JP3510324B2 - Urea derivatives - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel urea derivative, a method for producing the same, and a pharmaceutical composition containing the derivative. In particular, the present invention provides a compound having an acylcoenzyme A cholesterol acyltransferase (hereinafter abbreviated as ACAT) inhibitory activity and a protective ability against oxidative changes of low density lipoprotein (hereinafter abbreviated as LDL).

[0002]

2. Description of the Related Art In recent years, there has been a strong interest in the relationship between an increase in blood cholesterol level and health status. It has been pointed out that the cholesterol level in blood is related to the amount of cholesterol deposited in the vascular system, and that the cholesterol deposit in the vascular system causes ischemic diseases such as arteriosclerosis.

Although a drug for lowering the amount of cholesterol in the blood has been developed so far, such a drug has been effective for controlling the cholesterol level in the blood at an appropriate level. It was not effective in suppressing the absorption of cholesterol in the digestive tract and the deposition of cholesterol in the blood vessel wall.

By the way, ACAT is an enzyme that catalyzes the synthesis of acyl coenzyme A and cholesterol into cholesterol ester, and plays an important role in cholesterol metabolism and absorption in the digestive tract. And A
CAT is present at the site of intestinal mucosal cells, and is considered to act when esterifying dietary cholesterol and taking it up. On the other hand, the cholesterol deposited on the blood vessel wall is esterified cholesterol, and the cholesterol accumulated in foamed macrophages, which plays an important role in the formation of atherosclerotic lesions, is also esterified. It is cholesterol. And
The enzyme that catalyzes the esterification of cholesterol at these sites is also ACAT. Therefore, this AC
By inhibiting the action of AT, it is possible to suppress the intake of dietary cholesterol into the body and further suppress the production of cholesterol ester at a specific cell site.

As such a compound having an ACAT inhibitory activity, a urea derivative having a structure similar to the compound of the present invention is disclosed in, for example, JP-A-2-188568 and JP-A-2-
No. 92950. However, although the drugs shown in these known documents have an ACAT inhibitory activity, they exert a different action on the oxidative alteration of LDL which causes foaming of macrophages important for the formation of atherosclerotic plaque. It does not affect.

[0006]

By the way, foam cells, which play an important role in the formation of atherosclerotic plaque, are incorporated into macrophages by LDL that has undergone oxidative alteration, and as a result, the macrophages become foamed. It was done. It has been reported by Diane W. Morel et al. (ARTERIOSCLEROSIS, 4) that LDL that has undergone oxidative deterioration causes foaming of macrophages and plays an important role in the formation of atherosclerotic plaques. Volume, Pages 357-364, 1984
Furthermore, the prevention of oxidative alteration of LDL causes regression of atherosclerotic plaques by TORU KITA et al. (Proc. Natl. Acad. Sci. USA, 84, 5928-5931).
Page, 1987). Therefore, suppressing the oxidative deterioration of LDL in addition to the above-described ACAT inhibitory action is extremely important for the formation of atherosclerotic plaques, prevention of their expansion, and their regression.

From the above, substances having an ACAT inhibitory activity and capable of suppressing the oxidative deterioration of LDLs at the same time lower the blood cholesterol level and at the same time oxidize LDL cholesterol deposited in blood vessels or tissues. It is effective for the formation of atherosclerotic lesions, the prevention of their expansion, and their regression by suppressing the physical alteration, and therefore, the development of a drug having such properties is needed.

[0008]

In order to solve the above problems, the inventors of the present invention, as a result of diligent research, suppress the absorption of cholesterol from the intestinal tract by the ACAT inhibitory action, lower the cholesterol level in the blood, By suppressing the accumulation of cholesterol ester in blood vessel wall, arteriosclerotic lesion and macrophage, and by having a protective effect against oxidative alteration of LDL involved in foam formation of macrophage, formation and expansion of atherosclerotic lesion The present invention has been completed by discovering a novel urea derivative that is effective in suppressing the above-mentioned phenomenon and its regression. The present invention is to provide a novel urea derivative having an ACAT inhibitory action and an antioxidant action at the same time. These compounds are effective in the prevention and treatment of hypercholesterolemia, arteriosclerosis and the like.

That is, the present invention has the general formula (I)

[Chemical 3] [In the formula, R ₁ and R ₂ are the same or different and each represents a hydrogen atom, a halogen atom, a linear or branched (C ₁ -C ₆ ) alkyl group, a linear or branched (C ₁ -C _6). ) Represents an alkoxy group, R ₃ and R ₄ are the same or different, and are a hydrogen atom, a linear or branched (C ₁ -C ₁₂ ) alkyl group, a linear or branched (C ₁ -C ₂₀ ). Alkenyl group, (C ₁ -C ₆ ) alkoxy (C ₁ -C ₆ ) alkyl group, (C ₁ -C ₆ ) alkoxycarbonyl (C ₁ -C ₉ ) alkyl group, benzyloxycarbonyl (C ₁ -C ₆ ). Alkyl group (where alkyl group,
That is, the alkylene chain may be optionally substituted with a phenyl group), N, N-di (C ₁ -C ₆ ) alkylamino (C ₁ -C ₆ ) alkyl group, N- (C ₁ -C _6). ) Alkyl-N-benzylamino (C ₁ -C ₆ ) alkyl group, (C ₁
To C ₆ ) alkylthio (C _{1 to} C ₆ ) alkyl group, oxo (C _{1 to} C ₉ ) alkyl group, hydroxy (C _{1 to} C ₆ ) alkyl group, dihydroxy (C _{1 to} C ₆ ) alkyl group, cyclo ( C ₃ -C ₁₅₎ alkyl, cycloalkyl (C ₃ -C ₈₎ alkyl (C ₁ -C ₆₎ alkyl group, dicyclohexyl (C ₃ -C ₉₎ alkyl (C ₁ -C ₆₎ alkyl group, bicyclo (C _{3 to} C ₉ ) alkyl group, tricyclo (C _{9 to} C ₁₂ ) alkyl group (the above-mentioned cycloalkyl group or cycloalkyl moiety may optionally be a (C _{1 to} C ₆ ) alkyl group, a hydroxy group, an amino group, acetoxy. Group, acetamide group, phenyl group, benzyloxy group, dimethylaminophenyl group, methylenedioxyphenyl group may be mono- or di-substituted by a substituent, and further condensed with a benzene ring. May be),

[0010] aryl, aryl (C ₁ -C ₆₎ alkyl group, diaryl (C ₁ -C ₆₎ alkyl group (the aryl group described above, or aryl moiety, optionally (C ₁ ~
C ₆ ) alkyl group, (C ₁ -C ₆ ) alkyloxy group, halogen atom, nitro group, hydroxy group, amino group, dimethylamino group, methylenedioxy group, pyrrolidinyl group as a substituent, mono, di, Or optionally tri-substituted), a heterocyclic group or a heterocyclic group via a (C ₁ -C ₆ ) alkylene chain (the above-mentioned heterocyclic group is a hetero atom selected from a sulfur atom, an oxygen atom and a nitrogen atom). Including 1 to 3,
It represents a saturated or unsaturated 5- to 8-membered monocyclic heterocyclic group or bicyclic heterocyclic group, and these heterocyclic groups may be optionally mono- or di-substituted. Is an acetyl group, a hydroxy group, a (C ₁ -C ₉ ) alkyl group, (C _1- )
C ₉₎ alkyl group, cyclo (C ₃ ~C ₈₎ alkyl, cyclo (C ₃ ~C ₈₎ alkyl (C ₃ ~C ₁₀₎ alkyl group, a pyridyl (C ₁ ~C ₆₎ alkyl group, a phenyl group ,
Phenyl (C ₁ ~C ₆₎ alkyl group, diphenyl (C ₁ ~
A C ₆ ) alkyl group, a phenylpiperazinyl group (the phenyl group or the phenyl moiety may be a halogen atom, a (C ₁ -C ₆ ) alkyl group, a (C ₁ -C ₆ ) alkoxy group, a cyano group, Diethylamino group, mono- or di-substituted with a substituent selected from a trifluoromethyl group), further, these heterocyclic groups may be condensed with a benzene ring),

Further, R ₃ and R ₄ may be combined with the nitrogen atom to which they are bonded to form a saturated or unsaturated heterocyclic group, and these heterocyclic groups are 5- to 8-membered rings. Represents a group derived from a monocyclic heterocyclic group, a bicyclic heterocyclic group, or a heterocyclic spiro compound, and each of these groups further includes a hetero atom selected from a sulfur atom, an oxygen atom, and a nitrogen atom. 1 or 2 may be contained. These heterocyclic groups may be optionally mono- or di-substituted, and the substituents are (C ₁ -C ₆ ) alkyl groups, hydroxy groups, hydroxy (C ₁ -C ₆ ) alkyl groups, (C ₁ -C ₆₎ alkoxy (C _{1 ~C 6)} alkyl group, acetoxy (C _{1 ~C 6)} alkyl, (C _{1 ~C 9)} alkylcarbonyl group, (C ₁
To C ₆ ) alkoxycarbonyl group, amino group, tosyl group, phenyl group, halogenophenyl group, (C ₁ -C ₆ ) alkoxyphenyl group, phenyl (C ₁ -C ₆ ) alkyl group, benzyloxy group, benzyloxy ( C ₁ -C ₆₎ alkyl group, toluyl group, xylyl group, a benzoyl group, methylenedioxyphenyl (C ₁ ~C ₆₎ alkyl group, a pyridyl group, pyridylcarbonyl group, piperidyl group, pyrrolidinyl (C ₁ ~C ₆₎ It is selected from an alkyl group and a pyrrolidinylcarbonyl (C ₁ -C ₆ ) alkyl group, and these heterocyclic groups may be condensed with a benzene ring. However,
When R ₃ and R ₄ simultaneously represent a hydrogen atom, they are excluded. The alkyl moiety and alkoxy moiety of each of the above substituents may be linear or branched. R ₅ and R ₆ are the same or different and represent a linear or branched (C ₁ -C ₆ ) alkyl group, and

[Chemical 4] Represents —CH ₂ —CH ₂ — or —CH═CH—] and a pharmacologically acceptable salt thereof. The present invention also relates to an ACAT inhibitor containing the compound represented by the general formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient.

Examples of the halogen atom represented by R ₁ and R ₂ in the general formula (I) of the above urea derivative of the present invention include fluorine, chlorine, bromine and iodine, and (C ₁
To C ₆ ) alkoxy groups include methoxy, ethoxy,
Examples thereof include propoxy, iso-propoxy, butoxy, iso-butoxy, sec-butoxy, tert-butoxy, pentyloxy and hexyloxy groups, and the (C ₁ -C ₆ ) alkyl group includes methyl, ethyl, propyl and iso. -Propyl, butyl, iso-butyl, tert-butyl, pentyl, hexyl groups and the like.

The (C ₁ -C ₁₂ ) alkyl group represented by R ₃ and R ₄ in the general formula (I) includes methyl, ethyl, propyl, iso-propyl, butyl, iso-butyl, sec. -Butyl, tert-butyl, pentyl, iso-pentyl, neopentyl, hexyl, iso-hexyl, heptyl, octyl, 2,4,4-trimethyl-2-pentyl, nonyl, decyl, dodecyl group and the like, (C ₂
-C ₂₀₎ Examples of the alkenyl group include vinyl, allyl, iso
-Propenyl, 2-butenyl, 2-pentenyl, 4-pentenyl, 3-hexenyl, 5-hexenyl, 4-octenyl, 7-octenyl, 7-decenyl, 3,7-dimethyl-2,6-octadienyl, 10-tetradecenyl , 8-heptadecenyl, 8-octadecenyl, 4,7,
Examples thereof include a 10,13,16-nonadecapentaenyl group, and examples of the (C ₁ -C ₆ ) alkoxy (C ₁ -C ₆ ) alkyl group include 2-methoxyethyl, 4-methoxybutyl and 2
-Methoxybutyl, 6-methoxyhexyl, ethoxymethyl, 3-ethoxypropyl, 2-propoxyethyl,
4-propoxybutyl, 5-propoxypentyl, iso
-Propoxymethyl, butoxymethyl, 2-iso-butoxyethyl, sec-butoxymethyl, tert-butoxymethyl, 4-butoxybutyl, 6-butoxyhexyl, pentyloxymethyl, 2-pentyloxyethyl, hexyloxymethyl groups, etc. Named

(C ₁ -C ₆ ) alkoxycarbonyl (C ₁
The -C ₉₎ alkyl group, 2- (methoxycarbonyl) ethyl, 7- (methoxycarbonyl) heptyl, 2
-(Ethoxycarbonyl) ethyl, 4- (ethoxycarbonyl) butyl, propoxycarbonylmethyl, 3-
(Propoxycarbonyl) butyl, iso-propoxycarbonylmethyl, butoxycarbonylmethyl, 1- (butoxycarbonyl) ethyl, 2- (iso-butoxycarbonyl) ethyl, sec-butoxycarbonylmethyl, 2
-(Tert-butoxycarbonyl) ethyl, pentyloxycarbonylmethyl, 2- (hexyloxycarbonyl) ethyl, α- (methoxycarbonyl) benzyl, α
Examples of the benzyloxycarbonyl (C ₁ -C ₆ ) alkyl group include 2- (benzyloxycarbonyl) ethyl and 6- (ethoxycarbonyl) benzyl.
Examples thereof include (benzyloxycarbonyl) hexyl, 4- (benzyloxycarbonyl) butyl, benzyloxycarbonylmethyl, α- (benzyloxycarbonyl) benzyl group, and N, N-di (C ₁ -C ₆ ) alkylamino ( As the C ₁ -C ₆ ) alkyl group, 2- (N, N-dimethylamino) ethyl, 4- (N, N-dimethylamino) butyl, 2- (N, N-diethylamino) ethyl,
3- (N, N-diethylamino) propyl, N, N-di-
iso-propylaminomethyl, N, N-dibutylaminomethyl, 2- (N, N-dibutylamino) ethyl, 2-
(N, N-di-iso-butylamino) ethyl, N, N-dipentylaminomethyl, 2- (N, N-dihexylamino) ethyl, N, N-di-iso-hexylaminomethyl group and the like can be mentioned. ,

Examples of N- (C ₁ -C ₆ ) alkyl-N-benzylamino (C ₁ -C ₆ ) alkyl groups include 2- (N-benzyl-N-methylamino) ethyl and 2- (N-benzyl). -N-ethylamino) ethyl, 4- (N-benzyl-)
N-methylamino) butyl, 2- (N-benzyl-N-
Examples thereof include ethylamino) ethyl, 3- (N-benzyl-N-ethylamino) propyl group, and the (C ₁ -C ₆ ) alkylthio (C ₁ -C ₆ ) alkyl group is 2- (methylthio) ethyl. , 2- (ethylthio) ethyl, propylthiomethyl, 2- (iso-propylthio) ethyl, 1-
(Butylthio) ethyl, iso-butylthiomethyl, tert
-Butylthiomethyl, pentylthiomethyl, hexylthiomethyl groups and the like, and examples of the oxo (C ₁ -C ₉ ) alkyl group include 2-oxopropyl, 2-oxobutyl,
4-oxopentyl, 6-oxoheptyl, 2-oxooctyl group and the like can be mentioned, and as the hydroxy (C ₁ -C ₆ ) alkyl group, 2-hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, 3- Hydroxybutyl, 6-hydroxyhexyl group and the like can be mentioned. As the dihydroxy (C ₁ -C ₆ ) alkyl group, 2,3-dihydroxypropyl, 4,5-dihydroxypentyl,
1,5-dihydroxy-3-pentyl, 2-ethyl-1,
3-dihydroxy-2-propyl, 2,4-dihydroxy-3-methylpentyl group and the like,

Cyclo (C ₃ -C ₁₅ ) alkyl groups include cyclopropyl, cyclobutyl, cyclopentyl,
Cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl, silocdodecyl, 1-phenylcyclopentyl, 4- (benzyloxy) cyclohexyl, 4-aminocyclohexyl, 4-acetamidocyclohexyl, 4-hydroxycyclohexyl, 4-acetoxycyclohexyl, 4-tert-butyl. Cyclohexyl, 2,
3-dimethylcyclohexyl, 1,2,3,4-tetrahydronaphthyl, cyclododecyl, benzyloxycyclohexyl group and the like can be mentioned, and as the cyclo (C ₃ -C ₈ ) alkyl (C ₁ -C ₈ ) alkyl group, cyclo can be used. Propylmethyl, 2-cyclobutylethyl, 2-cycloheptylethyl, cyclohexylmethyl, 3-cyclohexylpropyl, 4-cyclohexylbutyl, cyclooctylmethyl, 5-cyclooctylpentyl, 1- (4-dimethylaminophenyl) cyclopentylmethyl, 1- (3,4
-Methylenedioxyphenyl) cyclopentylmethyl group and the like,

Dicyclo (C ₃ -C ₉ ) alkyl (C _1-
As the C ₆ ) alkyl group, dicyclohexylmethyl,
2,2-dicyclohexylethyl, 3,3-dicyclohexylpropyl group and the like can be mentioned. Examples of the bicyclo (C ₆ -C ₉ ) alkyl group include bicyclo [3.3.0] -2-octyl and bicyclo [3.3]. .1] -2-nonyl, bicyclo [3.2.1] -2-octyl group, and the like, and the tricyclo (C ₉ -C ₁₂ ) alkyl group includes tricyclo [5.
2.1.0 ^2.6 ] decyl, tricyclo [3.3.1.1 ^3.7 ]
Examples of the aryl group include phenyl, 1-naphthyl, 2-naphthyl, 3-naphthyl, 4- and the like.
Methylphenyl, 2,6-diisopropylphenyl, 3,
5-di-tert-butyl-4-hydroxyphenyl, 2-
Methoxyphenyl, 4-hexyloxyphenyl, 4-
Fluorophenyl, 2-nitrophenyl, 4-chloronaphthyl, 3-amino-2-naphthyl, 5-hydroxynaphthyl, 5-methoxynaphthyl, anthryl group and the like,

The aryl (C ₁ -C ₆ ) alkyl group includes benzyl, phenethyl, 3-phenylpropyl, 4
-Phenylbutyl, 9-anthrylmethyl, 4-ethylbenzyl, 4-ethoxybenzyl, 4-fluorobenzyl, 3,4-methylenedioxybenzyl, 3,4,5-trimethoxybenzyl, 4-methylphenethyl, 2 -Methoxyphenethyl, 4-methoxyphenethyl, 3,4-dimethoxyphenethyl, 3-chlorophenethyl, 4-chlorophenethyl, 4-fluorophenethyl, 4-nitrophenethyl, 3,4,5-trimethoxyphenethyl, 4-nitrophenyl Butyl, 1- (4-fluorophenyl)-
2-methylpropyl, 3,4-dichlorophenylpropyl, 4-dimethylaminophenethyl, 2- (3,4-dichlorophenyl) -2-propyl, 2- (3,4-dichlorophenyl) -2-methylpropyl, 2- ( 2-fluorophenyl) -2-methylpropyl, 2- (3-fluorophenyl) -2-methylpropyl, 2- (4-fluorophenyl) -2-methylpropyl, 2- [4- (1
-Pyrrolidinyl) phenyl] -2-methylpropyl, and the like. Examples of the diaryl (C ₁ -C ₆ ) alkyl group include diphenylmethyl, 1,2-diphenylethyl,
2,2-diphenylethyl, 4,4-diphenylbutyl,
6,6-diphenylhexyl group and the like,

As the monocyclic heterocyclic group, 3-furyl, 2
-Thienyl, 3-pyrrolyl, 2-pyrrolidinyl, 2H-
Pyran-3-yl, 2-pyridyl, 4-piperidyl, 3
-Morpholinyl, 2-piperazinyl, 1-methyl-4-
Piperidyl, 1-benzyl-4-piperidyl, 1-methyl-3-piperidyl, 1- (2,4-difluorobenzyl) -4-piperidyl, 1- (3,4-difluorobenzyl) -4-piperidyl, 1- (3,5-Difluorobenzyl) -4-piperidyl, 1- [2,4-bis (trifluoromethyl) benzyl] -4-piperidyl, 1-
(4-Methoxybenzyl) -4-piperidyl, 1-phenethyl-4-piperidyl, 1- (2-fluorobenzyl) -4-piperidyl, 1- (3-fluorobenzyl)
-4-piperidyl, 1- (4-fluorobenzyl) -4
-Piperidyl, 1- (4-chlorobenzyl) -4-piperidyl, 1- (4-hydroxybenzyl) -4-piperidyl, 1- (3,4-dihydroxybenzyl) -4-piperidyl, 1- (4-cyano Benzyl) -4-piperidyl, 1- (2-pyridylmethyl) -4-piperidyl, 1
-(3-Pyridylmethyl) -4-piperidyl, 1- (4
-Pyridylmethyl) -4-piperidyl, 1- [4-
(N, N-diethylamino) benzyl] -4-piperidyl, 1- [bis (4-fluorophenyl) methyl] -4
-Piperidyl, 1- (4-fluorophenethyl) -4-
Piperidyl, 1- (2,4-dimethylbenzyl) -4-
Piperidyl, 1-acetyl-4-piperidyl, 1-ethyl-4-piperidyl, 1-neopentyl-4-piperidyl, 1-cyclohexyl-4-piperidyl, 1-heptyl-4-piperidyl, 1- (2-propyl)- 4-piperidyl, 1-benzyl-3-piperidyl, 2-phenyl-3-piperidyl, 1-cyclohexylmethyl-3-piperidyl, 1-benzyl-3-pyrrolidinyl, 2-methoxy-5-pyridyl, 2- (4 -Phenylpiperazinyl) -5-pyridyl, 5,6-dimethyl-1,2,4-triazin-3-yl group and the like,

Examples of the bicyclic heterocyclic group include 3-indolyl, 5-indazolyl, 2-quinolyl, 5-isoquinolyl, 2,4-dimethyl-1,8-naphthyridin-7-yl and 3,9-dimethyl-. 3,9-diazabicyclo [3.3.
1] -7-nonyl, 9-methyl-3-oxa-9-azabicyclo [3.3.1] -7-nonyl, 9- (4-fluorobenzyl) -3-oxa-9-azabicyclo [3.3] .
1] -7-nonyl, 9-methyl-3-thia-9-azabicyclo [3.3.1] -7-nonyl, 8-methyl-8-azabicyclo [3.2.1] -3-octyl, 1 -Azabicyclo [2.2.2] -3-yl group and the like,

The heterocyclic group via the alkylene chain is
An alkylene group may be interposed in the monocyclic heterocyclic group or bicyclic heterocyclic group shown above, and examples thereof include 2-furylmethyl, 3- (2-thienyl) propyl, and 2- (3-indolyl. ) Ethyl, 2- (3-pyrrolyl) ethyl, 2-pyrrolidinylmethyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, 2- (2-piperidyl)
-Ethyl, 2- (4-piperidyl) -ethyl, 3- (3
-Morpholinyl) propyl, 3-indolylmethyl, 2
-(5-indazolyl) ethyl, 2-quinolylmethyl,
3- (1-imidazolyl) propyl, 2-morpholinoethyl, 3-morpholinopropyl, 3- (2-methylpiperidyl) propyl, 2- (1-pyrrolidinyl) ethyl,
[4- (4-fluorobenzyl) -3-morpholinyl]
Methyl, (1-benzyl-4-hydroxy-4-piperidyl) methyl group and the like can be mentioned.

When R ₃ and R ₄ in the general formula (I) together with the nitrogen atom to which they are bonded form a heterocycle, the monocyclic heterocyclic group is: Pyrrolidinyl, 2,5-dimethyl-1-pyrrolidinyl, 3-hydroxy-1-pyrrolidinyl, 2-hydroxymethyl-1-
Pyrrolidinyl, 2-hydroxyethyl-1-pyrrolidinyl, 2-methoxymethyl-1-pyrrolidinyl, 2- (1
-Pyrrolidinylmethyl) pyrrolidinyl, 3-pyrroline-
1-yl, 2,5-dimethyl-3-pyrrolin-1-yl, piperidino, 2-methylpiperidino, 2-ethylpiperidino, 3-methylpiperidino, 4-methylpiperidino, 4-piperidinopiperidino, 3,3-dimethyl Piperidino, 2,6-dimethylpiperidino, 3,5-dimethylpiperidino, 2,4-dimethylpiperidino, 2- (hydroxymethyl) piperidino, 2- (2-hydroxyethyl) piperidino, 2 -(2-acetoxyethyl) piperidino, 3-hydroxypiperidino, 4-hydroxypiperidino, 4-oxopiperidino, 4-aminopiperidino, 4- (aminomethyl) piperidino, 4-benzylpiperidino, 2- [2 -(Benzyloxy) ethyl] piperidino, 3- (benzyloxy) piperidino, 1,2,
3,6-tetrahydropyridyl, perhydroazepinyl, perhydroazocinyl, piperazinyl, 4-methyl-1-piperazinyl, 3-methyl-1-piperazinyl,
3,5-Dimethyl-1-piperazinyl, 2,5-dimethyl-1-piperazinyl, 4- (2-hydroxyethyl)-
1-piperazinyl, 4-pentanoyl-1-piperazinyl, 4-acetyl-1-piperazinyl, 4-p-toluenesulfonyl-1-piperazinyl, 4-benzoyl-1
-Piperazinyl, 4- (3,4-methylenedioxybenzyl) -1-piperazinyl, 4- (2-pyridyl) -1
-Piperazinyl, 4-nicotinoyl-1-piperazinyl, 4- (1-pyrrolidinylcarbonylmethyl) -1-
Piperazinyl, 4-benzyl-1-piperidyl, 4-phenyl-1-piperidyl, 4-phenyl-1,2,3,6
-Tetrahydropyridinyl, 4-phenyl-1-piperazinyl, 4-benzyl-1-piperazinyl, 4- (o-
Toluyl) -1-piperazinyl, 4- (2-fluorophenyl) -1-piperazinyl, 4- (2,3-xylyl) -1-piperazinyl, 4- (2-chlorophenyl)
-1-Piperazinyl, 4- (2-methoxyphenyl)-
1-piperazinyl, 4- (2-ethoxyphenyl) -1
-Piperazinyl, 4- (m-toluyl) -1-piperazinyl, 4- (3,4-difluorophenyl) -1-piperazinyl, 4- (4-chlorophenyl) -1-piperazinyl, 4- (3,4-dimethoxy) Phenyl) -1-piperazinyl, homopiperazinyl, morpholino, 2,6-
Dimethylmorpholino, thiazolidinyl, thiomorpholino, pyrrolyl, 2-ethyl-1-pyrrolyl, 2,5-dimethyl-1-pyrrolyl, pyrazolyl, 3-methyl-1-
Pyrazolyl, 4-methyl-1-pyrazolyl, imidazolyl, 4-methyl-1-imidazolyl, 4-phenyl-1
-Imidazolyl, 1H-1,2,3-triazole-1-
Yl, 1,2,4-triazol-1-yl, imidazolidinyl, 2-imidazolin-1-yl, pyrazolidinyl, 2-pyrazolin-1-yl groups and the like,

As the bicyclic heterocyclic group, 4,5,6,7-
Tetrahydroindol-1-yl, 1,5,6,7-tetrahydro-4-oxoindol-1-yl, indolinyl, isoindolinyl, perhydroindole-1
-Yl, decahydroquinolinyl, perhydroisoquinolin-2-yl, 1,2,3,4-tetrahydrocarbazol-1-yl, 1,2,3,4-tetrahydroquinoline-
1-yl, 1,2,3,4-tetrahydroisoquinoline-
1-yl, 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl, 5H-dibenz [b,
f] Azepin-5-yl, 10,11-dihydro-5H
-Dibenz [b, f] azepin-5-yl, 3-azabicyclo [3.2.2] nonan-3-yl, 3-methyl-
3,9-diazabicyclo [3.3.1] nonane-9-yl, 3-oxa-9-azabicyclo [3.3.1] nonane-9-yl, 3-thia-9-azabicyclo [3.3. 1]
Examples of the group derived from a heterocyclic spiro compound include 1,4-dioxa-8-
Azaspiro [4.5] -decane-8-yl, 1,4-dioxa-7-azaspiro [4.4] nonane-7-yl, 1,
5-dithia-9-azaspiro [5.5] undecane-9
Examples include -yl and 1-phenyl-4-oxo-1,3,8-triazaspiro [4.5] decan-8-yl groups.

The present invention includes all possible isomers, stereoisomers, mixtures of isomers and stereoisomers, metabolites, metabolic precursors or metabolic bioprecursors of the compounds of general formula (I).

The compound represented by the general formula (I) of the present invention can be produced by various conventional methods, for example, the methods shown below. That is, the compound represented by the general formula (I) is represented by the general formula (II)

[Chemical 5] (Wherein R ₁ and R ₂ and R ₅ and R ₆ are the same as defined above,

[Chemical 6] Represents —CH ₂ —CH ₂ — or —CH═CH—) and a compound represented by the general formula (III) R—NCO (III) (R represents R ₃ or R ₄ , and R ₃ and R ₄ are Same as above)
It is manufactured by reacting with an isocyanate represented by the following in an organic solvent under ice cooling to room temperature. This reaction has the general formula (I
This is carried out using 0.1 to 2 mol of the compound represented by the general formula (III) per 1 mol of the compound represented by I).

The compound represented by the general formula (I) has the general formula (IV)

[Chemical 7] (Wherein R ₁ and R ₂ and R ₅ and R ₆ are the same as defined above,

[Chemical 8] Represents an —CH ₂ —CH ₂ — or —CH═CH—) and a general formula (V)

[Chemical 9] (R represents R ₃ or R ₄ , and R ₃ and R ₄ are the same as above)
And an amine represented by in an organic solvent under ice-cooling to room temperature,
It is manufactured by reacting. This reaction is carried out using 0.1 to 2 mol of the compound represented by the general formula (IV) per 1 mol of the compound represented by the general formula (V).

Further, the compound represented by the general formula (I) has the general formula (VI)

[Chemical 10] (Wherein R ₁ and R ₂ and R ₅ and R ₆ are the same as above,

[Chemical 11] Represents —CH ₂ —CH ₂ — or —CH═CH—) and a general formula (V) (R represents R ₃ or R ₄ , and R ₃ and R ₄ are the same as above). It is manufactured by reacting with an amine represented by in an organic solvent under heating at 50 to 150 ° C. This reaction is carried out using 0.1 to 2 mol of the compound represented by the general formula (VI) per 1 mol of the compound represented by the general formula (V).

Further, the compound represented by the general formula (I) is the compound represented by the general formula (II) and the compound represented by the general formula (VII).

[Chemical 12] (R represents R ₃ or R ₄ , and R ₃ and R ₄ are the same as above)
And a carbamic acid ester represented by
It is produced by reacting under heating at 150 ° C. This reaction is carried out using 0.1 to 2 mol of the compound represented by the general formula (II) per 1 mol of the compound represented by the general formula (VII).

The isocyanate represented by the above general formula (III) or (IV) is, for example, a carboxylic acid represented by the general formula RCOOH (R represents R ₃ or R ₄ , R ₃ and R ₄ are the same as above). 1 to 10 mol amount, preferably 1 to 3 mol amount of diphenylphosphoryl azide, trimethylsilyl azide or the like is reacted with an acid or a derivative thereof in an organic solvent to form an acyl azide, which is rearranged under heating at 50 to 150 ° C. It is produced by a reaction method, a method of reacting a compound represented by the general formula (V) or (II) with phosgene, and the like.

The carbamic acid ester represented by the above general formula (VI) or (VII) is 0.1 to 10 molar amount, preferably 0, based on the compound represented by the general formula (II) or (V). It is produced by reacting 0.5 to 2 molar amount of phenyl chloroformate in an organic solvent under ice cooling to room temperature. At this time, acid binders, for example, inorganic basic substances such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, etc., and secondary amines such as diisopropylamine, tertiary amines such as triethylamine, methylmorpholine and pyridine. The reaction may be carried out in the presence of an organic basic substance such as amine.

Examples of the organic solvent for each of the above reactions include aliphatic hydrocarbon solvents such as hexane, petroleum ether and cyclohexane, aromatic hydrocarbon solvents such as benzene, toluene and xylene, methylene chloride, chloroform and carbon tetrachloride. , Halogenated hydrocarbon solvents such as dichloroethane, ether solvents such as ethyl ether, isopropyl ether, tetrahydrofuran, dioxane, ketone solvents such as acetone and methyl ethyl ketone, ethyl acetate, acetonitrile, N, N-dimethylformamide, etc. You can The production process of the compound of the present invention by the above reaction is shown in the following scheme 1.

[0032]

[Chemical 13] In addition, the compound represented by the general formula (II) is represented by the general formula (IX)

[Chemical 14] A nitrophenylacetic acid derivative represented by the formula (wherein R ₁ and R ₂ are the same as above);

[Chemical 15] (Wherein R ₅ and R ₆ are the same as described above) are reacted with a benzaldehyde derivative in the presence of a catalytic amount of a basic substance such as piperidine to give a compound represented by the general formula (X)

[Chemical 16] (In the formula, R ₅ and R ₆ are the same as above), and produced by reducing the compound.

In this reaction, 0.1 mol of the compound represented by the general formula (VIII) is added to 1 mol of the compound represented by the general formula (IX).
It is carried out in an amount of 1 to 10 mols, preferably 0.5 to 2 mols. As a reducing method, zinc, iron, tin, tin (II) chloride, etc. are used in an acidic solution such as hydrochloric acid or acetic acid. And a method of catalytic hydrogenation using palladium-carbon, platinum oxide or the like in an alcohol solvent such as methanol or ethanol. The manufacturing process by the above reaction is shown in the following scheme 2.

[0034]

[Chemical 17]

The acid addition salt of the compound represented by the general formula (I) of the present invention is a pharmacologically acceptable salt, for example, hydrochloride, hydrobromide, hydroiodide, sulfuric acid. Inorganic acid salts such as salts and phosphates, and organic acids such as oxalate, maleate, fumarate, lactate, malate, citrate, tartrate, benzoate and methanesulfonate. Examples include salt.

The compounds of the present invention can be administered orally or parenterally, usually in the form of pharmaceutical preparations. The form of the pharmaceutical preparation includes tablets, capsules, troches, syrups, granules, powders, injections, suspensions and the like. Further, it can be made into a double-layer tablet or a multi-layer tablet together with other drugs. Further, the tablets may be tablets coated with a usual coating as necessary, for example, sugar-coated tablets, enteric-coated tablets and film-coated tablets. In the case of a solid preparation, solid additives such as lactose, sucrose, crystalline cellulose, corn starch,
Calcium phosphate, sorbitol, glycine, carboxymethyl cellulose, acacia, polyvinylpyrrolidone, hydroxypropyl cellulose, polyethylene glycol, stearic acid, magnesium stearate,
Talc or the like is used. In the case of a semi-solid preparation, vegetable or synthetic wax or fat is used.

In the case of liquid preparations, liquid additives such as sodium chloride aqueous solution, sorbitol, glycerin,
Olive oil, almond oil, propylene glycol, ethyl alcohol and the like are used. The amount of active ingredient in these preparations is 0.0001-100% by weight of the preparation, suitably 0.001-5 in the case of preparations for oral administration.
0% by weight, and 0.00 for injectable formulations
It is from 01 to 10% by weight. The administration method and dose of the compound of the present invention are not particularly limited and may be appropriately selected depending on various dosage forms, disease grade, patient age, sex, etc., but the daily dose of the active ingredient is 0.01 mg. ~ 1000 mg. No toxicity is observed within this range.

Hereinafter, specific synthetic methods for the compounds of the present invention will be shown as examples. Example 1 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(4-hexyloxyphenyl) urea

[Chemical 18] A solution of 0.93 g (3.4 mmol) of diphenylphosphoryl azide, 0.68 g (3.1 mmol) of 4-hexyloxybenzoic acid and 0.34 g (3.4 mmol) of triethylamine in toluene (10 ml) was stirred at room temperature for 3.5 hours. After doing about 90
The mixture was heated and stirred at 0 ° C for 2 hours. After further cooling this mixture,
4- (2-aminophenethyl) -2,6-under stirring under ice cooling
A toluene solution (4 ml) of 1.0 g (3.1 mmol) of di-t-butylphenol was added dropwise. After that, the temperature was gradually returned to room temperature and the mixture was stirred overnight. After evaporating the solvent, the residue was purified by silica gel column chromatography and recrystallized from ethyl acetate-hexane to give N- [2- (3,5-di-t-butyl-4]
Crystals of 1.2 g (71%) of -hydroxyphenethyl) phenyl] -N '-(4-hexyloxyphenyl) urea were obtained. mp174-176 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.40-7.42 (m, 1H), 7.14-7.26
(m, 5H), 6.81 (s, 2H), 6.76-6.79 (m, 2H), 5.98 (s, 1
H), 5.39 (s, 1H), 5.13 (s, 1H), 3.88 (t, J = 7Hz, 2H),
2.83-2.87 (m, 2H), 2.76-2.80 (m, 2H), 1.70-1.77 (m, 2
H), 1.38 (s, 18H), 1.30-1.45 (m, 6H), 0.87-0.93 (m, 3
H) IR (cm ^-1 ) 3640, 3310, 2950, 1630, 1560, 1490, 144
0, 1230

Example 2 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(8-heptadecenyl) urea

[Chemical 19] Instead of 4-hexyloxybenzoic acid of Example 1, 9-
The title compound was obtained by the same reaction procedure using octadecenoic acid. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.16-7.26 (m, 4H), 6.78 (s, 2
H), 5.29-5.34 (m, 2H), 5.12 (s, 1H), 5.00 (s, 1H), 4.
19 (t, J = 6Hz, 1H), 3.11 (dd, J = 14, 6Hz, 2H), 2.77-2.8
7 (m, 4H), 1.93-2.02 (m, 4H), 1.38 (s, 18H), 1.18-1.3
8 (m, 25H) IR (cm ^-1 ) 3642, 3288, 2926, 1639, 1558, 1435, 123
3,750

Example 3 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(7-methoxycarbonylheptyl) urea

[Chemical 20] Instead of 4-hexyloxybenzoic acid of Example 1, 8-
The title compound was obtained by the same reaction procedure using methoxycarbonyloctanoic acid. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.16-7.26 (m, 4H), 6.78 (s, 2
H), 5.12 (s, 1H), 4.98 (s, 1H), 4.17 (t, J = 6Hz, 1H),
3.66 (s, 3H), 3.09-3.14 (m, 2H), 2.77-2.87 (m, 4H),
2.28 (t, J = 8Hz, 2H), 1.53-1.61 (m, 2H), 1.38 (s, 18
H), 1.18-1.30 (m, 6H), 0.88 (t, J = 7Hz, 2H) IR (cm ^-1 ) 3640, 2928, 1737, 1639, 1547, 1436, 1234

Example 4 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-cycloheptylurea

[Chemical 21] The title compound was obtained by the same reaction procedure using cycloheptanecarboxylic acid in place of 4-hexyloxybenzoic acid of Example 1. mp177-178 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.17-7.26 (m, 4H), 6.79 (s, 2
H), 5.10 (s, 1H), 5.05 (bs, 1H), 4.19 (d, J = 8Hz, 1H),
3.75-3.85 (m, 1H), 2.80-2.88 (m, 2H), 2.75-2.80 (m,
2H), 1.83-1.90 (m, 2H), 1.38 (s, 18H), 1.21-1.58 (m,
10H) IR (cm ^-1 ) 3650, 3300, 2930, 2860, 1630, 1570, 144
0, 1240

Example 5 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-phenethylurea

[Chemical formula 22] Instead of 4-hexyloxybenzoic acid of Example 1, 3-
The title compound was obtained by the same reaction procedure using phenylpropionic acid. mp197-198 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.08-7.25 (m, 9H), 6.76 (s, 2
H), 5.10 (s, 1H), 5.00 (s, 1H), 4.24 (t, J = 6Hz, 1H),
3.36-3.41 (m, 2H), 2.72-2.80 (m, 6H), 1.36 (s, 18H) IR (cm ^-1 ) 3632, 3284, 2954, 1640, 1559, 1436, 123
5,748

Example 6 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(2,2-diphenylethyl) urea

[Chemical formula 23] In place of 4-hexyloxybenzoic acid of Example 1, 3,
The title compound was obtained by the same reaction procedure using 3-diphenylpropionic acid. mp 179 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.09-7.44 (m, 12H), 6.97-7.0
1 (m, 1H), 6.78 (d, J = 8Hz, 1H), 6.72 (s, 2H), 5.07 (s,
1H), 4.93 (s, 1H), 4.23 (t, J = 6Hz, 1H), 4.15 (t, J = 8
Hz, 1H), 3.77 (dd, J = 8, 6Hz, 2H), 2.70 (s, 4H), 1.35
(s, 18H) IR (cm ^-1 ) 3644, 2930, 1650, 1553, 1510, 1234

Example 7 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(2,6-diisopropylphenyl) urea

[Chemical formula 24] Instead of 4-hexyloxybenzoic acid of Example 1, 2,
The title compound was obtained by the same reaction procedure using 6-diisopropylbenzoic acid. mp209-210 ° C ¹ H-NMR (δ ppm, DMSO) 8.01 (bs, 1H), 7.85 (bs, 1H),
7.65 (d, J = 8Hz, 1H), 7.20-7.24 (m, 1H), 7.10-7.14 (m,
4H), 6.93-6.97 (m, 3H), 6.62 (s, 1H), 3.32-3.53 (m, 1
H), 3.18-3.25 (m, 1H), 2.75-2.85 (m, 4H), 1.37 (s, 18
H), 1.13 (d, J = 7Hz, 12H) IR (cm ^-1 ) 3612, 3320, 2958, 1646, 1586, 1534, 143
5, 1231, 745

Example 8 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(3-cyclohexylpropyl) urea

[Chemical 25] Instead of 4-hexyloxybenzoic acid of Example 1, 4-
The title compound was obtained by the same reaction procedure using cyclohexylbutanoic acid. mp 166 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.18-7.26 (m, 4H), 6.78 (s, 2
H), 5.11 (s, 1H), 5.02 (s, 1H), 4.20 (t, 1H), 3.10 (d
t, J = 6, 7Hz, 2H), 2.83-2.85 (m, 2H), 2.76-2.80 (m, 2
H), 1.56-1.68 (m, 4H), 1.38 (s, 18H), 1.33-1.43 (m, 2
H), 1.04-1.30 (m, 6H), 0.75-0.88 (m, 3H) IR (cm ^-1 ) 3640, 3316, 2924, 1640, 1558, 1436, 123
3,749

Example 9 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[3- (2-thienyl) propyl] urea

[Chemical formula 26] Instead of 4-hexyloxybenzoic acid of Example 1, 4-
The title compound was obtained by the same reaction procedure using (2-thienyl) butanoic acid. mp 150 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.19-7.27 (m, 4H), 7.07 (dd,
J = 4, 1Hz, 1H), 6.87 (dd, J = 3, 2Hz, 1H), 6.77 (s, 2
H), 6.71 (t, J = 2Hz, 1H), 5.11 (s, 1H), 4.96 (s, 1H),
4.21 (t, 1H), 3.20 (s, 2H), 2.77-2.87 (m, 6H), 1.81 (q
ui, J = 7Hz, 2H), 1.37 (s, 18H) IR (cm ^-1 ) 3638, 3286, 2918, 1630, 1570, 1434, 123
3,696

Example 10 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-phenylurea

[Chemical 27] The title compound was obtained by the same reaction procedure using benzoic acid instead of 4-hexyloxybenzoic acid of Example 1. mp 207 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.22-7.36 (m, 8H), 7.02 (t, J
= 7Hz, 1H), 6.80 (s, 2H), 6.02 (s, 1H), 5.18 (s, 1H),
5.15 (s, 1H), 2.79-2.91 (m, 4H), 1.38 (s, 18H) IR (cm ^-1 ) 3630, 3350, 2950, 1650, 1600, 1550, 150
0, 1230, 750

Example 11 (1) Phenyl N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamate

[Chemical 28] 4- (2-aminophenethyl) 2,6-di-t-butylphenol 7.00 g (21.5 mmol) and diisopropylamine 3.4 ml (24 mmol) dichloromethane (50 m
l) A solution of 3.60 g (23.0 mmol) of phenylchloroformate in dichloromethane (10 ml) was added dropwise to the solution in a salt ice water bath so that the internal temperature did not exceed 0 ° C. The mixture was further stirred at the same temperature for 2 hours, washed with water, dried (MgSO ₄ ) and concentrated, and the residue was purified by silica gel column chromatography and N-.
Phenyl 2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamate 8.16 g
A viscous oil (85.2%) was obtained. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.63 (bs, 1H), 7.34 (t, J = 8H
z, 2H), 7.08-7.29 (m, 6H), 6.80 (s, 2H), 5.74 (bs, 1
H), 5.13 (s, 1H), 2.8-2.9 (m, 4H), 1.35 (s, 18H)

(2) N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-
Decyl urea

[Chemical 29] Phenyl N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamate 1.0 g
(2.2 mmol) and decylamine (0.38 g, 2.4 mmol)
A xylene (10 ml) solution of was heated under reflux for 2.5 hours.
After distilling off the solvent, the residue was purified by silica gel column chromatography to obtain waxy N- [2- (3,5-di-t
-Butyl-4-hydroxyphenethyl) phenyl]-
0.93 g (85%) of N'-decylurea was obtained. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.17-7.26 (m, 4H), 6.78 (s, 2
H), 5.11 (s, 1H), 4.98 (s, 1H), 4.17 (t, J = 6Hz, 1H),
3.09-3.16 (m, 2H), 2.76-2.87 (m, 4H), 1.50-2.50 (m, 1
6H), 1.38 (s, 18H), 0.87 (t, J = 7Hz, 3H) IR (cm ^-1 ) 3650, 3350, 2960, 2930, 2850, 1640, 1570

Example 12 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-heptylurea

[Chemical 30] The title compound was obtained by the same reaction procedure using heptylamine in place of decylamine of Example 11. m.
p.100 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.18-7.27 (m, 4H), 6.78 (s, 2
H), 5.11 (s, 1H), 4.99 (s, 1H), 4.18 (bt, J = 5Hz, 1H),
2.89 (q, J = 6Hz, 2H), 2.79-2.85 (m, 4H), 1.38-1.45
(m, 2H), 1.38 (s, 18H), 1.15-1.30 (m, 8H), 0.86 (t, J
= 7Hz, 3H) IR (cm ^-1 ) 3650, 3320, 2970, 2940, 2870, 1640, 157
0, 1440, 1240, 760

Example 13 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(3,7-dimethyl-
2,6-octadienyl) urea

[Chemical 31] The title compound was obtained by the same reaction procedure using 3,7-dimethyl-2,6-octadienylamine instead of decylamine in Example 11. mp87.0 ~ 87.5
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 7.16-7.30 (m, 4H), 6.78 (s, 2
H), 5.10 (s, 1H), 5.05-5.13 (m, 1H), 5.02 (bs, 2H),
4.05-4.12 (m, 1H), 3.75 (t, J = 6Hz, 2H), 2.80-2.85 (m,
2H), 2.75-2.80 (m, 2H), 1.95-2.08 (m, 2H), 1.89-1.9
5 (m, 2H), 1.65 (s, 3H), 1.60 (s, 3H), 1.57 (s, 3H),
1.37 (s, 18H) IR (cm ^-1 ) 3628, 3312, 2956, 1638, 1585, 1436, 123
3, 752

Example 14 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] N '-(2,4,4-trimethyl-2-pentyl) urea

[Chemical 32] The title compound was obtained by the same reaction procedure using 2,2,4-trimethyl-2-pentylamine instead of decylamine of Example 11. mp168-169 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.15-7.26 (m, 4H), 6.83 (s, 2
H), 5.09 (s, 2H), 4.18 (s, 1H), 2.71-2.87 (m, 4H), 1.
64 (s, 2H), 1.39 (s, 18H), 1.34 (s, 6H), 0.90 (s, 9H) IR (cm ^-1 ) 3640, 3334, 2956, 1645, 1556, 1437, 136
5, 1226

Example 15 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(3-ethoxypropyl) urea

[Chemical 33] The title compound was obtained by the same reaction procedure using 3-ethoxypropylamine in place of decylamine of Example 11. mp136-137 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.16-7.27 (m, 4H), 6.79 (s, 2
H), 5.10 (s, 1H), 5.06 (s, 1H), 4.78 (t, J = 5Hz, 1H),
3.40 (t, J = 6Hz, 2H), 3.32 (dd, J = 14,7Hz, 2H), 3.28
(q, J = 6Hz, 2H), 2.84-2.88 (m, 2H), 2.77-2.80 (m, 2
H), 1.67-1.73 (m, 2H), 1.38 (s, 18H), 0.99 (t, J = 7Hz,
3H) IR (cm ^-1 ) 3600, 3346, 2952, 1638, 1563, 1436, 128
8, 1238, 1108, 753

Example 16 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-cyclopentylurea

[Chemical 34] The title compound was obtained by the same reaction procedure using cyclopentylamine instead of decylamine of Example 11. mp186-187 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.15-7.28 (m, 4H), 6.79 (s, 2
H), 5.11 (s, 1H), 5.08 (s, 1H), 4.17 (d, J = 7Hz, 1H),
4.01-4.10 (m, 1H), 2.76-2.87 (m, 4H), 1.89-1.96 (m, 2
H), 1.50-1.61 (m, 4H), 1.39 (s, 18H), 1.22-1.29 (m, 2
H) IR (cm ^-1 ) 3650, 3350, 2950, 1640, 1580, 1560, 144
0, 1240

Example 17 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-cyclohexylurea

[Chemical 35] Using cyclohexylamine instead of decylamine in Example 11, the title compound was obtained by the same reaction procedure. mp198-200 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.16-7.25 (m, 4H), 6.78 (s, 2
H), 5.14 (s, 1H), 4.99 (s, 1H), 4.09 (d, J = 5Hz, 1H),
3.59-3.62 (m, 1H), 2.83 (d, J = 6Hz, 2H), 2.79 (d, J = 6H
z, 2H), 1.95-1.99 (m, 2H), 1.53-1.64 (m, 4H), 1.38
(s, 18H), 1.26-1.30 (m, 2H), 0.96-0.99 (m, 2H) IR (cm ^-1 ) 3290, 2930, 1630, 1561, 1232

Example 18 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-cyclooctylurea

[Chemical 36] The title compound was obtained by the same reaction procedure using cyclooctylamine instead of decylamine of Example 11. mp174-176 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.17-7.24 (m, 4H), 6.79 (s, 2
H), 5.10 (s, 1H), 5.05 (s, 1H), 4.19 (d, J = 5Hz, 1H),
3.68-3.98 (m, 1H), 2.83 (d, J = 6Hz, 2H), 2.79 (d, J = 6H
z, 2H), 1.74-1.81 (m, 2H), 1.42-1.58 (m, 12H), 1.38
(s, 18H) IR (cm ^-1 ) 3308, 2922, 1630, 1554, 1435, 1233

Example 19 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-adamantyl urea

[Chemical 37] The title compound was obtained by the same reaction procedure using 1-adamantaneamine instead of decylamine of Example 11. mp197-199 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.14-7.29 (m, 4H), 6.83 (s, 2
H), 5.11 (s, 1H), 5.10 (s, 1H), 4.06 (s, 1H), 2.79-2.
85 (m, 4H), 1.91-2.05 (m, 9H), 1.60-1.70 (m, 6H), 1.39
(s, 18H) IR (cm ^-1 ) 3350, 2900, 2850, 1640, 1550, 1440, 130
0, 1240

Example 20 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-benzylurea

[Chemical 38] The title compound was obtained by the same reaction procedure using benzylamine instead of decylamine of Example 11. m.
p.181-183 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.15-7.30 (m, 9H), 6.77 (s, 2
H), 5.13 (s, 1H), 5.08 (s, 1H), 4.54 (t, J = 6Hz, 1H),
4.33 (d, J = 6Hz, 2H), 2.82 (d, J = 6Hz, 2H), 2.78 (d, J =
6Hz, 2H), 1.35 (s, 18H) IR (cm ^-1 ) 3294, 2956, 1629, 1579, 1435, 1233, 741

Example 21 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(4-methylphenethyl) urea

[Chemical Formula 39] The title compound was obtained by the same reaction procedure using 4-methylphenethylamine instead of decylamine of Example 11. mp 170-172 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.12-7.23 (m, 4H), 7.04 (d, J
= 8Hz, 2H), 6.98 (d, J = 8Hz, 2H), 6.76 (s, 2H), 5.09
(s, 1H), 4.96 (s, 1H), 4.22 (t, J = 6Hz, 1H), 3.36 (q,
J = 6Hz, 2H), 2.80 (d, J = 6Hz, 2H), 2.69 (t, J = 6Hz, 2
H), 2.68 (d, J = 6Hz, 2H), 2.29 (s, 3H), 1.36 (s, 18H) IR (cm ^-1 ) 3342, 2950, 1643, 1563, 1435

Example 22 -N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] N '-(4-methoxyphenethyl) urea

[Chemical 40] The title compound was obtained by the same reaction procedure using 4-methoxyphenethylamine instead of decylamine of Example 11. mp148-149 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.10-7.24 (m, 4H), 7.00 (d, J
= 9Hz, 2H), 6.77 (d, J = 9Hz, 2H), 6.76 (s, 2H), 5.09
(s, 1H), 4.95 (s, 1H), 4.20 (t, J = 6Hz, 1H), 3.76 (s,
3H), 3.33 (q, J = 6Hz, 2H), 2.80 (d, J = 6Hz, 2H), 2.77
(d, J = 6Hz, 2H), 2.67 (t, J = 6Hz, 2H), 1.36 (s, 18H) IR (cm ^-1 ) 3420, 2960, 1641, 1561, 1525, 1249

Example 23 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-cyclododecylurea

[Chemical 41] The title compound was obtained by the same reaction procedure using cyclododecylamine instead of decylamine of Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.06-7.29 (m, 4H), 6.80 (s,
2H), 5.10 (s, 2H), 4.05 (d, J = 9Hz, 1H), 3.89 (s, 1H),
2.76-2.87 (m, 4H), 1.38 (s, 18H), 1.20-1.30 (m, 22H) IR (cm ^-1 ) 3650, 3340, 2950, 2920, 1640, 1560, 144
0, 1240

Example 24 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-butylurea

[Chemical 42] The title compound was obtained by the same reaction procedure using butylamine instead of decylamine of Example 11. mp
133-134 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.16-7.26 (m, 4H), 6.78 (s, 2
H), 5.12 (s, 1H), 4.97 (s, 1H), 4.16 (t, J = 6Hz, 1H),
3.11-3.16 (m, 2H), 2.77-2.87 (m, 4H), 1.38 (s, 18H),
1.21-1.34 (m, 4H), 0.87 (t, J = 7Hz, 3H) IR (cm ^-1 ) 3450, 3320, 2960, 1640, 1570, 1460, 144
0, 1250, 1230

Example 25 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[2- (N, N-dibutylamino) ethyl] urea

[Chemical 43] The title compound was obtained by the same reaction procedure using N, N-dibutylethylenediamine in place of decylamine of Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.18-7.26 (m, 4H), 6.80 (s, 2
H), 5.18 (s, 1H), 5.10 (s, 1H), 5.02 (bs, 1H), 3.17-
3.21 (m, 2H), 2.76-2.87 (m, 4H), 2.40 (t, J = 6Hz, 2H),
2.24 (t, J = 7Hz, 4H), 1.38 (s, 18H), 1.04-1.26 (m, 8
H), 0.82 (t, J = 7Hz, 6H) IR (cm ^-1 ) 3650, 3360, 2960, 2880, 1640, 1560, 144
0, 1240 Furthermore, the hydrochloride salt of the title compound was prepared by the following method. After 0.15 ml of concentrated hydrochloric acid was added to a solution of 0.95 g of the present compound in 12 ml of ethanol, the solvent was distilled off to obtain 1.05 g of the hydrochloride of the title compound as a wax.

Example 26 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(3,4-dimethoxyphenethyl) urea

[Chemical 44] The title compound was obtained by the same reaction procedure using 3,4-dimethoxyphenethylamine instead of decylamine of Example 11. mp158-160 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.10-7.24 (m, 4H), 6.76 (s, 2
H), 6.70-6.75 (m, 1H), 6.60-6.65 (m, 2H), 5.10 (s, 1
H), 5.00 (s, 1H), 4.27 (t, J = 6Hz, 1H), 3.83 (s, 3H),
3.81 (s, 3H), 3.35-3.40 (dt, J = 6,7Hz, 2H), 2.72-2.84
(m, 4H), 2.68 (t, J = 7Hz, 2H), 1.36 (s, 18H) IR (cm ^-1 ) 3628, 3318, 1632, 1562, 1518, 1264, 1234

Example 27 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(3-phenylpropyl) urea

[Chemical formula 45] The title compound was obtained by the same reaction procedure using 3-phenylpropylamine in place of decylamine of Example 11. mp 161-162 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.13-7.25 (m, 7H), 7.10 (d, J
= 8Hz, 2H), 6.77 (s, 2H), 5.10 (s, 1H), 4.98 (s, 1H),
4.20 (t, J = 7Hz, 1H), 3.17 (q, J = 7Hz, 2H), 2.83 (d, J =
6Hz, 2H), 2.79 (d, J = 6Hz, 2H), 2.56 (t, J = 7Hz, 2H),
1.74 (qui, J = 7Hz, 2H), 1.36 (s, 18H) IR (cm ^-1 ) 3628, 3328, 2952, 1637, 1562, 1435, 123
4, 748, 697

Example 28 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(4-chlorophenethyl) urea

[Chemical formula 46] The title compound was obtained by the same reaction procedure using 4-chlorophenethylamine instead of decylamine of Example 11. mp 173-174 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.09-7.20 (m, 6H), 7.02 (d, 2
H), 6.75 (s, 2H), 5.10 (s, 1H), 4.91 (s, 1H), 4.16 (t,
J = 6Hz, 1H), 3.35 (q, J = 6Hz, 2H), 2.78 (q, J = 5Hz, 4
H), 2.70 (t, J = 7Hz, 2H), 1.35 (s, 18H) IR (cm ^-1 ) 3626, 3322, 2950, 1638, 1561, 1493, 143
6, 1234

Example 29 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-diphenylmethylurea

[Chemical 47] The title compound was obtained by the same reaction procedure using benzhydrylamine instead of decylamine of Example 11. mp187.4 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.14-7.33 (m, 14H), 6.75 (s,
2H), 6.10 (d, J = 8Hz, 1H), 5.17 (s, 1H), 5.08 (s, 1H),
4.86 (d, J = 8Hz, 1H), 2.73-2.81 (m, 4H), 1.35 (s, 18H) IR (cm ^-1 ) 2960, 1640, 1560, 1500, 1460, 1440, 124
0, 740, 700

Example 30 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[(2-furyl) methyl] urea

[Chemical 48] The title compound was obtained by the same reaction procedure using 2-aminomethylfuran in place of decylamine in Example 11. mp169.7 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.15-7.28 (m, 5H), 6.76 (s, 2
H), 6.26-6.27 (m, 1H), 6.14-6.15 (m, 1H), 5.10 (s, 1
H), 4.99 (s, 1H), 4.45 (t, J = 6Hz, 1H), 4.32 (d, J = 6H
z, 2H), 2.76-2.86 (m, 4H), 1.36 (s, 18H) IR (cm ^-1 ) 3320, 2950, 1640, 1590, 1570, 1460, 144
0, 1240, 730

Example 31 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(4-phenylbutyl) urea

[Chemical 49] The title compound was obtained by the same reaction procedure using 4-phenylbutylamine instead of decylamine of Example 11. mp157.0 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.11-7.27 (m, 9H), 6.77 (s, 2
H), 5.10 (s, 1H), 4.95 (s, 1H), 4.15 (t, 1H), 3.12-3.
17 (m, 2H), 2.74-2.86 (m, 4H), 2.58 (t, J = 8Hz, 2H),
1.39-1.61 (m, 4H), 1.37 (s, 18H) IR (cm ^-1 ) 3300, 2950, 2860, 1620, 1600, 1580, 144
0, 1250, 1240

Example 32 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[3- (1-imidazolyl) propyl] urea

[Chemical 50] The title compound was obtained by the same reaction procedure using N- (3-aminopropyl) imidazole instead of decylamine in Example 11. mp163.5 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.39 (s, 1H), 7.20-7.29 (m, 4
H), 7.01 (s, 1H), 6.85-6.86 (m, 1H), 6.77 (s, 2H), 5.
15 (s, 1H), 4.97 (s, 1H), 4.25 (t, J = 6Hz, 1H), 3.92
(t, J = 7Hz, 2H), 3.13 (dt, J = 8,7Hz, 2H), 2.77-2.86
(m, 4H), 1.88-1.95 (m, 2H), 1.37 (s, 18H) IR (cm ^-1 ) 3360, 3320, 2960, 1640, 1570, 1520, 144
0, 1240

Example 33 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[2- (2-pyridyl) ethyl] urea

[Chemical 51] The title compound was obtained by the same reaction procedure using 2- (2-aminoethyl) pyridine instead of decylamine of Example 11. mp179.7 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 8.32 (d, J = 4Hz, 1H), 7.52-7.
56 (m, 1H), 7.06-7.27 (m, 6H), 6.77 (s, 2H), 5.21 (t,
J = 6Hz, 1H), 5.11 (s, 1H), 5.10 (s, 1H), 3.56 (q, J = 6H
z, 2H), 2.93 (t, J = 6Hz, 2H), 2.67-2.83 (m, 4H), 1.37
(s, 18H) IR (cm ^-1 ) 3350, 2960, 1650, 1590, 1570, 1440, 760

Example 34 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[1- (4-fluorophenyl) -2-methyl-2-propyl ]urea

[Chemical 52] 4-Fluoro-in place of the decylamine of Example 11
The title compound was obtained by the same reaction procedure using α, α-dimethylphenethylamine. mp 150.6 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 6.84-7.26 (m, 8H), 6.80 (s, 2
H), 5.10 (s, 1H), 5.09 (s, 1H), 3.95 (s, 1H), 2.95 (s,
2H), 2.72-2.82 (m, 4H), 1.37 (s, 18H), 1.25 (s, 6H) IR (cm ^-1 ) 3350, 2960, 1640, 1560, 1510, 1440, 1240

Example 35 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(1-benzyl-4-)
Piperidyl) urea

[Chemical 53] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using benzylpiperidine. mp 79-81 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.20-7.34 (m, 9H), 6.77 (s, 2
H), 5.10 (s, 1H), 4.99 (s, 1H), 4.07-4.15 (m, 1H), 3.
58-3.72 (m, 1H), 3.44 (s, 2H), 2.68-2.86 (m, 6H), 2.00
-2.10 (m, 2H), 1.80-1.90 (m, 2H), 1.37 (s, 18H), 1.24
-1.35 (m, 2H) IR (cm ^-1 ) 3632, 3350, 1640, 1552

Example 36 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[2- (3-indolyl) ethyl] urea

[Chemical 54] The title compound was obtained by the same reaction procedure using 3- (2-aminoethyl) indole instead of decylamine of Example 11. mp 193-194 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.92 (s, 1H), 7.54 (d, J = 8Hz,
1H), 7.33 (d, J = 8Hz, 1H), 7.05-7.26 (m, 6H), 6.90 (d,
J = 2Hz, 1H), 6.77 (s, 2H), 5.10 (s, 1H), 5.00 (s, 1
H), 4.32 (t, J = 6Hz, 1H), 3.47 (dt, J = 6,7Hz, 2H), 2.9
0 (t, J = 7Hz, 2H), 2.73-2.81 (m, 4H), 1.35 (s, 18H) IR (cm ^-1 ) 3430, 3340, 2880, 1640, 1560, 1440, 124
0, 750

Example 37 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(1,2,3,4-tetrahydro-1-naphthyl) urea

[Chemical 55] The title compound was obtained by the same reaction procedure using 1,2,3,4-tetrahydro-1-naphthylamine instead of decylamine of Example 11. mp168-169 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.01-7.27 (m, 8H), 6.77 (s, 2
H), 5.08 (s, 1H), 5.01-5.06 (m, 2H), 4.42 (d, J = 8Hz,
1H), 2.65-2.90 (m, 6H), 1.50-2.10 (m, 4H), 1.35 (s, 1
8H) IR (cm ^-1 ) 3650, 3350, 2960, 1640, 1560, 1440, 1240

Example 38 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(2-ethylthioethyl) urea

[Chemical 56] The title compound was obtained by the same reaction procedure using 2-ethylthioethylamine instead of decylamine of Example 11. mp131-132 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.19-7.28 (m, 4H), 6.78 (s, 2
H), 5.12 (s, 1H), 5.03 (s, 1H), 4.63 (t, J = 6Hz, 1H),
3.33 (dt, J = 6,7Hz, 2H), 2.80-2.85 (m, 4H), 2.60 (t, J
= 7Hz, 2H), 2.48 (q, J = 7Hz, 2H), 1.38 (s, 18H), 1.20
(t, J = 7Hz, 3H) IR (cm ^-1 ) 3570, 3320, 2950, 2920, 1640, 1570, 144
0, 1250, 1240

Example 39 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(3,9-dimethyl-
3,9-diazabicyclo [3.3.1] -7-nonyl)
urea

[Chemical 57] 7-amino-3 instead of decylamine of Example 11
The title compound was obtained by the same reaction procedure using 9-dimethyl-3,9-diazabicyclo [3.3.1] nonane. ¹ H-NMR (δ ppm, CDCl ₃ ) 8.55 (d, J = 10Hz, 1H), 7.14-
7.27 (m, 4H), 6.85 (s, 2H), 5.14 (s, 1H), 5.09 (s, 1H),
4.10-4.26 (m, 1H), 2.87-2.90 (m, 2H), 2.77-2.80 (m,
2H), 2.70 (bs, 2H), 2.41 (s, 3H), 2.19-2.38 (m, 7H),
1.39 (s, 18H), 1.23-1.37 (m, 4H) IR (cm ^-1 ) 3638, 2926, 1651, 1509, 1435, 1377, 733

Example 40 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-benzyl-N'-heptylurea

[Chemical 58] Using N-heptylbenzylamine instead of decylamine of Example 11, the title compound was obtained by the same reaction procedure. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.7-7.75 (m, 1H), 6.9-7.3 (m,
8H), 6.78 (s, 2H), 5.96 (s, 1H), 5.06 (s, 1H), 4.49
(s, 2H), 3.30 (t, J = 8Hz, 2H), 2.65-2.69 (m, 2H), 2.5
1-2.54 (m, 2H), 1.59-1.63 (m, 2H), 1.38 (s, 18H), 1.2
2-1.28 (m, 8H), 0.86 (t, J = 7Hz, 3H) IR (cm ^-1 ) 3640, 2960, 2940, 2870, 1660, 1530, 146
0, 1440, 1240, 760

Example 41 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-heptyl-N'-methylurea

[Chemical 59] The title compound was obtained by the same reaction procedure using N-methylheptylamine in place of decylamine of Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.36 (d, J = 8Hz, 1H), 7.18-7.
22 (m, 2H), 7.07-2.10 (m, 1H), 6.81 (s, 2H), 5.66 (s,
1H), 5.08 (s, 1H), 3.23 (t, J = 8Hz, 2H), 2.82 (s, 4H),
2.71 (s, 3H), 1.45-1.55 (s, 2H), 1.36 (s, 18H), 1.20
-1.30 (m, 8H), 0.86 (t, J = 7Hz, 3H) IR (cm ^-1 ) 2880, 2870, 2820, 1660, 1520, 1490, 145
0, 1440, 1250, 760

Example 42 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N ', N'-dibenzylurea

[Chemical 60] The title compound was obtained by the same reaction procedure using N, N-dibenzylamine instead of decylamine of Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.69 (d, J = 8Hz, 1H), 7.15-7.
29 (m, 10H), 7.00 (m, 1H), 6.90 (t, J = 8Hz, 1H), 6.80
(d, J = 8Hz, 1H), 6.74 (s, 2H), 6.01 (bs, 1H), 5.05 (s,
1H), 4.54 (s, 4H), 2.59 (t, J = 8Hz, 2H), 2.38 (t, J = 8H
z, 2H), 1.37 (s, 18H) IR (cm ^-1 ) 3628, 3280, 2958, 1710, 1645, 1594, 149
8, 1475, 1362, 1231,754, 696

Example 43 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-cyclohexyl-N '
-Methylurea

[Chemical formula 61] The title compound was obtained by the same reaction procedure using N-methylcyclohexylamine instead of decylamine of Example 11. Amorphous powder ¹ H-NMR (δ ppm, CDCl ₃ ) 7.65 (d, J = 7Hz, 1H), 7.15-7.
21 (m, 2H), 7.06 (t, J = 7Hz, 1H), 6.81 (s, 2H), 5.68 (b
s, 1H), 5.08 (s, 1H), 4.13 (m, 1H), 2.82 (s, 4H), 2.54
(s, 3H), 1.75-1.81 (m, 2H), 1.60-1.75 (m, 3H), 1.25-
1.40 (m, 23H) IR (cm ^-1 ) 3638, 3426, 2930, 1639, 1520, 1484, 145
0, 1314, 1249, 1166, 1121, 751

Example 44 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(9-anthryl) methyl-N'-methylurea

[Chemical formula 62] The title compound was obtained by the same reaction procedure using 9- (methylaminomethyl) anthracene instead of decylamine in Example 11. mp205-206 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 8.47 (s, 1H), 8.37 (d, J = 9Hz,
2H), 8.02-8.04 (m, 2H), 7.70 (d, J = 8Hz, 1H), 7.43-
7.57 (m, 4H), 7.15-7.31 (m, 3H), 6.67 (s, 2H), 5.67 (s,
1H), 5.59 (s, 2H), 4.94 (s, 1H), 2.76-2.86 (m, 4H),
2.34 (s, 3H), 1.19 (s, 18H) IR (cm ^-1 ) 3420, 2950, 1640, 1520, 1490, 1450, 144
0, 1250, 740

Example 45 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N ', N'-dioctylurea

[Chemical formula 63] The title compound was obtained by the same reaction procedure using N, N-dioctylamine instead of decylamine of Example 11. mp 55-60 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.73 (dd, J = 8,1Hz, 1H), 7.13
-7.25 (m, 2H), 7.00-7.05 (m, 1H), 6.85 (s, 2H), 5.94
(s, 1H), 5.07 (s, 1H), 3.18 (t, J = 8Hz, 4H), 2.81 (s,
4H), 1.51-1.61 (m, 4H), 1.39 (s, 18H), 1.20-1.34 (m,
20H), 0.87 (t, J = 7Hz, 6H) IR (cm ^-1 ) 3646, 3420, 3322, 1626, 1511

Example 46 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N ', N'-dicyclohexylurea

[Chemical 64] The title compound was obtained by the same reaction procedure using N, N-dicyclohexylamine instead of decylamine of Example 11. mp149-152 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.73 (dd, J = 8, 1Hz, 1H), 7.15
-7.20 (m, 1H), 7.13 (dd, J = 7,2Hz, 1H), 7.00-7.05 (m,
1H), 6.94 (s, 2H), 6.15 (s, 1H), 5.06 (s, 1H), 3.42-
3.52 (m, 2H), 2.84 (s, 4H), 1.55-1.83 (m, 14H), 1.41
(s, 18H), 1.22-1.34 (m, 4H), 0.98-1.13 (m, 2H) IR (cm ^-1 ) 3474, 3400, 1644, 1588, 1517

Example 47 N- [2- (3,5-diisopropyl-4-hydroxyphenethyl) phenyl] -N'-heptylurea

[Chemical 65] A solution of 0.88 g (3.2 mmol) of diphenylphosphoryl azide, 0.42 g (2.9 mmol) of octanoic acid and 0.32 g (3.2 mmol) of triethylamine in toluene (10 ml) was stirred at room temperature for 1.5 hours, and then stirred. The mixture was heated and stirred at 90 ° C for 2 hours. After the mixture was allowed to cool, it was stirred under ice cooling to 0.8.
5 g (2.9 mmol) 4- (2-aminophenethyl) -2,
Toluene solution of 6-diisopropylphenol (2 ml)
Was dripped. After that, the temperature was gradually returned to room temperature and the mixture was stirred overnight. After distilling off the solvent, the residue was purified by silica gel column chromatography and recrystallized from ethyl acetate-hexane to give N-
[2- (3,5-diisopropyl-4-hydroxyphenethyl) phenyl] -N'-heptylurea 0.99 g
(76%) crystals were obtained. mp 150-151 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.16-7.26 (m, 4H), 6.69 (s, 2
H), 5.14 (s, 1H), 4.73 (s, 1H), 4.18 (t, J = 6Hz, 1H),
3.01-3.15 (m, 4H), 2.71-2.89 (m, 4H), 1.34-1.44 (m, 2
H), 1.2-1.3 (m, 8H), 1.20, (s, 6H), 1.19 (s, 6H), 0.8
6 (t, J = 7Hz, 3H) IR (cm ^-1 ) 3330, 2960, 2930, 1640, 1580, 1470, 145
0, 1260, 750

Example 48 N- [2- (3,5-di-t-butyl-4-hydroxystyryl) phenyl] -N'-heptylurea

[Chemical formula 66] A solution of 0.36 g (1.3 mmol) of diphenylphosphoryl azide, 0.17 g (1.2 mmol) of octanoic acid, and 0.13 g (1.3 mmol) of triethylamine in toluene (5 ml) was stirred at room temperature for 1.5 hours, and then stirred. The mixture was heated and stirred at 90 ° C for 2 hours. After the mixture was allowed to cool, 4- (2
-Aminostyryl) -2,6-di-t-butylpheno-
A solution of 0.89 g (1.2 mmol) of toluene in toluene (2 ml) was added dropwise. After that, the temperature was gradually returned to room temperature and the mixture was stirred overnight. After the solvent was distilled off, the residue was purified by silica gel column chromatography and recrystallized from ethyl acetate-hexane to give N- [2-
(3,5-di-t-butyl-4-hydroxystyryl)
Phenyl] -N'-heptylurea 0.39 g (70%)
Was obtained. mp 162-164 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.63 (dd, J = 7,2Hz, 1H), 7.33-
7.37 (m, 3H), 7.21-7.28 (m, 2H), 7.08 (d, J = 16Hz, 1
H), 7.01 (d, J = 16Hz, 1H), 6.01 (bs, 1H), 5.33 (s, 1
H), 4.54 (t, J = 6Hz, 1H), 3.20 (dt, J = 6,7Hz, 2H), 1.4
2-1.47 (m, 20H), 1.20-1.36 (m, 8H), 0.83 (t, J = 7Hz, 3
H) IR (cm ^-1 ) 3626, 3334, 2954, 2926, 1642, 1568, 145
4, 1439, 1235, 1152, 960, 751

Example 49 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[2- (4-phenyl-1-piperazinyl) -5-pyridyl] urea

[Chemical formula 67] Instead of the hexyloxybenzoic acid of Example 1, 6- (4
The title compound was obtained by the same reaction procedure using -phenyl-1-piperazinyl) nicotinic acid. mp197
~ 199 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.95 (d, J = 2Hz, 1H), 7.67 (dd,
J = 9.2Hz, 1H), 7.39 (d, J = 9Hz, 1H), 7.17-7.33 (m, 5
H), 6.94-7.00 (m, 2H), 6.89 (dd, J = 7, 7Hz, 1H), 6.81
(s, 2H), 6.65 (d, J = 9Hz, 1H), 5.85 (bs, 1H), 5.22 (b
s, 1H), 5.16 (s, 1H), 3.62 (t, J = 5Hz, 4H), 3.28 (t, J
= 5Hz, 4H), 2.76-2.92 (m, 4H), 1.38 (s, 18H) IR (cm ^-1 ) 3620, 3330, 3290, 2954, 1646, 1600, 154
7, 1492, 1233, 951, 760

Example 50 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(dicyclohexylmethyl) urea

[Chemical 68] The title compound was obtained by the same reaction procedure using dicyclohexyl acetic acid instead of hexyloxybenzoic acid of Example 1. mp194-195 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.29-7.18 (m, 4H), 6.81 (s, 2)
H), 5.19 (bs, 1H), 5.09 (s, 1H), 4.00 (d, J = 10Hz, 1
H), 3.47 (bs, 1H), 2.88 (t, J = 7Hz, 2H), 2.80 (t, J = 7H
z, 2H), 1.54-1.70 (m, 10H), 1.38 (s, 18H), 1.38-1.42
(m, 2H), 1.01-1.19 (m, 8H), 0.73-0.80 (m, 2H) IR (cm ^-1 ) 3642, 3362, 2924, 2852, 1641, 1553, 143
6, 1235, 744

Example 51 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(6-oxoheptyl) urea

[Chemical 69] The title compound was obtained by the same reaction procedure using 7-oxooctanoic acid instead of hexyloxybenzoic acid of Example 1. mp73-76 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.16-7.25 (m, 4H), 6.77 (s, 2
H), 5.12 (s, 1H), 4.97 (s, 1H), 4.17-4.24 (m, 1H), 3.
12 (td, J = 7, 6Hz, 2H), 2.76-2.86 (m, 4H), 2.38 (t, J =
7Hz, 2H), 2.10 (s, 3H), 1.49-1.57 (m, 2H), 1.33-1.45
(m, 4H), 1.37 (s, 18H) IR (cm ^-1 ) 3368, 2950, 1712, 1632, 1574

Example 52 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(4-t-butylcyclohexyl) urea

[Chemical 70] Instead of the hexyloxybenzoic acid of Example 1, 4-t-
The title compound was obtained by the same reaction procedure using butylcyclohexanecarboxylic acid. mp206-208 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.15-7.25 (m, 4H), 6.78 (s, 2
H), 5.10 (s, 1H), 5.00 (s, 1H), 4.02 (d, J = 8Hz, 1H),
3.47-3.57 (m, 1H), 2.76-2.86 (m, 4H), 1.96-1.98 (m, 2
H), 1.70-1.73 (m, 2H), 1.38 (s, 18H), 0.84-1.13 (m, 5
H), 0.81 (s, 9H) IR (cm ^-1 ) 3642, 3356, 2948, 1640, 1585, 1436, 1234

Example 53 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-cycloheptyl-N '
-Heptyl urea

[Chemical 71] The title compound was obtained by the same reaction procedure using N-heptylcycloheptylamine in place of decylamine of Example 11. mp 70-72 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.77 (dd, J = 8, 1 Hz, 1 H), 7.20
(ddd, J = 8, 8, 2Hz, 1H), 7.13 (dd, J = 8, 1Hz, 1H), 7.
02 (ddd, J = 8, 8, 1Hz, 1H), 6.89 (s, 2H), 6.04 (s, 1
H), 5.06 (s, 1H), 4.02 (bs, 1H), 3.07-3.11 (m, 2H),
2.82 (s, 4H), 1.82-1.87 (m, 2H), 1.58-1.70 (m, 8H),
1.40-1.56 (m, 4H), 1.40 (s, 18H), 1.25 (bs, 8H), 0.84
-0.90 (m, 3H) IR (cm ^-1 ) 3642, 3296, 2910, 1631, 1588, 1435, 123
5,751

Example 54 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-benzyl-N'-cycloheptylurea

[Chemical 72] The title compound was obtained by the same reaction procedure using benzilcycloheptylamine instead of decylamine of Example 11. mp183-184 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.74 (d, J = 8 Hz, 1 H), 7.25-7.3
0 (m, 2H), 7.07-7.21 (m, 4H), 6.90-6.93 (m, 2H), 6.76
(s, 2H), 5.95 (s, 1H), 5.06 (s, 1H), 4.42-4.50 (m, 1
H), 4.43 (s, 2H), 2.52 (t, J = 8Hz, 2H), 2.23 (t, J = 8H
z, 2H), 1.92-1.99 (m, 2H), 1.43-1.72 (s, 10H), 1.42
(s, 18H) IR (cm ^-1 ) 3638, 3402, 2926, 1671, 1589, 1527, 145
5,1232,1213,752

Example 55 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-{[1- (4-dimethylaminophenyl) cyclopentyl] methyl} urea

[Chemical formula 73] The title compound was obtained by the same reaction procedure using 4- [1- (aminomethyl) cyclopentyl] -N, N-dimethylaniline instead of decylamine of Example 11. mp174-175 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.08-7.21 (m, 3H), 7.03 (d, J =
7Hz, 1H), 6.92 (d, J = 9Hz, 2H), 6.77 (s, 2H), 6.54
(d, J = 8Hz, 2H), 5.07 (s, 2H), 4.07-4.15 (m, 1H), 3.2
2 (d, J = 5Hz, 2H), 2.88 (s, 6H), 2.69-2.79 (m, 4H), 1.
63-1.83 (m, 8H), 1.36 (s, 18H) IR (cm ^-1 ) 3640, 3360, 1644, 1525, 1435, 1233, 814,
749

Example 56 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(2-ethyl-1,3)
-Dihydroxy-2-propyl) urea

[Chemical 74] 2-amino-2-instead of decylamine of Example 11
The title compound was obtained by the same reaction procedure using ethyl-1,3-propanediol. mp145-146
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 7.16-7.31 (m, 4H), 6.78 (s, 2
H), 5.12 (s, 1H), 5.11 (s, 1H), 4.61 (s, 1H), 3.75-3.
89 (m, 4H), 3.46-3.55 (m, 2H), 2.75-2.88 (m, 4H), 1.5
1 (q, J = 8Hz, 2H), 1.38 (s, 18H), 0.75 (t, J = 8Hz, 3H) IR (cm ^-1 ) 3640, 3570, 3400, 3340, 2970, 1660, 161
0, 1560, 1440, 1250, 750, 650

Example 57 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(4-benzyloxycyclopropyl) urea

[Chemical 75] The title compound was obtained by the same reaction procedure using 4-benzyloxycyclohexylamine instead of decylamine of Example 11. mp. 152-153 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.16-7.36 (m, 9H), 6.77 (s, 2
H), 5.11 (s, 1H), 4.94 (s, 1H), 4.51 (s, 2H), 4.00
(d, J = 8Hz, 1H), 3.56-3.68 (m, 1H), 3.18-3.28 (m, 1
H), 2.74-2.86 (m, 4H), 1.93-2.15 (m, 4H), 1.31-1.47
(m, 2H), 1.38 (s, 18H), 0.94-1.08 (m, 2H) IR (cm ^-1 ) 3630, 3370, 3330, 2950, 1645, 1565, 123
5,1090,750

Example 58 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(2-ethoxycarbonylethyl) urea

[Chemical 76] The title compound was obtained by the same reaction procedure using ethyl 3-aminopropionate instead of decylamine in Example 11. mp158-159 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.14-7.28 (m, 4H), 6.78 (s, 2)
H), 5.12 (s, 1H), 5.08 (s, 1H), 4.75 (t, J = 6Hz, 1H),
4.07 (q, J = 7Hz, 2H), 3.41 (dt, J = 6, 6Hz, 1H), 2.74-
2.86 (m, 4H), 2.49 (t, J = 6Hz, 2H), 1.38 (18H.s, 18
H), 1.18 (t, J = 7Hz, 3H) IR (cm ^-1 ) 3630, 3320, 3270, 2960, 1730, 1630, 157
0, 1440, 1235, 1190, 745

Example 59 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(4-aminocyclohexyl) urea

[Chemical 77] The title compound was obtained by the same reaction procedure using 1,4-diaminocyclohexane instead of decylamine in Example 11. mp> 280 ° C (decomposition) ¹ H-NMR (δ ppm, CDCl ₃ ) 7.14-7.28 (m, 4H), 6.77 (s, 2
H), 5.12 (bs, 1H), 4.97 (bs, 1H), 3.98-4.05 (m, 1H),
3.53-3.64 (m, 1H), 2.74-2.87 (m, 4H), 2.52-2.62 (m, 1
H), 1.89-1.97 (m, 2H), 1.77-1.86 (m, 2H), 1.38 (s, 18
H), 0.97-1.24 (m, 4H) IR (cm ^-1 ) 3630, 3420, 3340, 2940, 1635, 1590, 157
0, 1240, 935

Example 60 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(4-acetamidocyclohexyl) urea

[Chemical 78] Using N- (4-aminocyclohexyl) acetamide in place of decylamine in Example 11, the title compound was obtained by the same reaction procedure. mp 250 ° C (decomposition) ¹ H-NMR (δ ppm, CDCl ₃ ) 7.16-7.30 (m, 4H), 6.77 (s, 2
H), 5.26 (bd, J = 8Hz, 1H), 5.11 (s, 1H), 4.93 (s, 1
H), 4.05 (d, J = 8Hz, 1H), 3.54-3.73 (m, 2H), 2.74-2.8
7 (m, 4H), 1.92-2.00 (m, 4H), 1.93 (s, 3H), 1.37 (s, 1
8H), 1.03-1.27 (m, 4H) IR (cm ^-1 ) 3640, 3290, 2950, 1635, 1550, 1440, 123
5,760

Example 61 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(4-hydroxycyclohexyl) urea

[Chemical 79] The title compound was obtained by the same reaction procedure using 4-aminocyclohexanol instead of decylamine of Example 11. mp202-203 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.17-7.29 (m, 4H), 6.77 (s, 2)
H), 5.12 (s, 1H), 4.94 (s, 1H), 3.99 (d, J = 8Hz, 1H),
3.43-3.69 (m, 2H), 2.75-2.87 (m, 4H), 1.87-2.01 (m, 4
H), 1.28-1.43 (m, 2H), 1.38 (s, 18H), 0.97-1.12 (m, 2
H) IR (cm ^-1 ) 3645, 3320, 2950, 1640, 1570, 1440, 123
5,1070,880,745

Example 62 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(4-acetoxycyclohexyl) urea

[Chemical 80] The title compound was obtained by the same reaction procedure using 4-aminocyclohexyl acetate instead of decylamine of Example 11. mp 92-94 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.17-7.28 (m, 4H), 6.77 (s, 2
H), 5.12 (s, 1H), 4.93 (s, 1H), 4.53-4.64 (m, 1H), 4.
02 (d, J = 8Hz, 1H), 3.57-3.71 (m, 1H), 2.78-2.87 (m, 4
H), 2.01 (s, 3H), 1.87-2.02 (m, 4H), 1.32-1.52 (m, 2
H), 1.38 (s, 18H), 1.02-1.16 (m, 2H) IR (cm ^-1 ) 3640, 3380, 2960, 1740, 1645, 1560, 144
0, 1245, 1050, 765

Example 63 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(3-pyridylmethyl) urea

[Chemical 81] The title compound was obtained by the same reaction procedure using 3- (aminomethyl) pyridine instead of decylamine in Example 11. mp163-164 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 8.48 (dd, J = 5, 1 Hz, 1 H), 8.45
(d, J = 2Hz, 1H), 7.58 (d, J = 8Hz, 1H), 7.18-7.27 (m, 5
H), 6.75 (s, 2H), 5.12 (s, 1H), 4.95 (s, 1H), 4.45-4.
50 (m, 1H), 4.34 (d, J = 6Hz, 2H), 2.75-2.86 (m, 4H),
1.35 (s, 18H) IR (cm ^-1 ) 3294, 1634, 1574, 1430, 1239, 1119, 760,
712

Example 64 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(4-pyridylmethyl) urea

[Chemical formula 82] The title compound was obtained by the same reaction procedure using 4- (aminomethyl) pyridine instead of decylamine of Example 11. mp214-215 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 8.50 (dd, J = 4, 1 Hz, 2H), 7.30
-7.25 (m, 2H), 7.20-7.24 (m, 2H), 7.12 (d, J = 6Hz, 2
H), 6.77 (s, 2H), 5.13 (s, 1H), 5.00 (s, 1H), 4.54
(t, J = 6Hz, 1H), 4.34 (d, J = 6Hz, 2H), 2.86-2.90 (m, 2
H), 2.79-2.82 (m, 2H), 1.35 (s, 18H) IR (cm ^-1 ) 3292, 1632, 1573, 1436, 1237, 761

Example 65 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(2-pyridylmethyl) urea

[Chemical 83] The title compound was obtained by the same reaction procedure using 2- (aminomethyl) pyridine instead of decylamine of Example 11. mp189-190 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 8.42 (dd, J = 4, 1 Hz, 1H), 7.61
(ddd, J = 8, 8, 2Hz, 1H), 7.38 (dd, J = 8, 1Hz, 1H), 7.
12-7.24 (m, 5H), 6.80 (s, 2H), 5.48 (bs, 1H), 5.36
(t, J = 5Hz, 1H), 5.29 (s, 1H), 4.47 (d, J = 6Hz, 2H),
2.78-2.89 (m, 4H), 1.36 (s, 18H) IR (cm ^-1 ) 3632, 3612, 3296, 1627, 1576, 1437, 123
4,755

Example 66 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-ethyl-N '-(4-
Pyridylmethyl) urea

[Chemical 84] The title compound was obtained by the same reaction procedure using 4- (ethylaminomethyl) pyridine instead of decylamine of Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 8.51 (dd, J = 4, 1Hz, 2H), 7.66
(dd, J = 8, 1Hz, 1H), 7.09-7.25 (m, 5H), 6.79 (s, 2
H), 5.85 (s, 1H), 5.09 (s, 1H), 4.50 (s, 2H), 3.09
(q, J = 7Hz, 2H), 2.74-2.82 (m, 4H), 1.36 (s, 18H), 1.
14 (t, J = 7Hz, 3H) IR (cm ^-1 ) 3266, 3060, 1630, 1606, 1516, 1492, 145
1,1431,1269,755,746

Example 67 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(8-methyl-8-azabicyclo [3.2.1] -3 -Octyl) urea

[Chemical 85] 3-amino-8-instead of decylamine of Example 11
The title compound was obtained by the same reaction procedure using methyl-8-azabicyclo [3.2.1] octane. mp2
29-230 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.27 (d, J = 4 Hz, 1 H), 7.13-7.2
1 (m, 3H), 6.79 (s, 2H), 5.51 (bs, 1H), 5.14 (s, 1H),
4.77 (bs, 1H), 4.07-4.13 (m, 1H), 3.51 (bs, 2H), 2.76
-2.87 (m, 4H), 2.51 (s, 3H), 2.13-2.15 (m, 2H), 1.89-
1.96 (m, 6H), 1.38 (m, 18H) IR (cm ^-1 ) 3360, 1645, 1565, 1435, 1240, 745

Example 68 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(2-pyridylmethyl) -N'-(3-pyridylmethyl) urea

[Chemical 86] The title compound was obtained by the same reaction procedure using N- (3-pyridylmethyl) -2-pyridylmethylamine in place of decylamine of Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 9.47 (s, 2H), 8.52 (d, J = 4Hz,
1H), 8.48 (dd, J = 5, 1Hz, 1H), 7.89 (d, J = 6Hz, 1H),
7.76 (dd, J = 8, 1Hz, 1H), 7.67 (ddd, J = 8, 8, 2Hz, 1
H), 7.54 (dd, J = 8, 2Hz, 1H), 7.23 (t, J = 7Hz, 2H), 7.
14-7.18 (m, 1H), 7.02-7.06 (m, 2H), 6.97 (d, J = 8Hz, 1
H), 6.93 (s, 2H), 5.19 (s, 1H), 4.60 (s, 2H), 4.37
(s, 2H), 2.96-3.05 (m, 2H), 2.90-2.94 (m, 2H), 1.35
(s, 18H) IR (cm ^-1 ) 3632, 3250, 1661, 1591, 1533, 1480, 143
6, 1393, 1362, 1295, 1214, 755

Example 69 (S) -N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(α-ethoxycarbonyl) benzylurea

[Chemical 87] The title compound was obtained by the same reaction procedure using (S) -α-phenylglycine ethyl ester instead of decylamine of Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.44 (d, J = 8Hz, 1H), 7.19-7.3
3 (m, 8H), 6.78 (s, 2H), 5.90 (s, 1H), 5.74 (d, J = 7H
z, 1H), 5.59 (d, J = 8Hz, 1H), 5.16 (s, 1H), 4.10-4.24
(m, 2H), 2.89-2.92 (m, 2H), 2.82-2.85 (m, 2H), 1.43
(s, 18H), 1.21 (t, J = 7Hz, 3H) IR (cm ^-1 ) 3636, 3294, 1737, 1643, 1542, 1435, 123
3,1181,754

Example 70 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(1-methyl-3-piperidyl) urea

[Chemical 88] 3-amino-1-in place of decylamine in Example 11
The title compound was obtained by the same reaction procedure using methylpiperidine. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.45 (d, J = 8Hz, 1H), 7.16-7.2
6 (m, 3H), 6.92 (s, 2H), 6.35 (bs, 1H), 5.40 (bs, 1
H), 5.17 (s, 1H), 3.45 (bs, 1H), 3.18-3.23 (m, 1H),
2.93-3.01 (m, 1H), 2.83-2.92 (m, 4H), 2.45-2.51 (m, 1
H), 2.34 (s, 3H), 2.18-2.27 (m, 1H), 1.82-1.95 (m, 1
H), 1.60-1.73 (m, 3H), 1.46 (s, 18H) IR (cm ^-1 ) 3638, 3250, 1643, 1548, 1436, 1235, 910,
733

Example 71 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-benzyl-N '-(2
-Pyridylmethyl) urea

[Chemical 89] N-benzyl-2 instead of decylamine of Example 11
The title compound was obtained by the same reaction procedure using -pyridylmethylamine. ¹ H-NMR (δ ppm, CDCl ₃ ) 9.20 (bs, 1H), 7.92 (d, J = 4H
z, 1H), 7.78 (d, J = 7Hz, 1H), 7.52 (ddd, J = 8, 8, 2H
z, 1H), 7.19-7.30 (m, 7H), 7.01-7.05 (m, 2H), 6.93
(s, 2H), 6.92-6.94 (m, 1H), 5.06 (s, 1H), 4.60 (s, 2)
H), 4.41 (s, 2H), 2.88-3.00 (m, 4H), 1.36 (s, 18H) IR (cm ^-1 ) 3620, 3250, 2244, 1657, 1590, 1532, 145
3, 1436, 1213, 752, 732

Example 72 (R) -N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(α-ethoxycarbonyl) benzylurea

[Chemical 90] The title compound was obtained by the same reaction procedure using (R) -α-phenylglycine ethyl ester instead of decylamine of Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.18-7.35 (m, 9H), 6.77 (s, 2
H), 5.50 (d, J = 8Hz, 1H), 5.37 (d, J = 8Hz, 1H), 5.33
(s, 1H), 5.09 (s, 1H), 4.07-4.18 (m, 2H), 2.78-2.84
(m, 4H), 1.35 (s, 18H), 1.17 (t, J = 7Hz, 3H) IR (cm ^-1 ) 3636, 3330, 1739, 1640, 1542, 1436, 123
4, 1180, 935, 751, 698

Example 73 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(1-azabicyclo [2.2.2] -3-octyl) urea

[Chemical Formula 91] 3-amino-1-in place of decylamine in Example 11
The title compound was obtained by the same reaction procedure using azabicyclo [2.2.2] octane. mp227-229
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 7.21-7.27 (m, 4H), 6.77 (s, 2
H), 5.11 (s, 1H), 5.07 (s, 1H), 4.43 (d, J = 7Hz, 1H),
3.78-3.85 (m, 1H), 3.28 (ddd, J = 14, 10, 2Hz, 1H), 2.
65-2.89 (m, 8H), 2.29-2.33 (m, 1H), 1.85-1.87 (m, 1
H), 1.55-1.70 (m, 4H), 1.38 (s, 18H) IR (cm ^-1 ) 3636, 3368, 3260, 1640, 1587, 1564, 143
4, 1237, 1122, 765, 753

Example 74 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[2- (3,4-dichlorophenyl) -2-propyl] urea

[Chemical Formula 92] The title compound was obtained by the same reaction procedure using 3,4-dichloro-α, α-dimethylbenzylamine instead of decylamine in Example 11. mp203-205
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 7.41 (d, J = 2Hz, 1H), 7.16-7.3
2 (m, 6H), 6.81 (s, 2H), 5.17 (s, 1H), 5.11 (s, 1H),
4.60 (s, 1H), 2.79-2.83 (m, 4H), 1.56 (s, 6H), 1.39
(s, 18H) IR (cm ^-1 ) 3638, 3352, 3284, 1644, 1564, 1558, 143
7, 1235, 1171, 1030, 768, 745

Example 75 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(4-dimethylaminophenethyl) urea

[Chemical formula 93] The title compound was obtained by the same reaction procedure using 4-dimethylaminophenethylamine instead of decylamine of Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.11-7.24 (m, 4H), 6.96 (d, J =
9Hz, 2H), 6.77 (s, 2H), 6.62 (s, 2H), 5.09 (s, 1H),
5.08 (s, 1H), 4.03 (t, J = 6Hz, 1H), 3.33 (td, J = 7, 6H
z, 2H), 2.89 (s, 6H), 2.72-2.86 (m, 4H), 2.64 (t, J = 7
Hz, 2H), 1.37 (s, 18H) IR (cm ^-1 ) 3640, 3342, 2940, 1640, 1562, 1521, 143
9,1232,660,643

Example 76 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-{[1- (3,4-methylenedioxyphenyl) cyclopentyl] methyl }urea

[Chemical 94] The title compound was obtained by the same reaction procedure using 5- {1- (aminomethyl) cyclopentyl} -1,3-dioxaindane instead of decylamine of Example 11. mp188-189 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.12-7.22 (m, 3H), 7.03 (d, J =
7Hz, 1H), 6.75 (s, 2H), 6.59 (d, J = 2Hz, 1H), 6.57
(d, J = 8Hz, 1H), 6.47 (dd, J = 8, 2Hz, 1H), 5.88 (s, 2
H), 5.08 (s, 1H), 5.00 (s, 1H), 3.95-4.00 (m, 1H), 3.
21 (d, J = 5Hz, 2H), 2.70-2.80 (m, 4H), 1.55-1.85 (m, 8
H), 1.36 (s, 18H) IR (cm ^-1 ) 3640, 3388, 3328, 1645, 1561, 1488, 143
5, 1363, 1234, 1042, 940, 760

Example 77 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[2- (3,4-dichlorophenyl) -2-methylpropyl] urea

[Chemical 95] The title compound was obtained by the same reaction procedure using 3,4-dichloro-β, β-dimethylphenethylamine instead of decylamine in Example 11. mp165 ~ 16
7 ℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 6.95-7.29 (m, 7H), 6.73 (s, 2
H), 5.09 (s, 1H), 4.90-5.00 (m, 1H), 3.96 (bs, 1H),
3.29 (d, J = 6Hz, 2H), 2.65-2.75 (m, 4H), 1.35 (s, 18
H), 1.23 (s, 6H) IR (cm ^-1 ) 3638, 3364, 1646, 1587, 1563, 1475, 143
7, 1235, 762

Example 78 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-methyl-N '-(1-
Methyl-4-piperidyl) urea

[Chemical 96] 1-Methyl-4-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using (methylamino) piperidine. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.63 (d, J = 7Hz, 1H), 7.19-7.2
6 (m, 2H), 7.10 (ddd, J = 7, 7, 1Hz, 1H), 6.79 (s, 2
H), 5.63 (s, 1H), 5.08 (s, 1H), 4.20-4.27 (m, 1H), 2.
85-2.90 (m, 2H), 2.82 (s, 4H), 2.48 (s, 3H), 2.28 (s,
3H), 1.98-2.07 (m, 2H), 1.55-1.90 (m, 4H), 1.35 (s, 1
8H) IR (cm ^-1 ) 3424, 1638, 1511, 1484, 1450, 1436, 128
7, 1042, 754

Example 79 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(4-fluorophenethyl) urea

[Chemical 97] The title compound was obtained by the same reaction procedure using 4-fluorophenethylamine instead of decylamine of Example 11. mp177-179 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.03-7.26 (m, 6H), 6.89-6.93
(m, 2H), 6.76 (m, 2H), 5.10 (s, 1H), 4.94 (s, 1H), 4.
15-4.20 (m, 1H), 3.35 (q, J = 7Hz, 2H), 2.76-2.82 (m, 4
H), 2.71 (t, J = 7Hz, 2H), 1.36 (s, 18H) IR (cm ^-1 ) 3636, 3348, 1643, 1563, 1511, 1438, 123
4,831,747

Example 80 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[1- (2,4-difluorobenzyl) -4-piperidyl] urea

[Chemical 98] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using (2,4-difluorobenzyl) piperidine. mp157
~ 158 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.15-7.36 (m, 5H), 6.89-6.72
(m, 4H), 5.11 (s, 1H), 4.97 (s, 1H), 4.09 (d, J = 8Hz,
1H), 3.57-3.72 (m, 1H), 3.47 (s, 2H), 2.68-2.88 (m, 6
H), 2.14-2.20 (m, 2H), 1.82-1.95 (m, 2H), 1.58-1.74
(m, 2H), 1.20-1.40 (m, 2H), 1.37 (s, 18H) IR (cm ^-1 ) 3640, 3370, 3250, 2960, 1690, 1650, 159
0, 1565, 1505, 1235, 850, 760

Example 81 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[1- (4-methoxybenzyl) -4-piperidyl] urea

[Chemical 99] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using (4-methoxybenzyl) piperidine. mp152-15
3 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.14-7.30 (m, 6H), 6.74-6.88
(m, 4H), 5.11 (s, 1H), 4.97 (s, 1H), 4.09 (d, J = 8Hz,
1H), 3.79 (s, 3H), 3.56-3.72 (m, 1H), 3.38 (s, 2H),
2.67-2.88 (m, 6H), 1.96-2.09 (m, 2H), 1.82-1.92 (m, 2
H), 1.37 (s, 18H), 1.18-1.35 (m, 2H) IR (cm ^-1 ) 3640, 3360, 3260, 2950, 1645, 1595, 156
5,1515,1245,1045,760

Example 82 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(1-phenethyl-4)
-Piperidyl) urea

[Chemical 100] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using phenethylpiperidine. mp175-176 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.15-7.31 (m, 9H), 6.78 (s, 2
H), 5.12 (s, 1H), 5.01 (s, 1H), 4.13 (d, J = 8Hz, 1H),
3.58-3.73 (m, 1H), 2.72-2.91 (m, 8H), 2.50-2.57 (m, 2
H), 2.05-2.16 (m, 2H), 1.38 (s, 18H), 1.24-1.35 (m, 2
H) IR (cm ^-1 ) 3640, 3340, 2950, 1640, 1590, 1565, 143
5, 1235, 770, 750, 700

Example 83 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[1- (4-fluorobenzyl) -4-piperidyl] urea

[Chemical 101] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using (4-fluorobenzyl) piperidine. mp174-17
5 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.16-7.29 (m, 6H), 6.93-7.00
(m, 2H), 6.77 (s, 2H), 5.11 (s, 1H), 4.97 (s, 1H), 4.
09 (d, J = 8Hz, 1H), 3.57-3.71 (m, 1H), 3.39 (s, 2H),
2.66-2.87 (m, 6H), 1.98-2.08 (m, 2H), 1.82-1.90 (m, 2
H), 1.37 (s, 18H), 1.22-1.34 (m, 2H) IR (cm ^-1 ) 3645, 3370, 2950, 1540, 1590, 1560, 151
0, 1225, 750

Example 84 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[1- (4-cyanobenzyl) -4-piperidyl] urea

[Chemical 102] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using (4-cyanobenzyl) piperidine. mp197-198
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 7.58 (d, J = 8Hz, 2H), 7.40 (d,
J = 8Hz, 2H), 7.17-7.29 (m, 4H), 6.77 (s, 2H), 5.12
(s, 1H), 4.97 (s, 1H), 4.10 (d, J = 8Hz, 1H), 3.59-3.7
2 (m, 1H), 3.48 (s, 2H), 2.75-2.87 (m, 4H), 2.64-2.73
(m, 2H), 2.03-2.13 (m, 2H), 1.83-1.91 (m, 2H), 1.37
(s, 18H), 1.23-1.35 (m, 2H) IR (cm ^-1 ) 3580, 3355, 3250, 2960, 2240, 1645, 159
0, 1560, 1235, 825, 765, 550

Example 85 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-{[1- [2,4-bis (trifluoromethyl) benzyl] -4-piperidyl} urea

[Chemical 103] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using [2,4-bis (trifluoromethyl) benzyl] piperidine. mp156-157 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.92 (d, J = 8 Hz, 1 H), 7.85 (s,
1H), 7.73 (d, J = 8Hz, 1H), 7.17-7.29 (m, 4H), 6.78
(s, 2H), 5.12 (s, 1H), 4.98 (s, 1H), 4.11 (d, J = 8Hz,
1H), 3.61-3.74 (m, 1H), 3.64 (s, 2H), 2.75-2.88 (m, 4
H), 2.64-2.73 (m, 2H), 2.13-2.23 (m, 2H), 1.84-1.92
(m, 2H), 1.38 (s, 18H), 1.27-1.36 (m, 2H) IR (cm ^-1 ) 3645, 3350, 2955, 1600, 1565, 1440, 135
0,1280,1175,1130,1060,750,680

Example 86 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[1- (3-pyridylmethyl) -4-piperidyl] urea

[Chemical 104] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using (3-pyridylmethyl) piperidine. mp156-158
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 8.46-8.52 (m, 2H), 7.60 (d, J =
8Hz, 1H), 7.16-7.28 (m, 5H), 6.77 (s, 2H), 5.12 (s, 1
H), 5.02 (s, 1H), 4.13 (d, J = 8Hz, 1H), 3.58-3.72 (m,
1H), 3.45 (s, 2H), 2.67-2.87 (m, 6H), 2.03-2.12 (m, 2
H), 1.82-1.90 (m, 2H), 1.37 (s, 18H), 1.22-1.37 (m, 2
H) IR (cm ^-1 ) 3632, 3362, 2950, 1645, 1561, 1433, 123
2,759,713

Example 87 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[1- (4-pyridylmethyl) -4-piperidyl] urea

[Chemical 105] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using (4-pyridylmethyl) piperidine. mp156-158
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 8, 51 (dd, J = 4, 2Hz, 2H), 7.1
6-7.28 (m, 6H), 6.77 (s, 2H), 5.12 (s, 1H), 5.00 (s, 1
H), 4.12 (d, J = 8Hz, 1H), 3.60-3.72 (m, 1H), 3.44 (s,
2H), 2.74-2.88 (m, 4H), 2.66-2.74 (m, 2H), 2.04-2.14
(m, 2H), 1.83-1.92 (m, 2H), 1.38 (s, 18H), 1.25-1.38
(m, 2H) IR (cm ^-1 ) 3630, 3292, 2948, 1620, 1560, 1435, 123
7, 1109, 759

Example 88 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[1- (4-diethylaminobenzyl) -4-piperidyl] urea

[Chemical formula 106] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using (4-diethylaminobenzyl) piperidine. mp138
~ 141 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.16-7.27 (m, 4H), 7.09 (d, J =
8Hz, 2H), 6.77 (s, 2H), 6.60 (d, J = 8Hz, 2H), 5.11
(s, 1H), 4.99 (s, 1H), 4.12 (bd, J = 7Hz, 1H), 3.58-3.
70 (m, 1H), 3.28-3.40 (m, 6H), 2.73-2.86 (m, 6H), 1.9
8-2.08 (m, 2H), 1.82-1.89 (m, 2H), 1.37 (s, 18H), 1.2
5-1.37 (m, 2H), 1.14 (t, J = 7Hz, 6H) IR (cm ^-1 ) 3630, 3410, 2950, 1641, 1553, 1520, 123
2,758

Example 89 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[1- (2-pyridylmethyl) -4-piperidyl] urea

[Chemical formula 107] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using (2-pyridylmethyl) piperidine. mp106-109
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 8, 54 (d, J = 4Hz, 1H), 7.58-7.
65 (m, 1H), 7.33 (d, J = 8Hz, 1H), 7.12-7.27 (m, 6H),
6.77 (s, 2H), 5.11 (s, 1H), 5.01 (s, 1H), 4.14 (d, J = 7
Hz, 1H), 3.61-3.73 (m, 1H), 3.59 (s, 2H), 2.70-2.86
(m, 6H), 2.12-2.21 (m, 2H), 1.83-1.91 (m, 2H), 1.37
(s, 18H), 1.30-1.42 (m, 2H) IR (cm ^-1 ) 3630, 3330, 2948, 1639, 1589, 1543, 143
6,1233,1121,756

Example 90 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(cyclohexylmethyl) urea

[Chemical 108] The title compound was obtained by the same reaction procedure using aminomethylcyclohexane instead of decylamine in Example 11. mp 208-210 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.18-7.24 (m, 4H), 6.78 (s, 2)
H), 5.11 (s, 1H), 4.98 (bs, 1H), 4.18-4.28 (m, 1H),
2.97 (t, J = 6Hz, 2H), 2.74-2.90 (m, 4H), 1.55-1.70
(m, 5H), 1.38 (s, 18H), 1.08-1.30 (m, 4H), 0.78-0.90
(m, 2H) IR (cm ^-1 ) 3616, 3304, 2922, 1627, 1579, 1435, 1233

Example 91 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(1-benzyl-4-)
Piperidyl) -N '-(3-pyridylmethyl) urea

[Chemical 109] 1-Benzyl-4 instead of decylamine of Example 11
The title compound was obtained by the same reaction procedure using-(3-pyridylmethylamino) piperidine. mp127
~ 130 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 8, 55 (d, J = 2Hz, 1H), 8.41 (d
d, J = 5, 2Hz, 1H), 7.65 (d, J = 8Hz, 1H), 7.59 (d, J = 8H
z, 1H), 7.13-7.30 (m, 6H), 7.18 (m, 1H), 7.10 (dd, J =
8, 5Hz, 1H), 7.01 (d, J = 4Hz, 2H), 6.75 (s, 2H), 5.90
(bs, 1H), 5.11 (s, 1H), 4.45 (s, 2H), 4.22-4.33 (m, 1
H), 3.47 (s, 2H), 2.86-2.97 (m, 2H), 2.61 (t, J = 7Hz,
2H), 2.44 (t, J = 7Hz, 2H), 2.00-2.14 (m, 2H), 1.60-1.
86 (m, 4H), 1.38 (s, 18H) IR (cm ^-1 ) 3450, 3290, 1628, 1512, 1264, 1121, 102
9,742

Example 92 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(1-benzyl-4-)
Piperidyl) -N'-methylurea

[Chemical 110] 1-Benzyl-4 instead of decylamine of Example 11
The title compound was obtained by the same reaction procedure using-(methylamino) piperidine. mp 144-146 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.62 (d, J = 8 Hz, 1 H), 7.10-7.3
0 (m, 7H), 7.10 (d, J = 7Hz, 1H), 6.78 (s, 2H), 5.62 (b
s, 1H), 5.08 (s, 1H), 4.23 (s, 1H), 3.48 (s, 2H), 2.8
6-2.98 (m, 2H), 2.81 (s, 4H), 2.50 (s, 3H), 1.98-2.10
(m, 2H), 1.50-1.70 (m, 4H), 1.35 (s, 18H) IR (cm ^-1 ) 3328, 2954, 1632, 1512, 1196, 1041, 755,
701

Example 93 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(1-benzyl-4-
Piperidyl) -N'-cycloheptyl urea

[Chemical 111] 1-Benzyl-4 instead of decylamine of Example 11
The title compound was obtained by the same reaction procedure using-(cycloheptylamino) piperidine. mp107-1
09 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.72 (d, J = 8 Hz, 1 H), 7.23-7.3
6 (m, 5H), 7.19 (t, J = 7Hz, 1H), 7.13 (d, J = 6Hz, 1H),
7.02 (t, J = 7Hz, 1H), 6.93 (s, 2H), 6.12 (bs, 1H), 5.0
5 (s, 1H), 4.04-4.154 (m, 1H), 3.49 (s, 2H), 3.37-3.5
0 (m, 1H), 2.90-3.00 (m, 2H), 2.84 (s, 4H), 1.97-2.10
(m, 4H), 1.78-1.89 (m, 4H), 1.20-1.65 (m, 28H) IR (cm ^-1 ) 3476, 2922, 1662, 1528, 1454, 1236, 753

Example 94 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(1-acetyl-4-)
Piperidyl) urea

[Chemical 112] 1-Acetyl-4 instead of decylamine of Example 11
The title compound was obtained by the same reaction procedure using -aminopiperidine. mp218-221 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.15-7.29 (m, 4H), 6.76 (s, 2)
H), 5.13 (s, 1H), 4.93 (bs, 1H), 4.43-4.52 (m, 1H),
4.05-4.13 (m, 1H), 3.76-3.90 (m, 1H), 3.66-3.73 (m, 1
H), 3.04-3.14 (m, 1H), 2.71-2.85 (m, 4H), 2.58-2.70
(m, 1H), 2.05 (s, 3H), 1.95-2.06 (m, 1H), 1.82-1.90
(m, 1H), 1.37 (s, 18H), 1.10-1.20 (m, 2H) IR (cm ^-1 ) 3302, 2952, 1629, 1561, 1434, 1234

Example 95 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(1-ethyl-4-piperidyl) urea

[Chemical 113] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using ethylpiperidine. mp182-184 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.10-7.30 (m, 4H), 6.77 (s, 2)
H), 5.11 (s, 1H), 5.00 (bs, 1H), 4.14 (bd, J = 8Hz, 1
H), 3.58-3.72 (m, 1H), 2.70-2.90 (m, 6H), 2.39 (q, J =
7Hz), 1.97-2.12 (m, 2H), 1.85-1.97 (m, 2H), 1.37 (s,
18H), 1.30-1.40 (m, 2H), 1.07 (t, J = 7Hz, 3H) IR (cm ^-1 ) 3362, 2950, 1640, 1563, 1435, 1235

Example 96 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(1-methyl-4-piperidyl) urea

[Chemical 114] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using methylpiperidine. mp193-195 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.15-7.25 (m, 4H), 6.77 (s, 2
H), 5.12 (s, 1H), 4.97 (bs, 1H), 4.10 (bd, J = 8Hz, 1
H), 3.58-3.70 (m, 1H), 2.70-2.85 (m, 6H), 2.25 (s, 3
H), 2.02-2.12 (m, 2H), 1.84-1.93 (m, 2H), 1.38 (s, 18
H), 1.30-1.43 (m, 2H) IR (cm ^-1 ) 3360, 2944, 1639, 1562

Example 97 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[1- (2,2-dimethylpropyl) -4-piperidyl] urea

[Chemical 115] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using (2,2-dimethylpropyl) piperidine. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.18-7.26 (m, 4H), 6.78 (s, 2
H), 5.11 (s, 1H), 5.06 (bs, 1H), 4.12 (bd, J = 8Hz, 1
H), 3.53-3.65 (m, 1H), 2.75-2.90 (m, 4H), 2.60-2.68
(m, 2H), 2.22-2.32 (m, 2H), 1.98 (s, 2H), 1.73-1.83
(m, 2H), 1.38 (s, 18H), 1.20-1.40 (m, 2H), 0.81 (s, 9
H) IR (cm ^-1 ) 3322, 2952, 1638, 1536, 1435, 1234

Example 98 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(1-benzyl-3-
Pyrrolidinyl) urea

[Chemical formula 116] 3-amino-1-in place of decylamine in Example 11
The title compound was obtained by the same reaction procedure using benzilpyrrolidine. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.10-7.30 (m, 9H), 6.78 (s, 2
H), 5.37 (bs, 1H), 5.10 (s, 1H), 4.71 (bd, J = 8Hz, 1
H), 4.23-4.34 (m, 1H), 3.55 (d, J = 13Hz, 1H), 3.50
(d, J = 13Hz, 1H), 2.70-2.81 (m, 6H), 2.49 (d, J = 4Hz,
2H), 2.14-2.36 (m, 2H), 1.37 (s, 18H) IR (cm ^-1 ) 3634, 3304, 2954, 1638, 1559, 1436, 123
4,749,699

Example 99 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(1-benzyl-3-
Piperidyl) -N'-methylurea

[Chemical 117] The title compound was obtained by the same reaction procedure using 3-amino-1-benzilpiperazine instead of decylamine of Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.59 (d, J = 8Hz, 1H), 7.15-7.4
0 (m, 7H), 7.08 (t, J = 7Hz, 1H), 6.79 (s, 2H), 5.72 (b
s, 1H), 5.06 (s, 1H), 4.22-4.34 (m, 1H), 3.48 (s, 2
H), 2.70-2.80 (m, 6H), 2.58 (s, 3H), 1.60-1.90 (m, 4
H), 1.30-1.46 (m, 2H), 1.35 (s, 18H) IR (cm ^-1 ) 3630, 3422, 2940, 1639, 1520, 1485, 145
2, 1312, 1249, 1122, 752, 699

Example 100 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-{1- [bis (4-fluorophenyl) methyl] -4-piperidyl }urea

[Chemical 118] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using [bis (4-fluorophenyl) methyl] piperidine. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.65-7.80 (m, 4H), 7.15-7.30
(m, 4H), 7.12 (t, J = 7Hz, 2H), 6.84 (d, J = 9Hz, 2H),
6.77 (s, 2H), 5.11 (s, 1H), 5.01 (bs, 1H), 4.13 (t, J =
7Hz, 2H), 3.75-3.95 (m, 3H), 2.91-3.03 (m, 2H), 2.75
-2.90 (m, 4H), 1.92-2.03 (m, 2H), 1.25-1.40 (m, 2H),
1.37 (s, 18H) IR (cm ^-1 ) 3314, 2948, 1638, 1602, 1544, 1303, 122
6,1153,768

Example 101 N- [2- (3,5-di-t-butyl-4-hydroxystyryl) phenyl] -N '-(2-pyridylmethyl)
urea

[Chemical formula 119] (1) 4- (2-aminostyryl) -2,6-di-t
-Butylphenol (4.85 g, 15.0 mmol) and diisopropylamine (1.72 g, 17.0 mmol) in methylene chloride (30 ml) were added to phenyl chloroformate under ice cooling.
51 g (16.0 mmol) was added dropwise, and the mixture was stirred for 7 hours while gradually returning to room temperature. To this was added 0.51 g (5.0 mmol) of diisopropylamine, 0.78 g (5.0 mmol) of phenyl chloroformate was added dropwise under ice cooling, and the mixture was stirred for 3 hours while gradually returning to room temperature. The reaction mixture was washed with water, saturated brine, dried (MgSO ₄ ), concentrated, and the residue was purified by silica gel column chromatography to give N- [2
Phenyl- (3,5-di-t-butyl-4-hydroxystyryl) phenyl] carbamate 6.65 g (99
%) Viscous oil was obtained. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.91 (b, 1H), 6.90-7.53 (m, 13
H), 5.35 (s, 1H), 1.49 (s, 18H)

(2) 1.00 g (2.25 mmol) of phenyl N- [2- (3,5-di-t-butyl-4-hydroxystyryl) phenyl] carbamate and 2- (aminomethyl) pyridine. A solution of 27 g (2.50 mmol) of xylene (5 ml) was stirred at 80-100 ° C for 3 hours. After evaporating the solvent, the residue was purified by silica gel column chromatography to give N- [2- (3,5-di-t-butyl-4].
0.54 g (71%) of crystals of -hydroxystyryl) phenyl] -N '-(2-pyridylmethyl) urea were obtained.
mp207-210 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 8.37 (d, J = 4 Hz, 1 H), 7.59 (d
d, J = 8, 2Hz, 1H), 7.51 (d, J = 7Hz, 1H), 7.43-7.50
(m, 1H), 7.31 (s, 2H), 7.16-7.28 (m, 3H), 7.17 (d, J =
16Hz, 1H), 7.02-7.07 (m, 1H), 6.99 (d, J = 16Hz, 1H),
6.68-6.91 (m, 1H), 5.79-5.87 (m, 1H), 5.32 (s, 1H),
4.51 (d, J = 5Hz, 2H), 1.45 (s, 18H) IR (cm ^-1 ) 3350, 3270, 2960, 1640, 1560, 1475, 144
0, 1235, 1010, 755, 740

Example 102 N- [2- (3,5-di-t-butyl-4-hydroxystyryl) phenyl] -N'-cycloheptylurea

[Chemical 120] The title compound was obtained by the same reaction procedure using cycloheptylamine in place of 2- (aminomethyl) pyridine in Example 101. mp. 203-206 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.61 (d, J = 8 Hz, 1 H), 7.38 (d,
J = 8Hz, 1H), 7.33 (s, 2H), 7.18-7.28 (m, 2H), 7.06
(d, J = 16Hz, 1H), 7.00 (d, J = 16Hz, 1H), 6.05 (s, 1
H), 5.33 (s, 1H), 4.48-4.55 (m, 1H), 4.04-4.16 (m, 1
H), 1.88-2.00 (m, 2H), 1.48-1.62 (m, 4H), 1.47 (s, 18
H), 1.22-1.37 (m, 2H) IR (cm ^-1 ) 3630, 3310, 2950, 1630, 1560, 1440, 123
5,960,745

Example 103 N- [2- (3,5-di-t-butyl-4-hydroxystyryl) phenyl] -N'-adamantyl urea

[Chemical 121] The title compound was obtained by the same reaction procedure using 1-adamantanamine in place of 2- (aminomethyl) pyridine of Example 101. mp 205 to 211 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.66 (dd, J = 7, 2 Hz, 1 H), 7.34
(s, 2H), 7.29-7.36 (m, 1H), 7.15-7.29 (m, 2H), 7.06
(d, J = 16Hz, 1H), 7.00 (d, J = 16Hz, 1H), 5.90 (s, 1
H), 5.33 (s, 1H), 4.34 (s, 1H), 1.82-2.06 (m, 9H), 1.
52-1.67 (m, 6H), 1.47 (s, 18H) IR (cm ^-1 ) 3630, 3330, 2900, 1640, 1560, 1525, 123
5, 740,

Example 104 N- [2- (3,5-di-t-butyl-4-hydroxystyryl) phenyl] -N ', N'-dibenzylurea

[Chemical formula 122] The title compound was obtained by the same reaction procedure using N, N-dibenzylamine instead of 2- (aminomethyl) pyridine of Example 101. mp175-178 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.79 (dd, J = 8, 1 Hz, 1H), 7.36
(dd, J = 8, 1Hz, 1H), 7.02-7.30 (m, 13H), 7.02-7.08
(m, 1H), 6.78 (d, J = 16Hz, 1H), 6.65 (d, J = 16Hz, 1
H), 5.31 (s, 1H), 4.60 (s, 4H), 1.47 (s, 18H) IR (cm ^-1 ) 3420, 3390, 2940, 1660, 1580, 1520, 145
0, 1435, 1230, 960, 755

Example 105 N- [2- (3,5-di-t-butyl-4-hydroxystyryl) phenyl] -N'-methyl-N'-heptylurea

[Chemical 123] The title compound was obtained by the same reaction procedure using N-methylheptylamine in place of 2- (aminomethyl) pyridine of Example 101. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.81 (d, J = 8Hz, 1H), 7.44 (d,
J = 8Hz, 1H), 7.32 (s, 2H), 7.22-7.27 (m, 1H), 7.05-7.
10 (m, 1H), 7.00 (d, J = 16Hz, 1H), 6.93 (d, J = 16Hz, 1
H), 6.36 (s, 1H), 5.32 (s, 1H), 3.34 (d, J = 8Hz, 2H),
3.02 (s, 3H), 1.54-1.65 (m, 2H), 1.47 (s, 18H), 1.16-
1.32 (m, 8H), 0.84 (t, J = 7Hz, 3H) IR (cm ^-1 ) 3640, 3450, 3300, 2960, 2930, 1640, 158
0,1520,1485,1440,1240,1155,960,750

Example 106 N- [2- (3,5-di-t-butyl-4-hydroxystyryl) phenyl] -N'-benzyl-N '-(2-
Pyridylmethyl) urea

[Chemical formula 124] The title compound was obtained by the same reaction procedure using 2- (benzylaminomethyl) pyridine instead of 2- (aminomethyl) pyridine of Example 101. ¹ H-NMR (δ ppm, CDCl ₃ ) 9.74 (b, 1H), 8.14 (d, J = 4Hz,
1H), 7.87 (d, J = 8Hz, 1H), 7.47-7.57 (m, 1H), 7.18-7.
34 (m, 9H), 6.88-7.11 (m, 4H), 5.26 (s, 1H), 4.65 (s,
2H), 4.49 (s, 2H), 1.40 (s, 18H) IR (cm ^-1 ) 3390, 2950, 1660, 1580, 1525, 1455, 123
0,960,755,735,700

Example 107 N- [2- (3,5-di-t-butyl-4-hydroxystyryl) phenyl] -N '-(3,9-dimethyl-3,
9-diazabicyclo [3.3.1] -7-nonyl) urea

[Chemical 125] The title compound was obtained by the same reaction procedure using 7-amino-3,9-dimethyl-3,9-diazabicyclo [3.3.1] nonane instead of 2- (aminomethyl) pyridine of Example 101. It was mp188-191 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 8.78 (d, J = 10 Hz, 1 H), 7.64 (d
d, J = 7, 2Hz, 1H), 7.30-7.35 (m, 3H), 7.13-7.27 (m, 2
H), 7.13 (d, J = 2Hz, 1H), 7.02 (d, J = 2Hz, 1H), 5.93
(s, 1H), 5.35 (s, 1H), 4.22-4.33 (m, 1H), 2.66-2.72
(m, 2H), 2.41 (s, 3H), 2.22-2.40 (m, 6H), 1.48 (s, 3
H), 1.47 (s, 18H), 1.28-1.38 (m, 2H) IR (cm ^-1 ) 3410, 2940, 1630, 1600, 1510, 1440, 139
0, 1265, 1185, 965, 760

Example 108 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -4,6-difluorophenyl] -N'-
(1-benzyl-4-piperidyl) urea

[Chemical formula 126] (1) 4- (2-amino-3,5-difluorophenethyl) -2,6-di-t-butylphenol 1.37 g
(3.8 mmol) and 0.50 g of diisopropylamine (4.
To a solution of 9 mmol) in methylene chloride (20 ml) was added dropwise 0.66 g (4.2 mmol) of phenyl chloroformate under ice cooling, and the mixture was stirred for 3 hours while gradually returning to room temperature. To this, 0.19 g (1.9 mmol) of diisopropylamine was added, 0.30 g (1.9 mmol) of phenyl chloroformate was added dropwise under ice cooling, and the mixture was stirred for 3 hours while gradually returning to room temperature. The reaction solution was washed with water, saturated brine, dried (MgSO ₄ ), concentrated, and the residue was purified by silica gel column chromatography to give N- [2- (3,5-di-t-butyl-4-hydroxy]. 1.82 g (99%) of phenethyl) -4,6-difluorophenyl] carbamate phenyl oil was obtained. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.04-7.42 (m, 5H), 6.67-6.85
(m, 4H), 5.16 (s, 1H), 4.94 (s, 1H), 2.76-3.02 (m, 4
H), 1.37 (s, 18H)

(2) 1.82 g (3.8 mm) of phenyl N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -4,6-difluorophenyl] carbamate
ol) and 4-amino-1-benzylpiperidine 0.72 g
Toluene (10 ml) solution of (3.8 mmol) 100-1
The mixture was stirred at 20 ° C for 2 hours. After distilling off the solvent, the residue was purified by silica gel column chromatography to obtain N- [2-
Amorphous solid of (3,5-di-t-butyl-4-hydroxyphenethyl) -4,6-difluorophenyl] -N '-(1-benzyl-4-piperidyl) urea 1.39
g (64%) was obtained. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.20-7.30 (m, 5H), 6.65-6.80
(m, 4H), 5.12 (s, 1H), 4.79 (bs, 1H), 4.14 (bd, J = 8H
z, 1H), 3.54-3.66 (m, 1H), 3.44 (s, 2H), 2.84 (d, J = 7
Hz, 2H), 2.70-2.79 (m, 4H), 1.98-2.10 (m, 2H), 1.80-
1.92 (m, 2H), 1.30-1.40 (m, 20H) IR (cm ^-1 ) 3638, 3316, 2952, 1639, 1562, 1494, 143
6, 1235, 1122

Example 109 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -4-fluorophenyl] -N '-(1-
Benzyl-4-piperidyl) urea

[Chemical 127] 4- (2-Amino-5-fluorophenethyl) -instead of 4- (2-amino-3,5-difluorophenethyl) -2,6-di-t-butylphenol of Example 108.
The title compound was obtained by the same reaction procedure using 2,6-di-t-butylphenol. mp108-109
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 7.21-7.31 (m, 5H), 7.16 (dd, J
= 9, 5Hz, 1H), 6.87-6.96 (m, 2H), 6.77 (s, 2H), 5.12
(s, 1H), 4.86 (s, 1H), 3.99 (d, J = 8Hz, 1H), 3.55-3.7
0 (m, 1H), 3.44 (s, 1H), 2.70-2.85 (m, 6H), 2.05 (t, J
= 11Hz, 2H), 1.85 (d, J = 10Hz, 2H), 1.38 (s, 18H), 1.2
5-1.35 (m, 2H) IR (cm ^-1 ) 3636, 3280, 1634, 1561, 1495, 1435, 123
4,1213,1120,739,699

Example 110 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -5-fluorophenyl] -N '-(1-
Benzyl-4-piperidyl) urea

[Chemical 128] 4- (2-amino-4-fluorophenethyl) -instead of 4- (2-amino-3,5-difluorophenethyl) -2,6-di-t-butylphenol of Example 108
The title compound was obtained by the same reaction procedure using 2,6-di-t-butylphenol. mp118-119
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 7.20-7.32 (m, 5H), 7.13-7.20
(m, 2H), 6.84 (dt, J = 3, 8Hz, 1H), 6.78 (s, 2H), 5.13
(s, 1H), 5.01 (s, 1H), 4.02 (d, J = 8Hz, 1H), 3.46-3.6
3 (m, 1H), 3.46 (s, 2H), 2.77 (bs, 6H), 2.06 (t, J = 11H
z, 2H), 1.86 (d, J = 11Hz, 2H), 1.38 (s, 18H), 1.30-1.
40 (m, 2H) IR (cm ^-1 ) 3630, 3350, 1640, 1602, 1563, 1434, 123
3,738,700

Example 111 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -4-methoxyphenyl] -N '-(1-
Benzyl-4-piperidyl) urea

[Chemical formula 129] 4- (2-Amino-5-methoxyphenethyl) -instead of 4- (2-amino-3,5-difluorophenethyl) -2,6-di-t-butylphenol of Example 108.
The title compound was obtained by the same reaction procedure using 2,6-di-t-butylphenol. mp174-175
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 7.20-7.30 (m, 5H), 7.00-7.07
(m, 1H), 6.78 (s, 2H), 6.70-6.75 (m, 2H), 5.09 (s, 1
H), 4.91 (s, 1H), 4.05 (d, J = 8Hz, 1H), 3.79 (s, 3H),
3.60-3.65 (m, 1H), 3.43 (s, 2H), 2.70-2.80 (m, 6H),
2.05 (t, J = 11Hz, 2H), 1.85 (d, J = 11Hz, 2H), 1.38 (s,
18H), 1.20-1.40 (m, 2H) IR (cm ^-1 ) 3630, 3312, 1634, 1561, 1501, 1436, 128
2,1231,1055,880,750,710

Example 112 N- [4- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-phenylurea

[Chemical 130] In place of 4- (2-aminophenethyl) -2,6-di-t-butylphenol of Example 1, 4- (4-aminophenethyl) -2,6-di-t-butylphenol was replaced with hexyloxybenzoic acid. The title compound was obtained by the same reaction procedure using benzoic acid instead. mp206 ~
207 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.22-7.38 (m, 6H), 7.18 (d, J =
9Hz, 2H), 7.08-7.14 (m, 1H), 6.55 (bs, 1H), 6.47 (b
s, 1H), 2.77-2.92 (m, 4H), 1.43 (s, 18H) IR (cm ^-1 ) 3640, 3330, 2960, 1655, 1605, 1565, 144
0, 1320, 1240, 760, 695

Example 113 N- [4- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-hepeptylurea

[Chemical 131] In place of 4- (2-aminophenethyl) -2,6-di-t-butylphenol of Example 1, 4- (4-aminophenethyl) -2,6-di-t-butylphenol was replaced with hexyloxybenzoic acid. The title compound was obtained by the same reaction procedure using n-octanoic acid instead. mp1
51-152 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.13-7.21 (m, 4H), 6.95 (s, 2
H), 6.22 (bs, 1H), 5.06 (s, 1H), 4.73 (bt, J = 5Hz, 1
H), 3.23 (dt, J = 5, 7Hz, 2H), 2.75-2.90 (m, 42H), 1.4
5-1.54 (m, 2H), 1.42 (s, 18H), 1.21-1.36 (m, 8H), 0.8
8 (t, J = 7Hz, 3H) IR (cm ^-1 ) 3630, 3120, 2960, 2930, 2860, 1645, 160
5, 1575, 1520, 1440, 1235

Example 114 1-Benzyl-4- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} piperazine

[Chemical 132] The title compound was obtained by the same reaction procedure using 1-benzylpiperazine instead of decylamine of Example 11. mp 70-72 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.49-7.51 (m, 1H), 7.09-7.33
(m, 8H), 6.78 (s, 2H), 5.61 (s, 1H), 5.06 (s, 1H), 3.
50 (s, 2H), 3.22 (t, J = 5Hz, 4H), 2.80 (s, 4H), 2.39
(t, J = 5Hz, 4H), 1.33 (s, 18H) IR (cm ^-1 ) 3636, 3310, 2952, 1635, 1516, 1435, 123
4,1001,754

Example 115 4-Benzyl-1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} piperidine

[Chemical 133] The title compound was obtained by the same reaction procedure using 4-benzylpiperidine instead of decylamine of Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.52 (d, J = 8Hz, 1H), 7.06-7.3
2 (m, 8H), 6.79 (s, 2H), 5.67 (s, 1H), 5.06 (s, 1H),
3.68-3.76 (m, 2H), 2.81 (s, 4H), 2.62-2.72 (m, 2H),
2.53 (t, J = 7Hz, 4H), 1.50-1.73 (m, 3H), 1.35 (s, 18
H), 1.10-1.23 (m, 2H) IR (cm ^-1 ) 3645, 3440, 3330, 2960, 2925, 1645, 152
5, 1455, 1440, 1250, 755, 705

Example 116 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -1,2,
3,4-tetrahydroquinoline

[Chemical 134] The title compound was obtained by the same reaction procedure using 1,2,3,4-tetrahydroquinoline instead of decylamine of Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.82 (d, J = 7Hz, 1H), 7.36 (d,
J = 7Hz, 1H), 7.13-7.21 (m, 2H), 7.16 (d, J = 7Hz, 1H),
6.99-7.09 (m, 3H), 6.89 (bs, 1H), 6.82 (s, 2H), 5.06
(s, 1H), 3.80 (t, J = 6Hz, 2H), 2.78 (t, J = 6Hz, 2H),
2.69 (s, 4H), 1.98 (m, 2H), 1.39 (s, 18H) IR (cm ^-1 ) 3630, 3434, 2946, 1671, 1524, 1492, 143
5, 1304, 1236, 753

Example 117 2- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -1,2,
3,4-tetrahydroisoquinoline

[Chemical 135] The title compound was obtained by the same reaction procedure using 1,2,3,4-tetrahydroisoquinoline instead of decylamine of Example 11. mp. 148-150 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.55 (d, J = 8Hz, 1H), 7.10-7.2
6 (m, 7H), 6.83 (s, 1H), 5.73 (bs, 1H), 5.10 (s, 1H),
4.52 (s, 2H), 3.44 (t, J = 6Hz, 2H), 2.86 (t, J = 6Hz, 2
H), 2.84 (s, 4H), 1.36 (s, 18H) IR (cm ^-1 ) 3628, 3312, 1630, 1515, 1459, 1437, 137
3,1231,747

Example 118 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -4-
(3,4-Methylenedioxybenzyl) piperazine

[Chemical 136] The title compound was obtained by the same reaction procedure using 1- (3,4-methylenedioxybenzyl) piperazine instead of decylamine in Example 11. mp149-15
1 ℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 7.50 (d, J = 7Hz, 1H), 7.18-7.2
3 (m, 2H), 7.11 (dd, J = 7, 7Hz, 1H), 6.83 (s, 1H), 6.7
0-6.76 (m, 2H), 5.95 (s, 2H), 5.61 (bs, 1H), 5.06 (s,
1H), 3.40 (s, 2H), 3.22 (t, J = 5Hz, 4H), 2.80 (s, 4
H), 2.36 (t, J = 5Hz, 4H), 1.34 (s, 18H) IR (cm ^-1 ) 3626, 3302, 2956, 1632, 1504, 1491, 143
8, 1247, 1040, 999, 759

Example 119 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} indoline

[Chemical 137] The title compound was obtained by the same reaction procedure using indoline in place of decylamine in Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.91 (d, J = 8Hz, 1H), 7.61 (d,
J = 8Hz, 1H), 7.10-7.30 (m, 2H), 6.91 (dd, J = 8, 8Hz, 2
H), 6.81 (d, J = 8Hz, 2H), 6.78 (s, 2H), 5.65 (bs, 1
H), 5.10 (s, 1H), 3.57 (t, J = 8Hz, 2H), 3.14 (t, J = 8H
z, 2H), 2.86 (s, 4H), 1.35 (s, 18H) IR (cm ^-1 ) 3622, 3272, 2952, 1654, 1594, 1507, 148
5, 1448, 1347, 1234, 753

Example 120 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -4-methylpiperazine

[Chemical 138] The title compound was obtained by the same reaction procedure using 1-methylpiperazine instead of decylamine of Example 11. mp134-137 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.47 (d, J = 8Hz, 1H), 7.17-7.2
6 (m, 2H), 7.12 (ddd, J = 7, 7, 2Hz, 1H), 6.79 (s, 2
H), 5.56 (s, 1H), 5.10 (s, 1H), 3.25 (t, J = 5Hz, 4H),
2.82 (s, 4H), 2.35 (t, J = 5Hz, 4H), 2.29 (s, 3H), 1.37
(s, 18H) IR (cm ^-1 ) 3632, 3440, 2940, 1636, 1511, 1437, 100
2,750

Example 121 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} perhydroazepine

[Chemical 139] The title compound was obtained by the same reaction procedure using hexamethyleneimine instead of decylamine in Example 11. mp 136-138 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.67 (dd, J = 7, 2 Hz, 1 H), 7, 1
7-7.24 (m, 2H), 7.08 (ddd, J = 7, 7, 2Hz, 1H), 6.82
(s, 2H), 5.78 (s, 1H), 5.08 (s, 1H), 3.26-3.34 (m, 4
H), 2.82 (bs, 1H), 1.66-1.74 (m, 4H), 1.52-1.59 (m, 4
H), 1.37 (s, 18H) IR (cm ^-1 ) 3460, 1660, 1587, 1525, 1453, 1436, 755

Example 122 4- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} morpholine

[Chemical 140] The title compound was obtained by the same reaction procedure using morpholine in place of decylamine in Example 11. mp1
86-189 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.47 (dd, J = 8, 2 Hz, 1H), 7.19
-7.27 (m, 2H), 7.14 (ddd, J = 7, 7, 2Hz, 1H), 6.78 (s,
2H), 5.52 (s, 1H), 5.09 (s, 1H), 3.64 (t, J = 5Hz, 4
H), 3.19 (t, J = 5Hz, 4H), 2.82 (s, 4H), 1.36 (s, 18H) IR (cm ^-1 ) 3644, 3420, 3290, 2956, 1631, 1525, 143
5,1262,1118,756

Example 123 3- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -3-azabicyclo [3.2.2] nonane

[Chemical 141] The title compound was obtained by the same reaction procedure using 3-azabicyclo [3.2.2] nonane instead of decylamine of Example 11. mp184-186 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.52 (d, J = 8 Hz, 1 H), 7.26-7.3
4 (m, 2H), 7.09 (dd, J = 7, 7Hz, 1H), 6.81 (s, 2H), 5.7
1 (s, 1H), 5.08 (s, 1H), 3.40 (d, J = 4Hz, 4H), 2.82
(s, 4H), 1.96-2.04 (m, 2H), 1.57-1.72 (m, 8H), 1.37
(s, 18H) IR (cm ^-1 ) 3630, 3430, 3334, 2930, 2860, 1627, 151
1,754

Example 124 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -4-phenylpiperazine

[Chemical 142] The title compound was obtained by the same reaction procedure using 1-phenylpiperazine instead of decylamine of Example 11. mp155-156 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.11-7.48 (m, 6H), 6.88-6.92
(m, 1H), 6.89 (d, J = 8Hz, 2H), 6.79 (s, 2H), 5.61 (t,
J = 5Hz, 4H), 3.12 (t, J = 5Hz, 4H), 2.83 (s, 4H), 1.37
(s, 18H) IR (cm ^-1 ) 3584, 3372, 2960, 1639, 1601, 1505, 143
5,1234,999,753

Example 125 8- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -1,4
-Dioxa-8-azaspiro [4.5] decane

[Chemical 143] The title compound was obtained by the same reaction procedure using 1,4-dioxa-8-azaspiro [4.5] decane instead of decylamine in Example 11. mp163-164
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 7.45 (d, J = 7Hz, 1H), 7.17-7.2
6 (m, 2H), 7.12 (dd, J = 7, 7Hz, 1H), 6.78 (s, 2H), 5.5
9 (bs, 1H), 5.09 (s, 1H), 3.96 (s, 4H), 3.30 (t, J = 6H
z, 4H), 2.82 (s, 4H), 1.65 (t, J = 6Hz, 4H), 1.36 (s, 1
8H) IR (cm ^-1 ) 3430, 3300, 2955, 1645, 1510, 1490, 145
5, 1440, 1250, 1120, 950, 750

Example 126 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -4-
(1-Pyrrolidinylcarbonylmethyl) piperazine

[Chemical 144] The title compound was obtained by the same reaction procedure using 1- (1-pyrrolidinylcarbonylmethyl) piperazine instead of decylamine of Example 11. mp212 ~ 21
4 ℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 7.47 (d, J = 8Hz, 1H), 7.16-7.2
5 (m, 2H), 7.11 (ddd, J = 7, 7, 1Hz, 1H), 6.78 (s, 2
H), 5.59 (s, 1H), 5.10 (s, 1H), 3.45-3.52 (m, 4H), 3.
28 (t, J = 5Hz, 4H), 3.11 (s, 2H), 2.81 (s, 4H), 2.50
(t, J = 5Hz, 4H), 1.80-2.00 (m, 4H), 1.36 (s, 18H) IR (cm ^-1 ) 3500, 3328, 2960, 1626, 1521, 1457, 143
7,750

Example 127 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -4-piperidinopiperidine

[Chemical 145] The title compound was obtained by the same reaction procedure using 4-piperidinopiperidine instead of decylamine of Example 11. mp 64-67 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.48 (d, J = 7 Hz, 1 H), 7.16-7.2
5 (m, 2H), 7.11 (ddd, J = 7, 7, 2Hz, 1H), 6.79 (s, 2
H), 5.62 (s, 1H), 5.09 (s, 1H), 3.73-3.81 (m, 2H), 2.
81 (s, 4H), 2.65-2.75 (m, 2H), 2.44-2.51 (m, 4H), 2.3
3-2.44 (m, 1H), 1.75-1.82 (m, 2H), 1.54-1.62 (m, 4
H), 1.39-1.50 (m, 4H), 1.37 (s, 18H) IR (cm ^-1 ) 3636, 3420, 2934, 1640, 1520, 1450, 125
0,750

Example 128 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -4-
(P-Toluenesulfonyl) piperazine

[Chemical 146] The title compound was obtained by the same reaction procedure using 1- (p-toluenesulfonyl) piperazine instead of decylamine of Example 11. mp195-197 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.61 (d, J = 8Hz, 2H), 7.29-7.3
6 (m, 3H), 7.19-7.24 (m, 3H), 6.73 (s, 2H), 5.41 (bs,
1H), 5.12 (s, 1H), 3.26 (t, J = 5Hz, 4H), 2.93 (t, J = 5H
z, 4H), 2.70-2.83 (m, 4H), 2.45 (s, 3H), 1.35 (s, 18
H) IR (cm ^-1 ) 3630, 3410, 2950, 1635, 1625, 1350, 117
0,730

Example 129 1-benzoyl-4- {N- [2- (3,5-di-t-
Butyl-4-hydroxyphenethyl) phenyl] carbamoyl} piperazine

[Chemical 147] The title compound was obtained by the same reaction procedure using 1-benzoylpiperazine instead of decylamine of Example 11. mp207-209 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.37-7.48 (m, 6H), 7.12-7.27
(m, 3H), 6.76 (s, 2H), 5.52 (bs, 1H), 5.08 (s, 1H),
3.12-3.85 (m, 8H), 2.82 (s, 4H), 1.33 (s, 18H) IR (cm ^-1 ) 3570, 3266, 2950, 1629, 1530, 1435, 126
0, 1007, 754

Example 130 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} decahydroquinoline

[Chemical 148] The title compound was obtained by the same reaction procedure using decahydroquinoline instead of decylamine in Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.57 (d, J = 8Hz, 1H), 7.12-7.2
1 (m, 2H), 7.07 (dd, J = 7, 7Hz, 1H), 6.86 (s, 2H), 5.8
8 (bs, 1H), 5.08 (s, 1H), 4.06 (m, 1H), 3.45 (m, 1H),
2.75-2.90 (m, 5H), 1.90 (m, 1H), 1.63-1.80 (m, 4H),
1.20-1.60 (m, 8H), 1.39 (m, 18H) IR (cm ^-1 ) 3430, 2924, 1632, 1510, 1434, 750

Example 131 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -4-pentanoylpiperazine

[Chemical 149] The title compound was obtained by the same reaction procedure using 1-pentanoylpiperazine instead of decylamine of Example 11. mp126-128 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.44 (d, J = 9 Hz, 1 H), 7.12-7.2
7 (m, 3H), 6.77 (s, 2H), 5.52 (bs, 1H), 5.12 (s, 1H),
3.56-3.63 (m, 2H), 3.40-3.46 (m, 2H), 3.27-3.34 (m, 2
H), 3.08-3.14 (m, 2H), 2.82 (s, 4H), 2.30 (t, J = 5Hz,
2H), 1.58-1.67 (m, 2H), 1.36 (s, 18H), 1.28-1.38 (m,
4H) IR (cm ^-1 ) 3300, 2952, 1636, 1530, 1435, 1240, 994,
755

Example 132 1- {N- [2- (3,5-di-t-butyl-4-hydroxystyryl) phenyl] carbamoyl} -4-methylpiperazine

[Chemical 150] The title compound was obtained by the same reaction procedure using 1-methylpiperazine instead of 2- (aminomethyl) pyridine of Example 101. mp 192-194 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.65 (d, J = 8 Hz, 1 H), 7.46-7.5
0 (m, 1H), 7.33 (s, 2H), 7.20-7.26 (m, 1H), 7.11 (dd,
J = 9, 1Hz, 1H), 6.99 (d, J = 16Hz, 1H), 6.94 (d, J = 16H
z, 1H), 6.39 (bs, 1H), 5.34 (s, 1H), 3.51 (t, J = 5Hz,
4H), 2.43 (t, J = 5Hz, 4H), 2.32 (m, 3H), 1.47 (s, 18H) IR (cm ^-1 ) 3636, 3420, 3288, 2952, 1635, 1525, 148
5, 1439, 1236, 1149, 959, 765, 755

Example 133 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -4-nicotinoylpiperazine

[Chemical 151] The title compound was obtained by the same reaction procedure using 1-nicotinoylpiperazine instead of decylamine of Example 11. mp171-172 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 8.70 (dd, J = 5, 2 Hz, 1H), 8.66
(d, J = 1Hz, 1H), 7.75 (ddd, J = 8, 8, 2Hz, 1H), 7.36-
7.42 (m, 2H), 7.14-7.27 (m, 3H), 6.75 (s, 2H), 5.52
(s, 1H), 5.11 (s, 1H), 3.10-3.80 (m, 8H), 2.82 (s, 4
H), 1.33 (s, 18) IR (cm ^-1 ) 3636, 3420, 3288, 2952, 1635, 1525, 148
5, 1439, 1236, 1149, 959, 765, 755

Example 134 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(1-cyclohexyl-4-piperidyl) urea

[Chemical 152] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using cyclohexylpiperidine. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.15-7.25 (m, 4H), 6.79 (s, 2
H), 5.38 (bs, 2H), 5.12 (s, 1H), 4.55 (bs, 1H), 3.65-
3.75 (m, 1H), 2.90-2.98 (m, 2H), 2.75-2.90 (m, 4H),
2.35-2.45 (m, 3H), 1.85-2.00 (m, 4H), 1.78 (bs, 2H),
1.45-1.65 (m, 3H), 1.38 (s, 18H), 1.00-1.35 (m, 5H) IR (cm ^-1 ) 3638, 3262, 1658, 1643, 1560, 1542, 143
5,1233,754

Example 135 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(3-morpholinopropyl) urea

[Chemical 153] The title compound was obtained by the same reaction procedure using 4- (3-aminopropyl) morpholine instead of decylamine of Example 11. mp138-139 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.19-7.29 (m, 4H), 6.80 (s, 2)
H), 5.19 (bs, 1H), 5.12 (s, 1H), 5.04 (t, J = 5Hz, 1
H), 3.44 (bs, 4H), 3.25 (q, J = 6Hz, 2H), 2.77-2.87
(m, 4H), 2.25-2.35 (m, 6H), 1.60 (quint., J = 7Hz, 2
H), 1.38 (s, 18H) IR (cm ^-1 ) 3528, 3304, 1633, 1565, 1436, 1238, 111
6,872,752

Example 136 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(2-morpholinoethyl) urea

[Chemical 154] The title compound was obtained by the same reaction procedure using 4- (2-aminoethyl) morpholine instead of decylamine of Example 11. mp166-167 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.19-7.28 (m, 4H), 6.80 (s, 2
H), 5.19 (s, 1H), 5.14 (s, 1H), 4.91 (s, 1H), 3.56
(t, J = 6Hz, 4H), 3.24 (t, J = 6Hz, 2H), 2.75-2.89 (m, 4
H), 2.30-2.42 (m, 6H), 1.38 (s, 18H) IR (cm ^-1 ) 3566, 3326, 1643, 1574, 1436, 1300, 123
8, 1116, 755

Example 137 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[3- (2-methyl-
1-piperidyl) propyl] urea

[Chemical 155] The title compound was obtained by the same reaction procedure using 1- (3-aminopropyl) -2-methylpiperidine in place of decylamine of Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.14-7.30 (m, 4H), 6.81 (s, 2
H), 5.43 (bs, 1H), 5.36 (bs, 1H), 5.11 (s, 1H), 3.15-
3.30 (m, 2H), 2.70-2.87 (m, 6H), 2.20-2.30 (m, 2H),
2.01 (t, J = 10Hz, 1H), 1.40-1.65 (m, 5H), 1.38 (s, 18
H), 1.00-1.40 (m, 3H), 0.98 (d, J = 6Hz, 3H) IR (cm ^-1 ) 3638, 3294, 1643, 1543, 1436, 1234, 754

Example 138 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[2- (1-pyrrolidinyl) ethyl] urea

[Chemical 156] Using 1- (2-aminoethyl) pyrrolidine in place of decylamine in Example 11, the title compound was obtained by the same reaction procedure. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.37 (d, J = 7Hz, 1H), 7.11-7.2
1 (m, 3H), 6.82 (s, 2H), 5.55 (bs, 1H), 5.26 (s, 1H),
5.03 (s, 1H), 3.29 (t, J = 6Hz, 2H), 2.65-2.85 (m, 5
H), 2.59 (t, J = 6Hz, 2H), 2.53 (bs, 3H), 1.74 (bs, 4
H), 1.38 (s, 18H) IR (cm ^-1 ) 3638, 3350, 1686, 1546, 1436, 1234, 753

Example 139 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[1- (2-propyl) -4-piperidyl] urea

[Chemical 157] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using (2-propyl) piperidine. mp191-193 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.15-7.26 (m, 4H), 6.78 (s, 2
H), 5.11 (bs, 2H), 4.30 (bs, 1H), 3.59-3.72 (m, 1H),
2.73-2.90 (m, 7H), 2.25-2.37 (m, 2H), 1.87-1.98 (m, 2
H), 1.30-1.50 (m, 2H), 1.38 (s, 18H), 1.07 (d, J = 6H
z, 6H) IR (cm ^-1 ) 3358, 2948, 1641, 1561, 1435, 1235

Example 140 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[2- (4-fluorophenyl) -2-methylpropyl] urea

[Chemical 158] 4-Fluoro-in place of the decylamine of Example 11
The title compound was obtained by the same reaction procedure using β, β-dimethylphenethylamine. mp179-180
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 7.14-7.20 (m, 4H), 7.08 (t, J =
7Hz, 1H), 6.87-6.96 (m, 3H), 6.74 (s, 2H), 5.08 (s, 1
H), 5.00 (s, 1H), 3.95-4.05 (m, 1H), 3.30 (d, J = 6Hz,
2H), 2.70-2.80 (m, 4H), 1.36 (s, 18H), 1.24 (s, 6H) IR (cm ^-1 ) 3638, 3370, 1644, 1653, 1613, 1436, 123
1,1166,833,762

Example 141 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-{2- [4- (1-pyrrolidinyl) phenyl] -2-methyl Propyl} urea

[Chemical 159] Instead of decylamine of Example 11, 1- [4- (1-
The title compound was obtained by the same reaction procedure using amino-2-methyl-2-propyl) phenyl] pyrrolidine. mp195-196 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.02-7.18 (m, 6H), 6.77 (s, 2
H), 6.43 (d, J = 9Hz, 2H), 5.08 (s, 2H), 4.14 (t, J = 6H
z, 1H), 3.28 (t, J = 6Hz, 2H), 3.22-3.25 (m, 4H), 2.70
-2.78 (m, 4H), 1.97-2.01 (m, 4H), 1.37 (s, 18H), 1.23
(s, 6H) IR (cm ^-1 ) 3642, 3354, 1642, 1615, 1562, 1524, 136
9, 1234, 814, 750

Example 142 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(1-benzyl-3-
Piperidyl) urea

[Chemical 160] 3-amino-1-in place of decylamine in Example 11
The title compound was obtained by the same reaction procedure using benzylpiperidine. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.20-7.40 (m, 9H), 6.79 (s, 2
H), 5.12 (bs, 1H), 5.09 (s, 1H), 3.87-3.96 (m, 1H),
3.49 (bs, 1H), 3.37 (d, J = 13Hz, 1H), 3.28 (d, J = 13H
z, 1H), 2.70-2.90 (m, 4H), 2.40-2.50 (m, 2H), 1.30-
1.70 (m, 24H) IR (cm ^-1 ) 3632, 3338, 2948, 1639, 1542, 1435, 123
4,744,699

Example 143 N- [2- (3,5-di-t
-Butyl-4-hydroxyphenethyl) phenyl] -N '-[2- (2-fluorophenyl) -2-methylpropyl] urea

[Chemical 161] 2-Fluoro-in place of the decylamine of Example 11
The title compound was obtained by the same reaction procedure using β, β-dimethylphenethylamine. mp182-183
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 6.88-7.21 (m, 8H), 6.75 (s, 2
H), 5.07 (s, 1H), 5.02 (s, 1H), 4.02-4.09 (m, 1H), 3.
50 (d, J = 6Hz, 2H), 2.67-2.78 (m, 4H), 1.36 (s, 18H),
1.33 (s, 6H) IR (cm ^-1 ) 3650, 3330, 2960, 1640, 1575, 1445, 125
5,765

Example 144 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[2- (3-fluorophenyl) -2-methylpropyl] urea

[Chemical 162] Instead of the decylamine of Example 11, 3-fluoro-
The title compound was obtained by the same reaction procedure using β, β-dimethylphenethylamine. mp165-166
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 7.04-7.23 (m, 4H), 6.80-7.00
(m, 4H), 6.74 (s, 2H), 5.08 (s, 1H), 4.94 (s, 1H), 3.
98 (t, J = 6Hz, 1H), 3.32 (d, J = 6Hz, 2H), 2.68-2.79
(m, 4H), 1.36 (s, 18H), 1.25 (s, 6H) IR (cm ^-1 ) 3640, 3350, 2970, 1645, 1615, 1590, 156
0, 1440, 910, 765, 700

Example 145 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(1-benzyl-4-)
Piperidyl) -N'-ethylurea

[Chemical formula 163] The title compound was obtained by the same reaction procedure using 4-ethylamino-1-benzylpiperidine in place of decylamine of Example 11. mp149-151 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.72 (d, J = 8 Hz, 1 H), 7.15-7.3
3 (m, 7H), 7.07 (t, J = 7Hz, 1H), 6.83 (s, 2H), 5.91 (b
s, 1H), 5.07 (s, 1H), 4.16-4.38 (m, 1H), 3.48 (s, 2
H), 3.02 (q, J = 7Hz, 2H), 2.93 (d, J = 12Hz, 2H), 2.82
(bs, 4H), 2.03-2.10 (m, 2H), 1.60-1.75 (m, 4H), 1.37
(s, 18H), 1.16 (t, J = 7Hz, 3H) IR (cm ^-1 ) 3334, 2954, 1631, 1520, 1502, 1263, 120
2,743

Example 146 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(1-benzyl-4-)
Piperidyl) -N'-propylurea

[Chemical 164] 1-Benzyl-4 instead of decylamine of Example 11
The title compound was obtained by the same reaction procedure using -propylaminopiperidine. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.76 (d, J = 7Hz, 1H), 7.10-7.3
5 (m, 7H), 7.04 (td, J = 6, 1Hz, 1H), 6.87 (s, 2H), 6.0
7 (bs, 1H), 5.06 (s, 1H), 4.12-4.23 (m, 1H), 3.48 (s,
2H), 3.04 (bt, J = 8Hz, 2H), 2.94 (d, J = 12Hz, 2H), 2.8
1 (s, 4H), 2.00-2.10 (m, 2H), 1.50-1.75 (m, 6H), 1.39
(s, 18H), 0.86 (t, J = 7Hz, 3H) IR (cm ^-1 ) 3634, 3450, 2956, 1650, 1509, 1451, 123
4,742

Example 147 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(1-benzyl-4-)
Piperidyl) -N '-(2-propyl) urea

[Chemical 165] 1-Benzyl-4 instead of decylamine of Example 11
The title compound was obtained by the same reaction procedure using-[(2-propyl) amino] piperidine. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.65 (d, J = 8Hz, 1H), 7.10-7.3
0 (m, 7H), 7.04 (td, J = 7, 1Hz, 1H), 6.89 (s, 2H), 6.0
3 (bs, 1H), 5.05 (s, 1H), 3.70-3.90 (m, 2H), 3.47 (s,
2H), 2.75-2.98 (m, 6H), 1.90-2.05 (m, 4H), 1.55-1.70
(m, 2H), 1.39 (s, 18H), 1.31 (d, J = 7Hz, 6H) IR (cm ^-1 ) 3450, 2954, 1650, 1521, 1451, 1237, 744

Example 148 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[1- (2-fluorobenzyl) -4-piperidyl] urea

[Chemical 166] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using (2-fluorobenzyl) piperidine. mp136-13
7 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.14-7.34 (m, 6H), 6.95-7.10
(m, 2H), 6.77 (s, 2H), 5.10 (s, 1H), 4.99 (s, 1H), 4.
10 (d, J = 8Hz, 1H), 3.55-3.71 (m, 1H), 3.52 (s, 2H),
2.68-2.88 (m, 6H), 2.07-2.17 (m, 2H), 1.82-1.90 (m, 2
H), 1.37 (s, 18H), 1.24-1.35 (m, 2H) IR (cm ^-1 ) 3640, 3340, 2960, 1650, 1590, 1570, 149
5,1235,765

Example 149 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[1- (3-fluorobenzyl) -4-piperidyl] urea

[Chemical 167] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using (3-fluorobenzyl) piperidine. mp99-100
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 7.15-7.27 (m, 5H), 7.67-7.04
(m, 2H), 6.86-6.94 (m, 1H), 5.10 (s, 1H), 4.12 (d, J =
8Hz, 1H), 3.57-3.70 (m, 1H), 3.42 (s, 2H), 2.66-2.86
(m, 6H), 2.06 (t, J = 12Hz, 2H), 1.86 (d, J = 12Hz, 2
H), 1.38 (s, 18H), 1.24-1.35 (m, 2H) IR (cm ^-1 ) 3635, 3340, 2950, 1640, 1590, 1565, 149
0, 1440, 1235, 880, 750, 690

Example 150 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[1- (4-chlorobenzyl) -4-piperidyl] urea

[Chemical 168] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using (4-chlorobenzyl) piperidine. mp184-185
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 7.15-7.32 (m, 8H), 6.77 (s, 2
H), 5.10 (s, 1H), 4.98 (s, 1H), 4.09 (d, J = 8Hz, 1H),
3.57-3.70 (m, 1H), 3.39 (s, 2H), 2.74-2.87 (m, 4H),
2.69 (d, J = 11Hz, 2H), 2.04 (t, J = 11Hz, 2H), 1.81-1.8
8 (m, 2H), 1.37 (s, 18H), 1.14-1.22 (m, 2H) IR (cm ^-1 ) 3645, 3360, 2940, 1640, 1590, 1555, 149
0, 1435, 1295, 1235, 1095, 750

Example 151 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[1- (3,4-difluorobenzyl) -4-piperidyl] urea

[Chemical 169] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using (3,4-difluorobenzyl) piperidine. mp155
~ 156 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 6.92-7.28 (m, 7H), 6.77 (s, 2
H), 5.10 (s, 1H), 4.97 (s, 1H), 4.08 (d, J = 8Hz, 1H),
3.58-3.72 (m, 1H), 3.37 (s, 2H), 2.74-2.87 (m, 4H),
2.05 (t, J = 11Hz, 2H), 1.82-1.90 (m, 2H), 1.38 (s, 18
H), 1.24-1.35 (m, 2H) IR (cm ^-1 ) 3650, 3370, 2965, 1645, 1570, 1525, 144
0, 1295, 1240, 885, 785, 765

Example 152 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[1- (4-fluorophenethyl) -4-piperidyl] urea

[Chemical 170] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using (4-fluorophenethyl) piperidine. mp117-1
19 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.10-7.20 (m, 6H), 6.94 (td, J
= 7, 2Hz, 2H), 6.78 (s, 2H), 5.11 (s, 1H), 5.04 (bs, 1
H), 4.13 (bd, J = 8Hz, 1H), 3.58-3.70 (m, 1H), 2.70-2.
90 (m, 8H), 2.45-2.55 (m, 2H), 2.08-2.12 (m, 2H), 1.8
5-1.95 (m, 2H), 1.30-1.40 (m, 2H), 1.38 (s, 18H) IR (cm ^-1 ) 3630, 3314, 2948, 1634, 1565, 1510, 122
8,748

Example 153 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[1- (3,5-difluorobenzyl) -4-piperidyl] urea

[Chemical 171] 4-amino-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using (3,5-difluorobenzyl) piperidine. mp119
~ 120 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.17-7.28 (m, 4H), 6.82 (d, J =
6Hz, 2H), 6.77 (s, 2H), 6.62-6.69 (m, 1H), 5.11 (s, 1
H), 4.97 (s, 1H), 4.09 (d, J = 8Hz, 1H), 3.58-3.71 (m,
1H), 3.40 (s, 2H), 2.66-2.88 (m, 6H), 2.07 (t, J = 11H
z, 2H), 1.83-1.92 (m, 2H), 1.38 (s, 18H), 1.25-1.36
(m, 2H) IR (cm ^-1 ) 3640, 3350, 2960, 1635, 1605, 1505, 144
0, 1325, 1235, 1120, 995, 855

Example 154 2- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -cis-
Decahydroquinoline

[Chemical 172] The title compound was obtained by the same reaction procedure using cis-decahydroquinoline instead of decylamine in Example 11. mp132-133 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.64 (d, J = 8 Hz, 1 H), 7.23-7.3
0 (m, 2H), 7.11 (t, J = 7Hz, 1H), 6.93 (s, 2H), 5.94
(s, 1H), 5.14 (s, 1H), 4.09-4.20 (m, 1H), 3.48-3.59
(m, 1H), 2.83-2.94 (m, 5H), 1.50-2.00 (m, 9H), 1.45
(s, 18H), 1.24-1.42 (m, 4H) IR (cm ^-1 ) 3640, 3320, 2925, 2860, 1630, 1515, 143
5, 1360, 1275, 1235, 1160, 755

Example 155 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -3-fluorophenyl] -N '-(1-
Benzyl-4-piperidyl) urea

[Chemical 173] 4- (2-Amino-6-fluorophenethyl) -instead of 4- (2-amino-3,5-difluorophenethyl) -2,6-di-t-butylphenol of Example 108.
The title compound was obtained by the same reaction procedure using 2,6-di-t-butylphenol. mp103-105
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 7.20-7.35 (m, 5H), 7.13 (t, J =
8Hz, 1H), 7.03 (d, J = 8Hz, 1H), 6.93 (t, J = 9Hz, 1H),
6.75 (s, 2H), 5.13 (s, 1H), 4.60 (bs, 1H), 3.95 (bd, J
= 8Hz, 1H), 3.54-3.66 (m, 1H), 3.44 (s, 2H), 2.70-2.9
0 (m, 6H), 2.00-2.10 (m, 2H), 1.80-1.90 (m, 2H), 1.30
-1.40 (m, 2H), 1.36 (s, 18H) IR (cm ^-1 ) 3630, 3300, 2948, 1632, 1565, 1452, 123
5,699

Example 156 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-[1- (4-fluorobenzyl) -4-piperidyl] -N' -Methylurea

[Chemical 174] The title compound was obtained by the same reaction procedure using 1- (4-fluorobenzyl) -4- (methylamino) piperidine instead of decylamine of Example 11. mp1
77-178 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.63 (d, J = 8 Hz, 1 H), 7.17-7.2
8 (m, 4H), 7.08-7.13 (m, 1H), 6.95-7.03 (m, 2H), 6.78
(s, 2H), 5.61 (s, 1H), 5.08 (s, 1H), 4.17-4.28 (m, 1
H), 3.43 (s, 2H), 2.90 (d, J = 12Hz, 2H), 2.81 (s, 4
H), 2.50 (s, 3H), 1.98-2.07 (m, 2H), 1.54-1.68 (m, 4
H), 1.35 (s, 18H) IR (cm ^-1 ) 3630, 3330, 2970, 1635, 1520, 1440, 133
0, 1230, 1050, 760

Example 157 N- [2- (3,5-di-t-butyl-4-hydroxystyryl) phenyl] -N '-[1- (4-fluorobenzyl) -4-piperidyl] -N' -Methylurea

[Chemical 175] The title compound was obtained by the same reaction procedure using 1- (4-fluorobenzyl) -4- (methylamino) piperidine instead of 2- (aminomethyl) pyridine of Example 101. mp174-175 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.79 (d, J = 8 Hz, 1 H), 7.45 (d
d, J = 7, 1Hz, 1H), 7.31 (s, 2H), 7.20-7.30 (m, 3H),
7.05-7.13 (m, 1H), 6.93-7.03 (m, 4H), 6.38 (s, 1H),
5.32 (s, 1H), 4.14-4.26 (m, 1H), 3.46 (s, 2H), 2.85-
2.96 (m, 5H), 1.99-2.10 (m, 2H), 1.63-1.82 (m, 4H),
1.46 (s, 18H) IR (cm ^-1 ) 3640, 3450, 2960, 1640, 1510, 1225, 116
0, 1045, 965, 760

Example 158 N- [2- (3,5-di-t-butyl-4-hydroxystyryl) phenyl] -N '-(1-benzyl-4-piperidyl) -N'-methylurea

[Chemical 176] The title compound was obtained by the same reaction procedure using 1-benzyl-4- (methylamino) piperidine instead of 2- (aminomethyl) pyridine of Example 101. mp
163-164 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.78 (d, J = 7 Hz, 1 H), 7.45 (d
d, J = 8, 1Hz, 1H), 7.20-7.35 (m, 8H), 7.04-7.12 (m, 1
H), 7.00 (d, J = 16Hz, 1H), 6.93 (d, J = 16Hz, 1H), 6.38
(s, 1H), 5.32 (s, 1H), 4.14-4.27 (m, 1H), 3.48 (s, 2
H), 2.94 (d, J = 12Hz, 2H), 2.90 (s, 3H), 2.00-2.11
(m, 2H), 1.60-1.84 (m, 4H), 1.46 (s, 18H) IR (cm ^-1 ) 3625, 3440, 3260, 2960, 1635, 1530, 148
5, 1240, 1150, 1045, 960, 755, 745, 700

Example 159 2- {N- [2- (3,5-di-t-butyl-4-hydroxystyryl) phenyl] carbamoyl} -cis-decahydroquinoline

[Chemical 177] The title compound was obtained by the same reaction procedure using cis-decahydroquinoline in place of 2- (aminomethyl) pyridine of Example 101. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.71 (d, J = 8Hz, 1H), 7.46 (d,
J = 6Hz, 1H), 7.33 (s, 2H), 7.20-7.28 (m, 1H), 7.05-7.
11 (m, 1H), 7.00 (d, J = 16Hz, 1H), 6.93 (d, J = 16Hz, 1
H), 6.41 (s, 1H), 5.32 (s, 1H), 3.85-4.07 (m, 2H), 1.
68-1.97 (m, 5H), 1.47-1.64 (m, 5H), 1.47 (s, 18H), 1.
18-1.43 (m, 3H) IR (cm ^-1 ) 3640, 3450, 3300, 2930, 2870, 1645, 152
5, 1445, 1240, 1160, 965, 755

Example 160 N- [4- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(1-benzyl-4-)
Piperidyl) urea

[Chemical 178] 4- (2-aminophenethyl) -2,6-of Example 11
4- (4-aminophenethyl) -2,6-di-t-butylphenol instead of di-t-butylphenol,
The title compound was obtained by the same reaction procedure using 4-amino-1-benzylpiperidine instead of decylamine. mp195-197 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.22-7.34 (m, 5H), 7.15 (s, 4)
H), 6.92 (s, 2H), 6.10 (s, 1H), 5.06 (s, 1H), 4.56
(d, J = 8Hz, 1H), 3.66-3.78 (m, 1H), 3.49 (s, 2H), 2.7
5-2.90 (m, 6H), 2.07-2.18 (m, 2H), 1.91-1.99 (m, 2
H), 1.36-1.47 (m, 2H), 1.43 (s, 18H) IR (cm ^-1 ) 3620, 3378, 2946, 1659, 1604, 1542, 151
5, 1435, 1324, 1234, 740

Example 161 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N'-allylurea

[Chemical 179] The title compound was obtained by the same reaction procedure using allylamine instead of decylamine of Example 11. mp
169-172 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.16-7.32 (m, 5H), 6.78 (s, 2)
H), 5.73-5.85 (m, 1H), 4.96-5.14 (m, 3H), 4.20-4.26
(m, 1H), 3.73-3.80 (m, 2H), 2.76-2.90 (m, 4H), 1.37
(s, 18H) IR (cm ^-1 ) 3632, 3334, 2956, 1653, 1587, 1570, 156
1, 1436, 1235, 924, 769

Example 162 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(4-nitrophenethyl) urea

[Chemical 180] The title compound was obtained by the same reaction procedure using 4-nitrophenethylamine instead of decylamine of Example 11. mp134-136 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 8.08 (d, J = 8Hz, 1H), 7.10-7.2
9 (m, 6H), 6.75 (s, 2H), 5.12 (s, 1H), 5.05 (s, 1H),
4.28 (t, J = 6Hz, 1H), 3.39 (td, J = 7, 6Hz, 2H), 2.73-
2.90 (m, 6H), 1.35 (s, 18H) IR (cm ^-1 ) 3630, 3314, 2954, 1639, 1561, 1519, 143
6, 1347, 753

Example 163 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -6-methoxyphenyl] -N '-(1-
Benzyl-4-piperidyl) urea

[Chemical 181] 4- (2-Amino-3-methoxyphenethyl) -instead of 4- (2-amino-3,5-difluorophenethyl) -2,6-di-t-butylphenol of Example 108.
The title compound was obtained by the same reaction procedure using 2,6-di-t-butylphenol. mp184-185
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 7.20-7.30 (m, 6H), 6.88 (d, J =
8Hz, 1H), 6.80 (s, 2H), 6.77 (d, J = 8Hz, 1H), 5.07
(s, 1H), 4.88 (s, 1H), 4.09 (d, J = 8Hz, 1H), 3.76 (s,
3H), 3.60-3.70 (m, 1H), 3.43 (s, 2H), 2.86-2.90 (m, 2
H), 2.70-2.77 (m, 4H), 2.05 (t, J = 11Hz, 2H), 1.86
(d, J = 10Hz, 2H), 1.38 (s, 18H), 1.25 (q, J = 10Hz, 2H) IR (cm ^-1 ) 3638, 3308, 1653, 1589, 1563, 1556, 146
8, 1454, 1435, 1260, 1232, 738

Example 164 N- [2- (3,5-di-t
-Butyl-4-hydroxyphenethyl) phenyl] -N '-[endo-9- (4-fluorobenzyl) -3
-Oxa-9-azabicyclo [3.3.1] non-7-yl] urea

[Chemical 182] Instead of decylamine in Example 11, endo-7-amino-9- (4-fluorobenzyl) -3-oxa-9-
The title compound was obtained by the same reaction procedure using azabicyclo [3.3.1] nonane. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.18-7.29 (m, 6H), 7.06 (d, J =
11Hz, 1H), 6.99 (d, J = 9Hz, 1H), 6.96 (d, J = 9Hz, 1
H), 6.83 (s, 2H), 5.22 (s, 1H), 5.09 (s, 1H), 4.37 (d
d, J = 17, 7Hz, 1H), 3.73 (d, J = 15Hz, 2H), 3.71 (s, 2
H), 3.39 (d, J = 11Hz, 2H), 2.84-2.87 (m, 2H), 2.76-2.
79 (m, 2H), 2.52 (s, 2H), 2.30-2.37 (m, 2H), 1.39 (s,
18H), 1.31-1.40 (m, 2H) IR (cm ^-1 ) 3636, 3324, 1652, 1525, 1511, 1506, 143
6,1223,787,759

Example 165 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -4,6-difluorophenyl] -N'-
(1-benzyl-4-piperidyl) -N'-methylurea

[Chemical 183] The title compound was obtained by the same reaction procedure using 1-benzyl-4- (methylamino) piperidine in place of 4-amino-1-benzylpiperidine of Example 108. mp187-191 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.20-7.40 (m, 5H), 6.70-6.80
(m, 4H), 5.09 (s, 1H), 4.91 (bs, 1H), 4.10-4.23 (m, 1
H), 3.47 (s, 2H), 2.90-3.00 (m, 2H), 2.80-2.90 (m, 4
H), 2.58 (s, 3H), 2.00-2.10 (m, 2H), 1.60-1.80 (m, 4
H), 1.36 (s, 18H) IR (cm ^-1 ) 3616, 3312, 1638, 1510, 1436, 1323, 1118

Example 166 2- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -4,6-difluorophenyl] carbamoyl} -cis-decahydroquinoline

[Chemical 184] The title compound was obtained by the same reaction procedure using cis-decahydroquinoline in place of 4-amino-1-benzylpiperidine of Example 108. mp83-85 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 6.83 (s, 2H), 6.70-6.80 (m, 2
H), 5.26 (bs, 1H), 5.09 (s, 1H), 4.05 (bs, 1H), 3.49
(bs, 2H), 2.70-2.90 (m, 5H), 1.84-1.94 (m, 1H), 1.65
-1.80 (m, 4H), 1.20-1.60 (m, 8H), 1.39 (s, 18H) IR (cm ^-1 ) 3588, 3316, 2924, 1713, 1638, 1511, 143
5,1120

Example 167 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -4,6-difluorophenyl] -N'-
(1-Benzyl-4-piperidyl) urea monohydrochloride

[Chemical 185] N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -4,6-difluorophenyl] -N'-
1.15 g of (1-benzyl-4-piperidyl) urea was suspended in 20 ml of ethanol and heated to 50 ° C. to dissolve.
To this was added 0.5 ml of 4N hydrochloric acid-ethyl acetate solution (anhydrous), and the solution was concentrated to 5 ml. This was cooled to 0 to 5 ° C. and allowed to stand for 4 hours, then the resulting crystals were filtered and dried to obtain 1.00 g (81%) of the title compound. mp17
0-175 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 12.09 (bs, 1H), 7.55 (d, J = 6H
z, 2H), 7.30-7.40 (m, 3H), 6.84 (s, 2H), 6.72 (d, J = 8
Hz, 1H), 6.65 (td, J = 8, 2Hz, 1H), 5.10 (s, 1H), 4.12
(d, J = 7Hz, 1H), 3.75-3.86 (m, 1H), 3.35-3.40 (m, 2
H), 2.65-2.85 (m, 6H), 2.10-2.25 (m, 4H), 1.39 (s, 18
H) IR (cm ^-1 ) 3430, 3300, 2952, 1680, 1554, 1436, 123
6,1122

Example 168 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -6-methylphenyl] -N '-(1-benzyl-4-piperidyl) urea

[Chemical 186] 4- (2-Amino-3-methylphenethyl) -instead of 4- (2-amino-3,5-difluorophenethyl) -2,6-di-t-butylphenol of Example 108.
The title compound was obtained by the same reaction procedure using 2,6-di-t-butylphenol. mp185-186
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 7.04-7.34 (m, 8H), 6.78 (s, 2
H), 5.08 (s, 1H), 4.83 (s, 1H), 3.90 (d, J = 8Hz, 1H),
3.57-3.72 (m, 1H), 3.42 (s, 2H), 2.62-2.90 (m, 6H),
2.19 (s, 3H), 2.03 (dd, J = 12, 11Hz, 2H), 1.83 (d, J = 1
1Hz, 2H), 1.38 (s, 18H), 1.16-1.32 (m, 2H) IR (cm ^-1 ) 3638, 3324, 2950, 1639, 1555, 1436, 123
3,769,734,698

Example 169 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -4,6-difluorophenyl] -N'-
(1-benzyl-4-piperidyl) urea 1 methanesulfonic acid

[Chemical 187] N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -4,6-difluorophenyl] -N'-
0.50 g of (1-benzyl-4-piperidyl) urea was suspended in 10 ml of ethanol and heated to 50 ° C. to dissolve. To this was added 56 μl of methanesulfonic acid and the mixture was concentrated, and ethyl acetate (1 ml) -diisopropyl ether (3 ml) was added to this.
The mixed solvent of was added and dissolved. This was cooled to 0 to 5 ° C. and allowed to stand overnight, then the resulting crystals were filtered and dried to obtain 0.51 g (87%) of the title compound. mp252-
254 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 10.23 (bs, 1 H), 7.30-7.45 (m,
5H), 6.80-6.92 (m, 3H), 6.57-6.68 (m, 1H), 5.10 (s, 1
H), 4.30 (bs, 1H), 4.12 (bs, 1H), 3.74-3.88 (m, 1H),
3.40-3.50 (m, 2H), 3.20-3.32 (m, 1H), 2.60-2.80 (m, 9
H), 1.90-2.15 (m, 4H), 1.39 (s, 18H) IR (cm ^-1 ) 3262, 2954, 1657, 1562, 1438, 1220, 116
3,1119,1041

Example 170 (S) -N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(α-methoxycarbonyl) benzylurea

[Chemical 188] The title compound was obtained by the same reaction procedure using (S) -α-phenylglycine methyl ester instead of decylamine of Example 11. mp145-150 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.170-7.34 (m, 9H), 6.76 (s, 2
H), 5.51 (d, J = 8Hz, 1H), 5.23 (d, J = 7Hz, 1H), 5.13
(s, 1H), 5.09 (s, 1H), 3.68 (s, 3H), 2.74-2.88 (m, 4
H), 1.35 (s, 18H) IR (cm ^-1 ) 3644, 3345, 2944, 1752, 1644, 1546, 143
6,1211

Example 171 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(2,4-dimethyl-
1,8-Naphthyridin-7-yl) urea

[Chemical 189] 7-amino-2 instead of decylamine of Example 11
The title compound was obtained by the same reaction procedure using 4-dimethyl-1,8-naphthyridine. mp235-23
7 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 8.22 (d, J = 9Hz, 1H), 7.86-7.9
6 (m, 1H), 7.10-7.30 (m, 3H), 7.02 (s, 1H), 6.80 (s, 2
H), 4.93 (s, 1H), 3.15-3.27 (m, 2H), 2.90-3.01 (m, 2
H), 2.62 (s, 3H), 2.56 (bs, 3H), 1.23 (s, 18H) IR (cm ^-1 ) 3636, 2952, 1687, 1615, 1599, 1560, 152
7,1403,1307,751

Example 172 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(bicyclo [3.3.
0] -2-octyl) urea

[Chemical 190] The title compound was obtained by the same reaction procedure using 1-aminobicyclo [3.3.0] octane instead of decylamine in Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.14-7.29 (m, 4H), 6.80 (s, 2
H), 5.11 (s, 1H), 5.060 (s, 1H), 4.15 (d, J = 8Hz, 1
H), 3.62-3.72 (m, 1H), 2.75-2.88 (m, 4H), 2.34-2.45
(m, 1H), 1.87-2.01 (m, 2H), 1.72-1.83 (m, 1H), 1.43-
1.63 (m, 4H), 1.38 (s, 18H), 1.07-1.31 (m, 3H) IR (cm ^-1 ) 3634, 2948, 2864, 1637, 1563, 1434, 123
1,760

Example 173 (S) -N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(α-benzyloxycarbonyl) benzylurea

[Chemical 191] The title compound was obtained by the same reaction procedure using (S) -α-phenylglycine benzyl ester instead of decylamine of Example 11. mp 132-134 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.13-7.33 (m, 14H), 6.75 (s, 2
H), 5.57 (d, J = 8Hz, 1H), 5.27 (d, J = 7Hz, 1H), 5.15
(s, 1H), 5.11 (s, 2H), 5.08 (s, 1H), 2.74-2.87 (m, 4
H), 1.34 (s, 18H) IR (cm ^-1 ) 3642, 3344, 2944, 1749, 1643, 1587, 155
3, 1168, 749, 697

Example 174 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -2-ethylpiperidine

[Chemical 192] The title compound was obtained by the same reaction procedure using 2-ethylpiperidine instead of decylamine of Example 11. mp137-138 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.52-7.58 (m, 1H), 7.16-7.23
(m, 2H), 7.04-7.10 (m, 1H), 6.84 (s, 2H), 5.78 (s, 1
H), 5.08 (s, 1H), 3.91-4.00 (m, 1H), 3.51-3.61 (m, 1
H), 2.76-2.87 (m, 5H), 1.45-1.80 (m, 8H), 1.38 (s, 18
H), 0.86 (t, J = 7Hz, 3H) IR (cm ^-1 ) 3450, 3300, 2960, 1640, 1510, 1490, 145
5, 1250, 885, 765

Example 175 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -3-methylpiperidine

[Chemical formula 193] The title compound was obtained by the same reaction procedure using 3-methylpiperidine instead of decylamine of Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.49-7.54 (m, 1H), 7.16-7.24
(m, 2H), 7.07-7.13 (m, 1H), 6.83 (s, 2H), 5.72 (s, 1
H), 5.09 (s, 1H), 3.80-3.87 (m, 1H), 3.46-3.54 (m, 1
H), 2.82 (s, 4H), 2.70-2.82 (m, 2H), 2.35-2.44 (m, 1
H), 1.76-1.84 (m, 1H), 1.40-1.67 (m, 3H), 1.38 (s, 18
H), 1.02-1.14 (m, 1H), 0.88 (t, J = 6Hz, 3H) IR (cm ^-1 ) 3645, 3430, 3310, 2960, 2870, 1640, 152
5, 1435, 1250, 1150, 750

Example 176 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -2-
[2- (benzyloxy) ethyl] piperidine

[Chemical 194] The title compound was obtained by the same reaction procedure using 2- [2- (benzyloxy) ethyl] methylpiperidine instead of decylamine of Example 11. mp113-1
14 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.53 (d, J = 8Hz, 1H), 7.02-7.2
2 (m, 8H), 6.89 (s, 2H), 6.74 (bs, 1H), 5.05 (s, 1H),
4.35-4.44 (m, 2H), 4.23-4.32 (m, 1H), 4.03-4.15 (m, 1
H), 3.44-3.59 (m, 2H), 2.63-2.77 (m, 5H), 2.00-2.12
(m, 1H), 1.44-1.82 (m, 7H), 1.37 (s, 18H) IR (cm ^-1 ) 3600, 3420, 2940, 2870, 1665, 1595, 153
5, 1450, 1400, 1380, 1270, 1240, 1100, 765, 745

Example 177 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -3,3
-Dimethylpiperidine

[Chemical 195] The title compound was obtained by the same reaction procedure using 3,3-dimethylpiperidine in place of decylamine of Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.54 (dd, J = 8, 1Hz, 1H), 7.16
-7.23 (m, 2H), 7.04-7.12 (m, 1H), 6.84 (s, 2H), 5.77
(s, 1H), 5.08 (s, 1H), 3.19 (t, J = 6Hz, 2H), 3.05 (s,
2H), 2.82 (s, 4H), 1.52-1.61 (m, 2H), 1.33-1.43 (m, 2
H), 1.39 (s, 18H), 0.92 (s, 6H) IR (cm ^-1 ) 3645, 3430, 3320, 2960, 2870, 1640, 152
0, 1440, 1250, 1165, 755

Example 178 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(4-fluorobenzyl) -N'-methylurea

[Chemical 196] 4-Fluoro-N instead of decylamine of Example 11
The title compound was obtained by the same reaction procedure using -methylphenethylamine. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.63 (d, J = 8Hz, 1H), 7.17-7.2
6 (m, 4H), 7.11 (dd, J = 8, 7Hz, 1H), 6.97 (dd, J = 9, 9H
z, 2H), 6.75 (s, 2H), 5.66 (s, 1H), 5.06 (s, 1H), 4.4
5 (s, 2H), 2.73-2.84 (m, 4H), 2.64 (s, 3H), 1.33 (s, 1
8H) IR (cm ^-1 ) 3645, 3430, 3320, 2965, 1650, 1515, 144
0, 1380, 1300, 1230, 1160, 760

Example 179 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] -N '-(3,4-methylenedioxybenzyl) -N'-methylurea

[Chemical 197] The title compound was obtained by the same reaction procedure using 5- (methylaminomethyl) -1,3-dioxaindane instead of decylamine of Example 11. mp152-1
53 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.65 (d, J = 8 Hz, 1 H), 7.16-7.2
5 (m, 2H), 7.10 (dd, J = 7, 7Hz, 1H), 6.76 (s, 2H), 6.6
5-6.73 (m, 2H), 5.92 (s, 2H), 5.69 (s, 1H), 5.06 (s, 1
H), 4.39 (s, 2H), 2.72-2.83 (m, 4H), 2.66 (s, 3H), 1.
34 (s, 18H)

Example 180 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -3-
(Benzyloxy) piperidine

[Chemical 198] The title compound was obtained by the same reaction procedure using 3-benzyloxypiperidine instead of decylamine of Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.44 (d, J = 8Hz, 1H), 7.22-7.3
4 (m, 5H), 7.18 (dd, J = 7, 7Hz, 1H), 7.08 (dd, J = 7, 7H
z, 1H), 6.80 (s, 2H), 5.82 (s, 1H), 5.06 (s, 1H), 4.4
7-4.56 (m, 2H), 3.68-3.76 (m, 1H), 3.43-3.51 (m, 1
H), 3.09-3.22 (m, 3H), 2.71-2.83 (m, 4H), 1.61-1.96
(m, 3H), 1.38-1.50 (m, 1H), 1.36 (s, 18H) IR (cm ^-1 ) 3625, 3280, 2960, 1635, 1525, 1490, 144
5, 1245, 1045, 940, 765

Example 181 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -2-
(2-hydroxyethyl) piperidine

[Chemical formula 199] The title compound was obtained by the same reaction procedure using 2- (2-hydroxyethyl) piperidine in place of decylamine of Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.46 (d, J = 8Hz, 1H), 7.16-7.2
4 (m, 2H), 7.11 (ddd, J = 8, 7, 1Hz, 1H), 6.84 (s, 2
H), 6.00-6.21 (br, 1H), 5.08 (s, 1H), 4.51-4.62 (m, 1
H), 3.57-3.66 (m, 1H), 3.48-3.18 (m, 3H), 2.69-2.88
(m, 5H), 1.40-2.03 (m, 8H), 1.38 (s, 18H) IR (cm ^-1 ) 3640, 3320, 2950, 2870, 1640, 1530, 144
0, 1275, 1230, 1175, 755

Example 182 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -2-
(2-acetoxyethyl) piperidine

[Chemical 200] The title compound was obtained by the same reaction procedure using 2- (2-acetoxyethyl) piperidine in place of decylamine of Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.49 (d, J = 8Hz, 1H), 7.17-7.2
3 (m, 2H), 7.09 (d, J = 7Hz, 1H), 6.84 (s, 2H), 5.84
(s, 1H), 5.08 (s, 1H), 4.33-4.43 (m, 1H), 4.00-4.16
(m, 2H), 3.41-3.51 (m, 1H), 2.76-2.90 (m, 5H), 2.00-
2.12 (m, 1H), 1.97 (s, 3H), 1.74-1.85 (m, 1H), 1.38-
1.72 (m, 6H), 1.38 (s, 18H) IR (cm ^-1 ) 3640, 3425, 2960, 2870, 1740, 1640, 152
0, 1435, 1370, 1235, 750

Example 183 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -5-chlorophenyl] -N '-(1-benzyl-4-piperidyl) urea

[Chemical 201] 4- (2-amino-4-chlorophenethyl) -instead of 4- (2-amino-3,5-difluorophenethyl) -2,6-di-t-butylphenol of Example 108
The title compound was obtained by the same reaction procedure using 2,6-di-t-butylphenol. mp155-156
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 7.41 (s, 1H), 7.22-7.31 (m, 5
H), 7.08 (s, 2H), 6.77 (s, 2H), 5.22 (s, 1H), 5.12
(s, 1H), 4.20 (d, J = 8Hz, 1H), 3.45-3.65 (m, 1H), 3.4
5 (s, 2H), 2.75 (s, 4H), 2.73-2.77 (m, 2H), 2.04 (t, J
= 11Hz, 2H), 1.85 (d, J = 11Hz, 2H), 1.38 (s, 18H), 1.2
2-1.42 (m, 2H) IR (cm ^-1 ) 3645, 3370, 1633, 1545, 1438, 1234, 699

Example 184 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -5-chlorophenyl] -N '-[2-
(2-Fluorophenyl) -2-methylpropyl]-
N'-methylurea

[Chemical 202] 2-Fluoro-in place of the decylamine of Example 11
The title compound was obtained by the same reaction procedure using β, β-dimethylphenethylamine. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.53 (d, J = 8Hz, 1H), 7.17-7.2
8 (m, 4H), 7.05-7.14 (m, 2H), 6.94-7.03 (m, 1H), 6.73
(s, 2H), 5.49 (s, 1H), 5.01 (s, 1H), 3.70 (s, 2H), 2.
73-2.83 (m, 4H), 2.21 (s, 3H), 1.37 (s, 6H), 1.29 (s,
18H) IR (cm ^-1 ) 3640, 3430, 2965, 1660, 1510, 1490, 144
0,1210,760

Example 185 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -5-chlorophenyl] -N'-methyl-
N '-[1- (3,4-methylenedioxyphenyl) cyclopentyl] methylurea

[Chemical 203] Instead of decylamine of Example 11, 5- [1- (N-
The title compound was obtained by the same reaction procedure using methylaminomethyl) cyclopentyl] -1,3-dioxaindane. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.45 (d,
J = 7Hz, 1H), 7.16-7.24 (m, 2H), 7.06-7.13 (m, 1H), 6.
78 (s, 1H), 6.72 (s, 4H), 5.92 (s, 2H), 5.32 (s, 1H),
5.03 (s, 1H), 3.42 (s, 2H), 2.73-2.82 (s, 4H), 2.02
(s, 3H), 2.58-2.98 (m, 8H), 1.30 (s, 18H) IR (cm ^-1 ) 3640, 3430, 2960, 1660, 1510, 1490, 143
5, 1235, 1450, 760

Example 186 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -5-chlorophenyl] -N '-(α-methylbenzyl) urea

[Chemical 204] The title compound was obtained by the same reaction procedure using α-methylbenzylamine instead of decylamine of Example 11. mp167-168 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.12-7.33 (m, 9H), 6.77 (s, 2)
H), 5.15 (s, 1H), 5.09 (s, 1H), 4.96 (dq, J = 7.7Hz, 1
H), 4.53 (d, J = 7Hz, 1H), 2.70-2.82 (m, 4H), 1.40 (d, J
= 7Hz, 3H), 1.37 (s, 18H) IR (cm ^-1 ) 3625, 3320, 3275, 2960, 1630, 1565, 143
5, 1235, 745, 700

Example 187 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -5-chlorophenyl] -N '-[2-
(3,4-dichlorophenyl) -2-methylpropyl]
-N'-methylurea

[Chemical 205] N-methyl-3 instead of decylamine of Example 11
The title compound was obtained by the same reaction procedure using 4-dichloro-β, β-dimethylphenethylamine. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.48 (d, J = 8Hz, 1H), 7.43 (d,
J = 2Hz, 1H), 7.37 (d, J = 10Hz, 1H), 7.17-7.27 (m, 3
H), 7.09-7.15 (m, 1H), 6.71 (s, 2H), 5.38 (s, 1H), 5.
08 (s, 1H), 3.48 (s, 2H), 2.72-2.84 (m, 4H), 2.13 (s,
3H), 1.36 (s, 6H), 1.29 (s, 18H) IR (cm ^-1 ) 3640, 3430, 3330, 2970, 1660, 1515, 148
0, 1450, 1440, 1310, 1250, 1030, 880, 760

Example 188 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -5-chlorophenyl] -N '-[4-
(4-Fluorobenzyl) -3-morpholinyl] methylurea

[Chemical 206] The title compound was obtained by the same reaction procedure using 3-methylamino-4- (4-fluorobenzyl) morpholine instead of decylamine in Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.19-7.37 (m, 4H), 6.80-6.89
(m, 4H), 6.76 (s, 2H), 5.11 (s, 1H), 5.05 (s, 1H), 4.
96 (bs, 1H), 3.89 (d, J = 13Hz, 1H), 3.74 (dd, J = 12.3H
z, 1H), 3.64 (d, J = 12Hz, 1H), 3.31-3.42 (m, 4H), 3.0
3 (d, J = 13Hz, 1H), 2.70-2.88 (m, 4H), 2.48-2.56 (m, 1
H), 2.45 (d, J = 12Hz, 1H), 2.10 (dt, J = 11.3Hz, 1H),
1.37 (s, 18H)

Example 189 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -5-chlorophenyl] -N '-[2-
(3,4-Dichlorophenyl) -2-propyl] -N '
-Methylurea

[Chemical formula 207] The title compound was obtained by the same reaction procedure using 3,4-dichloro-N, α, α-trimethylbenzylamine instead of decylamine in Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.36-7.42 (m, 2H), 7.24-7.29
(m, 1H), 7.09-7.17 (m, 3H), 7.02-7.07 (m, 1H), 6.79
(s, 2H), 5.52 (s, 1H), 5.09 (s, 1H), 2.81 (s, 3H), 2.
61-2.78 (m, 4H), 1.63 (s, 6H), 1.38 (s, 18H) IR (cm ^-1 ) 3640, 3290, 2960, 2875, 1640, 1520, 148
5, 1440, 1340, 1245, 1140, 1030, 755

Example 190 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -5-chlorophenyl] -N '-[2-
(N-benzyl-N-ethylamino) ethyl] urea

[Chemical 208] N-benzyl-N instead of decylamine of Example 11
The title compound was obtained by the same reaction procedure using -ethylethylenediamine. mp132-133 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.16-7.36 (m, 7H), 6.92-6.98
(m, 2H), 6.79 (s, 2H), 5.12 (bs, 1H), 5.09 (s, 1H),
5.00-5.05 (m, 1H), 3.43 (s, 2H), 3.21 (td, J = 6, 5Hz,
2H), 2.74-2.90 (m, 4H), 2.46 (t, J = 6Hz, 2H), 2.37
(q, J = 7Hz, 2H), 1.38 (s, 18H), 0.87 (t, J = 7Hz, 3H) IR (cm ^-1 ) 3650, 3340, 3280, 2960, 2810, 1640, 158
5, 1560, 1440, 1235, 1150, 865, 745, 705

Example 191 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) phenyl] carbamoyl} -3-ethoxycarbonylpiperidine

[Chemical 209] The title compound was obtained by the same reaction procedure using 3-ethoxycarbonylpiperidine instead of decylamine of Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.53 (d, J = 8Hz, 1H), 7.15-7.2
2 (m, 2H), 7.04-7.09 (m, 1H), 6.84 (s, 2H), 6.30 (s, 1
H), 5.07 (s, 1H), 4.06-4.15 (m, 2H), 3.74-3.81 (m, 1
H), 3.30-3.42 (m, 2H), 3.10-3.17 (m, 1H), 2.78-2.92
(m, 4H), 2.52-2.59 (m, 1H), 1.83-2.00 (m, 2H), 1.46-
1.66 (m, 2H), 1.38 (s, 18H), 1.22 (t, J = 7Hz, 3H) IR (cm ^-1 ) 3425, 2945, 2870, 1725, 1650, 1595, 153
0, 1450, 1375, 1300, 1210, 1030, 885, 760

Example 192 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -5-chlorophenyl] -N '-(1-phenylcyclopentyl) -N'-methylurea

[Chemical 210] N-methyl-1-in place of decylamine of Example 11
The title compound was obtained by the same reaction procedure using phenylcyclopentylamine. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.47 (d, J = 8Hz, 1H), 7.33 (d
d, J = 8, 1Hz, 1H), 7.08-7.18 (m, 3H), 6.93-7.02 (m, 3
H), 6.78 (s, 2H), 5.75 (s, 1H), 5.07 (s, 1H), 3.15
(s, 3H), 2.57 (t, J = 8Hz, 2H), 2.23-2.39 (m, 4H), 2.2
0 (t, J = 8Hz, 2H), 1.64-1.85 (m, 4H), 1.42 (s, 18H) IR (cm ^-1 ) 3630, 3410, 2950, 1640, 1520, 1440, 134
5,1230,755,700

Example 193 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -5-chlorophenyl] -N '-(1-benzyl-4-hydroxy-4-piperidyl) methyl urea

[Chemical 211] The title compound was obtained by the same reaction procedure using 4-aminomethyl-1-benzyl-4-hydroxypiperidine in place of decylamine in Example 11. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.15-7.35 (m, 9H), 6.76 (s, 2
H), 5.12 (s, 1H), 5.08 (bs, 1H), 4.56 (t, J = 5Hz, 1
H), 3.51 (s, 2H), 3.37 (bs, 1H), 3.14 (d, J = 5Hz, 2
H), 2.70-2.85 (m, 4H), 2.50-2.60 (m, 2H), 2.30-2.40
(m, 2H), 1.45-1.60 (m, 4H), 1.36 (s, 18H) IR (cm ^-1 ) 3350, 2952, 1639, 1550, 1435, 1234, 741,
699

Example 194 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -4,6-difluorophenyl] -N'-
Cyclohexyl-N'-methylurea

[Chemical 212] The title compound was obtained by the same reaction procedure using N-methylcyclohexylamine in place of 4-amino-1-benzylpiperidine of Example 108. ¹ H-NMR (δ ppm, CDCl ₃ ) 6.70-6.80 (m, 2H), 6.79 (s, 2
H), 5.09 (s, 1H), 4.98 (bs, 1H), 4.00-4.10 (m, 1H),
2.75-2.90 (m, 4H), 2.60 (s, 3H), 1.60-1.80 (m, 4H),
1.20-1.50 (m, 24H) IR (cm ^-1 ) 3630, 3420, 2930, 1639, 1499, 1435, 131
7, 1237, 1119

Example 195 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -4,6-difluorophenyl] -N'-
[2- (3,4-dichlorophenyl) -2-methylpropyl] urea

[Chemical 213] The title compound was obtained by the same reaction procedure using 3,4-dichloro-β, β-dimethylphenethylamine in place of 4-amino-1-benzylpiperidine of Example 108. mp159-160 ° C ¹ H-NMR (δ ppm, CDCl ₃ ) 7.05-7.30 (m, 3H), 6.65-6.78
(m, 4H), 5.08-5.11 (m, 1H), 4.27 (bs, 1H), 3.72 (bt,
J = 6Hz, 1H), 3.28-3.31 (m, 2H), 2.65-2.80 (m, 4H), 1.
30-1.40 (m, 18H), 1.20-1.30 (m, 6H) IR (cm ^-1 ) 3640, 3310, 2958, 1638, 1566, 1436, 123
5,1118

Example 196 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -4,6-difluorophenyl] -N'-
(1-adamantyl) urea

[Chemical 214] The title compound was obtained by the same reaction procedure using 1-adamantanamine in place of 4-amino-1-benzylpiperidine of Example 108. mp218-220 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 6.81 (s, 2H), 6.70-6.80 (m, 2
H), 5.12 (s, 1H), 4.60 (bs, 1H), 3.93 (bs, 1H), 2.88
(t, J = 7Hz, 2H), 2.78 (t, J = 7Hz, 2H), 2.03 (bs, 3H),
1.91 (d, J = 3Hz, 6H), 1.64 (bs, 6H), 1.40 (s, 18H) IR (cm ^-1 ) 3642, 3375, 2910, 1650, 1562, 1495, 143
6, 1235, 1120

Example 197 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -4,6-difluorophenyl] -N'-
[2- (3,4-dichlorophenyl) -2-methylpropyl] -N'-methylurea

[Chemical 215] The title compound was obtained by the same reaction procedure using N-methyl-3,4-dichloro-β, β-dimethylphenethylamine in place of 4-amino-1-benzylpiperidine of Example 108. mp145-147 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.15-7.40 (m, 3H), 6.65-6.80
(m, 4H), 5.04-5.06 (m, 1H), 4.70-4.73 (m, 1H), 3.46-
3.49 (m, 2H), 2.75-2.85 (m, 4H), 2.20-2.24 (m, 3H),
1.30-1.34 (m, 24H) IR (cm ^-1 ) 3572, 3420, 2954, 1665, 1505, 1434, 1120

Example 198 (R) -N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -4,6-difluorophenyl]
-N '-(α-ethoxycarbonylbenzyl) urea

[Chemical 216] The title compound was obtained by the same reaction procedure using (R) -α-phenylglycine ethyl ester in place of 4-amino-1-benzylpiperidine of Example 108.
mp 162-164 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.26-7.32 (m, 5H), 6.73-6.80
(m, 4H), 5.45 (d, J = 7Hz, 1H), 5.22 (bd, J = 7Hz, 1H),
5.12 (s, 1H), 4.68 (bs, 1H), 4.08-4.20 (m, 2H), 2.72-
2.89 (m, 4H), 1.37 (s, 18H), 1.18 (t, J = 7Hz, 3H) IR (cm ^-1 ) 3640, 3350, 2956, 1737, 1641, 1561, 143
8,1122

Example 199 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -4,6-difluorophenyl] -N'-
[2- (3,4-dichlorophenyl) -2-propyl]
urea

[Chemical 217] The title compound was obtained by the same reaction procedure using 3,4-dichloro-α, α-dimethylbenzylamine instead of 4-amino-1-benzylpiperidine of Example 108. mp224-226 ° C. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.42 (d, J = 2 Hz, 1 H), 7.31 (d,
J = 9Hz, 1H), 7.18 (dd, J = 9, 2Hz, 1H), 6.75-6.80 (m, 4
H), 5.13 (s, 1H), 4.62 (bs, 1H), 4.53 (bs, 1H), 2.56
(t, J = 7Hz, 2H), 2.77 (t, J = 7Hz, 2H), 1.57 (s, 6H),
1.40 (s, 18H) IR (cm ^-1 ) 3634, 3354, 2954, 1649, 1562, 1435, 127
7, 1238, 1122

Example 200 1- {N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -4,6-difluorophenyl] carbamoyl} -4-benzylpiperidine

[Chemical 218] The title compound was obtained by the same reaction procedure using 4-benzylpiperidine in place of 4-amino-1-benzylpiperidine of Example 108. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.25-7.31 (m, 2H), 7.20 (t, J =
7Hz, 1H), 7.12 (d, J = 7Hz, 2H), 6.71-6.80 (m, 2H), 6.
75 (s, 2H), 5.09 (s, 1H), 4.96 (s, 1H), 3.73 (bd, J = 13
Hz, 2H), 2.78-2.85 (m, 4H), 2.67 (t, J = 12Hz, 2H), 2.
53 (d, J = 7Hz, 2H), 1.58-1.71 (m, 3H), 1.36 (s, 18H),
1.12-1.22 (m, 2H) IR (cm ^-1 ) 3636, 3418, 3026, 1627, 1499, 1435, 1235,
1120, 789, 748, 700

Example 201 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -4,6-difluorophenyl] -N'-
[1- (4-dimethylaminophenyl) cyclopentyl] methylurea

[Chemical 219] The title compound was obtained by the same reaction procedure using 4-[(1-aminomethyl) -1-cyclopentyl] -N, N-dimethylaniline in place of 4-amino-1-benzylpiperidine of Example 108. . mp165-166
℃ ¹ H-NMR (δ ppm, CDCl ₃ ) 6.92 (d, J = 9Hz, 2H), 6.75 (s,
2H), 6.68-6.76 (m, 2H), 6.54 (d, J = 9Hz, 2H), 5.08
(s, 1H), 4.59 (s, 1H), 3.82 (bs, 1H), 3.19 (d, J = 6H
z, 2H), 2.89 (s, 6H), 2.76 (t, J = 7Hz, 2H), 2.67 (t, J
= 7Hz, 2H), 1.67-1.90 (m, 8H), 1.37 (s, 18H) IR (cm ^-1 ) 3674, 3250, 1615, 1520, 1435, 1233, 1121

Example 202 N- [2- (3,5-di-t-butyl-4-hydroxyphenethyl) -4,6-difluorophenyl] -N'-
Heptyl-N'-methylurea

[Chemical 220] The title compound was obtained by the same reaction procedure using N-methylheptylamine in place of 4-amino-1-benzylpiperidine of Example 108. ¹ H-NMR (δ ppm, CDCl ₃ ) 6.70-6.80 (m, 2H), 6.77 (s, 2
H), 5.10 (s, 1H), 4.96 (s, 1H), 3.21 (t, J = 8Hz, 2H),
2.75-2.86 (m, 4H), 2.75 (s, 3H), 1.42-1.56 (m, 2H),
1.37 (s, 18H), 1.20-1.35 (m, 8H), 0.87 (t, J = 7Hz, 3H) IR (cm ^-1 ) 3640, 3300, 1638, 1503, 1435, 1236, 1120

Next, a production example of the compound represented by the general formula (II), which is the starting material used in each of the above-mentioned examples, is shown as a reference example. Reference Example 1 4- (2-aminophenethyl) -2,6-di-t-butylphenol (1) 2,6-di-t-butyl-4- (2-nitrostyryl) phenol

[Chemical 221] To a solution of 8.05 g (34.5 mmol) of 3,5-di-t-butyl-4-hydroxybenzaldehyde and 9.40 g (51.9 mmol) of 2-nitrophenylacetic acid in xylene (60 ml) was added 0.3 ml of piperidine, The mixture was heated under reflux for 26 hours while removing water produced as the reaction proceeded. After cooling overnight, hexane was added to crystallize to give 2,6-di-t.
-Butyl-4- (2-nitrostyryl) phenol 7.
67 g (62.9%) of crystals were obtained. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.94 (dd, J = 8,1Hz, 1H), 7.76
(d, J = 8Hz, 1H), 7.57 (dd, J = 8,8Hz, 1H), 7.44 (d, J = 1
6Hz, 1H), 7.33-7.37 (m, 3H), 7.07 (d, J = 16Hz, 1H),
5.38 (s, 1H), 1.48 (s, 18H)

(2) 4- (2-aminophenethyl)-
2,6-di-t-butylphenol

[Chemical 222] 2,6-di-t-butyl-4- (2-nitrostyryl)
Phenol 16.4 g (23.3 mmol) ethanol (1
(50 ml) A catalytic amount of 10% palladium carbon was added to the suspension, and catalytic reduction was carried out at 1 to 2.5 atm at room temperature for 8 hours and at 40 ° C for 3 hours. After filtering the catalyst, the solvent was distilled off to obtain 15.1 g (100%) of viscous oil of 4- (2-aminophenethyl) -2,6-di-t-butylphenol. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.02-7.07 (m, 2H), 6.94 (s, 2
H), 6.74-6.78 (m, 1H), 6.67 (d, J = 8Hz, 1H), 5.06 (s,
1H), 3.41 (bs, 2H), 2.73-2.87 (m, 4H), 1.41 (s, 18H)

Reference Example 2 (1) 2,6-Diisopropyl-4- (2-nitrostyryl) phenol

[Chemical formula 223] 0.05 ml of piperidine was added to a xylene (10 ml) solution of 0.95 g (4.6 mmol) of 3,5-diisopropyl-4-hydroxybenzaldehyde and 1.1 g (6.2 mmol) of 2-nitrophenylacetic acid, and the reaction mixture was formed. The mixture was heated under reflux for 8 hours while removing water. After evaporating the solvent, the residue was purified by silica gel column chromatography and recrystallized from hexane to give 2,6-diisopropyl-4- (2
Crystals of 1.3 g (87%) of -nitrostyryl) phenol were obtained. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.93-7.95 (m, 1H), 7.75-7.77
(m, 1H), 7.55-7.57 (m, 1H), 7.45 (d, J = 16Hz, 1H), 7.
34-7.38 (m, 1H), 7.24 (s, 2H), 7.07 (d, J = 16Hz, 1H),
4.95 (s, 1H), 3.12-3.22 (m, 2H), 1.32 (s, 6H), 1.30
(s, 6H)

(2) 4- (2-aminophenethyl)-
2,6-diisopropylphenol

[Chemical formula 224] 2,6-diisopropyl-4- (2-nitrostyryl)
Phenol 1.3g (4.0mmol) ethanol (20m
l) Add a catalytic amount of 10% palladium carbon to the suspension,
The catalytic reduction was carried out at room temperature at 1 to 2.5 atm for 7 hours. After filtering the catalyst, the solvent was distilled off and 4- (2-aminophenethyl)-
1.0 g (84%) of 2,6-diisopropylphenol was obtained as a viscous oil. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.02-7.06 (m, 2H), 6.83 (s, 2
H), 6.70-6.77 (m, 1H), 6.65 (d, J = 7Hz, 1H), 4.67 (s,
1H), 3.43 (bs, 2H), 3.08-3.18 (m, 2H), 2.73-2.87 (m,
4H), 1.24 (s, 6H), 1.22 (s, 6H)

Reference Example 3 4- (2-aminostyryl) -2,6-di-t-butylphenol

[Chemical formula 225] 2,6-di-t-butyl-4- (2-nitrostyryl)
Phenol 1.1 g (3.1 mmol) methanol (15 m
l) Water 4 ml, concentrated hydrochloric acid 0.2 ml, iron powder 1.7 g (30 m)
mol) was added and the mixture was heated under reflux for 5 hours. After filtration, ethyl acetate and water were added for extraction, followed by washing with water, drying (MgSO ₄ ) and concentrating. The residue was purified by silica gel column chromatography and recrystallized from hexane to give 4- (2-aminostyryl) -2, 0.70 g of 6-di-t-butylphenol (7
0%) crystals were obtained. ¹ H-NMR (δ ppm, CDCl ₃ ) 7.36-7.38 (m, 1H), 7.34 (s, 2
H), 7.06-7.10 (m, 1H), 6.91-7.10 (m, 2H), 6.78-6.82
(m, 1H), 6.70-6.72 (m, 1H), 5.29 (s, 1H), 3.79 (s, 2
H), 1.47 (s, 18H)

Pharmacological Tests For the compounds prepared according to the above examples, ACA
Tested for T inhibitory effect, antioxidant effect and cholesterol lowering effect. 1. ACAT inhibition method Enzyme preparation ACAT can be performed by the method of EE Largis (Journal o
f Lipid Research, 30, 681-690, 1989), and prepared from liver microsomal fractions of male rabbits.
Kazuichi NATORI and other methods (Japan. J. Pharmacol. 42
, Pp. 517-523, in accordance 1986) was calculated by measuring the production amount of labeled cholesterol ester from ^[1-14 C] oleoyl -CoA and endogenous cholesterol.

Results In Tables 1 and 2 below, the inhibitory rate (%) of the production of labeled cholesterol ester when the compound was added at 10 ⁻⁷ M was measured by AC.
Shown as an index of AT inhibitory action. The compounds are shown by the numbers in the examples. From Tables 1 and 2, the compound A of the present invention was superior to A
It is proved to have CAT inhibitory activity.

2. Antioxidation method Human LDL was added in the presence of copper sulfate (5 × 10 ⁻⁶ M), with a compound (10 ⁻⁵ M) or in the absence of a compound to give 5
Incubate for hours. After incubation,
Method of Simon JT Mao et al. (J. Med. Chem. 34, 298-30
2 page, 1991), the formation of LD by the formation of malondialdehyde (MDA), one of the products of lipid peroxides.
The peroxidation of L-group is evaluated. The activity of the compounds showed a percentage inhibition of MDA production relative to the control.

Results From the following Tables 1 and 2, the compounds of the present invention were treated with lipid peroxide (MD
It is shown to significantly reduce the production of A).

[0252]

[Table 1]

[0253]

[Table 2]

3. Cholesterol-lowering action method Sprague-Dawley male rats were given powdered material containing 1% cholesterol and 0.5% cholic acid in an amount of 15g per day for 3 days to produce rats with high cholesterol. did. On the fourth day, the compounds were suspended in 0.5% methylcellulose and orally administered by gavage in an amount of 30 mg / kg. Blood was collected before and 5 hours after the administration of the compound, and the amount of plasma cholesterol was measured by a commercially available measurement kit (cholesterol E
Test Wako Wako Pure Chemical Industries, Ltd.). Results Table 3 below shows that the compounds of the present invention significantly reduce blood cholesterol levels.

[0255]

[Table 3] Compound (Example No.) Cholesterol reduction rate (%) 35 48.4 83 44.6 92 79.9 105 45.9 108 71.8 130 71.5

Finally, formulation examples containing the compound of the present invention as an active ingredient are shown below. Formulation Example 1 Tablets were manufactured by a conventional method according to the following formulation. [Formulation] Tablet (1 tablet) Compound of Example (6) 50 mg Hydroxypropyl cellulose 2 mg Wheat starch 10 mg Lactose 100 mg Magnesium stearate 3 mg Talc 3 mg

Formulation Example 2 A capsule was manufactured by a conventional method according to the following formulation. [Prescription] Capsule (1 tablet) 200 mg of the compound of Example (17) Starch 8mg Microcrystalline cellulose 23mg Talc 8 mg Magnesium stearate 5mg

Formulation Example 3 Granules were manufactured by a conventional method according to the following formulation. [Prescription] Granule (1 packet) Compound of Example (41) 1 mg Lactose 99mg Corn starch 50mg Crystalline cellulose 50mg Hydroxypropyl cellulose 10mg Ethanol 9mg

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁷ Identification code FI A61K 31/435 A61K 31/435 31/44 31/44 31/445 31/445 31/455 31/455 31/47 31/47 31/495 31/495 31/535 31/535 31/54 31/54 31/55 31/55 A61P 3/00 A61P 3/00 9/10 101 9/10 101 C07C 323/44 C07C 323/44 C07D 207 / 14 C07D 207/14 209/20 209/20 211/14 211/14 211/22 211/22 211/42 211/42 211/44 211/44 211/56 211/56 211/60 211/60 213 / 40 213/40 213/74 213/74 213/82 213/82 215/08 215/08 217/06 217/06 223/14 223/14 233/64 105 233/64 105 265/30 265/30 295 / 12 295/12 Z 295/20 295/20 A Z 295/22 295/22 A 307/52 307/52 317/58 317/58 333/00 333/00 401/06 401/06 451/02 451/02 453/02 453/02 471/04 114 471/04 114A 471/08 471/08 491/113 491/113 498/08 498/08 C12N 9/99 C12N 9 / 99 (72) Inventor Masaru Miura 5-3 Tsurugaoka, Oi-cho, Iruma-gun, Saitama Prefecture Pharmaceutical Research Institute, Nisshin Seifun Co., Ltd. (72) Masato Horigome 5-3 Tsurugaoka, Oi-cho, Iruma-gun, Saitama Prefecture No. 1 Nisshin Seifun Co., Ltd. Pharmaceutical Research Institute (72) Inventor Norio Oshida 5-3 Tsurugaoka, Oi-cho, Iruma-gun, Saitama Prefecture Nisshin Seifun Co., Ltd. Pharmaceutical Research Institute (72) Inventor Shigeru Hiramoto Saitama 5-3 Tsurugaoka, Oi-cho, Iruma-gun, Nisshin Seifun Co., Ltd. Pharmaceutical Research Institute (72) Koichi Katsuyama 5-3-1 Tsurugaoka, Oi-cho, Iruma-gun, Saitama Nisshin Seifun Co., Ltd. In the laboratory (72) Fumihisa Nakata 5-3 Tsurugaoka, Oi-cho, Iruma-gun, Saitama Prefecture Nisshin Seifun Co., Ltd. Pharmaceutical Research Institute (72) Nobusuke Kinoshita 5 Tsurugaoka, Oi-cho, Iruma-gun, Saitama Prefecture 3-3-1 Nisshin Seifun Co., Ltd. Pharmaceutical Research Laboratory (72) Inventor Yoko Tsukada 5-3-1 Tsurugaoka, Oi-cho, Iruma-gun, Saitama Nisshin Seisakusho Co., Ltd. pharmaceutical research laboratories (56) Reference Patent flat 2-188568 (JP, A) JP-T flat 6-510030 (JP, A) (58 ) investigated the field (Int.Cl. ^7, DB name) CA ( STN) REGISTRY (STN)

Claims (6)

(57) [Claims] 1. A compound represented by the general formula (I): [In the formula, R ₁ and R ₂ are the same or different and each represents a hydrogen atom, a halogen atom, a linear or branched (C ₁ -C ₆ ) alkyl group, a linear or branched (C ₁ -C _6). ) Represents an alkoxy group, R ₃ and R ₄ are the same or different, and are a hydrogen atom, a linear or branched (C ₁ -C ₁₂ ) alkyl group, a linear or branched (C ₂ -C ₂₀ ). Alkenyl group, (C ₁ -C ₆ ) alkoxy (C ₁ -C ₆ ) alkyl group, (C ₁ -C ₆ ) alkoxycarbonyl (C ₁ -C ₉ ) alkyl group, benzyloxycarbonyl (C ₁ -C ₆ ). An alkyl group (wherein the alkyl group, that is, the alkylene chain may be optionally substituted with a phenyl group), N, N-di (C ₁ -C ₆ ) alkylamino (C ₁ -C ₆ ) alkyl group, N-(C ₁ -C ₆₎ alkyl -N- benzylamino (C ₁
-C ₆₎ alkyl group, (C ₁ -C ₆₎ alkylthio (C ₁ -C ₆₎ alkyl group, oxo (C ₁ -C ₉₎ alkyl group, hydroxy (C ₁ -C ₆₎ alkyl group, dihydroxy (C ₁ -C ₆₎ alkyl, cycloalkyl (C ₃ ~C ₁₅₎ alkyl, cycloalkyl (C ₃ ~C ₈₎ alkyl (C ₁ -C ₆₎ alkyl group, dicyclohexyl (C ₃ ~C ₉₎ alkyl (C ₁ -C ₆₎ alkyl group, bicyclo (C ₆ -C ₉₎ alkyl group, a tricyclo (C ₉ -C ₁₂₎ alkyl group (cycloalkyl group described above, or cycloalkyl moieties, optionally (C ₁ -C ₆₎ Mono- or di-substituted with a substituent selected from an alkyl group, a hydroxy group, an amino group, an acetoxy group, an acetamide group, a phenyl group, a benzyloxy group, a dimethylaminophenyl group and a methylenedioxyphenyl group. Or better, further may be engaged benzene ring and condensed), an aryl group, an aryl (C ₁ -C ₆₎ alkyl group, diaryl (C ₁ -C ₆₎ alkyl group (the aryl group described above, or aryl moiety Optionally selected from (C ₁ -C ₆ ) alkyl groups, (C ₁ -C ₆ ) alkyloxy groups, halogen atoms, nitro groups, hydroxy groups, amino groups, dimethylamino groups, methylenedioxy groups, pyrrolidinyl groups. Mono-, di-, or tri-substituted with a substituent), a heterocyclic group or a heterocyclic group via a (C ₁ -C ₆ ) alkylene chain, (the above-mentioned heterocyclic group is a sulfur atom, an oxygen atom, Represents a saturated or unsaturated 5- to 8-membered monocyclic heterocyclic group or bicyclic heterocyclic group containing 1 to 3 heteroatoms selected from nitrogen atoms, and these heterocyclic groups are Mono- or di-substituted by At best, the substituent is an acetyl group, hydroxy group, (C ₁ -C ₉₎ alkyl group, (C ₁ -C ₉₎ alkyl group, cyclo (C ₃ -C ₈₎ alkyl, cycloalkyl (C
_{3 to} C ₈ ) alkyl (C _{3 to} C ₁₀ ) alkyl group, pyridyl (C _{1 to} C ₆ ) alkyl group, phenyl group, phenyl (C ₁
To C ₆ ) alkyl group, diphenyl (C ₁ -C ₆ ) alkyl group, phenylpiperazinyl group (the above-mentioned phenyl group or phenyl moiety may be a halogen atom, a hydroxy group, or (C ₁ -C ₆ ) alkyl. Group, (C ₁ -C ₆ ) alkoxy group, cyano group, diethylamino group, may be mono- or di-substituted with a substituent selected from trifluoromethyl group), and further, these heterocyclic groups are Optionally condensed with a benzene ring), and R ₃ and R ₄ together with the nitrogen atom to which they are bonded may form a saturated or unsaturated heterocyclic group, Is a 5- to 8-membered monocyclic heterocyclic group,
It represents a bicyclic heterocyclic group or a group derived from a heterocyclic spiro compound, and each of these groups further contains one or two heteroatoms selected from a sulfur atom, an oxygen atom and a nitrogen atom. May be. These heterocyclic groups may be optionally mono- or di-substituted, and the substituent is (C ₁
~ C ₆ ) alkyl group, hydroxy group, hydroxy (C ₁ ~
C ₆₎ alkyl groups, (C ₁ ~C ₆₎ alkoxy (C ₁ ~
C ₆₎ alkyl group, acetoxy (C ₁ ~C ₆₎ alkyl, (C ₁ ~C ₉₎ alkylcarbonyl group, (C ₁ ~C ₆₎
Alkoxycarbonyl group, amino group, tosyl group, phenyl group, halogenophenyl group, (C ₁ -C ₆ ) alkoxyphenyl group, phenyl (C ₁ -C ₆ ) alkyl group, benzyloxy group, benzyloxy (C ₁ -C) ₆ ) Alkyl group, toluyl group, xylyl group, benzoyl group, methylenedioxyphenyl (C ₁ -C ₆ ) alkyl group, pyridyl group, pyridylcarbonyl group, piperidyl group, pyrrolidinyl (C ₁
To C ₆ ) alkyl group, pyrrolidinylcarbonyl (C _{1 to} C
₆ ) selected from alkyl groups, and these heterocyclic groups may be condensed with a benzene ring. However, the case where R ₃ and R ₄ simultaneously represent a hydrogen atom is excluded. The alkyl moiety and alkoxy moiety of each of the above substituents may be linear or branched. R ₅ and R ₆ are the same or different and represent a linear or branched (C ₁ -C ₆ ) alkyl group, and It is -CH ₂ -CH ₂ - denote the or -CH = CH-. ] The urea derivative shown by these, and its pharmacologically acceptable salt. 2. The above-mentioned general formula (I) [in the formula, R ₃ and R ₄ are the same or different, a hydrogen atom, a linear or branched (C ₁ -C ₁₀ ) alkyl group, a linear or branched (C ₃ ~C ₁₇₎ alkenyl, (C ₁ ~C ₄₎ alkoxy (C ₁ ~C ₄₎ alkyl group, (C ₁ ~C ₄₎ alkoxycarbonyl (C ₁ ~C ₄₎ alkyl group, Benzyloxycarbonyl (C ₁ -C ₄ ) alkyl group (wherein the alkyl group, that is, the alkylene chain may be optionally substituted with a phenyl group), (C ₁ -C ₄ ) alkylthio (C ₁ -C _4). ) alkyl, cycloalkyl (C ₃ -C ₁₂₎ alkyl, cycloalkyl (C ₅ -C ₇₎ alkyl (C ₁ -C ₄₎ alkyl group,
(The above cycloalkyl group or cycloalkyl moiety may be a (C ₁ -C ₄ ) alkyl group, a hydroxy group, an amino group, an acetoxy group, an acetamide group, a phenyl group, a benzyloxy group, a dimethylaminophenyl group,
It may be mono-substituted with a substituent selected from a methylenedioxyphenyl group or may be further condensed with a benzene ring), dicyclohexyl (C ₁ -C ₄ ) alkyl group, bicyclooctyl group, adamantyl group Phenyl group, naphthyl group, anthryl group, phenyl (C ₁ -C ₄ ) alkyl group, diphenyl (C ₁ -C ₄ ) alkyl group (the above-mentioned phenyl group or phenyl moiety may be (C ₁ -C ₄ )) Mono- or di-substituted with a substituent selected from an alkyl group, a (C ₁ -C ₄ ) alkyloxy group, a halogen atom, a nitro group, a hydroxy group, an amino group, a dimethylamino group, a methylenedioxy group and a pyrrolidinyl group. may also), a heterocyclic group or a (C ₁ -C ₄₎ heterocyclic group which is a Hajime Tamaki (the via alkylene chain containing 1 or 2 nitrogen atoms, Heteromonocyclic group having 5 or 6-membered ring of the sum or unsaturated, represents a bicyclic heterocyclic group, these heterocyclic groups may optionally acetyl group, hydroxy group, (C ₁ -C ₆₎ alkyl Group, cyclohexyl group, pyridyl (C ₁ -C ₄ ) alkyl group, phenyl (C ₁ -C ₄ ) alkyl group, diphenyl (C ₁ -C ₄ ).
Alkyl group (wherein the phenyl moiety is a substituent selected from a halogen atom, a (C ₁ -C ₄ ) alkyl group, a (C ₁ -C ₄ ) alkoxy group, a cyano group, a diethylamino group, and a trifluoromethyl group. Mono- or di-substituted), mono- or di-substituted with a substituent selected from a phenylpiperazinyl group, or these heterocyclic groups may be fused with a benzene ring), Further, R ₃ and R ₄ may form a saturated or unsaturated heterocyclic group together with the nitrogen atom to which they are bound, and these heterocyclic groups contain 1 or 2 nitrogen atoms. 5-
Represents a 7-membered monocyclic heterocyclic group, a bicyclic heterocyclic group, or a group derived from a heterocyclic spiro compound, and these heterocyclic groups may be a (C ₁ -C ₄ ) alkyl group, Hydroxy (C ₁ -C ₄ ) alkyl group, acetoxy (C ₁ -C ₄ ) alkyl group, (C ₁ -C ₆ ) alkylcarbonyl group, (C _1- )
C ₄ ) alkoxycarbonyl group, tosyl group, phenyl group, phenyl (C ₁ -C ₄ ) alkyl group, benzyloxy group, benzyloxy (C ₁ -C ₄ ) alkyl group, benzoyl group, methylenedioxyphenyl (C ₁ To C ₄ ) alkyl group, pyridylcarbonyl group, piperidyl group, pyrrolidinylcarbonyl (C ₁ -C ₄ ) alkyl group may be mono- or di-substituted, and further, these heterocycles The group may be fused with a benzene ring. However, the case where R ₃ and R ₄ simultaneously represent a hydrogen atom is excluded. The alkyl moiety and the alkoxy moiety of each of the above substituents may be linear or branched] and the compound according to claim 1 and pharmaceutically acceptable thereof. salt. 3. The above-mentioned general formula (I) [in the formula, R ₃ and R ₄ are the same or different, a hydrogen atom, a linear or branched (C ₁ -C ₇ ) alkyl group, cyclo (C ₄ To C ₈ ) alkyl group, heterocyclic group or heterocyclic group via a (C _{1 to} C ₄ ) alkylene chain (the above-mentioned heterocyclic group contains one nitrogen atom, and is a saturated or unsaturated 5- or 6-membered ring). Represents a monocyclic heterocyclic group, a bicyclic heterocyclic group, and these heterocyclic groups may be a methyl group,
Ethyl group, cyclohexyl group, pyridylmethyl group, phenyl (C ₁ -C ₃ ) alkyl group (wherein the phenyl moiety is a substituent selected from a halogen atom, a methoxy group, a cyano group, a diethylamino group, and a trifluoromethyl group as the case may be). Or optionally di-substituted), which may be mono- or di-substituted, and these heterocyclic groups may be condensed with a benzene ring). However, the case where R ₃ and R ₄ simultaneously represent a hydrogen atom is excluded. The alkyl moiety and alkoxy moiety of each of the above substituents may be linear or branched, and the compound according to claim 2 and pharmacologically acceptable thereof. salt. 4. The above-mentioned general formula (I) [in the formula, R ₃ and R ₄ are the same or different, a hydrogen atom, a linear or branched (C ₁ -C ₄ ) alkyl group, a cyclohexyl group, a cyclohexyl group, Heptyl group, pyrrolidinyl group (this pyrrolidinyl group may be a methyl group, an ethyl group, a cyclohexyl group, a pyridylmethyl group, a phenyl (C ₁ -C ₃ ) alkyl group (the phenyl moiety may be a halogen atom, a methoxy group, a cyano group, Base,
It may be mono- or di-substituted by a substituent selected from a substituent selected from a diethylamino group and a trifluoromethyl group, and may be mono- or di-substituted by a substituent selected from the group consisting of a pyrrolidinyl group condensed with a benzene ring. A piperidyl group (this piperidyl group may be a methyl group, an ethyl group, a cyclohexyl group, a pyridylmethyl group,
From a phenyl (C ₁ -C ₃ ) alkyl group (the phenyl part may be mono- or di-substituted by a substituent selected from a halogen atom, a methoxy group, a cyano group, a diethylamino group and a trifluoromethyl group) It may be mono- or di-substituted with a selected substituent, and this piperidyl group may be condensed with a benzene ring). However, the case where R ₃ and R ₄ simultaneously represent a hydrogen atom is excluded. The alkyl moiety and alkoxy moiety of each of the above substituents may be linear or branched. ] The compound of Claim 3 shown by these, and its pharmacologically acceptable salt. 5. The above general formula (I) [wherein R ₃ and R ₄ together with the nitrogen atom to which they are bonded form a saturated or unsaturated heterocyclic group, The heterocyclic group contains a nitrogen atom of 1 or 2 and represents a 5- or 6-membered monocyclic heterocyclic group or bicyclic heterocyclic group.
In some cases, methyl group, hydroxyethyl group, acetoxyethyl group, pentylcarbonyl group, ethoxycarbonyl group, tosyl group, phenyl group, benzyl group, benzyloxy group, benzyloxyethyl group, benzoyl group, methylenedioxybenzyl group, pyridylcarbonyl group. Group, or a substituent selected from a piperidyl group, which may be mono- or di-substituted, and these heterocyclic groups may be condensed with a benzene ring]. A physically acceptable salt. 6. ACAT comprising the compound or pharmacologically acceptable salt thereof according to any one of claims 1 to 5 as an active ingredient, and optionally a pharmaceutically acceptable carrier or excipient.
Inhibitor.