- (5-isopropylphenyloxy) aniline was obtained.

Starting compound: 4- (3-isopropylphenoxy) nitrobenzene

Physicochemical properties

 Mass spec (mZz): 2 27 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 6: 1.21 (6 H, d), 2.86 (1 H, m),

 3.5 3 (2 H, m), 6.6 to 7.0 (7 Η, m),

7.1 to 7.3 (1 Η, m)

Reference example 1 4 9

 In the same manner as in Reference Example 61, 41- (3-isopropyl-12-methylphenoxy) aniline was obtained.

Starting compound: 4- (5-Isopropyl-2-methylphenoxy) di-pi

Physicochemical properties

 Mass spec (m / z): 2 4 1 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard) δ: 1.16 (6 Η, d), 2.2 2 (3 Η, s),

 2.78 (1 Η, m), 3.49 (2 Η, m), 6.6 to 7.0 (6 Η, m), 7.13 (1 Η, d) Reference example 1 5 0

 In the same manner as in Reference Example 128, ethyl 4- [2- [N- [4-1- (3-isopropylphenoxy) phenyl] -lubamoyl] phenoxy] butylate was obtained.

Raw material compound: 4- (3-isopropylphenoxy) aniline Physicochemical properties

Mass spec (mZz): 6 1 (M ⁺ )

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 1.2 to: I.3 (9Η, m), 2.31 (2H, m),

2.58 (2 H, t), 2.88 (1 H, m),

4.14 (2 H, q), 4.28 (2 H, t),

6.80 (1 H, d d), 6.91 (1 H, t),

 6.96 (1H, d), 7.02 (3H, m), 7.14 (1H, t), 7.23 (1H, t),

7.48 (1 H, d t), 7.65 (2 H, d d),

8.2 9 (1 H, d d), 9.83 (1 H, s) Reference example 1 5 1

 In the same manner as in Reference Example 128, ethyl 4- [2- [N- [4-[(5-isopropyl-1-2-methylphenoxy) phenyl] caprubamoyl] phenoxy] butylate was obtained.

Starting compound: 4- (5-isopropyl-1-2-methyl) aniline Physicochemical properties

 Mass spec (mZz): 4 7 5 (M +)

Nuclear magnetic resonance spectra (CD C 1 _3, TMS internal standard)

δ: 1.1 to: I.3 (9 H, m), 2.20 (3 H, s), 2.30 (2 H, m), 2.58 (2 H, t), 2.83 (1 H, m) 4.13 (2 H, q),

 4.27 (2 H, t) 6.79 (1 H, d),

6.90 (2 H, d) 6.94 (1 H, d d)

7.01 (1H, d) 7.13 (1H, t), 716 (1H, d) 7.47 (1H, dt) 761 (2H, d) 8. 28 (1 H, d)

 9 79 (1 H, s)

Example 1

 Ethyl 4- [o— [N— [2,3-Dimethyl-41- (p-isobutyl-methylbenzyloxy) phenyl] capillubamoyl] phenoxy] butylate 1.75 g of tetrahydrofuran (8 ml) A 1N aqueous sodium hydroxide solution (8 ml) was added to a mixed solution of methanol (8 ml), and the mixture was stirred at room temperature for 1.5 hours. 1N hydrochloric acid (8.5 ml) was added to the reaction mixture, and the mixture was extracted with ether. The extract was washed with saturated saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was recrystallized from a mixture of hexane and ether to form 4- [o- [N- [2,3-dimethyl-41- (p-isobutyl-methylbenzyloxy) phenyl] -pyrvamoyl] phenoxy] butanoic acid 1. 36 g were obtained. Physicochemical properties

 Melting point 1 40-1 4 1 ° C Recrystallized from methylene chloride-hexane

Elemental analysis (as C ₃₁ H ₃₇ N0 ₅₎

 C (%) H (%) N () Theoretical 73.93 7.40 2.78 Experimental 73.82 7.57 2.77 Mass Spec. (M / z): 504 (M + 1) +

Infrared absorption spectrum (KB r) cm— ¹ : 3600-2700 (br),

3400 (m), 2970 (s), 1716 (s), 1 666 (s), 1 604 (s), 1 534 (s), 1 258 (s), 1 1 66 (s), 756 (s)

Nuclear magnetic resonance spectrum (DMS 0—d ₆ , TMS internal standard)

 δ: 0.84 (6Η, d), I. 55 (3 H, d),

 1.75 ~: I.84 (1H, m),

 2.00 (1 H, qu int) 2.13 (3 H, s), 2.20 (3 H, s), 2.40 (2 H, t), 2.41 (2 H, d) , 4.15 (2 H, t), 5.42 (1 H, q), 6.70 (1 H, d), 7.02 to 7.08 (2H, m), 7.12 (2 H , D),

7.16 (1H, d), 7.31 (2H, d), 7.46 (1H, t), 7.68 (1H, d), 9.47 (1H, s ), 12.14 (1 H, s) Example 2

 In the same manner as in Example 1, forty-one [o- [N- (p-phenyloxyphenyl) pyruvamoyl] phenoxy] butanoic acid was obtained.

Raw material compound: Ethyl 4- [0— [N— (p-phenyloxyphenyl) pothamamoyl] phenoxy] butyrate Physicochemical properties

Melting point 1 twenty-nine to thirteen 1 ° recrystallization Elemental analysis of C ethanol monohydrate (as C ₂₃ H ₂₁ N0 ₅₎

C (%) H (%) N (%) Theoretical 70. 58 5. 4 1 3.58 Experimental 70. 6 1 5. 46 3.54 Mass spectrometry (m / z): 392 (M + 1) ⁺

Infrared absorption spectrum (KB r) cm— ¹ : 3335 (s), 3500-3000 (br), 1735 (s), 1650 (s), 1605 (s), 1560 (s), 1505 (s) ), 1490 (s), 1 455 (s), 1 4 10 (s), 1 24 0 (s), 1 1 7 5 (s), 7 45 (s)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 5: 1.96 ~ 2.05 (2 H, m), 2.42 (2 H, t), 4.15 (2 H, m), 6.99 '7.20 (7 H, m) , 7.36-7.43 (2 H, m)

 7 4 7 ~ 7.53 (1 H, m)

 7 64 to 7.67 (1 H, m), 7.76 (2 H, d),

1 0 1 2 (1 H, s), 1 2. 1 2 (1 H, br) Example 3

 In the same manner as in Example 1, 4- [o— [N— [p- (3-methyl-3-phenylbutoxy) phenyl] -lubamoyl] phenyloxy] butanoic acid was obtained.

Starting compound: ethyl 4- [o— [N- [p- (3-methyl-3

 -Phenylbutoxy) phenyl] carbamoyl] phenoxy] butylate

Physicochemical properties

 Melting point 1 54〜1 56 ° C Recrystallized from ether

Elemental analysis value (as C ₂₈ H ₃₁ N05)

 C () H (%) N (%) Theoretical 72.86 6.77 3.03 Experimental 72.89 6.85 2.96 Mass Spec (mZz): 461 (M +)

Infrared absorption spectrum (KB r) cm— ¹ : 3 380 (s),

 3 600 to 300 0 (br), 2950 (s),

2 900 (s), 1 740 (s), 1655 (s), 1605 (s), 1550 (s), 1515 (s), 1250 (s), 1175 ( s), 1 16 0 (s), 760 (s) Nuclear magnetic resonance scan Bae-vector (DMS O d _6, TMS internal standard) δ 1 3 6 (6 Η , s), 2 0 0 (2 H, quint), 2 0 9 (2 Η, t), 2 4 0 (2 H, t), 3 7 5 (2 H, t), 4 13 (2 H, t), 676 (2 H, d), 7 0 5 (1 H, t), 7 1 5 (1 H, d), 7 1 9 (1 H, t) Example 4

 Ethyl 4- [o— [N— [p- (ρ-isobutylbenzyloxy) phenyl] -lvamoyl] -14-methylphenoxy] butylate 10 Omg of ethanol in 1.2 ml solution of dioxane 0 4 ml and 1.6 ml of a 5N aqueous sodium hydroxide solution were added, and the mixture was heated to 50 and stirred for 20 minutes. The reaction mixture was concentrated under reduced pressure, adjusted to pH 6 or lower with 10% hydrochloric acid, and extracted with ethyl ethyl sulfate. The extract was washed with saturated saline and dried over anhydrous sodium sulfate. The crystalline residue obtained by concentration under reduced pressure was recrystallized from aqueous ethanol to give 4-o- [N- [p- (p- (p-isobutylbenzyloxy) phenyl] pyruvamoyl] -14-methylphenoxy. 7 Omg of butanoic acid was obtained.

Physicochemical properties

 Melting point 1 2 1 to 1 2 2. C

Elemental analysis value (as C _2e H ₃₃ NO _s )

 C (%) H (%) N (%) Theoretical value 73.2 4 6.99 9 2.95 Experimental value 73.1 8 6.99 8 2.83 Mass spectrometry value (mZz): 4 76 (M + 1) +

Nuclear magnetic resonance spectrum (DMS 0—d ₆ , TMS internal standard)

 6: 0.86 (6 H, d), 1.83 (1 H, m),

1.99 (2 H, m), 1.28 (3Η, s), 2.4 to 2.5 (4Η, m), 4.10 (2Η, t), 5.04 (2 H, s) 6.99 (2 H, d)

 7.06 (1 H, d) 7.18 (2 H, d)

7 29 (1 H, d) 7.37 (2 H, d) 7 50 (1 H, s) 7.63 (2 H, d) 9 94 (1 H, s) 1 2.1 (1 H, d) s) Example 5

 In the same manner as in Example 4, 41- [0- [N- [p- (p-isobutylbenzyloxy) phenyl] -lubamoyl] phenoxy] -1,2,2-dimethylbutanoic acid was obtained.

Starting compound: ethyl 4- [0-N- [p- (p-isobutylbenzyloxy) phenyl] -l-bamoyl] phenyloxy] -1,2-dimethylbutyrate

Physicochemical properties

Melting point 1 52 ~ 1 53 ^e C

Elemental analysis (as C ₃₀ H ₃₅ NO _B)

C (%) H (%) N (%) Theoretical 73.60 7.2 1 2.86 Experimental 73.44 7.34 2.81 Mass Spec (mZz): 489 (M ⁺ )

Nuclear magnetic resonance scan Bae-vector (DMSO- d _6, TMS internal standard)

 δ 0.87 (6 Η, d) 1.16 (6 H, s)

 1.83 (1H, m) 2.03 (2H, t)

 2.46 (2 H, d) 4.17 (2 H, t)

 5.05 (2 H, s) 7.01 (2 H, d)

 7.07 (2 H, t) 7.19 (3 H, m)

 7.37 (2 H, d) 7.48 (1 H, t)

 7.6 to 7.7 (3 Hm), 9.95 (1 Hs)

In the same manner as in Example 4, 41 [o [N— [p- (p-isobutyl [Benzyloxy] phenyl] -N-methylcarbamoyl] phenoxy] butanoic acid was obtained.

 Starting compound: ethyl 4- [0— [N— [p— (p-isobutylbenzyloxy) phenyl] -1-N-methylcarbamoyl] phenoxy] butylate

 Physicochemical properties

Mass spec (mZ z): 4 7 6 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.89 (6H, d), 1.84 (1H, m),

 2.1-2.6 (6 H, m),

 3.17, 3.46 (total 3mm, each s),

3.92, 4.30 (total 2H, each t),

4.90, 5.02 (2 合 わ せ in total, each s),

 6.6 to 6.8 (3 H, m),

 6. 9 to 8.2 (10H, m)

Example 7

 In the same manner as in Example 4, [o— [N— [p- (p-isobutylbenzyloxy) phenyl] -lubamoyl] phenoxy] drunkic acid was obtained. Raw material compound: Ethyl [0— [N— [p— (p-isobutylbenzyloxy) phenyl] dirubamoyl] phenoxy]

Physicochemical properties

 Melting point 15 1 to: I 52. C

 Mass spec (mZ z): 4 3 4 (M + 1) +

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 6: 0.90 (6 H, d), 1.95 (1 H, m),

2.47 (2 H, d), 4.79 (2Η, s), 4.98 (2Η, s), 6.9 to 7.0 (3 9, m), 7.1 ~ 7.2 (3 Η, m), 7.32 (2 Η, d), 7.47 (1 H, t), 7.75 (2H, d),

 8.26 (1 H, d), 10.1 (1 H, s) Example 8

 In the same manner as in Example 4, [m- [N- [p- (p-isobutylbenzoyloxy) phenyl] -lubamoyl] phenoxy] acetic acid was obtained. Raw material compound: Ethyl [m— [N— [p— (p-isobutylbenzyloxy) phenyl] lubamoyl] phenoxyacetate

Physicochemical properties

 Melting point 2 14 to 2 15. C

 Mass spec (m / z): 434 (M + 1) +

Nuclear magnetic resonance spectrum (DMS 0—d ₆ , TMS internal standard)

 (5: 0.86 (6 H, d), 183 (1 H, m),

 2.45 (2 H, d), 478 (2 H, s), 5.06 (2 H, s), 70 1 (2 H, d), 7.1 to 7.2 (3 H.d) m) 7.3 to 7.5 (4H, m), 7.57 (1 H, d), 767 (2 H, d), 10.09 (1 H, s)

Example 9

 In the same manner as in Example 4, 41 [m [N- [p- (p-isobutylbenzyloxy) phenyl] -lubamoyl] phenyloxy] butanoic acid was obtained.

Raw material compound: ethyl 4- [m- [N- [p- (p-isobutylbenzyloxy) phenyl] -lubamoyl] phenyloxy] butylate

Physicochemical properties

 Melting point 1 69-1 70 ° C

Elemental analysis value (as C ₂₈ H ₃₁ N05 · 0.2H ₂₀ ) C (%) H (%) N (%) Theoretical 72.30 6.80 3.01 Experimental 72.22 6.74 3.03 Mass spec (m / z): 462 (M + 1) +

Nuclear magnetic resonance spectrum (DMS 0 - d _6, TMS internal standard)

 δ: 086 (6Η, d), 1.83 (1Η, m),

 97 (2 Η, m), 1.4: I.5 (4 H, m),

4 07 (2 Η, t), 5.05 (2 H, s),

7.0 1 (2 Η, d), 7.1 to 7.2 (3 H, m), 7.3 to 7.6 (5 Η, m), 7.68 (2 H _t d),

1 2. 2 (1 Η, s)

Example 10

 In the same manner as in Example 4, 41- [4-chloro-2- [Ν- [ρ- (ρ-isobutylbenzyloxy) phenyl] -lubamoyl] phenyl] butanoic acid was obtained.

Starting compound: Ethyl 4- [4-chloro-2- [Ν- [ρ- (ρ-isobutylbenzyloxy) phenyl] potylbamoyl] phenyloxy] butylate

Physicochemical properties

 Melting point 140 ~: 142 ° C

Elemental analysis value (C ₂₈ H _{3, as} N 0 ₅ CI)

 C (%) H (%) N (%) Theoretical 67.80 6.10 2.82 Experimental 68.05 6.2 1 2.67 Mass Spec (mZz): 496 (M +)

Nuclear magnetic resonance spectrum (DMS 0—d ₆ , TMS internal standard)

 δ: 0.87 (6 Η, d), 1.83 (1 H, m),

1.98 (2 H, m), 2.39 (2 H, t), 2.45 (2 H, d), 4.13 (2 H, t), 5.05 (2 H, s), 7.00 (2 H, d),

 7.1 to 7.3 (3H, m), 7.37 (2H, d), 7.53 (1H, dd), 7.6 (3H, m), 10.0 2 (1 H, s), 1 2. 1 2 (1 H, s)

Example 1 1

 In the same manner as in Example 4, 4- [2- [N- [p- (p-isobutylbenzyloxy) phenyl] -lubamoyl] -14-methoxyphenoxy] butanoic acid was obtained.

Starting compound: ethyl 4- [2- [N- [p- (p-isobutylbenzyloxy) phenyl] -lubamoyl] 4-methoxyphenoxy] butylate

Physicochemical properties

 Melting point 103 to 105 ° C

Elemental analysis value (as C _2e H ₃₃ N0 ₆ · 0 2 H ₂₀ )

C (%) H (%) N (%) Theoretical 70.34 6.80 2.83 Experimental 70.42 6.82 2.66 Mass spec (mZ z): 492 (M + 1) ⁺

Nuclear magnetic resonance spectra (D ₂ 0, TMS internal standard)

 5: 0.86 (6 H, d) 1.83 (1 H, m),

 1.99 (2 H, m) 2.40 (2 H, t), 2.45 (2 H, d) 3.75 (3 H, s), 4.08 (2 H, t) 5 . 04 (2 H, s),

6.98 (2 H, d) 7.05 (1 H, d d),

7.10 (1 H, d) 7.17 (2 H, d),

7.24 (1 H, d) 7.35 (2 H, d), 7.63 (2 H, dd), 10.0.0 (1 H, s) 1 2.13 (1 H, d) m)

Example 1 2 In the same manner as in Example 4, 4- [4-monofluoro-2- [N- [ρ- (ρ-isobutylbenzyloxy) phenyl] -lubamoyl] phenoxy] butanoic acid was obtained.

 Raw material compound: ethyl 4- [4-fluoro-2-— [Ν- [ρ-(ρ

 —Isobutylbenzyloxy) phenyl] lvamoyl] phenyloxy] butyrate

 Physicochemical properties

 Melting point 144-1 45 ° C

Elemental analysis value (C ₂₈ H _{3, as} NO _s F)

 C (%) H (%) N (%) Theoretical 7 0.1 3 6.3 1 2.92 2 Experimental 6 9.73 6.4 0 2.94 Mass Spec (mZ z): 4 8 0 (M + 1) +

Nuclear magnetic resonance spectrum (DMS 0- d _e, TMS internal standard)

 δ: 0.8 7 (6 Η. d), 1.83 (1 H, m),

 1.98 (2 H, m), 2.40 (2 H, t), 2.46 (2 H, d), 4 12 (2 H, t), 5.06 (2 H, t) s), 70 1 (2 H, d), 7.1 to 7.2 (3H, m) 7.3 to 7.4 (3H, m), 7.46 (1 H, dd), 7 6 3 (2 H, d),

1 0.0 (1 H, s), 1 2 1 (1 H, m)

Example 13

 4-Hydroxy 4 11 (p-isobutylbenzyloxy) 1-5 1-Benzanilide as raw material for ethyl 4- [p- [N- [p- (p-isobutylbenzyloxy) phenyl] pyruvamoyl] phenoxy Then, in the same manner as in Example 4, 41- [p- [N- [P- (P- (isobutylbenzyloxy) phenyl] -pyrvamoyl] phenoxy] butanoic acid was obtained.

Physicochemical properties Melting point 228 ~ 230 ° C

 Mass spec (m / z): 462 (M + 1) +

Nuclear magnetic resonance spectrum (DMS 0—d ₆ , TMS internal standard)

 δ: 0.87 (6 Η, d) 83 (1 H, m),

 1.97 (2 H, m) 4 to 2.5 (4 H, m),

4.08 (2 H, t) 05 (2 H, s),

7.00 (2 H, d) 06 (2 H, d),

7.19 (2 H, d) 37 (2 H, d),

7. 67 (2H, d) 95 (2H, d), 995 (1H, s). 15 (1H, s) Example 14

 Ethyl 4- [o- [N- [p- (p-isobutylbenzyloxy) phenyl] caprubayl] phenoxy] butylate 430 mg, methanol 3 ml and tetrahydrofuran 1.5 ml 1.5 ml of an aqueous sodium solution was added, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was acidified by adding 3 ml of 2N hydrochloric acid, and extracted with ether. The extract was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethanol / water to obtain 31 Omg of 41 [o- [N- [ρ- (ρ-isobutylbenzyloxy) phenyl] -caproluvyl] phenoxy] butanoic acid.

Physicochemical properties

 Melting point 1 32 to 1 35. C

Elemental analysis (as C ₂₈ H ₃₁ N0 ₅₎

 C (%) H (%) N (%) Theoretical 72.86 6.77 3.03 Experimental 72.62 6.86 2.84 Example 15

Ethyl 4- [N- [N- [2,3-dimethyl-41- (4-iso-butyl-propylbenzyloxy) phenyl] dirubamoyl] [Phenoxy] butyrate] To a mixed solution of 2.95 g of dioxane, 12 ml of dioxane and 35 ml of ethanol, 44 ml of a 5N aqueous sodium hydroxide solution was added, and the mixture was heated to 40 and stirred for 1.5 hours. The reaction solution was concentrated under reduced pressure, and the obtained residue was adjusted to pH <5 with 10% hydrochloric acid and extracted with ^ ethyl acetate. The extract was washed with saturated saline, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the obtained crystalline residue was recrystallized with a mixture of getyl ether and hexane. — 1.9 g of [2,3-dimethyl-41- (4-isobutyl-1-propylbenzyloxy) phenyl] lubamoyl] phenoxy] butanoic acid were obtained.

Physicochemical properties

Melting point 120-; 123 ° C (hexane-Et ₂₀ )

 Elemental analysis value (as C H ^ NOs)

C% H% N% Theoretical value 7 4. 5 5 7. 7 7 2. 6 3 Experimental value 74.5 8 7. 9 1 2. 6 2 Mass spectrometry value (mz): FAB (Pos.) 532 (M + 1) * nuclear magnetic resonance spectrum (50 OMH z, DMS 0- d 6, TMS Internal standard)

 δ: 0 83 (6 H, d), 0.89 (3 H, t),

 2.39 (2Η, t), 1.30 ~: I.49 (2H, m), 17 1 ~: I.86 (2 H, m),

 1 89 ~: I. 9 8 (1 H, m),

 2 0 2 (2 H, Qu int),

 2 1 3 (3 H, s), 2 2 1 (3 H, s)

 2, 3 9 (2 H, t), 2 4 0 (2 H, d)

 4.1 5 (2 H, t), 5 2 5 (1 H, t)

 6.62 (1 H, d), 70 2 (1 H, d)

 7.03 (1 H, t), 7 1 1 (2 H, d)

7.16 (1 H, d), 7 2 8 (2 H, d) 7.43 to 7.48 (1H, m), 7.68 (1H, dd), 9.46 (1H, s), 12.15 (1H, br) Example 16

 Example 911 In the same manner as in Example 5, 4- [2— [N— (4-isobutyl)

 .7

 N-dioxy-2-methylphenyl] lubamoyl] phenoxy] butanoic acid was obtained.

Starting compound: ethyl 4- [2- [N- (4-isobutyl) benzyloxy-2-methylphenyl] -lubamoyl] phenoxy] petitate

Physicochemical properties

Melting point 84 to 86 ° C (Hexane-Et ₂₀ )

Elemental analysis value (as C ₂₈ H ₃₃ NOs)

C (%) H (%) N (%) Theoretical 73.24 6.99 2.95 Experimental 73.07 6.97 2.94 Mass spectrometry (mZz): FAB (P 0 s.) 476 ( M + 1) ⁺ nuclear magnetic resonance spectrum (27 OMHz, CDC1a, TMS internal standard)

 δ: 0.90 (6Η, d), 1.78-: I. 94 (1H, m), 2.22 (2H, quint),

 2.29 (3 H, s),

 2.48 (2H, d), 2.56 (2 H, t), 4.30 (2 H, t), 5.02 (3 H, s),

6.84 to 6, 98 (2H, m), 7.05 (1H, d), 7.14 (1H, t), 7.18 (2H, d),

7. 3377 ((22 HH ,, dd)), 7.45 to 7.52 (1 H, m), 79 (1 H, d) 8.29 (1 H, d d),

 3 1 (1 H, s)

Example In the same manner as in Example 15, 4- [2- [N- [2,3-dimethyl-41- (4-isobutyl) benzyloxyphenyl] -caproluvamoyl] phenoxy] butanoic acid was obtained.

 Starting compound: ethyl 4- [2,3-dimethyl-41- (4-isobutyl) benzyloxyphenyl] rubamoyl] phenoxy] butylate

 Physicochemical properties

Melting point 92-94 ° C (Hexane-Et ₂₀ )

Elemental analysis (as C ₃ .H ₃₅ N0 ₅₎

C (%) H (%) N (%) Theoretical value 73.60 7.2 1 2.86 Experimental value 73.33 7.2 1 2.87 Mass spectrometry value (m / z): FAB (P 0 s .) 490 (M + 1) + nuclear magnetic resonance spectrum _{(27 OMH z, CDC 1 3} , TMS internal standard)

 5: 00.90 (6 H, d), 1.86 (1 H, m),

 2 22 (2 H, qu i n t),

 2 23 (3Η, s), 2.24 (3Η, s)

 2 48 (2Η, d), 2 55 (2H, t)

 4 29 (2 H, t), 5 04 (2 H, s)

 6 84 (1 H, d), 7 04 (1 H, d)

 7 14 (1H, t), 717 (2H, d)

 37 (2H, d) 7.44 to 7.52 (1H, m),

7.49 (1 H, d) 8 28 (1 H, d d), 9.27 (1 H, s)

Example 18

In the same manner as in Example 15, 4- [2- [N- [4- (4-isobutyl-methyl) benzyloxyphenyl] -lubamoyl] phenoxy] butanoic acid was obtained. Starting compound: ethyl 4- [2- [N- [4-1- (4-isobutyl-α-methyl) benzyloxyphenyl] rubamoyl] phenoxy] petitate

Physicochemical properties

 Mass spectrometry (m / z): FAB (P 0 s.) 476 (M + 1) +,

 1 6 1, (base peaK

Nuclear magnetic resonance spectra (27 OMH z, DMS 0- d 6, TMS Internal standard)

 (5: 00..82 (6 H, d), 1.5 1 (3 H, d),

 1. 7 1.90 (1 H, m),

 1.97 (2 H, qu int),

 2.39 (2 H, t) 2.40 (2 H, t) 4.1 2 (2 H, t) 5.43 (1 H, q)

6.87 (2 H, d) 7.05 (1 H, t)

7.13 (2H, d) 7.16 (1H, d) 7.32 (2H, d) 7.47 (1H, t) 7.54 (2H, d) 7.64 (1 H, d) 9.9 1 (1 H, s)

Example 19

 In the same manner as in Example 15, 5, 4- [2- [N- [4- (α-ethyl-41-isobutyl) benzyloxyphenyl] lubamoyl] phenoxy] butanoic acid was obtained.

Ingredients: Ethyl 4-1 [2— [Ν— [4-1]

 Isoptyl) benzyloxyphenyl] rubamoyl] phenoxy] butylate

Physicochemical properties

 Mass spectrometry (m / z): FAB (P 0 s.) 490 (M + 1) +, 70, (base peak)

Nuclear magnetic resonance spectra _{(40 OMH z, CDC 1 3} , TMS internal standard Associate)

 δ 0 8 7 (6 H, d), 0.98 (3 H, t),

 1 79 ~ 1.90 (2 H, m),

 1 9 4 to 2.02 (1 H, m),

 2 2 4 (2 H, q u int), 2.42 (2 H, d)

2 5 8 (2 H, t), 4.2 2 (2 H, t)

4, 9 6 (1 H, t), 6.8 4 (2 H, d)

6.96 (1H, d), 7.08 (2H, d)

7.09 (1H, t), 7.23 (2H, d)

7.43 (1H, t), 7.45 (2H, d)

8.22 (1 H, d), 9.60 (1 H, s)

H of COOH was detected with the solvant

Example 20

 In the same manner as in Example 15, 41- [2- [N- [4- (4-isobutyl α-methyl) benzyloxy-2-methylphenyl] carbamoyl] phenoxy] butanoic acid was obtained.

Starting compound: ethyl 4- [2- [Ν- [4-[(4-isobutyl-1-methyl) benzyloxy-2-methylphenyl] caphamb] ylphenoxy] butyrate Physicochemical properties

 Mass spectrometry value (mZz): FAB (P 0 s.) 490 (M + 1)

 1 6 1, (base peak)

Nuclear magnetic resonance spectra (40 OMH z, CD C 1 3, TMS internal standard)

 5: 0.89 (6 H, d), 1.6 1 (3 H, d),

 1. 7 7 to 1.89 (1 H, m),

 2. 2 1 (H, q u i n t),

2.24 (3 H, s), 2.44 (2 H, d), 2.53 (2 H, t), 4.27 (2 H, t), 4.5 6 (1 H, q) 6 7 2 (1 H, dd)

 6.77 (1H, d) 701 (1H, d), 7.10 (2H, d) 1 1 (1H, t),

7.2 7 (2 H, d) 7 4 6 (1 H, t)

 8.2 4 (1 H, d) 9 1 9 (1 H, s)

Example 2 1

 In the same manner as in Example 15, 5, 4- [2- [N— [4- (naethyl-4-isobutyl) benzyloxy-2-methylphenyl] carbamoyl] phenoxy] butanoic acid was obtained.

Raw material compound: ethyl 4- [2- [N- [4-1 (naethyl-4-1-isobutyl) benzyloxy-2-methylphenyl] -lubamoyl] phenoxy] butyrate Physicochemical properties

Mass spectrometry value (mZz): FAB (Pos.) 504 (M + 1) ⁺ ,

 1 7 5, (base peak)

 Nuclear magnetic resonance spectrum (40 OMHz, CDC1a, TMS internal standard)

 δ: 0.88 (6 Η, d), 0.98 (3 Η, t),

 1. 81 to: I.90 (2 H, m),

 1 · 9 3 to 2.0 2 (1 H, m),

 2.20 (2H, quint), 2.22 (3H, s), 2.43 (2H, d), 2.53 (2H, t), 4.27 (2 H, t), 4.96 (1 H, dd),

6.70 (1 H, d d), 6.76 (1 H, d), 7.01 (1 H, d), 7.09 (2 H, d),

7.10 (1H, t), 7.24 (2H, d),

7.43 to 7.47 (1 H, m), 8.23 (1 H, d d) 9.17 (1 H, s)

Example 22 4- [2- [N- [4-((4-Isobutyl-1-α-methylbenzyloxy) —3-methyl-phenyl] pothambamoyl] phenoxy] butylate in the same manner as in Example 15

 Ingredients: Ethyl 4— [2— [Ν- [4— (4-Isobutyl)

 α-methylbenzyloxy) -3-methyl-phenyl]

 Physicochemical properties

Mass spectrometry value (mZz): (. P o s) FAB 4 9 G (M +), nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 1.89 (6 Η, d) 6 1 (3 H, d),

 1.8.4 (1 H, m)

 2.27 (2 H, m)

 2 3 1 (3 H, s) 2 4 5 (2 H, d), 2 62 (2 H, t) 4 2 6 (2 H, t), 5 47 (1 H, q) 6 70 (1 H, d), 700 (1 H, d) 7 1 to 7.2 (3 H, m), 72 to 7.4 (3 H, m), 7.43 s), 7 4 7 (1 H, dt), 8.26 (1 H, dd),

9 5 8 (1 H, s)

 Example 23

 In the same manner as in Example 15, 45- [2- [N- [4- (4-isobutyl-isopropyl) benzyloxyphenyl] -lubamoyl] phenoxy] butanoic acid was obtained.

 Starting compound: ethyl 4- [2— [N— [4-(4-isobutyl) —

 Na-isopropyl) benzyloxyphenyl] lvamoyl] phenoxy] butylate

 Physicochemical properties

Nuclear magnetic resonance spectra (27 OMH z, CD C 1 3, TMS internal standard) δ 0 87 (6 H, d), 0.88 (3 H, d),

 1 05 (3 H, d), 1.77 to 1.91 (1 H, m), 204 to 2.16 (1 H, m),

 2 2 1 ~ 2.23 (2 H, m),

 2 44 (2H, d), 2.60 (2H, t), 426 (2 H, t) 4.77 (1 H, d), 685 (2 H, d) 7.0 1 (1 H , d), 7 1 1 (2 H, d) 7.14 (1 H, t), 723 (2 H, d) 7.47 (2 H, d), 7, 44 to 7.52 ( 1 H, m), 8.25 (1 H, dd),

9 60 (1 H, s)

Example 24

 In the same manner as in Example 15, 5, 4- [2- [N- [4- (4-isobutyl-1-isopropyl) benzyloxy-2-methylphenyl] capitarubumoyl] phenyloxy] butanoic acid was obtained.

Raw material compound: Ethyl 4- [2- [N- [4-1- (4-isobutyl-α-isopropyl) benzyloxy-2-methylphenyl] caprubamoyl] phenyloxy] butylate Physicochemical properties

Nuclear magnetic resonance spectra _{(27 ΟΜΗ ζ, CDC 1 3} , TMS internal standard)

 δ: 0.86 (6 Η, d), 0.86 (3 H, d),

 1.04 (3Η, d), 1.76 to 1.90 (1 H, m),

2.04 to 2.14 (1H, m),

 2. 1 9 (2 H, qu int),

 2.22 (3 H, s), 2.44 (2H, d),

2.52 (2 H, t), 4.28 (2 H, t),

4, 67 (1 H, d), 4.67 (1 H, d),

6.77 (1 H, dd), 6.77 (1 H, d), 7.03 (1 H, d), 7.1 1 (2 H, d),

 7.13 (1 H, t), 7.23 (2 H, d),

7.44 to 7.51 (1H, m), 7.63 (1H, d),

8.26 (1 H, dd), 9.22 (1 H, s) Example 25

 In the same manner as in Example 15, forty-one [2- [N- [4- [3-chloro-4- (4-isobutyl-α-methyl) benzyloxy] phenyl] pyruvamoyl] phenoxy] butanoic acid was obtained.

 Raw material compound: ethyl 4- [2— [Ν— [4— [3-chloro-4—

 (4-Isobutyl-methyl) benzyloxy] phenyl] lvamoyl] phenoxy] butyrate Physicochemical properties

 Mass spec (mZz): 5 10 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

δ: 0.87 (6 H _f d), 1 65 (3 H, q),

 6.78 (1H, d), 1.83 (1H, m), 2.26 (2H, m), 2.44 (2H, d), 2.60 (2H, t), 4.25 (2 H, t), 5.29 (1 H, q), 6.78 (1 H, d),

7.00 (1 H, d), 7.2 7.2 (3 H, m), 7.1 to 7.2 (3 H, m), 7.2 to 7.4 (3H, m), 7.00 (1 H, d), 7.1 to 7.2 (3 H, m),

7, 2 to 7.4 (3H, s), 7.2 to 7.4 (3H, m), 746 (1H, t), 7.75 (1H, d), 823 (1H , dd), 9.67. (1H, s) Example 26

In the same manner as in Example 15, 41- [2- [N- [4- (4-isobutyl-1-propyl) benzyloxy-2-methylphenyl] potumbayl] phenoxy] butanoic acid was obtained. Raw material compound: ethyl 4- [2- [Ν- [4- (4-isobutyl-α-propyl) benzyloxy-2-methylphenyl] lubamoyl] phenyloxy] butylate Physicochemical properties

 Melting point amo r p h o u s c r y s t a l

Elemental analysis (C ₃₂ H _3e NO _s)

 C (%) H (%) Ν (%) Theoretical value 74.25 7.59 2.71 Experimental value 74.25 7.69 2.66 Nuclear magnetic resonance spectrum (27 OMH z CDC 1 a, TMS internal standard)

 δ 0 88 (6 H, d), 0.95 (3 H,),

 1 32 to 1.58 (2 H, m),

 1 69 to 1.88 (2 H, m),

 1 88 ~ 2.02 (1 H, m),

 2 1 8 (2 H, qu i n t),

 2 22 (3 H, s), 2.43 (2 Η, d)

 2 52 (2Η, t), 4.27 (2Η, t), 505 (1Η, dd), 6.71 (1Η, dd), 677 (1Η, d), 7.02 (1 Η, d), 7 10 (2 Η, d), 7.26 (2 Η, d),

7.44 to 7.50 (1Η, m), 7.64 (1Η, d), 826 (1Η, dd) 9.23 (1Η, s)

Example 27

 In the same manner as in Example 15, 4, 4- [2- [Ν- [5-bromo-2,3-dimethyl-41- (4-isobutyl-na-methyl) benzyloxyphenyl] caprubamoyl] phenoxy] butanoic acid was obtained.

Starting compound: ethyl 4- [2— [Ν— [5-promo 2,3-dimethyl-4-1 (4-isobutyl-methyl) benzyl] Roxyphenyl] Lubamoyl] Funoxy] Butyrate

 Physicochemical properties

 Mass spectrometry value (m / z): FAB (Pos.) 584 (M + 1)

 1 6 1 (base peak)

Nuclear magnetic resonance spectra (2 7 OMH z, CDC 1 3, TMS internal standard)

 δ: 0.89 (6 H, d) .1.65 (3 H, d),

 1.77 to 1.92 (1H, m),

 1.93 (3H, s), 2.09 (3H, s), 2.22 (2H, quint), 2.47 (2H, d), 2.56 (2H , t), 4.30 (2 H, t), 5.22 11 ((11 HH ,, qq)), 70 5 (1 H, d), 13 (2 H, d) 7 1 5 (1 H, t),

 736 (2H, d), 7.46 to 7.53 (1H, m), 797 (1H, s) 829 (IH, dd), Example 28

 In the same manner as in Example 15, forty-one [2- [N- [3,5-dimethyl-4- (4-isobutyl-methyl) benzyloxyphenyl]]-rubumoyl] phenoxy] butanoic acid was obtained.

Starting compound: ethyl 4- [2— [N— [3,5-dimethyl-4-1

 (4-Isobutyl-methyl) benzyloxyphenyl] lvamoyl] phenyloxy] butylate Physicochemical properties

Melting point 97-98. C hexane-E t ₂ 0

Elemental analysis (as C ₃₁ H ₃₇ N0 ₅₎

C (%) H (%) N (%) Theoretical 73.9 3 7.4 0 2.78 8 Experimental 73.9 3 7.45 2.76 Mass spectrometry value (mZ z): EI504 (M + 1) ⁺

Nuclear magnetic resonance spectrum (5 0 OMH z, DMS 0 - d 6, TMS Internal standard)

 δ: 0.86 (6Η, d), 1.55 (3Η, d),

 1. 8 3 (1 Η, s e p t),

 1.99 to 2.07 (2 Η, m), 2.03 (6 Η, s), 2.41 to 2.46 (4 Η, m), 4.14 (2 Η, m) , t), 4.88 (1 (, q), 7.06 (1Η, t), 7.10-7.17 (3Η, m), '7.30 (2Η , d), 7.32 (2 Η, s), 7.47 (1 Η, t),

7.65 (1H, d), 9.87 (1H, s), 12.14 (1H, brs)

Example 2 9

 In the same manner as in Example 15, 4— [2— [N- [4-1 (a, 4-diisobutyl) benzyloxy 2,3-methylphenyl] carbamoyl] phenoxy] butanoic acid was obtained.

Raw material compound: Ethyl 4- [2- [N- [4- (N, 4-diisobutyl) benzyloxy)-1,2,3-dimethylphenyl] -lvamoyl] phenoxy] butylate Physicochemical properties

Melting point 1 2 5~ 1 2 6 ° C fr om hexane - E t 2 0 Elementary analysis (as C ₃₄ H ₄₃ N 0 ₆₎

C (%) H (%) N () Theoretical 7 4. 8 3 7. 9 4 2.5.7 7 Experimental 7 4. 9 4 7. 8 6 2.5.2 2 Mass spectrometry (mZ z): FAB (. P os) 5 4 6 (M + 1) + nuclear magnetic resonance spectrum (5 0 OMH z, DMS O - d 6, TMS Internal standard)

5: 0.83 (6 H, d), 0.91 (3 H, d), 0 96 (3 H, d), 1.54-160 (1 H, m)

73 ~; I. 82 (2 H, m),

 1 88-: L. 94 (1 H, m),

 1 99 (2 H, qu i n t),

 2 1 4 (3 H, s), 2.23 (3 H, s), 238 (2H, t), 2.39 (2 H, d), 4 1 (2 H, t), 5.28 (1H, dd), 664 (1H, d), 7.01 (1H, d), 703 (1H, t), 7.10 (2H, d), 13 (1H , d), 7.29 (2 H, d),

 45 (1 H, t), 7.67 (1 H, d),

 9 45 (1 H, s), 12.14 (1 H, br) Example 30

 In the same manner as in Example 15, 4- [2- [N- [4-(, 4-diisobutylbenzyloxy) -1,3,5-dimethylphenyl] -lubamoyl] phenoxy] butanoic acid was obtained.

Starting compound: ethyl 4- [2— [N— [2-methyl-4-1 (α,

 4-diisobutylbenzyloxy) phenyl] carbamoyl] phenoxy] butyrate

Physicochemical properties

 Mass spec (mZz): 532 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.87 (6 Η, d), 0.96 (6 H, d d),

 1.52 ~: I.59 (1H, m)

 1.79-: I.88 (2 H, m),

 1.92〜2.02 (1 H, m),

 2. 10-2. 1 6 (2 H, m),

2.20 (3 H, s), 2.41 to 2.47 (4H, m), 4.20 (2 H, t), 5.11 (1 H, q), 6.69 (1 H, q) 6.74 (1 H, d),

 6.97 (1 H, d) 7.05 (3 H, m),

7.24 (2 H, t) 7.40 (1 H, q u int),

7.60 (1H, d) 8.22 (1H, q), 929 (1H, s) 10.50 (1H, br), Example 3 1

 In the same manner as in Example 15, 5- [2- [N- [4- (4-iso-isobutyl-α-methylbenzyloxy)-1,2,5-dimethylphenyl] capitarubumoyl] phenoxy] butanoic acid was obtained.

Starting compound: Ethyl 4- [2— [Ν— [4- (4-Isobutyl-methylbenzyloxy) -1,2,5-dimethylphenyl] dirubamoyl] f X-Noxy] Butyrate Physicochemical properties

Elemental analysis (as C ₃₁ H ₃₇ N0 ₅₎

C (%) H (%) N (%) Theoretical 73.93 7.40 2.78 Experimental 73.89 7.39 2.72 Mass spec (mZz): 504 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.89 (6Η, d), 1.60 (3 H, d),

 1.85 (1H, m), 2.16 (3H, s), 2.17 to 2.22 (2H, m),

 2.27 (3H, s), 2.45 (2H, d), 2.52 (2H, t), 4.26 (2H, t), 5.25 (1H, q), 6. 56 (1 H, s)

 7.01 (1 H, d), 7.09 to 7.13 (3H, m),

7.26 to 7.29 (3H, m),

 7.42 to 7.47 (1 H, m),

7.58 (1 H, s), 8.25 (1 H, dd), 9.1 7 (1 H, s)

 Example 3 2

 In the same manner as in Example 15, 5-1,2- [N- [4- [4- (4-isobutyl-methylbenzyloxy)-1,2,6-dimethylphenyl] -lubamoyl] phenoxy] butanoic acid was obtained. .

 Starting compound: ethyl 4- [2- [N- [4- (4-isobutyl-methylbenzyloxy) -1-2,6-dimethylphenyl] potumbamoyl] phenoxy] butylate Physicochemical properties

Elemental analysis (as C _3I H ₃₇ N0 ₅₎

C (%) H (%) N (%) Theoretical value 7 3.93 3 7.4 0 2.78 8 Experimental value 7 3. 6 9 7. 4 8 2.72 2 Mass spectrometry value (mZz): 5 0 4 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDCI ₃ , TMS internal standard)

 δ: 0 8 9 (6 Η, d), 1 6 0 (3 H, d),

 8 5 (1 H, m), 2.6 to 2.2 1 (8 H, m),

2 4 5 (2 H, d), 2 5 1 (2 H, t), 4 2 3 (2 H, t), 5 2 6 (1 H, q), 6 6 4 (1 H, s), 7 0 1 (1 H, d)

 7 0 8 to 7.1 2 (3 H, m),

 7 2 6 ~ 7.2 9 (2 H, m),

 7 4 6 (1 H, t), 8.2 1 (1 H, d), 8.78 (1 H, s),

Example 3 3

 In the same manner as in Example 15, 5, 4- [2- [N- [4- (4-isobutyl-methyl-methylbenzyloxy)-1,2,3,5-trimethylphenyl] -lubamoyl] phenoxy] butanoic acid was used. Obtained.

Raw material compound: ethyl 4- [2— [N— [4-1 (4-isobutyl) 1,2-methylbenzyloxy) 1,2,3,5-trimethyl phenyl] lvamoyl] phenoxy] petite Physicochemical properties

Elemental analysis (as _{C 32 H 39 N0 5 · 0} 2 H 2 0)

 C (° / o) H (%) N () Theoretical 73.73 7.62 2.69 Experimental 73.70 7.65 2.71 Mass spec (m / z): 5 18 (M + 1) +

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.91 (6 Η, d) 1 59 (3 H, d),

 1.86 (1 H, m) 2 08 (3 H, s), 2.15 (6 H, s) 2 20 to 2.24 (2 H, m),

4.47 (2 H, d) 2 54 (2 H, t),

4.27 (2 H, t) 4 85 (1 H, q)

 7.02 (1 H, d) 7 1 1 to 7.13 (3 H, m), 7.30 to 7.3 1 (2 H, m),

 7.42 to 7.47 (2 H, m), 8.27 (1 H, dd), 9.30 (1 H, s)

Example 34

 In the same manner as in Example 15, 5, 4- [2- [N- [2-ethyl-41- (4-isobutyl-α-methylbenzyloxy) phenyl] -potamoyl] phenoxy] butanoic acid was obtained.

Raw material compound: Ethyl 4- [2- [Ν- [2-ethyl-4-1 (4-isobutyl-methylbenzyloxy) phenyl] dirubamoyl] phenyloxy] butylate Physicochemical properties

 Melting point 65-66 ° C

Elemental analysis (as C ₃₁ H _3e N0 ₅₎ C (%) H (%) N (%) Theoretical 74.08 7.22 2.74 Experimental 73.79 7.48 2.71 Mass spec (m / z): 504 (M + 1) +

 Nuclear magnetic resonance spectrum (CDC1, TMS internal standard)

 δ: 0.88 (6 Η, d) 1 16 (3 H, t),

 1.62 (3 H, d) 1 84 (1 H, m),

2.22 (2 H, q) 2 44 (2 H, d),

2.57 (4 H, m) 4 28 (2 H, t),

5.27 (2 H, q) 6 73 (1 H, d d)

6.79 (1 H, d) 7 20 (1 H, d), 7.1 1 (2 H, m) 25 (3 H, m),

7.45 (1 H, m) 62 (1 H, d),

8 24 (1 H, d) 9 16 (1 H, s) Example 35

 In the same manner as in Example 15, 4- [2- [N- [4- (4-isobutyl-α-propyl) benzyloxyphenyl] carbamoyl] phenoxy] butanoic acid was obtained.

Raw material compound: Ethyl 4- [2- [Ν- (4-Isoptyl loop pill) benzyloxyphenyl] phorbamoyl] phenyloxy] butyrate

Physicochemical properties

 Amo r phou s c r y s t a l

Elemental analysis (as C ₃₁ H ₃₇ N0 ₅₎

 C (%) H (%) N (%)

73.93 7.40 2.78

73.66 7.55 2.69 Nuclear magnetic resonance spectrum _{(27 OMH z, CDC 1 3} , TMS internal standard) δ 0 8 7 (6 H, d), 0.93 (3 H, t),

 1 32 to: I.60 (2H, m),

 1 6 8-: I. 8 8 (2 H, m),

 1 9 1 ~ 2.03 (1 H, m),

 2 2 6 (2 H, q u i n t),

 2 4 3 (2 H, d), 2.60 (2 H, t),

4 2 5 (2 H, t), 5 0 5 (1 H, d d)

6 8 5 (2 H, d), 7 0 0 (1 H, d),

7 1 0 (2 H, d), 7 1 2 (1 H, t),

7, 2 6 (2 H, d), 7.4 2 to 7.5 0 (1 H, m),

7 4 8 (2 H, d), 8 2 4 (1 H, d d),

 9 5 7 (1 H, s)

Example 3 6

 In the same manner as in Example 15, 5- [2- [N- [4- (, 4-diisobutyl) benzyloxy-2-methylphenyl] caprubamoyl] phenoxy] butanoic acid was obtained.

Starting compound: Ethyl 4- [2— [N- [4-1 (a, 4-diisobutyl) benzyloxy-2-methylphenyl] dibutyl moyl] phenoxy] petitate

Physicochemical properties

 Melting point a m o r p h o u s c r y s t a l

Elemental analysis (as C ₃₃ H ₄₁ N0 ₅₎

 C (%) H (%) N (%) Theoretical value 7 4.5 5 7.7 7 2.63 Experimental value 7 4. 3 1 7. 9 1 2.5.8 Nuclear magnetic resonance spectrum (27 OMH z, CDC 1a TMS internal standard)

 5: 0.8.8 (6 H, d), 0.9.4 (3 H, d),

0.98 (3 H, d), 1.48-: I. 60 (1 H, m), 7 6 ~: I. 9 1 (2 H, m),

 1.89-: I.99 (1H, m),

 2.18 (2 H, q u i n t)

 2.22 (3 H, s), 2.44 (2 H, d), 2.50 (2 H, t), 4.26 (2 H, t), 5.15 (1 H, dd), 6.72 (1H, dd), 6.77 (1H, d), 7.03 (1H, d), 7.11 (2H, d) 7. 1 3 (1 H, t), 7.27 (2 H, d) 7.43 to 7.5 1 (1 H, m), 6 4 (1 H, d) 8.2 6 (1 H, dd )

 9.25 (1 H, s)

 Example 3 7

 In the same manner as in Example 15, forty-one [2- [N- [4- [α-, 4-dibutyl] benzyloxyphenyl] caprubamoyl] phenoxy] butanoic acid was obtained.

Starting compound: ethyl 4- [2 — [—— [4- (a, 4-diisobutyl) benzyloxyphenyl] dirubamoyl] phenoxy] butylate

Physicochemical properties

Melting point 1 2 5~1 2 7 ° C (hexane one CH ₂ C 1 ₂ to) Elemental analysis (as C ₃₂ H ₃₉ N0 ₅₎

 C (%) H (%) N (%) Theoretical value 74.2 5 7.5 9 2.71 Experimental value 74.3 3 7.44 2.70 Mass spectrometry value (mZz): FAB (P o s.) 5 18 (M + 1) 'Nuclear magnetic resonance spectrum (27 OMHz CDC 1a, TMS internal standard)

 δ: 0.87 (6 Η, d), 0.94 (3 H, t),

0.98 (3 H, d), 1.5 0 to: 1.6 1 (1 H, m), 1 75 to 1.86 (2 H, m),

 1 86 ~ 2.02 (1 H, m),

 2 26 (2 H, q u i n t)

 2 43 (2 H, d), 2.60 (2 H,:), 425 (2 H, t), 5 12 (1 H, dd), 685 (2 H, d), 700 (1 H H, d), 1 0 (2 H, d), 7 1 1 (1 H, t),

 7 26 (2 H, d), 7.43 to 7.49 (1 H, m),

47 (2 H, d), 8 24 (1 H, d d), 9 58 (1 H, s)

Example 38

 In the same manner as in Example 15, 41- [2- [N- [2,3-dimethyl-41- (naethyl-41-isobutyl) benzyloxyphenyl] potumbamoyl] phenoxy] butanoic acid was obtained.

Starting compound: ethyl 4- [2— [N— [2,3-dimethyl-4-1

 (Naethyl-4-isobutyl) benzyloxyphenyl] lvamoyl] phenyloxy] petite Physicochemical properties

Melting point 127-130. C (E t ₂₀ )

Elemental analysis (as C ₃₂ H _3e N0 ₅₎

C (%) H (%) N () theoretical 74.25 7.59 2.7 1 Found 74.08 7.68 2.7 1 nuclear magnetic resonance spectra _{(27 OMH z, DMSO- d 6} , TMS internal standard)

 6: 0.84 (6H, d), 0.94 (3H, t),

 1. 76 ~: I. 96 (3 H, m),

 2.00 (2 H, qu i n t),

2.13 (3H, s), 2.23 (3H, s) 2.40 (2 H, t), 2 41 (2 H, d)

 4.17 (2H, t), 5 2 1 (1H, t)

6.64 (1 H, d), 705 (1 H, t)

7.06 (1 H, t), 7 1 4 (2 H, d) 7.19 (1 H, d), 7 30 (2 H, d)

7.45 to 7.53 (1 H, m),

 7.71 (1H, dd), 9.49 (1H, s) Example 39

 In the same manner as in Example 15, 41- [2- [N- [2,3-dimethyl-4- (4-isobutyl-iso-isopropyl) benzyloxyphenyl] potumbamoyl] phenoxy] butanoic acid was obtained.

Starting compound: ethyl 4- [2— [N— [2,3-dimethyl-4-1

 (4-Isobutyl-α-isopropyl) benzyloxyphenyl] lvamoyl] phenoxy] butyrate Physicochemical properties

Elemental analysis (hexane one E t ₂ 0 to) Melting point 137~139 ° C (as C _a3 H ₄₁ N05)

C (%) H (%) N (%) Theoretical 74, 55 7.77 2.63 Experimental 74.50 7.80 2.65 Nuclear magnetic resonance spectrum (27 OMH z, DMS 0-d ₆ , TMS internal standard)

 δ: 0.84 (6 Η, d), 0.94 (3 H, d),

 1.00 (3 H, d), 1.81 (1 H, set), 2.00 (2H, qu int), 2.10 (1 H, set)

2.14 (3 H, s), 2.26 (3 H, s), 2.40 (2 H, t), 2.42 (2 H, d), 4.17 (2 H, t), 5.04 (1 H, d), 6.59 (1 H, d), 7.03 (IH, d), 7.05 (1 H, t), 7.14 (2 H, d),

 7.18 (1 H, d), 7.27 (2 H, d), 7.45 to 7.52 (1 H, m),

 7.73 (1 H, d d), 9.49 (1 H, s) 1 2.17 (1 H, br)

Example 40

 In the same manner as in Example 15, 5, 4- [N- [N- [2,3-dimethyl-4- (4-methylpropylbenzyloxy) phenyl]]-rubumoyl] phenoxy] butanoic acid was obtained.

Raw material compound: ethyl 4- [2-N- [2,3-dimethyl-4-1 (4-propyl-l-methylbenzyloxy) phenyl] -caprolbamoyl] phenyloxy] butylate physicochemical properties

 Mass spec (mZ z): 490 (M + 1) +

Nuclear magnetic resonance spectrum (CDC 1 _3, TMS internal standard)

 δ: 0.93 (3 Η, t), 1.6 to 1.65 (5 H, m),

2 2 1 (3 H, s), 2.18 to 2.2 1 (2 H, m), 2 2 7 (3 H, s) 2 5 5 (4 H, d t),

 4 2 5 (2 H, t) 5 2 5 (1 H, q), 6 62 (1 H, d) 6 0 1 (1 H, d), 7 08 to 7.14 (3 H, t) m),

 7 2 5 to 7.3 3 (3 H, m),

 7 4 5 (1 H, q u int),

 8 2 3 (1 H, d d), 9.18 (1 H, s) Example 4 1

 In the same manner as in Example 15, 5, 4- [2— [N— [2,3-dimethyl-4- [4-ethyl-α-methylbenzyloxy] phenyl] carbamyl] phenoxy] butanoic acid was obtained.

Raw material: ethyl 4- [2—Ν— [2,3-dimethyl-4-1 [4 -Ethyl-N—methylbenzyloxy] phenyl] power rubamoyl] phenoxy] butylate physicochemical properties

 Melting point 1 27 to 8 ° C

Elemental analysis (as C ₂₉ H ₃₃ N0 ₅₎

 C (%) H (%) N (%) Theoretical 73.24 6.99 2.95 Experimental 73.44 6.97 2.92 Example 42

 In the same manner as in Example 15, 41- [2- [N- [2,3-dimethyl-14- (4, α-dimethylbenzyloxy) phenyl] caprumbyl] phenoxy] butanoic acid was obtained.

 Starting compound: Ethyl 4- [2 -—- [2,3-dimethyl-4-1 (4, α-dimethylbenzyloxy] phenyl] carbamoyl] phenoxy] butyrate

Physicochemical properties

 Melting point 1 47-2. C

Elemental analysis value (as C _2e H ₃₁ N0 ₅ )

 C (%) H (%) N (%) Theoretical value 72.86 6.77 3.03 Experimental value 73.1 1 6.95 3.03 Example 43

 In the same manner as in Example 15, 4-1 [2- [N- [2,3-dimethyl-4-1- (4-isopropyl-1-methylbenzyloxy) phenyl] -caprolvamoyl] phenoxy] butanoic acid was obtained.

Starting compound: ethyl 4- [2-N- [2,3-dimethyl-41- (4-isopropyl-1-methylbenzyloxy) phenyl] caproluvyl] phenyloxy] butyrate

Physicochemical properties Melting point 102 to 3 ° C

Elemental analysis (as C ₃ .H ₃₅ N0 ₅₎

 C (%) H (%) N (%) Theoretical 73.60 7.2 1 2.86 Experimental 73.52 6.93 2.84 Example 44

 In the same manner as in Example 15, 5, 4- [2- [N- [3- (4-isobutylbenzyloxy) phenyl] -lubamoyl] phenyloxy] butanoic acid was obtained.

Starting compound: Echiru 4 one [2 -N- [3- (4 one Isobuchiruben Jiruokiji) phenylalanine] force Rubamoiru] off _Λ Roh carboxymethyl] Puchireto

Physicochemical properties

Mass spec (mZ z): 462 (M + 1) ⁺

Nuclear magnetic resonance spectrum (CDC ₁₈ , TMS internal standard)

 δ: 0.90 (6 Η, d) 1.86 (1 H, m),

 2.27 (2 H, m) 2.46 (2 H, d),

2.60 (2 H, t) 4.24 (2 H, t),

5.05 (2 H, s) 6.74 (1 H, d d),

6.98 (1 H, d) 7.0 to 7.3 (5 H, m),

7.34 (2 H, d) 7.45 (1 H, t), 7.62 (1 H, t) 8.25 (1 H, d d),

9 80 (1 H, s)

Example 45

 In the same manner as in Example 15, 5, 4- [2- [N- [3- (4-isobutyl-α-methylbenzyloxy) -12-methylphenyl] -potamoyl] phenoxy] butanoic acid was obtained.

Starting compound: Ethyl 4- [2-- [-[3- (4-Isobutyl-methyl-1-methylbenzyloxy) -1-2-methylphenyl] Lubamoyl] Phanoxy] Butyrate

 Physicochemical properties

Mass spec (mZz): 489 (M ⁺ )

Nuclear magnetic resonance spectrum (CDC 13 _: TMS internal standard)

 δ: 0.88 (6 Η, d), 1.62 (3 H, d),

1.84 (1 H, m), 2.24 (2 H, m), 2.29 (3 H, s), 2, 43 (2 H, d), 2.55 (2 H _f t), 4.30 (2 H, t), 5.28 (1 H, q), 6.58 (1 H, d), 7.0 to 7.2 (5 H.m), 7.26 (2 H , d),

7 47 (1 H, t), 7.55 (1 H, d), 827 (1 H, d), 9.45 (1 H, s) Example 46

 In the same manner as in Example 15, 41- [2- [N- [3-isobutyl-α-methylbenzyloxy) -14-methylphenyl] -lubamoyl] phenoxy] butanoic acid was obtained.

Starting compound: ethyl 4- [2-2- [3-(4-isobutyl-α-methylbenzyloxy] -14-methylphenyl]] force rubamoyl] phenoxy] butylate Physicochemical properties

 Melting point 120-: I21. C

Elemental analysis (as C ₃ .H ₃₅ N0 ₅₎

 C (%) H (%) N (%) Theoretical 73.60 7.2 1 2.86 Experimental 73.56 7.35 2.77 Mass spec (m / z): 490 (M + 1) +

Nuclear magnetic resonance scan Bae-vector (CDC 1 _3, TMS internal standard)

 δ: 0.88 (6Η, d), 1.63 (3 H, d),

1.83 (1 H, m), 2.22 (1 H, m), 2 2 6 (3 H, s), 2.43 (2 H, d),

 2 5 6 (2 H, s), 4.22 (2 H, t), 5 4 1 (2 H, q), 6.9 to 7.0 (2 H, m), 70 to 7. 2 (4 H, m), 7.32 (2 H, d), 740 (1 H, s), 7.44 (1 H, t), 8 2 2 (1 H, d), 9.5 8 (1 H, s)

 2 4 5 (2H, d), 4.14 (2H, t), 706 (1H, t), 7.14 to 7.19 (5H, m), 745 ~ 7.5 2 (1 H, m),

 77.4 9 (2 H, d), 7.55 (2 H, d),

7.65 (1 H, d d), 7.73 (2 H, d),

 1 0.17 (1 H, s), 1 2.13 (1 H, br) Example 4 7

 In the same manner as in Example 15, 5, 4- [2— [N— [4-[[4-isobutyl-N-methylanilino) methyl] phenyl] -lubamoyl] phenoxy] butanoic acid was obtained.

Raw material compound: ethyl 4- [2-N- [4-1- [4-isobutyl-N]

 -Methylanilino) methyl] phenyl] lvamoyl] phenoxy] butylate

Physicochemical properties

Elemental analysis (as _{C 2e H 34 N 2 0 4} · 0. 3 H 2 0)

C (%) H (%) N (%) Theoretical 7 2.5 7 7.2 7 5.8.4 4 Experimental 7 2. 2 8 6. 9 6 5.76 Mass Spec (mZ z): 4 7 4 (M ⁺ )

Nuclear magnetic resonance scan Bae-vector (CDC 1 _3, TM S internal standard)

 6: 0.85 (6 H, d), 1.75 (1 H, m),

2. 1 1 (2 H, m), 2.33 (2 H, d), 2.40 (2 H, m), 2.90 (3 H, s), . 1 1 (2 H, t), 4.39 (2 H, s)

 6.67 (2 H, d), 6.90 (1 H, d)

6.98 (2 H, d), 7.05 (1 H, t)

7.20 (2 H, d), 7.37 (1 H, t) 7.58 (2 H, d), 7.58 (2 H, d) 8.17 (1 H, dd), 9.66 (1 H, s) Example 4 8

 In the same manner as in Example 15, 41- [2- [N- [4-[(N-ethyl 4-isobutyranilino) methyl] phenyl] potumbamoyl] phenoxy] butanoic acid was obtained.

 Starting compound: ethyl 4- [2- [N- [4-[(N-ethyl-4-isobutylanilino) methyl] phenyl] carbamoyl] phenoxy] butylate

 Physicochemical properties

 Mass spec (mZ z): 489 (M + 1) +

Nuclear magnetic resonance scan Bae-vector (CDC 1 _3, TMS internal standard)

 6: 0.8.6 (6 H, d) 1.20 (3 Η, t),

 1. 7 8 (1 H, m) 2. 2 9 (2 Η, m),

2.38 (2 H, d), 2.61 (2 Η, t),

3.49 (2 Η, m), 4.27 (2 Η, t),

4.47 (2Η, s), 6.9 to 7.1 (5Η, m), 7.23 (1Η, t), 7.29 (2Η, d),

7. 4 8 (1 Η, d t) 7.6 1 (2 Η, d),

8.45 (1Η, d d), 9.86 (1Η, s) Example 4 9

 In the same manner as in Example 15, 5, 4- [2- [Ν- [4-[[Ν, 4-disobutylarilino) methyl] phenyl] pyruvamoyl] phenyloxy] butanoic acid was obtained.

Raw material compound: ethyl 4- [2—Ν— [4-1— [Ν, 4-diisobuty Luanilino) methyl] phenyl] lvamoyl] phenyloxy] petitate

Physicochemical properties

Elemental analysis (as _{C 32 H 4 .N 2 0 4} · 0. 7 H 2 0)

 C (%) H (%) N (%) Theoretical 7 2. 6 2 7. 8 8 5. 29 9 Experimental 7 2. 4 4 7. 6 6 5. 18 Mass spectrometry (m / z) : 5 1 6 (M +)

Nuclear magnetic resonance scan Bae-vector (CDC 1 _3, TM S internal standard)

 6: 0.85 (6 H, d), 0.91 (6 H, d),

 1.73 (1H, m), 1.9 to 2.2 (3H, m), Example 50

 In the same manner as in Example 15, 5, 4- [2— [N— [4-1 — ((4-isobutyl-N-propylanilino) methyl] phenyl] potumbamoyl] phenyloxy] butanoic acid was obtained.

Raw material: ethyl 4— [2— [N- [4 — [(4—isobutyl

 I-N-propylanilino) methyl] phenyl] lvamoyl] phenoxy] petite

Physicochemical properties

Elemental analysis (as _{C 31 H 38 N 2 0 4} )

 C (%) H (%) N (%) Theoretical value 7 4.0 8 7.6 2 5.5 7 Experimental value 7 3. 6 9 7. 6 8 5. 4. 7 Mass spectrometry value (mZ z): 5 0 2 (M +)

Nuclear magnetic resonance spectrum (CDC 1 _3, TM S internal standard)

 δ: 0.88 (6 Η, d), 0.90 (3 H, t),

1.65 (2H, m), 1.76 (1H, m), 2.27 (2H, m), 2.33 (2H, d), 2.60 (2 H, t), 3.30 (2 H, t), 4.25 (2 H, t), 4.47 (2 H, s),

 6.61 (2 H, d), 6.96 (2 H, d),

6.98 (1 H, d), 7.1 1 (1 H, t),

7.2 1 (1 H, t) 7.2 1 (2 H, d),

7.44 (1 H, d t), 7.58 (2 H, d),

8.2 5 (1 H, d d)

Example 5 1

 In the same manner as in Example 15, 5, 4- [2- [N- [4-[(4-isobutyl-N-methylanilino) methyl] -12-methylphenyl] power rubamoyl] phenoxy] butanoic acid was obtained.

Starting material: ethyl 4- [2- [N- [4-1-[(4-isobutyl-1-N-methylanilino) methyl] -12-methylphenyl] rubamoyl] phenoxy] petitate Physicochemical properties

Elemental analysis (as _{C 3 .H 3e N 2 0 4} · 0 5 H 2 0)

C () H (%) N (%) Theoretical 7 2. 4 1 7.4 9 5.6 3 Experimental 7 2. 4 7 77 .. 22 99 5.48 Mass Spec (mZz): 4 8 8 (M ⁺ )

Nuclear magnetic resonance scan Bae-vector (CD C 1 _3, TMS internal standard)

 δ: 0.88 (6 Η, d), 1.79 (1 Η, m)

 2.2 1 (2 H, m), 2.29 (3 Η, s)

 2.3 6 (2 Η, d), 2.53 (2 Η, t)

 2.94 (3 Η, s), 4.29 (2 Η, t)

 4.42 (2 Η, s), 6.70 (2 Η, d)

 6. 9 9 (2 Η, d), 7.02 (1 Η, d)

 7. 1 to 7.2 (3 Η, m), 7.46 (1 Η d t),

7.93 (1 Η, d), 8.27 (I Η, dd) 9.4 4 (1 Η, s) Example 5 2

 In the same manner as in Example 15, 5, 4- [2— [N— [4-1 — ((4-isobutyl-N-methylanilino) ethyl] phenyl] potumbamoyl] phenoxy] butanoic acid was obtained.

Starting compound: ethyl 4- [2— [N— [4 — [(4-isobutyl-1-N-methylanilino) ethyl] phenyl] carbamoyl] phenoxy] butylate

Physicochemical properties

 Mass spec (mZ z): 489 (M + 1) +

Nuclear magnetic resonance scan Bae-vector (CDC 1 _3, TMS internal standard)

 δ: 0.8 9 (6 Η, d), 1.81 (1 Η, m)

 2.30 (2 H, m), 2.38 (2 Η, d)

 2.63 (2 Η, m), 2.81 (2 Η, m)

 2.87 (3 Η, s), 3.5 1 (2 Η, t)

 4.27 (2 Η, t), 6.69 (2 Η, d)

 6. 9 to 7.2 (6 Η, m), 7.46 (1 Η d t),

7. 5 9 (2 Η, d), 8.26 (1 Η, d d)

9 7 7 (1 Η, s)

Example 5 3

 In the same manner as in Example 15, 5, 4- [2— [Ν— [3 — [(4-isobutyl- ー -methylanilino) methyl] phenyl] pyrubamoyl] phenoxy] butanoic acid was obtained.

Starting compound: ethyl 4- [2— [Ν— [4-1 [(4-isobutyl-1-methyl-methylanilino) methyl] -12-methylphenyl] -lubamoyl] phenyloxy] butyrate Physicochemical properties

 Mass spec (m / z): 4 8 8 (M +)

Nuclear magnetic resonance scan Bae-vector (CDC 1 _3, TMS internal standard)

6: 0.88 (6 H, d), 1.79 (1 H, m), 2.2 3 (2 H, m), 2 25 (3 H, s),

 2.36 (2 H, d), 25 4 (2 H, d), 2.97 (3 H, s), 43 0 (2 H, t), 4.44 (2 H, d) s), 6 6 5 (2 H, d),

6. 9 to 7.1 (4H, m) 7.1 to 7.2 (2H, m),

7.48 (1 H, d t), 7 69 (1 H, d),

 8.28 (1H, dd), 946 (1H, s) Example 5 4

 In the same manner as in Example 15, 5, 4- [2- [N- [4- (4-isobutylbenzyl) -1-N-methylamino] phenyl] -lubamoyl] phenoxy] butanoic acid was obtained.

Starting compound: ethyl 4- [2- [N- [4-1-[(4-isobutylbenzyl) -1-N-methylamino] phenyl] carbamoyl] phenoxy] butyrate

Physicochemical properties

 Melting point: 109-: I10. C

Elemental analysis value (as CH ^ NS C ^ · 0 2 H ₂₀ )

 C (%) H (%) N (%) Theoretical 7 2.8 4 7.25 5.86 6 Experimental 72.9 3 77 .. 22 55 5.70 Mass Spec (mZz): 4 7 4 (M +)

Nuclear magnetic resonance spectrum (CDC13 _; TMS internal standard)

 6: 0.87 (6 Η, d), 1.83 (1 Η, m)

 2.27 (2 H, m), 2.48 (2 Η, d)

 2.61 (2 Η, t), 2.97 (3 Η, s)

 4.24 (2 Η, t), 4.47 (2 Η, s)

 6.74 (2Η, m), 6.78 (2Η, m)

7.0 to 7.2 (5 Η, m), 7.43 (1 Η dt), 6.98 (1 Η, d), 7.49 (2 Η, d) 8. 24 (1H, dd), 9.56 (1H, s) Example 55

 In the same manner as in Example 15, 5, 4- [2- [N- [4-[(4-isobutylbenzyl) amino] -12-methylphenyl] -lubamoyl] phenoxy] butanoic acid was obtained.

Starting compound: ethyl 4- [2- [N- [N-[(4-isobutylbenzyl) amino] -12-methylphenyl] carbamoyl] phenyloxy] petite

Physicochemical properties

Elemental analysis (as _{C 29 H 34 N 2 0 4} · 0 2 H 2 0)

C (%) H (%) N (%) Theoretical 72.84 7.25 5.86 Experimental 72.77 7.23 5.80 Mass Spec (mZz): 474 (M ⁺ )

Nuclear magnetic resonance scan Bae-vector (CDC 1 _3, TMS internal standard)

 δ 0 89 (6 H, d), 1.84 (1 Η, m),

 2 1 5 (2Η, m), 2.2 1 (3Η, s), 2 43 to 2.48 (4Η, m), 4.21 (4 Η, m), 6 48 (2 Η, d), 6 68 (1 Η, m), 6 98 (1 Η, d), 7.05 to 7.10 (3 Η, m), 723 (2 Η, d), 7 41 (1 Η, t), 7 54 (1Η, d), 823 (1Η, s),

8 23 (1Η, d), 9 27 (1Η, s)

Example 56

 In the same manner as in Example 15, 5, 4- [2- [Ν-. [4-1 (4-isobutylbenzyl) -1-methylamino] -2-methylphenyl] carbamoyl] phenoxy] butanoic acid was obtained.

Starting compound: ethyl 4- [2- [Ν- [4-[(4-isobutylbenzyl) -1-methylamino] -12-methylphenyl Le] valvamoyl] phenoxy] butyrate physicochemical properties

Elemental analysis (as _{C 3 .H 36 N 2 0 4} · 0 5 H 2 〇)

 C (%) H (%) N (%) Theoretical value 72.41 7.49 5.63 Experimental value 72.5 1 7.46 5.57 Mass spectrometry value (mZz): 489 (M +)

Nuclear magnetic resonance scan Bae-vector (CDC 1 _3, TMS internal standard)

 δ: 0.89 (6 Η, d), 1 84 (1 H, m)

 2.22 (2 H, m) 2.27 (3 H, s)

2.44 (2 H, d) 2.55 (2 H, t)

2.98 (3 H, s) 4.28 (2 H, t)

4.47 (2 H, s) 6.67 (2 H, m)

7.01 (1 H, d): 7.07 to 7.15 (5 H, m)

7 45 (1 H, d t), 7.65 (1 H, t), 8 25 (1 H, d d), 9.20 (1 H, s) Example 57

 In the same manner as in Example 15, 41- [2- [N- (4-benzhydryllamino 2-methylphenyl) -capsulebamoyl] phenoxy] butanoic acid was obtained.

Raw material compound: Ethyl 4- [2- [N- (4-benzhydrylamino 2-methylphenyl) rubamoyl] phenoxy] butylate

Physicochemical properties

Elemental analysis (as _{C 31 H 3 .N 2 0 4} · 0 4 H 2 0)

C (%) H (%) N (%) Theoretical 74.20 6.1 9 5.58 Experimental 74.08 6.23 5.35 Mass spec (mZz): 494 (M +) Nuclear magnetic resonance spectrum (CΏC 1. TMS internal standard)

 Ό · 1 1 ク Q V I, 丄 i Q, 2.52 (2 H, m),

4.24 (2 Η, t), 5.48 (1 H, s),

6.42 (2 Η, m), 6 · 99 (1H, d),

7.09 (1Η, t), 7.2 to 7.4 (10H, m),

7.43 (1 Η, t), 7.49 (1 H, d),

8.22 (1 Η, d), 9.15 (1 H, s)

Example 58

 In the same manner as in Example 15-5, 4- [2- [N- [4- [bis (4-propylphenyl) methyl] -12-methylphenyl] -lubamoyl] phenoxy] butanoic acid was obtained.

Starting compound: Ethyl 4- [2-N- [4-[[bis (4-propylphenyl) methylamino] -12-methylphenyl] -lvamoyl] fluoro-X-noxy] petite Physicochemical properties

Elemental analysis (as _{C 37 H <2 N 2 0} 4 · 0 2 H 2 0)

 C (%) H (%) N (%) Theoretical value 76.3 1 7.34 4.81 1 Experimental value 76.29 7.25 4 3 Mass spectrometry value (mZz): 578 (M +)

 Nuclear magnetic resonance spectrum (CDC 1 TMS internal standard)

 δ: 0.93 (6 H, t), 1 61 (4 H, m),

 2.18 (5 H, m), 2 53 (6 H, m),

4.25 (2 H, t), 5 42 (1 H, s),

6.40 (2 H, m), 6 99 (1 H, d),

7. 08 to 7.1 2 (5H, m),

 7.23 (4 H, d), 7.43 (1 H, t),

7.47 (1 H, d), 8, 22 (1 H, d d)

9.10 (1 H, s) Example 59

 0.73 ml of phosphorus tribromide was added dropwise at room temperature to a solution of 360 mg of 1- (4-isobutylphenyl) pentanol and 0 ml of carbon tetrachloride I, and the mixture was stirred at room temperature overnight. The reaction solution was poured into ice water, neutralized with potassium carbonate, and extracted with black-mouthed form. The extract was washed with brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 46 Omg of crude 1- (4-isobutylphenyl) pentyl bromide. In a 25 ml solution of this in dimethylformamide, at room temperature, ethyl 4- [2- [N- (4-hydroxy-2,3-dimethylphenyl) -powerbamoyl] phenoxy] butylate 50 Omg, potassium carbonate 36 Omg and 100 mg of tetrabutylammonium ester were added, and the mixture was stirred at 100 ° C overnight. The solvent of the reaction solution was distilled off under reduced pressure, and the residue was extracted with ethyl acetate. The extract was washed with water and saturated saline, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel chromatography, eluted with a mixture of hexane: ethyl ethyl ester (4: 1), and crude ethyl 4- [2— [N— [2,3 — 54 mg of dimethyl-41- (4-isobutyl- and mono-butylbenzyloxy) phenyl [l-rubamoyl] phenoxy] butylate were obtained. To a mixed solution of 0.2 ml of dioxane and 0.6 ml of ethanol was added 0.8 ml of a 5N aqueous sodium hydroxide solution at room temperature, and the mixture was stirred at room temperature for 20 minutes. The solvent of the reaction solution was distilled off under reduced pressure, the residue was dissolved in water, adjusted to pH = 1 with concentrated hydrochloric acid, and extracted with ethyl acetate. The extract was washed with saturated saline and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 51 mg of 4- [2- [N- [2,3-dimethyl-41- (4-isobutyl-butyrylbenzyloxy) phenyl] potumbamoyl] phenyloxy] butanoic acid. .

Physicochemical properties

 Mass spec (mZ z): 546 (M + 1) +

Nuclear magnetic resonance scan Bae-vector (CDC 1 _3, TMS internal standard) δ: 0.87 to 0.91 (9 Η, m)

 1.26 to 1.47 (4 Η, m)

 1.78-: I.84 (2H, m)

 1.96 to 2.01 (1H, m)

 2.15 to 2.18 (2H, m)

 2.20 (3 H, s), 2.28 (3H, s), 2.42 (2 H, d), 2.50 (2 H, t), 4.23 (2 H, t), 5 .03〜 5.06 (1 H, m),

6.55 (1 H, d), 6.99 (1 H, d), 7.07 to 7.10 (3H, m),

 7.2 1 to 7.26 (3 H, m),

 7. 4 1 ~ 7.43 (1 H, m),

 8.2 1 to 8.23 (1 H, m), 920 (1Η, s) Example 60

 In the same manner as in Example 59, 4- [2- [N [2,3-dimethyl-41- (4-isobutyl-isoamylbenzyloxy) phenyl] -pyrvamoyl] phenoxy] butanoic acid was obtained.

Starting compound: 1- (4-isobutylphenyl) -1-methylpentanol

Physicochemical properties

 Mass spec (mZ z): 560 (M + 1) +

Nuclear magnetic resonance scan Bae-vector (CDC 1 _3, TMS internal standard)

 δ: 0.87-0.89 (1 2 Η, m),

 23〜: I. 30 (1 H, m)

 1.39 to 1.47 (1 H, m)

 53 to 1.60 (1H, m)

 80 ~: I. 86 (2 H, m)

 95-2.01 (1H, m)

2.15 to 2.19 (2H, m), 2.20 (3 H, s), 2.28 (3 H, s), 2.42 (2 H, d),

 4.23 (2 H, t), 5.0 0 to 5.0 4 (1 H, m),

6.55 (1 H, d), 6.99 (1 H, d),

7. 0 7 to 7.10 (3 H, m),

 7.2 2 to 7.26 (3 H, m),

 7. 4 1 to 7.4.5 (1 H, m),

 8.2 1 to 8.23 (1 H, m), 9 2 1 (1 H, s) Example 6 1

 In the same manner as in Example 15, 41- [2- [N- (4-isopropylphenoxy) phenyl] -lubamoyl] phenoxy] butanoic acid was obtained.

 Raw material compound: Ethyl 4- [2- [N- [4-1- (4-Isopropylphenyloxy) phenyl] potumbamoyl] phenyloxy] butylate

Physicochemical properties

Elemental analysis value (as C ₂₆ H ₂₇ N0 ₅ · 0.2 H ₂₀ )

 C (%) H (%) N (%) Theoretical 7 1.44 6.3 2 3.20 Experimental 7 1.5 1 6.2 6 3.16 Mass spec (mZz): 433 ( M +)

Nuclear magnetic resonance spectra (CD C 1 _3, TMS internal standard)

 6: 1.24 (6 H, d), 2 2 8 (2 Η, m),

 26 1 (2 H, t), 28 88 (1 8, m), 426 (2 H, t), 692 (2Η, d), 69 9 (3H, m), 7 1 1 (1Η, t), 7 16 (2H, d), 745 (1Η, dt) 7 6 0 (2Η, d), 8 25 (1Η, dd) 9 7 6 (1 Η, s)

Example 6 2 In the same manner as in Example 15, 5, 4- [2-[[N- [4- (4-butylphenyloxy) phenyl] -lubamoyl] phenoxy] butanoic acid was obtained.

Starting compound: ethyl 4- [2 -— [N- [4- (4- (4-butylphenyl) phenyl] phenyl] -lubamoyl] phenyloxy] butylate

Physicochemical properties

Elemental analysis (as C ₂₇ H ₂₉ N0 ₅₎

 C (%) H (%) N (%) Theoretical value 72.46 6.53 3.13 Experimental value 72.29 6.5 1 3.09 Mass spectrometry value (mZz): 447 (M +)

 Nuclear magnetic resonance spectrum (CDC 1 TMS internal standard)

 δ: 0.93 (3Η, t) 1 35 (2 H, m),

 1.58 (2 H, m) 2 29 (2 H, m),

2.60 (4 H, m) 4 26 (2 H, t),

6.91 (2 H, m) 6 98 (3 H, m), 7.12 (3 H, m) 7 46 (1 H, d t)

7.6 1 (2 H, m) 8 25 (1 H, d d)

9 76 (1 H, s)

Example 63

 In the same manner as in Example 15, 5, 4- [2- [N- [4-1- (3-isopyrupanoxy) phenyl] -lubamoyl] phenoxy] butanoic acid was obtained.

Starting compound: ethyl 4- [2- [N- [4- (3-isopropylphenoxy) phenyl] dirubamoyl] phenoxy] petitate

Physicochemical properties

Elemental analysis value (as C ₂₆ H ₂₇ N0 ₅ · 0.40 H ₂ O) C (%) H (%) N (%) Theoretical value 7 0.8 6 6. 3 6 3.18 Experimental value 7 0.8 9 6. 3 7 3.15 Mass spectrometry value (mZz): 4 3 3 (M +)

 Nuclear magnetic resonance spectrum (CD C 1 TMS internal standard)

 6: 1.22 (6 H, d), 2 28 (2 Η, m),

 2.61 (2 H, t), 287 (1 H, m), 4.26 (2 H, t), 678 (1 H, d d),

6.90 (1 H, s), 6 95 (1 Η, d),

7.00 (3 Η, m), 7 11 (1 Η, t), 7.2 1 (1 Η, t), 7 4 5 (1 Η, t), 7.62 (2 Η, t) d), 8 25 (1Η, d), 9.79 (1Η, s)

Example 6 4

 In the same manner as in Example 15, 5, 4- [2- [Ν- [4- [5- (5-isopropyl-pyr-1-2-methylphenoxy) dinyl] caprubamoyl] phenoxy] butanoic acid was obtained.

Starting compound: Ethyl 4- [2- [Ν- [4-1- (5-isopropyl-1-2-methylphenoxy) phenyl] dirubamoyl] phenoxy] butylate

Elemental analysis value (as C ₂₇ H _2fl N0 ₅ )

 C (%) H (%) Ν (%) Theoretical value 72.4 66.5 33.1 3 13 Experimental value 72.5 36.5 5 63.07 Mass spectrometry value (mZz): 447 ( M +)

Nuclear magnetic resonance scan Bae-vector (CDC 1 _3, TMS internal standard)

 6: 1.18 (6 H, d), 2.19 (3 H, s),

2.29 (2 H, m), 2.62 (2Η, t), 2.82 (1Η, m), 4.27 (2Η, t), 6.79 (1 H d), 6.89 (2 H, d),

6.93 (1H _; dd), 7.00 (1H, d)

7.12 (1H _; t), 7.15 (1H, d) 7.46 (1H _: t), 7.58 (2H, d), 8.26 (1H _; t) dd), 9.73 (1H, s) Tables 1 to 16 show the chemical structural formulas of the compounds obtained in the above Examples.

table 1

32

32

ST

Οΐ

 L 1

iri00 / Z6df / JDd

 ella

891

6df / JOd 8Z8 £ I / Z6 OAV

 Halla

691

l00 / Z6df / JOd 8∑8 £ l / Z6 Ο

 halla

 091

lZlQ0 / Z6dC / IDd 8Z8 £ I / r6 OAV Table 6

Z9T Table 8

 6 Halla 9T

IiI00 / Z6df / IDd Table 10

表 11

Table 11

表 12

Table 12

 ει Halla

891

lZl00 / r6df / JDd

 l 挲

691

lZlQ0 / Z6dt / lDd

 siala o

irioo / r6df / J3d Table 16

Claims

The scope of the claims 1. A benzanilide derivative represented by the following general formula (I) or a pharmaceutically acceptable salt thereof:

(I) (Wherein, R ¹ is a hydrogen atom, a lower alkyl group, a lower alkoxy group or a halogen atom, R ² is a hydrogen atom or a lower alkyl group, R ³ is a lower alkyl group or a halogen atom, and (R ³ ) n represents that the benzene ring is substituted with 0 to 4 R ³ groups which may be the same or different, represents a lower alkylene group, X ₂ represents 10-, and formula 1 — 0—. (Wherein is a linear or branched alkylene group having 1 to 10 carbon atoms), A group represented by the formula: CH—NR ⁵ — (wherein R ⁴ ′ is a lower alkyl group) I R ⁴ 'represents an optionally substituted phenyl group, and R ^s represents a hydrogen atom or a lower alkyl group, respectively. ), A group represented by the formula: NR ⁵ —Y ₂ — or the formula: Y ₂ —NR ⁵ — (wherein, R ⁵ has the same meaning as described above, and Y ₂ represents a lower alkylene group, respectively). , And R ^{4 each} represent a phenyl group which may be substituted with a lower alkyl group. ) 2. In the above general formula (I), Χ ₂ is a group represented by the formula: Y _t — 0— (where Y! Represents a linear or branched alkylene group having 1 to 10 carbon atoms) 2. The compound according to claim 1 or a pharmaceutically acceptable compound thereof. 3. In the compound according to claim 2,  Or a pharmaceutically acceptable salt thereof, which is ethylethylene, propylmethylene, isopropylmethylene, butylmethylene, isobutylmethylene, heptylmethylene, or isoheptylmethylene. 4. The compound according to claim 1, wherein in the general formula (I), X ₂ is -0-, or a pharmaceutically acceptable salt thereof. 5 In the above general formula (I), X ₂ is a group represented by the formula —NR ⁵ —Y ₂ —, formula 1 Y ₂ —NR 1 or formula 1 CH—NR ⁵ — (wherein R ⁴ ′, R ⁵ and  I R ⁴ ' Y ₂ has the meaning described above. 2. The compound according to claim 1, which is or a pharmaceutically acceptable salt thereof. 6 Ethyl 4- [2— [Ν— [2,3-Dimethyl 4- (4-in-butyl-propyl-propyl-benzyloxy) phenyl]]-lvamoyl] phenyloxy] butylate according to claim 1 — [Ν- (4-isobutyl-α-isopropylbenzyloxy) -1-2-methylphenyl] -lubamoyl] phenoxy] butanoic acid, 4-1 3- [Dimethylphenyl] potumamoyl] phenoxy] butanoic acid. 4- [2- [Ν- [4- (a, 4-diisobutylbenzyloxy)-3,5-dimethylphenyl] potumbamoyl] butoxy] butanoic acid , 4-1 [2-[N-[4-(, 4 -diisobutylbenzyloxy)-1-2-methylphenyl] dirubamoyl] phenoxy] butanoic acid, 4-1 [2-[N-[2, 3-dimethyl-4-( 4-Isobutyl-isopropylbenzyloxy B) [Phenyl] carbamoyl] phenoxy] butanoic acid, 4- [2- [N- (4-iso-pyrupanoxy) phenyl] carbamoyl] phenoxy] butanoic acid, 4- [2- [N- [(4-Isobutyl-N-methyl Anilino) Methyl] -1-Methylphenyl] caphamyl] phenoxy] butanoic acid, or 4- [2- [N- [4-1-bis (4-propynylphenyl) methyl] -12-methylphenyl] caphamyl] phenoxy] Butanoic acid or their pharmaceutically acceptable 7. A pharmaceutical composition comprising the pharmacologically effective amount of the benzanilide derivative or the pharmaceutically acceptable salt thereof according to claim 1, and a pharmaceutically acceptable carrier.  8. General formula (I)

(I) (Wherein, R ¹ represents a hydrogen atom, a lower alkyl group, a lower alkoxy group or a halogen atom, R ² represents a hydrogen atom or a lower alkyl group, R ³ represents a lower alkyl group or a halogen atom, and (R ³ ) n Represents that the benzene ring is substituted with 0 to 4 R ³ groups which may be the same or different, X, represents a lower alkylene group, X ₂ represents 1 0—, and formula 1 — 0— A group represented by the formula (where Y! Is a straight-chain or branched alkylene group having 1 to 10 carbon atoms), A group represented by the formula: CH—NR ⁵ — (wherein R ⁴ ′ represents a phenyl group which may be substituted with R ⁴ ′ by a lower alkyl group, and R ⁵ represents a hydrogen atom or a lower alkyl group, respectively) ), A group represented by the formula: NR ⁵ -Y ₂ -or the formula — Υ ₂ -NR ⁵ — (wherein, R ⁵ has the same meaning as described above, and Υ ₂ represents a lower alkylene group, respectively) And R ⁴ is a lower grade And X represents an aryl group which may be substituted with a alkyl group. ) In the method for producing a benzanilide derivative or a pharmacologically acceptable salt thereof.  -General formula (I ')

(Wherein R ¹ , R ² , R ³ , (R ³ ) n, R ⁴ , ¾ and を have the above-mentioned meaning, and R ⁷ represents a carboxylic acid protecting group.) A method characterized by the hydrolysis of