WO1998056757A1 - Benzylamine derivatives - Google Patents

Abstract

Benzylamine derivatives represented by general formula (I) or pharmacologically acceptable salts thereof, which have an excellent ileal bile acid transporter inhibitory activity, wherein R1 represents substituted C¿6-10? aryl, optionally substituted tetrazolyl, C1-6 alkylsulfonyl, C1-6 alkylsulfinyl, or optionally substituted (C6-10 aryl)sulfonylcarbamoylamino; R?2, R3, and R4¿ each represents hydrogen; R5 represents optionally substituted C¿6-10? aryl; and R?6¿ represents C¿1-10? alkyl, a group having -W-R?7¿, or optionally substituted C¿7-16? aralkyl, provided when R?1¿ is C¿1-6? alkylsulfonyl or C1-6 alkylsulfinyl, then R?6¿ is not C¿1-10? alkyl.

Description

 Description Benzylamines [Technical field]

 The present invention relates to a benzylamine having an ileal bile acid transporter inhibitory activity or a pharmacologically acceptable salt thereof, a composition containing a benzylamine or a pharmacologically acceptable salt thereof as an active ingredient, a benzylamine or a pharmacologically acceptable salt thereof. Manufacture of a composition containing an acceptable salt as an active ingredient for inhibiting ileal bile acid transporter activity (especially a composition for treating or preventing hyperlipidemia or arteriosclerosis) and a medicament Of benzylamines or pharmacologically acceptable salts thereof, use of benzylamines or pharmacologically acceptable salts thereof to produce ileal bile acid transporter inhibitors, hyperlipidemia or artery Benzylamines or their pharmacologically acceptable for producing therapeutic or prophylactic agents for sclerosis The present invention relates to a method for treating or preventing hyperlipidemia or arteriosclerosis, which comprises using a salt or administering a pharmacologically effective amount of a benzylamine or a pharmacologically acceptable salt thereof to a warm-blooded animal.

[Background technology]

 Hyperlipidemia is one of the three major risk factors for ischemic heart disease, and it is widely accepted that lowering high cholesterol levels in blood is particularly useful for treating or preventing ischemic heart disease. I have. For example, HMG-CoA reductase inhibitors and ion-exchange resins are known as currently available therapeutic agents for hyperlipidemia, and these agents are effective in treating hyperlipidemia and arteriosclerosis. It has been used for therapeutic or prophylactic purposes [Am. J. Cardiol., 76, 899-905 (1995)].

ΗΜ G—C ο Α reductase inhibitor inhibits cholesterol synthesis, Has the effect of increasing LDL (low density lipoprotein) receptor in rats and taking blood cholesterol to promote excretion into bile. [Science, 232, 34 (1986)] Efficacy and safety are widely recognized and used by many patients.

 In addition, anion exchange resins adsorb bile acids and prevent reabsorption of bile acids in the intestine, thereby promoting the conversion of cholesterol to bile acids in the liver, thereby lowering blood cholesterol levels. N. Engl. J. Med., 302, 1219-1222 (1980)]. As such anion exchange resin, for example, a method using cholestyramine has already been put to practical use, and it is difficult for the drug to be absorbed into the body. It is the first-line drug in the treatment of hyperlipidemia. However, cholestyramine has the drawbacks that it is extremely difficult for patients to take because the dose per dose is extremely large and the rough feel of the resin when taken is left in the mouth. In addition, the anion exchange resin also adsorbs and discharges certain vitamins, minerals, drugs, etc.Therefore, it is necessary to consider replenishment of bismuthamine and changes in the administration method of concomitant drugs. Many.

 Recently, a protein acting in the first step of bile acid reabsorption in the ileum, a ileal bile acid transporter, has been cloned [Wong MH et al., I. Biol. Chem., 269, 1340-1347 (1994). ]. It is thought that the same pharmacological effect as cholestyramine can be obtained by inhibiting the ileal-type bile acid transporter activity. From such a background, it has been attempted to find an ileal-type bile acid transporter inhibitor. [Wess G, et al., J. Med. Chem .. 37. 873-875 (1994)].

By the way, JP-A-2-49771 and JP-A-1011064 disclose the following general compounds as intermediates of pyrazole carboxylic acid amides disclosed as insecticides. Equation (A) (A)

R ³ R:

[Wherein, R ³ , R ⁴ and R ^s each independently represent a hydrogen atom, a C 1, —C ₄ alkyl group or a phenyl group, R ⁶ and R ⁷ each independently represent a hydrogen atom, Halogen atom, -C 8 alkyl group, C ₃ -C 6 cycloalkyl group, C ₂ -C ₄ alkoxyalkyl group, d-C ₄ alkoxy group, d—C ₄ noroalkoxy group, nitro group, trifluoromethyl group, phenyl group, Penjiru group, Fuenoki sheet group, Benjiruokishi group, d - C ₄ alkylamino group, C ₂ - C 8 dialkylamino group, Shiano group, C ₂ - C beta alkylaminocarbonyl group, C ₃ - di § shows the C ₄ alkyl sulfonyl Le group - Le kill amino Cal Poni group, piperidinocarbonyl group, a morpholino force Ruponiru group, trimethylsilyl group, d - C ₄ alkylthio group, d - C ₄ Arukirusurufu Iniru group or d,. ] Has been disclosed. However, its use as an ileal bile acid transporter inhibitor is not known.

 Further, as conventionally known benzylamines, for example, Japanese Patent Application Laid-Open No.

No. 39 discloses a pyrimidine derivative, WO92 / 000067 an imidazole derivative, and WO95ZZ1966 a (1-phenyleneheterocyclyl) methylamine derivative. W097 / 400207 discloses substituted benzylamines. However, its use as an ileal bile acid transport inhibitor is not known.

 Further, as benzylamines useful for the treatment or prevention of hyperlipidemia or arteriosclerosis, for example, substituted benzofuran derivatives are listed in USP 44851 12 and WO 9

A phenoxyphenylacetic acid derivative is disclosed in 4/2159, and a substituted phenyl derivative is disclosed in W095 / 325284. [Disclosure of the Invention]

 The present inventors have conducted long-term studies on the synthesis of a series of benzylamines and their pharmacological actions, and as a result, benzylamines have an excellent ileal bile acid trans-sulfone inhibitory activity, They have found that they are useful as therapeutic or preventive agents for hyperlipidemia and arteriosclerosis, and have completed the present invention.

 That is, the present invention relates to a composition comprising, as an active ingredient, a benzylamine having a ileal bile acid transporter inhibitory activity or a pharmacologically acceptable salt thereof, a benzylamine or a pharmacologically acceptable salt thereof as an active ingredient, For inhibiting the activity of the ileal bile acid transporter, which contains an active ingredient or a pharmacologically acceptable salt thereof as an active ingredient (particularly, a composition for treating or preventing hyperlipidemia or arteriosclerosis). ), The use of benzylamines or pharmacologically acceptable salts thereof for the manufacture of a medicament, the use of benzylamines or pharmacologically acceptable salts thereof for the manufacture of an ileal bile acid transporter inhibitor, Benzylamines or their pharmacology for producing a therapeutic or prophylactic agent for lipemia or arteriosclerosis The present invention provides a method for treating or preventing hyperlipidemia or arteriosclerosis, which comprises using a pharmaceutically acceptable salt or administering a pharmacologically effective amount of a benzylamine or a pharmacologically acceptable salt thereof to a warm-blooded animal.

 The compound of the present invention has the general formula (I).

(I)

In the above formula R ¹ is a C _e —C ₁₀ aryl group substituted by 1 to 3 groups selected from the substituent group α, a tetrazolyl group optionally substituted by a group selected from the substituent group 3; (C - C beta cycloalkyl) force Rubamoiru group, (d - C alkyl) sulfonyl force Rubamoiru group, which may be 1 to 3 substituted with a group selected from substituent group δ (C - C ₁₀ 7 reel) sulfonylcarbamoyl group, a sulfo group, d - C alkyl Rusuruhoniru group, which may be 1 to 3 substituted with a group selected from substituent group 3 C β - C ₁₀ 7 reel sulfonyl group, mono- (d - C β alkyl) Aminosuruhoni group, di- (C - C alkyl) amino Nosuruhoniru group, C - C Arukirusu Rufieru group, which may be 1 to 3 substituted with a group selected from substituent group 3 C ₇ one C n Selected from arylcarbonylamino group and substituent group 3 And is has been Moyoi tetrazolyl Luca Lupo sulfonyl § amino group or 1 or may be three substituted with a group selected from Substituent Group / 3 substituted with a group (C ₆ - C ₁₀ Ariru) sulfonylcarbamoyl Ami A group

R ² , R ³ and R ⁴ may be the same or different and are each a hydrogen atom, a d-C β alkyl group, a d-C β alkoxy group, a hydroxyl group, a halogen atom, an amino group, a mono- (C

! -Cβalkyl) amino group or di (d-Calkyl) amino group

R ⁵ may be substituted with 1 to 3 groups selected from Substituent Group 3 and may be substituted with 1 to 3 C ₆ -C ₁₀ aryl groups or a group selected from Substituent Group J3. Which may be condensed with a benzene ring, represents a phenyl, a pyrrolyl, a 1,1-dioxocenyl, a thiazolyl or an oxazolyl group;

R ⁶ is d—C ₁₀ alkyl group, formula—W—R ⁷ [where W is a single bond or C! And R ⁷ represents a C ₃ -C β cycloalkyl group which may be substituted by 1 to 3 groups selected from Substituent Group 7 and may be condensed with a benzene ring. ] Group or 1 group selected from Substituent Group § to 3 optionally substituted C ₇ having - shows the C ₁₆ Ararukiru group. However, R ¹ is, d - may exhibit C _beta alkylsulfonyl group or a C one C _e Arukirusu sulfinyl group, R ^e is d - shows the C _{1 0} alkyl group other than the group.

<Substituent group

Substituted with a group selected from the substituent group) 3 which may be a tetrazolyl group, sulfo groups, C one C _e alkylsulfonyl group, d - is selected from C _theta alkylsulfonyl § amino group and substituent group / 3 that 1 may be three substituted with a group C _e - C _{1 0} Ari Le sulfonyl § amino group

<Substituent group β>

 C, -C alkyl group, d-C alkoxy group and substituent group for halogen atom Ύ>

 C-C alkyl group, -C alkoxy group, halogen atom and formula Z

-R ⁸ [wherein, Z represents a single bond or a d-C alkylene group, and R ⁸ represents a carboxy group, a CC alkoxycarbonyl group, a carbamoyl group, a mono- (C! -C alkyl) carbamoyl group , Di- (d-Calkyl) capillum, a d-Calkylsulfonyl group or a hydroxyl group. A group having

<Substituent group δ>

 A phenyl group which may be substituted with 1 to 3 groups selected from a CC alkyl group, a d-C alkoxy group, a halogen atom and a substituent group / 3.

 Further, the ileal bile acid transporter inhibitor of the present invention contains a compound having the general formula (II) or a pharmacologically acceptable salt thereof as an active ingredient.

In the above formula R ¹ is a C ₆ -C ₁₀ aryl group substituted with 1 to 3 groups selected from the substituent group α, a tetrazolyl group optionally substituted with a group selected from the substituent group / 3 , (C - C beta cycloalkyl) force Rubamoiru groups, (C i - C alkyl) sulfonyl force Rubamoiru group, 1 may be three substituted with a group selected from substituent group δ (C β - C ₁₀ 7 reel) sulfonylcarbamoyl group, sulfo group, C, -C alkylsulfonyl group, one or three groups selected from the substituent group / 3, which may be substituted by 1 to 3 C — (: ₁₀ arylsulfonyl group, mono- (d - C _beta alkyl) Aminosuruhoni group, di- (d - C alkyl) amino Nosuruhoniru groups, - C beta Arukirusu Rufiniru group may be 1 to 3 substituted with a group selected from substituent group 3 C ₇ one § Li one Luca Lupo sulfonyl § amino group, substituent group] 3 It is substituted by a group et selected Moyoi tetrazolyl carbonyl § amino group or 1 or may be three substituted with a group selected from Substituent Group 3 (C ₆ - C ₁₀ Ariru) sulfonylcarbamoyl Represents an amino group,

R ² , R ³ and R ⁴ are the same or different and are each a hydrogen atom, -C alkyl group, d-C β alkoxy group, hydroxyl group, halogen atom, amino group, mono- (C

! -C alkyl) amino group or di- (C, -C alkyl) amino group

R ⁵ is a substituent selected from the group of substituents 3) and may be substituted with 1 to 3 C _β -C ₁₀ aryl groups or a group selected from the group of substituents / 3 and is substituted with 1 to 3 groups. Which may be condensed with a benzene ring, represents a phenyl, pyrrolyl, 1,1-dioxocenyl, thiazolyl or oxazolyl group;

R ^θ is a d—C ₁₀ alkyl group, Formula I W—R ⁷ [where W is a single bond or C! - C _beta represents an alkylene group, R ⁷ is 1 to 3 may be substituted may be combined well benzene ring condensed C ₃ groups selected from Substituent Group § - a C cycloalkyl group. ] Group or 1 group selected from Substituent Group § to 3 optionally substituted C ₇ having - shows the C ₁₆ Ararukiru group. <Substituent group ot>

A group selected from a tetrazolyl group, a sulfo group, a C-Cβ alkylsulfonyl group, a d-Cβ alkylsulfonylamino group which may be substituted with a group selected from the substituent group 0, and a group selected from the substituent group i3 in 1 to 3 substituents which may be C _e - C _{1 0} 7 Li Rusuruhoniruami amino group

 <Substituent group β>

C! -C _β alkyl group, C,-C alkoxy group and halogen atom

 <Substituent group Ύ>

C t - C alkyl group, C, - C beta alkoxy group, a halogen atom and the formula - Zeta - R ⁸ [wherein, Zeta is a single bond or - a C alkylene group, R ⁸ is force Rupokishi group, C ₂ -C alkoxycarbonyl group, sorbamoyl group, Mono (C-Cβ alkyl) rubamoyl group, G (Ci-C alkyl) rubamoyl group, d-C alkylsulfonyl group or hydroxyl group. <Substituent group δ>

 A phenyl group which may be substituted by 1 to 3 groups selected from a C-C alkyl group, a d-Cβ alkoxy group, a halogen atom and a substituent group / 3.

In the above, C ₆ -d of “C ₆ —C ₁₀ aryl group substituted by 1 to 3 groups with a group selected from substituent group α” in the definition of R ¹ . The aryl moiety represents an aromatic hydrocarbon group having 6 to 10 carbon atoms, such as phenyl, indenyl, and naphthyl, and is preferably a phenyl group.

In the above, “(:, -C _β alkyl group)” in the definition of the substituent group) 3 and δ indicates a linear or branched alkyl group having 1 to 6 carbon atoms, for example, methyl, Ethyl, propyl, isopropyl, butyl, isoptyl, s-butyl, t-butyl, pentyl, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, hexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 2-ethylbutyl group, preferably C, —C ₄ alkyl group, more preferably Is a d-C alkyl group, particularly preferably a methyl group.

In the above, the substituent group ("(:, -C alkoxy group)" in the definition of 3 and <3 indicates a group in which an oxygen atom is bonded to the d- _Cβ alkyl group. Si, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, s-butoxy, t-butoxy, pentoxy, isopentoxy, 2-methylbutoxy, n-pentoxy, 1-ethylpropoxy, hexyloxy, 4-methylpentoxy Toxic, 3-methylpentoxy, 2-methylpentoxy, 1-methylpentoxy, 3,3-dimethylbutoxy, 2,2-dimethylbutoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1, 3-dimethylbutoxy, 2,3-dimethylbutoxy, 2-ethylbutoxy, preferably 1 C ₄ alkoxy, more preferably -C ₂ In the above, it is an alkoxy group, particularly preferably a methoxy group. In the above, the "halogen atom" in the definition of the substituent group 3) and <5 is, for example, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom. Atom, preferably a fluorine atom or a chlorine atom.

In the above, the “tetrazolyl group optionally substituted with a group selected from the substituent group 3” in the definition of the substituent groups α and R ¹ is, for example, 1 H-tetrazole-5-yl, 1 1-Methoxytetrazole-5-yl, 1-Methoxytetrazole-5-yl, 1-Ethoxytetrazole-5-yl, 1-Fluorotetrazole-5-yl 1-chlorotetrazole-5-yl group. In R ¹ , preferably a substituent group consisting of -C ₄ alkyl, -C alkoxy, a fluorine atom and a chlorine atom (hereinafter, substituted with a group selected from a substituent group (hereinafter referred to as 31)). And more preferably a tetrazolyl group. A tetrazolyl group which may be substituted with a group selected from a substituent group consisting of CC alkyl, d-C alkoxy, a fluorine atom and a chlorine atom (hereinafter referred to as “substituent group” 32); , Methyl, methoxy, a tetrazolyl group which may be substituted with a group selected from a substituent group consisting of a fluorine atom and a chlorine atom (hereinafter, referred to as a substituent group / 33). —It is a tetrazole-5-yl group. The substituent group α is preferably a tetrazolyl group which may be substituted with a group selected from the substituent group 32, and more preferably a group selected from the substituent group 33. A tetrazolyl group which may be substituted, particularly preferably a 1-tetrazol-5-yl group.

In the above, “d-Cβ alkylsulfonyl group” in the definition of Substituent group α, R ¹ and R ⁸ of Substituent group a indicates a group in which a sulfonyl group is bonded to the above-mentioned C alkyl group. For example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, s-butylsulfonyl, t-butylsulfonyl, pentylsulfonyl, isobenzylsulfonyl, 2-methylbutylsulfonyl, neopentyl Sulfonyl, 1-ethylpropylsulfonyl, hexylsulfonyl, 4-methylpentylsulfonyl, 3-methylpentylsulfonyl, 2-methylpentylsulfonyl, 1-methylpentylsulfonyl, 3,3-dimethylbutylsulfonyl, 2,2 —Dimethylbutylsulfonyl, 1 1 one-dimethylbutyl sulfonyl, 1, 2 _ Jimechirubu Chirusuruhoniru, 1, 3 - dimethyl-butylsulfonyl, 2, 3 - dimethyl-butyl sulfonyl, 2 - E chill butylsulfonyl group. In the substituent group α, it is preferably a C i -C alkylsulfonyl group, more preferably a methylsulfonyl, ethylsulfonyl, propylsulfonyl or butylsulfonyl group, more preferably methylsulfonyl or An ethylsulfonyl group, particularly preferably a methylsulfonyl group. R ¹ is preferably —C alkylsulfonyl group, more preferably methylsulfonyl, ethylsulfonyl, It is a pyrsulfonyl or butylsulfonyl group, more preferably a methylsulfonyl, ethylsulfonyl or butylsulfonyl group, particularly preferably a methylsulfonyl or ethylsulfonyl group. R ⁸ in the substituent group a is preferably a d-C ₄ alkylsulfonyl group.

 In the above, the “d-Cβ alkylsulfonylamino group” in the definition of the substituent group 0; indicates a group in which an amino group is bonded to one of the C: -Cβ alkylsulfonyl groups, For example, methylsulfonylamino, ethylsulfonylamino, propylsulfonylamino, isopropylsulfonylamino, butylsulfonylamino, isobutylsulfonylamino, s-butylsulfonylamino, t-butylsulfonylamino, pentylsulfonylamino, pentylsulfonylamino, Isopentylsulfonylamino, 2-methylbutylsulfonylamino, neopentylsulfonylamino, 1-ethylpyruspirylsulfonylamino, hexylsulfonylamino, 4-methylpentylsulfonylamino, 3-methylpentylsulfonylamino Amino, 2-Methylpentyl sulfonylua Roh, a 1 one methyl pentylsulfonyl § Mi amino group, preferably a methyl Suruhoniruamino group or E chill sulfonyl § amino group, particularly preferably a methylcarbamoyl Rusuruhoniruami cyano group.

In the above description, C in the definition of “C ₆ —C ₁₀ arylsulfonylamino group which may be substituted by 1 to 3 substituent (s) selected from Substituent Group 3” in the definition of Substituent Group α ₆ - C _{1 0} § reel sulfonyl § amino moieties, one C _e - C _{1 0} § reel sulfonyl group (wherein C ₆ - shows the C _{1 0} § Li Ichiru group sulfonyl group is bonded to the group, for example, Phenylsulfonyl, indenylsulfonyl, and naphthylsulfonyl groups) to which an amino group is bonded, for example, phenylsulfonylamino, indenylsulfonylamino, and naphthylsulfonylamino group. It is a phenylsulfonylamino group. In addition, one to three substituents (preferably one) selected from Substituent Group 3 are preferably groups selected from Substituent Group / 32. Such "optionally be 1 to 3 substituted with a group selected from substituent group / 3 C _e A “C ₁₀ arylsulfonylamino group” is, for example, phenylsulfonylamino, 2-methylphenylsulfonylamino, 3-methylphenylsulfonylamino, 4-methylphenylsulfonylamino, 2— Methoxyphenylsulfonylamino, 3-methoxyphenylsulfonylamino, 4-methoxyphenylsulfonylamino, 2-fluorophenylsulfonylamino, 3_fluorophenylsulfonylamino, 4-fluorophenylsulfonylamino Mino, 2—Cross-phenylphenylsulfonylamino, 3—Cross-phenylphenylsulfonylamino, 4 Monochrome phenylsulfonylamino, (Indone-1-yl) sulfonylamino, (Indane-2-yl) sulfonylamino, (11-naphthalene) sulfonylamino, (naphthalene-2 — A) phenylsulfonylamino group, preferably a phenylsulfonylamino group which may be substituted with a group selected from the substituent group β2, and particularly preferably a phenylsulfonylamino group. is there.

In the above, the substituent group α of the “C ₆ —C ₁₀ aryl group substituted by 1 to 3 groups selected from the substituent group α” in the definition of R ¹ is preferably Substituent group / 32 A tetrazolyl group, a sulfo group, a d-C alkylsulfonyl group, a methylsulfonylamino group, an ethylsulfonylamino group, and a substituent group 32 And a group selected from the group consisting of a phenylsulfonylamino group which may be substituted with a group selected from the following (hereinafter, referred to as a substituent group αΐ). More preferably, the group is selected from the substituent group 33. Group consisting of a tetrazolyl group, a methylsulfonyl group, an ethylsulfonyl group, a propylsulfonyl group, a butylsulfonyl group, a methylsulfonylamino group and a phenylsulfonylamino group which may be substituted with Is a group et selected, more preferably, 1 H- Tetorazoru 5 - I group, a methylsulfonyl group and Echirusuruhoniru group, particularly preferably a methylsulfonyl group.

Specific examples of such a “C ₆ -C ₁₀ aryl group substituted by 1 to 3 groups selected from the substituent group α” include, for example, 2 —, 3 — or 4- (1 H- Torazo I L-5-phenyl) 2-, 3- or 4- (1-methyltetrazole-5-yl) phenyl, 2-, 3- or 4- (1-ethylethyltetrazole-5-yl) ) Phenyl, 2-, 3-or 4-(1-methoxytetrazol-5-yl) phenyl, 2-, 3-or 4-(1-ethoxytetrazo-1-5-yl) phenyl, 2- , 3 — or 4-1 (1 -fluorotetrazo-1-yl 5-yl) phenyl, 2 —, 3-or 4-1 (1 -chlorotetrazole-5-yl) phenyl, 2 —, 3 — or 4-1-sulfophenyl , 2 —, 3 — or 4 monomethylsulfonylphenyl, 2 —, 3 — or 4ethylsulfonylphenyl, 2 —, 3 — or 4 — propylsulfonylphenyl, 2 —, 3 — or 4 — iso Propylsul Nylphenyl, 2 —, 3 — or 4-butylsulfonylphenyl, 2 —, 3 — or 4 —isobutylsulfonylphenyl, 2 —, 3 — or 4 — s —butylsulfonylphenyl, 2 —, 3 — or 4 1-tert-butylsulfonylphenyl, 2 — or 4 —pentylsulfonylphenyl, 2 — or 4 isopentylsulfonylphenyl, 2 — or 4-1- (2-methylbutylsulfonyl) phenyl, 2 — (1 _ Phenyl, 2 — or 4 hexylsulfonylphenyl, 2 —, 3 — or 4 — (methylsulfonylamino) phenyl, 2 —, 3 _ or 4 (ethylsulfonylamino) Phenyl, 2 _, 3 _ or 4 — (propylsulfonylamino) phenyl, 2 — or 4 −1 (isopropyls Honiruamino) phenyl, 2 - or 4 one

(Butylsulfonylamino) phenyl, 2- or 4- (isobutylsulfonylamino) phenyl, 2- or 4- (s-butylsulfonylamino) phenyl, 2- or 4- (t-butylsulfonyl) Amino) phenyl, 2 —, 3 — or 4-1 (phenylsulfonylamino) phenyl, 2 —, 3 — or 4-1 (

2 — methylphenylsulfonylamino) phenyl, 2 —, 3 _ or 4 _ (3 -methylphenylsulfonylamino) phenyl, 2 —, 3 _ or 4 — (4 — methylphenylsulfonylamino) ) Phenyl, 2 —, 3 — or 4 — (2 — Methoxyphenylsulfonylamino) phenyl, 2_3- or 4- (3-methoxyphenylsulfonylamino) phenyl, 2-3- or 4- (4-methoxyphenylsulfonylamino) phenyl , 2-3-or 4-(2-fluorophenylsulfonylamino) phenyl, 2-3-or 4-(3-fluorophenylsulfonylamino) phenyl, 2-3-or 4-(4 2-fluorophenylsulfonylamino) phenyl, 2 — 3 — or 4 — (2-chlorophenylsulfonylamino) phenyl, 2 —, 3 — or 4- (3-cyclomethylphenylsulfonylamino) ) Phenyl, 2 _, 3 _ or 4-(4-chloro-phenylsulfonylamino) phenyl, 2,4-di-(methylsulfonyl) phenyl, 2,4-di-(ethylsulfur) Nyl) phenyl, 2,4,6—tri (methylsulfonyl) phenyl, 2—, 3— or 4- (1H-tetrazol-5-yl) indenyl, 2— or 4-1-1 (1— Methyltetrazole-5-yl) indenyl, 2-sulfoindenyl, 2—, 3_ or 4-methylsulfonylindenyl, 2—, 3—or 4-ethylsulfonylindenyl, 2—or 4-propylsulfonylindenyl Nil, 2 _, 3 — or 4 — (methylsulfonylamino) indenyl, 2 —, 3 — or 4 — (ethylsulfonylamino) indenyl, 3 — or 4 mono (phenylsulfonylamino) indenyl, 2 — 3 — or 4-1- (1 H-tetrazole-5-yl) naphthyl, 2 — or 4--1- (1-methyltetrazol-5-yl) naphthyl , 2 —sulfonaphthyl, 2 —, 3 — or 4-methylsulfonylnaphthyl, 2 —, 3 — or 4 —ethylsulfonylnaphthyl, 2 — or 4 —propylsulfonylnaphthyl, 2 —, 3 1 or 4 (methylsulfonyl) Namino) naphthyl, 2 —, 3 — or 4 — (ethylsulfonylamino) naphthyl, 3 — or 4-1 (phenylsulfonylamino) naphthyl group, preferably 2 —, 3 — or 4-1 (1 H-tetrazol-5-yl) phenyl, 2 —, 3 — or 4 — (1 —methyltetrazol-5-yl) phenyl, 2 — 3 — or 4 — (1-methoxytetrazol) — 5 —yl) phenyl, 2 —, 3— or 4-one (1 -fluorotetrazole— 5 —yl) phenyl, 2 —, 3— or 4-one (1 -chlorotetrazole-5-) Le) phenyl, 2-, 3- or 4-methylsulfonylphenyl, 2-, 3- or 4-ethylsulfonylphenyl, 2-, 3- or 4-propylsulfonylphenyl, 2-, 3- or 4- Butylsulfonylphenyl, 2-, 3- or 4-methylsulfonylaminophenyl or 2-, 3- or 4-monophenylsulfonylaminophenyl, more preferably 2-, 3- Is a 4- (1H-tetrazol-5-yl) phenyl, 2-, 3- or 4-methylsulfonylphenyl, 2-, 3- or 4-ethylsulfonylphenyl group, and particularly preferably, 2 — Chill sulfonyl phenylalanine, a 3-Mechirusuruhoni Rufueniru or 4-methylsulfonyl-phenylalanine group.

In the above, the “(C ₃ -C cycloalkyl) caproluvyl group” in the definition of R ¹ is a C ₃ -C cycloalkyl group (a saturated cyclic hydrocarbon group having 3 to 6 carbon atoms) , Cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups) and a carbamoyl group bonded to, for example, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, and cyclohexylcarbamoyl. Is a C-C cycloalkyl group.

The At a, defined in "(C, - C beta alkyl) sulfonyl Rukaruba moil group" for R ^1, one of the C, - the C _beta alkylsulfonyl groups force Rubamoiru group is bonded to the group For example, methylsulfonylcarbamoyl, ethylsulfonyl carbamoyl, propylsulfonylcarbamoyl, isopropylsulfonylcarbamoyl, butylsulfonylcarbamoyl, isobutylsulfonylcarbamoyl, —butylsulfonylcarbamoyl, -butylsulfonylcarbamoyl, pentylsulfonylcarbamoyl, Isopentylsulfonylcarbamoyl, 2—methylbutylsulfonylcarbamoyl, neopentylsulfonylcarbamoyl, 1 1-ethylpropylsulfonylcarbamoyl, hexylsulfonylcarbamoyl, 4-methylpentylsulfonylcarbamoyl, 3—methylpentylsulfonylcarbamoyl, 2—methylpentylsulfonylcarbamoyl, 1—methylpentylsulfonylcarbamoyl, 3,3-dimethylbutylsulfonyl Carbamoyl, 2,2-dimethylbutylsulfonylcarbamoyl, 1,1-dimethylbutylsulfonylcarbamoyl, 1,2-dimethylbutylsulfonylcarbamoyl, 1,3-dimethylbutylsulfonylcarbamoyl, 2,3-dimethylbutylsulfonylcarbamoyl, 2 —Ethyl butylsulfonylcarbamoyl group, preferably (C 1 -C alkylsulfonyl) group, particularly preferably (d—C alkylsulfonyl) group A moil group.

In the above, C _{e of} “1 to 3 groups which may be substituted with a group selected from the substituent group δ in the definition of R ¹ (C ₆ —. Aryl) sulfonylcarbamoyl group” - C _{1 0} § Li Lumpur) sulfonylcarbamoyl portion shows the C _e _ C _{1 0} 7 Li Rusuruho sulfonyl groups force Rubamoiru group is bonded to the group, for example, phenylalanine sulfonyl Cal Bamoiru, Lee Ndeniru A sulfonylcarbamoyl group and a naphthylsulfonylcarbamoyl group, preferably a phenylsulfonylcarbamoyl group. In addition, the above-mentioned (C 1 -C ₁₀ aryl) sulfonylcarbamoyl group has 1 to 3 substituents (preferably 1) selected from substituent group δ in the -C alkyl. A phenyl group which may be substituted by 1 to 3 (preferably 1) groups selected from the group consisting of the aforementioned d-C alkoxy group, the halogen atom and the substituent group / 3. A group consisting of a d-C alkyl group, a d-C ^ alkoxy group, a halogen atom, and a phenyl group which may be substituted with a group selected from the above-mentioned substituent group i31 (hereinafter referred to as a substituent group ( . 3 1 hereinafter) is a group selected from, more preferably, - C z alkyl group, C _t - C ₂ alkoxy group, a fluorine atom, a group selected from a chlorine atom and the location substituent group 3 2 A group consisting of a phenyl group which may be substituted with (hereinafter, referred to as a substituent group (32)) Is a group et selected, more preferably, methyl, main bets Alkoxy, fluorine atom, chlorine atom and optionally substituted phenyl group optionally (the substituents, C - C ₂ alkyl, main butoxy, fluorine atom or chlorine atom) substituent group consisting of (hereinafter, substituent group [delta] 3 And particularly preferably a group selected from a substituent group consisting of a methyl group, a phenyl group, and a methylphenyl group (hereinafter, referred to as a substituent group <34).

Such "optionally be 1 to 3 substituted with a group selected from Substituent group [delta] (C _beta one C ₁₀ § Li Lumpur) sulfonylcarbamoyl group", for example, Fuenirusuruhoni carbamoyl, 2 -, 3 — Or 4 _methylphenylsulfonylcarbamoyl, 2 —, 3 — or 4 —ethylphenylsulfonylcarbamoyl, 2 —, 3 — or 4-methoxyphenylsulfonylcarbamoyl, 2 —, 3— or 4 monofluorophenylsulfonylcarbamoyl, 2 —, 3 — or 4 monophenylphenylsulfonylcarbamoyl, 2 —, 3 — or 4 _ (2 —, 3 — or 4 monomethylphenyl) phenylsulfonylcarbamoyl, 2 _ , 3 — or 4-(2 —, 3 — or 4 monoethylphenyl) phenylsulfonylcarbamoyl, 2 —, 3 — or 4 _ (2 —, 3 — or 4-methoxyphenyl) phenylsulfonylcarbamoyl, 2 —, 3 _ or 4 _ (2 —, 3 — or 4 —fluorophenyl) phenylsulfonylcarbamoyl, 2 —, 3 — Or 4-(2 —, 3 _ or 4 monophenyl) phenylsulfonylcarbamoyl, 5 —methylindene 1-yl, 5 —methylindene-2-yl, 5-methylnaphthalene 1 — A 5-phenylmethyl-2-phenyl-2-yl group, preferably a phenylsulfonylcarbamoyl group which may be substituted with a group selected from the aforementioned substituent group <51. Is a phenylsulfonylcarbamoyl group which may be substituted with a group selected from the substituent group <52, more preferably a phenyl group which may be substituted with a group selected from the substituent group δ3. Sulfo Ri carbamoylmethyl group der, in particular phenylene which may be substituted with a group selected from the substituent group [delta] 4 preferably Rusuru Honi carbamoyl group. The At a, in the definition of R ¹ in the "optionally be 1 to 3 substituted with a group selected from substituent group / 3 C ₆ - C ₁₀ § Li one Rusuruhoniru group" - C ₁₀ § Li one Rusuru Honiru moiety, the C _e _ C ₁₀ § indicates the same meaning as Li one Rusuruhoniru group, preferably a phenylalanine sulfonyl group. In addition, 1 to 3 substituents (preferably 1) selected from the substituent group 3 are preferably groups selected from the substituent group 31 and more preferably It is a group selected from the above-mentioned substituent group / 32, particularly preferably a group selected from the above-mentioned substituent group / 33.

Such a “C ₆ —C ₁₀ arylsulfonyl group optionally substituted by 1 to 3 groups selected from the substituent group β” is, for example, phenylsulfonyl, 2 —, 3 — or 4 1-methylphenylsulfonyl, 2—, 3— or 4 monoethylphenylsulfonyl, 2—, 3— or 4—methoxyphenylsulfonyl, 2—3— or 4 monofluorophenylsulfonyl, 2—, 3_ or 4 Phenylsulfonyl, (indene_1-, 2- or 3-yl) sulfonyl, (naphthalene-1--2-yl) sulfonyl, (naphthalene-111 or 2-yl) sulfonyl group, It is preferably a phenylsulfonyl group which may be substituted with a group selected from the above-mentioned substituent group / 31, and more preferably a phenylsulfonyl group which may be substituted with a group selected from the above-mentioned substituent group / 32. A There phenylalanine sulfonyl group, more preferably a good phenylalanine alkylsulfonyl group optionally substituted with a group selected from the substituent group beta 3, are particularly good suitable is a phenylalanine sulfonyl group.

The At a, in the definition of R ¹ "mono- (C, one C _e alkyl) Aminosuru Honiru group" include mono - (d - C _e alkyl) amino group (one of the d - C alkyl group Represents a group having an amino group bonded thereto, for example, a methylamino, ethylamino, propylamino, isopropylamino, butylamino, isobutylamino, s-butylamino, t-butylamino, pentylamino, hexylamino group. ) Represents a group to which a sulfonyl group is bonded, for example, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl Honyl, butylaminosulfonyl, isobutylaminosulfonyl, s-butylaminosulfonyl, t-butylaminosulfonyl, pentylaminosulfonyl, hexylaminonosulfonyl, preferably methylaminosulfonyl or ethylaminosulfonyl It is.

In the above, the “di (d-C _β alkyl) aminosulfonyl group” in the definition of R ¹ is a di (d-C alkyl) amino group (two identical or different C i- C represents a group in which an alkyl group is bonded to an amino group, such as dimethylamino, getylamino, N—ethyl_N—methylamino, dipropylamino, disopropylamino, N—methyl-N_propylamino, dibutylamino, Diisobutylamino, di-s-butylamino, di-t-butylamino, dipentylamino, N-ethyl-N-propylamino, dihexylamino), and a sulfonyl group. For example, dimethylaminosulfonyl, getylaminosulfonyl, N-ethyl-N-methylaminosulfonyl, dipropylaminosulfonyl Nyl, diisopropylaminosulfonyl, N—methyl-N—propylaminosulfonyl, dibutylaminosulfonyl, diisobutylaminosulfonyl, dys—butylaminosulfonyl, di-t-butylaminonosulfonyl, dipentylaminosulfonyl, N—ethylethyl N —Propylaminosulfonyl, dihexylaminosulfonyl, preferably dimethylaminosulfonyl or getylaminosulfonyl.

In the above, “C! -C alkylsulfinyl group” in the definition of R ¹ indicates a group in which a sulfinyl group is bonded to the above-mentioned C 1 -C alkyl group, for example, methylsulfinyl, ethylsulfinyl , Propylsulfinyl, isopropylsulfinyl, butylsulfinyl, isobutylsulfinyl, s-butylsulfinyl, t-butylsulfinyl, pentylsulfinyl, isopentylsulfinyl, 2 —methylbutylsulfinyl, neopentylsulfinyl, 1 —Ethylpropylsulfinyl, hexylsulfinyl, 4-methylpentylsulfinyl Nyl, 3-methylpentylsulfinyl, 2-methylpentylsulfinyl, 1-methylpentylsulfinyl, 3,3-dimethylbutylsulfinyl, 2,2-dimethylbutylsulfinyl, 1,1-dimethylbutylsulfinyl, 1,2-dimethylbutylsulfinyl sulfinyl, 1, 3 _ dimethyl-butylsulfinyl, 2, 3 one-dimethylbutyl sulfinyl, 2 - E chill Petit Rusuru arylsulfinyl group, preferably a d - a C ₄ alkylsulfinyl group, particularly preferably a d - C ₂ alkyl It is a rusulfinyl group.

In the definition of R ¹ , C ₇ — C n of “C ₇ —C n arylarylcarbonylamino group which may be substituted by 1 to 3 groups selected from substituent group 3” in the definition of R ¹ Ari Luca Lupo sulfonyl § amino moiety, the C _e - shows the C _{1 0} Ariru carbonyl § amino group is bonded group to group, for example, phenylene Luca Lupo sulfonyl § Mino, in Denis Luca Lupo sulfonyl amino, be naphthylcarbonyl § amino group And preferably a phenylcarbonylamino group. In addition, 1 to 3 substituents (preferably 1) selected from Substituent Group 3 are preferably groups selected from Substituent Group 32, and are particularly preferable. Suitably, it is a group selected from the substituent group β3.

Such “C ₇ -Cuarylcarbonylamino group optionally substituted by 1 to 3 groups selected from substituent group i3” is, for example, phenylcarponylamino, 2 —, 3 — Or 4 — methylphenylcarbonylamino, 2 —, 3 — or 4-ethylphenylcarponylamino, 2 —, 3 _ or 4 — methoxyphenylcarponylamino, 2 —, 3 — or 4 Fluorophenylcarbonylamino, 2-, 3- or 4-fluorophenylcarbonylamino, (indene-1-yl) carbonylamino, (indene-2-yl) carbonylamino, (naphthalene1-1-) Phenylamino, (naphthylene-1-yl) carbonylamino group, which is preferably substituted with a group selected from the substituent group 32. Niruami Bruno a group, particularly preferably the substituent group is | a 3 3 is substituted with a group selected from or phenylalanine carbonyl § amino group. In the above, the “tetrazolylcarbonylamino group which may be substituted by 1 to 3 groups selected from the substituent group i3” in the definition of R ¹ is, for example, (1 H-tetrazol- 5 -yl) carbonylamino, (1 -methyltetrazole-5-yl) carbonylamino, (1 -ethyltetrazole-5 -yl) -power-ponylamino, (1 -methoxytetrazole-5 -yl) ) Carbonylamino, (1 -fluorotetrazol-5-yl) carbonylamino, (1 -chlorotetrazol-5-yl) carbonylamino group, preferably from the substituent group 32 A tetrazolylcarponylamino group which may be substituted with a selected group, particularly preferably a tetrazolylcarponylamino group which may be substituted with a group selected from the substituent group 33. .

In the above, in the definition of R ¹ , one to three substituents selected from the substituent group / 3 may be substituted (C ₆ — < ₁₀ aryl) sulfonylcarbamoylamino group ”

(C-Caryl) The sulfonylcarbamoylamino moiety is as defined in the above (C-C

₁₀ aryl) a group in which an amino group is bonded to a sulfonylcarbamoyl group, for example, phenylsulfonylcarbamoylamino, indenylsulfonylcarbamoylamino, naphthylsulfonylcarbamoylamino group, and preferably phenylsulfonylcarbamoylamino group. It is a honylcarbamoylamino group. In addition, 1 to 3 substituents (preferably 1) selected from the substituent group / 3 are preferably groups selected from the substituent group 31 and more preferably It is a group selected from the aforementioned substituent group / 32, more preferably d-C alkyl, methoxy, a fluorine atom or a chlorine atom, and particularly preferably a methyl group.

Such “C 1-3 d-aryl” sulfonylcarbamoylamino group which may be substituted by 1 to 3 groups selected from a substituent group is, for example, phenylsulfonylcarbamoylamino, 2 — , 3 — or 4 — methylphenylsulfonylcarbamoylamino, 2 _, 3 — or 4 -ethylphenylsulfonylcarnomoylamino, 2 —, 3 _ or 4-methoxyphenylsulfonylcarbamo Ilamino, 2 —, 3 — or 4 monoethoxyphenylsulfonylcarbamoylamino, 2 —, 3 — or 4 monofluorophenylsulfonylcarbamoylamino, 2 —, 3 — or 4 monophenylphenylsulfonylcarbamoylamino An indenylsulfonylcarbamoylamino group, a naphthylsulfonylcarbamoylamino group, and preferably a phenylsulfonylcarbamoylamino group which may be substituted with a group selected from the substituent group i31. preferably a said good-phenylalanine sulfo be substituted with a group selected from substituent group 0 2 carbamoylmethyl § amino group, more preferably a d - substituted with C ₂ alkyl, main butoxy, fluorine atom or chlorine atom And more preferably a phenylsulfonylcarbamoylamino group. A which may phenylalanine sulfonyl be carbamoylmethyl § amino group substituted with a group, particularly preferably a tosylate carbamoyl § amino group.

In the above, "d- _Cβ alkyl group" in the definition of R ² , R ³ , R ⁴ and the group of substituents a has the same meaning as the above C i -C β alkyl group, R ² , R ³ and

R ⁴ is preferably a d-C alkyl group, particularly preferably a methyl group, and in the substituent group a, it is preferably a d-C ₂ alkyl group or a t-butyl group; More preferably, it is a methyl group or a t-butyl group, and particularly preferably, a methyl group.

In the above, “d-C alkoxy group” in the definition of R ² , R ³ , R ⁴ and the substituent group a has the same meaning as the d-C alkoxy group, and preferably d-C alkoxy group. _{2 is an} alkoxy group, particularly preferably a methoxy group.

In the above, “halogen atom” in the definition of R ² , R ³ , R ⁴ and the substituent group r has the same meaning as the above-mentioned halogen atom. In R ² , preferably a fluorine atom or It is a chlorine atom, particularly preferably a fluorine atom. R ³ and R ⁴ are preferably a fluorine atom or a chlorine atom.

The At a, R ^2, R ³ and the in the definition "mono - (d - C al Kill) amino group", said mono one (C, - C _s alkyl) § Mi Bruno as defined groups Shows And preferably a mono- (C, -C alkyl) amino group.

The At a, in the definition of R ^2, R ³ and R ⁴ "G (C i - C beta alkyl) amino group", the Gee - the same meaning as (d C _e alkyl) Amino group And preferably a di (Ci-Cz alkyl) amino group.

The At a, in "which may be 1 to 3 substituted with a group selected from Substituent Group 3 C _e - C ₁₀ Ariru group" in the definition of R ⁵ C ₆ of - C ₁₀ Ariru portion, the C beta the same meaning and one C ₁₀ Ariru group, preferably a phenyl or naphthyl group, particularly preferably a phenyl group. In addition, 1 to 3 substituents (preferably 1) selected from the substituent group i3 are preferably groups selected from the substituent group / 31, more preferably Is a group selected from the substituent group / 32, more preferably a group selected from the substituent group / 33, and particularly preferably a methoxy group. 1 to 3 C ₆ -C ₁₀ aryl groups which may be substituted by 1 to 3 groups selected from group / 3, are, for example, phenyl, 2_'3— or 4-methylphenyl, 2—, 3— or 4 _Ethylphenyl, 2 —, 3 — or 4-methoxyphenyl, 2 —, 3 — or 4 monophenyl phenyl, 2 —, 3 — or 4 — fluorophenyl, 4 _methyl-1-2-methoxyphenyl, 6 —Fluoro-4 —Methyl-2 —Metoxyphenyl, 2, 3 —Dimethoxif Nil, 2,4—Dimethoxyphenol, 3,4 Dimethoxyphenyl, 3,5—Dimethoxyphenyl, 2,3,4—Trimethoxyphenyl, 3,4,5—Trimethoxyphene Nyl, indene—2—or 3—yl, 5—methylindene—2—yl, 5—methylindene-1 3—yl, naphthylene-1—or 2-yl, 5—methylnaphthalene-1 1-yl, 5-methylnaphthylene-12-yl group, preferably a phenyl or naphthyl group which may be substituted with a group selected from the above-mentioned substituent group i31, more preferably Is a phenyl group which may be substituted with a group selected from the substituent group 32, more preferably the substituent group; a phenyl group which may be substituted with a group selected from 33. And even more preferably phenyl, 2 —, 3 — or 4 — methoxyphenyl, 2,3 — dimethoxyphenyl, 2,4 — dimethoxyphenyl, 3, 4 dimethoxyphenyl, 3, 5 —Dimethoxyphenyl or 3,4,5—trimethoxyphenyl, even more preferably phenyl or 2—, 3— or 4-methoxyphenyl, particularly preferably phenyl It is.

In the above, in the definition of R ⁵ , “1 to 3 substituents may be substituted with a group selected from the substituent group <3, and may be condensed with a benzene ring, chenyl, pyrrolyl, 1, 1 1 to 3 substituents (preferably 1) selected from the substituent group of “dioxenyl, thiazolyl or oxazolyl group” are preferably groups selected from the substituent group 31 described above. And more preferably a group selected from the substituent group 02, and particularly preferably a group selected from the substituent group 33.

Such a “Chenyl, pyrrolyl or 1,1 dioxenyl group which may be substituted by 1 to 3 groups selected from the substituent group 3 and may be condensed with a benzene ring” is, for example, Thiofen _ 2 _yl, 3 —, 4 1- or 5-methylthiophene 1-2-yl, 3 —, 4 — or 5 —ethylthiophene — 2 — yl, 3 —, 4 1 or 5 — methoxythiophene — 2 — yl, 3 —, 4 yr or 5 — Fluorochiophen-1 2 — yl, 3 —, 4-1 or 5 — chlorothiophene 2 — yl, thiofen-1 3 — yl, 2 — , 4 — or 5-methylthiophene-3-yl, 2 _, 4 _ or 5 —ethylthiophene-3-yl, 2 —, 4 or 5 — methoxythiophene-3-yl, 2 —, 4 _ or 5 — Fluorothiophene 3 — yl, 2 , 4 1 or 5 —Chlorothiophene-3-yl, Pyroyl 1-yl, Pyroyl 2 —yl, 1 —, 3 —, 4 — or 5 —Methylpyrroyl 2 —yl , 1 _, 3 —, 4 — or 5 —Ethylpyrroyl 2 —yl, 1 1,3-, 4 or 5 —Methoxypyrroyl 2 —yl, 1 —, 3 —, 4 _ Or 5 — Fluoropyrrole 1 2 — yl, 1 1, 3 —, 4 — or 5 — black mouth 1-, 2--3, 4 — or 1-, 2 —, 4 — or 5—Met Rubilol—3—yl, 1—1, 2—, 4— or 5—Ethylpyrroyl 3—yl, 1—1, 2—, 4— or 5—Methoxypyrroyl—3—yl, 1—, 2 —, 4 — or 5 — Fluoropyrrole 3 — yl, 1 —, 2 —, 4 — or 5 — Chloropyrrole 3 — yl, 1, 1 — dioxochiophene 1 2 — yl, 3 —, 4 1 or 5 — Methyl-1, 1 1 dioxotiophene 1 2 — yl, 1, 1 dioxotiophene 1 3 — yl, 3 —, 4 1 or 5 — Methyl — 1, 1 dioxochiofen 1 3 _yl, thiazole — 5 — yl, 2 — or 4-methylthiazoyl 5 — yl, oxazolu 5 — yl, 2 — or 4 — methyloxazolu 5 — yl, benzothiophene — 2 _ yl , 3 —, 4 1 or 5 — methylbenzothiophene 1 — , 3 _, 4 1 or 5 — methoxybenzothiophene — 2 — yl, 3 —, 4 — or 5 — fluorobenzothiophene 1 2 — yl, 3 —, 4 1 or 5 — black Mouth benzothiophene — 2 — yl, benzothiophene — 3 — yl, 2 —, 4 — or 5 — methylbenzothiophene 1 — 3-yl, 2 _, 4 or 5 — methoxybenzothiophene 1 3 —Ill, 2 —, 4 1 or 5 —Fluorobenzothiophene 1 —Ill, 2 —, 4 — or 5 —Chlorobenzothiophene — 3 —Ill, Indore 1 —I Le, indole-2 _

3 —, 4 _ or 5 — methyl indole 2 — yl, 3 —, 4 — or 5 — methoxine ind 2 — yl, 3 —, 4 — or 5 — fluorinated d'or 2 — yl , 3 —, 4 — or 5 — black mouth indole — 2 — yl, indole — 3 — yl, 1 1, 2 —, 4 1 or 5 — methylindole — 3 — yl, 2 —,

4 or 5 — methoxyindole — 3 — yl, 2 —, 4 1 or 5 — fluoroindole 3 — yl, 2 —, 4 — or 5 — black mouth indole — 3 — yl, 1, 1-dioxobenzothiophene 1-2-yl, 3-, 4-, 5-, 6-or 7-methyl-1, 1-dioxobenzothiophene-2-yl, 3 —, 4 1, 5 —, 6 _ or 7 —Methoxy 1, 1 dioxobenzothiophene 2 —yl, 3 —, 4 1, 5 —, 6 — or 7 —Fluoro 1, 1 Dioxobenzo Thiophene-1-yl, 3 —, 4 —, 5-, 6— or 7—clo mouth — 1,1 dioxobenzothiophene 1-2 —yl, 1,1 dioxobenzothiophene — 3-yl, 2-—, 4--1, 5--, 6- or 7-methyl— 1, 1, 1-dioxobenzothiophene-3-yl, 2-—, 4-—, 5-—, 6—, or 7—methoxy-1 , 1 dioxobenzothiophene-3-yl, 2 —, 4-1, 5 —, 6— or 7 — fluoro-1, 1 — dioxobenzothiophene-3-yl, 2 —, 4 -, 5-, 6-or 7-chloro-1, 1-dioxobenzothiophene 1-3-yl, benzothiazol-2-yl, 4-1, 5-, 6-or 7-methylbenzothia Zolu-2-yl, benzoxazole-2-yl, 4-, 5-, 6- or 7 _ methylbenzoxazole-2-yl Suitably substituted with a group selected from the above-mentioned substituent group / 31/1, phenyl, 1,1-dioxocenyl, thiazolyl, benzocenyl, 1,1-dioxobenzocenyl or benzyl. A benzothiazolyl group, more preferably a phenyl, a thiazolyl, a benzophenyl or a 1,1-dioxobenzothienyl group which may be substituted with a group selected from the substituent group 32. More preferably, it is a benzothenyl group or a 1,1-dioxobenzocenyl group which may be substituted with a group selected from the above-mentioned substituent group 33, and particularly preferably a 1,1-di-substituted group. Oxobenzothiophene 3-yl.

The At a, in the definition of R ⁶ 'd - C ₁₀ alkyl group "is a hydrocarbon group of 0 1 to 1 carbon atoms straight-chain or branched-chain, for example, the d - C _beta alkylene 1-methylhexyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 1-propylbutyl, 1-ethylpentyl, 2-ethylpentyl, 3— Ethylpentyl, 4-ethylpentyl, 4,4-dimethylpentyl, octyl, 1-methylheptyl, 2—methylheptyl, 3—methylheptyl, 4-methylheptyl, 5—methylheptyl, 6—methylheptyl, 1-propylpentyl, 2 —Propylpentyl, 3 —Propylpentyl, 4 —Propylpentyl, 1-Ethylhexyl, 2 —Ethylhexyl, 3—Ethyl Tylhexyl, 4-ethylhexyl, 5-ethylhexyl, 5,5-dimethylhexyl, nonyl, 3-methyloctyl, 4-methyloctyl, 5-methyloctyl, 6-methyloctyl, 1-propylhexyl, 2-propyl Hexyl, 3 — propylhexyl, 4 — propylhexyl, 5 — propylhexyl, 2 — ethyl heptyl, 6, 6 — dimethylheptyl, 1 — butylpentyl, 2 — butylpentyl, 3 — butylpentyl, 4 — Butylpentyl, 1-butylhexyl, 2-butylhexyl, 3-butylhexyl, 4-butylhexyl, 5-butylhexyl, decyl, 1-methylnonyl, 3-methylnonyl, 8-methylnonyl, 3-ethylethyl , 3, 7 - Jimechiruokuchiru, 7, 7 - Jimechiruokuchiru a group, is a prime suitable C ₃ - C alkyl , Still preferably, isopropyl, heptyl, Ri t-butyl, neopentyl, hexyl group der to 1 Echirupenchiru or 2 _ Echiru, particularly preferably from 1 Echirupenchiru group.

 In the above, the “d-Cβ alkylene group” in the definition of W and Z is, for example, methylene, methylmethylene, ethylene, propylene, trimethylene, 1-methylethylene, tetramethylene, 1-methyltrimethylene, 2-methyltrimethylene, 3-methyltrimethylene, 1-methylpropylene, 1,1-dimethylethylene, pentamethylene, 1-methyltetramethylene, 2-methyltetramethylene, 3-methyltetramethylene, 4-methyltetramethylene, 1,1 —Dimethyltrimethylene, 2,2—dimethyltrimethylene, 3,3-dimethyltrimethylene, hexamethylene, 1-methylpentamethylene, 2—methylpentamethylene, 3—methylpentamethylene, 4-methylpentamethylene, 5— Methyl pentamethylene, 1,1 dim Letetramethylene, 2,2-dimethyltetramethylene, 3,3-dimethyltetramethylene, 4,4-dimethyltetramethylene group, preferably a d-C alkylene group, and particularly preferably a methylene group .

In the above, in the definition of R ⁷ , “C ₃ -C cycloalkyl group which may be substituted by 1 to 3 groups selected from substituent group a and may be condensed with a benzene ring” C - C _e cycloalkyl moiety is the C ₃ - shows the C beta as defined cycloalkyl group may be condensed with a benzene ring. Examples of such a C ₃ -C cycloalkyl group include the aforementioned C ₃ -C β cycloalkyl, indanyl, and benzocyclohexyl groups, and preferably a C _5- that may be condensed with a benzene ring. A C β cycloalkyl group, particularly preferably a cyclohexyl group.

In addition, one to three substituents (preferably one) selected from the substituent group a are the d-Cβ alkyl group, the -Cβ alkoxy group, the halogen atom and the formula Ζ—R ⁸ {wherein, Ζ is a single bond or the above-mentioned C 3 alkylene group, and R ⁸ is a carboxy group, a C ₂ -C alkoxyl propyl group (see above.

-C β indicates a group in which a carbonyl group is bonded to an alkoxy group, such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, s-butoxycarbonyl, t-butoxy. Carbonyl, pentoxycarbonyl, isopentoxycarbonyl, 2-methylbutoxycarbonyl, neopentoxycarbonyl, 1-ethylpropoxycarbonyl, hexyloxycarbonyl, 4-methylpentoxycarbonyl, 3-methylpentoxycarbonyl, 2-Methylpentoxycarbonyl, 1-Methylpentoxycarbonyl, 3,3-Dimethylbutoxycarbonyl, 2,2—Dimethylbutoxycarbonyl, 1,1—Dimethylbutoxycarbonyl, 1,2-Dimethylbut Toxoxycarbonyl, 1,3-dimethylbutoxycarbonyl, 2,3_dimethylbutoxycarbonyl, 2-ethylbutyloxycarbonyl group, preferably C ₂ -C alkoxycarbonyl group, particularly preferably methoxycarbonyl group It is. ), Carbamoyl group, mono (C, -C β alkyl) carbamoyl group (a group in which one C, -C alkyl group is bonded to a levamoyl group, for example, methylcarbamoyl, ethylcarbamoyl, Propyl carbamoyl, isop Mouth pill rubamoyl, butyl carbamoyl, isoptyl carbamoyl, s — butyl carbamoyl, t — butyl carbamoyl, pentyl carbamoyl, isopench Rucarbamoyl, 2-methylbutylcarbamoyl, neopentylcarbamoyl, 1-ethylpropyl-based rubamoyl, hexylcarbamoyl, and preferably a C-Calkyl-based rubamoyl. ), Di (C i -C alkyl) carbamoyl group [shows a group in which two identical or different C t -C β alkyl groups are bonded to a carbamoyl group, for example, dimethylcarbamoyl, getylcarbamoyl, N— Ethyl N-methylcarbamoyl, dipropyl carbamoyl, diisopropyl propylcarbamoyl, N-methyl-N-propyl propylcarbamoyl, dibutylcarbamoyl, diisobutylcarbamoyl, ges-butylcarbamoyl, di-t-butylcarbamoyl, N- Butyl-N-methylcarbamoyl, dipentylcarbamoyl, N-ethyl-N-propyl-capillyl, N-butyl_N-ethyl-carbamoyl, dihexylcarbamoyl, N-butyl-N-propyl-caprolumyl di - (C t - C ₂ alkyl) force Rubamoiru group There are particularly preferably dimethylcarbamoyl group. And the aforementioned C i -C alkylsulfonyl group or hydroxyl group. }. Preferably, a d-C alkyl group, a t-butyl group, a d-C alkoxy group, a fluorine atom, a chlorine atom and a formula —Z—R ^{8 wherein} Z is a single bond or a —C alkylene group; R ⁸ is a carboxyl group, a C ₂ -C a alkoxycarbonyl group, a rubamoyl group, a mono- (d-C alkyl) rubumboyl group, a di- (d-C ₂ alkyl) rubumbamoyl group, a C-C ₄ It is an alkylsulfonyl group or a hydroxyl group. ], And more preferably a group selected from the group consisting of a group having the following formula (hereinafter, referred to as a substituent group a1). More preferably, a methyl group, a t-butyl group, a methoxy group, a fluorine atom, a chlorine atom And a carboxy group, a methoxycarbonyl group, a dimethylcarbamoyl group and a hydroxymethyl group (hereinafter, referred to as a substituent group a2), and particularly preferably a methyl group, It is a group selected from a substituent group consisting of a methoxy group, a fluorine atom and a chlorine atom (hereinafter referred to as a substituent group a3).

One to three substituents may be substituted with a group selected from the group A C ₃ -C cycloalkyl group which may be condensed with a zen ring is, for example, cyclopentyl, cyclohexyl, 2-, 3- or 4-methylcyclohexyl, 2-,

3 — or 4-ethylcyclohexyl, 2 —, 3 — or 4 — t —butylcyclohexyl, 2 —, 3 _ or 4 — methoxycyclohexyl, 2 —, 3 — or 4 monofluorocyclo Xyl, 2 —, 3 — or 4 monochlorocyclohexyl, 2 —, 3 — or 4 monocarboxycyclohexyl, 2 —, 3 — or

4-Methoxycarbonyl-cyclohexyl, 2—, 3— or 4 rubamoylcyclohexyl, 2—, 3— or 4-methylcarbamoylcyclohexyl, 2—, 3—, or 4-dimethylcarbamoylcyclo Hexyl, 2-, 3- or 4-methylsulfonylcyclohexyl, 2-, 3-, or 4-hydroxycyclohexyl, 2-, 3- or 4-hydroxymethylcyclohexyl, indane one 1 one i le, Lee Ndan - 2 - i group, suitably may be condensed with a good benzene ring substituted with a group selected from the substituent group § 1 C ₅ - C beta A cycloalkyl group, more preferably a C ₅ -C β cycloalkyl group which may be substituted with a group selected from the above-mentioned substituent group a 2 and may be condensed with a benzene ring. Is the A has been key sill group to be cycloalkyl substituted by a group selected from Group "gamma 3, particularly preferably a cyclohexyl group.

The At a, in "which may be 1 to 3 substituted with a group selected from Substituent group § C ₇ - C _{1 6} Ararukiru group" in the definition of R ⁶ C ₇ of - C _{1 6} Ararukiru portion Represents a group in which the Ci-Cβ alkyl group is bonded to the aforementioned C ₆ _C aryl group, for example, benzyl, naphthylmethyl, indenylmethyl, 1-phenylenyl, 2-phenylenyl, 1-naphthylethyl, 2-naphthylethyl, 1-phenylpropyl, 2-phenylpropyl, 3-phenylpropyl, 1-naphthylpropyl, 2-naphthylpropyl, 3-naphthylpropyl, 1-phenylbutyl, 2-phenylbutyl, 3-phenylbutyl, 4 —Phenylbutyl, 1 —naphthylbutyl, 2 —naphthylbutyl, 3 —naphthylbutyl, 4 —naphthylbutyl, 1 —phenyl Pentyl, 2 — phenylpentyl, 3 — phenylpentyl, 4 phenylpentyl, 5 — phenylpentyl, 1 _ naphthylpentyl, 2 — naphthylpentyl, 3 naphthylpentyl, 4 naphthylpentyl, 5 — naphthylpentyl, 1 1 phenylhexyl, 2 — phenylhexyl, 3 — phenylhexyl, 4 phenylhexyl, 5 — phenylhexyl, 6 — phenylhexyl, 1 naphthyl Xyl, 2—naphthylhexyl, 3—naphthylhexyl, 4—naphthylhexyl, 5—naphthylhexyl, 6—naphthylhexyl, preferably an aryl moiety is a phenyl group and an alkyl moiety is d -An aralkyl group which is a C ₄ alkyl group, more preferably a benzyl, 1-phenylethyl or 2-phenylethyl group, particularly preferably 1 One phenylethyl group.

 In addition, one to three substituents (preferably one) selected from the substituent group a have the same meaning as the substituent group a, and preferably one to three. It is a group selected, more preferably a group selected from the substituent group a2, and particularly preferably a group selected from the substituent group a3.

Such "one 1 to 3 may be substituted C ₇ groups selected from substituent group § C _ie Ararukiru group", for example, benzyl, 2 -, 3- or 4 one Mechirube Njiru, 2 - , 3 — or 4 monoethylbenzyl, 2 —, 3 — or 4-methoxybenzyl, 2 —, 3 — or 4 monofluorobenzyl, 2 _, 3 — or 4 — cyclobenzyl, 2 —, 3 — or 4 Power-loxybenzyl, 2 —, 3-or 4-Powerbamoyl benzyl, 2 —, 3 _ or 4 _dimethylcarbamoylbenzyl, 2 _, 3 — or 4 —hydroxybenzyl, 2 —, 3 — 4-hydroxymethylbenzyl, 1- or 2-phenylenyl, 1- or 2- (2-, 3- or 4-methylphenyl) ethyl, 1-1 or 2— (2—, 3— Or 4 Ruphenyl) ethyl, 1 or 2_ (2-, 3—or 4—methoxyphenyl) ethyl, 1_ or 2— (2—, 3_ or 4—fluorophenyl) ethyl, 1—or 2— (2 —, 3 — or 4 phenyl) ethyl, 1 1 or 2 — (2 —, 3 — or 4 — phenyl) ethyl, 1 or 2 _ (2-, 3 — or 4 — bromophenyl) ethyl, 1 — Or 2 — (2 —, 3 — or 4 ruboxyphenyl) ethyl, 1 or 2 — (2 —, 3 — or 4 rubamoyl phenyl) ethyl, 1 or 2 — (2 —, 3 — Or 4-dimethylcarbamoylphenyl) ethyl, 1- or 2- (2-, 3- or 4-hydroxyphenyl) ethyl, 1- or 2- (2-, 3- or 4-hydroxymethylphenyl) ) Ethyl, 1 — or 2 — (naphthalene- 1 -yl) ethyl, 1 — or 2-(naphthalene 1-2 -yl) ethyl group, and is preferably selected from the substituent group a 1 Based on Conversion is may Ariru portion is alkyl moiety is phenyl group - a C ₄ Ararukiru group which is an alkyl group, more preferably, may be substituted with a group selected from the substituent group Guna 2 Ariru The aralkyl group is a phenyl group and the aralkyl part is a d-C alkyl group; more preferably, benzyl, 1-phenyl which may be substituted with a group selected from the substituent group a3; It is a 2-phenyl or 2-phenylethyl group, particularly preferably 1-phenylethyl.

Of the compounds (I) or (II) of the present invention, a compound having a basic group such as an amino group can be converted into a pharmacologically acceptable salt by treating it with an acid according to a conventional method, if necessary. it can. Such salts include hydrofluorides, hydrochlorides, hydrobromides, hydrohalides such as hydroiodates: nitrates, perchlorates, sulfates, phosphates, etc. Inorganic acid salt of: C i -C β alkane sulfonate which may be substituted with fluorine such as methane sulfonate, trifluoromethane sulfonate, and ethane sulfonate: benzene sulfonate, toluene sulfonic acid C _6, such as a salt - C _{1 0} § Li one Rusuruhon salt sulfonates such as: fumaric acid salts, succinic acid salts, Beautique down, tartrate, oxalic acid salts, such as maleic phosphate salt Carboxylates: or glutamates, amino acids such as aspartate: Preferred are hydrohalides, d-C alkane sulfonates or carbonates (particularly preferred are hydrochloride, methanesulfonate, fumarate, oxalate or maleate. ).

 Further, of the compounds (I) or (II) of the present invention, a compound having an acidic group such as a carboxy group may be treated with a base according to a conventional method, if necessary, to obtain a pharmacologically acceptable salt. Can be. Examples of such salts include: alkali metal salts such as lithium salts, sodium salts and potassium salts: metal salts such as alkaline earth metal salts such as calcium salts and magnesium salts; metal salts such as aluminum salts and iron salts. Organic base salts such as ammonium salt, glucosamine salt, phenyldaricin alkyl ester salt, ethylenediamine salt, N-methyldalkamine salt, guanidine salt, getylamine salt, triethylamine salt, dicyclohexylamine salt. And preferably an alkali metal salt.

 The compound (I) or (II) of the present invention or a pharmacologically acceptable salt thereof is allowed to absorb moisture, adhere to water, or hydrate when left in the air or recrystallized. Such cases are also included in the present invention. The compound (I) or (II) of the present invention or a pharmacologically acceptable salt thereof may absorb some other solvent and form a solvate, and such a compound is also included in the present invention. Is done.

 The compound (I) or (II) of the present invention or a pharmacologically acceptable salt thereof may have an asymmetric carbon atom in the molecule, and there are stereoisomers in R-coordination and S-coordination. In some cases, each of them, or any proportion thereof, of compounds is encompassed by the present invention. Such a stereoisomer can be obtained by synthesizing compound (I) or (II) using the optically resolved starting compound, or by subjecting the synthesized compound (I) or (II) to an ordinary optical resolution or separation method as desired. Can be used for optical resolution.

Further, the compound (I) or (II) of the present invention or a pharmacologically acceptable compound thereof. In the case where R ^e is a group having the formula W—R ⁷ , there are geometrical isomers. The present invention includes such geometrical isomers, and preferably includes trans isomers. Can be.

 The present invention also includes all compounds that are metabolized in vivo and converted into benzylamines having the general formula (I) or (II) of the present invention or pharmacologically acceptable salts thereof, so-called prodrugs.

 In the present invention, the compound having the general formula (I) or the compound having the general formula (II) contained as an active ingredient of the bile acid transport inhibitor is preferably a compound shown below. Can be mentioned.

(1) R ¹ , a phenyl group substituted with a group selected from substituent group α1, a tetrazolyl group optionally substituted with a group selected from substituent group j31, (C ₅ -C cycloalkyl alkyl) force Rubamoiru groups, (C, one C ₄ alkyl) sulfonyl Rukarubamoi group, phenylpropyl sulfo which may be substituted with a group selected from substituent group [delta] 1 two Luke Rubamoiru group, sulfo group, - C alkylsulfonyl group, substituted by a group selected from substituent group 3 1 which may be phenylalanine sulfonyl group, methylamino sulfonyl group, E chill aminosulfonyl group, dimethylaminopyridine Nosuruhoniru group, Jechiruami Nosuruhoniru group, d - C ₄ An alkylsulfinyl group, a substituent group / a phenylcarbonylamino or tetrazolylcarbonylamino group or a substituent group which may be substituted with a group selected from 32 / 31 A compound which is a phenylsulfonylcarbamoylamino group which may be substituted with a group selected from 1.

 <Substituent group a 1>

Substituent group | selected from tetrazolyl group, sulfo group, C, -C ₄ alkylsulfonyl group, methylsulfonylamino group, ethylsulfonylamino group and substituent group / 32 which may be substituted with a group selected from 32 A phenylsulfonylamino group which may be substituted with

Substituent group β 1> C, -C alkyl, d -C alkoxy, fluorine and chlorine

<Substituent group i3 2>

C - C alkyl group, d - C ₂ alkoxy group, fluorine atom and chlorine atom <substituent group [delta] 1>

C - C ₄ alkyl, d - C alkoxy, a phenyl group which may be substituted with a group selected from halogen atom and the substituent group / 3 1

(2) R ¹ is 2-, 3- or 4- (1H-tetrazol-5-yl) phenyl group; 2—, 3- or 4- (1-methyltetrazol-5-yl) phenyl A 2-, 3- or 4- (1-methoxytetrazole-5-yl) phenyl group, a 2-, 3- or 4- (1-fluorotetrazol-5-yl) phenyl group, 2-, 3-, or 4- (1-chlorotetrazo-1-yl-5-phenyl) phenyl, 2-, 3-, or 4-methylsulfonylphenyl, 2-, 3-, or 4-ethyl Sulfonylphenyl, 2-, 3- or 4-propylsulfonylphenyl, 2-, 3- or 4-butylsulfonylphenyl, 2-, 3- or 4-methylsulfonylaminophenyl , 2 —, 3 — or 4-phenylsulfonylaminophenyl group It may be substituted with a group selected from Substituent group / 32. Tetrazolyl group, (C i -C alkyl) sulfonylcarbamoyl group, It may be substituted with a group selected from Substituent group 32. A phenylsulfonylcarbamoyl group, a C ₄ alkylsulfonyl group, a phenylsulfonyl group which may be substituted with a group selected from the group of substituents / 32, a —C alkylsulfinyl group, a group of substituents; 33 A phenylsulfonylamino or a tetrazolylcarbonylamino group which may be substituted with a group selected from 3 or phenylsulfonyl which may be substituted with a group selected from a substituent group 32. A compound that is a carbamoylamino group. <Substituent group 3 2>

C-C alkyl group, d-C alkoxy group, substituent group of fluorine atom and chlorine atom / 3 3> Methyl group, methoxy group, fluorine atom and chlorine atom

Substituent group <5 2>

C - C ₂ alkyl group, d - C alkoxy group, a fluorine atom, a chlorine atom and Substituent Group] 3 2 from the selected is a phenyl group which may be substituted with group

(3) R ¹ force 2-, 3-or 4- (1H-tetrazol-5-yl) phenyl group, 2-, 3-or 4-methylsulfonylphenyl group, 2-, 3-or 4-ethylsulfonylphenyl group, a tetrazolyl group optionally substituted with a group selected from Substituent Group 2, a phenylsulfonylcarbamoyl group optionally substituted with a group selected from Substituent Group δ3, A methylsulfonyl group, an ethylsulfonyl group, a propylsulfonyl group, a butylsulfonyl group, a phenylsulfonyl group which may be substituted with a group selected from Substituent group i33, or a phenylsulfonylcarbamoylamino group which may be substituted (The substituent is d-C alkyl, methoxy, fluorine or chlorine).

<Substituent group 3 2>

 C-C alkyl group, -C alkoxy group, fluorine atom and chlorine atom

<Substituent group / 3 3>

 Methyl group, methoxy group, fluorine atom and chlorine atom

<Substituent group δ 3>

Methyl group, methoxy group, fluorine atom, chlorine atom and phenyl group which may be substituted with d-C ₂ alkyl, methoxy, fluorine or chlorine

(4) R ¹ is a tetrazolyl group optionally substituted with a group selected from a 2-methylsulfonylphenyl group, a 3-methylsulfonylphenyl group, a 4-methylsulfonylphenyl group and a substituent group i33 A phenylsulfonylcarbamoyl group, a methylsulfonyl group, a methylsulfonyl group, a butylsulfonyl group, a phenylsulfonyl group which may be substituted with a group selected from the substituent group δ4, and a phenylsulfonyl group which may be substituted with methyl A compound that is a carbamoylamino group. <Substituent group / 3 3>

 Methyl group, methoxy group, fluorine atom and chlorine atom

<Substituent group <3 4>

 Methyl group, phenyl group and methylphenyl group

(5) A compound which is an R ¹ 1-tetrazole-5-yl group, a methylsulfonyl group, an ethylsulfonyl group or a tosylcarbamoylamino group.

(6) The compound wherein R ¹ is a 1 H-tetrazole-5-yl group.

(7) R ² , R ³ and R ⁴ force same or different, hydrogen atom, d-C alkyl group, C, -C ₂ alkoxy group, hydroxyl group, fluorine atom, chlorine atom, amino group, mono (C i- A compound which is a C ₂ alkyl) amino group or a di (C, -C z alkyl) amino group.

(8) A compound in which R ² , R ³ and R ^{4 are} the same or different and are a hydrogen atom, a methyl group, a methoxy group, a hydroxyl group, a fluorine atom or a chlorine atom.

(9) The compound wherein R ² is a hydrogen atom, a methoxy group or a fluorine atom, and R ³ and R ⁴ are hydrogen atoms.

(10) The compound wherein R ² , R ³ and R ⁴ are hydrogen atoms.

(11) R ⁵ force Substituent group / 31 It may be substituted with a group selected from the group consisting of phenyl, naphthyl, phenyl, 1.1 dioxocenyl, thiazolyl, benzocenyl, 1, 1 Compounds that are dioxobenzophenyl or benzothiazolyl groups Substituent groups β 1>

C! -C ₄ alkyl group,-C alkoxy group, fluorine atom and chlorine atom

(1 2) R ⁵ may be substituted with a group selected from Substituent Group 3 2, is phenylene Le, thienyl, thiazolyl, Benzoche alkenyl or 1, 1 over-di O Kiso benzo Choi sulfonyl group Compound.

<Substituent group 13 2> C-C alkyl group, d-C alkoxy group, fluorine atom and chlorine atom

(13) R ⁵ force A compound which is a phenyl group, a benzochenyl group or a 1,1-dioxobenzochenyl group which may be substituted with a group selected from substituent group / 33. <Substituent group 0 3>

 Methyl group, methoxy group, fluorine atom and chlorine atom

(1 4) R ⁵ force phenyl, 2 —, 3 — or 4 — methoxyphenyl, 2, 3 — dimethoxyphenyl, 2, 4- dimethoxyphenyl, 3, 4-dimethoxyphenyl, 3, 5 — Compounds which are dimethoxyphenyl or 3,4,5-trimethoxyphenyl or 1,1-dioxobenzothiophene-3-yl group.

(15) A compound which is an R ⁵ phenyl or a 2-, 3- or 4-methoxyphenyl group.

(1 6) compounds is R ⁵ force phenyl group.

(1 7) R ⁶ force ^ C-C alkylene group, formula 1 W— R ⁷ [wherein W is a single bond or d-C ₂ alkylene group, and R ⁷ is a substituent group a 1 It is a C ₅ -C ₆ cycloalkyl group which may be substituted with a selected group or may be condensed with a benzene ring. Or a aralkyl group (an aryl moiety is a phenyl group and an alkyl moiety is a CC alkyl group) which may be substituted with a group having the formula:

Substituent group T 1>

C - C alkyl group, a butyl group, d - C ₂ alkoxy group, a fluorine atom, a chlorine atom and Shikiichi Z - R ⁸ [wherein, Z is a single bond or - C alkylene radical, R ⁸ is carboxy , C ₂ -C alkoxycarbonyl, sorbamoyl, mono (C! -C alkyl) rubamoyl, ji (Ci-Calkyl) rubamoyl, -C ₄ alkylsulfonyl or hydroxyl group

⁽¹ 8) R β force ^ C - C alkylene group, a group [wherein having the formula one W- R ^7, W is a single bond or a methylene group, R ⁷ is selected from substituent group § 2 Group And is a C ₅ -C cycloalkyl group which may be substituted with a benzene ring. Or an aralkyl group which may be substituted with a group selected from substituent group a2 (where the aryl moiety is a phenyl group and the alkyl moiety is a C 1, —C ₄ alkyl group).

<Substituent group a 2>

 Methyl group, t-butyl group, methoxy group, fluorine atom, chlorine atom, carboxy group, methoxycarbonyl group, dimethylcarbamoyl group and hydroxymethyl group

(19) R ⁶ force may be substituted with a group selected from isopropyl group, butyl group, t-butyl group, neopentyl group, 1-ethylpentyl group, 2-ethylhexyl group or substituent group a3; Compounds which are cyclohexyl, benzyl, 1-phenylethyl or 2-phenylethyl group.

Substituent group 3>

 Methyl group, methoxy group, fluorine atom and chlorine atom

(2 0) R ^e is, 1 - Echirupenchiru group, compounds which are a cyclohexyl group or 1 one phenylene Ruechiru group.

(2 1) R ^e is, 1 - Echirupenchiru group or 1 - Fueniruechiru is of compounds group.

 In addition, any combination selected from the group consisting of (1)-(6), (7)-(10), (11)-(16) and (17)-(21) is combined. The following are also suitable. For example, the following can be mentioned.

(22) R ¹ , a phenyl group substituted with a group selected from substituent group αΐ, a substituent group; a tetrazolyl group optionally substituted with a group selected from 31, (C _5- C cycloalkyl) carbamoyl group, (C i -C alkyl) sulfonylcarbamoyl group, phenylsulfonyl carbamoyl group optionally substituted with a group selected from substituent group δ 1, sulfo group, C! -A C alkylsulfonyl group, a phenylsulfonyl group optionally substituted with a group selected from substituent group i31, methylaminosulfo Phenylcarbonylamino or tetrazolylcarbonylamino, which may be substituted with a group selected from a phenyl group, a methylaminosulfonyl group, a dimethylaminosulfonyl group, a acetylaminosulfonyl group, a monoalkylsulfinyl group and a substituent group 132. Phenylsulfonylcarbamoylamino group which may be substituted with a group selected from

R ² , R ³ and R ⁴ same or different, hydrogen atom, d-C alkyl group, d-C alkoxy group, hydroxyl group, fluorine atom, chlorine atom, amino group, mono- (C i -C alkyl) amino Group or a di- (C i -C alkyl) amino group,

R ⁵ force Substituent group 31 ^{May be} substituted with a group selected from 1, phenyl, naphthyl, phenyl, thienyl, thiazolyl, 1,1 dioxocenyl, benzocenyl, 1,1-dioxo A benzochenyl or benzothiazolyl group,

R ⁶ is a C-C alkylene group, a formula W—R ^{7 wherein} W is a single bond or a d-C ₂ alkylene group, and R ⁷ is a group selected from substituent group a1 And a C ₅ -C cycloalkyl group which may be substituted with a benzene ring. Or a aralkyl group (the aryl moiety is a phenyl group and the alkyl moiety is a C i -C alkyl group) which may be substituted with a group having the formula

<Substituent group α 1>

 Substituent group 32 A tetrazolyl group, a sulfo group, a C! -C alkylsulfonyl, methylsulfonylamino, ethylsulfonylamino and phenylsulfonylamino optionally substituted by a group selected from substituent group 32

 <Substituent group β 1>

C, -C alkyl group, -C alkoxy group, fluorine atom and chlorine atom <Substituent group 2> C! -C alkyl group, d-C alkoxy group, fluorine atom and chlorine atom

<Substituent group (5 1>

C - C alkyl, d - C ₄ alkoxy, a phenyl group which may be substituted with a group selected from halogen atom and the substituent group / 3 1

<Substituent group a 1>

C - C z alkyl group, t _ butyl group, d - C ₂ alkoxy group, a fluorine atom, a chlorine atom and the formula - Z - R ⁸ [wherein, Z is a single bond or - C ₂ alkylene radical, R ⁸ has carboxy, C ₂ -C alkoxycarbonyl, carbamoyl, mono- (d-C ₂ alkyl) levavamoyl, g- (d-C alkyl) carbamoyl, d—C ₄ alkylsulfonyl or hydroxyl group Base

(2 3) R ¹ force ^ 2 —, 3 _ or 4 1 (1 H-tetrazol-5-yl) phenyl group, 2 —, 3 — or 4 1 (1-methyltetrazol _ 5 _yl) Phenyl group, 2 —, 3 — or 4 — (1-methoxytetrazol-5-yl) phenyl group, 2 —, 3 _ or 4 — (1 —fluoro-α-tetrazol-5-yl) Phenyl, 2-, 3- or 4- (1-chlorotetrazol-5-yl) phenyl, 2-, _ or 4-methylsulfonylphenyl, 2-, 3- or 4 —ethylsulfonylphenyl, 2 —, 3 — or 4 monopropylsulfonylphenyl, 2 —, 3 _ or 4 monobutylsulfonylphenyl, 2 —, 3 — or 4-methylsulfonylaminophenyl , 2 —, 3 — or 4 — phenylsulfonylaminoue A tetrazolyl group, (C i -C alkyl) sulfonylcarbamoyl group

, Substituent group <5 may be substituted with 2 groups selected from phenylalanine sulfonyl carbamoyl group, d - C ₄ alkylsulfonyl group, optionally off be substituted with a group selected from Substituent Group 3 2 Phenylsulfonyl group, -C ₂ alkylsulfinyl group, phenylcarbonylamino or tetrazolylcarbonylamino group, which may be substituted with a group selected from substituent group 03, or substituent group 32 Group A phenylsulfonylcarbamoylamino group which may be substituted with

R ² , R ³ and R ⁴ force same or different, hydrogen atom, methyl group

, A methoxy group, a hydroxyl group, a fluorine atom or a chlorine atom,

R ⁵ is phenyl, phenyl, thienyl, thiazolyl, benzothenyl or a 1,1-dioxobenzophenyl group, which may be substituted with a group selected from substituent group 02;

R ⁶ , a C-C alkylene group, a group having the formula —W—R ⁷ [wherein

W is a single bond or a methylene group, and R ⁷ is a C _S -C cycloalkyl group which may be substituted with a group selected from substituent group r 2 and may be condensed with a benzene ring. Or an aralkyl group which may be substituted with a group selected from substituent group "r2"

(Where the aryl moiety is a phenyl group and the alkyl moiety is a C i -C ₄ alkyl group

. )

Substituent group 0 2>

 C! -C alkyl group, C i-C alkoxy group, fluorine atom and chlorine atom

<Substituent group / 3 3>

 Methyl group, methoxy group, fluorine atom and chlorine atom

 <Substituent group <5 2>

 C-C alkyl group, d-C alkoxy group, fluorine atom, chlorine atom and phenyl group which may be substituted with a group selected from substituent group / 32

<Substituent group a 2>

 Methyl group, t-butyl group, methoxy group, fluorine atom, chlorine atom, carboxy group, methoxycarbonyl group, dimethylcarbamoyl group and hydroxymethyl group

(2 4) R ¹ is 2 —, 3 — or 4 — (1 H-tetrazol-5-yl) phenyl, 2 —, 3 — or 4 —methylsulfonylphenyl, 2 —, 3 — or 4 _Ethylsulfonylphenyl group, a tetrazolyl group optionally substituted with a group selected from substituent group 32, and a tetrazolyl group optionally substituted with a group selected from substituent group δ3 Good phenylsulfonylcarbamoyl group, methylsulfonyl group, ethylsulfonyl group, propylsulfonyl group, butylsulfonyl group, phenylsulfonyl group optionally substituted with a group selected from substituent group 33 or phenyl optionally substituted A sulfonylcarbamoylamino group (the substituent is d—C ₂ alkyl, methoxy, fluorine or chlorine),

R ² is a hydrogen atom, a methoxy group or a fluorine atom,

R ³ and R ⁴ are hydrogen atoms,

R ⁵ is a phenyl group, a benzochenyl group or a 1,1-dioxobenzochenyl group which may be substituted with a group selected from the substituent group / 33,

R ^e force isopropyl, butyl, t-butyl, neopentyl, 1-ethylpentyl, 2-ethylhexyl or a group selected from substituent group r3, cyclohexyl, benzyl A compound which is a 1-phenylethyl or 2-phenylethyl group.

<Substituent group / 32>

C! -C ₂ alkyl group, d-C ₂ alkoxy group, fluorine atom and chlorine atom <Substituent group i3 3>

 Methyl group, methoxy group, fluorine atom and chlorine atom

<Substituent group δ 3>

Methyl group, main butoxy group, a fluorine atom, a chlorine atom and d - C ₂ alkyl, main bets alkoxy, a phenyl group which may be substituted with fluorine or chlorine

 Substituent group 3>

 Methyl group, methoxy group, fluorine atom and chlorine atom

(25) R ¹ , 2-methylsulfonylphenyl group, 3-methylsulfonylphenyl group, 4-methylsulfonylphenyl group, Substituent group / 33 Tetrazolyl optionally substituted by a group selected from the group Phenylsulfonylcarbamoyl, methylsulfonyl, ethylsulfo which may be substituted with a group selected from the group of substituents δ4 A phenylsulfonylcarbamoylamino group optionally substituted with a phenyl group, a butylsulfonyl group, a phenylsulfonyl group or methyl;

R ² is a hydrogen atom, a methoxy group or a fluorine atom,

R ³ and R ⁴ are hydrogen atoms,

R ⁵ force, ', phenyl, 2-, 3- or 4-methoxydiphenyl, 2,3-dimethoxyphenyl, 2,4-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethyphenyl Toxifenyl or 3,4,5-trimethoxyphenyl or 1,1-dioxobenzothiophene-3-yl

R ^e is, 1 - Echirupenchiru group, cyclohexyl group or a cyclohexylene - Hue is a two Ruechiru group compound.

<Substituent group) 3 3>

 Methyl group, methoxy group, fluorine atom and chlorine atom

Substituent group δ 4>

 Methyl group, phenyl group and methylphenyl group

(26) R ^{1 is a} 1 H-tetrazole-5-yl group, a methylsulfonyl group, an ethylsulfonyl group or a tosylcarbamoylamino group;

R ² , R ³ and R ⁴ are hydrogen atoms,

R ⁵ , phenyl or 2 —, 3 _ or 4 -methoxyphenyl

A compound in which R ⁶ is 1-ethylpentyl or 1-phenylethyl,

(27) R ¹ is a 1 H-tetrazole-5-yl group,

R ² , R ³ and R ⁴ are hydrogen atoms,

R ^{5 is} a phenyl group,

A compound in which R ⁶ is 1-ethylpentyl or 1-phenylethyl. As the representative compounds of the present invention, for example, the compounds described in Table 1, Table 2 and Table 3 can be exemplified, but the present invention is not limited to these compounds. The compounds in Tables 1, 2, and 3 have the structural formulas (IIa), (lib), and (IIc), respectively, and the compound having the general formula (I) is also a compound (IIa). ), (Ilb) and (IIc).

However, in the above formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ^e have the same meanings as described above, and R ^Sa is a group selected from the substituent group i3. 3 represents a phenyl group which may be substituted, and R ^Sb represents an indenyl group or a naphthyl group which may be substituted by 1 to 3 groups selected from a substituent group) 3; 1 to 3 groups selected from the group / 3 may be substituted or may be condensed with a benzene ring, thienyl, pyrrolyl, 1,1-dioxocenyl, thiazolyl or oxa Shows a zolyl group.

 Abbreviations in the table are as follows. BOxa: Benzoxazolyl group

BThi: Benzochenyl group

BThiz: benzothiazolyl group

Bu: butyl group

tBu: t-butyl group

Bz: benzyl group

Et: ethyl group

Hx: Hexyl group

cHx: cyclohexyl group

Ind: Indrill group

Inda: Indanyl group

Inde: Indenyl group

Me: methyl group

Np: naphthyl group

Oxa: Oxazolyl group

Ph: phenyl group

cPn: cyclopentyl group

nPn: neopentyl group

Pn: Pentyl group

Pr: propyl group

iPr isopropyl group

Pyrr Pyralyl group

Thi chenyl group

Thiz thiazolyl group £ SS / S6c 9S / 86 ΟΛν

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-307 2- (4-BuSO: ₂ -Ph) HHH Ph 1-Et-Pn-308 2- (4-BuSO ₂ -Ph) HHH Ph cHx-309 2- (4-BuSO ₂ -Ph) HHH Ph- CH (Ph) Me-310 2- (2-MeS0 2 HN-Ph) HHH Ph 1-Et-Pn-311 2- (2-MeS0 2 HN-Ph) HHH Ph cHx-312 2- (2-MeS0 2 HN-Ph) HHH Ph -CH (Ph) Me-313 2- (4-MeSO ₂ HN-Ph) HHH Ph 1-Et-Pn-314 2-(4-MeSO ₂ HN-Ph) HHH Ph cHx-315 2- (4-MeSO ₂ HN-Ph) HHH Ph -CH (Ph) Me-316 4- (2-MeS0 ₂ HN-Ph) HHH Ph 1-Et-Pn-317 4- (2-MeS0 ₂ HN- Ph) HHH Ph cHx-318 4- (2-MeS0 2 HN-Ph) HHH Ph -CH (Ph) Me-319 4- (4-MeSO 2 HN-Ph) HHH Ph 1-Et-Pn-320 4- (4-MeSO ₂ HN-Ph) HHH Ph cHx-321 4-(4-MeSO ₂ HN-Ph) HHH Ph -CH (Ph) Me-322 2- (2-EtSO ₂ HN-Ph) HHH Ph 1- Et-Pn-323 2- (2-EtSO ₂ HN-Ph) HHH Ph cHx-324 2- (2-EtSO ₂ H -Ph) HHH Ph -CH (Ph) Me-325 2- (4-EtSO ₂ HN -Ph) HHH Ph 1-Et-Pn-326 2-(4-EtSO ₂ H -Ph) HHH Ph cHx-327 2- (4-EtSO ₂ HN-Ph) HHH Ph -CH (Ph) Me-328 4 _{- (2- EtSO 2 HN-Ph} ) HHH Ph 1-Et-Pn-329 4 - (2 - EtSO 2 HN-Ph) HHH Ph cHx-330 4- (2-EtS0 2 HN-Ph) HHH Ph -CH (Ph) Me-331 4- (4-EtSO ₃ HN-Ph) HHH Ph 1-Et-Pn-332 4- (4-EtSO ₂ HN— Ph) HHH Ph cHx oo

_{4- (4-EtS0 2 HN-} Ph) HHH Ph - CH (Ph) Me

2- [4- (2-Tol) S0 2 HN- Ph] HHH Ph cHx

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2- [4- (4-Tol) S0 2 HN-Ph] HHH Ph 4-Me-cHx-339 2- [4- (4-Tol) SOzHN-Ph] HHH Ph -CH (Ph) Me

3- [4- (4-Tol) S0 2 HN-Ph] HHH Ph cHx-341 4- [4- (4-Tol) S0 2 HN-Ph] HHH Ph cHx

2- [4- (4-MeO-Ph) S0 ₂ HN -Ph]

HHH Ph cHx-343 2- [4- (4-F-Ph) S0 2 HN-Ph]

HHH Ph cHx -344 2- [4- ( 4-Cl-Ph) S0 2 HN- Ph]

 HHH Ph cHx -345 2- (3-Tz-Ph) HHH 4- e- -Ph cHx -346 3- (3-Tz-Ph) HHH 4-Me- -Ph 1-Et-Pn -347 4-( 2-Tz-Ph) HHH 4- Me.-Ph -CH (Ph) Me

1-348 4- (3-Tz-Ph) H H H 4- Me.- Ph 1-Et-Pn

_{1-349 2- (2-MeS0 2 -Ph} ) HHH 4 -Me. -Ph -CH (Ph) Me

_{1-350 2- (3-MeS0 2 -Ph} ) HHH 4 -. Me -Ph cHx

_{1-351 2- (4-MeS0 2 -Ph} ) HH u

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-432 2-Tz Η Η Η Ph -CH (cHx) Me-433 2-Τζ Η Η Η 4-Me-Ph -CH (cHx) Me-434 2-Τζ Η Η-Ph -CH (4-Br- Ph) Me-435 2-Τζ Η Η Η 4-Me-Ph -CH (4-Br-Ph) Me-436 2-Τζ 4-Me Η Η Ph -CH (4-Br-Ph) Me-437 2 -Τζ 4-F Η Η Ph -CH (4-Br-Ph) Me-438 2-Τζ Η Η Η Ph -CH ₂ (4-H ₂ N0C-Ph) -439 2-Τζ Η Η Η 4-Me -Ph -CH ₂ (4-H ₂ N0C-P) -440 2-Τζ Η Η Η Ph -CH (l-Np) Me-441 2- Τζ Η Η Η 4-Me-Ph -CH (1-Np ) Me

-448 3-Τζ -Me H H Ph 1-Et-Pn

-449 3-Τζ 4-OMe H H Ph 1-Et-Pn

-450 3-Τζ 4-OMe 6-OH H Ph 1-Et-Pn

-451 3-Τζ 4-OMe 5-F 6-OH Ph 1-Et-Pn

-452 3-Τζ 6-OMe H H Ph 1-Et-Pn

-453 3-Τζ 4-OH H H Ph 1-Et-Pn

-454 3-Τζ 4-F H H Ph 1-Et-Pn

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-508 3-Tz Η Η Η -CH (Ph) Me

R ^5a = 6-F-4-Me-2- e0-Ph

-509 3-Τζ Η Η Η Ph -CH (4-Me-Ph) Me-510 3-Τζ Η Η Η Ph -CH (4-MeO-Ph) Me-511 3-Τζ Η Η Η Ph -CH ( 4-F-Ph) Me-512 3-Τζ Η Η Η Ph -CH (4-Cl-Ph) Me

-514 3-Τζ Η Η Η 4-Me-Ph 3-Pn

-515 3-Τζ Η Η Η Ph -CH (cHx) Me-516 3-Τζ Η Η Η 4-Me-Ph -CH (cHx) Me-517 3-Τζ Η Η Η Ph -CH (4-Br- Ph) Me-518 3-Τζ Η Η Η 4-Me-Ph -CH (4-Br-Ph) Me -519 3-Τζ 4-Me Η Η Ph -CH (4-Br-Ph) Me -520 3 -Τζ 4-F Η Η Ph -CH (4-Br-Ph) Me -521 3-Τζ Η Η Η Ph -CH ₂ (4-HzNOC-Ph) -522 3-Τζ Η Η Η 4-Me-Ph -CH ₂ (4-H ₂ N0C-Ph) -523 3-Τζ Η Η Η Ph -CH (1-Np) e -524 3- Τζ Η Η Η 4-Me-Ph-CH (卜 Np) Me

1-529 4-Τζ Η Η Η Ph 2-Hx £ ss / 86: fcv il: £

-554 4-Tz 2-OMe Η Η Ph cHx

-555 4-Tz 2-OMe 6-OH H Ph cHx

-556 4-Tz 6-OMe H H Ph cHx

-558 4-Τζ H H H Ph 4- e-cHx

-559 4-Τζ H H H Ph 4-tBu-cHx

-560 4-Τζ HHH Ph 4-MeO-cHx

-562 4-Τζ H H H Ph 4-Cl-cHx

-563 4-Τζ H H H Ph 4-HO-cHx

-564 4-Τζ HHH Ph 4-H0H ₂ C-cHx-565 4-Τζ HHH Ph -CH _2- (4-H0H ₂ C-cHx) -566 4-Τζ HHH Ph -CH _2- (4-H00C- cHx) -567 4-Τζ HHH Ph -CH _2- [4- (Me) ₂ NOC-cHx]

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_{-951 2-MeS0 2 HHH Ph -CH} (4-Me-Ph) Me-952 2-MeS0 2 HHH Ph -CH (4-MeO-Ph) Me-953 2-MeS0 2 HHH Ph -CH (4-F -Ph) Me-954 2-MeS0 2 HHH Ph -CH (4-Cl-Ph) Me-955 2-MeS0 2 HHH Ph 3-Pn

_{-956 2-MeS0 2 HHH 4-} Me-Ph 3-Pn

_{-957 2-MeS0 2 HHH Ph -CH} (cHx) Me-958 2-MeS0 2 HHH 4-Me-Ph -CH (cHx) Me -959 2-MeS0 2 HHH Ph -CH (4-Br-Ph) Me _{-960 2-MeS0 2 HHH 4-} Me-Ph -CH (4-Br-Ph) Me -961 2-MeS0 2 4-Me HH Ph -CH (4-Br-Ph) Me -962 2-MeS0 2 4 -FHH Ph -CH (4-Br- Ph) Me -963 2-MeS0 2 HHH Ph -CH 2 (4-H 2 N0C-Ph)

_{1-964 2-MeS0 2 HHH 4-} Me-Ph - CH 2 (4- H 2 NOC-Ph)

1-965 2 -Me SO H H H Ph -CH (l-Np) Me

1-966 2- eS0 ₂ HHH 4-Me-Ph -CH (l-Np) Me

1-967 3- MeS0 ₂ HHH Ph iPr

1-968 3-MeS0 ₂ HHH Ph Bu

1-969 3-MeS0 ₂ HHH Ph tBu

1-970 3-MeS0 ₂ HHH Ph nPn

1-971 3-MeS0 ₂ HHH Ph 2-Hx

_{1-972 3-MeS0 2 HHH Ph 1} -Et-Pn

1-973 3-MeS0 ₂ 4-Me HH Ph 1-Et-Pn

1-974 3-MeS0 ₂ 4-0Me HH Ph 1-Et-Pn

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1654 2-PhOCHN H H H Ph cHx

1655 2- PhOCHN H H H Ph -CH (P) Me1656 3-PhOCHN H H H Ph 1- Et-Pn1657 3- PhOCHN H H H Ph 2- Et-Hx

1658 3-PhOCHN H H H Ph cHx

• 1659 3-PhOCHN H H H Ph Bz

1660 3-PhOCHN H H H Ph -CH (Ph) Me • 1661 3- (4-Tol) OCHN H H H Ph -CH (Ph) Me

1662 4- PhOCHN H H H Ph 1-Et-Pn

-1663 4- PhOCHN H H H Ph cHx

• 1664 4- PhOCHN H H H Ph -CH (Ph) Me

■ 1665 2- TzOCHN H H H Ph 1-Et-Pn

■ 1666 2-TzOCHN H H H Ph cHx

-1667 2-TzOCHN H H H Ph -CH (Ph) Me

1668 3- TzOCHN H H H Ph 1-Et-Pn

• 1669 3- TzOCHN H H H Ph 2- Et-Hx

1670 3-TzOCHN H H H Ph cHx -1671 3-TzOCHN H H H Ph Bz

1672 3- TzOCHN H H H Ph -CH (Ph) Me

1673 4-TzOCHN H H H Ph 1-Et-Pn

1674 4-TzOCHN H H H Ph cHx

-1675 4- TzOCHN H H H Ph -CH (Ph) Me

■ 1676 2- (2-Tol) S0 2 HNOCHN HHH Ph tBu

■ 1677 2- (2-Tol) S0 2 HNOCHN HHH Ph 1- Et-Pn 678 2- (2-Tol) S0 2 HNOCHN HHH Ph 2- Et-Hx 1679 2- 2-Tol S0 ₂ HNOCHN HHH Ph cHx

1680 2- 2-Tol S0 ₂ HNOCHN HHH Ph 4-Me-cHx 1681 2- 2-Tol S0 ₅ HNOCHN HHH Ph Bz

_{• 1682 2- 2-Tol S0 2} HNOCHN HHH Ph -CH (Ph) Me

_{■ 1683 2- 2- Tol S0 2 HNOCHN} HHH Ph -CH (4-Me-Ph) Me

■ 1684 2-3- Tol SO: HNOCHN H H H Ph tBu

 • 1685 2- 3-Tol SO: HNOCHN H H H Ph 1-Et-Pn

■ 1686 2- 3-Tol S0 _: HNOCHN HHH Ph 2-Et-Hx

-1687 2- 3-Tol SO: HNOCHN H H H Ph cHx

 ■ 1688 2- 3-Tol SO: HNOCHN H H H Ph 4-Me-cHx

■ 1689 2- 3-Tol SO: HNOCHN H H H Ph Bz

 1690 2- 3-Tol so: HNOCHN H H H Ph -CH (Ph) Me -1691 2-3- Tol so: HNOCHN H H H Ph -CH (4- Me-Ph) Me

-1692 2- 4- Tol so: HNOCHN H H H Ph iPr

 -1693 2- 4-Tol so: HNOCHN H H H Ph Bu

 -1694 2- 4-Tol so: HNOCHN H H H Ph tBu

 -1695 2- 4-Tol so: HNOCHN H H H Ph nPn

 -1696 2- 4-Tol SO: HNOCHN H H H Ph 2-Hex

 -1697 2-4-Tol SO: HNOCHN H H H Ph 1-Et-Pn

-1698 2- 4-Tol SO2HNOCHN 4-Me H H Ph 1-Et-Pn

-1699 2- 4-Tol SO2H OCHN 4-OMe H H Ph 1-Et-Pn

-1700 ₂ - 4-Tol S0 2 strokes CHN 4-OMe 6 - OH H Ph 1-Et-Pn -1701 2- 4-Tol S0 2 HNOCHN 4-OMe 5-F 6- OH Ph 1-Et-Pn

_{-1702 2 - 4-Tol S0 2} HNOCHN 6-O e HH Ph 1-Et-Pn

-1703 2- 4-Tol SO2HNOCHN 4-OH H H Ph 1-Et-Pn

-1704 2- 4-Tol SO2HNOCHN 4-one FHH Ph 1-Et-Pn

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1738 2- (4- -Tol) SO: ₂ HN0CHN HHH Ph 1 ― (CH ₂ ) ₂ -Ph

1739 2- (4.-Tol) S0 _{; 2} HN0CHN HHH Ph -CH (Ph) Me

1740 2- (4- -Tol) SO: ₂ HNOCHN 4-Me HH Ph -CH (Ph) Me

1741 2- (4- -Tol) SO: ₂ HNOCHN 4-OMe HH Ph -CH (Ph) Me

1742 2- (4-Tol) SO: ₂ HN0CHN 4-OMe 6-OH H Ph-CH (Ph) Me

1743 2- (4-Tol) SO2HNOCHN 4-OMe 5-F 6- OH Ph -CH (Ph) Me

• 1744 2- (4-Tol) S0 2 HNOCHN 6-OMe HH Ph - CH (Ph) Me

• 1745 2- (4-Tol) S0 2 HNOCHN 4- OH HH Ph -CH (Ph) Me

■ 1746 2- (4-Tol) S0 2 HNOCHN 4-FHH Ph -CH (Ph) Me

■ 1747 2- (4-Tol) S0 2 HNOCHN 4- CI HH Ph - CH (Ph) Me

■ 1748 2- (4-Tol) S0 2 HNOCHN 4-NH 2 HH Ph -CH (Ph) Me

• 1749 2- (4-Tol) S0 2 HNOCHN 4-NHMe HH Ph -CH (Ph) Me

-1750 2- (4-Tol) SO2HNOCHN 4- -N (Me) 2 H H Ph -CH (Ph) Me

-1751 2 - (4-Tol) S0 2 HNOCHN HHH -CH (Ph) Me

-1752 2 one _{(4-Tol) S0 2 HNOCHN} HHH 3- Me - Ph -CH (Ph) Me

-1753 2- (4-Tol) S0 ₂ H OCHN HHH 4- Me- Ph -CH (Ph) Me

-1754 2-(4-Tol) S0 ₂ HNOCHN HHH 4-1 MeO-Ph -CH (Ph) Me £ ss /

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-144 2-MeSO HHH 2-Thi cHx-145 2-MeSO HHH 2- Thi -CH (Ph) Me-146 2-MeSO HHH 3- Thi 1-Et-Pn-147 2-MeSO HHH 3-Thi cHx- 148 2-MeSO HHH 3-Thi -CH (Ph) Me-149 4-MeSO HHH 2-Thi cHx-150 4-MeSO HHH 3-Thi cHx-151 2-EtSO HHH 2- Thi cHx-152 2-EtS0 HHH 3- Thi cHx-153 2- (4-Tol) S0 ₂ HN0CHN HHH 2- Thi -CH (Ph) Me-154 2- (4-Tol) S0 ₂ HN0CHN HHH 3- Thi-CH (Ph) Me-155 4- (4-Tol) S0 ₂ HN0CHN HHH 2- Thi -CH (Ph) Me-156 4- (4-Tol) SO2HNOCHN HHH 3- Thi -CH (Ph) Me-157 3-Tz HHH 2-Thi- CH (4- Br-Ph) Me -158 4-Tz HH 3-Thi -CH (4-Br-Ph) Me-159 2- (2-MeS0 2 -Ph) HHH 2 - l-dioxo-Thi) cHx _{-160 2 - (2-MeS0 2} -Ph) HHH 3- l-dioxo-Thi) cHx-161 4 - (2-MeS0 2 -Ph) HHH 2- 1 -di oxo-Thi) cHx-162 4- ( _{2-MeS0 2 -Ph) HHH 3-} l-dioxo-Thi) cHx-163 3- Tz HHH 2- l-dioxo-Thi) 1-Et-Pn-164 3-Tz HHH 2- l-dioxo-Thi) cHx-165 3-Tz HHH 2- l-dioxo-Thi) -CH (Ph) Me-166 3-Tz HHH-CH (Ph) Me

R ^5c = 2- (1, l-dioxo-4- -Me-Thi) -167 3-Tz HH 3- (1, l-dioxo-Thi) 1-Et-Pn-168 3-Tz HH 3- (1 , l-dioxo-Thi) cHx

Dimension

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_{-189 4-MeS0 2 HHH 2- (} 1, l-dioxo-Thi) -CH (Ph) Me-190 4 - MeS0 2 HHH 3- (1, l-dioxo-Thi) 1-Et-Pn-191 4 _{- MeS0 2 HHH 3- (1,} l-dioxo-Thi) cHx-192 4-MeS0 2 HHH 3- (1, l-dioxo-Thi) -CH (Ph) Me-193 2 - EtS0 2 HHH 2- ( (1, l-dioxo-Thi) 1-Et-Pn-194 2-EtS0 ₂ HHH 2- (1, l-dioxo-Thi) cHx-195 2-EtS0 ₂ HHH cHx

R ^5c = 2- (1, l-dioxo-4-Me-Thi) -196 2- EtS0 ₂ HHH 2- (i, l-dioxo-Thi) -CH (Ph) Me-197 2-EtS0 ₂ HHH 3 - (1, l-dioxo- Thi) 1-Et-Pn-198 2 - EtS0 2 HHH 3- (1, l-dioxo-Thi) cHx-199 2-EtS0 2 HHH cHx

R ^5c = 3- (1, l-dioxo-5-Me-Thi) -200 2-EtS0 ₂ HHH 3- (1, l-dioxo-Thi) -CH (Ph) Me-201 4-EtS0 ₂ HHH 2 -(1, l-dioxo-Thi) 1-Et-Pn-202 4-EtS0 ₂ HHH 2- (1, l-dioxo-Thi) cHx-203 4-EtS0 ₂ HHH 2- (1, l-dioxo- Thi) -CH (Ph) Me-204 4-EtS0 ₂ HHH 3- (1, l-dioxo-Thi) 1-Et-Pn-205 4-EtS0 ₂ HHH 3- (1, l-dioxo-Thi) cHx -206 4- EtS0 ₂ HHH 3- (1.l-dioxo-Thi) -CH (Ph) Me-207 2-BuS0 ₂ HHH 2- (1, l-dioxo-Thi) 1-Et-Pn -208 2 -BuS0 ₂ HHH 2- (1, l-dioxo-Thi) cHx -209 2-BuS0 ₂ HHH 2- (l, l-dioxo-Thi) -CH (Ph) Me -210 2-BuS0 ₂ HHH 3- ( (1, l-dioxo-Thi) 1-Et-Pn -211 2-BuSOi HHH 3- (1, l-di ₀ xo-Thi) cHx -212 2-BuSO: HHH 3- (1, l-dioxo-Thi )-CH (Ph) Me £ szo / 86fcvl: 9 / 86sSAS, 〇Λν C

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-239 3-Tz HHH 2- Thiz -CH (Ph) Me-240 3-Tz HHH 3- Thiz 1-Et-Pn-241 3-Tz HHH 3-Thiz cHx-242 3-Tz HHH 3-Thiz -CH (Ph) Me-243 4-Tz HHH 3-Thiz 1-Et-Pn-244 4-Tz HHH 3-Thiz cHx-245 4-Tz HHH 3-Thiz -CH (Ph) Me-246 3- (4- _{tol) S0 2 HN0C HHH 2- Thiz} -CH (Ph) Me-247 3- (4-tol) S0 2 HN0C HHH 3- Thiz -CH (Ph) Me-248 3- [2- (2-tol) Ph ] SO2HNOC

HH 2-Thiz -CH (Ph) Me-249 3- [2- (2-Tol) Ph] S0 2 HN0C

HHH 3-Thiz -CH (Ph) Me-250 2-MeS0 2 HHH 2-Thiz 1-Et-Pn-251 2- eS0 2 HHH 2-Thiz cHx-252 2-MeS0 2 HHH 2- Thiz -CH (Ph _{) Me-253 2-MeS0 2} HHH 3- Thiz 1-Et-Pn-254 2-MeS0 2 HHH 3-Thiz cHx-255 2-MeSOj HHH 3-Thiz -CH (Ph) Me-256 4-MeS0: HHH 2-Thiz 1-Et-Pn -257 4-MeS0 2 HHH 2-Thiz cHx-258 4 - MeS0 2 HHH 2- Thiz -CH (Ph) Me -259 4-MeS0 2 HHH 3- Thiz 1-Et-Pn -260 4-MeSO: HHH 3-Thiz cHx -261 4-MeS0 _: HHH 3-Thiz -CH (Ph) Me -262 2-EtSO, HHH 2-Thiz 1-Et-Pn -263 2-EtS0 ₂ HHH 2- Thiz cHx-264 2-EtS0 ₂ HHH 2- Thiz -CH (Ph) Me-265 2-EtS0 ₂ HHH 3- Thiz 1-Et-Pn-266 2-EtS0 ₂ HHH 3 -Thiz cHx-267 2-EtS0 ₂ HHH 3- Thiz -CH (Ph) Me-268 4-EtS0 ₂ HHH 2-Thiz 1-Et-Pn-269 4-EtS0 ₂ HHH 2- Thiz cHx-270 4-EtS0 ₂ HHH 2- Thiz -CH (Ph) Me-271 4-EtS0 ₂ HHH 3-Thiz 1-Et-Pn-272 4- EtS0 ₂ HHH 3- Thiz cHx-273 4-EtS0 ₂ HHH 3-Thiz -CH ( Ph) Me-274 2-BuS0 ₂ HHH 2-Thiz 1-Et-Pn-275 2-BuS0 ₂ HHH 2-Tiz cHx-276 2-BuS0 ₂ HHH 2-Thiz-CH (Ph) Me-277 2- BuS0 ₂ HHH 3- Thiz 1-Et-Pn-278 2-BuS0 ₂ HHH 3- Thiz cHx-279 2-BuS0 ₂ HHH 3- Thiz -CH (Ph) Me-280 4- BuS0 ₂ HHH 2-Thiz 1- Et-Pn-281 4-BuS0 ₂ HHH 2-Thiz cHx-282 4-BuS0 ₂ HHH 2- Thiz -CH (Ph) Me-283 4-BuS0 ₂ HHH 3-Thiz 1-Et-Pn-284 4-BuS0 ₂ HHH 3- Thiz cHx-285 4-BuSOz HHH 3-Thiz -CH (Ph) Me-286 2-PhS0 ₂ HHH 2- Thiz tBu-287 2-PhS0 ₂ HHH 3-Thiz tBu-288 2- (4- Tol) SO2HNOCHN HHH 2-Thiz -CH (Ph) Me -289 2- (4-Tol) SO2HNOCHN HHH 3-Thiz-CH (Ph) Me-290 4- (4-Tol) SO2HNOCHN HHH 2- Thiz -CH (Ph) Me-291 4- (4-Tol) S0 ₂ HN0CHN HHH 3- Thiz -CH (Ph) Me-292 3- Tz HHH 2- Thiz -CH (4-Br-Ph) Me-293 4- Tz HHH 3- Thiz -CH (4- Br- Ph) Me _{-294 2- (2-MeS0 2 -Ph} ) HHH 2- Ind cHx-295 2- (2-MeS0 2 -Ph) HHH 3- lnd cHx-296 4- (2-MeS0 2 -Ph) HHH 2- Ind cHx-297 4- (2-MeS0 2 -P) HHH 3- Ind cHx-298 3- Tz HHH 2- Ind -CH (Ph) Me-299 3- Tz HHH 3- Ind - CH (Ph) Me-300 4- Tz HHH 2- Ind 1-Et-Pn-301 4-Tz HHH 3- Ind 1-Et-Pn-302 3- (4-Tol) SO2HNOC HHH 2- Ind-CH (Ph) Me-303 3- _{(4-toL) S0 2 HN0C} HHH 3- Ind -CH (Ph) Me-304 3- [2- (2-tol) Ph] S0 2 HN0C

 H H H 2-Ind -CH (Ph) Me-305 3-[2- (2-Tol) Ph] SO2HNOC

HH 3-Ind -CH (Ph) Me-306 2-MeSOj HHH 2-Ind 1-Et-Pn-307 2-MeSOi HHH 2-Ind cHx-308 2-MeS0 2 HHH cHx

5 ^c = 2- (4-Me-Ind)

-309 2-MeSOi HHH 2- Ind-CH (Ph) Me-310 2-MeSO- HHH 3- Ind 1-Et-Pn-311 2-MeSO: HHH 3-Ind cHx en

M ffi ffi ffi

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O o o

-335 2-PhS0 ₂ HHH 3-Ind tBu-336 2- (4-Tol) SO2HNOCHN HHH 2- Ind -CH (Ph) Me-337 2- (4-Tol) SO2HNOCHN HHH 3- Ind -CH (Ph) Me-338 3- Tz HHH 2- Ind -CH (4- Br- Ph) Me-339 4- Tz HHH 3- Ind -CH (4 - Br- Ph) Me-340 2- (2-MeS0 2 -Ph ) HHH 2- BThi cHx-341 2- (2-MeS0 2 -Ph) HHH 3- BThi cHx-342 4- (2-MeS0 2 -Ph) HHH 2- BThi cHx-343 4- (2- eS0 2 - Ph) HHH 3- BThi cHx-344 3- Tz HHH 2- BThi -CH (Ph) Me-345 3- Tz HHH 3- BThi-CH (Ph) Me-346 4- Tz HHH 2- BThi 1-Et- Pn-347 4-Tz HHH 3- BThi 1-Et-Pn-348 3- (4-Tol) S0 ₂ HN0C HHH 2- BThi -CH (Ph) Me-449 3- (4-Tol) S0 ₂ HN0C HHH 3- BThi -CH (Ph) Me-350 3- [2- (2-Tol) Ph] S0 ₂ strokes C

 H H H 2-BThi -CH (Ph) Me-351 3- [2- (2-Tol) Ph] SO2HNOC

HHH 3-BThi -CH (Ph) Me-352 2-MeSOi HHH 2-BThi 1-Et-Pn-353 2-MeSO _∑ HHH 2-BThi cHx-354 2-MeS0 ₂ HHH 2- (4-Me-BThi ) cHx-355 2- eS0 ₂ HHH 2-BThi -CH (Ph) Me-356 2-MeSO _∑ HHH 3-BThi 1-Et-Pn-357 2-MeSO: HHH 3-BThi cHx-358 2- eS0 _; HHH 3- (5- e-BThi; cHx

m M ¾

M i:

szo / 86dT / :; £ Ġ

-406 3-Tz HHH 3- (1, l-dioxo-BThi) 1-Et-Pn-407 3-Tz HHH 3- (1, l-dioxo-BThi) cHx-408 3-Tz HHH 3- (1 , l-dioxo-BThi) -CH (PH) Me

R ^So = 3- (1, l-dioxo-5-Me-BThi) -410 4-Τζ HHH 3- (1, l-dioxo-BThi) 1-Et-Pn-411 4-Τζ HHH 3- (1 , l-dioxo-BThi) cHx-412 4-Τζ HHH 3- (1, l-dioxo-BThi) -CH (PH) Me

R ^5c = 3- (1, l-dioxo-5-Me-BThi) -414 3- (4-Tol) S0 ₂ HN0C Η Η H 2- (1, l-dioxo-BThi) -CH (Ph) Me -415 3- (4-Tol) S0 2 HN0C Η Η H 3- (1, l-dioxo-BThi) -CH (Ph) Me-416 3- [2- (2-Tol) Ph] S0 2 HN0C

Η Η H 2- (1, l -dioxo-BThi) -CH (Ph) Me-417 3- [2- (2-Tol) Ph] S0 2 HN0C

Η Η H 3- (1, l-dioxo-BThi) -CH (Ph) Me-418 2-MeS0 ₂ Η Η H 2- (1, l-dioxo-BThi) 1-Et-Pn-419 2-MeS0 ₂ Η Η H 2- (1, l-dioxo-BThi) cHx-420 2-MeS0 ₂ Η Η H cHx

R ^So = 2- (1, l-dioxo-4-Me-BThi) -421 2- MeSO: HHH 2- (l, l-dioxo-BThi) -CH (Ph) Me-422 2-MeS0 ₅ HHH 3 -(1, l-dioxo-BThi) 1-Et-Pn-423 2-MeS0 _: HHH 3- (1, l-dioxo-BThi) cHx-424 2-MeSO _: HHH cHx

5 ^c = 3- (1, l-dioxo-5-Me-BThi) -425 2-MeS0 _: HHH 3- (1, l-dioxo-BThi) -CH (Ph) Me _{-426 4-MeS0 2 HHH 2- (} 1 - di oxo-BTh i) 1-Et-Pn-427 4-MeSO- HHH 2 - (1-dioxo-BThi) cHx-428 4-MeS0 2 HHH 2- ( 1-dioxo-BThi) -CH ( Ph) Me-429 4-MeS0 2 HHH 3- (1-dioxo-BThi) 1-Et-Pn-430 4-MeS0 2 HHH 3 - (1-dioxo-BThi) cHx -431 4-MeS0 ₂ HHH 3- (1 -di oxo-BTh i) -CH (Ph) Me-432 2-EtS0 ₂ HHH 2-(1-dioxo-BThi) 1-Et-Pn-433 2-EtS0 ₂ HHH 2-(1-di oxo-BTh i) cHx-434 2-EtSOj HHH cHx

R ^Sc = 2- (1, l-dioxo-4-Me -BThi) -435 2-EtS0 _: HHH 2- (1, 1-dioxo-BThi) -CH (Ph) Me-436 2-EtSO: HHH 3 -(1, 1-dioxo-BThi) 1-Et-Pn-437 2-EtS0 _: HHH 3- (1, 1-dioxo-BThi) cHx-438 2-EtSO: HHH cHx

^{R 5c = 3- (1, l} -dioxo-5-Me -BThi) -439 2-EtS0 2 HHH 3- (1-dioxo-BThi) - CH (Ph) Me-440 4-EtS0 2 HHH 2- ( 1-dioxo-BThi) 1- Et-Pn-441 4- EtS0 2 HHH 2- (1-dioxo-BThi) cHx-442 4 one _{EtS0 2 HHH 2 - (1-} dioxo-BThi) -CH (Ph) Me -443 4- EtSO: HHH 3-(1-dioxo-BThi) 1-Et-Pn-444 4— EtSO: HHH 3- (1-di oxo-BTh i) cHx-445 4- EtS0 ₂ HHH 3-( 1-dioxo-BThi) -CH (Ph) Me-446 2-BuS0 ₂ HHH 2- (1-dioxo-BThi) 1-Et-Pn-447 2-BuS0 _: HHH 2- (1-dioxo-BThi) cHx -448 2-BuS0 _∑ HHH 2- (1-dioxo-BThi) -CH (Ph) Me-449 2-BuS0 _; HHH 3- (1 -di oxo-BTh i) 1-Et-Pn -450 2-BuSOz HHH 3-1-dioxo-BThi cHx

-451 2-BuS0 ₂ HHH 3-1-di oxo-BTh i-CH (Ph) Me-452 4-BuS0 ₂ HHH 2-1-di oxo-BTh i 1-Et-Pn-453 4-BuS0 ₂ HHH 2- 1-di oxo-BTh i cHx

-454 4-BuS0 ₂ HHH 2- 1-dioxo-BThi -CH (Ph) Me-455 4-BuS0 ₂ HHH 3-1 -di oxo-BTh i 1-Et-Pn-456 4-BuS0 ₂ HHH 3- 1-dioxo-BThi cHx

_{-457 4-BuS0 2 HHH 3 -} 1-dioxo-BThi -CH (Ph) Me-458 2- PhS0 2 HHH 2- 1 -di oxo-BTh i tBu

_{-459 2- PhS0 2 HHH 3- 1 -di} oxo-BTh i tBu-460 2- (4-Tol) S0 2 HN0CHN HHH 2- 1 - di oxo-BTh i -CH (Ph) Me-461 2- ( 4-Tol) SO2HNOCHN HHH 3-1-di oxo-BTh i -CH (Ph) Me-462 4- (4-Tol) SO2HNOCHN HHH 2-1-di oxo-BTh i -CH (Ph) Me-463 4 -(4-Tol) S0 ₂ HN0CHN HHH 3-1-dioxo-BThi -CH (Ph) Me-464 3- Tz HHH CH (4-Br-Ph) Me

R ^5c = 2- (1, 1-dioxo-BThi)

-465 4-Tz H H H -CH (4-Br-Ph) Me

R ^5c = 2- (1, 1-dioxo-BThi)

_{-466 2- (2- eS0 2 -Ph)} HHH 2-BT iz cHx-467 2- (2-MeS0 2 -Ph) HHH 3-BThiz cHx-468 4- (2-MeS0 2 -Ph) HHH 2- BThiz cHx-469 4- (2- MeS0 2 -Ph) HHH 3-BThiz cHx-470 3-Tz HHH 2-BThiz -CH (Ph) Me-471 3-Tz HHH 3-BThiz - CH (Ph) Me- 472 4-Tz HHH 2-BThiz 1-Et-Pn-473 4-Tz HHH 3-BThiz 1-Et-Pn -474 3- (4-Tol) SO2HNOC HHH 2-BThiz -CH (Ph) Me-475 3- (4-Tol) SO2HNOC HHH 3-BThiz -CH (Ph) Me-476 3- [2- (2- Tol) Ph] SO: HNOC

HHH 2-BThiz -CH (Ph) Me-477 3- [2- (2-Tol) Ph] S0 ₂ HN0C

HHH 3-BThiz -CH (Ph) Me-478 2-MeS0 2 HHH 2-BThiz 1-Et-Pn-479 2 - MeS0 2 HHH 2-BThiz cHx-480 2 - MeS0 2 HHH 2- (4-Me- (BThiz) cHx-481 2-MeS0 ₂ HHH 2-BThiz -CH (Ph) Me-482 2-MeS0 ₂ HHH 3-BThiz 1-Et-Pn-483 2-MeS0 ₂ HHH 3-BThiz cHx -484 2-MeS0 _{2 HHH 3- (5-Me-} BThiz) cHx -485 2-MeS0 2 HHH 3-BThiz -CH (Ph) Me -486 4-MeS0 2 HHH 2-BThiz 1-Et-Pn -487 4- MeS0 2 HHH 2-BThiz cHx -488 4-MeS0 2 HHH 2-BThiz -CH (Ph) Me -489 4- MeS0 2 HHH 3-BThiz 1-Et-Pn -490 4-MeS0 2 HHH 3-BThiz cHx -491 4 - _{MeS0 2 HHH 3-BThiz -CH (} Ph) Me -492 2-EtS0 2 HHH 2-BThiz 1-Et-Pn -493 2-EtS0 2 HHH 2-BThiz cHx -494 2 - EtS0 2 HHH 2- (4- Me-BThiz) cHx

3-495 2-EtS0 ₂ HHH 2-BThiz -CH (Ph) Me

_{3-496 2 - EtS0 2 HHH 3-} BThiz 1-Et-Pn

3-497 2-EtS0 ₂ HHH 3-BThiz cHx -498 2-EtS0 ₂ HHH 3- (5-Me-BThiz) cHx

_{-499 2-EtS0 2 HHH 3-} BThiz -CH (Ph) Me-500 4-EtS0 2 HHH 2-BThiz 1-Et-Pn-501 4-EtS0 2 HHH 2-BThiz cHx

_{-502 4-EtS0 2 HHH 2-} BThiz -CH (Ph) Me-503 4-EtS0 2 HHH 3-BThiz 1-Et-Pn-504 4-EtS0 2 HHH 3-BThiz cHx

-505 4-EtS0 ₂ HHH 3-BThiz -CH (Ph) Me-506 2-PhS0 ₂ HHH 2-BThiz tBu

-507 2-PhS0 ₂ HHH 3-BThiz tBu

-508 2- (4-Tol) SO ₂ HN0CHN HHH 2-BThiz -CH (Ph) Me-509 2- (4-Tol) S0 ₂ HN0CHN HHH 3-BThiz -CH (Ph) Me-510 3- Tz- HHH 2-BThiz -CH (4- Br- Ph) Me-511 4- Tz HHH 3-BThiz ■ CH (4-Br-Ph) Me-512 2- (2-MeS0 2 -Ph) HHH 2-0xa cHx _{-513 2 - (2- MeS0 2 -} Ph) HHH 3-0xa cHx-514 4- (2-MeS0 2 -Ph) HHH 2-Oxa cHx-515 4- (2-MeS0 2 -Ph) HHH 3-0xa cHx-516 3-Tz HHH 2-Oxa -CH (Ph) Me-517 3-Tz HHH 3-0xa -CH (Ph) Me-518 4-Tz HHH 2-Oxa 1-Et-Pn-519 4-Tz HHH 3 -Ox a 1-Et- Pn-520 3- (4-Tol) SO2HNOC HHH 2-Oxa -CH (Ph) Me-521 3- (4-Tol) S0 2 HN0C HHH 3-Oxa -CH (Ph ) Me-522 3- [2- (2-Tol) Ph] S0 ₂ HN0C

HHH 2-Oxa -CH (Ph) Me

One ooww ¾ m ffi M tr; ffi rc ί = α a:

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K ffi ί 3 ffi ij iz: n

t¾ K ffi K C¾ ffi ffi W M

O

3-598 2-PhS0 ₂ HHH 2-B0xa tBu

3-599 2-PhS0 ₂ HHH 3-B0xa tBu

 3-600 2- (4-Tol) SO2HNOCHN H H H 2-B0xa -CH (Ph) Me

3-601 2- (4-Tol) SO2HNOCHN H H H 3-B0xa -CH (Ph) Me

3-602 3-Tz H H H 2-B0xa -CH (4-Br-Ph) Me

3-603 4-Tz H H H 3 -BOx a -CH (4-Br-Ph) Me In the above table, preferred compounds of the benzylamines having the general formula (I) include:

Compound No. 1-1, 1-3 1-4, 1-5, 1-6, 1-87, 1-125, 1-176, 1-236, 266, 1-366, 1-367 1-410, 1-417, 1-418, 1-427, 1-442, 1-444,

447 1-461 1-467 1-489, 1-503, 1-510, 1-518, 1-525, 1-527, 529 1-530 1-550 1-568, 1-572, 1-575, 1-586, 1-587, 1-593, 616 1-617 1-633 1-637, 1-638, 1-639, 1-640, 1-641, 1-643, 654 1-655 1-665 1-667, 1-669, 1-670, 1-675, 1-677, 1-679, 687 1-696 1-705 1-707, 1-709, 1-710, 1-711, 1-712 , 1-767, 768 1-769 1-771 1-775, 1-782, 1-784, 1-786, 1-802, 1-811, 815 1-816 1-820 1-843, 1-847 , 1-853, 1-873, 1-875, 1-876, 878 1-910 1-927 1-931, 1-945, 1-946, 1-952, 1-994, 1014, 1019, 1 -1028, 10 1035, 1-1077, 1-1097, 1-1110, 1-1160, 1 1172, 1-1174, 1177.1-1180, 1 -1193, 1 1195, 1-1196, 1 -1202,卜 1264, 1 -1267. 1-1270, 1285, 1 -1346, 1-1387, 1-1456, 1 1458, 1 1461, 1-1477, 15 1512, 1-1522, 1609. 1 -1645. 16 1649 , 1 -1697, 1 -1739, U 1754, 1-1769. U 1775, U 1780,

1782, 2-15, 2-18, 2-2 2-24, 2-28, 2-31, 2-32, 2-94. 2-98, 2-119, 2-12

2, 2-131, 2-136, 2-140, 2-144, 2-147, 2-152, 2-214, 2-220, 2-229, 2-242, 2-247, 2-248 , 2-255, 2-260, 2-274, 2-276, 2-290, 2-29 7, 2-311, 2-315, 2-320, 2-339, 2-341 2-344 2-357 2-360, 2-366, 2-375, 2-377, 2-399, 2- 404, 2-405 2-406 2-408 2-412, 2-422, 2-426, 2-447, 2-449, 2-454, 2-472 2-499 2-504 3--7, 3 -7U 3-77. 3-83, 3-86, 3-89. 3-90, 3-91. 3-100 3-120 3-132 3-135, 3-14

1, 3-144, 3-153 3-163, 3-165 3-171 3-173 3-196 3-215 3-22 3, 3-228, 3-237 3-242, 3-243 3-245 3-263 3-270 3-289 3-29 8, 3-301, 3-306 3-319, 3-323 3-338 3-344 3-347 3-362 3-40 2, 3-410, 3 -423 3-437, 3-451 3-453 3-456 3-464 3-466 3-470, 3-488, 3-510 3-562 and 3-573 Compound

Compound numbers 1-410, 1-417, 1-427, -447, 1-489, 1-510, 1-530, 1-550, 1-568, 1-572, 1-587, 1-593,- 616, 1-617, 1-640, 1-669, 1-675, 1-677, 1-679, 1-687, 1-696, -711, 1-712, 1-786, 1-802, 1 -811, 1-815, 1-816, 1-820, 1-843, -847, 1-853, 1-931, 1-945, 1-1019

, 1-1035, 1-1077, 1-1097, 1-1160, -1177, 1-1180, 1 -1202, 1 -1267, 1-1461

, 15 1512, 1-1522. 1 -1645, 17 1739, • 1754, 2-15, 2-18, 2-2, 2-24, 2-242, 2-247, 2-255, 2-320, 2-344, 2-399, 2-404, 2-405, 2-406, 2-408, 2-412, 2-422, 2-426, 2-449, 2-504, 3-7, 3- 71, 3-77, 3-83, 3-89, 3-91, 3-141, 3-153, 3-223, 3-237, 3-242, 3-245, 3-298, 3-338, 3-344, 3-347, 3-402, 3-410, 3-423, 3-464, 3-488, 3-510, 3-562 and 3-573.

 Particularly preferred compounds include

Compound No. 4Π: N- (1 -phenylethyl) -1- {phenyl [6-hydroxy-1 4 -methoxy-2-(1 H-tetrazol-5 -yl) phenyl] methyl} amine ,

Compound No. 1-447: N- (1-ethylpentyl)-(phenyl- [3- (1H— Tetrazole-5- (yl) phenyl] methyl} amine

Compound No. 1-489: N— (1 phenylethyl) 1 {phenyl [3— (1H—tetrazoyl5—yl) phenyl] methyl} amine,

Compound No. 1-530: N- (1-ethylpentyl) -1- (phenyl (4- (1H-tetrazol-5-yl) phenyl) methyl} amine,

Compound No. 572: N- (1 -phenylethyl) -1- {phenyl [4- (1 H-tetrazol-5-yl) phenyl] methyl} amine;

Compound No. 1 -587: N— (1-phenylethyl) 1-{(4-methoxyphenyl)-[4- (1H-tetrazol-5-yl) phenyl] methyl} amine, Compound No. 640: N- (1-phenylethyl) -1- [phenyl (3-methylsulfonylcarbamoylphenyl) methyl] amine,

Compound No. 679: N— (1-ethylpentyl) -1- [phenyl (3-N-tosylcarbamoylphenyl) methyl] amine,

Compound No. 687: N-cyclohexyl [phenyl (3-N-tosylcarbamoylphenyl) methyl] amine,

Compound No. 696: N- (1-phenylenyl)-[phenyl- (3-N-tosylcarbamoylphenyl) methyl] amine,

Compound number 802: N-(1 phenylethyl) 1 {phenyl [3 — (2-(

2 —methylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} amine,

Compound number 815: N-(1 phenylethyl)-{phenyl [3 — (2-(

3—Methylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} Compound No. 820: N- (1 phenylethyl) — (phenyl-2-3- [2— (

4 monomethylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} amine, Compound number 1-847: N- (1-phenylethyl) -1- {phenyl [4 -— (2- (2-methylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} amine,

Compound No. 853: N- (1-phenylenyl) -1- {phenyl- [4- (2- (4-methylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} amine,

Compound No. 1Π7: Ν— (Indone-1-1-yl) -1- [phenyl- (2-ethylsulfonylphenyl) methyl] amine,

Compound No. 1180: Ν— (2-phenylenyl)-[phenyl (2-ethylphenyl) methyl] amine,

Compound No. 1512: -tert e-butyl- [phenyl- (2-phenylsulfonylphenyl) methyl] amine,

Compound No. Π39: N—-{2_ [1—phenyl-2— (N—1—phenylethyl) amino] methyl} phenyl N'—tosylperia,

Compound No. 1754: N— {2- [1- (4-Methoxyphenyl) —1— (N—1-phenylethyl) amino] methyl} phenyl—N′—tosyldiarea, Compound No. 2-15: N— (1 —ethylpentyl) 1 {2 —indenyl— [3— (1 H—tetorazol-5-yl) phenyl] methyl} amine

Compound No. 2-24: N— (1-phenylenyl) -1- {2-indenyl— [4- (1H—tetrazol-5-yl) phenyl] methyl} amine;

Compound No. 2-242: N— (1—ethylpentyl) — {1—naphthyl [3— (1H—tetrazol-5—yl) phenyl] methyl} amine;

Compound No. 2-247: N- (1-phenylethyl) -1- {1-naphthyl— [3- (1H-tetrazolu-5-yl) phenyl] methyl} amine;

Compound No. 2-255: N- (1-phenylethyl)-{1-naphthyl- [4- (1H-tetrazol-5-yl) phenyl] methyl} amine, Compound No. 3-223: N- [1- (4-bromophenyl) ethyl]-{(1,1-dioxothiophene-2-yl) -1- [3— (1H-tetrazole-5-yl) Phenyl] methyl} amine,

Compound No. 3-237: N- (1-ethylpentyl) -1- {2_thiazolyl— [3— (1H—tetorazol-5—yl) phenyl] methyl} amine;

Compound No. 3-242: N— (1 phenylethyl) 1 {3—thiazolyl [3- (1H—tetrazol-5—yl) phenyl] methyl} amine;

Compound No. 3-298: N- (1-phenylenyl) -1- {2-indolyl— [3- (1H-tetrazol-5-yl) phenyl] methyl} amine;

Compound No. 3-338: N- [1— (4-bromophenyl) ethyl] — {2_indolyl-1- [3— (1H-tetrazol-5-yl) phenyl] methyl} amine; Compound No. 3-423: N-cyclohexyl _ [(1,1-dioxybenzothiophen-3-yl)-(2-methylsulfonylphenyl) methyl] amine, Compound No. 3-464: N-[1-(4- Bromophenyl) ethyl] -1-{(1,1-dioxybenzothiophene-2-yl) -1- [3_ (1H-tetrazol-5-yl) phenyl] methyl} amine;

Compound No. 3-510: N— [1— (4-bromophenyl) ethyl] 1 {2—benzothiazolyl [3— (1H—tetrazol-5-yl) phenyl] methyl} amine and

Compound No. 3-562: N- (1 phenylethyl) 1 {3—benzoxazolyl—

[3— (1H-tetrazol-5-yl) phenyl] methyl} amine

Can be mentioned. Further, in the above table, compounds suitable as benzylamines having the general formula (II) which are contained as an active ingredient of the bile acid transporter inhibitor of the present invention include:

Compound number 1, 1-3, 1-4, 1-5, 1-6, 87, 1-125, 1-176, 1-236, 1- 266, 1-366, 1-367, 1-410, 1-417, 1-418 1-427, 1-442, 1-444, 447, 1-461, 1-467, 1-489, 1-503 , 1-510 1-518, 1-525, 1-527, 529, 1-530, 1-550, 1-568, 1-572, 1-575 1-586, 1-587, 1-593, 616 , 1-617, 1-633, 1-637, 1-638, 1-639 1-640, 1-641, 1-643, 654, 1-655, 1-665, 1-667, 1-669, 1-670 1-675, 1-677, 1-679, 687, 1-696, 1-705, 1-707, 1-709, 1-710 1-711, 1-712, 1-767, 768, 1-769, 1-771, 1-775, 1-782, 1-784 1-786, 1-802, 1-811, 815, 1-816, 1-820, 1-843, 1-847, 1 -853 1-873, 1-875, 1-876, 878, 1-879, 1-881, 1-884, 1-910, 1-927 1-931, 1-945, 1-946, 952, 1 -967, 1-968, 1-969, 1-972, 1-975 1-994, 1-1014, 1-1019, 1028, 1-1035, 1-1051, 1-1053, 1-1055, -1067 , -1068, 1-1077. 1-1097, 1110, 1-1133, 1-1135, 1-1138, 1-1150, -1153, -1160, G 1172, 1-1174 1177, 1-1180, 1-1193, 1-1195. 1-1196, -1202, -1219, U1220, U1222, 1237, 1-1264, 1-1267, 1-1270, 1-1285, -1305 , -1318, 1346, 1-1387, 1392, 1-1400, 1-1409, 1-1410, 1-141 Κ -1412, -1456, 1-1458. 1-1461, 1477, 1-1512, 1 -1522, 1-1609, U 1645, --1649, -1697, 1-1737, 1-1754

1769, 1-1775. 1-1780, 1-1782, 2-15, 28, 2-21, 2-24, 2-28, 2 -31, 2-32, 2-94, 2-98, 2 -119, 2-122, 2-131, 2 [36, 2-140, 2- -144, 2 -147, 2-15

2, 2-214, 2-220, 2-229, 2-242 • 247, 2-248, 2-255 260 2-27

276 290, 2-297, 2-311 315, 2-320, 2-339 341 2-34 357360, 2366, 2-375-377, 2-399, 2-404 405 2-40 408 ■ 412, 2-422, 2-426 -447, 2-449, 2- ■ 454 472 2-49 504 ■ 7, 3-71. 3-77, 3-83, 3--86, 3-89 , 3-90, 3-91, 3-100 3-12 132 135, 3-141, 3-144, 3--153, 3-163, 3- • 165, 3-171 3-17 196 • 201, 3-215, 3-223, 3--228, 3-237, 3- • 242, 3-243 3-24 250 ■ 263, 3-270, 3-289, 3--298, 3-301, 3 .-306, 3 • 319 3-32 3 3-338 3-344 3-347 3-352 3-362 3-374 3-402 3-410 3-42 3 3-437 3-451 3-453 3-456 3-464 3-466 3-470 3-488 3-51 0 The compounds of 3-562 and 3-573 can be mentioned,

 As further preferred compounds,

Compound number 1-410 1-417 1 -427 -447 1-489 1-510 550 568 1-572 1-587 1 -593 69 675 677 1-679 1-687 1-696 -71

811 815 1-816 1-820 1-843 -847, 1-853 1-881 884 931 1-945 1-1019 1-1035-1077 1 -1097, 1 -1133, 1 -1135 1138

-1150 1160 1 -1177, 1 -1180-1202 1 -1267 1-1411 1-1412 1461-1512 1-1522, 1 -1645, 1-1739,-1754 2-15 2-18. 2-2K 2- 24. 2-242

2-247 2-255 2-320 2-344 2-399 2-404 2-405 2-406 2-408 2-412 2-422 2-426 2-449 2-504 3-7 3-71.3 -77, 3-83 3-89

3-91 3-141 3-153 3-223 3-237 3-242 3-245 3-298 3-338 3_ 344 3-347 3-402 3-410 3-423 3-464 3-488 3-510 3-562 and 3-573 compounds,

 Particularly preferred compounds include

Compound No. 1-417: N- (1-phenylenyl) {phenyl [6-hydroxy-4-methoxy-2- (1-H-tetrazole-5-yl) phenyl] methyl} amine

Compound No. 447: N- (1-ethylpentyl) -1- {phenyl [3- (1H-tetrazol-5-yl) phenyl] methyl} amine;

Compound No. 1-489: N- (1-phenylethyl)-{phenyl-2 [3- (1H-tetrazol-5-yl) phenyl] methyl} amine;

Compound No. 530: N- (1-ethylpentyl) -1- {phenyl [4- (1H-tetrazol-5-yl) phenyl] methyl} amine; Compound No. 572: N- (1-phenylenyl) -1- {phenyl- [4- (1H-tetrazol-5-yl) phenyl] methyl} amine;

Compound No. 587: N- (1-phenylenyl)-{(4-methoxyphenyl) -1- [41- (1H-tetrazol-5-yl) phenyl] methyl} amine, Compound No. 640: N- ( 1-phenylethyl)-[phenyl- (3-methylsulfonylcarbamoylphenyl) methyl] amine,

Compound No. 679: N- (1-ethylpentyl) -1- [phenyl (3-N-tosylcarbamoylphenyl) methyl] amine,

Compound No. 687: N-cyclohexyl [3- (N-tosylcarbamoylphenyl) methyl] amine,

Compound No. 696: N- (1-phenylphenyl)-[phenyl (3-N-tosylcarbamoylphenyl) methyl] amine,

Compound No. 802: N— (1 phenylethyl) 1 {phenyl [3— (2 — (

2—Methylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} a Compound No. 815: N— (1—phenylethyl) 1 {phenyl-2 [3— (2— (

3 —methylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} amine,

Compound number 820: N-(1 phenylethyl) 1 {phenyl [3 — (2-(

4 monomethylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} amine,

Compound No. 847: N- (1-phenylenyl)-{phenyl [4-1 (2- (2-methylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} amine,

Compound No. 853: N- (1-Phenylethyl) -1- (phenyl- [4- (2- (4-methylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} methyl ,

Compound No. 1138: N— (1-ethylpentyl) -1- [phenyl (2-ethylsulfonylphenyl) methyl] amine,

Compound No. 1177: N— (Indan-1-yl) -1- [2- (2-ethyldiphenyl) methyl] amine,

Compound No. 1180: N— (2-phenylethyl)-[phenyl— (2-ethylsulfonylphenyl) methyl] amine,

Compound No. 1512: N—tert—butyl— [phenyl (2-phenylphenylsulfonyl) methyl] amine,

Compound number 1739: N— {2-[1 phenyl— 1 — (N— 1 —phenylethyl

) Amino] Methyl} Hueneru N '— Tosylpere,

Compound No. 1754: N— {2- [1- (4-methoxyphenyl) 1-111 (N-1 phenylethyl) amino] methyl} phenyl N'—tosylperia

Compound No. 2-15: N— (1 —ethylpentyl) 1 {2 —indenyl- [3-(1

H-tetrazole-5-yl) phenyl] methyl} amine,

Compound No. 2-24: N— (1 phenylethyl) 1 {2 —indenyl- [4 1 (1

H-tetrazo-lu-5-yl) phenyl] methyl} amine,

Compound No. 2-242: N- (1-ethylpentyl) 1 {1 1 naphthyl [3-(1

H-tetrazole-5-yl) phenyl] methyl} amine,

Compound No. 2-247: N- (1 phenylethyl) 1 {1 1 naphthyl [3-(1

H-tetrazole-5-yl) phenyl] methyl} amine,

Compound No. 2-255: N- (1—phenylethyl) 1 {1 1 naphthyl [4-(1

H-tetrazole-5-yl) phenyl] methyl} amine,

Compound number 3-223: N-[1 — (4-bromophenyl) ethyl] 1 {(1, 1 — dioxothiophene 1 2 —yl) 1 [3 — (1 H-tetrazole-5-yl) Phenyl] methyl} amine, Compound No. 3-237: N- (1-ethylpentyl) -1- {2-thiazolyl [3— (

1H-tetrazol-5-yl) phenyl] methyl} amine

Compound number 3-242: N-(1-phenylethyl)-{3 -thiazolyl [3-(

1 H-tetrazole-5-yl) phenyl] methyl} amine,

Compound No. 3-298: N— (1—phenylethyl) — {2—indolyl— [3— (

1 H-tetrazole-5-yl) phenyl] methyl} amine,

Compound No. 3-338: N- [1- (4-bromophenyl) ethyl]-{2-indolyl-1- [3- (1H-tetrazol-5-yl) phenyl] methyl} amine; Compound No. 3-423: N-cyclohexyl [(1,1-dioxybenzothiophene-3-yl)-(2-methylsulfonylphenyl) methyl] amine, Compound No. 3-464: N- [1-(4 -Bromophenyl) ethyl]-{(1,1-dioxybenzothiophene-2-yl)-[3- (1H-tetrazole-5-yl) phenyl} methyl} -amine,

Compound No. 3-510: N- [1- (4-bromophenyl) ethyl] -1- {2-benzothiazolyl- [3- (1H-tetrazol-5-yl) phenyl] methyl} amine and-,

Compound No. 3-562: N- (1-phenylethyl) -1- {3-benzoxazolyl-

[3- (1H-tetrazole-5-yl) phenyl] methyl} amine

Can be mentioned.

The compound having the general formula (II) of the present invention can be easily produced according to the following method. Further, the compound having the general formula (I) of the present invention can also be produced by the same method as the method for producing the compound having the general formula (II). Method A

 (Π)

B method

(VI) (lid)

(VII) (lie) C method

In the above process, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ have the same meanings as described above, and R ^2a , R ^3a and R ^4e are The amino group contained in each group is an amino group which may be protected and each has the same meaning as R ² , R ³ and R ^4, and R ⁹ is a d-C alkyl group or a substituent group / 3 Represents a C _e —C ₁₀ aryl group which may be substituted by 1 to 3 groups selected from: R ^{1 C>} represents a d—C _e alkyl group; and Ar represents a substituent selected from the substituent group α. _{Β or} C i may be substituted with one or two groups. Represents an aryl group, and T z represents a tetrazolyl group.

 The protecting group for the amino group is not particularly limited as long as it is commonly used in the field of synthetic organic chemistry. For example, t-butoxycarbonyl group: benzyl, methylbenzyl

, Main Bok Kishibenjiru, Furuorobenjiru, C _t one C § alkyl such as black port base Njiru, d - Ce alkoxy, or halogen-substituted base may Nji Le group: benzyl O alkoxycarbonyl, methylbenzyl O carboxymethyl Cal Poni Le, C ₁ -C alkyl, such as methoxy benzyloxycarbonyl, fluorobenzyloxycarbonyl, and cyclobenzyloxycarbonyl, -C alkoxy or a benzyloxycarbonyl group optionally substituted with halogen Or a halogenoacetyl group such as acetyl, bromoacetyl, or iodoacetyl; preferably, t-butoxycarbonyl group, p-methoxybenzyl group, p-methoxybenzyloxycarbonyl. Group, chloroacetyl group, promoacetyl group or iodoacetyl , And the more preferably a t one butoxide deer Lupo alkenyl group or p _ main butoxy benzyl O alkoxycarbonyl group, particularly preferably a t one Butokishikaru Poniru group.

 Method A is a method for producing compound (II).

Step A1 is a step of producing a compound having the general formula (V), and in an inert solvent, a compound having the general formula (III) and a compound having the general formula (IV) or an acid addition salt thereof (for example, Reacting mineral salts such as hydrochloride, nitrate, sulfate) For example, the heat condensation is performed by using an organic sulfonic acid such as P-toluenesulfonic acid as a catalyst, or the condensation is performed using a Lewis acid such as titanium tetrachloride.

 The inert solvent used in the above reaction is not particularly limited as long as it does not participate in the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene, toluene, and xylene: dichloromethane, 1, 2-Halogenated hydrocarbons such as dichloroethane and carbon tetrachloride: alcohols such as methanol and ethanol; ethers such as ether, tetrahydrofuran and dioxane; ketones such as acetone: N, N-dimethyl Amides such as formamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, hexamethylphosphoramide

Sulfoxides such as dimethylsulfoxide: When heat condensation is carried out using an organic sulfonic acid as a catalyst, hydrocarbons (particularly preferably xylene) are preferred. When the condensation is carried out using a Lewis acid, halogenated hydrocarbons (particularly preferably dichloromethane) are preferred.

 Further, in the above reaction, when compound (IV) is an acid addition salt, the reaction can be carried out using a base. Such bases include, for example, organic amines such as triethylamine, N-methylmorpholine, pyridine and 4-dimethylaminopyridine: alkali metal bicarbonates such as sodium bicarbonate and potassium bicarbonate

: Alkali metal carbonates such as sodium carbonate and potassium carbonate: and preferably organic amines (particularly preferably triethylamine).

 The reaction temperature varies depending on the type of the starting compound, the base, the solvent and the like, but is usually from 120 to 200. When the condensation is carried out using a Lewis acid, it is preferably from 10 to 4

In the case of performing heat condensation using an organic sulfonic acid as a catalyst, the ratio is preferably from 50 to 150.

The reaction time varies depending on the starting compound, the base, the solvent, the reaction temperature and the like, but is usually 15 minutes to 48 hours, preferably 1 hour to 30 hours. After completion of the reaction, the target compound (V) of this reaction is collected from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and if insolubles are present, they are removed by filtration, and then an immiscible organic solvent such as water and ethyl acetate is added to separate the organic layer containing the target compound. It is obtained by washing with water or the like, drying with anhydrous magnesium sulfate or the like, and distilling off the solvent. If necessary, the desired compound obtained can be combined with a conventional method, such as recrystallization, reprecipitation, etc., which is commonly used for the separation and purification of organic compounds, and then chromatographed with an appropriate eluent. It can be separated and purified by elution.

 The step A2 is a step for producing the compound (II), which is carried out by reducing the compound (V) in an inert solvent and then removing the protecting group for the amino group of the obtained compound.

 The inert solvent used in the above reaction is not particularly limited as long as it does not participate in the reaction, and is, for example, the same as that used in the step A1, preferably alcohols or ethers. (Particularly preferably, methanol or tetrahydrofuran).

 The reducing agent used in the above reaction includes, for example, alkali metal borohydrides such as sodium borohydride, lithium borohydride, sodium cyanoborohydride: diisobutylaluminum hydride, lithium aluminum hydride, Aluminum hydride compounds such as lithium triethoxyaluminum hydride: and preferably alkali metal borohydrides (particularly preferably sodium cyanoborohydride).

The reaction temperature varies depending on the starting compound, the reducing agent used, the type of the solvent, and the like, but is usually from 120 to 150, and preferably from 10 to 80. The reaction time varies depending on the starting compound, the reducing agent used, the solvent, the reaction temperature and the like, but is usually from 15 minutes to 24 hours, preferably from 30 minutes to 16 hours. After the above reaction, the protecting group for the amino group is usually used in the field of organic synthetic chemistry. Removed by the method.

 When the protecting group is a t-butoxycarbonyl group, a methoxybenzyl group or a methoxybenzyloxycarbonyl group, the corresponding compound is converted into an inert solvent (for example, ether such as getyl ether, tetrahydrofuran, dioxane). , Halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, aromatic hydrocarbons such as benzene, toluene and xylene, and preferably ethers, in an acid (eg, hydrochloric acid, A mineral acid such as sulfuric acid or nitric acid, an organic acid such as acetic acid, trifluoroacetic acid, methanesulfonic acid or p-toluenesulfonic acid, preferably hydrochloric acid) and 0 to 50 (preferably room temperature). (In the vicinity) for 30 minutes to 5 hours (preferably 1 hour to 2 hours) to remove the protecting group.

 When the protecting group is a halogenoacetyl group, the corresponding compound is preferably used as an inert solvent (for example, amides such as dimethylformamide and dimethylacetamide, sulfoxides such as dimethylsulfoxide, etc.). Are reacted with thioprea in amides at 0 to 50 (preferably around room temperature) for 30 minutes to 5 hours (preferably 1 hour to 2 hours), The protecting group is removed.

 Further, when the protecting group is a benzyl group which may be substituted or a benzyloxycarbonyl group which may be substituted, the corresponding compound may be converted into an inert solvent (eg, dimethyl ether, tetrahydrofuran). In the presence of a catalytic reduction catalyst (eg, palladium-carbon, platinum oxide, etc.) in ethers such as dioxane, alcohols such as methanol and ethanol, and preferably alcohols. To 3 to 30 atm (preferably around room temperature) for 30 minutes to 10 hours (preferably 1 to 5 hours) to form a protecting group. Removed.

After completion of the reaction, the target compound (II) of this reaction is collected from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and if insolubles are present, they are removed by filtration, and then an immiscible organic solvent such as water and ethyl acetate is added. The organic layer containing the compound is separated, washed with water or the like, dried over anhydrous magnesium sulfate or the like, and then obtained by distilling off the solvent. If necessary, the target compound obtained may be combined with a conventional method, for example, recrystallization, reprecipitation, etc., which is commonly used for the separation and purification of organic compounds. It can be separated and purified by elution.

Method B, in the compound (II), a compound wherein R ¹ is a tetrazolyl group (II d) and C R ¹ is substituted with a tetrazolyl group ₆ - preparation C ₁ compound is ₀ Ariru based on (II e) How to

 Step B1 is a step for producing a compound having the general formula (IId), in which a compound having the general formula (VI) is reacted with an azide compound in an inert solvent, and then the amino compound of the obtained compound is reacted. It is carried out by removing the protecting group of the group.

 The inert solvent used in the above reaction is not particularly limited as long as it does not participate in the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene, toluene and xylene: dichloromethane, 1, 2 — Halogenated hydrocarbons such as dichloroethane and carbon tetrachloride; ethers such as getyl ether, tetrahydrofuran, and dioxane: nitriles such as acetonitrile: N, N—dimethylformamide, N, N Amides, such as —dimethylacetamide, N—methyl-2-pyrrolidone, hexamethylphosphoramide: sulfoxides, such as dimethylsulfoxide: and preferably hydrocarbons (particularly preferably toluene) It is.

The azide compounds used in the above reaction include, for example, lithium metal azides such as lithium azide, sodium azide, and potassium azide: alkaline earth metal azides such as magnesium azide and calcium azide: trimethylsilyl azide C-C alkylsilyl azides: tri-C-C _β- alkyltin azides such as trimethyltin azide: and are preferably alkali metal azides (particularly preferably sodium azide).

In the above reaction, the azide compound is used alone, for example, aluminum chloride Palladium, stannic chloride, tri-n-butyltin chloride, Lewis acids such as zinc chloride, titanium chloride, trifluoroborane-getyl ether complex, ammonium chloride, tetramethylammonium chloride It may be used in combination with ammonium salts such as aluminum, sulfonic acids such as methanesulfonic acid and ethanesulfonic acid, alkali metal chlorides such as lithium chloride, and amine salts such as triethylamine hydrochloride, and preferably Lewis. Acid (particularly preferably tri-n-butyltin chloride).

 The reaction temperature varies depending on the starting material compound, the azide compound used, the type of the solvent, and the like, but is usually 20 to 200 (preferably 50 to 150). The reaction time varies depending on the starting compound, the azide compound used, the solvent, the reaction temperature and the like, but is usually 15 minutes to 24 hours (preferably 30 minutes to 16 hours). After the above-mentioned reaction, the removal of the protecting group for the amino group is carried out in the same manner as in the latter stage of the above-mentioned Method A, Step A2.

 After completion of the reaction, the target compound (Id) of this reaction is collected from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and if insolubles are present, they are removed by filtration. Then, an immiscible organic solvent such as water and ethyl acetate is added, and the organic layer containing the target compound is separated. It is obtained by washing with water, etc., drying with anhydrous magnesium sulfate, etc., and distilling off the solvent. If necessary, the target compound obtained is eluted with an appropriate eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for the separation and purification of organic compounds, applying chromatography. Can be separated and purified.

 Step B2 is a step of producing a compound having the general formula (IIe), in which a compound having the general formula (VII) is reacted with an azide compound in an inert solvent, and then the amino compound of the obtained compound is reacted. This step is carried out by removing the protecting group of the group, and this step is carried out in the same manner as the above-mentioned Method B, Step B1.

Method C is a method of compound (II), wherein ^{one to} three R ⁶ -C ¹ -C β alkylsulfonyl groups or a group selected from substituent group / 3 may be substituted with C ₆ —C ₁₀ -C Li Rusuruhoniru group, compound (II f), R ¹ is - C alkylsulfonyl C replaced by ₆ - C _{1 0} § a Li Lumpur group compound (II g) and R ¹ is C! -Step C1, which is a method for producing a compound (IIh) which is a C alkylsulfinyl group, is a step of producing a compound having the general formula (IIf), wherein the compound represented by the general formula (VIII) is prepared in an inert solvent. The reaction is carried out by reacting a compound having the following formula with an oxidizing agent, and then removing the amino-protecting group of the obtained compound.

 The solvent used in the above reaction is not particularly limited as long as it does not participate in the reaction. For example, aromatic hydrocarbons such as hexane, cyclohexane, benzene, toluene and xylene: dichloromethane, 1, 2 —Halogenated hydrocarbons such as dichloroethane and carbon tetrachloride; methanol, ethanol, n—propanol, isopropanol, n—alcohols such as butanol, isobutanol, and isoamyl alcohol: ethers, tetrahydrofuran, dioxane Ethers such as dimethoxetane: halogenated fatty acids such as trifluoroacetic acid: amides such as N, N-dimethylformamide, N, N-dimethylacetamide and hexamethylphosphorotriamide : Sulfoxides such as dimethyl sulfoxide : Dilute acid such as sulfuric acid water: Dilute base such as sodium hydroxide water: Ketones such as acetone and methyl ethyl ketone: Organic bases such as pyridine: Nitriles such as acetonitrile; Water: Preferred are halogenated fatty acids (particularly preferred is trifluoroacetic acid).

The oxidizing agent used in the above reaction is not particularly limited as long as it is used in a normal oxidation reaction. For example, manganese oxides such as potassium permanganate and manganese dioxide: such as ruthenium tetroxide Ruthenium oxides: Selenium compounds such as selenium dioxide: Iron compounds such as iron chloride; Osmium compounds such as osmium tetroxide: Silver compounds such as silver oxide: Mercury compounds such as mercury acetate: Lead oxide, Lead oxide compounds such as lead tetraacetate: potassium chromate, chromate-sulfate complex, chromium Chromic acid compound such as acid-pyridine complex: Inorganic metal oxidizing agent such as cerium compound such as ammonium cerium nitrate (CAN): Halogen molecule such as chlorine molecule, bromine molecule, iodine molecule: periodic acid Periodic acids such as sodium; Oxidizing gases such as ozone; Hydrogen peroxide, nitrites such as nitrous acid: chlorites, chlorites such as sodium chlorite: Inorganic oxidants such as persulfate compounds such as potassium persulfate and sodium persulfate: peroxides such as topyl hydroperoxide; hydrogen peroxide, m-chloroperbenzoic acid (mCPBA), peracetic acid Organic peracids such as: Stable cations such as triphenylmethyl cation: Hypochlorites such as t-butyl hypochlorite: Suboxides such as methyl nitrite Acid esters: organic oxidizing agents such as quinone compounds such as 2,3-dichloro-5,6-dicyano-P-benzoquinone (DDQ); and preferably, peroxides or organic peracids (particularly, Preferably, it is hydrogen peroxide solution or m-chloroperbenzoic acid).

 The reaction temperature varies depending on the starting compound, the oxidizing agent used, the type of the solvent, and the like, but is usually from 120 to 100 (preferably from 110 to 50).

 The reaction time varies depending on the starting compound, the oxidizing agent used, the solvent, the reaction temperature and the like, but is usually 15 minutes to 24 hours (preferably 30 minutes to 16 hours).

 After the above reaction, the protecting group for the amino group is removed in the same manner as in the latter stage of Step A2 of Method A.

After completion of the reaction, the target compound (IIf) of the reaction is collected from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and if insolubles are present, they are removed by filtration. Then, an immiscible organic solvent such as water and ethyl acetate is added, and the organic layer containing the target compound is separated. It is obtained by washing with water, etc., drying with anhydrous magnesium sulfate, etc., and distilling off the solvent. If necessary, the target compound obtained is eluted with an appropriate eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for the separation and purification of organic compounds, applying chromatography. Can be separated and purified. Step C2 is a step for producing a compound having the general formula (IIg), in which a compound having the general formula (IX) is reacted with an oxidizing agent in an inert solvent, and then the amino compound of the obtained compound is reacted. This step is performed by removing the protecting group of the group. This step is performed in the same manner as in the above-mentioned Method C, Step C1.

 Step C3 is a step of producing a compound having the general formula (IIh), in which a compound having the general formula (X) is reacted with an oxidizing agent in an inert solvent. This step is carried out by removing the protecting group of the amino group, and this step is carried out in the same manner as the above-mentioned Method C, Step C1.

 The reaction temperature varies depending on the starting compound, the oxidizing agent used, the type of the solvent, and the like, but is usually from −50 ° C. to 100 ° C. (preferably from 120 ° C. to 10 ° C.). The time varies depending on the starting compound, the oxidizing agent used, the solvent, the reaction temperature and the like, but is usually 15 minutes to 12 hours (preferably 15 minutes to 5 hours).

 The starting compounds (111), (IV), (VI), (VII), (VIII), (IX) and (X) are known or are easily produced according to known methods or methods similar thereto. . [For example, Can. J. Chem., 66, 1405 (1988), J. Chem. Soc., 352 (1949), Chem. Abstr., 62, 11709 (1965), J. Am. Chem. So. 98 , 2928 (1976), J. Org. Chem., 47, 34 (1982), etc.].

The starting compounds (111), (VI), (VII), (VIII), (IX) and (X) can also be produced by the following method.

D method

(XI) (XII) (ΧΠΙ) (IV)

(XIV) (XV)

E method

 (xvm)

F method

(Xlllb) Law

 (XIIIc) (XX) (Ilia)

H method

 (Xllld) (XXI) (nib)

I law

(XXII) (IIIc)

Law

Step K2

L

 Law

 192

 (XVb) (XXVI)

 (VII)

In the above formula, R ^2a , R ^3a , R ^4a , R ^s , R ⁶ and Ar have the same meanings as described above, and R ^2b , R ^3b and R ^4b represent an amino group contained in each group. R ^5d is the same as R ² , R ³ and R ⁴ except that it is a protected amino group, and R ^5d is 2-phenyl, 2-pyrrolyl, 2-thiazolyl, 2-oxazolyl, 2-benzothienyl, 2 - indolyl, shows a 2-base Nzochiazoriru or 2-benzo O hexa benzotriazolyl group, R ¹¹ is, d - C _e represents an alkyl group, R ¹² is Karupokishi group, Xia amino group, an amino group, wherein one SR ^{9 represents} a group having the formula 1 SR ^1D or a carboxyl, cyano or C _{e —}若 し く は₁₀ aryl group substituted by a group having the formula 1 SR ^1Q , and R ¹³ represents a d-C β alkyl group or It may be 1乃optimum three optionally substituted with a group selected from substituent group (5 C ₆ - C ₁₀ Ariru Are shown, R ¹⁴ is lithium, sodium, represents an alkali metal such as potassium, R ¹⁵ is optionally be 1 to 3 substituted with a group selected from Substituent Group 0 C _e - C ₁₀ Ariru group And R ^ie is d — A C alkyl group; R ¹⁷ represents a hydrogen atom or a d-C alkyl group; D represents a halogen atom; and Ar 1 is substituted with 1 to 3 substituents selected from the substituent group α. Indicates a C ₆ _C ₁₀ aryl group.

 Method D is a method for producing a compound (XV) containing the compounds (VI), (VII), (VIII), (IX) and (X).

 Step D1 is a step of producing a compound (XIII), in which a compound having the general formula (XI) is dissolved in an inert solvent (preferably, hexane, cyclohexane, benzene, toluene, xylene). Such hydrocarbons) and a compound having the general formula (XII) at −20 ° C. to 200 (preferably at 0 to 150) for 15 minutes to 24 hours (preferably, (30 minutes to 16 hours).

 The step D2 is a step of producing a compound having the general formula (XIV). The compound (XIII) is reacted with the compound (IV) or an acid addition salt thereof (eg, hydrochloride, nitrate, sulfate) in an inert solvent. This step is carried out in the same manner as in the above-mentioned Method A, Step A1.

 Step D3 is a step of producing a compound having the general formula (XV), which is carried out by reducing compound (XIV) in an inert solvent. This step is the same as in the above-mentioned Method A, Step A2. Done in

The step D4 is a step of preparing the compound (XIII) separately from the step D1, and the compound having the general formula (XVI) is placed in an inert solvent (preferably hexane, cyclohexane). Benzene, toluene, xylene and hydrocarbons, and a base (preferably organic lithiums such as n-butyllithium, t-butyllithium and phenyllithium) in the presence of the general formula (XV II) With the compound having the following formula: for 150 to 50 (preferably —100 to 0) for 15 minutes to 24 hours (preferably 30 minutes to 16 hours) It is performed by The reaction can be carried out in the presence of an organic amine or the like (preferably N, N, N ', N'-tetramethylethylenediamine) to supplement the acid generated during the course of the reaction. Method E is a compound of formula (XIII) in which R ^{5 is} 2-Chenyl, 2-pyrrolyl, 2-thiazolyl, 2-oxazolyl, 2-benzochenyl, 2-indolyl, 2-benzothiazolyl or 2-benzozoazozolyl group. This is a method for producing a compound (XIIIa) which is a compound.

 Step E1 is a step for producing a compound having the general formula (XVIII), in which the compound (XI) is dissolved in an inert solvent (preferably, a solvent such as getyl ether, tetrahydrofuran or dioxane). Monoters or organic amines such as triethylamine, N-methylmorpholine, pyridine, 4-dimethylaminopyridine, 2,4,6-trimethylpyridin), bases (preferably, triethylamine, N-methylmorpholine) Pyridine, 4-dimethylaminopyridine, 2,4,6-organic amines such as trimethyl pyridine) in the presence or absence of 2-hydroxypyridin and from 120 to 200 (preferably). The reaction is carried out at 0 to 150) for 15 minutes to 24 hours (preferably 30 minutes to 16 hours). The step E2 is a step of producing the compound (XIIIa), wherein the compound having the compound (XVII 1) is mixed with a compound having the general formula (XIX) in trifluoroacetic acid by means of 120 to 200 (Preferably around the boiling point of trifluoroacetic acid) for 15 minutes to 24 hours (preferably 30 minutes to 16 hours).

F method is R ⁵ in the compound (XIII) is a method for producing a compound which is a phenyl group (XIII b).

 Step F1 is a step of producing a compound (XII lb), in which a compound having the general formula (XI) is dissolved in an inert solvent (preferably hexane, cyclohexane, benzene, toluene, or xylene). Such as hydrocarbons) and benzene at a temperature of 20 to 200 V (preferably 0 to 150 C) for 15 minutes to 24 hours (preferably 30 minutes to 20 hours). This is done by letting

Compound (XI) is dissolved in an inert solvent (preferably, dichloromethane, 1.2. —Condensation using halogenated hydrocarbons such as dichloroethane, carbon tetrachloride, sulfoxides such as dimethylsulfoxide), and benzene with Lewis acids (preferably aluminum chloride, zinc chloride). The reaction is carried out at 20 to 200 (preferably 50 to 150 X) for 15 minutes to 24 hours (preferably 30 minutes to 16 hours). This is done by:

The G method may be such that, in the compound (III), R ¹ may be substituted with 1 to 3 (C ¹ , -C alkyl) sulfonylcarbamoyl groups or a group selected from substituent group δ (C β 1 C _This is a method for producing a compound (IIIa) which is a sulfonylcarbamoyl group.

 Step G1 is a step of producing a compound having the general formula (Ilia),

(XIIIc) or a reactive derivative thereof in an inert solvent (preferably, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone). Amides such as xamethylphosphoramide, sulfoxides such as dimethyl sulfoxide), bases (preferably, triethylamine, N-methylmorpholine, pyridine, 4-dimethylaminopyridine, 2, 4, 6) An organic amine such as trimethylpyridine) in the presence or absence of

Reacting with the compound having the formula (XX) for 15 minutes to 24 hours (preferably 30 minutes to 16 hours) with 1 2 O: to 150 (preferably 0 to 50) It is done by doing.

Method H is a compound (III) in which 1 to 3 groups selected from the group consisting of R ¹ substituents 3 may be substituted (C ₆ -C ₁₀ aryl), a compound which is a sulfonylcarbamoylamino group (IIIb).

The HI step is a step of producing the compound (IIIb), in which a compound having the general formula (XIIId) is dissolved in an inert solvent (preferably, hexane, cyclohexane, benzene, toluene, or xylene). A compound having the general formula (XXI): 0 to 150 (preferably at 0 ° C to 50) for 15 minutes to 24 hours The reaction is carried out for a period of time (preferably 30 minutes to 16 hours).

Method I is a compound (III) in which R ¹ is a C ₆ —C ₁₀ aryl group in which 1 to 3 substituents are substituted with a group selected from the substituent group α, and R ² , R ³ and R ⁴ are hydrogen. This is a method for producing a compound (IIIc) which is an atom.

 Step I1 is a step of producing a compound (IIIc), in which a compound having the general formula (XIIIe) is dissolved in an inert solvent (preferably, hexane, cyclohexane, benzene, toluene, xylene). Bases (preferably lithium carbonate, sodium carbonate, and carbonate) under a transition metal catalyst such as hydrocarbons such as methanol, alcohols such as methanol and ethanol, water or a mixed solvent of the above solvents, and palladium hydroxide. A compound having the general formula (XXII) in the presence or absence of an alkali metal carbonate such as potassium) under a nitrogen pressure, from 120 to 200 (preferably from 0 to 150) For 15 minutes to 48 hours (preferably, 30 minutes to 24 hours).

 This reaction can be carried out using a catalyst such as tetra-n-butylammonium.

Method J, in the compounds (III), R ¹ is a mono - in - (C alkyl d) aminosulfonyl group der Ru compound (III e) a method for producing a - (C _t C alkyl) aminosulfonyl group or a di is there.

 Step J1 is a step for producing a compound having the general formula (XXIII), and a compound having the general formula (IIId) is dissolved in an inert solvent (preferably dichloromethane, 1,2-dichloroethane, A halogenating agent such as halogenated hydrocarbons such as carbon chloride), thionyl chloride, sulfuryl chloride, phosphorus oxychloride, phosphorus pentachloride, phosgene, and chlorosulfonic acid; (Preferably 0 to 150) for 15 minutes to 24 hours (preferably 30 minutes to 16 hours).

Step J2 is a step for producing a compound (IIIe), which is a step of producing a compound (XXIII). In an inert solvent (preferably, hydrocarbons such as hexane, cyclohexane, benzene, toluene, and xylene; halogen hydrocarbons such as dichloromethane, 1,2-dichloroethane, and carbon tetrachloride; Ethers such as tyl ether, tetrahydrofuran and dioxane) and bases (preferably organic amines such as triethylamine, N-methylmorpholine, pyridine, 4-dimethylaminopyridine, 2, 4, 6-trimethylpyridine). In the presence or absence of the compound represented by the general formula (XXIV) or an acid addition salt thereof (preferably a hydrochloride), for 15 minutes at —20 to 150 (preferably 0 to 100) The reaction is carried out for up to 24 hours (preferably 30 minutes to 16 hours).

 Method K is a method for producing compound (VI) separately from method D.

 The K1 step is a step of producing a compound having the general formula (XXV), in an inert solvent, a compound having the general formula (XV a) or an acid addition salt thereof (for example, hydrochloride, nitrate, sulfate) The reaction is carried out by reacting a mineral salt such as) or a reactive derivative thereof (acid halides, mixed acid anhydrides, active esters) with aqueous ammonia, for example, acid halide method, mixed acid anhydride. It is carried out by the method, active ester method or condensation method.

 In the acid halide method, the compound (XV a) is reacted with a halogenating agent (eg, thionyl chloride, oxalic acid chloride, phosphorus pentachloride, etc.) to produce acid halides, and the acid halides and ammonia It is achieved by reacting water in an inert solvent in the presence or absence (preferably in the presence) of a base.

The inert solvent used in the above reaction is not particularly limited as long as it does not participate in the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene, toluene, and xylene: dichloromethane, 1, Halogenated hydrocarbons such as 2-dichloroethane and carbon tetrachloride: ethers such as getyl ether, tetrahydrofuran, and dioxane: nitriles such as acetonitrile: N, N—dimethylformamide, N, N N—dimethylacetamide, N—methyl-2-pyrrolidone Amides such as hexamethylphosphoramide; sulfoxides such as dimethylsulfoxide: preferably ethers, nitriles, amides or sulfoxides (particularly preferably Is N, N-dimethylformamide). Bases used in the above reaction include, for example, organic amines such as triethylamine, N-methylmorpholine, pyridine, and 4-dimethylaminopyridin: alkali metal hydrogencarbonates such as sodium hydrogencarbonate and potassium hydrogencarbonate. Alkali metal carbonates such as sodium carbonate and potassium carbonate; and organic amines (particularly preferably triethylamine).

 The reaction temperature varies depending on the type of the starting compound, the reagent, the solvent, and the like. 20 ° C. to 150 ° C .; preferably, the reaction between the halogenating agent and the compound (XV a) or an acid addition salt thereof is 10 ° to 50 °; Is from 0 to 100.

The reaction time varies depending on the starting compound, the reagent, the solvent, the reaction temperature and the like, but is usually 15 minutes to 24 hours, preferably 30 minutes to 16 hours for both reactions. In the mixed acid anhydride method, the compound (XV a) is reacted with d-Cβ-alkyl halogenocarbonate, d-Cβ-alkylcyanophosphoric acid or di-C ₆ —C: ο-arylphosphoryl azide, This is performed by producing mixed acid anhydrides and reacting the mixed acid anhydrides with aqueous ammonia.

The reaction for preparing the mixed acid anhydride compound is chlorocarbonate Echiru, halogeno carbonate such as chloroformate isobutyl C: - C beta alkyl dimethyl cyano-phosphate, di-like Jechirushi Ano-phosphate C - C _beta alkyl row by reacting C i o § reel azide with the compound (XV a) - or Jifue two sulfo Suhoriruajido, di (.rho. two Torofueniru) phosphoryl azide, di C ₆ such as Jinafuchiruhosu Horiruaji de: cyano-phosphate It is preferably carried out in an inert solvent in the presence of a base. The base and the inert solvent used in the above reaction are the same as those used in the above-mentioned acid halide method.

 The reaction temperature varies depending on the type of the starting compound, the reagent, the solvent and the like, but is usually from 120 to 50 ° C, and preferably from 0 to 30 ° C.

 The reaction time varies depending on the starting compound, reagent, solvent, reaction temperature and the like, but is usually 15 minutes to 24 hours, and preferably 30 minutes to 16 hours.

 The reaction between the mixed acid anhydrides and aqueous ammonia is carried out in an inert solvent in the presence or absence (preferably in the presence) of a base. The base and the inert solvent used are as follows: It is the same as that used in the above-mentioned acid halide method.

 The reaction temperature varies depending on the starting compound, the base used, the type of the solvent and the like, but is usually from 20 to 100 ° C, and preferably from −10 to 50 ° C.

The reaction time varies depending on the starting compound, the base used, the solvent, the reaction temperature and the like, but is usually 15 minutes to 24 hours, and preferably 30 minutes to 16 hours. Further, in this method, di - C ₆ alkyl cyano-phosphate or di - when using C ₆ one _{1 0} § reel azide in the presence of a base, compound (XV a) and aqueous ammonia direct reaction It can also be done.

 In the active ester method, the compound (XV a) is converted into an active esterifying agent (for example, N-hydroxysuccinimide, in the presence of a condensing agent (for example, dicyclohexyl carbodiimide, carbonyldiimidazole, etc.) N-hydroxy compounds such as N-hydroxybenzotriazole) are reacted to produce active esters, and the active esters are reacted with aqueous ammonia.

 The reaction for producing active esters is preferably performed in an inert solvent, and the inert solvent used is the same as that used in the above-mentioned acid halide method.

The reaction temperature varies depending on the type of the starting compound, the reagent, the solvent, and the like.In the case of the active esterification reaction, it is usually from 120 to 50, preferably from 110 to 30. In the reaction of And preferably −10 to 30.

 The reaction time varies depending on the starting compound, reagent, solvent, reaction temperature and the like, but is usually 15 minutes to 24 hours (preferably 30 minutes to 16 hours) for both reactions.

 The condensation method is carried out in the presence of a compound (XV) in the presence of a condensing agent (for example, dicyclohexyl carbodiimide, carbonyldiimidazole, 11- (N, N-dimethylaminopropyl) -13-ethylcarbodiimide hydrochloride, etc.). a) is directly reacted with aqueous ammonia. This reaction is carried out in the same manner as the above-mentioned reaction for producing active esters.

 The K2 step is a step of producing a compound having the compound (VI), and is carried out by reacting the compound (XXV) with a dehydrating agent in an inert solvent.

 The inert solvent used in the above reaction is not particularly limited as long as it does not participate in the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene, toluene and xylene: dichloromethane, 1, 2 — Halogenated hydrocarbons such as dichloroethane and carbon tetrachloride; ethers such as getyl ether, tetrahydrofuran, and dioxane: nitriles such as acetonitrile: N, N-dimethylformamide, N And amides such as N-dimethylacetamide, N-methyl-2-pyrrolidone and hexamethylphosphoramide: sulfoxides such as dimethylsulfoxide; Hydrogens (particularly preferably dichloromethane).

 The dehydrating agent used in the above reaction is, for example, a phosphorus halide compound such as phosphorus pentachloride, phosphorus oxychloride, or phosphorus oxybromide: a thionyl halide compound such as thionyl chloride or thionyl bromide: Trifluoroacetic anhydride, methanesulfonyl chloride, para-toluenesulfonyl chloride, trifluoromethanesulfonic anhydride: preferably a halogenated phosphorus compound (particularly preferably phosphorus oxychloride).

The reaction temperature varies depending on the starting compound, the dehydrating agent used, the type of solvent, and the like, but is usually from −20 to 100 (preferably 1 lot) to 50. The reaction time is usually 15 minutes to 24 hours (preferably 30 minutes to 16 hours) depending on the starting compound, the dehydrating agent used, the solvent, the reaction temperature and the like.

 Method L is a method for producing compound (V I I) separately from method D.

 Step L1 is a step of producing a compound having the general formula (XXVI), and in an inert solvent, a compound having the general formula (XVb) or an acid addition salt thereof (for example, hydrochloric acid, nitrate, sulfuric acid) This step is carried out by reacting a mineral salt such as a salt) or a reactive derivative thereof (acid halides, mixed acid anhydrides, active esters) with aqueous ammonia. The same is done.

 The L2 step is a step of producing a compound having the compound (VII), which is carried out by reacting the compound (XXVI) with a dehydrating agent in an inert solvent. It is performed in the same manner as the process.

 After completion of the reaction, the target compound of each reaction is collected from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and if insolubles are present, they are removed by filtration. Then, an immiscible organic solvent such as water and ethyl acetate is added, and the organic layer containing the target compound is separated. It is obtained by washing with water or the like, drying with anhydrous magnesium sulfate or the like, and distilling off the solvent. If necessary, the target compound obtained may be appropriately combined with a conventional method, for example, recrystallization, reprecipitation, etc., ordinarily used for the separation and purification of organic compounds. Separation and purification can be performed by eluting with.

 Are the starting compounds (XI), (XI1), (XVI), (XVI1), (XIX), (XX), (XXI), (XXII) and (XXIV) known? It is easily manufactured by known methods. [For example, Acta. Chim. Acad. Humg., 34, 75-76 (1962), Chera. Ber., 28, 1625 (1895), Chera. Abstr., 71, 123951 j (1969) and the like].

 (The invention's effect)

The compound (I) or (II) of the present invention or a pharmaceutically acceptable salt thereof is excellent. It has an inhibitory effect on ileal bile acid transport and is useful as a therapeutic or preventive agent for hyperlipidemia and arteriosclerosis.

[Industrial applicability]

 When the compound (I) or (II) of the present invention or a pharmacologically acceptable salt thereof is used as an ileal bile acid transporter inhibitor or a therapeutic or prophylactic agent for hyperlipidemia or arteriosclerosis, As such or mixed with an appropriate pharmacologically acceptable excipient or diluent, and administered orally in tablets, capsules, granules, powders, syrups, etc., or parenterally by injection, etc. Can be.

These preparations may contain excipients (eg, lactose, sucrose, glucose, saccharide derivatives such as mannitol, sorbitol: corn starch, potato starch, starch derivatives such as α-starch, dextrin; Gum arabic: Dextran: Organic excipients such as pullulan: and silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, calcium silicate, magnesium aluminate silicate: hydrogen hydrogen phosphate Phosphates such as calcium: carbonates such as calcium carbonate: inorganic excipients such as sulfates such as calcium sulfate, etc.), lubricants (eg, stearate, stearate) Metal stearate such as calcium stearate and magnesium stearate: tal Colloidal force: waxes such as gum and gum: boric acid: adipic acid: sulfates such as sodium sulfate: glycol; fumaric acid: sodium benzoate: DL leucine: fatty acid sodium salt: lauryl sulfate Lauryl sulfates such as sodium and magnesium lauryl sulfate: silicic acids such as silicic anhydride and silicic acid hydrate: and the above-mentioned starch derivatives.), Binders (for example, hydroxypropyl cellulose) , Hydroxypropylmethylcellulose, polyvinylpyrrolidone, macrogol, and the same compounds as the above-mentioned excipients), disintegrants (for example, low-substituted hydroxypropylcellulose, carboxymethylcellulose) , Power Cellulose derivatives such as ropoxymethylcellulose calcium and internally crosslinked carboxymethylcellulose sodium; and chemically modified starch'celluloses such as carboxymethylstarch, carboxymethylstarch sodium and crosslinked polyvinylpyrrolidone. . ), Stabilizers (paraoxybenzoic acid esters such as methylparaben and propylpyrparaben: alcohols such as chlorobutanol, benzyl alcohol, and phenylethyl alcohol); phenols such as benzalconidum chloride; phenol and cresol: Thimerosal: dehydroacetic acid; and sorbic acid.), Flavoring agents (for example, commonly used sweeteners, sour agents, flavors, etc.), diluents, etc. It is manufactured by a well-known method using the additive of (1).

 The dosage varies depending on symptoms, age, etc. ^ In the case of oral administration, the lower limit is 1 mg (preferably 10 mg) per day, the upper limit is 200 mg (preferably 400 mg) per dose. In the case of intravenous administration, the minimum daily dose of 0.1 mg (preferably 1 mg) and the maximum upper limit of 500 mg (preferably 300 mg) should be It is desirable to administer 1 to 6 times a day depending on the symptoms.

[Best Mode for Carrying Out the Invention]

 Examples, Reference Examples, Test Examples and Formulation Examples are shown below, and the power for explaining the present invention in more detail and the scope of the present invention are not limited thereto.

 Example 1

 N- (1-ethylpentyl) 1-phenyl [3- (1H-tetrazo-l-yl-5-yl) phenyl] methyl} ammonium oxalate (Exemplified Compound No. 1-447)

1 \ '_ (1-Ethylpentyl) -1- [phenyl- (3-cyanophenyl) methyl] amine of 1 431118 was dissolved in 4.2 ml of anhydrous toluene, and 43 mg of sodium azide and 0.19 m l of tri-n-butyltin chloride was added, and the mixture was stirred at room temperature for 30 minutes and heated under reflux for 2 hours. Add 43 mg of sodium azide and 0 Add 19 ml of tri-n-butyltin chloride, heat to reflux for 2 hours, add 43 mg of sodium azide and 0.19 ml of tri-n-butyltin chloride, and add Refluxed for 1 hour. To the reaction solution, 1.98 ml of 1N hydrochloric acid was added, extracted with ethyl acetate, washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (elution solvent: cyclohexane ethyl acetate = 1/1) to obtain 54 mg of the free form as colorless crystals, and then 54 mg of the free form. Using this, 44 mg of the title compound was obtained as an oxalate.

 Melting point: 2 0 9-2 1 1

NMR spectrum _{(d e -DMS0) δ ppm:} .. 0. 75-0.90 (6H, m) 1. 10-1.35 (4H, m), 1. 50-1 80 (4H, m), 2. 60 -2.75 (1H, m), 5.60 (1H, s), 7.30-8.00 (8H, m), 8.36 (1H, s Example 2-

N— (1-ethylpentyl)-[phenyl (2-methylsulfonylphenyl) methyl] amine hydrochloride (Exemplary Compound No. 1884)

 (2a) N— (1—ethylpentyl)-[Fenryl (2-methylthiophenyl) methyl] amine

Dissolve 1.966 g of 2-methylthiobenzophenone and 1.96 g of 1-ethylpentylamine hydrochloride in 46 ml of anhydrous dichloromethane, and stir under ice-cooling with nitrogen under a flow of 6.75 m. A 1 molar solution of 1 triethylamine and 9.70 ml of titanium tetrachloride dichloromethane was added, and the reaction solution was stirred at room temperature for 17 hours. The reaction solution was diluted with ethyl acetate, washed with 0.5N hydrochloric acid and saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was dissolved in 56 ml of methanol, 0.74 ml of acetic acid and 2.162 g of sodium cyanoborohydride were added, and the mixture was heated under reflux for 1 hour. The reaction solution is diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate, water and saturated saline, dried over anhydrous sodium sulfate, and reduced in pressure. Under the solvent was distilled off. The obtained residue was separated and purified by silica gel column chromatography (eluting solvent: ethyl cyclohexanoacetate = 91) to obtain 2.584 g of the desired product as a colorless oil.

NMR spectrum _{(CDC1 3) δ ρριη: 0.80-0.95} (6H, m), 1.20- 1.60 (9H, m), 2.35 -2.45 (1H, m), 2.41 (3H, s), 5.46 (1H, s) , 7.10-7.70 (9H, m) „

 (2b) N- (1-ethylpentyl) -1- [phenyl (2-methylsulfonylphenyl) methyl] amine hydrochloride

 Under ice salt cooling, 0.59 ml of 30% hydrogen peroxide solution was added dropwise to 1.2 ml of trifluoroacetic acid, and then the compound N_ (1-ethylpentyl)-[phenyl] of Example (2a) was added. — (2-Methylthiophenyl) methyl] amine 618 mg was dissolved in 1.4 ml of trifluoroacetic acid, added dropwise, and stirred at room temperature overnight. The reaction mixture was neutralized by adding aqueous sodium bicarbonate, extracted with ethyl acetate, washed with saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (eluting solvent: ethyl cyclohexanoacetate == 8Z1) to obtain 383 mg of the title compound as a colorless oil. 338 mg of the oil was obtained as the hydrochloric acid salt.

 Melting point: 180-180

NMR spectrum _{(CDC1 3) δ ppffl: 0.75-0.95} (6Η, m), 1.10-1.80 (8Η, m), 2.68 (1.5H, s), 2.70-2.90 (1H, m), 3.08 (1.5H, s), 6.96 (1H, br.s), 7.25-8.15 (8H, m), 8.65 (0.5H, d, J = 7.9 Hz), 8.73 (0.5H, d, J = 8.0 Hz), 9.70-10.25 (2H, br. S).

 Example 3

 N- (1-ethylpentyl) -1- [phenyl (2-n-butylsulfonylphenyl) methyl] amine oxalate (Exemplary Compound No. 1 — 1 4 14)

 (3a) N— (1-ethylpentyl) — [phenyl— (2-n-butylthiophenyl) methyl] amine

1.50 g of 2_n_butylthiobenzophenone and 1.68 g of 1-ethyl The reaction was carried out in the same manner as in Example (2a) using ethylenediamine hydrochloride, followed by purification to obtain 1.45 g of the title compound as a pale brown oil.

NMR spectrum _{(CDC1 3) δ ppm:.} 0.80-0.95 (9H, m), 1. 15-1.70 (12H, m), 2.3 5-2 50 (1Η, m), 2.75-2.90 (2H, m) , 5.58 (1H, s), 7.10-7.70 (9H, m).

 (3b) N- (1-ethylpentyl) -1- [phenyl- (2-n-butylsulfonylphenyl) methyl] amine oxalate

 N- (1-ethylpentyl)-[phenyl (2-n-butylthiophenyl) methyl] amine of Example (3a) 1.25 g, 4.3 m 1 of trifluoroacetic acid and 0.96 The reaction was carried out in the same manner as in Example (2b) using 30 ml of 30% aqueous hydrogen peroxide and purified to obtain 1.33 g of the title compound as a pale yellow oil. From 0.50 g of the oily substance, 353 mg was obtained as an oxalate.

 Melting point: 1 4 3 — 1 4 5 X

NMR spectrum (CDU ₃ ) δ ppm: 0.70-1.05 (9H, m), 1.00-1.95 (12H, m), 2.70-3.10 (3Η, m), 6.71 (0.7Η, s), 6.74 ( 0.3Η, s), 7.30-8.10 (9Η, m).

 Example 4

 N-cyclohexyl [phenyl (2-methylsulfonylphenyl) methylamine] (Exemplary Compound No. 1-1096)

 (4a) N-cyclohexyl [phenyl- (2-methylthiophenyl) methyl] amine

 2. O g of 2-methylthiobenzophenone and 3.0 ml of cyclohexylamine were reacted in the same manner as in Example (2a) and purified to give the title compound as a yellow oil. 8 mg were obtained.

NMR spectrum _{(CDC1 3) δ ppm: 1.00-1.30} (5H, m), 1.40-2.05 (6Η, m), 2.30 -2.45 (1Η, m), 2.42 (. 3H s), 5.51 (1H, s) , 7.10-7.60 (9H, in) „

(4b) N-cyclohexyl [phenyl (2-methylsulfonylphenyl) methyl] amine Example (4a) N-cyclohexyl [phenyl- (2-methylthiophenyl) methyl] amine 222 mg, 2.38 m 1 of trifluoroacetic acid and 0.46 m 1 of 3 The reaction was carried out in the same manner as in Example (2b) using 0% aqueous hydrogen peroxide and purified to obtain 65 mg of the title compound as colorless crystals.

 Melting point: 105-107

NMR spectrum _{(CDC1 3) δ ppm:.} 0.95-1.30 (5H, m), 1. 5-2 10 (. 6Η m), 2.38 -2.53 (1Η, m), 2.78 (3H, s), 6. 32 (1H, s). 7. 20-8.10 (9H, m) ₀

 Example 5

 N-cyclohexyl- [phenyl- (2-n-butylsulfonylphenyl) methyl] amine hydrochloride (Exemplary Compound No. 1 1 1 4 3 6)

 (5a) N-cyclohexyl [phenyl- (2-n-butylthiophenyl) methyl] amine

 2. O g of 2 — n-butylthiobenzophenone and 1.7 ml of cyclohexylamine were reacted in the same manner as in Example (2a) and purified to give the title compound as a pale brown oil. 2.49 g were obtained.

NMR spectrum _{(CDC1 3) δ ppm:.} 0.90 (3H, t, J = 7.3Hz), 1.00-1.28 (5H, m), 1. 30-1 75 (8H, m) ', 1.85-2.05 (2H , m), 2.30-2.48 (1H, m), 2.75-2.90 (2H, m), 5.63 (1H, s), 7.10-7.60 (9H, m).

 (5b) cyclohexyl [phenyl- (2-n-butylsulfonylphenyl) methyl] amine hydrochloride

 Example 5 (a) N-cyclohexyl [phenyl (2-n-butylthiophenyl) methyl] amine 1.4.9 g, 5.8 ml trifluoroacetic acid and 1.3 ml 30% The reaction was carried out in the same manner as in Example (2b) using aqueous hydrogen peroxide, purified, and further converted to a hydrochloride to obtain 1.59 g of the title compound as colorless crystals.

 Melting point: 2 6 6-2 6 9

NMR spectrum _{(CDC1 3) δ ppm: 0.73} (. 3H, t J = 7.3Hz), 0.80- 1.75 (12H, m), 1.85- 1.98 (1H, m), 2.15-2.28 (1H, m), 2.55-2.80 (3H, m), 6.99 (1H, s), 1.5-7.80 (7H, m m), 8.05 (1H, d, J = 8.0Hz), 8.70 (1H, d, J = 7.9Hz) „

 Example 6

 N-cyclohexyl- [phenyl- (2-n-butylsulfinylphenyl) methyl] amine oxalate (Exemplary compound No. 1-1645)

 In Example (5a), N-cyclohexyl- [phenyl (2-n-butylthiophenyl) methyl] amine (283 mg) was dissolved in 3.0 ml of trifluoroacetic acid, and the solution was cooled to 0% under ice-cooling. After adding 0.8 ml of 30% aqueous hydrogen peroxide and stirring for 30 minutes, the reaction solution was neutralized with sodium bicarbonate and extracted with ethyl acetate. The extract was washed with saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (elution solvent: cyclohexane ethyl acetate = 9 Z 1) to obtain 212 mg of an oily substance. This colorless oil was used as an oxalate to give 188 mg of the title compound as colorless crystals.

 Melting point: 16.6-16.8 ° C (decomposition)

NMR spectrum _{(CDC1 3) δ ppm: 0.77} (3H, t, J = 7.3Hz), 0.90-2.00 (14H, m),

2.25-2.40 (2H, m), 2.75-2.95 (2H, m), 5.99 (1H, s), 7.20-8.30 (9H, m).

 Example 7

 N-cyclohexyl [phenyl (4-methylsulfonylphenyl) methyl] amine oxalate (Exemplary Compound No. 1 1 10 7 7)

 (7a) N-cyclohexyl [phenyl (4-methylthiophenyl) methyl] amine

 Using 1.0 g of 4-methylthiobenzophenone and 1.0 ml of cyclohexylamine, the reaction was carried out in the same manner as in Example (2a), purification was carried out, and the title compound was obtained as a pale pink oil. 12 mg were obtained.

NMR spectrum _{(CDC1 3) δ ppm: 1.00-1.25} (5H, m), 1. 0-2.00 (6Η, ra), 2.30 -2.45 (. 1Η m), 2.45 (3Η, s), 4. 99 ( 1Η, s), 7.10-7.40 (9Η, m) „ (7b) N-cyclohexyl [phenyl (4-methylsulfonylphenyl) methyl] amine oxalate

 Example 5 (7a) of N-cyclohexyl [phenyl- (4-methylthiophenyl) methyl] amine (51 mg), 5.1 ml of trifluoroacetic acid and 1.1 ml of 30% hydrogen peroxide solution The product was reacted in the same manner as in Example (2b) and purified to obtain 426 mg of the title compound as colorless crystals.

 Melting point: 106 (decomposition)

NMR spectrum _{(CDC1 3) δ ppm:.} 0.90-1.30 (5H, m), 1.50-2.00 (5Η, m), 2.80 - 95 (1Η, m), 3.01 (3H, s), 5.67 (1H, s ), 7.30-7.95 (9H, m).

 Example 8

 N-isopropyl- [phenyl (2-n-butylsulfonylphenyl) methyl] amine oxalate (Exemplary Compound No. 1-414 9)

 (8a) N-isopropyl- [phenyl (2-n-butylthiophenyl) methyl] amine

 1. O g of 2 — n-butylthiobenzophenone and 0.63 ml of isopropylamine were reacted in the same manner as in Example (2a) and purified to give the title compound as a pale brown oil. 95 O mg were obtained.

NMR spectrum _{(CDC1 3) <5 ppm:} . 0.90 (3H, t, 1 = 7.3Hz), 1.09 (6Η, d, J = 6.3Hz), 1. 30-1 70 (5H, m), 2.70- 2.90 (3H, m), 5.57 (1H, s), 7.10-7.55 (9H, m).

 (8b) N-isopropyl- [phenyl (2-n-butylsulfonylphenyl) methyl] amine oxalate

Example 8a) N-Isopropyl-1- [phenyl (2-n-butylthiophenyl) methyl] amine 42.27 mg, 4.76 ml of trifluoroacetic acid and 0.92 ml of 30 The reaction was carried out in the same manner as in Example (2b) using an aqueous solution of hydrogen peroxide and purified to give 159 mg of the title compound as colorless crystals as oxalate. Melting point: 1 5 8 — 1 6 0

NMR spectrum _{(CDC1 3) (5 ppm:} 0.73 (3H, t, J = 7.3Hz), 1.00-1.70 (4H, m), 1.20 (3H, d, J = 6.3Hz), 1.31 (3H, d, J = 6.3Hz), 2.55-2.80 (2H.m), 3.20-3.45 (1H, m), 6.81 (1H, s), 7.30-8.40 (9H, m).

 Example 9

 N—t e rt —butyl— [phenyl (2-n-butylsulfonylphenyl) methyl] amine (Exemplary Compound No. 1 1 1 4 1 1)

 (9 a) N—t e r t —butyl- [phenyl (2-n-butylthiophenenyl) methyl] amine

 1. The reaction was carried out in the same manner as in Example (2a) using 2.77 g of 2 — n-butylthiobenzophenone and 0.77 ml of tert-butylamine, and the title compound was purified by yellow oil. 32.6 mg was obtained.

NMR spectrum _{(CDC1 3) δ ppra: 0.89} (3H, t, J = 7.3Hz), 1.07 (9H, s), 1.30- 1. 65 (5H, m), 2.70-2.90 (2H, m), 5.61 (1H, s), 7.10-7.40 (8H, m), 7.88 (1H, d, J = 7.2 Hz).

 (9 b) N— t e r t — butyl- [phenyl (2-n-butylsulfonylphenyl) methyl] amine

 N-tert-butyl- [phenyl (2-n-butylthiophenyl) methyl] amine of Example (9a) 1 85 mg, 3.0 m 1 of trifluoroacetic acid and 0.42 m 1 of 3 The reaction was carried out in the same manner as in Example (2b) using 0% hydrogen peroxide solution and purified to obtain 115 mg of the title compound as colorless columnar crystals.

 Melting point: 7 4 — 7 6

NMR spectrum _{(CDC1 3) δ ppra: 0.62} (3H, t, J = 7.2Hz), 0.75-1.05 (2H, m), 1.08 (9H, s), 1.35- 1.58 (3H, m), 2.20-2.50 (2H, m), 6.39 (1H.s) .7.12-7.30 (5H, m), 7.40-7.48 (1H.in), 7.67-7.75 (1H, m), 7.95 (1H, d, J = 7.9 Hz) ), 8.61 (1H, d, J = 7.9 Hz). Example 10 0 '

 N-neopentyl— [phenyl (2- η-butylsulfonylphenyl) methyl] amine oxalate (Exemplary compound number 1 1 1 4 1 2)

 (10a) N-neopentyl- [phenyl (2-n-butylthiophenyl) methyl] amine

 5 OO mg of 2-n-butylthiobenzophenone and 0.44 ml of neopentylamine were reacted in the same manner as in Example (2a), purified, and the title compound was converted into a light brown oily substance. O mg was obtained.

NMR spectrum _{(CDC1 3) δ ppm: 0.80-1.00} (12H, πι), 1.35-1.70 (. 5Η m), 2. 3 4 (2Η, s), 2.75-2.95 (. 2Η m), 5.33 (1Η , s), 7. 10-7. 55 (9H, m).

 (10b) N-neopentyl- [phenyl- (2-n-butylsulfonylphenyl) methyl] amine oxalate

 Example (10a) N-neopentyl- [phenyl (2_n-butylthiophenyl) methyl] amine 250 mg, 2.0 ml of trifluoroacetic acid and 0.4 ml of 30% excess The reaction was carried out in the same manner as in Example (2b) using aqueous hydrogen oxide, followed by purification to obtain 533.3 mg of a colorless oil. The title compound was obtained as colorless crystals from 276 mg of the oil. mg was obtained.

 Melting point: 1 5 5 — 1 5 7

NMR spectrum _{(CDC1 3) δ ppm:.} 0.91 (3H, t, J = 7.3Hz), 1.07 (9H, s) 1.27- 1.95 (4H, m), 2.80 (2H, dd, J = 12.0Hz, J = 7.3Hz), 2.95-3.30 (2H, m), 6.18 (1H, s), 7.40-7.75 (8H, m), 8.00 (1H, d, J = 7.1Hz).

 Example 1 1

 N-cyclohexyl [(1,1—dioxybenzothiophene-3-yl) -1- (2-methylsulfonylphenyl) methyl '] amine (Exemplified Compound No. 3 — 4 2 3

)

(1 la) N-cyclohexyl-1 [(benzothiophene 3 -yl) one (2- Methylthiophenyl) methyl] amine

 Example 2 (a) using 399 mg of (benzothiophene-3-yl) mono (2-methylthiothioenyl) ketone obtained in Reference Example 5 and 0.96 m 1 of cyclohexylamine. In the same manner as described above, to obtain 346 mg of the title compound as a yellow oily substance.

NMR spectrum _{(CDC1 3) (5 ppm:} . 1.00-1.80 (9H, m), 1.90-2 15 (2Η, m), 2.43 (3H, s), 2.50-2.65 (1H, m), 5. 88 (1H, s), 7.05- 7.90 (9H, m).

 (1 l b) N-cyclohexyl — [(1,1-dioxybenzothiophen-3-yl) -1- (2-methylsulfonylphenyl) methyl] amine

 Example 11-a) N-cyclohexyl-1-[(benzothiophen-3-yl)-(2-methylthiophenyl) methyl] amine 3464 mg, 5. O ml of trifluoroacetic acid and Using 0.5 ml of 30% aqueous hydrogen peroxide, the reaction was carried out in the same manner as in Example (2b) to obtain 115 mg of the title compound as colorless crystals.

 Melting point: 1 4 7 — 1 5 0 X

NMR spectrum (d _e -DMS0) δ pm: 0.95-1.25 (5H, m), 1.45-2.05 (5Η, m), 2.40-2.55 (1H, m), 2.91 (1H, d, J = l 1.2Hz), 3.35 (3H, s), 6.32 (1H, d, J = l 1.1Hz), 6.96 (1H, s), 7.55-7.90 (7H, m), 8.05 (1H, d, J = 7.6Hz).

 Example 1 2

 (1 2 — 1) N-cyclohexyl [2 — Chenyl (2 — methylsulfinylphenyl) methyl] amine oxalate (Exemplified Compound No. 3 — 144) and

(1 2 — 2) N-cyclohexyl [2-Chenyl (2-methylsulfonylphenyl) methyl] amine oxalate (Exemplified Compound No. 3-100)

 (1 2 a) N-cyclohexyl [2-Chenyl (2-methylthiophenyl) methyl] amine

As in Example (2a), using 455 mg of (2-thenyl) -12-methylthiophenenyl ketone obtained in Reference Example 2 and 0.89 ml of cyclohexylamine The residue was purified to give 435 mg of the title compound as a pale yellow oil.

NMR spectrum _{(CDC1 3) δ ppm:.} . 1.03-1 30 (5H, in), 1.50-1.80 (. 4Η m), 1.85 -2 10 (2Η, m), 2.35-2.55 (1Η, m), 2.45 (3H, s), 5.77 (1H, s), 6.80-6.95 (2H, m), 7.10-7.30 (4H, m), 7.54 (1H, d, J = 6.8Hz).

 (1 2 b-1) N-cyclohexyl [2-chenyl (2-methylsulfinylphenyl) methyl] amine oxalate and

 (12b-2) N-cyclohexyl- [2-Chenyl- (2-methylsulfonylphenyl) methyl] amine oxalate

 In Example (12a), 43.5 mg of N-cyclohexyl-1- [2-phenyl-1- (2-methylthiophenyl) methyl] amine was dissolved in 3.0 ml of trifluoroacetic acid, and cooled with ice salt. Under stirring, 0.26 m 1 of 30% aqueous hydrogen peroxide was added, and the mixture was stirred under ice salt cooling for 45 minutes. After neutralizing with saturated aqueous sodium hydrogen carbonate and extracting with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was separated and purified by silica gel column chromatography (eluent: dichloromethane / ethyl acetate = 2/1) to obtain 52 mg of the first effluent. When this was used as an oxalate, 49.9 mg of the title compound (12b-2) was obtained as colorless crystals. The next outflow was 387 mg. Using this 387 mg as an oxalate, 411 mg of the title compound (12b-1) was obtained as colorless crystals.

 (1 2 b-1)

 Melting point: 1 3 8 — 1 4 3

NMR spectrum _{(d 6 -DMS0) δ ppm:} 0. 95-1.30 (5H, m), 1. 0-2.05 (5Η, m), 4.41 (2Η, s), 2.79 (1Η, s), 5.76 ( 0.33H, s), 5.79 (0.67H, s), 6.90-8.00 (7H.m).

 (1 2 b-2)

 Melting point: 1 84 (decomposition)

NMR spectrum (d ₆ — DMS0) <3 ppm: 1.00-1.30 (5H, m), 1.40-2.05 (5H.m). 2.45-2.60 (1H, m). 3.14 (3H.m) s), 6.53 (1H, s), 6.95-7.10 (2H, m) .7.50 (1H.d, J = 4. 9Hz), 7.61 (1H, t, J = 7.5Hz), 7.81 (1H, t, J = 7.3Hz), 7.98 (1H, d, J = 8.0Hz), 8.06 (1H, d, J = 7.8 Hz).

 Example 13

 N-cyclohexyl- [phenyl- (2-phenylsulfonylphenyl) methyl] amine (Exemplary Compound No. 1—1522)

 (13a) N-cyclohexyl [phenyl- (2-phenylthiophenyl) methyl] amine

 Using 50 O mg of 2-phenylthiobenzophenone and 0.4 ml of cyclohexylamine, the reaction was carried out in the same manner as in Example (2a), and the title compound was purified to give a pale yellow oil. As a result, 62 O mg was obtained.

NMR spectrum _{(CDC1 3) δ ρρπι: 0.90-1.25} (5Η, m), 1.40-2.00 (6Η, m), 2.25 -2.42 (1Η, m), 5.67 (1H, s), 7. 10-7.70 ( 14H, m).

 (13b) N-cyclohexyl [phenyl (2-phenylsulfonylphenyl) methyl] amine

 Example (13a) of N-cyclohexyl- [phenyl- (2-phenylthiophenyl) methyl] amine 500 mg, 2.0 ml of trifluoroacetic acid and 0.77 ml of 3 The reaction was carried out in the same manner as in Example (2b) using 0% aqueous hydrogen peroxide, and the product was purified to obtain 300 mg of the title compound as colorless crystals.

 Melting point: 9 6 — 9 8

NMR spectrum _{(CDC1 3) δ ppm: 0.80-1.20} (5H, m), 1.35-1.85 (6Η, π), 2. 10 -2.28 (1Η, m), 5.86 (. 1Η m), 6. 98- 7.20 (5Η, m), 7.35-7.70 (5Η, m), 7.75-7.90 (3Η, m), 8.20 (1Η, d, J = 7.9Hz).

 Example 14

 Ν—Cyclohexyl— [phenyl (2-ethylsulfonylphenyl) methyl] amine (Exemplary Compound No. 1—116)

(14a) N-cyclohexyl- [phenyl- (2-ethylthiophenenyl) Chill]

 Using 0.50 g of 2-ethylthiobenzophenone obtained in Reference Example 6 and 0.5 ml of cyclohexylamine, the reaction was carried out in the same manner as in Example (2a), and the title compound was purified. 0.75 g was obtained as a tan oil.

NMR spectrum _{(CDC1 3) δ ppm:.} I.00-1.25 (5H, m), 1.28 (3H, t, J = 7.4Hz), 1.45-1.78 (4H, m), 1.88-2 18 (2H, m), 2.30-2.45 (1H, m), 2.80-2.95 (2H.m), 5.62 (1H, s). 7. 12-7.55 (9H, m).

 (14b) N-cyclohexyl- [phenyl- (2-ethylsulfonylphenyl) methyl] amine

 Example (14a) N-cyclohexyl- [phenyl- (2-ethylthiooffenyl) methyl] amine 0.50 g, 2.0 ml trifluoroacetic acid and 0.87 ml The reaction was carried out in the same manner as in Example (2b) using 30% aqueous hydrogen peroxide, and the mixture was purified to obtain 0.38 g of the title compound as colorless crystals.

 Melting point: 9 3 — 9 4

NMR spectrum _{(CDC1 3) δ ppm: 0.90-1.25} (8H, m), 1. 0-2.08 (. 6Η m), 2.38 -2.50 (1Η, m), 2.73-2.95 (. 2H m), 6.29 ( 1H, s), 7.20-7.50 (6H, m), 7.60-7.70 (1H, m), 7.93 (1H, d, J = 6.9 Hz), 8.02 (1H, dd, J = l.2 Hz, J = 7.9 Hz).

 Example 15

 N-benzyl [phenyl (2-ethylsulfonylphenyl) methyl] amine hydrochloride (Exemplary Compound No. 1-11-178)

 (15a) N-benzyl- [phenyl (2-ethylthiophenyl) methyl] amine

 The same procedure as in Example (2a) was carried out using 0.50 g of 2- (ethylthiobenzophenone) obtained in Reference Example 6 and 0.45 ml of benzylamine, followed by purification to give the title compound. As a pale yellow oil.

NMR spectrum _{(CDC1 3) δ ppm: 1.26} (3H, t, J = 7.3Hz), 2.84 (.. 2H q J = 7.3Hz) , 3.75 (2H, s), 5.48 (2H, s), 7.15-7.65 (14H, m)

 (15b) N-benzyl [phenyl- (2-ethylsulfonylphenyl) methyl] amine hydrochloride

 Example (15a) of N-benzyl [2- (2-ethylthiophenenyl) methyl] amine 0.50 g, 2.0 ml of trifluoroacetic acid and 0.83 ml of 3 The reaction was carried out in the same manner as in Example (2b) using 0% aqueous hydrogen peroxide, followed by purification to obtain 0.48 g of the title compound as colorless crystals.

 Melting point: 2 4 7 — 2 4 8 (decomposition)

NMR spectrum _{(CDC1 3) δ ppm:.} . 1.09 (3H, t, J = 7.3Hz), 2. 50-2.85 (2H, m), 3.70-4 15 (2H, m) 6.39 (1H, d, H = 6.1 1Hz), 7.25-7.70 (10H, m), 7.85-8.10 (3H, m), 8.51 (1H, d, J = 7.8Hz), 10.60-11.20 (2H, br.s) ₀

 Example 16

 N-trans-4-methoxycarbonylcyclohexylmethyl- [phenyl (2-ethylsulfonylphenyl) methyl] amine oxalate (Exemplary Compound No. 1-11-175)

 (16 a) N-trans-1-4-methoxycarbonylcyclohexylmethyl- [phenyl- (2-dithiophenyl) methyl] amine

 Using 1.50 g of 2-ethylthiobenzophenone obtained in Reference Example 6 and 2.60 g of trans-14-methoxycarboxylic hexylmethylamine, Example (2a) was used. The reaction was carried out in the same manner and purification was performed to obtain 2.32 g of the title compound as a pale yellow oil.

NMR spectrum _{(CDC1 3) δ ppm:.} 0.85-1.05 (2H, m), 1.29 (3Η, t, J = 7.5Hz), 1.30-1 65 (4H, m), 1.82-2.05 (4H, m) , 2.15-2.30 (1H, m), 2.44 (2H, d, J = 6.6 Hz), 2.88 (2H, q, J = 7.4 Hz), 3.66 (3H, s), 5.34 (1H , s), 7.10-7.53 (9H, m).

(16b) N-trans-4-methoxycarbonylcyclohexylmethyl- [phenyl- (2-ethylsulfonylphenyl) methyl] amine oxalate Example 1 (16a) of N-trans-14-methoxycarbonylcyclohexylmethyl- [phenyl (2-ethylthiophenyl) methyl] amine 2.0 g, 8.0 m 1 The reaction was carried out in the same manner as in Example (2b) using trifluoroacetic acid and 2.9 ml of 30% aqueous hydrogen peroxide, followed by purification to obtain 1.83 g of a colorless oil. From 0.2 g of this oily substance, 0.15 g of the title compound was obtained as colorless crystals.

 Melting point: 1 3 2 — 1 3 4

NMR spectrum _{(CDC1 3) δ ppm:.} 0.80-1.05 (2H, in), 1. 14 (3Η, t, J = 7.4Hz), 1.30-1 65 (4H, m), 2. 15-2.30 ( 1H, m), 2.38 (1H, dd, J = 6.8Hz, J = l 1.3Hz), 2.55 (1H, dd, J = 6.2Hz, J = l 1.3Hz), 2.80-3.05 (2H. m), 3.65 (3H, s), 5.94 (1H, s), 7.20-7.50 (6H, m), 7.55-7.65 (1H, m), 7.77 (1H.d, J = 6.9 Hz), 8.02 (1H, dd, J = l.2Hz.1 = 7.9Hz) Example 1 7

 N—4-Methylcyclohexyl [phenyl (2_n-butylsulfonylphenyl) methyl] amine oxalate (Exemplary Compound No. 1—1442)

 (17a) N—4-Methylcyclohexyl— [phenyl— (2-n-butylthiophenyl) methyl] amine

 Using 500 mg of 2_n-butylthiobenzophenone and 0.49 ml of 4-methylcyclohexylamine, the reaction was carried out in the same manner as in Example (2a), and the two title compounds were purified. To give 27 mg of the intermediate (17a-l) and 104 mg of the intermediate (17a-2) as pale yellow oil.

 (1 7 a-1)

 R f = 0.7 (Developing solvent: cyclohexane / ethyl acetate = 91)

NMR spectrum _{(CDC1 3) δ ppm:.} 0.80-1.00 (6H, πι), 1.20-1.75 (14H, m), 2.6 0-2 70 (1Η, m), 2.75-2.90 (2H, m), 5 54 (1H, s), 7. 13-7.60 (9H, ra).

 (1 7 a-2)

R f = 0.5 (Developing solvent: cyclohexane ethyl acetate = 9-1) NMR spectrum _{(CDC1 3) δ ppm:.} 0.83 (3H, d, J = 6.5Hz), 0.90 (3H, t, J = 7.3Hz), 1.00- 1.75 (12H, m), 1.93-2 10 (2H , m), 2.26-2.40 (1H, m), 2.78-2.90 (2H, ηι), 5.63 (1H, s), 7.10-7.60 (9H, m).

 (17b-1) N-4-Methylcyclohexyl [phenyl- (2-n-butylsulfonylphenyl) methyl] amine oxalate

 Intermediate (17a-1) 2 11 mg> 3. Using O ml of trifluoroacetic acid and 0.5 ml of 30% aqueous hydrogen peroxide, react in the same manner as in Example (2b). Purification was further performed to obtain an oxalate, and 174 mg of the title compound was obtained as colorless crystals.

Melting point: 202-204

NMR spectrum _{(d s -DMS0) δ ppm:} 0.71 (. 3H t, J = 7.3Hz), 0.89 (.. 3H d J = 6.7H z), 1.05- 1.80 (13H, m), 2.62-2.78 ( 1H, m), 2.90-3.15 (2H, m), 6.34 (1H, s), 7.25 -8.10 (9H, m)

 (17b—2) N—4-Methylcyclohexyl [phenyl (2-n-butylsulfonylphenyl) methyl] amine

 A mixture of the intermediates (17a-2) and (17a-1) was carried out using 31 mg, 2.5 ml of trifluoroacetic acid and 0.5 ml of 30% aqueous hydrogen peroxide. The reaction was carried out in the same manner as in Example (2b), purification was carried out, and only the portion of R f = 0.48 (developing solvent: cyclohexane / ^ ethyl acetate = 41) was taken. 2 mg were obtained.

 Melting point: 8 9—9 1

NMR spectrum _{(CDC1 3) δ ppm: 0.75} (3H, t, J = 7.3Hz), 0.83 (3H, d, J = 6.5Hz), 1.00-1.75 (12H, m), 1.88-2.00 (1H, m ), 2.00-2.12 (1H, m), 2.30-2.45 (1H, m), 2.65-2.90 (2H, m) .6.30 (1H, s), 7.20-8.05 (9H, m) ₀

 Example 18

N-4-tert-butylcyclohexyl [phenyl- (2-n-butylsulfonylphenyl) methyl] amine (Exemplary Compound No. 1-11443) (18 a) N— 4 — tert —butylcyclohexyl [phenyl (2-n-butylthiophenyl) methyl] amine

 6 OO mg of 2_n-butylthiobenzophenone and 0.79 ml of 4-tert-butylcyclohexylamine were reacted in the same manner as in Example (2a) and purified to give the title compound as colorless crystals 36.2 mg was obtained.

 Melting point: 8 1-8 3

NMR spectrum _{(CDC1 3) δ ppm: 0.80} (9H, s), 0.85-1.15 (4Η, m), 0.91 (3Η, t, J = 7.3Hz), 1.30-1.80 (8Η, m), 2.00-2.15 (2Η, m), 2.22-2.40 (1Η, πι), 2.75-2.90 (2Η, m), 5.63 (1Η, s), 7.10-7.55 (9Η.m).

 (18 b) Ν— 4 — tert —butylcyclohexyl [phenyl (2-n-butylsulfonylphenyl) methyl] amine

 Example (18a) N-4-tert-Butylcyclohexyl- [phenyl-1- (2-n-butylthiophenenyl) methyl] amine 3.58 mg, 1.5 ml trifluoroacetic acid and 0.1 ml The reaction was carried out in the same manner as in Example (2b) using 4 ml of a 30% aqueous hydrogen peroxide solution, followed by purification to obtain 272 mg of the title compound as colorless crystals. Melting point: 1 2 0— 1 2 2

NMR spectrum _{(CDC1 3) 6 ppm: 0.75} (. 3H, t J = 7.3Hz), 0.80 OH, s), 0.85- 1.80 (12H, m), 1.93-2.20 (2H, m), 2.30-2.45 ( 1H, m), 2.70-2.90 (2H, m), 6.30 (1H, s), 7.20-8.05 (9H, m).

 Example 19

 N-cyclohexyl [p-tolyl-1- (2-cyclohexylcarbamoylphenyl) methyl] amine oxalate (Exemplary Compound No. 1630)

 Using 500 mg of 2- (4-methylbenzoyl) benzoic acid and 0.71 ml of cyclohexylamine, react in the same manner as in Example (2a), purify, and The compound was obtained as colorless crystals, 78.5 mg.

Melting point: 1 8 3 _ 1 8 5 NMR spectrum _{(d 6 - DMSO) δ ppin} :. 0.95-2.20 (20H, in), 2.27 (. 3H s) 2.50- 2.70 (1H, m), 6.01 (1H, s), 7.10-7.65 (7h, m), 7.79 (1H, d, J = 7.7Hz), 8.52 (1H.d, J = 7.7Hz).

 Example 20

 N-((1R) 1-1-phenylethyl)-(phenyl [6-fluoro-3- (1H-tetrazol-5-yl) phenyl] methyl} amine and its hydrochloride (Exemplary Compound No. 1—1 8 7 6)

 (20a) N-((1R) 1-1-phenylethyl) 1-phenyl (3-cyano 6 _fluorophenyl) methyl] amine

 Reference Example 28 Using 3-benzoyl 4-one-fluorene benzonitrile obtained in 8-4 20 m1 and 0.48 ml of (R) _1-phenylphenylamine, the working example (2 The reaction was carried out in the same manner as in a), and purification was carried out to obtain 23 Omg of isomer A of the title compound as a yellow oil and 203 mg of isomer B as a yellow oil.

 Isomer A

NMR spectrum _{(CDC1 3) (5 ppm:} 1.40 (3H, d, J = 6.7Hz), 3.61 (1H, q, J = 6.7Hz), 4.93 (1H, s), 7.06 (1H, dd, J = 8.7Hz. J = 9.7Hz), 7.19-7.39 (10H, m), 7.53-7.58 (1H, m). 8.09 (1H, dd, J = 2.1Hz, J = 6.7Hz). '

 Isomer B

NMR spectrum _{(CDC1 3) δ ppm: 1.39} (3H, d, J = 6.7Hz), 3.70 (1H, q, J = 6.7Hz), .97 (1H, s), 6.98 (1H, dd, J = 8.6Hz, J = 9.7Hz), 7.19-7.39 (10H, m), 7.43-7.48 (1H, m), 7.89 (1H, dd, J = 2.1Hz, J = 6.7Hz).

 (20b) N-((1R) 1-1-phenylethyl) -1- {phenyl [6-fluoro-3- (1H-tetrazol-5-yl) phenyl] methyl} amine and its hydrochloride

225 mg of isomer 8 of Example (20a), 133 mg of sodium azide and 158 ml of tributyltin chloride were reacted in the same manner as in Example 1. The residue was purified to give 115 mg of the isomer A of the title compound as a white powder as a white powder.

 Isomer A

 Melting point: 1 2 2-1 2 5 (decomposition)

NMR spectrum _{(CDC1 3) δ ppm: 1.55} (3H, d, J = 6.6Hz), 3.99-4.06 (1H, m), 5 .22 (1H, s), 7.09-7.41 (11H, m), 8.24 -8.29 (1H, m), 8.79-8.81 (1H, m) »

 The same reaction as in Example 1 was carried out using 200 mg of isomer B of Example (20a), 118 mg of sodium azide and 0.52 ml of tributyltin chloride. Purification gave 210 mg of the free form of isomer B of the title compound as a white powder. Using 200 mg of the free form, the title compound was converted into a hydrochloride to obtain 98 mg as a yellow powder.

 Isomer B

 Melting point: 1 3 0 _ 1 3 4

NMR spectrum _{(CDC1 3) δ ppm: 1.47} (3H, d, J = 6.6Hz), 4. 19-4.29 (1H, m), 5 .36 (1H, s), 7.42-7.60 (11H, m) , 8.05-8.09 (1H, m), 8.60-8.63 (1H, πι), 10.1-11.0 (1H, br. S).

 Example 2 1

 N-cyclohexyl {phenyl [4- (4-methylsulfonylphenyl) phenyl] methyl] amine oxalate (Exemplary Compound No. 1-211)

 (21 a) N-cyclohexyl- {phenyl— [4- (4-methylsulfonylphenyl) phenyl] methyl} amine

 The reaction was carried out in the same manner as in Example (2a) using 312 mg of 4— (4-methylthiophenenyl) benzophenone obtained in Reference Example 8 and 0.23 ml of cyclohexylamine. Purification gave 309 mg of the title compound as colorless crystals.

 Melting point: 8 0 — 8 2

NMR spectrum _{(CDC1 3) δ ppm: 1.00-1.30} (5H, m), 1.45-2.05 (6Η, m), 2.35 -2.55 (1H, m), 2.51 (3H, s). 5.07 (1H, s). 7. 15-7.55 (13H, in).

 (2 1 b) N-cyclohexyl- {phenyl [4-1 (4-methylsulfonylphenyl) phenyl] methyl} amine oxalate

 Example (21a) of N-cyclohexyl {phenyl [4- (4-methylsulfonylphenyl) phenyl] methyl} amine 95 mg and 3. O ml of trifluoroacetic acid and 0.5 ml of The reaction was carried out in the same manner as in Example (2b) using 30% aqueous hydrogen peroxide, followed by purification to obtain 20 mg of the title compound as colorless crystals.

 Melting point: 2 1 1 — 2 1 3

NMR spectrum (d ₆ -DMS0) δ ppm: 1.00-1.80 (8H, m), 2.Οδ-2.20 (2Η, m), 2.55-2.70 (1Η, m), 3.26 (3H, s), 5.67 ( 1H, br.s), 7.30-8.05 (13H, m) „

 Example 22

 N-trans-l-4oxyloxycyclohexylmethyl- [phenyl- (2-ethylsulfoerphenyl) methyl] amine hydrochloride (Exemplary Compound No. 1—11174)

 N-trans-14-methoxycarbonylcyclohexylmethyl- [phenyl (2-ethylsulfonylphenyl) methyl] amine obtained in Example 16 0.3 Og in 6.0 m 1 of methanol Was added and 2.1 ml of 1 N sodium hydroxide was added under ice-cooling and stirring. After stirring at room temperature for 6.5 hours, the mixture was allowed to stand overnight. Under ice-cooling and stirring, 2.1 ml of 1N hydrochloric acid was added, the solvent was distilled off under reduced pressure, and benzene was added to the obtained residue, which was azeotropically dried to dryness. The obtained residue was dissolved in ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography using ethyl acetate as an eluting solvent to obtain 75 mg of the title compound as colorless crystals.

 Melting point: 2 5 3 — 2 5 5 (decomposition)

NMR spectrum _{(d e -DMS0) δ ppm:} .. 0. 80-1.35 (4H, m) 1.07 (3H, t, J = 7.3Hz) 1. 70- 1. 98 (4H, in), 2.05- 2.20 (1H, m), 2.75 (2H, d, J = 3.3Hz), 3.21 (2H, q, J = 7.3Hz) ), 3.25-3.50 (1 H, m), 6.46 (1H, br.s), 7.30-7.50 (3H, m), 7.65-7.80 (3H.in), 7.93 (1H, t, J = 7.6Hz) .8.01 (1H, d, J = 7.9Hz), 8.41 (1H, d.J = 7.8Hz), 10.00 (1H, br.s), 10.15 (1H, br.s) ), 12.06 (1H, br. S).

 Example 23

 N— [trans-14_ (N, N-dimethylcarbamoyl) cyclohexylmethyl] -1- [phenyl (2-ethylsulfonylphenyl) methyl] amine (exemplified compound number 1—1176)

 (23a) N- [trans-14_ (N, N-dimethylcarbamoyl) cyclohexylmethyl]-[phenyl (2-ethylthiophenenyl) methyl] amine Obtained in Reference Example 6. Using 50 g of 2-ethylthiobenzophenone and 0.91 g of trans- (N, N-dimethylcarbamoyl) cyclohexylmethylamine hydrochloride in the same manner as in Example (2a) And purified to give 0.67 g of the title compound as a pale yellow oil.

NMR spectrum _{(CDC1 3) δ ppm: 0.85-1.08} (2H, m), 1.30 (3Η, t, J = 7.3Hz), 1.45-2.00 (8H, m), 2. 35-2.50 (1H, m) , 2.46 (2H, d, J = 6.3 Hz), 2.80-3.00 (2H, m), 2.94 (3H, s), 3.03 (3H, s), 5.36 (lH, s), 7.10-7.55 (9H , m).

 (23b) N— [trans-41- (N, Ν-dimethylcarbamoyl) cyclohexylmethyl]-[phenyl (2-ethylsulfonylphenyl) methyl] amine

 0.60 g of N- [trans-4- (N, N-dimethylcarbamoyl) cyclohexylmethyl]-[phenyl (2-ethylthiophenenyl) methyl] amine of Example (23a) , 2.4 ml of trifluoroacetic acid and 0.83 ml of 30% aqueous hydrogen peroxide, and reacted in the same manner as in Example (2b). Purification was performed to give the title compound as colorless columnar crystals. 0.36 g was obtained.

 Melting point: 1 5 4 — 1 5 5

NMR spectrum _{(CDC1 3) δ ppm:.} 0.85-1 10 (2H, in), 1. 15 (. 3Η, t J = 7.4Hz), 1.40-2.00 (8H, m), 2.30-2.60 (3H, m), 2.85-3.10 (2H, m), 2.93 (3H, s), 3.02 (3H.s), 5.94 (1H , s), 7.20-7.50 (6H, m), 7.55-7.65 (1H, m), 7.77 (1H, d, J = 7.7 Hz), 8.0 3 (1H, dd.J = l. 2 Hz , J = 7.9Hz).

 Example 2 4

 N-trans-1-hydroxymethylcyclohexylmethyl- [phenyl (2-ethylsulfonylphenyl) methyl] amine hydrochloride (Exemplary Compound No. 1-11-173)

 N-trans-4-Methoxycarbonylcyclohexylmethyl- [phenyl (2-ethylsulfonylphenyl) methyl] amine obtained in Example 16 0.5 g of 0.5 Og was added to 10 ml of anhydrous tetrahydrofuran. After dissolving in drofuran, 1.8 ml of a 1 mol solution of lithium aluminum hydride in anhydrous tetrahydrofuran was added under ice-cooling, followed by stirring at room temperature for 4 hours. Further, under ice-cooling and stirring, 1.0 mL of sodium sulfate 10 hydrate was added to the reaction solution, and the mixture was stirred for 30 minutes. The insolubles were removed by filtration using celite, the filtrate was distilled off under reduced pressure, and the obtained residue was subjected to silica gel gel chromatography (elution solvent: cyclohexane Z ethyl acetate = 2-1 to 1). Separation and purification yielded 0.32 g of a colorless oil. This oil was dissolved in 2.0 ml of dioxane, 2.0 O ml of a 4N solution of nodioxane hydrochloride was added, and the solvent was distilled off under reduced pressure. The obtained residue was filtered using acetone and dried to obtain 0.22 g of the title compound as colorless crystals.

 Melting point: 182-184 (decomposition)

NMR spectrum _{(CDC1 3) δ pm:.} .. 0.75-1 10 (4H, m), 1. 19 (3Η, t, J = 7.3Hz), 1.30-1.98 (6H, m) 2.50-3 10 ( 4H, m), 3.43 (2H, d, J = 6.2Hz), 6.70 (1H, br.s), 7.25-7.90 (7H, m), 8.04 (1H, d, J = 6.0Hz), 8.46 (1H, d, J = 7.8Hz).

 Example 2 5

N- (1-ethylpentyl) 1-phenyl [3- (1H-tetrazol-5-yl) phenyl] methyl} amine hydrochloride (Exemplary Compound No. 1-447) Obtained in Example 1 N— (1—Ethyl pentyl) One (Fenru [3— (1H -Tetrazole-5-yl) phenyl] methyl} amine Free-form 1.45 g was dissolved in 100 ml of ethyl acetate by heating, and 2.4 ml of 4N ethyl acetate hydrochloride was added, followed by concentration under reduced pressure. did. The obtained residue was crystallized by adding isopropyl ether, and collected by filtration to obtain 1.41 g of the title compound as pale yellow crystals.

 Melting point: 2 0 9-2 1 1

NMR spectrum _{(d e -DMS0) δ ppm:} 0.75-0.90 (6H, ni), 1.10-1.37 (4Η, m), 1.52-1.90 (4Η, m), 2.80-2.90 (1Η, m), 5.87 ( 1H, s), 7.30-8.20 (8H.m), 8.52 (1H, s

 N-cyclohexyl-1-phenyl [2- (4-methylsulfonylphenyl) phenyl] methyl} amine (Exemplary Compound No. 1-125)

 (26 a) N-cyclohexyl {phenyl-2 [(4-methylthiophenyl) phenyl] methyl} -amine

 Using 1.47 g of 2- (4-methylthiophenenyl) benzophenone and 0.87 ml of cyclohexylamine, the reaction was carried out in the same manner as in Example (2a), and the title compound was purified by colorless purification. 1.34 g was obtained as an oil.

NMR spectrum _{(CDC1 3) δ ppm: 0.85-1.20} (5H, m), 1.40-1.80 (6Η, m), 2. 18 one 2.30 (1Η, m), 2.54 (3H, s), 5. 14 ( 1H, s), 7.10-7.60 (13H, m).

 (26 b) N-cyclohexyl {phenyl [2- (4-methylsulfonylphenyl) phenyl] methyl}

 Example 26-N-cyclohexyl {phenyl-2- [4- (4-methylthiophenyl) phenyl] methyl} amine 46 2 mg, 3. Oml of trifluoroacetic acid and 0.5 ml of 30 The reaction was carried out in the same manner as in Example (2b) using aqueous% hydrogen peroxide, and the mixture was purified to obtain 379 mg of the title compound as colorless crystals.

 Melting point: 1 1 6—1 1 9

NMR spectrum _{(CDC1 3) δ ppm:.} 0.80-1.20 (5H, m), 1.40-1.80 (6Η, m) 2.20 -2.35 (1H, m), 3.12 (3H, s), 5.01 (1H.s), 7.05-8.05 (13H, m).

 Example 2 7

 N-cyclohexyl [phenyl (2-hydroxy-4-methyoxy-5-N, N-dimethylsulfamoylphenyl) methyl] amine oxalate (Exemplified Compound No. 1-162)

 Reference Example 11 180 mg of 2-Hydroxy-4-Methoxy-5-N, N-dimethylsulfamoylpenzophenone obtained in 1 and 0.135 m1 cyclohexylamine and catalyst An amount of P-toluenesulfonic acid monohydrate was refluxed and dehydrated in 3 O ml of xylene for 20 hours. To the reaction solution, 20 ml of anhydrous tetrahydrofuran and 0.27 ml of a 10 mol solution of borohydride-dimethyl sulfide complex were added at room temperature, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (elution solvent: cyclohexane / ethyl acetate = 5/1) to obtain colorless crystals. The crystals were dissolved in 5.0 ml of methanol and heated under reflux for 1 hour. The solvent was distilled off under reduced pressure, diluted with ethyl acetate, washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (eluent: cyclohexane Z-ethyl acetate = 2/1) to give 12.9 mg of the title compound as colorless crystals.

 Melting point: 1 6 8 — 1 7 0

NMR spectrum _{(CDC1 3) δ ρπι:.} 1.00-1.80 (8Η, m), 1.95-2 10 (2Η, ηι), 2.55 -2.70 (1Η, m), 2.61 (6H, s), 5.60 (1H, s), 6.63 (1H, s), 7.30-7.55 (5H, m), 7.68 (1H, s).

 Example 2 8

N-cyclohexyl- [phenyl (3-N-tosylcarbamoylphenyl) methyl] amine oxalate (Exemplary Compound No. 1 — 687) The reaction was carried out in the same manner as in Example (2a) using 9488 mg of N-tosyl-3-benzoylbenzoic acid amide obtained in Reference Example 13 and 0.57 ml of cyclohexylamine, and purified. This gave 275 mg of the title compound as colorless crystals.

 Melting point: 2 25-2 27 ° C

NMR spectrum (d ₆ —DMS0) δ ppm: 0.90-1.75 (8H, m), 2.05-2.20 (2Η, m), 2.34 (3Η, s), 2.65-2.75 (1Η, m), 5.79 (1H, s), 7.24 (2H, d, J = 8.2Hz), 7.30-7.50 (4H, m), 7.60-7.70 (3H, m), 7.76 (2H, d, J = 8.3Hz), 7.87 (1H.d, J = 7.7Hz), 8.17 (1H, s

 N-((1R) 1-1_phenylethyl) -1- [phenyl (2-ethylphenyl) phenyl] methyl] amine (Exemplary compound number 1—111)

 (29 a) N-((1 R) 1-1-phenylethyl)-[phenyl (2-ethylthiophenyl) methyl] amine

 Reaction was carried out in the same manner as in Example (2a) using 1.0 g of 2-Oethylthiobenzophenone obtained in Reference Example 6 and 1.1 ml of (R) -1 -phenylethylamine. Purification gave 1.41 g of the title compound as a pale brown oil.

NMR spectrum _{(CDC1 3) δ ppm: 1.07} (2H, t, J = 7.3Hz), 1. 18 (1H, t, 1 = 7.3Hz), 1.55-1.75 (. 4H m), 2. 50-2.83 (2H, m), 5.63 (0.35H, s), 5.68 (0.65H, s), 7.10-7.65 (13H, m), 8.12 (1H, d, J = 7.5Hz).

 (29b) N — ((1R) 1-11-phenylethyl) -1- [phenyl— (2-ethylsulfonylphenyl) methyl] amine

Example (29a) of N — ((1R) -11-phenylethyl) -1- [phenyl— (2-ethylthiophenenyl) methyl] amine 1.2 g and 6. O ml of trifluoroacetic acid and 1 The reaction was carried out in the same manner as in Example (2b) using 6 ml of a 30% aqueous hydrogen peroxide solution, and purified to give isomer A of the title compound as colorless crystals (R f = 0.25, (Hexane hexane 4: 1 ethyl acetate) was obtained as colorless needles in an amount of 0.21 g. Isomer B ( R f = 0.43, cyclohexane 4: 1 ethyl acetate) was obtained as a colorless oil, 0.54 g, and this oil was converted into a hydrochloride to obtain 0.52 g as colorless crystals.

 Isomer A

 Melting point: 1 1 3 _ 1 1 4

NMR spectrum _{(CDC1 3) δ ppm 0.91 (} 3H, t, J = 7.3Hz), 1.47 (3H, d, J = 6.7Hz), 1.69 (1Η, br. S), 2.20-2.40 (2H, m) 3.76 (1H, q, J = 6.7Hz), 5.82 (1H, s), 7.20-7 • 67 (12H, m), 7.80-8.00 (2H, m).

 Isomer B

 Melting point: 203-205 ° C (decomposition)

NMR spectrum (d ₆ -DMS0) δ ppm: 0.84 (3H, t, J = 7.3 Hz), 1.72 (3H, d. J = 6.2 Hz), 2.45-2.60 (2H, m), 4.20-4.40 ( 1H, br.s), 6.42 (1H, br.s), 7.25-8.05 (13H, m), 8.72 (1H, d, J = 7.5Hz), 10.15-10.35 (1H, br.s), 11.10-11.35 (1H, br.s) „Example 30-

N—t ert —butyl- [phenyl— (2-phenylsulfonylphenyl) methyl] amine hydrochloride (Exemplary compound number 1 1 1 5 1 2)

 (30 a) N _ t er t —butyl— [phenyl (2-phenylthiophenyl) methyl] amine oxalate

 5 OO mg of 2-phenylthiobenzophenone and 0.36 ml of tert-butylamine were reacted in the same manner as in Example (2a) and purified to give the title compound as colorless crystals. O mg was obtained.

 Melting point: 178-180 (decomposition)

 NMR spectrum (ds-DMSO) δ ppm: 1.16 (9H, s), 6.00 (1Η, s), 7.20-7.65 (13H, m), 8.13 (1H, d, J = 7.9Hz) .

 (30b) N—t ert —butyl- [phenyl— (2-phenylsulfonylphenyl) methyl] amine hydrochloride

Example (30a) of N-tert-butyl-phenyl- (2-phenylphenylthio) (Phenyl) methyl] amine oxalate Using 200 mg, 1.6 ml of trifluoroacetic acid and 0.3 ml of 30% aqueous hydrogen peroxide, the reaction was carried out in the same manner as in Example (2b). Purification gave 11 O mg of the title compound as colorless crystals.

 Melting point: 25 2-25 3 (decomposition)

NMR spectrum _{(d e -DMS0) δ ppm:} 1.23 (9H, s), 6.62 (. 1Η, br s), 7.20-8.05 (13H, m), 8.88 (1H, d, J = 8.0Hz), 9.64 (1H, br.s, J-9.6Hz), 9.95-10.20 (1H, br.s) Example 3 1

 N-cyclohexyl [phenyl (2-methylsulfonyl-6-methoxyphenyl) methyl] amine salt (Exemplary Compound No. 1-910)

 (31a) N-cyclohexyl [phenyl (2-methylthio-6-methoxyphenyl) methyl] amine oxalate

 Using 30 mg of 2-methylthio-16-methoxybenzophenone obtained in Reference Example 14 and 0.26 ml of cyclohexylamine, the reaction was carried out in the same manner as in Example (2a), and purification was performed. The imino form obtained in the above was reacted in the same manner as in Example 27 using 0.57 m 1 of a 10 mol solution of borohydride-dimethyl sulfide complex, purified, and the title compound was converted to colorless crystals. 26 mg were obtained.

 Melting point: 173-174 (decomposition)

NMR spectrum _{(d 6 -DMS0) δ ppm:} 0.90-2.10 (10H, m), 2.50-2.70 (1H, m), 3.88 (3H, s), 5.82 (1H, s), 7.00-7.60 (8H, m).

 (3 1 b) N-cyclohexyl [phenyl (2-methylsulfonyl-6-methoxyphenyl) methyl] amine oxalate

Example 31-N-cyclohexyl [phenyl- (2-methylthio-16-methoxyphenyl) methyl] amine oxalate 26 mg, 1.0 ml of trifluoroacetic acid and 0.3 ml The reaction was carried out in the same manner as in Example (2b) using 30% aqueous hydrogen peroxide and purified to obtain 11.5 mg of the title compound as colorless crystals. Melting point: 9 2-9 5 (decomposition)

NMR spectrum _{(d e -DMS0) δ ppm:} .... 1.00-1 0 (5H, m) 1.45-2 15 (. 5H m), 2. 50-2 70 (1H, m), 3.09 (3H , s), 3.83 (3H, s), 6.40-6.80 (1H.br.s), 7.20-7.75 (8H, m).

 Example 3 2

 N-{4-(1 -Phenyl-1-[(N- (1 R)-1-Phenylethyl) amino] methyl) phenyl]-N '-p-Toluenesulfonyldiarea (Exemplary compound number 1- 1 7 9 1)

 (32a) N — ((1R) —1—phenylethyl) — {phenyl-2- [N-acetylamino) phenyl] methyl} amine

 The reaction was carried out in the same manner as in Example (2a) using 1.08 mg of 4- (N-acetylamino) benzophenone and 1.15 ml of (R) -1-phenylethylamino. Purification gave 1.34 g of a mixture of isomers of the title compound as a pale yellow foam.

NMR spectrum _{(CDC1 3) δ ppm: 1.35} (3H, d, J = 6.7Hz), 2. 12 and 2.15 (total 3 11, respectively 5), 3.65 (1H, q , J = 6.7Hz), 4.59 (1H, s), 7.11-7.64 (15H, in) „

 (32b) N-((1R) —1—phenylethyl) [phenyl (4-aminophenyl) methyl] amine

N-((1R) -11-phenylethyl)-{phenyl- [4-N-acetylamino) phenyl] methyl} amine obtained in Example (32a) in 20 ml of 1.3 g After 5 ml of concentrated hydrochloric acid was added to the methanol solution and the mixture was stirred at room temperature, the mixture was heated under reflux for 1 hour. After the reaction solution was cooled to room temperature, 10 O ml of water was added, and the mixture was washed with methylene chloride. After the aqueous layer was neutralized with excess sodium bicarbonate, it was extracted with ethyl acetate. The extract was washed with saturated saline and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (eluting solvent: cyclohexane ethyl acetate = 5Z1-1 to 1) to give 35 O mg of isomer A of the title compound as a colorless oil, 38 O mg of Form B was obtained as a colorless oil. Isomer A

NMR spectrum _{(CDC1 3) δ ppra 1. 35} (3H. D, J = 6. 7Hz), 3. 69 (1Η, q. J = 6. 7Hz). 4. 53 (1H, s), 6.65 (2H, d, J = 8.4Hz) 7.09 (2H, d, J = 8.4Hz), 7.11-7.35 (10H, m) isomer B

NMR spectrum _{(CDC1 3) δ ppm 1. 35} (3H, d. J = 6. 7Hz), 3. 65 (1H, q. 6. 7Hz), 4. 53 (1H, s), 6. 56 (2H, d, J = 8.5Hz) 7.04 (2H.d, or 8.4Hz), 7.18-7.35 (10H, m) ₀

(32C) N- {4- (1-phenyl: [(N- (1R) -1—phenylethyl) amino] methyl) phenyl} -N'p-toluenesulfonyldiarea

The reaction was carried out in the same manner as in Example (45a) using 232 mg of isomer 8 of Example (3213) and 0.12 ml of p-toluenesulfonyl isocyanate. Purification gave 25.5 mg of isomer A of the title compound as a yellow powder.

 Isomer A

 Melting point: 1 1 5 — 1 1 8 (decomposition)

 NMR spectrum (c_DMS0) <3 ppm: 1.29-1.40 (3H, br.s), 2.37 (3Η.s) .3.45 -3.75 (1H, in), 4. 35-4.80 (1H, m), 7.15-7.41 (16H, m), 7.80 d, J = 8.1 Hz), 8.73 (1H, s)

 264 mg of isomer B of Example (32b) was reacted in the same manner as in Example (45a) using 0.13 ml of p-toluenesulfonyl isocyanate. Purification gave 55.O mg of isomer B of the title compound as a white powder.

 Isomer B

 Melting point: 1 0 1 — 1 0 2

NMR spectrum _{(CDC1 3) δ ppm: 1.} 38 (3H, d, J = 6. 8Hz), 2. 41 (3H, s), 3. 68 (1 H, q, J = 6. 7Hz), 4.60 (1H, s), 7.20-7.36 (16H, m), 7.78 (2H, d, J = 8.4 Hz), 8.38 (1H.br.s).

 Example 3 3

N — {3-(1 phenyl-1 [[N — (1 R) — 1 phenylethyl) Mino] methyl) phenyl} -N'-i-p-toluenesulfonylprea (Exemplary Compound No. 1-17779)

 (33a) N-((1R) -1_phenylethyl)-{phenyl- [3-N-acetylamino) phenyl] methyl} amine

 2. Using Og of 3_ (N-acetylamino) benzophenone and 2.13 ml of (R) 111-phenylethylamine, react in the same manner as in Example (2a) and purify the product. Thus, 2.64 g of an isomer mixture of the title compound was obtained as a pale yellow foam.

NMR spectrum _{(CDC1 3) <5 ppm:} . 1.34 and 1.35 (total 3H, each d, 6.6Hz) 2 · 07 and 2.10 (total 3H, each s), 3.6 WINCH 3.71 (. 1H m), 4.59 And 4.60 (total 1H, s each), 7.00-7.67 (15H, m) „

 (33b) N — ((1R) —1_phenylenyl) 1- [phenyl (3-aminophenol) methyl] amine

 N-((1R) -1_phenylethyl) obtained in Example (32a)-{phenylu [3-N-acetylamino) phenyl] methyl} amine 2.64 g was used. The reaction was carried out in the same manner as in Example (32b) and purification was performed to obtain 287 mg of isomer A of the title compound as a colorless oil and 265 mg of isomer B as a colorless oil.

 Isomer A

NMR spectrum _{(CDC1 3) δ ppm: 1.36} (3H, d, J = 6.7Hz), 3.72 (1H, q, J = 6.7Hz), 4.53 (1H, s), 6.56 (1H, d, J = 6.8 Hz), 6.67 (1H, s), 6.72 (1H, d, J = 7.8 Hz), 7.10 (1 H, dd, J = 7.8 Hz), 7.16-7.36 (10H, m)

 Isomer B

NMR spectrum _{(CDC1 3) δ ppm: 1.36} (3H, d, J = 6.7Hz), 3.66 (. 1H, q J = 6.7Hz), 4.53 (1H, s), 6.50 (1H, dd, J = l .6Hz, J = 7.9Hz), 6.63-6.68 (2H, m), 7.03 (1H, dd. J = 7.7Hz, J = 7.8Hz), 7.23-7.36 (10H, in).

(33 c) N-{3-(1 —phenyl— 1 — [(N— (1 R) — 1 —phenylethyl) amino] methyl) phenyl}-'1 p—toluenesulfonyldiarea 180 5018 Isomer A of Example (33) 3), reacted with 0.12 ml of p-toluenesulfonylusocyanate in the same manner as in Example (45a), and purified. 70 mg of the isomer A of the title compound was obtained as a white powder.

 Isomer A

 Melting point: 1 1 1 1 1 1 5 (softening)

NMR spectrum _{(CDC1 3) <3 ppm:} . 1. 0 (3H, d, J = 6.5Hz), 2.35 (3H, s) 3.72-3 .78 (1H, m), 4.58 (1H, s), 6.91-7.52 (16H, m), 7.83 (2H, d, J = 8.2Hz), 8.56 (1H, br.s)

 The same reaction as in Example (45a) was carried out by using 220 mg of isomer 8 of Example (3313) and 0.12 ml of p-toluenesulfonyl isocyanate. Purification gave 195 mg of isomer B of the title compound as a white powder.

 Isomer B

 Melting point: 1 0 7 — 1 1 1 (softening)

NMR spectrum _{(CDC1 3) δ ppm: 1.} 0 (. 3H, d, J = 6 1Hz), 2.38 (3H, s), 3.65-3 .75 (1H, m), 4.59 (1H, s), 6.92-7.48 (16H, m), 7.81 (2H, br.s), 8.56 (1H, br.s) Example 3 4

 N-cyclohexyl [phenyl-1,2- (4,4-dimethyl-5-N, N-dimethylsulfamoylphenyl) methyl] amine oxalate (Exemplary Compound No. 11-1876)

Reference Example 28 Using 41 mg of 2,4-dimethoxy-5-N, N-dimethylsulfamoylpenzophenone obtained in Reference Example 8 and 0.61 ml of cyclohexylamine, an example was carried out. The reaction was carried out in the same manner as in (2a), and 45 mg of the imino form obtained by purification and 0.0145 ml of a 1 OM solution of borohydride-dimethylsulfide complex were used. The reaction was carried out in the same manner and purification was performed to obtain 41.2 mg of a free form of the title compound as a yellow foam. Using this free form as oxalate, The product was obtained as white powder (18.2 mg).

NMR spectrum _{(d 6 -DMS0) <5 ppm} :. 0.99-1 19 (3H, m), 1. 0- 1.40 (. 2H m), 1. 48- 1.58 (1Η, m), 1.65-1.78 ( 2H, m), 1.95-2.13 (2H, m), 2.50-2.70 (1H, m), 2.65 (6 H, s), 3.93 (3H, s), 3.96 (3H, s), 5.71 (1H, br. S), 6.84 (1H, s), 7.29-7.58 (5H, in), 7.95 (1H, s).

 Example 3 5

 N-cyclohexyl [1-naphthyl- (2-methylsulfonylphenyl) methyl] amine (Exemplary Compound No. 2—290)

 (35a) N-cyclohexyl [1-naphthyl- (2-methylthiophenyl) methyl] amine oxalate

 As in Example (2a), using 2.34 g of 2—N-methylthiophenyl— (1-naphthyl) ketone obtained in Reference Example 15 and 1.92 ml of cyclohexylamine And 2.73 g of the title compound was obtained as pale yellow crystals. Melting point: 1 8 9-1 9 1 (decomposition)

NMR spectrum _{(CDC1 3) δ ppm: 1.00-1.30} (4H, m), 1.45-1.90 (5Η, m), 2. 10 -2.30 (2Η, m), 2.67 (3Η, s), 3.05-3. 20 (1Η, m), 6.74 (1H, s), 6.95-8.15 (11H, m) ₀

(35b) N-cyclohexyl— [1-naphthyl— (2-methylsulfonylphenyl) methyl] amine

 N-Cyclohexyl [1-naphthyl- (2-methylthiophenyl) methyl] amine oxalate of Example (35a) 2.73 g, 15 m 1 of trifluoroacetic acid and 3.0 m 1 of 3 The reaction was carried out in the same manner as in Example (2b) using 0% aqueous hydrogen peroxide, followed by purification to obtain 363 mg of the title compound as colorless crystals.

 Melting point: 1 3 9-1 4 1

NMR spectrum _{(CDC1 3) δ ppm:.} .. 1.00-1 80 OH, m), 1.85-2.20 (2H m), 2.55 -2 70 (1H, m), 2.83 (3H, s), 7. 16 (1H, d, J = 7.1Hz), 7.20-7.90 (8H,), 8.15 (1H, dd, 1 = 1.2Hz, J = 7.9Hz), 8.34 (1H, d, J = 8.3Hz) . Example 3 6

 N-((1R) -11-cyclohexylethyl)-{phenyl [3- (1H-tetrazol-5-yl) phenyl] methyl} amine (Exemplary Compound No. 1151-15)

 (36a) N-((1R) _1-cyclohexylethyl) 1- [phenyl (3-cyanophenyl) methyl] amine

 5 OO mg of 3-cyanobenzophenone and 0.7 lml of (R) -1 -cyclohexylethylamine were reacted in the same manner as in Example (2a), purified, and purified. 557 mg of the title compound was obtained as a yellow oil.

NMR spectrum _{(CDC1 3) <5 ppm:} 0.94-1.26 (9H, m), 1.47-1.71 (5Η, m), 2.28 -2.44 (1H, m), 4.97 (1H, s), 7.22-7.77 (9H , m) „

 (36b) N-((1R) 1-1-cyclohexylethyl) -1- {phenyl [31- (1H-tetrazol-5-yl) phenyl] methyl} amine

 Example N-((1R) -1—cyclohexylethyl)-[phenyl (3-cyanophenyl) methyl] amine of (36a) 550 mg, 337 mg of sodium azide and 1 The reaction was carried out in the same manner as in Example 1 using 40 ml of tri-n-butyltin tin chloride, and purification was performed to obtain 132 mg of the title compound as colorless crystals. Melting point: 2 1 6—2 1 8

 NMR spectrum (c—DMSO) δ ppm: 0.94-1.26 (8H, m), 1.47-1.71 (6Η, m), 2.53-2.56 (1Η, m), 5.39 (1H, m), 7.25-7.60 (7H, m), 7.89 (1H, d, J = 7.7Hz), 8.24 (1H, d, J = 6.0Hz).

 Example 3 7

 N— (1-ethylpentyl) 1-phenyl [4- (1H-tetrazol-5-yl) phenyl] methyl} amine (Exemplary Compound No. 1-530)

(37a) N- (1-Ethylpentyl) -1- [phenyl- (4-cyanophenyl) methyl] amine The reaction was carried out in the same manner as in Example (2a) using 1.O g of 4-cyanobenzophenone and 1.46 g of 1-ethylpentylamine hydrochloride, followed by purification. 1.44 g of the compound was obtained as a pale yellow oil.

NMR spectrum _{(CDC1 3) δ ppm: 0.75-0.95} (6H, m), 1. 15-1.55 (9Η, m), 2.30 -2.42 (1Η, m), 4.98 (1H, s), 7. 10- 7.60 (9H, m) ₀

 (37b) N- (1-ethylpentyl) -l-phenyl- [4- (1H-tetrazol-5-yl) phenyl] methyl} amine

 Example (37a) of N— (1-ethylpentyl) -1- [phenyl (4-cyanophenyl) methyl] amine 1.16 g, 0.74 g of sodium azide and 3.1 ml of toluene The reaction was carried out in the same manner as in Example 1 using l-n-butyltin chloride, followed by purification to obtain 687 mg of the title compound as colorless crystals.

 Melting point: 2 1 9 — 2 2 1

NMR spectrum (d ₆ -DMS0) δ ppm: 0.75-0.95 (6H, π), 1.10-1.60 (8Η, m), 2.40-2.55 (1Η, m), 5.26 (1H, s), 7.20-7.45 (3H, m), 7.54 (2H, d, J = 7.7Hz), 7.66 (2H, d, J = 7.3Hz), 7.98 (2H, d, J = 8.2Hz).

 Example 3 8

 N- (1-ethylpentyl) -1- [phenyl (2-ethylsulfonylphenyl) methyl] amine hydrochloride (Exemplary Compound No. 1 — 1 1 3 8)

 (38a) N— (1-ethylpentyl) -1- [phenyl— (2-ethylthiophenyl) methyl] amine oxalate

 Using 0.50 g of 2 -ethylthiobenzophenone obtained in Reference Example 6 and 0.63 g of 1 -ethylpentylamine hydrochloride, the reaction was carried out in the same manner as in Example (2a). Purification gave 0.59 g of the obtained yellow oil as oxalate and 0.447 g of the title compound as colorless crystals.

 Melting point: 1 3 1 — 1 3 3

NMR spectrum _{(CDC1 3) δ ppm: 0.82-1.05} (6H, m), 1.20-1.45 (7Η, HI), 1.65 -1.95 (4H, m), 2.85-3.05 (3H, m), 6.07 (1H, s), 7.20-7.70 (9H, m).

 (38) N— (1-ethylpentyl)-[phenyl- (2-ethylsulfonylphenyl) methyl] amine hydrochloride

 N- (1-Ethylpentyl) -1- [phenyl (2-ethylthiophenyl) methyl] amine oxalate of Example (38a) 0.45 g, 2.5 ml of trifluoroacetic acid and 0.6 The same reaction as in Example (2b) was carried out using m 1 of 30% aqueous hydrogen peroxide, followed by purification to obtain 0.35 g of the title compound as colorless crystals.

 Melting point: 1 7 6-1 7 8 * (decomposition)

NMR spectrum (d ₆ —DMS0) <5 ppm: 0.80-1.40 (13H, m), 1.55-2.00 (4H, ηι), 3.05-3.30 (2Η, m), 6.81 (1H, s), 7.20-7.50 (6H, m), 7.60-7.70 (1H, m), 7.93 (1H, d, J = 6.9Hz), 8.02 (1H.dd, J = l.2Hz, J = 7.9Hz).

 Example 3 9

 N-cyclohexyl—. {Phenyl [2- (2-methylsulfonylphenyl) phenyl] methyl} amine (Exemplary Compound No. 187-17)

 (39 a) N-cyclohexyl {phenyl [2 — (2 —methylsulfonylphenyl) phenyl] methyl} amine oxalate

 Reaction was carried out in the same manner as in Example (2a) using 0.99 g of 2— (2-methylthiophenyl) benzophenone obtained in Reference Example 17 and 0.76 ml of cyclohexylamine. The residue was purified to give 925 mg of the title compound as colorless crystals.

 NMR spectrum (CDCls) 6 ppm: 0.90-2.15 (11H, m), 2.40 (3H, s), 2.85-3.0 O (lH'm), 5.11 (1H, s), 6.74 (1H, d, J = 7.7Hz), 7.10-7.70 (11H, m), 8.08 (1H, d, J = 7.7Hz).

 (39b) N-cyclohexyl {phenyl [2- — (2-methylsulfonylphenyl) phenyl] methyl}

Example 9 (39a) N-cyclohexyl {phenyl [2- (2-methylthiophenyl) phenyl] methyl] ammonium oxalate 925 mg, 10 ml The reaction was carried out in the same manner as in Example (2b) using fluoroacetic acid and 3. O ml of 30% aqueous hydrogen peroxide, followed by purification to obtain 70 mg of the title compound as pale pink crystals. Melting point: 1 3 7-1 3 8:

NMR spectrum _{(CDC1 3) δ ppm: 0.80-1.25} (6H, m), 1.30-1.95 (. 5Η m), 2.15 -2.30 (1Η, m), 2.90 (3H, s), 4.87 (1H, s) , 6.94 (1H, d, J = 7.5 Hz), 7.03-7.75 (10H, m), 7.95 (1H, d, J = 7.8 Hz), 8.31 (1H, d, 1 = 1.9 Hz).

 Example 40

 N-cyclohexyl {phenyl (4 — (2-methylsulfonylphenyl) phenyl] methyl} amine oxalate (Exemplary Compound No. 1-176)

 (40a) N-cyclohexyl {phenyl (4- (2-methylthiophenyl) phenyl] methyl} amine

 Reaction was carried out in the same manner as in Example (2a) using 0.93 g of 4- (2-methylthiophenyl) benzophenone obtained in Reference Example 18 and 0.7 lml of cyclohexylamine. And purified to give 1.14 g of the title compound as a pale yellow oil.

NMR spectrum _{(CDC1 3) δ ppm: 1.00-1.30} (6H, m), 1.50- 1.75 (. 3Η m), 1.85-2.05 (2Η, m), 2.35 (3Η, s), 2.35-2.50 (1Η, m), 5.08 (1H, s), 7.10-7.50 (13H, m).

 (40b) N-cyclohexyl— {phenyl [4-1 (2-methylsulfonylphenyl) phenyl] methyl] amine oxalate

 Example 1 (12a) N-cyclohexyl {phenyl [4- (2-methylthiophenyl) phenyl] methyl} amine 1.12 g, 5.O ml of trifluoroacetic acid and 1.0 ml The reaction was carried out in the same manner as in Example (2b) using 30% aqueous hydrogen peroxide and purified to obtain 1.26 g of the title compound as colorless crystals.

 Melting point: 2 1 7 — 2 19 ° C

NMR spectrum _{(d e -DMS0) δ ppm:} 1.05-2.30 (10H, ra), 2.65-2.80 (1 Η, m), 2.89 (3Η, s), 5.76 (1Η, s), 7.40-7.90 (12H , m), 8.16 (1Η, d, J = 7.6Hz) „ Example 4 1

 N—n—butyl— [phenyl— (2-butylsulfonylphenyl) methyl] amine oxalate (Exemplary compound number 1—1410)

 (41a) N-n-butyl- [phenyl (2-butylthiophenyl) methyl] amine oxalate

 The reaction was carried out in the same manner as in Example (2a) using 50 O mg of 2-n-butylthiobenzophenone and 0.37 ml of n-butylamine, followed by purification to give a light brown oil. O mg was obtained. Using the obtained oil (533 g) and oxalic acid (146 mg), the title compound was obtained as colorless crystals (366 mg).

 Melting point: 1 5 1 — 1 5 3

NMR spectrum _{(CDC1 3) δ ppm: 0.79} (3H, t, J = 7.3Hz), 0.88 (3H, t, J = 7.3Hz), 1. 10-1.65 (8H, m), 2.72-2.96 (4H , m), 6.07 (1H, s), 7.15-7.60 (8H, m), 7.90-8.00 (lH, m).

 (4 1 b) N-n-butyl- [phenyl (2-butylsulfonylphenyl) methyl] amine oxalate

 281.2 mg of N-n-butyl- [phenyl (2-butylthiophenyl) methyl] amine oxalate of Example (41a) was neutralized with 360 mg of aqueous sodium bicarbonate. Of N—n-butyl- [phenyl (2-butylthiophenyl) methyl] amine, 2.0 ml of trifluoroacetic acid and 0.5 ml of 30% aqueous hydrogen peroxide. The reaction was carried out in the same manner as in Example (2b) and purification was carried out to obtain 342 g of the title compound as colorless crystals.

 Melting point: 1 1 1 — 1 1 3

NMR spectrum _{(CDC1 3) (5 ppm:} 0.77 (3H, t, J = 7.3Hz), 0.81 (3H, t, J = 7.3Hz), 1.08- 1. 35 (4H, m), 1.35-1.70 ( 4H, m), 2.55-3.05 (4H, m), 6.59 (1H, s), 7.25- 7.80 (7H, m), 8.04 (1H, d, J = 7.9 Hz), 8.16 (1H, d, (J = 7.6Hz) ₀

Example 4 2 N-((1R) -1 1-phenylethyl)-{phenyl-2 [3- (1H-tetrazol-5-yl) phenyl] methyl} amine hydrochloride (Exemplary compound number 1-489)

 (4 2 a) N— ((1 R) — 1 phenylethyl) 1 [phenyl (methyl)] amine

 6 Reaction with 2 lmg of 3-cyanobenzophenone and 0.77 ml of (R)-1-phenethylamine as in Example (2a), purification, and title compound. 293 mg of isomer A of the product was obtained as a pale yellow oil, and 328 mg of isomer B was obtained as a pale yellow oil.

 Isomer A

NMR spectrum (CDCl ₃ ) δ ppm: 1.38 (3H, d, 1 = 6.7 Hz), 3.59 (1H, q. J = 6.7 Hz, 13.3 Hz), 4.64 (1H, s), 7.10-7.65 (13H, m), 7.72 (1H, s).

 Isomer B

NMR spectrum _{(CDC1 3) <5 ppm:} 1. 37 (3H, d, J = 6.6Hz), 3.66 (1H, q, J = 6.6Hz, have 13.2Hz), 4.61 (1H, s ), 7. 15-7.55 (13H, m), 7.65 (1H, s) ₀

 (4 2 b) N— ((1 R) — 1 phenylethyl) 1 {phenyl [3 — (1 H-tetrazo-1-yl 5 —yl) phenyl] methyl} amine hydrochloride

 The reaction was carried out in the same manner as in Example 1 using 293 mg of isomer A of Example (42a), 183 mg of sodium azide and 0.8 lml of tri-n-butyltin chloride. Purification gave 102 mg of isomer A of the title compound as colorless crystals.

 Isomer A

 Melting point: 2 4 7 — 2 4 9 (decomposition)

NMR spectrum (d ₆ -DMS0) δ ppm: 1.69 (3H, d, J = 6.7 Hz), 4.05-4.20 (1H, m), 5.46 (1H, s), 7.30-8.10 (13H, m), 8.34 (1H, s).

Reaction with 288 mg of isomer B of Example (42a), 204 mg of sodium azide and 0.9 O ml of tri-n-butyltin chloride in the same manner as in Example 1 The residue was purified to give 144 mg of isomer B of the title compound as colorless crystals.

 Isomer B

 Melting point: 1 7 4 (decomposition)

 NMR spectrum (c-DMSO) δ ppm: 1.70 (3H.d, J = 6.7Hz), 4.10-4.25 (1H, m), 5.30 (1H, s), 7.30-8.10 (13H , m), 8.33 (1H, s).

 Example 4 3

 N-((1R) —1 phenylethyl) 1-phenyl (3— [2— (2—methylphenyl) phenylsulfonylcarbamoyl] phenyl) methyl} amine hydrochloride (Exemplary compound number 1—80 2)

 (4 3 a)-((1 R) — 1 —phenylethyl) — {phenyl (3 — [2-(2 —methylphenyl) phenylsulfonylcarbamoyl〗 phenyl) methyl} amine

 N- [2- (2-Methylphenyl) phenylsulfonyl] —3-benzoylbenzamide obtained in Reference Example 19—250 mg and 0.14 ml of (R) —1-phenylphenylamine The reaction was carried out in the same manner as in Example (2a) and purified to obtain 100 mg of the title compound, Isomer A as a colorless oil, and 53 mg of Isomer B, as a colorless foam. Was.

 Isomer A

NMR spectrum _{(CDC1 3) δ ppm: 1.37} (3H, d, J = 6.2Hz), 1.82 (. 1.2H s), 1.85 (1.8H, s), 3.50-3.70 (1H, m), 4. 63 (1H, s), 6.80-7.75 (22H, m), 8.42 (1H, d, J = 7.2 Hz).

 Isomer B

NMR spectrum _{(CDC1 3) δ ppm:.} 1.37 (3H, d, J = 6.7Hz), 1.87 (. 1.4H s), 1.90 (. 1.6H s), 3.66 (1H q, J = 6.7Hz, J = 13.3Hz), 4.61 (1H, s), 6.85-7.70 (22H, m), 8.40 (1H, d, J = 8.1Hz).

(4 3 b) N-((1 R) — 1 _phenylenyl)-{phenyru (3 — [2 -(2-Methylphenyl) phenylsulfonylcarbamoyl〗 phenyl) methyl} amine hydrochloride

 The isomer Al O O mg of Example (43a) was dissolved in 2.O ml of ethyl acetate, 0.045 ml of a 4N hydrochloric acid / dioxane solution was added, and the mixture was concentrated under reduced pressure. The obtained residue was dissolved in 0.5 ml of ethyl acetate, and 10 ml of ether was further added to obtain 51 mg of the title compound as pale yellow crystals.

 In a similar manner, 3 O mg of the title compound was obtained as pale yellow crystals from 50 mg of isomer B of Example (43a) and a solution of 0.022 m 1 of 4 N hydrochloric acid / dioxane.

 Isomer A

 Melting point: 1 7 2 17 5 ° C

NMR spectrum (d ₆ —DMSO) δ ppm: I.67 (3H, d, J = 6.5 Hz), I.85 (1.7H.s), 1.89 (1.3H, s), 4.00-4.20 ( 1H, m), 5.36 (IH, s), 6.83-8.20 (22H, m), 9.90-10.15 (1H, m), 10.30-10.55 (1H, m), 12.14 (1H, br .s) ₀

 Isomer B

 Melting point: 1 7 2-1 75

NMR spectrum _{(d 6 -DMS0) δ ppm:} 1.67 (3H, d, J = 6.6Hz), 1.85 (1.5H, s), 1.86 (1. 5H, s), 4.05-4.20 (1H, m), 5.17 (1H, s), 6.85-8.20 (22H, m), 10.00-10.20 (1H, m), 10.50-10.70 (1H, m), 12.11 (1H, br. S).

 Example 4 4

 N — ((1R) 1-111phenylethyl) -1- [phenyl (2-butylbutylphenyl) methyl] amine hydrochloride (Exemplary compound number 1—1456)

 (4 4 a) N— ((1 R) — 1 phenylethyl)-[phenyl (2-butylthiophenyl) methyl] amine

The reaction was carried out in the same manner as in Example (2a) using 666 mg of 2-n-butylthiobenzophenone and 0.63 ml of (R) -1 monophenylethylamine, followed by purification. 919 mg of a light brown oil was obtained. NMR spectrum _{(CDC1 3) δ ppm:.} 0.87 (3H, in), 1. 0-1.55 (7H, m), 2.62- 2.80 (2H, m), 3.60-3.80 (1H, m) 5.21 (0.5H , s), 5.36 (0.5H, s), 7.10-7.70 (14H.m

) o

 (44b) N-((1R) _1 1-Phenylethyl) -1- [phenyl (2-butylsulfonylphenyl) methyl] amine hydrochloride

 908 mg of the example (44a) of N — ((1R) —1—phenylethyl)-[phenyl (2-butylthiophenyl) methyl] amine and 1.5 ml of trifluorophenol The reaction was carried out in the same manner as in Example (2b) using acetic acid and 4.0 ml of 30% aqueous hydrogen peroxide, and the mixture was purified to give the isomer A of the title compound as colorless crystals (402 mg, 201 mg of isomer B was obtained.

 Isomer A

 Melting point: 1 3 5 (decomposition)

NMR spectrum _{(CDC1 3) δ ppm 0.57 (} 3H, t. There 7 · 2Ηζ), 0.80-1.35 (7H . In), 1.85-2.05 (2H, m), 3.90-4.05 (1H, m) 6.43 (1Η , br. s), 7.10-8.00 (13H, m). 8.75-8.90 (1H, m).

 Isomer B

 Melting point: 209 (decomposition)

NMR spectrum _{(CDC1 3) δ ppm: 0.94} (. 3H, t, J = 7 1Hz), 1.25-1.65 (4H, m), 1.73 (3H, d, J = 6.9Hz), 2.65-2.98 (2H, m), 4.20-4.35 (1H, m), 6.32 (0.5H, s), 6.35 (0.5H, s), 7.30-7.95 (13H, m), 8.64 (1H, d, J = 8.1 Hz),

 Example 4 5

 N- {2- [1_phenyl-2- (N— (1R) —1-phenylethyl) amino] methyl} phenyl N'—tosyl peracid oxalate (Exemplified compound number 1 1 1 1 7 3 9)

 (45 a) N-(2 -benzoylphenyl) — N '— tosylperia

50 O mg of 2-aminobenzophenone and 0.385 ml of p-toluenesul After dissolving honyl isocyanate in 20 ml of anhydrous benzene and heating under reflux for 4 hours, the reaction solution was diluted with 100 ml of ethyl acetate, and 10% aqueous hydrochloric acid, saturated saline and saturated sodium bicarbonate were used. The extract was washed with saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel chromatography (elution solvent: cyclohexane Z-ethyl acetate = 3 Z 1) to obtain 60 O mg of the title compound as a pale yellow foam.

NMR spectrum _{(CDC1 3) (5 ppm:} 2.37 (3H, s), 7.05-8.00 (14H, m).

 (45b) N— {2- [1-Phenyl-1-1 (N— (1R) —1-Phenylethyl) amino] methyl} phenyl—N′—Trisylureacitrate

 Using 600 mg of the example (45a) of N— (2-benzoylphenyl) —X′—tosylperia and 0.39 ml of (R) —1—phenylenylamine Then, the reaction was carried out in the same manner as in Example (2a), and the mixture was purified. 85.9 mg of isomer A of the title compound as pale yellow crystals and oxalate of isomer B as oxalate were prepared as pale yellow crystals. mg was obtained. Isomer A

 Melting point: 1 3 4 _ 1 3 6

NMR spectrum _{(d s - DMS0) <5} ppm: 1.46 (3H, d, J = 6.7Hz), 2.44 (3Η, s), 3.6 2 (.. 1Η q, J = 6.7Hz J = 13.5Hz), 4.70 (1H, s), 6.90-7.90 (18H.m).

 Isomer B

 Melting point: 1 2 7 — 1 2 9 (decomposition)

NMR spectrum (d _e —DMS0) δ ppm: 1.0 (3H, d, J = 2.7 Hz), 2.39 (3H, s), 3.60-3.75 (1H, m), 4.76 (1H, s), 6 · 90-7.90 (18H, m).

 Example 4 6

 N-((1R) -11-phenylethyl)-{2-benzothiazolyl [3— (1H-tetrazol-5-yl) phenyl] methyl} amine (Exemplified Compound No. 3-470)

(4 6 a) N— ((1 R) 1 1 1 phenylethyl) 1 [2 —benzothiazolyl -(3_Cyanophenyl) methyl] amine

 Reference Example 20 From 53 O mg of (2—benzothiazolyl) —3—cyanophenylketone obtained in 20 and 0.5 lml of (R) —1—phenylethylamine, the working example (2 The reaction was carried out in the same manner as in a) and purification was carried out to obtain 685 mg of the title compound as a yellow foam.

NMR spectrum _{(CDC1 3) (5 ppm:} 1. 35- 1.55 (3H, m), 3.71 (0.4Η, q, J = 6.7Hz, J = 13.3Hz), 3.91 (0.6H, q, J = 6.7 Hz, J = 13.3Hz), 5.05 (0.4H.s), 5.08 (0.6H, s), 7.10-8.10 (13H, m).

 (46 b) N-((1 R) — 1 monophenylethyl) — {2 — benzothiazolyl-[3-(1 H-tetrazol-5-yl) phenyl] methyl} amine

 Example (46a) of N _ ((1R) —1—phenylethyl) — [2-benzothiazolyl- (3-cyanophenyl) methyl] amine 3884 mg and 203 mg of sodium azide and 0 The reaction was carried out in the same manner as in Example 1 using 8-9 ml of tri-n-butyltin chloride, and the product was purified to obtain 63 mg of the title compound as colorless crystals. Melting point: 1 7 7-1 7 8 (decomposition)

NMR spectrum (c-DMSO) δ ppm: 1.30-1.50 (3H, m), 3.60-4.00 (1Η, m), 5.00 (0.4H, s), 5.04 (0.6H, s), 7.20-8 . 15 (14H, m) ₀

 Example 4 7

 N-cyclohexyl [phenyl (2-n-propylsulfonylphenyl) methyl] amine (Exemplary Compound No. 1138)

 (47a) N-cyclohexyl [phenyl (2-n-propylthiophenyl) methyl] amine

 0.5 g of 2_n-propylthiobenzophenone and 0.5 ml of cyclohexylamine were reacted in the same manner as in Example (2a) and purified to give the title compound as a tan oil. 0.58 g was obtained as a product.

NMR spectrum _{(CDC1 3) δ ppm: 1.0} (3H, t, J = 7.3Hz), 0.97-1.29 (5H, m), 1. 43-1.71 (6H, m), 1.93-2.04 (2H, m), 2.36-2.44 (1H, m), 2.85-2.90 (2H, m), 5.64 (1 H, s), 7. 13-7.55 (9H, m).

 (47b) N-cyclohexyl [phenyl- (2-n-propylsulfonylphenyl) methyl] amine

 Example 47-N-cyclohexyl [phenyl (2-n-propylthiophenyl) methyl] amine 0.56 g, 2.4 ml trifluoroacetic acid and 0.93 ml The reaction was carried out in the same manner as in Example (2b) using 30% aqueous hydrogen peroxide, followed by purification to obtain 0.25 g of the title compound as colorless crystals.

 Melting point: 6 2 — 6 4

NMR spectrum _{(CDC1 3) δ ppm: 0.74} (3H, t, J = 7.5Hz), 0.98-1.69 (5H, m), 1 .69-1.73 (6H, m), 1. 73-2.06 (2H, m), 2.37-2.46 (1H, m), 2.66 (2H, m), 6.29 (1H, s), 7.20-8.04 (9H, m).

 Example 48,

 N-cyclohexyl-1-phenyl [4— (1H-tetrazol-5-yl) phenyl] methyl} amine hydrochloride (Exemplary Compound No. 1-552)

 (48a) N-Cyclohexyl [phenyl (4- (1-cyanophenyl) methyl] amine]

 The reaction was carried out in the same manner as in Example (2a) using 36 lmg of 4-cyanobenzophenone and 0.4 O ml of cyclohexylamine, followed by purification to give the title compound as a pale yellow oil. 562 mg were obtained.

NMR spectrum _{(CDC1 3) δ ppm: 1.00-1.30} (5H, m), 1. 0-2.00 (6Η, m), 2.30 -2.40 (1Η, m), 5.07 (1H, s), 7. 15- 7.65 (9H, m) ₀

 (48b) N-cyclohexyl {phenyl (41- (1H-tetrazol-5-yl) phenyl] methyl} amine hydrochloride

N-cyclohexyl- [phenyl- (4-cyanophenyl) methyl] amine of Example (48a) 546 mg, 366 mg of sodium azide and 1.61 m The reaction was carried out in the same manner as in Example 1 using tri-n-butyltin chloride of 1 and purified to obtain 319 mg of the title compound as colorless crystals.

 Melting point: 2 7 5-2 7 7 ° C (decomposition)

NMR spectrum _{(d e -DMS0) δ ppm:} 1.00- 1.80 (6H, m), 1.62- 1.82 (2Η, m), 2.

14- 2.30 (2Η, m), 2.70-2.90 (1Η, in), 5.88 (1H, s), 7.30-7.60 (3H, πι), 7.70-7.80 (2H.m), 7.90 -8.03 (2H, m), 8.10-8.20 (2H, m), 9.72 (1H.br.s) ₀

 Example 4 9

 N-cyclohexyl {phenyl (3- (1H-tetrazol-5-yl) phenyl] methyl} amine hydrochloride (Exemplary Compound No. 1—469)

 (49a) N-cyclohexyl [phenyl (3-cyanophenyl) methyl] amine

 4 Using 14 mg of 3-cyanobenzophenone and 0.46 ml of cyclohexylamine, react in the same manner as in Example (2.a) and purify the title compound to give a pale yellow oil. As a result, 53 lmg was obtained.

NMR spectrum _{(CDC1 3) δ ppu: 1.00-2.00} (10H, m), 2.30-2.40 (1H, m), 5. 1 0 (1H, s), 7.20-8.20 (9H, m) 0

 (49b) N-cyclohexyl {phenyl-2 [3- (1H-tetrazol-5-yl) phenyl] methyl} amine hydrochloride

 N-Cyclohexyl- [phenyl (3-cyanophenyl) methyl] amine of Example (49a) 53 1 mg, 3555 mg of sodium azide and 1.56 ml of tri-n— The reaction was carried out in the same manner as in Example 1 using butyltin chloride, followed by purification to obtain 455.3 mg of the title compound as colorless crystals.

 Melting point: 2 7 2-2 7 3 (decomposition)

NMR spectrum (d ₆ -DMSO) <5 ppm: 1.00-1.0 (2H, m), 1.30-1.80 (6H, m). 2.

15- 2.40 (2H.m). 2.70-- 2.90 (1H, m), 5.91 (1H, s), 7.30-7.90 (6H, m), 8.00-8.15 (2H, m). 8.45-8.50 (1H, m). Example 5 0

 N- (1 -ethylpropyl) 1 -phenyl [3-(1 1 ^ _tetrazol_ 5 1 -yl) phenyl] methyl} amine hydrochloride (Exemplary compound number 1-5 13)

 (50a) N- (1-ethylpropyl)-[phenyl (3-cyanophenyl) methyl] amine

 4 Using 14 mg of 3-cyanobenzophenone and 0.24 ml of 3-aminopentane, react in the same manner as in Example (2a) and purify the title compound to give the title compound as a pale yellow oil. As a result, 302 mg was obtained.

NMR spectrum _{(CDC1 3) δ ppni: 0.80-0.95} (6Η, m), 1.35- 1.60 (. 4Η m), 2.27 -2.40 (1H, m), 4.96 (1H, s), 7.20-7.80 (9H. m) ₀

 (50b) N— (1—Ethylpropyl) — {phenyl [3— (1H—tetrazol—5—yl) phenyl] methyl} amine hydrochloride

 Example (50a) of N- (1-ethylpropyl) -1- [phenyl- (3-cyanophenyl) methyl] amine 289 mg, 202 mg of sodium azide and 0.89 ml of trimethylamine The reaction was carried out in the same manner as in Example 1 using n-butyltin chloride, followed by purification to obtain 83 mg of the title compound as colorless crystals.

 Melting point: 2 2 9-23 2 ° C (decomposition)

NMR spectrum _{(d 6 - DMSO) <5} ppm: 0.75-0.95 (6H, m), 1.60-2.00 (4H, m), 2 .70-2.90 (1Η, m), 5.88 (1H, s), 7.30 -7.52 (3H, m), 7.60-7.90 (3H, m), 8.00-8.10 (2H, m), 8.50-8.55 (1H, m) ₀

 Example 5 1

 N-((1R) —1—cyclohexylethyl) — {phenyl [4— (1H-tetrazol-5—yl) phenyl] methyl} amine (Exemplified Compound No. 1159-188)

(5 1 a) N — ((1 R) — 1 — Cyclohexylethyl) [phenyl] (4 — cyanophenyl) methyl] amine The same reaction as in Example (2a) was carried out using 500 mg of 4-cyanobenzophenone and 0.7 lml of (R)-1-cyclohexylethylamine, purified and purified. Isomer A of the compound was obtained as a pale yellow oily substance (182 mg), and isomer B was obtained as a pale yellow oily substance (318 mg).

 Isomer A

NMR spectrum _{(CDC1 3) δ ppm:.} . 0.94-1 36 (9H, m), 1.61-1.81 (5Η, in), 2.27 -2 36 (1Η, m), 5.00 (1H, s), 7. 25-7. 33 (5H, m), 7.54-7.61 (4H, m)

 Isomer B

NMR spectrum _{(CDC1 3) (3 ppm:} . 0.91-1.40 (9H, m), 1.62- 1.77 (5H m), 2.35 -2.44 (1H, m), 4.98 (1H, s), 7. 19-7 . 36 (5H, m), 7.52-7.59 (4H, m)

 (51b) N-((1R) 1-1-cyclohexylethyl)-{phenyl [4- (1H-tetrazol-5-yl) phenyl] methyl} amine hydrochloride

 As in Example 1 with 177 mg of isomer A of Example (51a), 109 mg of sodium azide and 0.46 ml of tri-n-butyltin chloride The purified product was purified to give 149 mg of the hydrochloride salt of isomer A of the title compound as colorless crystals.

 Isomer A

 Melting point: 2 4 3— 2 4 5: (decomposition)

NMR spectrum (d _e —DMS0) δ ppm: 0.91-1.36 (6H, m), 1.61-1.82 (4Η, m), 1.91-2.02 (1Η, m), 2.87-2.90 (1H, m ), 5.81 (1H, s), 7.35-7.48 (3H, m), 7.85 (2H, d, J = 7.2 Hz), 8.03 (2H, d, J = 8.3 Hz), 8.15 (2H, d , J = 8.3 Hz), 9.37-9.89 (2H.m).

 306111 The isomer B of Example (513), 250 mg of sodium azide and 1.04 ml of tri-n-butyltin chloride were prepared in the same manner as in Example 1. The reaction was purified, and 185 mg of the title compound isomer B was obtained as colorless crystals. Isomer B

Melting point: 2 3 5 — 2 3 8 T; NMR spectrum (d ₆ — DMS0) δppra: 0.89-1.38 (9H, m), 1.45-2.56 (6H, m) .5.27 (1H, s), 7.26-7.39 (3H, ni), 7.53 ( 2H, d, J = 7.2Hz), 7.66 (2H, d, J = 8.3Hz), 7.98 (2H, d, J = 8.3Hz).

 Example 5 2

 N-C (1R) -1- (4-bromophenyl) ethyl]-(phenyl- [4- (1H-tetorazol-5-yl) phenyl] methyl} amine (Exemplified Compound No. 1-600)

 (52a) N — [(1R) 111- (4-bromophenyl) methyl]-[phenyl-1- (4-cyanophenyl) methyl] amine

 Reaction was carried out in the same manner as in Example (2a) using 518 mg of 4-cyanobenzophenone and lg (R) -11- (4-promophenyl) ethylamine, and the title compound was purified. Isomer A was obtained as colorless crystals, 347 mg, and Isomer B was obtained as pale yellow oil, 266 mg. -Isomer A

NMR spectrum _{(CDC1 3) δ pm 1.35 (} 3H, d, J = 6.6Hz), 3.57 (1H, q, J = 6.6Hz), 4.62 (1Η, s), 7.07 (2H, d, J = (8.3Hz) 7.19-7.28 (5H, m), 7.46 (2H, d, J = 8.3Hz), 7.62 (2H, d, J = 8.3Hz)

 Isomer B

NMR spectrum _{(CDC1 3) δ ppm: 1.34} (. 3H, d J = 6.6Hz), 3.64 (1H, q, J = 6.6Hz), 4.59 (lH, s), 7.13 (2H, d, J = 8.5 Hz), 7.21-7.48 (9H, m), 7.53 (2H, d, J = 8.3Hz) ₀

(52b) N-[(1R) -1- (4-bromophenyl) ethyl] 1- {phenyl [4— (1H-tetrazol-5-yl) phenyl] methyl} amine

Reaction was carried out in the same manner as in Example 1 using 247 mg of isomer A of Example (52a), 123 mg of sodium azide and 0.5 lml of tri-n-butyltin chloride. The residue was purified to give 135 mg of isomer A of the title compound as colorless crystals. Isomer A Melting point: 2 3 1-2 3 3

NMR spectrum (d ₆ _DMS0) δ ρΐί: 1.31 (3H, d, J = 6.6 Hz), 3.56 (1H.q, J = 6.6 Hz), 4.61 (1H, s), 7.16-7 .37 (7H.m), 7.50-7.60 (4H, m), 8.00 (2H, d, J-8.3Hz) ₀

26 As in example 1 using 1 mg of isomer B of example (52a), 131 mg of sodium azide and 0.55 ml of tri-n-butyltin chloride. The mixture was reacted and purified to obtain 43 mg of isomer B of the title compound as pale yellow crystals. Isomer B

 Melting point: 2 3 0 — 2 3 2 ^

NMR spectrum (c — DMSO) δρι: 1.31 (3H.d, J = 6.6Hz), 3.56 (1H.q.J = 6.6Hz), 4.61 (1H, s), 7.21-7.40 (7H , n \). 7.50-7.57 (4H, in), 7.92 (2H, d, 1 = 8.2Hz) ₀ Example 5 3

 N-((Is) 1-1_phenylethyl)-{phenyl [4— (1H-tetrazol-5-yl) phenyl] methyl} amine (Exemplified compound number 1_572)

(53a) N-((1S) 111-phenylethyl)-[(4-cyanophenyl) phenylmethyl] amine

 The reaction was carried out in the same manner as in Example (2a) using lg 4-cyanobenzophenone and 1.22 ml of (S) -1-phenylethylamine, followed by purification and isomerization of the title compound. Isomer A was obtained as a pale yellow oily substance (413 mg), and isomer B was obtained as a pale yellow oily substance (155 mg).

 Isomer A

NMR spectrum _{(CDC1 3) δ ppm:.} 1.38 (3H, d, J = 6.7Hz) 3.60 (. 1H, q J-6.7Hz), 4. 65 (1H, s), 7. 14-7.38 (10H , m), 7.49 (2H, d, J = 8.3Hz). 7.61 (2H, d, J = 8.3Hz) Isomer B

NMR spectrum _{(CDC1 3) δ ppm:.} 1.37 (. 3H, d J = 6.6Hz), 3.67 (. 1H, q J = 6.6Hz), 4. 64 (1H, s) 7.21-7.38 (10H, m ), 7.41 (2H, d. 8.4Hz), 7.52 (2H. D. J = 8.4Hz) „(53 b) N-((IS) 1 1 _ phenylenyl)-{phenyl 2 [4 — (1 H-tetrazole-5-yl) phenyl] methyl} amine

 395 mg of isomer A of Example (53a), 246 mg of sodium azide and 1.03 ml of tri-n-butyltin chloride were prepared in the same manner as in Example 1. The mixture was reacted and purified to obtain 3883 mg of isomer A of the title compound as colorless crystals. Isomer A

 Melting point: 200-202 ° C

NMR spectrum _{(d 6 -DMS0) d ppm:} 1.34 (. 3H, d J = 6.6Hz), 3.60 (. 1H q, J = 6.6H z), 4.67 (1H, s), 7. 16-7.38 ( 10H, m), 7.58 (2H, d, J = 8.2Hz), 7.99 (2H, d, J = 8.2Hz)

145 mg of isomer B of Example (53a), 9 lmg of sodium azide and 0.38 ml of tri-n-butyltin chloride as in Example 1 The reaction was followed by purification to give 129 mg of isomer B of the title compound as colorless crystals. Isomer B

 Melting point: 2 2 2 — 2 24 ° C

 NMR spectrum (c—DMSO) δ ppm: 1.34 (3H, d, J = 6.7 Hz), 3.59 (1H.q, J = 6.7Hz), 4.65 (1H, s), 7.21-7.41 (10H.m ), 7.54 (2H, d, J = 8.3Hz), 7.93 (2H, d.J = 8.3Hz)

 N- (1-Methylethyl) 1-phenyl [3— (1H-tetrazol-5-yl) phenyl] methyl} amine hydrochloride (Exemplary Compound No. 1-442)

 (54a) N— (1-Methylethyl) -1- [phenyl-1- (3-cyanophenyl) methyl] amine

 The reaction was carried out in the same manner as in Example (2a) using 2.0 g of 3-cyanobenzophenone and 4.3 ml of isopropylamine, followed by purification. The title compound was obtained as a pale yellow oily substance. 65 g were obtained.

NMR spectrum _{(CDC1 3) δ ppra:.} . 1.00-1 16 (6H, m) 2.60-2.80 (1H, m), 4.98 (1H, s), 7.20-7.80 (9H, m).

 (5 4 b) N-(1-methylethyl)-{phenyl [3-(1H-tetrazo-1-5-yl) phenyl] methyl}

 Example (54a) of N— (1-Methylethyl)-[phenyl (3-cyanophenyl) methyl] amine 1.64 g, 1.28 g of sodium azide and 3.74 ml of The reaction was carried out in the same manner as in Example 1 using tri-n-butyltin chloride, followed by purification to obtain 112 mg of the title compound as colorless crystals.

 Melting point: 2 73-27 5 ° C (decomposition)

NMR spectrum (d ₆ —DMS0) δ ρρπι: 1.20-1.30 (6Η, m), 3.00-3.20 (1Η, m). 5.87 (1H.s), 7.35-7.50 (3H, m), 7.65-7.85 (3H, m), 7.95-8.10 (2H, m), 8.45-8.50 (1H, m).

 Example 5 5

 N—t—butyl— {phenyl [3— (1H—tetrazol-5—yl) phenyl] methyl} amine hydrochloride (Exemplary Compound No. 1-444)

 (55a) N-t-butyl- [phenyl- (3-cyanophenyl) methyl] amine

 4 Using 14 mg of 3-cyanobenzophenone and 1.05 ml of t-butylamine, the reaction was carried out in the same manner as in Example (2a), and the title compound was purified as a pale yellow oil. 132 mg were obtained.

NMR spectrum _{(CDC1 3) δ ppm: 1.05} (. 9H s), 5.02 (1Η, s), 7. 15-7.50 (7H, m), 7.63-7.72 (1H, m), 7.84-7.90 (1H, m).

 (55b) N—t—butyl— {phenyl— [3— (1H—tetrazol—5—yl) phenyl] methyl} amine hydrochloride

N-t-butyl- [phenyl- (3-cyanophenyl) methyl] amine of Example (55a) 119 mg, 176 mg of sodium azide and 0.52 ml of tri-n Reaction was carried out in the same manner as in Example 1 using butyltin chloride and purified. 92 mg of the title compound were obtained as colorless crystals.

 Melting point: 26 2-26 4 ° C (decomposition)

NMR spectrum (d ₆ — DMS0) δ ppm: 1.29 (9H, s), 5.89 (1Η, s), 7.30-7.50 (3H, m), 7.60-7.72 (1Η, m), 7.85-8.06 (3H, m), 8.10-8.22 (1H, m), 8.54-8.63 (1H, m)

 N-((Is) -1 1-phenylethyl) 1-phenyl [3- (1H-tetrazol-5-yl) phenyl] methyl} amine hydrochloride (Exemplary Compound No. 1-489)

 (56 a) N-((1 S)-1-phenylethyl) 1 [phenyl-(3-cyanophenyl) methyl] amine

 The reaction was carried out in the same manner as in Example (2a) using 6 210 of 3_cyanobenzofenone and 0.77 ml of (S) -1) -phenethylamine, followed by purification and labeling. 33 mg of isomer A of the product was obtained as a pale yellow oil, and 33 33 mg of isomer B was obtained as colorless crystals.

 Isomer A

NMR spectrum _{(CDC1 3) δ ppm: 1.38} (3H, d, J = 6.7Hz), 3.59 (. 1H, q J = 6.7Hz), 4.64 (1H, s), 7. 10-7.65 (13H, m ), 7.72 (1H, s)

 Isomer B

NMR spectrum _{(CDC1 3) δ ppm: 1.37} (3H, d, J = 6.6Hz), 3.66 (. 1H, q J = 6.6Hz), 4. 61 (1H, s), 7. 15-7.55 (13H , m), 7.65 (1H, s) „

 (5 6 b)-((I S)-1-phenylethyl)-{phenyl [3-(1 H-tetrazol-5-yl) phenyl] methyl}

32 1 mg of isomer A of Example (56a), 200 mg of sodium azide and 0.88 ml of tri-n-butyltin chloride were used as in Example 1 React and purify in the same manner to give the hydrochloride of isomer A of the title compound as colorless crystals. g obtained.

 Isomer A

 Melting point: 2 4 1 — 2 4 4 (decomposition)

NMR spectrum _{(d 6 -DMS0) <5 ppm} :. 1. 69 (3H, d, J-6.7Hz), 4.05-4.20 (1Η, m), 5.46 (1H, s), 7.30-8 10 (13H , m), 8.34 (1H.s).

 31 Same as Example 1 with 12 mg of isomer B of Example (56a), 195 mg of sodium azide and 0.86 ml of tri-n-butyltin chloride The residue was purified to give 179 mg of isomer B of the title compound as colorless crystals. Isomer B

 Melting point: 16 8 ° C (decomposition)

NMR spectrum _{(d 6 -DMS0) (5 ppm} : 1. 70 (3H, d, J = 6.7Hz), 4. 10-4.25 (1H, m), 5. 30 (1H, m), 7. 30 -8. 10 (13H, in), 8.33 (1H, m).

 Example 5 7

 N-((1 R) — 1 —phenylethyl) 1 {phenyl — [4 — (1 H—tetrazoruyl 5 —yl) phenyl] methyl} amine (Exemplified compound number 1 — 57 2)

(57a) N-((1R) _1-phenylethyl)-[phenyl- (4-cyanophenyl) methyl] amine

 Using lg of 4-cyanobenzophenone and 1.22 ml of (R) -l-phenylethylamine, the reaction was carried out in the same manner as in Example (2a), purification was carried out, and the title compound was purified. 197 mg of isomer A was obtained as a pale yellow oil, and 165 mg of isomer B was obtained as a pale yellow oil.

 Isomer A

NMR spectrum _{(CDC1 3) δ ppra: 1.38} (. 3H, d J = 6.7Hz), 3.59 (1H, q,] = 6.7Hz), 4.65 (. 1H s), 7. 17-7.38 (10H, m ), 7.49 (2H.d,] = 8.2Hz), 7.61 (2H, d, J = 8.2Hz) Isomer B

NMR spectrum _{(CDC1 3) <5 ppm:} 1.37 (. 3H, d J = 6.6Hz), 3.67 (1H, q, J = 6.6Hz) , 4.64 (1H.s), 7.23-7.38 (10H.m), 7.41 (2H.d, J = 8.2Hz), 7.52 (2H, d.J = 8.2Hz) „(57b) N -((1 R) 1 1 1 phenylethyl)-{phenyl [4 — (1H-tetrazol-5-yl) phenyl] methyl}

 Reaction as in Example 1 with 193 mg of isomer A of Example (57a), 120 mg of sodium azide and 0.5 ml of tri-n-butyltin chloride The residue was purified to give 185 mg of the hydrochloride of isomer A of the title compound as colorless crystals.

 Isomer A

 Melting point: 222-229 (decomposition)

NMR spectrum _{(CDC1 3) δ ppm:.} 1.86 (3H, d, J = 6.7Hz), 4. 12 (1H, m) 4.77 (1 H, s), 7. 13 (3H, m), 7.34- 7.52 (7H, m), 7.92 (2H, d, J = 8.2Hz), 8.44 (2H, d.J = 8.2Hz), 10.20-10.43 (1H, m), 11.13-11.36 ( 1H, m) „

 As in Example 1 using 160 mg of isomer B of Example (57a), 99 mg of sodium azide and 0.42 ml of tri-n-butyltin chloride. The reaction was followed by purification to obtain 18 mg of isomer B of the title compound as colorless crystals.

 Isomer B

 Melting point: 2 2 6 1 2 2 8 ° C (decomposition)

NMR spectrum _{(d 6 -DMS0) <5 ppm} : 1. 34 (. 3H, d J = 6. 6Hz), 3.59 (. 1Η q, J = 6.6H z), 4.65 (1H, s), 7. 23-7.40 (10H, m), 7.54 (2H, d.J = 8.2Hz), 7.93 (2H, d, J = 8.2Hz) Example 5 8

 N-((1R) _1 1-naphthylethyl)-{phenyl- [4— (1H-tetrazo-l-uyl-5-yl) phenyl] methyl} amine (Exemplified compound number 1—606)

(5 8 a) N-((1 R) — 1-naphthylethyl)-[phenyl (4-cyanophenyl) methyl] amine

5 OO mg of 4-cyanobenzophenone and 0.77 ml of (R) -1-naphthy The reaction was carried out in the same manner as in Example (2a) using lutetylamine, followed by purification to obtain 885 mg of the title compound as a pale yellow oil.

NMR spectrum _{(CDC1 3) δ ppm:.} . 1.49-1 54 (3H, m), 4.47-4 58 (. 1Η ra), 4.72 and 4.75 (total 1H, each S), 7. 18-7.67 (13H , πι), 7. ΤΤ-7.94 (3Η, πι).

 (5 8 b) Ν— ((1 R) 1 1 —naphthylethyl) 1 {phenyl (4 — (1Η-tetrazol-5-yl) phenyl] methyl} amine

 Example N-((1R) -1-1-naphthylethyl) -1- [phenyl- (4-cyanophenyl) methyl] amine of (58a) 880 mg, 468 mg of sodium azide and 1.95 The reaction was carried out in the same manner as in Example 1 using ml of tri-n-butyltin chloride and purified to obtain 177 mg of the title compound as colorless crystals.

 Melting point: 204-206 ° C (decomposition)

NMR spectrum _{(d 6 -DMS0) δ ppm:} 1.47 (3H, d, J = 6.5Hz), 4.49 (1H, q, J = 6.5H z), 4.79 (1H, s), 7. 24-7. -62 (10H, m), 7.78-7.84 (3H, m), 7.91-7.96 (3H, m) ₀ Example 5 9

 N-((1R) -11-phenylethyl)-[phenyl (3-mesylcarbamoylphenyl) methyl] amine hydrochloride (Exemplary Compound No. 1-640)

 248 mg of N-mesyl-3-benzoylbenzoamide and 0.2 lml of (R) -11-phenylethylamine were reacted in the same manner as in Example (2a) and purified. This gave 190 mg of the title compound as colorless crystals.

 Melting point: 1 4 8-1 5 2

NMR spectrum (de-MSO) δ ppm: 1.65-1.75 (3H, m), 3.35 (3Η, s), 4.10 (1Η, S), 5.20 and 5.35 (total 1H, each s), 7 . 30-8. 20 (14H, m) ₀

 Example 6 0

 N-((1R) -1 1-phenylethyl) 1-phenyl (3-tosylcarbamoylphenyl) methyl] amine hydrochloride (Exemplary compound number 1-696)

4 78 mg of N-tosyl-3-benzoylbenzoic acid amide and 0.32 ml of ( R) —1—Phenylethylamine was reacted and purified in the same manner as in Example (2a) to give the free isomer A of the title compound as a pale yellow oil. mg. Isomer B was obtained as a pale yellow oil in the form of 218 mg.

 Using 117 mg of isomer A, 99 mg of the title compound was obtained as a hydrochloride, and similarly, using 132 mg of isomer B, 115 mg of the title compound was obtained as a hydrochloride.

 Isomer A

 Melting point: 1 4 7-1 4 9 ° C

NMR spectrum (d ₆ —DMS0) <5 ppm: 1.69 (3H, d, J = 6.7 Hz), 2.40 (3Η.s), 4.00 -4.15 (1Η, m), 5.33 (1H, s), 7.25-8.10 (18H, m)

 Isomer B

 Melting point: 1 4 4 — 1 4 6

NMR spectrum (d ₆ -DMSO) δ ppm: 1.68 (3H, d, J = 6.7 Hz), 2.40 (3H, s), 4.00-4.20 (1H, m). 5.20 (1H, s), 7 22-8. 10 (18H, in).

 Example 6 1

 N-((1R) 1-indan- 1-yl) 1-phenyl- [4— (1H-tetrazol-5-yl) phenyl] methyl} amine (Exemplified Compound No. 1—5 6 8)

(6 1 a) N-((1 R)-indian-1-1-yl) [phenyl (4-cyanophenyl) methyl] amine '

 Using 300 mg of 4-cyanobenzophenone and 0.37 ml of (R) -1 -aminoindan, the reaction was carried out in the same manner as in Example (2a), and the title compound was purified. 478 mg were obtained as a pale yellow oil.

NMR spectrum _{(CDC1 3) δ ppra:.} 1.72-1.88 (1H, m), 2.35-2.53 (1Η, m), 2.69 -I.81 (1H, m), 2.90-3 13 (1H, m), 4.12 (1H, q. 1 = 6.7Hz), 5.15 (1H, s). 7. 19-7.71 (13H, m).

(6 1 b) N-((1 R)-indane-1-yl)-{phenyl-[4- (1H-tetrazo-1-yl) phenyl] methyl} N-((1R) -Indane-1-yl) of Example (61a)-[phenyl (4-cyanophenyl) methyl] amine 470 mg, 283 mg of sodium azide The reaction was carried out in the same manner as in Example 1 using 1.18 ml of tri-n-butyltin chloride and purified, to obtain 309 mg of the title compound as colorless crystals.

 Melting point: 2 1 2

 NMR spectrum (c—DMSO) δ ppm: 1.83-2.01 (1H, m), 2.23-2.36 (1H, ηι), 2.62-2.74 (1H, m), 2.90-3.01 (1H, m) ), 4.05-4. 10 (1H, m). 5.27 (1H, s), 7.19-7. 39 (6 H, m), 7.51-7.64 (3H, m), 7.73-7 82 (2H, m), 7.96-8.04 (2H.m).

 Example 6 2

 N- (4-Rubemoylphenylmethyl)-(phenyl-2- (1H-tetrazol-5-yl) phenyl] methyl} amine (Exemplary Compound No. 1_521)

(62a) N— (4-Methoxycarbonylphenylmethyl) -1- [phenyl (3-cyanophenyl) methyl] amine

 Using 1 g of 3-cyanobenzophenone and 1.944 g of methyl hydrochloride of 4-aminomethylbenzoic acid, the reaction was carried out in the same manner as in Example (2a), purified and purified. 1.81 g of the compound was obtained as a yellow oil.

NMR spectrum _{(CDC1 3) <5 ppm:} 3.79 (2H, s), 3.92 (3Η, s), 4.85 (1H, s), 7. 17-7.72 (10H, m), 7.77 (1H, s), 7. 99-8.02 (2H, m).

 (6 2 b) N-(4-rubamoylphenylmethyl)-[phenyl-(3-cyanophenyl) methyl] amine

In Example (62a), N_ (4—methoxycarbonylphenylmethyl) -1- [phenyl (3-cyanophenyl) methyl] amine was dissolved in 300 mg and 1.5 ml of dimethylformamide. After 0.1 ml of formamide and 0.12 ml of a 28% sodium methoxide methanol solution were added at room temperature, the mixture was heated and stirred for 8 hours. To the reaction solution was added 20 ml of aqueous sodium bicarbonate, extracted twice with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel chromatography (elution solvent: high-pressure hexane Z ethyl acetate = 1 Z 2) to obtain 21.6 mg of the title compound as a pale yellow foam.

NMR spectrum _{(CDC1 3) δ ppm:.} 3.79 (2H, s), 4.85 (1Η, s), 5.60-6 16 (. 2H in), 7.29-7.43 (8H, m), 7. 52 (1H, d, J = 7.8Hz), 7.66 (1H, d, J = 7.8Hz), 7.79 (3H, d. J = 8.3Hz).

 (6 2 c) N-(4-rubamoylphenylmethyl) 1 {phenyl [3-(1 H-tetrazol-5 _ yl) phenyl] methyl} amine

 Example (62b) N_ (4—pothamoylphenylmethyl)-[phenyl (3—cyanophenyl) methyl] amine 210 mg, 120 mg sodium azide and 0.50 The reaction was carried out in the same manner as in Example 1 using tri-n-butyltin chloride of m 1, followed by purification to obtain 34 mg of the title compound as yellow crystals.

 Melting point: 1 4 4 1 1 5 4

 NMR spectrum (de-DMSO) δ ppm: 3.73 (2H, s), 4.96 (1Η, s), 7.18-7.62 (8H, m), 7.82-7.91 (4Η, m), 8 17 (1Η, s).

 Reference example 1

 2—Methylthiobenzoic acid—2—Pyridyl ester

 5.54 g of 12-methylthiobenzoyl chloride and 1.4 lg of 2-hydroxypyridine were heated to reflux in 12 ml of pyridine for 3 hours. The pyridine was distilled off under reduced pressure, and the obtained residue was separated and purified by silica gel chromatography — (eluting solvent: ethyl hexyl acetate = 1: 1) to give the title compound as a pale yellow oil. g obtained.

NMR spectrum _{(CDC1 3) δ ppm: 2.47} (3H, s), 7.20-8.50 (8Η, m).

 Reference example 2

 (2 —Chenyl) 1 2 —Methylthiophenyl ketone

680 mg of 2-methylthiobenzoic acid-2-pyridyl ester obtained in Reference Example 1 0.23 ml of thiophene was heated to reflux in 5.0 ml of trifluoroacetic acid for 2 hours and 40 minutes. The reaction solution was poured into aqueous sodium bicarbonate, neutralized, extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The obtained residue was separated and purified by silica gel chromatography- (elution solvent: cyclohexanedichloromethane = 21) to obtain 434 mg of the title compound as a pale brown oil.

NMR spectrum _{(CDC1 3) δ ppm: 2.44} (3H, s), 7. 10-7.60 (6Η, m), 7.73 (1Η, d, J = 4.6Hz).

Reference example 3

 3-Methoxycarbonylbenzoic acid mono 2-pyridyl ester

 5.96 g of 1,3-methoxycarbonylbenzoyl chloride and 1.43 g of 2-hydroxypyridine were heated under reflux in 12.1 ml of pyridine for 3 hours. Pyrididine was distilled off under reduced pressure, and the obtained residue was separated and purified by silica gel chromatography (elution solvent: cyclohexane Z ethyl acetate = 21) to give the title compound as a pale yellow oil (2.68 g). Obtained.

NMR spectrum _{(CDC1 3) <5 ppm:} 3.87 (3H, s), 7. 20-8.50 (7Η, m), 8.79 (1H, s).

 Reference example 4

 (2-Chenyl) 1-3-Methoxycarbonylphenylketone

 3-Methoxycarbonylbenzoic acid 1-2-pyridyl ester obtained in Reference Example 3 1.02 and 0.32 ml of thiophene were heated and refluxed in 5.O ml of trifluoroacetic acid for 4 hours. The reaction solution was poured into aqueous sodium bicarbonate, neutralized, extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The obtained residue was separated and purified by silica gel column chromatography (elution solvent: cyclohexanedichloromethane = 1/2) to obtain 530 mg of the title compound as pale brown crystals.

 Melting point: 9 3 9 5

NMR spectrum _{(CDC1 3) δ ppm:.} .. 3.87 (3H, s) 7. 15-7.80 (. 4H m) 8.01 (1H d , J = 7.8Hz), 8.22 (1H, d, J = 7.9Hz), 8.48 (1H, s) „

 Reference example 5

 (Benzothiophene-3-yl) mono (2-methylthiophenyl) ketone 2-methylthiobenzoic acid mono-2-pyridyl ester obtained in Reference Example 1 5.56 mg and 456 mg of benzothiophene were added in 5.O ml of The mixture was heated under reflux in trifluoroacetic acid for 3.5 hours. The reaction solution was poured into aqueous sodium bicarbonate, neutralized, extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The obtained residue was separated and purified by silica gel column chromatography (elution solvent: cyclohexane / dichloromethane = 4/1) to give 399 mg of the title compound as a yellow oil.

NMR spectrum _{(CDC1 3) δ ppm: 2.44} (3H, s), 7. 20-7.95 (8Η, m), 8.73 (1Η, d, J = 7.6Hz) "

 Reference example 6

 2 —Ethylthiobenzofunone

 11.0 g of 2-ethylthiobenzoyl chloride and 7.3 g of aluminum chloride were suspended in 12 O ml of anhydrous benzene and stirred at room temperature for 18 hours. The reaction solution was poured into ice water and extracted with ethyl acetate. The extract was washed with aqueous sodium bicarbonate solution and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (elution solvent: cyclohexane / ethyl acetate = 19/1) to give 8.73 g of the title compound as a yellow oil.

NMR spectrum _{(CDC1 3) 6 ppm:.} 1.24 (3H, t, J = 7.4Hz), 2.88 (2H, q, J = 7.4Hz), 7.20-7 65 (7H, in), 7.79 (2H, d , J-7.2Hz).

 Reference Example 7

 N, N-dimethyl 2- (4-methylbenzoyl) benzamide

Dissolve 50 mg of 4-methylbenzoylbenzoic acid in 20 ml of anhydrous tetrahydrofuran and add 0.73 ml of triethylamine and 0.3 ml of isobutyl chloroformate under ice-cooling and stirring. Stirred for a while. Add 204 mg of dimethyla to the reaction mixture. The mixture was stirred at room temperature for 2 hours. The mixture was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (eluent: high-pressure hexane Z ethyl acetate = 10Zl to 2: 1) to give 170 mg of the title compound as a colorless oil. Obtained.

NMR spectrum _{(CDC1 3) δ ppra: 2.42} (3H, s), 2.90 (3Η, s), 2.94 (3Η, s), 7. 25 (2Η, d, J = 7. 9Hz), 7. 35- 7.60 (4H, m), 7.71 (2H, d, J = 8.2Hz).

 Reference Example 8

 4 —Methylthiophenyl _ 4 —Benzophenone

 Dissolve 757 mg of 4-bromobenzophenone in 7.O ml of toluene and 7.O ml of ethanol, and stir at room temperature, and then add 66 mg of 4-methylthiophenenylsulfonic acid, 75 mg Then, 20% of palladium hydroxide monocarbon and 7. O ml of saturated aqueous sodium hydrogen carbonate were added, and the mixture was heated under reflux for 9 hours under a nitrogen stream. The reaction solution was filtered using celite, diluted with ethyl acetate, washed with aqueous potassium hydrogen sulfate and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (elution solvent: cyclohexane / dichloromethane = 41) to obtain 312 mg of the title compound as colorless crystals.

 Melting point: 1 6 2-1 6 4

NMR spectrum _{(CDC1 3) δ pm: 2.54} (3H, s), 7.35 (2Η, d, J = 8.5Hz), 7.45- 7. 95 (11H, m).

 Reference Example 9

 3- (2-benzothiazolylcarbonyl) benzoic acid methyl ester

1.10 g of 13-methoxycarbonylbenzoyl and 1.15 g of 2-trimethylsilylbenzothiazole were heated and refluxed in 3 O ml of anhydrous toluene for 20 hours. The mixture was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue obtained is silica gel Separation and purification by column chromatography (elution solvent: cyclohexane / ethyl acetate = 20/1), yielded 700 mg of the title compound as colorless crystals.

 Melting point: 1 3 2 — 1 3 51:

NMR spectrum _{(CDC1 3) δ ppm:.} 3.99 (3H, s), 7.50-7.75 (3Η, m), 8.00-8.80 (4Η, m) 9. 18 (1Η, s).

 Reference example 10

 4-methylthiophenenyl-1—benzophenone

 1. Dissolve O g of 2-bromobenzophenone in 1 O ml of toluene and 1 O ml of ethanol, and stir at room temperature, 870 mg of 4-methylthiophenenyl boric acid, 10 O mg Was added with 20% palladium hydroxide monocarbon and 1 O ml of saturated aqueous sodium hydrogen carbonate, and the mixture was refluxed for 3.5 hours under a nitrogen stream. The reaction solution was filtered using celite, diluted with ethyl acetate, washed with aqueous potassium hydrogen sulfate and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (elution solvent: cyclohexane / dichloromethane = 19/1) to obtain 1.36 g of the title compound as a pale yellow oil.

NMR spectrum _{(CDC1 3) δ ppm: 2.40} (3H, s), 7.05-7.70 (13H, m) 0 Reference Example 1 1

 Ν, Ν-dimethyl (2-methoxy-1-hydroxy-5-benzoyl) benzenesulfonamide

 (1 1a) (2—Methoxy—4—Hydroxy-5-benzoyl) benzenesulfonyl chloride

5. Suspend Og (2-Methoxy-4-Hydroxy-5-Benzyl) benzenesulphonic acid in 10 O ml of anhydrous dichloromethane, and add 13.7 ml of thionyl chloride and 0.06 at room temperature. ml of anhydrous dimethylformamide was added and stirred for 15 minutes. Further, the mixture was heated under reflux overnight, and the solvent was distilled off under reduced pressure. The obtained residue was treated with isopropyl ether to give 3.58 g of the title compound as orange crystals. Melting point: 1 1 8 — 1 2 6 (decomposition)

 (lib) N, N-dimethyl (2-methoxy 4-hydroxy 5_benzoyl) benzenesulfonamide

 483 mg of dimethylamine hydrochloride was suspended in 5 O ml of anhydrous tetrahydrofuran, and 1.65 ml of triethylamine was added under stirring at room temperature. After 15 minutes, the mixture was obtained in Reference Example (11a). A solution of 1.29 g of (2-methoxy-4-hydroxy-5-benzoyl) benzenesulfonyl chloride in 10 ml of anhydrous tetrahydrofuran was added dropwise and stirred for 15 minutes. The solvent was distilled off under reduced pressure, and the obtained residue was diluted with ethyl acetate, washed with 3N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate, and then with saturated saline, dried over anhydrous magnesium sulfate, and dried under reduced pressure. The solvent was distilled off. The resulting residue was separated and purified by silica gel column chromatography (elution solvent: cyclohexane / ethyl acetate = 10/1) to obtain 280 mg of the title compound as a colorless foam.

NMR spectrum _{(CDC1 3) δ ppm: 2.82} (6H, s), 4.00 (3Η, s), 6.61 (1Η, s), 7.40-7.75 (5H, m), 8.26 (1H, s), 13.03 (1H , s) ₀

 Reference example 1 2

 3—Benzylbenzoic acid benzyl ester

 2. Dissolve 262 g of 3-benzoyl benzoic acid in 45 ml of anhydrous methyl ethyl ketone, and at room temperature, with 264 g of anhydrous potassium carbonate and 32 32 mg of lithium iodide. 1.44 ml of benzyl chloride was added and stirred for 24 hours. Further, 1.382 g of anhydrous potassium carbonate, 166 mg of potassium iodide and 2.1 ml of benzyl chloride were added, and the mixture was heated under reflux for 2 hours. The reaction solution was diluted with ethyl acetate, washed with water and saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (elution solvent: ethyl hexanoacetate = 6/1) to give 2.972 g of the title compound as a colorless oil.

NMR spectrum _{(CDC1 3) δ ppm:.} 5.39 (2H, s) 7.30-7.70 (9H, m), 7.80 (2H, d , J = 7.0Hz). 8.01 (1H, d, J = 7.8Hz), 8.29 (1H, d, J = 7.7Hz), 8.49 (1H, s).

 Reference Example 1 3

 N—Tosyl-3—Benzoylbenzoate amide

 (13a) Potassium P—toluenesulfonamide

 856 mg of ρ-toluenesulfonamide and 56 lmg of potassium tert-butoxide were dissolved in 8.5 ml of methanol, and the solvent was distilled off under reduced pressure. The obtained residue was treated with ethyl acetate to give 1.025 g of the title compound as colorless crystals. Melting point: 24.5-24.8

 (13b) N-Tosyl_3-benzoyl benzoate amide

 Dissolve 90.4 mg of 3-benzoylbenzoic acid in 8.5 ml of anhydrous dimethylacetamide and, under a stream of nitrogen and stirring under ice-cooling, 0.6 ml of triethylamine and 0.42 ml of chloroformic acid. After adding ethyl, the mixture was stirred for 1 hour. After adding 8.5 ml of anhydrous dimethylacetamide, 1.04 g of potassium p-toluenesulfonamide obtained in Reference Example (13a) was added, and the mixture was added at room temperature for 14 hours. Stirred. The reaction solution was poured into 0.101 1 of 0.1N hydrochloric acid and extracted with ethyl acetate. After washing with water, 0.1N sodium hydroxide and saturated saline, the mixture was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was treated with ethyl acetate to give 980 mg of the title compound as colorless crystals.

 Melting point: 1 2 7 (decomposition)

NMR spectrum _{(d e -DMS0) δ ρρπι:} . 2.31 (3Η, s), 7.17 (. 2Η, d, J-8 OHz) 7.45 -7.85 (9H, m), 8. 16 (1H, d, J -7.8Hz), 8.23 (1H, s).

 Reference example 1 4

 6—Methoxy_2—Methylthiobenzophenone

Dissolve 1.42 g of 6-methoxy_2-methylthiobenzene in 20 ml of n-hexane and 1.55 ml of N, N, ', N'-tetramethylethylenediamine. A Min was added. Under ice salt cooling and stirring, 6.2 ml of a 1.6 mol solution of n-butyllithium n-hexane was added dropwise, and the reaction solution was stirred at room temperature for 28 hours. To the reaction solution was added a 1.15 ml benzoyl quencher under ice salt cooling and stirring, followed by stirring at room temperature for 3.5 hours. Aqueous sodium bicarbonate and ethyl acetate were added, and the ethyl acetate layer was washed with saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (elution solvent: cyclohexane Z ethyl acetate = 50 51 to 10Ζ1) to give 60 lmg of the title compound as colorless crystals. .

 Melting point: 1 1 8 — 1 1 9 V

NMR spectrum _{(CDC1 3) δ ppm: 2.37} (3H, s), 3.70 (. 3Η s), 6.83 (1Η, d, J = 8. 3Hz), 7.02 (IH, d, J = 8.0Hz), 7.30 -7. 90 (6H, m).

 Reference example 1 5

 (1 naphthyl)-(2-methylthiophenyl) ketone

 10.2 lg of 2-methylthiobenzoyl chloride and 3.65 g of aluminum chloride were suspended in 20 ml of anhydrous dichloroethane, and 3.5 g of naphthalene in 7.0 ml of dichloroethane was added. The mixture was added dropwise and stirred at room temperature for 2 days. The reaction solution was poured into ice-dilute hydrochloric acid and extracted with ethyl acetate. The extract was washed with aqueous sodium bicarbonate and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (elution solvent: ethyl cyclohexanoacetate = 19/1) to obtain 2.34 g of the title compound as a yellow oil.

NMR spectrum (d ₆ -DMS0) δ ppm: 2.47 (3H, s), 7.05-8.40 (11Η, m) »Reference Example 16

 2—Methylthiophenenylboric acid

590 mg of magnesium were suspended in 1 O ml of anhydrous tetrahydrofuran, and under nitrogen flow, at 60, 4.7 O g of 2-O-methylthiobromobenzene was added. A solution of tetrahydrofuran in water was added dropwise, and the mixture was heated under reflux for 3 hours. The above reaction solution was added dropwise to 3.4 lml of 20 ml of anhydrous ether of trimethoxyboron at −50 ° C., stirred at room temperature for 2 hours, and left overnight. Under ice cooling and stirring, 20 ml of saturated aqueous potassium bisulfate was added, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was poured into water, extracted with ethyl acetate, and the extract was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (elution solvent: cyclohexane: ethyl acetate = 4.1) to obtain 2.03 g of the title compound as colorless crystals.

 Melting point: 8 3 _ 8 5

NMR spectrum _{(CDC1 3) δ ppm:.} 2.51 (3H, s) 6.40 (2H, s), 7.30-7.60 (. 3H m), 8.02 (1H, dd, J = l.5Hz, J = 7.3Hz) .

 Reference Example 1 7

 2 —Methylthiophene 2 —Benzophenone

 1.0 g of 2-bromobenzophenone and 87 O mg of 2-methylthiophenenyl boric acid obtained in Reference Example 16 were suspended in 20 ml of water, and 2 O mg of acetic acid Then, 1.30 g of anhydrous potassium carbonate and 1.40 g of tetra-n-butylammonium ester were added, and the mixture was heated and stirred at 70 ° C. for 17 hours. The reaction solution was filtered using celite, and diluted with ethyl acetate. The ethyl acetate layer was washed with 0.1N aqueous hydrochloric acid and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (elution solvent: cyclohexane ethyl acetate = 19/1) to obtain 0.99 g of the title compound as a pale yellow oil.

NMR spectrum _{(CDC1 3) (5 ppm:} 2.26 (3H, s), 7.00- 7 · 75 (13Η, m).

 Reference Example 1 8

 2 —Methylthiophenenyl-1 4 —Benzophenone

1.0 g of 4-bromobenzophenone and 87 O mg of 2 obtained in Reference Example 16 — Suspend methylthiophenenyl borate in 20 ml of water, add 2 O mg of palladium acetate, 1.3 O g of anhydrous potassium carbonate and 1.40 g of tetra-n-butylammonium bromide. The mixture was heated and stirred at 70 for 3 hours. The reaction solution was filtered using celite, and diluted with ethyl acetate. The ethyl acetate layer was washed with 0.1N aqueous hydrochloric acid and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (elution solvent: cyclohexane Z ethyl acetate = 19 Z 1) to obtain 0.94 g of the title compound as pale yellow crystals.

 Melting point: 1 1 9 — 1 2 1

NMR spectrum _{(CDC1 3) δ ppm:.} 2.40 (3H, s) 7.20-7.95 (13H, m) 0 Reference Example 1 9

 N- (2- (2-Methylphenyl) phenylsulfonyl) —3-Benzylbenzamide

 4 Dissolve 2 mg of 3-benzoylbenzoic acid in 2 O ml of anhydrous N, N-dimethylacetamide and, with ice cooling and stirring, add 0.305 ml of triethylamine and 0.21 ml of chloroformic acid Then, the mixture was stirred for 1 hour. On the other hand, 420 mg of 2-((2-methylphenyl) benzenesulfonamide was dissolved in 10 ml of anhydrous N, N-dimethylacetamide, and 269 mg of potassium t-butoxide was added. The mixture was stirred for 45 minutes. The two reaction solutions were combined, stirred at room temperature overnight, and further stirred at 50 for 1 hour. The reaction solution was diluted with ethyl acetate, washed with diluted hydrochloric acid, saturated saline, saturated aqueous sodium bicarbonate, and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel gel chromatography (elution solvent: high-pressure hexane / ethyl acetate = 3 to 1 to 13) to give the title compound as light brown crystals. mg was obtained.

 Melting point: 170 (decomposition)

NMR spectrum (c-DMSO) δ ppm: 1.86 (3H.s), 6.85-8.15 (17Η, ra). Reference Example 20

 (2 —benzothiazolyl) 1 3 —cyanophenyl ketone

 The reaction was carried out in the same manner as in Reference Example 9 using 1. O g of 3-cyanobenzoyl alcohol and 1.25 g of 2-trimethylsilylbenzothiazole, and the title compound was purified. 53 O mg were obtained as yellow crystals.

 Melting point: 1 4 4 1 1 4 5

NMR spectrum _{(CDC1 3) (3 ppm:} 7.55-8.80 (7H, m), 9.02 (1Η, s).

 Reference Example 2 1

 N- (1-ethylpentyl)-[phenyl (3-carboxyphenyl) methyl] amine oxalate

 (21 a) N-(1-ethylpentyl)-[phenyl-(3-methoxycarbonylphenyl) methyl] amine

 2.337 g of methyl 3-benzoylbenzoate and 2.952 g of 1-ethylpentylamine hydrochloride were dissolved in 46 ml of anhydrous dichloromethane, and the mixture was stirred under ice-cooling under a nitrogen stream. 6.75 ml of triethylamine and 9.70 ml of a 1 molar solution of titanium dichloromethane were added, and the reaction solution was stirred at room temperature for 17 hours. The reaction solution was diluted with ethyl acetate, washed with 0.5N hydrochloric acid and saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was dissolved in 56 ml of methanol, 0.74 ml of acetic acid and 2.162 g of sodium cyanoprohydride were added, and the mixture was heated under reflux for 1 hour. The reaction solution was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate, water and saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (elution solvent: cyclohexane ethyl acetate = 9/1) to obtain 2.584 g of the desired product as a colorless oil. From the obtained colorless oil (136 mg) and oxalic acid (36 mg), 1 I (4 mg) of the title compound, oxalate, was obtained.

Melting point: 70-78 ° C NMR spectrum (ds-DMSO) δ ppm: 0.84 (6H, t, J = 6.7 Hz). 1.10-1.30 (4H, m). 1.40- 1.75 (4H, m), 2.55 -2.68 (1H, m), 3.86 (3H, s) .5.58 (1H, s), 7.28-7.70 (6H, m), 7.90 (2H, d, J = 7.6Hz), 8.24 (1H s).

 (2 1 b) N- (1-ethylpentyl) -1- [phenyl (3-carboxyphenyl) methyl] amine oxalate

 168 mg of N_ (1-ethylpentyl)-[phenyl (3- (methoxycarbonylphenyl) -methyl] amine obtained in Reference Example (21a) was added to 8.1 ml of tetrahydrofuran. Under ice-cooling and stirring, 448 mg of potassium tert-butoxide and 181 of water were added, and the reaction solution was stirred at room temperature for 3 hours. 4. O ml of 1N aqueous hydrochloric acid was added to the reaction solution, the solvent was distilled off under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (elution solvent: methanol / ethyl acetate = 1/1 to 1: 1). Separation and purification by 5/1) yielded 84 mg of the title compound as an oil.

 Melting point: 1 9 5 — 1 9 7 X:

NMR spectrum _{(d 6 -DMS0) δ ppm:} . 0.70-0.90 (6H, m), 1. 10-1.70 (6Η, m), 2. 50-2 65 (1H, m), 5.40-5.55 (1H , br. s), 7.25-7.65 (6H, m), 7.75-7.90 (2H, m), 8.20 (1H, s).

 Reference Example 2 2

 N— (1-ethylpentyl) -1- [phenyl (3-N, N-dimethylcarbamoylphenyl) methyl] amine

Dissolve 1.383 of 1 ^, N-dimethyl-3-benzoylbenzoate and 1.6566 g of 1-ethylpentylamine hydrochloride in 28 ml of anhydrous dichloromethane. Under a stream of ice and stirring under ice cooling, 3.80 ml of a 1 molar solution of triethylamine and 5.50 ml of titanium tetrachloride dichloromethane were added, and the reaction solution was stirred at room temperature for 23 hours. The reaction solution was diluted with ethyl acetate, washed with 0.5N hydrochloric acid and saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was dissolved in 38 ml of methanol, and 0.47 ml of sulfuric acid and 1.372 g Of sodium cyanoborohydride was added thereto, and the mixture was heated under reflux for 1 hour. The reaction solution was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate, water, and saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (elution solvent: cyclohexane ethyl acetate = 1/1) to obtain 1.314 g of the target substance as a colorless oil.

NMR spectrum _{(CDC1 3) δ ρρηι:.} 0.75-0.95 (6Η, m), 1. 10-1 65 (. 9Η m), 2. 3 0-2.45 (1H, m), 2.92 (3H, s) , 3.09 (3H, s), 4.96 (1H, s), 7.10-7.50 (9H.m).

 Reference Example 2 3

 N— (1—Ethylpentyl) -1- [phenyl— (3-rubamoylphenyl) methyl] amine oxalate

 Reference Example 21 0.626 g of N- (1-ethylpentyl)-[phenyl (3-carboxyphenyl) -methyl] amine hydrochloride obtained in 1 was added to 12.4 ml of anhydrous dimethylformamide. Then, under ice-cooling and stirring, 0.46 ml of triethylamine and 0.19 ml of ethyl chloroformate were added, and the reaction solution was stirred at room temperature for 1 hour, and 0.56 ml of 28%. % Aqueous ammonia was added, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was added to a saline solution, extracted with ethyl acetate, washed with a saturated saline solution, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (elution solvent: cyclohexane / ethyl acetate = 1/1) to obtain 0.354 g of a monolith as colorless crystals. Using 0.111 g of the free form, 87 mg of the title compound was obtained as an oxalate.

 Melting point: 1 6 9 — 1 7 3

 NMR spectrum (c-DMS0) δ ppm: 0.84 (6H, t, J = 7.4Hz), 1.10-1.30 (4H, m), 1.40-1.70 (4H, m), 2.50-2.65 (1H , m), 5.46 (1H, br. s), 7.20-8.20 (11H, m).

 Reference example 2 4

N— (1-ethylpentyl) -1- [phenyl— (3-cyanophenyl) methyl] amine hydrochloride Reference Example 23 Dissolve 227 mg of N- (1-ethylpentyl)-[phenyl- (3-carbylylphenyl) -methyl] amine obtained in Reference Example 3 in 46 ml of anhydrous dichloromethane and add ice. Under cold stirring, 0.10 ml of oxychlorine was added, and the reaction solution was stirred at room temperature for 1 hour, and then 0.10 ml of oxychlorine was added, followed by stirring for 1 hour. The reaction solution was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate, water, and saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (elution solvent: cyclohexane Z ethyl acetate = 9/1) to obtain 201 mg of a colorless oil. 63 mg of the title compound was obtained as the hydrochloride from 63 mg of the obtained oil.

 Melting point: 1 5 1 — 15 5 ° C

NMR spectrum _{(d 6 -DMS0) δ ppm:} .. 0.75-0.95 (6H, m), 1. 10-1.35 (4Η, m), 1. 55-1 95 (4Η, m), 2.70-2 90 (1Η, m), 5.79 (1H, br.s), 7.35-8.20 (8H.m), 8.34 (1H, s), 9.68 (2H, br.s).

 Reference Example 2 5

 N-cyclohexyl [phenyl (3-hydroxymethylphenyl) methyl] amine oxalate

 Reference Example 26 32 mg of N-cyclohexyl- [phenyl- (3-methoxycarbonylcarbonyl) methyl] amine obtained in Reference Example 6 and 1.0 O ml of lithium hydride-hydrogentetrahydroanhydride The reaction was carried out in the same manner as in Example 24 using a 1 mol solution of drofuran, followed by purification to obtain the title compound as colorless crystals (307 mg).

 Melting point: 180-180

NMR spectrum _{(d e -DMS0) δ ppm:} . 0.90-1.80 (8H, m), 2.05-2.22 (2Η, m), 2. 60-2 75 (1Η, m), 4.50 (2H, s), 5.62 (1H, s), 7.20-7.80 (9H, m) „

 Reference Example 2 6

N-cyclohexyl [phenyl (3-methoxycarbonylphenyl) methyl] amine The reaction was carried out in the same manner as in Example (2a) using 2.138 g of methyl 3-benzoylbenzoate and 2.04 ml of cyclohexylamine, followed by purification to give the title compound. Was obtained as a colorless oily substance.

 Melting point: 1 8 0 — 1 8 2

NMR spectrum _{(CDC1 3) <5 ppm:} 1.00-1.80 (9H, m), 1.85-2.05 (2Η, m), 2. 30-2.45 (1H, in), 3. 90 (3H, s), 5.08 (1H, s), 7.15-7.45 (6H, m), 7.61 (1H, d, J -7.8 Hz), 7.88 (1H, d, J = 7.8 Hz), 8.07 (1H, s) .

 Reference Example 2 7

 3-Benzoyl 4- 4-Fluorobenzonitril

 To a solution of 1. O g of 3-bromo-4-fluorobenzonitrile and 0.58 ml of benzoyl quenched light in 20 ml of anhydrous tetrahydrofuran, 3.1 ml of 1.6 M n-butyl A lithium n-hexane solution was added dropwise under a nitrogen atmosphere with a pressure of 165 to -66. After further stirring at −70 for 1 hour, 20 ml of ice was added to the reaction solution, and the temperature was raised to 0 ° C. The reaction solution was diluted with 100 ml of ethyl acetate, the aqueous layer was separated, and the organic layer was washed with aqueous citric acid, saturated saline, saturated aqueous sodium bicarbonate, and saturated saline, and then dried over anhydrous magnesium sulfate. It was dried and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (elution solvent: high-pressure hexane / ethyl acetate = 10/1) to obtain 45 O mg of the title compound as a white powder. Melting point: 90-92 ° C

NMR spectrum _{(CDC1 3) δ ppm:.} . 7.32 (. 1H, dd, J = 8.6Hz J = 8.8Hz), 7.52 (2H, m), 7.61 (1H, m) 7.79-7 89 (4H, m ).

 Reference Example 2 8

2,4—Dimethoxy-5—N, N—Dimethylsulfamoylpenzophenone 6 8.3 mg of sodium hydride in 10 m 1 anhydrous dimethylformamide in a suspension of 5 OO mg of 2 — Hydroxy-1-4—Methoxy-5—N, N-Dimethylsulfamoylpenzophenone in 1 O ml of anhydrous dimethylformamide in a nitrogen atmosphere The mixture was added dropwise at 3-4 ° C, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was cooled again, methyl iodide was added dropwise, and the mixture was stirred at room temperature for 15 hours. The reaction solution was diluted with 150 ml of ethyl acetate, and the mixture was diluted with saturated aqueous sodium bicarbonate, saturated saline, 3N-hydrochloric acid, saturated saline, aqueous sodium thiosulfate, saturated saline, saturated sodium bicarbonate, and then saturated saline. After washing, it was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was triturated with diisopropyl ether to obtain 410 mg of the title compound as a pale yellow powder.

 Melting point: 1 4 8 — 1 5 0

NMR spectrum _{(CDC1 3) (5 ppm:} . 2.84 (6H, s), 3. 83 (3Η, s), 4.02 (3H, s), 6. 56 (1H s), 7.44 (2H, dd, J = 7.3Hz, J = 7.9Hz), 7.57 (1H, t, J = 7.2Hz), 7.76 (2H, dd.J = 1.7Hz. J = 8.5Hz). 7.96 (1H, s) .

 Test example 1

 Measurement of ileal bile acid transporter inhibitory activity using C aco — 2 cells The measurement of ileal bile acid transporter inhibitory activity in this test example

 This was performed according to the method of Wong et al. Described in [J. Biol. Chem., 269, 1340-1347 (1994)].

 That is, Cac o — 2 cells described in [Am. J. Physiol., 264, Gl118-G1125 (1993)] were used as cells expressing the bile acid transporter.

Koragenkoto the 9 6 Ueru culture plates (trade name: View plate, pad force manufactured by one de Co.) C aco of ⁴ Χ 1 0 4 / ml to each Ueru of - 2 cells 2 0 0 / i 1 not a One seeded after For 15 days or more, the medium was appropriately replaced and cultured. After addition of the sample (the compound of Example 1, 1 1 and 1 5) to the culture system, 0. l C i radioactive Tauroko Lumpur acid ^{([3 H] - taurochol ic} acid: NEN Co.) was added for 1 hour Lee Nkyube preparative 5% C 0 ₂ of the presence 3 7, C aco by radioactive taurocholate ileal bile acid transformer Porter - were incorporated into 2 cells. Caco-2 cells were ice-cold in 0.2% bovine serum albumin, ImM Tauroko. — Washed 5 times with PBS containing phosphoric acid (cold) and left to dry. Liquid scintillation cocktail (trade name: Microscint20, manufactured by Packard) is added to each well of the 96-well culture plate in a volume of 250 u1. The radioactivity was measured by the manufacturer. The inhibition rate (%) was determined from the radioactivity of the control obtained without using the test compound and the radioactivity when the test compound was used at a certain concentration, and the percentage of the test compound that inhibited the ileal bile acid transporter activity by 50% was calculated. The concentration was determined. The results are shown in Table 4.

 [Table 4]

Example compound number I C so (g / m I)

3 2 (Isomer A) 1

 3 2 (Isomer B) 0.8

 3 7 2. 9

 4 2 (Isomer B) 2.1

 5 1 (Isomer B) 1.3

Test example 2

 Measurement of ileal bile acid transporter inhibitory activity using rat everted ileal rings

 The measurement of the ileal bile acid transporter inhibitory activity in this test example was performed according to the method of Stewart et al. Described in [Pharm. Res., 12, 693-699 (1995) 3].

That is, a rat inverted intestinal ring was used as a material for the bile acid transporter. A 6-10 week old male Wistar Mammichi rat was anesthetized with ether, the ileum was removed about 20 cm from the blind end, inverted, and then placed in the ice-cold Ringer's buffer from the blind end. Twenty-four rat inverting intestinal rings were obtained by applying a force of 5 mm in order. In order to correct the difference in bile acid transporter expression levels depending on the location of the ileum, rings were appropriately selected from the upper and lower parts of the ileum, and four rings were included in one group, for a total of six groups. The ileal bile acid transporter incorporates the radioactive taurocholic acid into the rings while shaking each ring in a 1 ml radioactive taurocholic acid solution at 37 rpm for 3 minutes at 90 rpm. I let you. The composition of the radioactive taurocholic acid solution consists of 1.0 Ci radioactive taurocholic acid, 0.037 mM taurocholic acid (cold), appropriate concentrations of various analytes and Ringer's buffer. After washing the ring three times with Ringer's buffer, the wet weight is measured, put in a vial, and add 0.5 ml of tissue lysing agent NCS-II (manufactured by AMERS HAM). Leave overnight to completely dissolve. 2. 5 ml of liquid scintillation cocktail was added, and the radioactivity was measured with a liquid scintillation force scintillation counter.

 The ileal-type bile acid transporter activity is calculated by correcting each radioactivity by wet weight and expressing it in dpm / mg (radioactivity per 1 mg). The inhibition rate of ileal bile acid transport activity at 10 O wg Zml was determined. Table 5 shows the results.

 [Table 5] Example compound number Inhibition rate (%)

1 7 2

4 2 (Isomer B) 7 7 Formulation Example 1

Tablets

 Compound of Example 1 10 mg Lactose 68.

 Microcrystalline cellulose 20 Sodium carboxymethyl starch 5 Light citric anhydride 0.5 Magnesium stearate

 1 0 5 mg

Claims

The scope of the claims

-General formula

[Wherein, R ¹ is a CC ₁₀ aryl group substituted by 1 to 3 偭 with a group selected from substituent group α, a tetrazolyl group optionally substituted with a group selected from substituent group / 3, ( (C ₃ -C cycloalkyl) dirubamoyl group, (d-C ₆ alkyl) sulfonylcarbamoyl group, one or three groups selected from substituent group δ may be substituted (Ce—C ₁₀ aryl) A sulfonylcarbamoyl group, a sulfo group, a d-C alkylsulfonyl group, and one or three C ₆ -C ₁₀ arylsulfonyl groups, which may be substituted with a group selected from the substituent group J3, a mono- (d-C alkyl) amino sulfonyl group, di- (d - C alkyl) aminosulfonyl group, d - C § Ruki Rusuru alkylsulfonyl group, which may be 1 to 3 substituted with a group selected from substituent group J3 C ₇ - C u7 reel Carbonylamino group, substituent group / 3 1 may be three substituents at selected by group replacement has been Ru is selected from good tetrazolyl Luca Lupo arylsulfonylamino group or an optionally substituted group 3 group (C ₆ - (: ₁₀ Ariru) sulfonyl Rukarubamo Iruamino Represents a group,

R ² , R ³ and R ⁴ are the same or different and are each a hydrogen atom, a d-C β alkyl group, a d-C alkoxy group, a hydroxyl group, a halogen atom, an amino group, a mono (C

! -C alkyl) amino group or di (d-C alkyl) amino group

R ⁵ is a group selected from substituent group / 3, and may be substituted with 1 to 3 C _e -C ₁₀ aryl group or a group selected from substituent group 3 may be substituted with 1 to 3 or may be condensed with a benzene ring, and represents a phenyl, pyrrolyl, 11-dioxocenyl, thiazolyl or oxazolyl group;

R ⁶ is a d—C ₁₀ alkyl group; formula—W—R ⁷ [wherein W represents a single bond or a C—C alkylene group, and R ⁷ is a group selected from substituent group a. And represents a C ₃ -C cycloalkyl group which may be substituted by 3 or 3 and may be condensed with a benzene ring. ] Represents a group or a substituent group "1 to 3 substituents which may be C ₇ _ C ₁₆ Ararukiru group with a group selected from the r having.

However, when R ^{1 represents} a C 1 -C ₆ alkylsulfonyl group or C i -C ₆ alkylsulfinyl group, R ⁶ represents a group other than a d—C ₁₀ alkyl group. ] Or a pharmacologically acceptable salt thereof.

<Substituent group a>

 May be substituted with a group selected from Substituent Group 3, tetrazolyl group, sulfo group,

A C ₆ -C ₁₀ arylsulfonylamino group which may be substituted by 1 to 3 groups selected from a CC alkylsulfonyl group, a -C alkylsulfonylamino group and a substituent group i3

 <Substituent group β>

 C-C alkyl group, C C alkoxy group and halogen atom

 <Substituent group>

C - C beta alkyl group, C one C alkoxy group, a halogen atom and the formula - Ζ - R ⁸ [wherein, Zeta is a single bond or d - a C alkylene group, R ⁸ is force Rupokishi group, C ₂ -Represents a C alkoxycarbonyl group, a rubamoyl group, a mono (C-Calkyl) rubamoyl group, a di- (Ct-Cβalkyl) rubamoyl group, a d-Calkylsulfonyl group, or a hydroxyl group. A group having

<Substituent group δ>

C-C alkyl group, -C alkoxy group, halogen atom and substituent A phenyl group which may be substituted by 1 to 3 groups selected from the group i3.

2. In claim 1, R ¹ , a phenyl group substituted by a group selected from the substituent group α1, a tetrazolyl group optionally substituted by a group selected from the substituent group 31 , (C ₅ -C β cycloalkyl) carbamoyl group, (d-C alkyl) sulfonylcarbamoyl group, phenylsulfonylcarbamoyl group, sulfo group which may be substituted with a group selected from substituent group δ 1 , -Cβ alkylsulfonyl group, phenylsulfonyl group, methylaminosulfonyl group, ethylaminosulfonyl group, dimethylaminosulfonyl group, dimethylamino, which may be substituted with a group selected from substituent group i31 a sulfonyl group, d - C ₄ alkylsulfinyl group, may be substituted with a group selected from the substituent group / 3 2, phenylene Rukaruponiruami Roh Wakashi Ku is tetrazolyl Luca Lupo Ruamino group or base Njiru Amin acids are substituent group 3 1 Good phenylalanine sulfo be substituted with a group selected from carbamoylmethyl § amino group or a pharmacologically acceptable salt thereof.

<Substituent group α 1>

Substituent group / 32 Tetrazolyl group, sulfo group, C! - C ₄ alkylsulfonyl group, methylsulfonyl § amino group, Echirusuruho Niruami amino group and substituent group / 3 2 is selected from the good phenyl Suruhoniruamino group optionally substituted with a group

<Substituent group β 1>

C-C ₄ alkyl group, CC ₄ alkoxy group, fluorine atom and chlorine atom substituent group 3 2>

 C-C alkyl group, C-C alkoxy group, fluorine atom and chlorine atom

<Substituent group δ 1>

C! A phenyl group which may be substituted with a group selected from -C ₄ alkyl, -C alkoxy, a halogen atom and a substituent group / 31;

3. In claim 1, R ¹ force, 2-, 3 — or 4 — (1 H — Tolazole-5-yl) phenyl group, 2—, 3—or 4— (1-methyltetrazol—5_yl) phenyl group, 2—, 3—or 4— (1—methoxytetrazol— 5 —yl) phenyl group, 2 —, 3 _ or 4 _ (1 —fluorotetrazol 5 —yl) phenyl group, 2 —, 3 _ or 4 — (1 monochlorotetrazole— 5 —yl) phenyl Group, 2 —, 3 — or 4-methylsulfonylphenyl group, 2 —, 3 — or 4 —ethylsulfonylphenyl group, 2 —, 3 — or 4 — propylsulfonylphenyl group, 2 _ , 3 — or 4-butylsulfonylphenyl group, 2 —, 3 — or 4-methylsulfonylaminophenyl group, 2-, 3 _ or 4 _phenylsulfonylaminophenyl group, substituent group 32 Even if it is Iterator Bok Razoriru group, (- C alkyl) S Le Honi carbamoyl group, substituent group (5 2 good full E sulfonyl sulfo be substituted with a group selected from carbamoylmethyl group, one C ₄ alkylsulfonyl group, Substituent group a phenylsulfonyl group which may be substituted with a group selected from β2, a d-C7alkylsulfinyl group, a group selected from Substituent group 33, phenylcarponylamino or Is a phenylsulfonylcarbamoylamino group optionally substituted with a tetrazolylcarbonylamino group or a group selected from substituent group 32, or a pharmaceutically acceptable salt thereof.

<Substituent group / 32>

C! -C ₂ alkyl group, d-C ₂ alkoxy group, fluorine atom and chlorine atom <Substituent group / 3 3>

 Methyl group, methoxy group, fluorine atom and chlorine atom

<Substituent group δ 2>

 C! A phenyl group which may be substituted with a group selected from -C alkyl group, -C alkoxy group, fluorine atom, chlorine atom and substituent group β2.

4. In claim 1, R ¹ , 2-, 3-or 4-(1 H-tetrazol-5 -yl) phenyl, 2 _, 3 — or 4 —methylsulfonyl Phenyl group, 2 —, 3 _ or 4 —ethylsulfonylphenyl group, tetrazolyl group which may be substituted with a group selected from substituent group 32, substituent group (selected from 53 Phenylsulfonylcarbamoyl group, methylsulfonyl group, ethylsulfonyl group, propylsulfonyl group, butylsulfonyl group, phenylsulfonyl group which may be substituted with group or replacement which may phenylalanine sulfonyl be carbamoylmethyl § amino group (the substituent is, d - C ₂ alkyl, main butoxy, fluorine or chlorine) Benjiruamin acids or pharmacologically acceptable salt thereof is.

<Substituent group i3 2>

 C-C alkyl group, d-C alkoxy group, fluorine atom and chlorine atom

<Substituent group / 3 3>

 Methyl group, methoxy group, fluorine atom and chlorine atom

 <Substituent group δ 3>

 A methyl group, a methoxy group, a fluorine atom, a chlorine atom and a phenyl group which may be substituted by d-C alkyl, methoxy, fluorine or chlorine;

5. The method according to claim 1, wherein R ¹ is substituted with a group selected from 2-methylsulfonylphenyl, 3-methylsulfonylphenyl, 4-methylsulfonylphenyl, and a substituent group β 3. Or a phenylsulfonylcarbamoyl group, a methylsulfonyl group, an ethylsulfonyl group, a butylsulfonyl group, a phenylsulfonyl group, or a phenylsulfonylcarbamoyl group which may be substituted with a group selected from the substituent group <54. Benzylamine which is a phenylsulfonylcarbamoylamino group which may be substituted with methyl, or a pharmacologically acceptable salt thereof.

<Substituent group β 3>

 Methyl group, methoxy group, fluorine atom and chlorine atom

Substituent group δ 4>

Methyl, phenyl and methylphenyl groups.

6. In Claim ¹ , benzylamine which is R ¹ , 1 H-tetrazol-5-yl group, methylsulfonyl group, ethylsulfonyl group or tosylcarbamoylamino group or a pharmacologically acceptable salt thereof. Salt.

7. A benzylamine or a pharmacologically acceptable salt thereof according to claim 1, wherein R ¹ is a 1 H-tetrazol-5-yl group.

8. In any one of claims 1 to 7, wherein R ² , R ³ and R ^{4 are the} same or different and are a hydrogen atom, d—C ₂ alkyl group, C—C ₂ Alkoxy group, hydroxyl group, fluorine atom, chlorine atom, amino group, mono- (C

! Benzylamines which are -C alkyl) amino group or di- (Ci-Calkyl) amino group, or pharmacologically acceptable salts thereof.

9. In any one of claims 1 to 7, wherein R ² , R ³ and R ^{4 are} the same or different and are a hydrogen atom, a methyl group, a methoxy group, a hydroxyl group, a fluorine atom. Benzamines which are atoms or chlorine atoms or pharmacologically acceptable salts thereof.

10. The benzylamine according to any one of claims 1 to 7, wherein R ² is a hydrogen atom, a methoxy group or a fluorine atom, and R ³ and R ⁴ are hydrogen atoms. Or a pharmacologically acceptable salt thereof.

11. The benzylamine or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 7, wherein R ² , R ³ and R ⁴ are hydrogen atoms.

1 2. In any one of claims 1 to 11, R ⁵ may be substituted with a group selected from substituent group 31, phenyl, naphthyl, phenyl. Benzodienyl, 1,1-dioxocenyl, thiazolyl, benzocenyl, 1,1-dioxobenzocenyl or benzothiazolyl group or a pharmacologically acceptable salt thereof.

<Substituent group β 1> C! One C ₄ alkyl group, d - C ₄ alkoxy group, fluorine atom and chlorine atom.

13. In Claims 1 to 11, R ⁵ , optionally substituted with a group selected from substituent group 32, phenyl, phenyl, thienyl, thiazolyl, benzophenyl or 1, 1 — Benzoamines which are dioxobenzothenyl groups or pharmacologically acceptable salts thereof.

 <Substituent group 3 2>

C! - C ₂ alkyl group, d - C ₂ alkoxy group, fluorine atom and chlorine atom.

14. In any one of claims 1 to 11, a phenyl group, benzothenyl which may be substituted with a group selected from R ⁵ substituent group 33. A benzylamine or a pharmacologically acceptable salt thereof, which is a 1,1-dioxobenzophenyl group.

 <Substituent group β 3>

 Methyl, methoxy, fluorine and chlorine atoms.

15. In any one of the claims 1 to 11, wherein R ⁵ is phenyl, 2 —, 3 — or 4-methoxyphenyl, 2, 3-dimethoxyphenyl. , 2,4-Dimethoxyphenyl, 3,4-Dimethoxyphenyl, 3,5—Dimethoxyphenyl or 3,4,5—Trimethoxyphenyl or 1,

1-Dioxobenzothiophene-3-benzyl-benzylamines or pharmacologically acceptable salts thereof.

16. In any one of claims 1 to 11, wherein R ^s is phenyl or benzylamine, which is a 2 —, 3 — or 4 — methoxyphenyl group. Or a pharmacologically acceptable salt thereof.

17. The benzylamine as defined in any one of claims 1 to 11, wherein R ^{5 is} a phenyl group, or a pharmacologically acceptable salt thereof.

18. In any one of claims 1 to 17, R ⁶ , a C—C alkylene group, a formula W—R ⁷ , wherein W is a single bond or C R ⁷ is a C ₅ -C cycloalkyl group which may be substituted with a group selected from the substituent group r 1 and may be condensed with a benzene ring. In -] group or substituted with a group selected from Substituent group § 1 may be Ararukiru group having (C ₄ Ru alkyl der § Li Ichiru portion alkyl moiety is phenyl group C tau.) Certain benzylamines or pharmacologically acceptable salts thereof.

<Substituent group 1>

C! - C alkyl group, t _ butyl group, C i - C alkoxy group, a fluorine atom, in a chlorine atom and Shikiichi Z _ R ⁸ [wherein, Z is a single bond or d - a C ₂ alkylene group, R ⁸ is carboxy, C ₂ - having C ₄ alkylsulfonyl or a hydroxyl group] - C alkoxy force Ruponiru force Rubamoi Le, mono - (C i - C alkyl) force Rubamoiru, di- (C i - C alkyl) force Rubamoiru, d Base.

1 9. In any one of claims 1 to 17, an R ⁶ -C C alkylene group, a group having the formula _W—R ⁷ , wherein W is A bond or a methylene group, and R ⁷ is a C ₅ -C β cycloalkyl group which may be substituted with a group selected from Substituent Group a2 or may be condensed with a benzene ring. Or a aralkyl group which may be substituted with a group selected from substituent group a2 (where the aryl moiety is a phenyl group and the alkyl moiety is a C i -C alkyl group) or a benzylamine or a pharmaceutically acceptable salt thereof. Above acceptable salts.

Substituent group 2>

 Methyl group, t-butyl group, methoxy group, fluorine atom, chlorine atom, carboxy group, methoxycarbonyl group, dimethylcarbamoyl group and hydroxymethyl group.

20. In Claims 1 to 17, R ⁶ is an isopropyl group, a butyl group, a t_butyl group, a neopentyl group, a 1-ethylpentyl group, a 2-ethylhexyl group or a group of substituents. A benzylamine which is cyclohexyl, benzyl, 1-phenylethyl or 2-phenylethyl group, or a pharmacologically acceptable salt thereof, which may be substituted with a group selected from α3. Substituent group 3>

 Methyl, methoxy, fluorine and chlorine atoms.

21. In any one of claims 1 to 17, wherein R ^e is 1-ethylpentyl, cyclohexyl or 1-phenylethyl, or a pharmacologically acceptable benzylamine. Acceptable salt.

22 2-A benzylamine or a pharmacologically acceptable salt thereof according to any one of claims 1 to 17, wherein R ⁶ , 1-ethylpentyl or 1-phenylethyl is a benzylamine. .

 2 3.-(1-phenylethyl) 1-(phenyl-[6-hydroxy-1-4-methoxy _ 2 _ (1 H-tetrazole-5 _ yl) phenyl] methyl}

N-(1 -ethylpentyl)-{phenyl [3-(1 H-tetrazol-5-yl) phenyl] methyl}

 N- (1-phenylenyl)-{phenyl [3_ (1H-tetrazole-5-yl) phenyl] methyl} amine

 N- (1-ethylpentyl)-{phenyl [4- (1H-tetrazol-5-yl) phenyl] methyl} amine

 N- (1-phenylenyl)-{phenyl- [4- (1H-tetrazole-5-yl) phenyl] methyl} amine;

 N- (1 1-phenylethyl) 1-((4-methoxyphenyl) 1- [1- (1H-tetrazol-5-yl) phenyl] methyl} amine

 N- (1 phenylethyl) 1-phenyl (3-methylsulfonylcarbamoylphenyl) methyl] amine,

 N- (1-ethylpentyl)-[phenyl- (3-N-tosylcarbamoylphenyl) methyl] amine,

N-cyclohexyl [phenyl (3-N-tosylcarbamoylphenyl) methyl] amine, N- (1-phenylenyl)-[phenyl (3-N-tosylcarbamoylphenyl) methyl] amine,

 N— (1—phenylethyl) 1 {phenyl [3— (2— (2-methylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} amine

 N- (1 -phenylethyl) 1 {phenyl [3 — (2-(3 -methylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} amine

 N- (1-phenylenyl)-{phenyl- [3- (2- (4-methylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} amine;

 N- (1-phenylethyl) 1-phenyl [4- (2— (2-methylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} amine

 N- (1 phenylethyl) 1 {phenyl [4 1 (2 — (4-methylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} amine

 N- (Indone-1-yl) -1- [phenyl- (2-ethylsulfonylphenyl) methyl] amine,

 N- (2-phenylenyl) methyl [phenyl (2-ethylsulfonylphenyl) methyl] amine,

 Ν—t e r t —butyl- [phenyl (2-phenylphenylsulfenyl) methyl] amine,

 N— {2-[1 — phenyl 1 _ (N— 1 —phenylethyl) amino] methyl} phenyl N '— tosylperia,

 N— {2- [1- (4-methoxyphenyl) 1-111 (N—1—phenylethyl) amino] methyl} phenyl N'—tosylperia,

 N— (1-ethylpentyl) — {2—indenyl— [3— (1H—tetrazo—5—yl) phenyl] methyl} amine

N— (1—phenylethyl) 1 {2—indenyl— [4-1 (1H—tetrazol-1-5-yl) phenyl] methyl} amine, N— (1-ethylpentyl) -1- {1-naphthyl- [3- (1H—tetrasol-5-yl) phenyl] methyl} amine

 N- (1 phenylethyl) 1 {1 —naphthyl— [3— (1 H—tetrazol — 5 —yl) phenyl] methyl} amine,

 N- (1 -phenylethyl) 1 {1 1 naphthyl [4- (1 H-tetrazole-5-yl) phenyl] methyl} amine,

 N- [1- (4-Bromophenyl) ethyl] 1 {(1,1_dioxothiophene 1—2-yl)-[3— (1H—tetrazo-lu-5-yl) phenyl] methyl} amimi ,

 N- (1—ethylpentyl) — {2—thiazolyl [3- (1H—tetrazo—ru5—yl) phenyl] methyl} amine

 N— (1—phenylethyl) — {3—thiazolyl [3— (1H—tetrazol-5-yl) phenyl] methyl} amine,

 -(1-phenylethyl)-{2-indrillone [3-(1H-tetrazol 5-yl) phenyl] methyl} amine,

 N— [1- (4-bromophenyl) ethyl] — {2_indryl— [3— (1H—tetrazol-5—yl) phenyl] methyl} amine;

 N-cyclohexyl-1-[(1,1-dioxybenzothiophene-3-yl)-(2-methylsulfonylphenyl) methyl] amine;

 N— [1— (4-bromophenyl) ethyl] — {(1,1,1-dioxybenzothiophene-2-yl) -1- [3— (1H—tetrazol-5-yl) phenyl] methyl} amine ,

 N- [1- (4-bromophenyl) ethyl] 1- {2-benzothiazolyl- [3- (1H-tetrazol-5-yl) phenyl] methyl} amine or

N-(1 -phenylethyl)-{3-benzoxazolyl-[3-(1 H-tetrazol- 1-5-yl) phenyl] methyl} amine Or a pharmacologically acceptable salt thereof.

2 4. —General formula

[Wherein, R ¹ is a C _e —C ₁₀ aryl group substituted by 1 to 3 groups with a group selected from substituent group α, a tetrazolyl group optionally substituted with a group selected from substituent group 0 , (C ₃ -C cycloalkyl) carbamoyl group, (d-C β alkyl) sulfonylcarbamoyl group, and one or three groups selected from substituent group δ may be substituted (C 1 -C ₁₀ Aryl) a sulfonylcarbamoyl group, a sulfo group, d—C β alkylsulfonyl group, and one or three substituents selected from the substituent group β. C ₆ —C ₁₀ arylsulfonyl group, mono (d - C _beta alkyl) amino sulfonyl group, di - (d - C alkyl) aminosulfonyl group, d - C 7 Ruki Rusuru alkylsulfonyl group, may be 1 to 3 substituted with a group selected from the substituent group beta C ₇ - C § reel carbonyl § amino group, substituent i3 may be 1 to 3 substituents in replacement has been Ru is selected from good tetrazolyl Luca Lupo arylsulfonylamino group or substituent group / 3 group by a group selected from (C ₆ - C ₁₀ Ariru) sulfonyl A rucarbamoylamino group;

R ² , R ³ and R ⁴ may be the same or different and each represents a hydrogen atom, a d-C alkyl group, a d-C alkoxy group, a hydroxyl group, a halogen atom, an amino group, a mono- (C-C alkyl) amino group or Di- (d-C alkyl) amino group

R ⁵ is a group selected from substituent group / 3, which may be substituted 1 to 3 偭 C _e —C ₁₀ aryl group or substituent group; 1 to 3 substituted with a group selected from 3 Well Which may be condensed with a benzene ring, represents a phenyl, pyrrolyl, 1,1-dioxophenyl, thiazolyl or oxazolyl group;

R ⁶ is a d—C ₁₀ alkyl group, formula —W—R ⁷ [where W is a single bond or C! Represents a -C _e alkylene group, and R ⁷ represents a C ₃ -C cycloalkyl group which may be substituted by 1 to 3 groups selected from substituent group a and may be condensed with a benzene ring. ] Group or 1 group selected from Substituent Group § to 3 optionally substituted C ₇ having - shows the C ₁₆ Ararukiru group. ]

A composition for inhibiting ileal bile acid transporter activity, comprising a benzylamine having the above formula or a pharmacologically acceptable salt thereof as an active ingredient.

<Substituent group α>

A tetrazolyl group, a sulfo group, a CC β alkylsulfonyl group, a —C alkylsulfonylamino group, and a group selected from the substituent group 3 which may be substituted with a group selected from the substituent group / 3. Up to 3 optionally substituted C ₆ _ C ₁₀ 7 arylsulfonylamino groups

 <Substituent group e>

 C-Cβ alkyl group, d-Cβ alkoxy group and halogen atom

<Substituent group Ύ>

C! -C β alkyl group, d-C _β alkoxy group, halogen atom and formula

-R ⁸ [wherein, Ζ represents a single bond or a d-C alkylene group, and R ⁸ represents a carbonyl group, a C ₂ -C alkoxycarbonyl group, a rubamoyl group, a mono (c

! -C alkyl) rubamoyl group, G (d-C alkyl) rubamoyl group, d-Cβ alkylsulfonyl group or hydroxyl group. ] <5>

 C! A phenyl group which may be substituted by 1 to 3 groups selected from -C alkyl group, d-C alkoxy group, halogen atom and substituent group i3.

2 5. In claim 24, a group selected from the group consisting of R ¹ and a substituent group α 、 A phenyl group substituted with, a tetrazolyl group optionally substituted with a group selected from substituent group 31, a (C-C cycloalkyl) carbamoyl group, a (C, -C alkyl) sulfonylcarbamoyl group A substituent group (a phenylsulfonylcarbamoyl group which may be substituted with a group selected from 51, a sulfo group, a -C alkylsulfonyl group, a substituent group / may be substituted with a group selected from 31) Fuenirusuruho group, Mechiruami Nosuruhoniru group, E chill aminosulfonyl group, dimethylaminopyridine Nosuruhoniru group, Jechiruami Nosuruhoniru group, - C ₄ alkylsulfinyl group, it may be substituted with a group selected from substituent group 3 2 Or a phenylcarbonylamino or tetrazolylcarbonylamino group or a group selected from substituent group i31. Sulfonyl sulfonylcarbamoyl § Mi amino group in which Ben Jiruami emissions such or a composition for inhibiting ileal type bile Shirusan transporter activity containing pharmacologically acceptable salt thereof as an active ingredient.

<Substituent group α 1>

Substituent group / Select from tetrazolyl group, sulfo group, C, -C ₄ alkylsulfonyl group, methylsulfonylamino group, ethylsulfonylamino group and substituent group 32 which may be substituted with a group selected from group 32 Phenyl sulfonylamino group which may be substituted with

<Substituent group / 3 1>

C - C ₄ alkyl group, C _t one C ₄ alkoxy group, fluorine atom and chlorine atom <substituent group i3 2>

 C! -C alkyl group, d-C alkoxy group, fluorine atom and chlorine atom

<Substituent group 1>

A phenyl group which may be substituted with a group selected from C 1, -C alkyl, -C ₄ alkoxy, a halogen atom and a substituent group 01;

26. In claim 24, the R ¹ force 2 —, 3 — or 4 1 (1 H—tetrazol-5 —yl) phenyl group, 2 —, 3 — or 4— (1 monomethyl) Tetrazole-5-yl) phenyl group, 2 —, 3 — or 4-1 (1-methoxytetrazol-5 —yl) phenyl group, 2 —, 3 _ or 4-1 (1 —Fluorotetrazoyl-5 —y) Le) phenyl, 2 —, 3 — or 4 — (1 monochlorotetrazol-5 —yl) phenyl, 2 —, 3 — or 4 —methylsulfonylphenyl, 2 —, 3 — or 4 —ethyl Sulfonylphenyl group, 2 _, 3 — or 4 —propylsulfonylphenyl group, 2 —, 3 _ or 4 —butylsulfonylphenyl group, 2 —, 3 — or 4 —methylsulfonylaminophenyl group, 2 —, 3 - or 4 _ phenylalanine sulfonyl § Mi Nofueniru group, may be substituted with a group selected from substituent group 3 2 Te Torazoriru group, (d - C ₂ alkyl) sulfonyl Rukarubamoi Group, but it may also be substituted with a group selected from the substituent group <5 2 phenylalanine sulfonylcarbamoyl group, - C ₄ alkylsulfonyl group, optionally off be substituted with a group selected from Substituent Group 3 2 An phenylsulfonyl group, a d-C alkylsulfinyl group, or a group selected from substituent groups / 33, a phenylcarbonylamino or tetrazolylcarbonylamino group or a substituent group / 32 A phenylsulfonylcarbamoylamino group which may be substituted with a group selected from the group consisting of benzylamines or a pharmacologically acceptable salt thereof as an active ingredient for inhibiting ileal bile acid transporter activity. Composition. <Substituent group β 2>

 C-C alkyl group, d-C alkoxy group, fluorine atom and chlorine atom

<Substituent group / 3 3>

 Methyl group, methoxy group, fluorine atom and chlorine atom

 <Substituent group δ 2>

 A phenyl group which may be substituted with a C-C alkyl group, a -C alkoxy group, a fluorine atom, a chlorine atom and a group selected from Substituent group 32;

27. In Claim 24, R ¹ , 2-, 3-or 4- (1 H-tetrazol_ 5 _yl) phenyl, 2 —, 3 — or 4-methylsulfo Nylphenyl group, 2 —, 3 — or 4-ethylsulferphenyl group, Substituent group / 32 Tetrazolyl group which may be substituted with a group selected from 2, Substituent group selected from δ 3 A phenylsulfonylcarbamoyl group, a methylsulfonyl group, an ethylsulfonyl group, a propylsulfonyl group, a butylsulfonyl group, a substituent group which may be substituted; a phenylsulfonyl group which may be substituted with a group selected from 33); Is an ileum containing, as an active ingredient, a benzylamine which is a phenylsulfonylcarbamoylamino group which may be substituted (the substituent is C-Calkyl, methoxy, fluorine or chlorine) or a pharmacologically acceptable salt thereof. A composition for inhibiting type 1 bile acid transport activity.

Substituent group 3 2>

C: -C ₂ alkyl group, -C alkoxy group, fluorine atom and chlorine atom <Substituent groups / 3 3>

 Methyl group, methoxy group, fluorine atom and chlorine atom

<Substituent group δ 3>

 A methyl group, a methoxy group, a fluorine atom, a chlorine atom and a phenyl group which may be substituted by d-C alkyl, methoxy, fluorine or chlorine;

28. In Claim 24, a group selected from the group consisting of R ¹ ^ 2-methylsulfonylphenyl group, 3-methylsulfonylphenyl group, 4-methylsulfonylphenyl group, and substituent group 33. A phenylsulfonylcarbamoyl group, a methylsulfonyl group, an ethylsulfonyl group, a butylsulfonyl group, a phenylsulfonyl group, or a tetrazolyl group which may be substituted with a group selected from the group of substituents δ4. A composition for inhibiting overnight activity of ileal bile acid transport, comprising as an active ingredient benzylamines which are a phenylsulfonylcarbamoylamino group which may be substituted with methyl or a pharmacologically acceptable salt thereof.

Substituent group 3 3>

Methyl group, methoxy group, fluorine atom and chlorine atom <Substituent group δ 4>

 Methyl, phenyl and methylphenyl groups.

2 9. In claim 24, benzylamines which are R ¹ force ^ 1 Η-tetrazol-5-yl group, methylsulfonyl group, ethylsulfonyl group or tosylcarbamoylamino group or pharmacologically thereof. A composition for inhibiting ileal bile acid transporter activity, comprising an acceptable salt as an active ingredient.

30. In Claim 24, the ileal bile acid transport comprising as an active ingredient a benzylamine or a pharmacologically acceptable salt thereof, wherein R ¹ is a 1 H-tetrazol-5-yl group. A composition for inhibiting evening activity.

31. In any one of claims 24 to 30, R ² , R ^3, and R ^{4 are the} same or different and are a hydrogen atom, a d-C alkyl group, d - C ₂ alkoxy group, a hydroxyl group, a fluorine atom, a chlorine atom, an amino group, a mono one. (C -! C alkyl) amino or di- (C i - C alkyl) Benjiruami emissions such or a pharmacologically an amino group tolerance A composition for inhibiting ileal bile acid transporter activity, comprising a salt to be used as an active ingredient.

3 2. In any one of claims 24 to 30, wherein R ² , R ^3, and R ^{4 are the} same or different and are a hydrogen atom, a methyl group, or a methoxy group. A composition for inhibiting ileal bile acid transporter activity, comprising a benzylamine having a hydroxyl group, a fluorine atom or a chlorine atom or a pharmacologically acceptable salt thereof as an active ingredient.

3 3. In any one of claims 24 to 30, wherein R ² is a hydrogen atom, a methoxy group or a fluorine atom, and R ³ and R ⁴ are hydrogen atoms. A composition for inhibiting ileal bile acid transport activity, comprising a certain benzylamine or a pharmacologically acceptable salt thereof as an active ingredient.

3 4. In any one of claims 24 to 30, wherein R ² , R ^3, and R ⁴ are hydrogen atoms, or pharmaceutically acceptable salts thereof. A composition for inhibiting ileal bile acid transporter activity, which comprises an acceptable salt as an active ingredient.

3 5. In any one selected from the second item 4 to the third item 4 claims, R ⁵ force, may be substituted with a group selected from Substituent group beta 1, phenyl, naphthyl , Cenyl, 1,1 dioxocenyl, thiazolyl, benzocenyl, 1,1-dioxobenzocenyl or benzothiazolyl benzylamines or pharmacologically acceptable salts thereof as active ingredients A composition for inhibiting ileal bile acid transporter activity.

 <Substituent group 3 1>

C! - C ₄ alkyl group, d - C ₄ alkoxy group, fluorine atom and chlorine atom. 36. In Claims 24 to 34, R ^s may be substituted with a group selected from substituent group / 32, phenyl, phenyl, thienyl, thiazolyl, benzophenyl or 1,, (1) A composition for inhibiting ileal bile acid transporter activity, comprising as an active ingredient a benzylamine which is a dioxobenzochelyl group or a pharmacologically acceptable salt thereof.

Substituent group / 3 2>

 C! -C alkyl group, d-C alkoxy group, fluorine atom and chlorine atom.

3 7. In any one selected from the second item 4 to the third item 4 claims, R ⁵ is a substituent group / 3 3 selected is that also may phenyl group substituted with a group, Ben A composition for inhibiting ileal bile acid transporter activity, comprising as an active ingredient a benzylamine which is a zochenil group or a 1,1-dioxobenzochenyl group or a pharmacologically acceptable salt thereof.

<Substituent group 0 3>

 Methyl, methoxy, fluorine and chlorine atoms.

38. In any one of claims 24 to 34, wherein R ⁵ , phenyl, 2 —, 3 _, or 4 methoxyphenyl, 2, 3 — dimethyl. Toxiphenyl, 2,4-Dimethoxyphenyl, 3,4-Dimethoxyphenyl, 3,5-Dimethoxyphenyl or 3,4,5-Trimethoxyphenyl or 1,1-Dioxobenzothio A composition for inhibiting ileal bile acid transporter activity, comprising a phenyl-3-yl group benzylamine or a pharmacologically acceptable salt thereof as an active ingredient.

39. In any one of claims 24 to 34, benzylamines which are R ⁵ , phenyl or 2 —, 3 — or 4 — methoxyphenyl group. Or a composition for inhibiting ileal bile acid transporter activity, comprising a pharmacologically acceptable salt thereof as an active ingredient.

40. In any one of claims 24 to 34, wherein R ⁵ contains a phenylamine, which is a phenyl group, or a pharmacologically acceptable salt thereof as an active ingredient. A composition for inhibiting ileal bile acid transporter activity.

41. In any one of the claims 24 to 40, R ⁶ force, C a -C alkylene group, Formula W—R ⁷ , wherein W is Join or C! - a C ₂ alkylene group, R ⁷ is substituted with a group selected from Substituent group r 1 may be condensed with a good benzene ring - a C beta cycloalkyl group.

Group or substituted by a group selected from Substituent group § 1 which may be Araruki Le group having (Ariru moiety is a phenyl group the alkyl moiety is C, an C ₄ alkyl group.) A is Benjiruamin acids Or a composition for inhibiting the activity of ileal bile acid transposon overnight containing a pharmacologically acceptable salt thereof as an active ingredient.

Substituent group 1>

C! - C alkyl group, t one-butyl group, d - C alkoxy group, a fluorine atom, in a chlorine atom and Shikiichi Z- R ⁸ [wherein, Z is a single bond or d - a C alkylene radical, R ⁸ is carboxy, C - C alkoxycarbonyl, force Rubamoi Le, mono one (C, - C alkyl) force Rubamoiru, di - (C - C ₂ alkyl) A group having a benzyl group, d-C alkylsulfonyl or a hydroxyl group]. 42. In any one of claims 24 to 40, wherein R ⁶ is a C ₃ -C alkylene group, a group having the formula W—R ⁷ , wherein W is Is a single bond or a methylene group, and R ⁷ is a C ₅ -C β cycloalkyl group which may be substituted with a group selected from Substituent Group a2 and may be condensed with a benzene ring. Or a benzylalkyl group which may be substituted with a group selected from substituent group a2 (where the aryl part is a phenyl group and the alkyl part is a C i -C alkyl group) or a pharmaceutically acceptable salt thereof. A composition for inhibiting ileal bile acid transporter activity, comprising a pharmaceutically acceptable salt as an active ingredient.

<Substituent group r 2>

 Methyl, butyl, methoxy, fluorine, chlorine, carboxy, methoxycarbonyl, dimethylcarbamoyl, and hydroxymethyl groups.

43. In Claims 24 through 40, R ⁶ is an isopropyl group, a butyl group, a butyl group, a neopentyl group, a 1-ethylpentyl group, a 2-ethylhexyl group or a substituent group a. Ileal bile acid trans containing, as an active ingredient, benzylamines which are cyclohexyl, benzyl, 1-phenylethyl or 2-phenylethyl group or a pharmacologically acceptable salt thereof, which may be substituted with a group selected from the group consisting of: A composition for inhibiting porter activity.

 <Substituent group a 3>

 Methyl, methoxy, fluorine and chlorine atoms.

44. In any one of claims 24 to 40, benzylamines wherein R ^e is a 1-ethylpentyl group, a cyclohexyl group or a 1-phenylethyl group, or a pharmacology thereof. A composition for inhibiting ileal bile acid transporter activity, which comprises an acceptable salt as an active ingredient.

45. The benzyl group according to any one of claims 24 to 40, wherein R ^{6 is a} 1-ethylpentyl group or a 1-phenylethyl group. A composition for inhibiting the activity of ileal bile acid transposon, which comprises a mineral or a pharmacologically acceptable salt thereof as an active ingredient.

 4 6. N— (1 phenylethyl) 1-phenyl [6-hydroxy-4- methoxy-2- 2— (1H-tetrazol-5-yl) phenyl] methyl} amine

N— (1-ethylpentyl) 1-phenyl [3— (1H-tetrazole-5-yl) phenyl] methyl} amine

 N- (1 -phenylethyl) 1 -phenyl [3- (1 H-tetrazo-lu-5-yl) phenyl] methyl} amine,

 N- (1-ethylpentyl) -1-phenyl [4_ (1H-tetrazole-5-yl) phenyl] methyl} amine,

 N- (1 -phenylenyl) 1 -phenyl- [4- (1H-tetrazol_ 5 -yl) phenyl] methyl} amine,

 N- (1 -phenylenyl) 1-{(4 -methoxyphenyl) 1-[1-(1 H-tetrazol-5-yl) phenyl] methyl} amine

 N- (1-phenylenyl)-[phenyl- (3-methylsulfonylcarbamoylphenyl) methyl] amine,

 N- (1-ethylpentyl)-[phenyl- (3-N-tosylcarbamoylphenyl) methyl] amine,

 N-cyclohexyl- [phenyl- (3-N-tosylcarbamoylphenyl) methyl] amine,

 N- (1-phenylenyl)-[phenyl (3-N-tosylcarbamoylphenyl) methyl] amine,

 N- (1-phenylethyl) 1-phenyl [3- (2- (2-methylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} amine

N— (1-phenylethyl) 1-phenyl [3— (2- (3-methylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} amine N- (1 phenylethyl) 1 {phenyl [3 — (2— (4-methylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} amine

 N- (1-phenylethyl) 1-phenyl [4- (2- (2-methylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} amine

 N- (1 -phenylethyl) 1 {phenyl (4- (2- (4-methylphenyl) phenyl) sulfonylcarbamoylphenyl] methyl} amine

 N- (1-ethylpentyl)-[phenyl (2-ethylsulfonylphenyl) methyl] amine,

 N- (Indone-1-yl) -1- [phenyl- (2-ethylsulfonylphenyl) methyl] amine;

 N- (2-phenylenyl) methyl [phenyl (2-ethylsulfonylphenyl) methyl] amine,

 N—tert—butyl— [phenyl— (2-phenylsulfonylphenyl) methyl] amine,

 N-{2-[1-phenyl-1-1 (N-1 -phenylethyl) amino] methyl} phenyl N '— tosylperia,

 N— {2-[1 — (4-methoxyphenyl) — 1 — (N— 1-phenylethyl) amino] methyl} phenyl N '— tosylperia,

 N- (1—ethylpentyl) -1- {2-indenyl— [3- (1H—tetrazol-1-5-yl) phenyl] methyl} amine;

 N- (1 -phenylenyl) 1 {2 -indenyl- [4- (1 H-tetrazol- 1 -yl) phenyl] methyl} amine

 N- (1-ethylpentyl) -1- {1_naphthyl [3_ (1H-tetrazole-15-yl) phenyl] methyl} amine;

N- (1—phenylethyl) — {1—naphthyl [3_ (1H—tetrazol-1-5—yl) phenyl] methyl} amine; N- (1 -phenylenyl)-{1 _naphthyl- [4-(1 H-tetrazole- 1 -yl) phenyl] methyl} amine

 N-[1-(4-bromophenyl) ethyl]-{(1, 1-dioxothiophene 1-2-yl)-[3-(1 H-tetrazol-5 -yl) phenyl] methyl}

 N— (1—ethylpentyl) 1 {2—thiazolyl [3— (1H—tetrazol-5-yl) phenyl] methyl} amine

 N- (1 -phenylethyl) 1 {3 -thiazolyl [3- (1 H-tetrazol-5-yl) phenyl] methyl} amine

 N- (1 -phenylenyl) 1-{2-indolyl— [3- (1H-tetrazole-5-yl) phenyl] methyl} amine

 N- [1- (4-bromophenyl) ethyl]-{2-indolyl- [3- (1H-tetrazol-5--yl) phenyl] methyl} amine;

 N-cyclohexyl [(1,1-dioxybenzothiophene-3-yl) -1- (2-methylsulfonylphenyl) methyl] amine,

 N-[1-(4-bromophenyl) ethyl]-{(1, 1-dioxybenzothiophene 1-2-yl)-[3-(1 H-tetrazol-5 -yl) phenyl] Methyl}

 N— [1— (4-bromophenyl) ethyl] — {2—benzothiazolyl [3- (1H—tetrazol-5—yl) phenyl] methyl} amine or

 N- (1 1-phenylethyl) 1 {3 —benzoxazolyl [3 — (1 H—te tolazoyl 5-yl) phenyl] methyl} amine

A composition for inhibiting ileal bile acid transporter activity, comprising as an active ingredient.