JP2005220133A5

JP2005220133A5 -

Info

Publication number: JP2005220133A5
Application number: JP2005020179A
Authority: JP
Filing date: 2005-01-27
Publication date: 2008-09-25
Anticipated expiration: 2023-02-28

Claims

General formula (1)

[Where,
R ¹ and R ² are the same or different and each represents a hydrogen atom, a C _1-6 alkyl group, a C _3-7 cycloalkyl group, a C _1-6 alkoxy group, a halo C _1-6 alkyl group, or a halo C _1-6 alkyl. An oxy group, an _optionally substituted C _6-14 aryl group, an _optionally substituted C _7-16 aralkyl group, an _optionally substituted C _6-14 aryloxy group, an _optionally substituted C _7-16 aralkyloxy group, C _7-15 arylcarbonyl group which may be substituted, heterocyclic group which may be substituted, C _2-7 alkoxycarbonyl group, halogen atom, C _2-6 alkenyl group or — N (R ⁴⁰ ) (R ⁴¹ ) (where R ⁴⁰ and R ⁴¹ are the same or different and are a hydrogen atom or an optionally substituted C _6-14 aryl group.)
Is;
Ring A is a C _6-14 aryl group, a heterocyclic group ,

Is;
X is —COO— (CH ₂ ) _n —, —CON (R ¹⁰ ) — (CH ₂ ) _n — or —N (R ¹⁰ ) —CO— (CH ₂ ) _n — (where R ¹⁰ is A hydrogen atom, a C _1-6 alkyl group or a C _3-7 cycloalkyl group, and n is 0 or an integer of 1 to 3);
R ³ and R ⁴ are the same or different and each represents a hydrogen atom, a hydroxyl group, a halogen atom, an optionally substituted C _1-6 alkyl group, a C _1-6 alkoxy group, a halo C _1-6 alkyl group, C _{7- 16} aralkyloxy group, C _1-6 acyl group, optionally substituted heterocyclic group, —CON (R ¹¹ ) (R ¹² ) [wherein R ¹¹ and R ¹² are the same or different and represent a hydrogen atom, A C _1-6 alkyl group, an optionally substituted C _6-14 aryl group, an optionally substituted C _7-16 aralkyl group or a C _1-6 alkoxy group, or together with a nitrogen atom to which it is bonded become

(Where p is an integer of 0 or 1 to 2) . ],
— (CH ₂ ) _q —N (R ¹³ ) (R ¹⁴ ) [wherein R ¹³ and R ¹⁴ are the same or different and each represents a hydrogen atom, a C _1-6 alkyl group, a C _2-7 alkoxycarbonyl group or C Together with a nitrogen atom which is a _1-6 acyl group or bonded

(Wherein p is as defined above). q is 0 or an integer of 1 to 3. ] Or -CO ^{(R 15) ^(wherein,} ^{R 15} represents a hydroxyl _{group, C 1-6} alkoxy groups, optionally substituted _{C 6-14} aryloxy group, an optionally _{C 7-16} aralkyl which may be substituted An oxy group or a C _1-6 alkyl group);

(Wherein K is 0 or an integer of 1 to 2), or the nitrogen atom to which R ³ , R ¹⁰ and R ¹⁰ are bonded together with ring B,

May form;
Alk ¹ is alkanediyl or alkenediyl;
Alk ² is alkanediyl or alkenediyl;
l is 0 or an integer from 1 to 3;
m is 0 or an integer from 1 to 3;
D represents a C _1-6 alkyl group, a C _2-6 alkenyl group, a C _2-7 alkoxycarbonyl group, —N (R ⁴² ) —CO (R ⁴³ ) (where R ⁴² represents a hydrogen atom or C _{1 1- 6 is} an alkyl group, and R ⁴³ is a C _6-14 aryl group or a C _7-16 aralkyl group.) Or the following formula:

(Where
R ⁵ , R ⁶ and R ⁷ are the same or different and are a hydrogen atom, a C _1-6 alkyl group, a C _1-6 alkoxy group, a C _2-7 alkoxycarbonyl group, a carboxyl group, a halogen atom, a cyano group or a nitro group. , A halo C _1-6 alkyl group, a C _1-6 acyl group, a hydroxyl group, an amino group, an optionally substituted C _6-14 aryl group, or — (CH ₂ ) _r —CON (R ¹⁶ ) (R ¹⁷ ) (Wherein R ¹⁶ and R ¹⁷ are the same or different and are a hydrogen atom, a C _1-6 alkyl group or a halo C _1-6 alkyl group. R is 0 or an integer of 1 to 3). ;
Ring C is a C _6-14 aryl group, a C _7-15 arylcarbonylamino group, a C _8-17 aralkylcarbonylamino group, a heterocyclic residue, a C _3-7 cycloalkyl group, a C _7-16 aralkyl group, or Ring C, R ⁷ and R ^{8 described} below together

May be formed. A group represented by
R ⁸ and R ⁹ are the same or different and each represents a hydrogen atom, a C _1-6 alkyl group, an optionally substituted C _6-14 aryl group, a hydroxy C _1-6 alkyl group, —CON (R ¹⁸ ) (R ¹⁹ ) (wherein R ¹⁸ and R ¹⁹ are the same or different and each represents a hydrogen atom, a C _1-6 alkyl group, a C _3-7 cycloalkyl group, a halo C _1-6 alkyl group, or a C _2-12 alkoxyalkyl group. Or an optionally substituted C _6-14 aryl group), —COO (R ²⁰ ) or — (CH ₂ ) _s —OCO (R ²⁰ ) (wherein R ²⁰ is a hydrogen atom, C _{1- 6 is} an alkyl group or a C _3-7 cycloalkyl group, s is 0 or an integer of 1 to 3) or —N (R ²¹ ) (R ²² ) (where R ²¹ and R ²² are the same) Or differently from a hydrogen atom, C _1-6 a Together with a rualkyl group, a C _1-6 acyl group, a C _1-6 alkylsulfonyl group, or a nitrogen atom to which R ²¹ and R ²² are bonded,

May be formed. Or R ⁸ and R ⁹ may be taken together to form a C _3-7 cycloalkyl group. However, D is following formula;

[Where:
R ⁵ , R ⁶ and R ⁷ are the same or different and are a hydrogen atom, a C _1-6 alkyl group, a C _1-6 alkoxy group, a C _2-7 alkoxycarbonyl group, a carboxyl group, a halogen atom, a cyano group or a nitro group. , A halo C _1-6 alkyl group, a C _1-6 acyl group, a hydroxyl group, an amino group, a C _6-14 aryl group _optionally substituted by a substituent Z (wherein the substituent Z is a C _1-6 alkyl Group, hydroxyl group, C _1-6 alkoxy group, halogen atom, nitro group, cyano group, C _1-6 acyl group, C _1-6 acyloxy group, mercapto group, C _1-6 alkylthio group, amino group, C _{1- 6} alkylamino group, di-C _1-6 alkylamino group, carboxy group, C _2-7 alkoxycarbonyl group, amide group, trifluoromethyl group, C _1-6 alkylsulfonyl group, aminosulfonyl Group, a C _3-7 cycloalkyl group, a phenyl group, or an acylamide group.) Or — (CH ₂ ) _r —CON (R ¹⁶ ) (R ¹⁷ ) (wherein R ¹⁶ and R ¹⁷ are the same or different. A hydrogen atom, a C _1-6 alkyl group or a halo C _1-6 alkyl group, r is 0 or an integer of 1 to 3);
Ring C is a C _6-14 aryl group, a heterocyclic residue or a C _3-7 cycloalkyl group. A group represented by
R ⁸ and R ⁹ are the same or different and are —CON (R ¹⁸ ) (R ¹⁹ ) [wherein R ¹⁸ and R ¹⁹ are the same or different and represent a hydrogen atom, a C _1-6 alkyl group, C _{3− 7 a} cycloalkyl group, a halo C _1-6 alkyl group, a C _2-12 alkoxyalkyl group or a C _6-14 aryl group optionally substituted by a substituent Z (wherein the substituent Z is the same as above) ]] Or —COO (R ²⁰ ) (wherein R ²⁰ is a hydrogen atom, a C _1-6 alkyl group or a C _3-7 cycloalkyl group). ]
In salt ester compound or to their pharmaceutically acceptable shown.

D is a C _1-6 alkyl group, a C _2-6 alkenyl group, a C _2-7 alkoxycarbonyl group, or —N (R ⁴² ) —CO (R ⁴³ ) (wherein R ⁴² and R ⁴³ are claimed in claim 1). The ester compound according to claim 1 or a pharmaceutically acceptable salt thereof.

D is the following formula:

The ester compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R ⁵ , R ⁶ and R ⁷ are as defined above.

Ring C is

(Wherein q is 0 or an integer of 1 to 3). The ester compound according to claim 1, or a pharmaceutically acceptable salt thereof.

Ring B is

The ester compound according to claim 1 or a pharmaceutically acceptable salt thereof.

Ring A is

X ^{is, -CON (R 10) - (} CH 2) n - is allowed ^{(where, R 10} and n are definitive and as defined in claim 1.) A which is an ester compound of claim 1, wherein or their pharmaceutically Salt.

Acceptable salt (here, n represents wherein definitive and as defined in claim 1.) A which is an ester compound of claim 1, wherein or their pharmaceutically - X is, -COO- _(CH _{2) n.}

9. The ester compound or a pharmaceutically acceptable salt thereof according to claim 7 or 8, wherein n is 0.

General formula (1)

[Where,
R ¹ and R ² are the same or different and each represents a hydrogen atom, a C _1-6 alkyl group, a C _3-7 cycloalkyl group, a C _1-6 alkoxy group, a halo C _1-6 alkyl group, or a halo C _1-6 alkyl. An oxy group, an _optionally substituted C _6-14 aryl group, an _optionally substituted C _7-16 aralkyl group, an _optionally substituted C _6-14 aryloxy group, an _optionally substituted C _{A 7-16} aralkyloxy group, an _optionally substituted C _7-15 arylcarbonyl group, or an _optionally substituted heterocyclic group;
Ring A is a C _6-14 aryl group, a heterocyclic group ,

Is;
X represents —COO— (CH ₂ ) _n —, —CON (R ¹⁰ ) — (CH ₂ ) _n — (where R ¹⁰ represents a hydrogen atom, a C _1-6 alkyl group or a C _3-7 cycloalkyl). And n is 0 or an integer of 1 to 3);
R ³ and R ⁴ are the same or different and are a hydrogen atom, a hydroxyl group, a halogen atom, a C _1-6 alkyl group, a C _1-6 alkoxy group, a halo C _1-6 alkyl group, —CON (R ¹¹ ) (R ¹² Wherein R ¹¹ and R ¹² are the same or different and each represents a hydrogen atom, a C _1-6 alkyl group, an _optionally substituted C _6-14 aryl group, or an _optionally substituted C _7-16 aralkyl. Together with the nitrogen atom to be bound or bound

(Where p is an integer of 0 or 1 to 2). ^{], - N (R 13)} (R 14) [ ^{wherein, R 13} and ^{R 14,} together with the same or different is a hydrogen atom or a _{C 1-6} alkyl group, or a bond to a nitrogen atom

(Where p is the same as above) may be formed. Or —CO (R ¹⁵ ) (where R ¹⁵ is a hydroxyl group, a C _1-6 alkoxy group, an optionally substituted C _6-14 aryloxy group, or an optionally substituted C _7-16 aralkyl. An oxy group); and ring B is

May form;
Alk ¹ is alkanediyl or alkenediyl;
Alk ² is alkanediyl or alkenediyl;
l is 0 or an integer from 1 to 3;
m is 0 or an integer from 1 to 3;
D, R ⁸ and R ⁹ are as defined in claim 1. ]
Or an pharmaceutically acceptable salt thereof.

The _optionally substituted C _6-14 aryl group represented by R ¹ and R ² is an _optionally substituted phenyl group, an optionally substituted naphthyl group or an optionally substituted biphenyl group; The ester compound or a pharmaceutically acceptable salt thereof according to claim 10, wherein the C _6-14 aryl group represented by ring A is a phenyl group, a naphthyl group or a biphenyl group.

Formula (1 ′);

[Wherein, R ^{2 ′} and R ^{2 ″} are the same or different and represent a hydrogen atom, a C _1-6 alkyl group, a C _3-7 cycloalkyl group, a C _1-6 alkoxy group, a halogen atom, a halo C _{1- A 6} alkyl group, a C _1-6 acyl group, a C _2-6 alkenyl group or a cyano group;
X ₁ is —O— or —NR ¹⁰ — (wherein R ¹⁰ is a hydrogen atom, a C _1-6 alkyl group or a C _3-7 cycloalkyl group);
R ¹ , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , ring C, l and m are as defined in claim 1 ]
The ester compound of Claim 1 shown by these, or those pharmaceutically acceptable salts.

Ring C is

(Wherein q is 0 or an integer of 1 to 3) The ester compound according to claim 12, or a pharmaceutically acceptable salt thereof.

13. The ester compound or a pharmaceutically acceptable salt thereof according to claim 12, wherein X ₁ is —NR ¹⁰ — (wherein R ¹⁰ has the same meaning as in claim 12).

The ester compound or a pharmaceutically acceptable salt thereof according to claim 12, wherein X ₁ is -O-.

In the general formula (1 ') - (CH 2 ) l - substitution positions on the benzene ring of _{(. L} is definitive and as defined in claim 1) is an ester compound according to claim 12 or 15 is h-position, or Their pharmaceutically acceptable salts.

In the general formula (1 ') - (CH 2 ) l - substitution positions on the benzene ring of _{(. L} is as defined above and definitive in claim 1) is an ester compound according to claim 12 or 15 which is i-position or Their pharmaceutically acceptable salts.

The ester according to claim 1 or 12, wherein R ⁸ and R ⁹ are the same or different and are -CON (R ¹⁸ ) (R ¹⁹ ) (wherein R ¹⁸ and R ¹⁹ are as defined in claim 1). A compound or a pharmaceutically acceptable salt thereof.

R ⁸ and R ⁹ are the same or different and are —COO (R ²⁰ ) (wherein R ²⁰ has the same meaning as in claim 1), or the ester compound according to claim 1 or 12, or a pharmaceutically acceptable salt thereof. Salt.

The ester compound or a pharmaceutically acceptable salt thereof according to claim 1 or 12, wherein Ring C is a _C6-14 aryl group.

_21. The ester compound or a pharmaceutically acceptable salt thereof according to claim 20, wherein the _C6-14 aryl group is a phenyl group.

Ring C, the ester compound or a pharmaceutically acceptable salt thereof according to claim 1 or 12, which is a C _3-7 cycloalkyl group.

Ring C is

The ester compound according to claim 1 or 12, or a pharmaceutically acceptable salt thereof.

2- (2- {3-methyl-4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetoxymethyl) -2-phenyl-malonic acid diethyl ester,
{4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 9- (2,2,2-trifluoro-ethylcarbamoyl) -9H-fluoren-9-ylmethyl ester ,
2- {4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -propionic acid 9- (2,2,2-trifluoro-ethylcarbamoyl) -9H-fluorene-9 -Ylmethyl ester,
{4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 2-phenyl-2- (2,2,2-trifluoro-ethylcarbamoyl) -ethyl ester,
2-phenyl-2- (2- {4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetoxymethyl) -malonic acid diethyl ester,
{4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 1- (2,2,2-trifluoro-ethylcarbamoyl) -cyclopentylmethyl ester,
2-phenyl-2- (2- {4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetoxymethyl) -malonic acid diisopropyl ester,
{4-[(4′-Trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 2-phenyl-2,2-bis- (2,2,2-trifluoro-ethylcarbamoyl)- Ethyl ester,
2-phenyl-2- (2- {4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetoxymethyl) -malonic acid dimethyl ester,
2-cyclopentyl-2- (2- {4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetoxymethyl) -malonic acid diethyl ester,
{4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 1- (2,2,2-trifluoro-ethylcarbamoyl) -cyclohexylmethyl ester,
2-benzyl-2- (2- {4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetoxymethyl) -malonic acid diethyl ester ,
{ 3- (Pyrrolidine-1-carbonyl) -4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 2-ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 2-phenyl-2-propionylamino-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 2-phenyl-2-propionylamino-ethyl ester,
{3-Dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 2- (2,5-dioxo-pyrrolidin-1-yl) -2-phenyl -Ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 2-ethylcarbamoyl-benzyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 2-ethylcarbamoylmethyl-benzyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 2-isopropylamino-2-phenyl-ethyl ester hydrochloride,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 2-acetylamino-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 2-butyrylamino-2-phenyl-ethyl ester,
2- {2- [4- (2-benzoyl-benzoylamino) -3-dimethylcarbamoyl-phenyl] -acetoxymethyl} -2-phenyl-malonic acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 2-methanesulfonylamino-2-phenyl-ethyl ester,
3- (2- {3-dimethylcarbamoyl-4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetoxy) -2-phenyl-propionic acid ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 2- (methyl-propionyl-amino) -2-phenyl-ethyl ester,
2- (2- {3-dimethylcarbamoyl-4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetoxymethyl) -2-phenyl-succinic acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 2-ethyl-2-phenyl-butyl ester,
{3-dimethylcarbamoyl-4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 1-phenyl-cyclopropylmethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 2,2-diphenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 1-phenyl-cyclopentylmethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 3-hydroxy-2-hydroxymethyl-2-phenyl-propyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetic acid 3-acetoxy-2-acetoxymethyl-2-phenyl-propyl ester,
2- (2- {3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetoxymethyl) -2-isopropyl-malonic acid diethyl ester,
2-sec-butyl-2- (2- {3-dimethylcarbamoyl-4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetoxymethyl) -malonic acid diethyl ester,
2- (2- {3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetoxymethyl) -2-isobutyl-malonic acid diethyl ester,
2- (2- {3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetoxymethyl) -2-propyl-malonic acid diethyl ester,
2- (2- {3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetoxymethyl) -2-ethyl-malonic acid diethyl ester,
2-butyl-2- (2- {3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetoxymethyl) -malonic acid diethyl ester,
2-allyl-2- (2- {3-dimethylcarbamoyl-4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetoxymethyl) -malonic acid diethyl ester,
Ethyl 3- (2- {3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetoxy) -2,2-bis-ethoxycarbonyl-propionic acid ester,
2- (2- {3-Dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetoxymethyl) -2- (1-methyl-butyl) -malon Acid diethyl ester,
4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -benzoic acid 2- [9- (2,2,2-trifluoro-ethylcarbamoyl) -9H-fluoren-9-yl] -Ethyl ester,
4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -benzoic acid 2- (9H-fluoren-9-yl) -ethyl ester,
N-biphenyl-2-yl-terephthalamic acid 2- [9- (2,2,2-trifluoro-ethylcarbamoyl) -9H-fluoren-9-yl] -ethyl ester,
4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -benzoic acid 2-[(biphenyl-2-carbonyl) -amino] -ethyl ester,
4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -benzoic acid 2- (2-biphenyl-2-yl-acetylamino) -ethyl ester,
4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -benzoic acid 3-naphthalen-1-yl-3- (2,2,2-trifluoro-ethylcarbamoyl) -propyl ester,
4-[(4′-Trifluoromethyl-biphenyl-2-carbonyl) -amino] -benzoic acid 3- [2- (2,2,2-trifluoro-ethylcarbamoyl) -naphthalen-1-yl] -propyl ester,
4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -benzoic acid 3,3-diphenyl-3- (2,2,2-trifluoro-ethylcarbamoyl) -propyl ester,
4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -benzoic acid 3-biphenyl-2-yl-3- (2,2,2-trifluoro-ethylcarbamoyl) -propyl ester,
4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -benzoic acid 3-phenyl-3- (2,2,2-trifluoro-ethylcarbamoyl) -propyl ester,
4-[(4′-Trifluoromethyl-biphenyl-2-carbonyl) -amino] -benzoic acid 2- [8- (2,2,2-trifluoro-ethylcarbamoyl) -naphthalen-1-yl] -ethyl ester,
4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -benzoic acid 3- (2,6-dichloro-phenyl) -3- (2,2,2-trifluoro-ethylcarbamoyl) -Propyl ester,
4-[(4′-Trifluoromethyl-biphenyl-2-carbonyl) -amino] -benzoic acid 3- (2-chloro-phenyl) -3- (2,2,2-trifluoro-ethylcarbamoyl) -propyl ester,
4-Methyl-4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -cyclohexanecarboxylic acid 2- [9- (2,2,2-trifluoro-ethylcarbamoyl) -9H-fluorene -9-yl] -ethyl ester,
4-[(4′-Trifluoromethyl-biphenyl-2-carbonyl) -amino] -cyclohexanecarboxylic acid 2- [9- (2,2,2-trifluoro-ethylcarbamoyl) -9H-fluoren-9-yl ] -Ethyl ester,
4-[(4′-trifluoromethyl-biphenyl-2-carbonyl) -amino] -cyclohexanecarboxylic acid 3-phenyl-3- (2,2,2-trifluoro-ethylcarbamoyl) -propyl ester, or 3- {4 - [(4'-trifluoromethyl - biphenyl-2-carbonyl) - amino] - phenyl} - propionic acid ethylcarbamoyl - phenyl - ester compound of claim 1 which is methyl ester or their pharmaceutically Top acceptable salt.

25. A pharmaceutical composition comprising the ester compound according to any one of claims 1 to 24 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

An MTP (microsomal triglyceride transfer protein) inhibitor comprising the ester compound according to any one of claims 1 to 24 or a pharmaceutically acceptable salt thereof as an active ingredient.

A therapeutic or prophylactic agent for hyperlipidemia comprising the ester compound according to any one of claims 1 to 24 or a pharmaceutically acceptable salt thereof as an active ingredient.

A therapeutic or prophylactic agent for arteriosclerosis comprising the ester compound according to any one of claims 1 to 24 or a pharmaceutically acceptable salt thereof as an active ingredient.

A therapeutic or prophylactic agent for coronary artery disease comprising the ester compound according to any one of claims 1 to 24 or a pharmaceutically acceptable salt thereof as an active ingredient.

A therapeutic or prophylactic agent for obesity comprising the ester compound according to any one of claims 1 to 24 or a pharmaceutically acceptable salt thereof as an active ingredient.

25. A therapeutic or prophylactic agent for diabetes comprising the ester compound according to any one of claims 1 to 24 or a pharmaceutically acceptable salt thereof as an active ingredient.

A therapeutic or prophylactic agent for hypertension comprising the ester compound according to any one of claims 1 to 24 or a pharmaceutically acceptable salt thereof as an active ingredient.

A therapeutic or prophylactic agent for hyperlipidemia, arteriosclerosis, coronary artery disease, obesity, diabetes or hypertension, comprising the MTP inhibitor according to claim 26 and a pharmaceutically acceptable carrier.

The therapeutic or prophylactic agent according to claim 33, wherein the MTP inhibitor does not substantially inhibit liver MTP but substantially inhibits only small intestine MTP.

The administered MTP inhibitor inhibits small intestine MTP and is then metabolized in the small intestine, blood and liver, and the remaining amount of MTP inhibitor in the liver is metabolized to an amount that does not substantially inhibit liver MTP. The therapeutic or prophylactic agent according to claim 34.

36. The therapeutic or prophylactic agent according to claim 35, wherein the remaining amount of the MTP inhibitor in the liver is metabolized to a state where the TG release function in the liver is maintained at about 80% or more of the normal value.

37. The therapeutic or prophylactic agent according to claim 33 to 36, wherein the MTP inhibitor is a compound having at least one ester bond.

38. The therapeutic or prophylactic agent according to claim 37, wherein after the compound having an ester bond exhibits MTP inhibitory activity, the ester moiety undergoes metabolism in blood and becomes an inactive substance.

The therapeutic or prophylactic agent according to claim 33 to 38, wherein the MTP inhibitor is the ester compound according to any one of claims 1 to 24 or a pharmaceutically acceptable salt thereof.

40. The therapeutic or prophylactic agent according to any one of claims 33 to 39, which is a therapeutic or prophylactic agent for hyperlipidemia and is used in combination with another therapeutic agent for hyperlipidemia.

The therapeutic or prophylactic agent according to claim 40, wherein the other therapeutic agent for hyperlipidemia is a statin drug.

The therapeutic or preventive drug according to claim 41, wherein the statin drug is one or more drugs selected from the group consisting of lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, and cerivastatin.

40. The therapeutic or prophylactic agent according to claim 33, which is a therapeutic or prophylactic agent for obesity, and is used in combination with another therapeutic agent for obesity.

44. The therapeutic or prophylactic agent according to claim 43, wherein the other obesity therapeutic agent is mazindol or / and orlistat.

The therapeutic or prophylactic agent according to any one of claims 33 to 39, which is a therapeutic or prophylactic agent for diabetes and is used in combination with another therapeutic agent for diabetes.

The other diabetes therapeutic drug is one or more drugs selected from the group consisting of insulin preparations, sulfonylurea drugs, insulin secretagogues, sulfonamide drugs, biguanide drugs, α-glucosidase inhibitors and insulin resistance improving drugs. 45. The therapeutic or prophylactic agent according to 45.

The other antidiabetic agent is selected from the group consisting of insulin, glibenclamide, tolbutamide, glyclopyramide, acetohexamide, glimepiride, tolazamide, gliclazide, nateglinide, glybsol, metformin hydrochloride, buformin hydrochloride, voglibose, acarbose and pioglitazone hydrochloride 46. The therapeutic or prophylactic agent according to claim 45, which is the above agent.

40. The therapeutic or prophylactic agent according to claim 33, which is a therapeutic or prophylactic agent for hypertension and is used in combination with another antihypertensive agent.

One or more other antihypertensive drugs selected from the group consisting of loop diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, Ca antagonists, β blockers, α, β blockers and α blockers 49. The therapeutic or prophylactic agent according to claim 48, which is a drug.

Other antihypertensive drugs are furosemide sustained release, captopril, captopril sustained release, enalapril maleate, alacepril, delapril hydrochloride, cilazapril, lisinopril, benazepril hydrochloride, imidapril hydrochloride, temocapril hydrochloride, quinapril hydrochloride, trandolapril, perindopril elb Min, losartan potassium, candesartan cilexetil hydrochloride, nicardipine hydrochloride, nicardipine hydrochloride sustained release agent, nilvadipine, nifedipine, nifedipine sustained release agent, benidipine hydrochloride, diltiazem hydrochloride, diltiazem hydrochloride sustained release agent, nisoldipine, nitrendipine, manidipine hydrochloride, varnidipine hydrochloride, Efonidipine hydrochloride, amlodipine besylate, felodipine, cilnidipine, alanidipine, propranolol hydrochloride, propranolol hydrochloride sustained release agent, pind , Pindolol sustained release agent, indenolol hydrochloride, carteolol hydrochloride, carteolol hydrochloride sustained release agent, bunitrolol hydrochloride, bunitrolol hydrochloride sustained release agent, atenolol, acebutol hydrochloride, metoprolol tartrate, meproprolol tartrate sustained release, nipradilol, penbutolol sulfate, Chirisolol hydrochloride, carvedilol, bisoprolol fumarate, betaxolol hydrochloride, seriprolol hydrochloride, bopindolol malonate, bevantolol hydrochloride, labetalol hydrochloride, allotinolol hydrochloride, amosulalol hydrochloride, prazosin, terazosin hydrochloride, doxazosin mesylate, bunazosin hydrochloride, bunazosin hydrochloride sustained release 49. The therapeutic or prophylactic agent according to claim 48, which is one or more agents selected from the group consisting of an agent, urapidil and phentolamine mesylate.

25. A pharmaceutical composition comprising an effective amount of the ester compound according to any one of claims 1 to 24 or a pharmaceutically acceptable salt thereof and an appropriate amount of pharmaceutically acceptable ethanol and propylene glycol fatty acid ester.

52. The pharmaceutical composition according to claim 51, comprising 25 to 35% by weight of ethanol and 65 to 75% by weight of propylene glycol fatty acid ester.

53. A capsule preparation containing the pharmaceutical composition according to claim 51 or 52.

The capsule preparation according to claim 53, wherein the capsule preparation is a hard capsule or a soft capsule.

(I) Each of R ⁸ and R ⁹ is CON (R ¹⁸ ) (R ¹⁹ ) [wherein R ¹⁸ and R ¹⁹ are the same or different and each represents a hydrogen atom, a C _1-6 alkyl group, a C _3-7 cyclo An alkyl group, a halo C _1-6 alkyl group, a C _2-12 alkoxyalkyl group, or a C _6-14 aryl group optionally substituted with a substituent Z (wherein the substituent Z is a C _1-6 alkyl group, Hydroxyl group, C _1-6 alkoxy group, halogen atom, nitro group, cyano group, C _1-6 acyl group, C _1-6 acyloxy group, mercapto group, C _1-6 alkylthio group, amino group, C _1-6 alkyl amino group, di _{C 1-6} alkylamino group, a carboxy _{group, C 2-7} alkoxycarbonyl group, an amide group, a trifluoromethyl _{group, C 1-6} alkylsulfonyl group, aminosulfonyl _{group, C 3-7} A cycloalkyl group, a phenyl group or an acylamido group.)] Or COO ^{(R 20)} ^{(wherein, R 20} represents a hydrogen _atom, a _{C 1-6} alkyl group or a _{C 3-7} cycloalkyl group.)
And
D represents a C _1-6 alkyl group, a C _2-6 alkenyl group, a C _2-7 alkoxycarbonyl group, or —N (R ⁴² ) —CO (R ⁴³ ) (where R ⁴² represents a hydrogen atom or C _1-6 An alkyl group, and R ⁴³ is a C _6-14 aryl group or a C _7-16 aralkyl group.)

(II) One of R ⁸ and R ⁹ is CON (R ¹⁸ ) (R ¹⁹ ) (R ¹⁸ , R ¹⁹ are as defined above) or COO (R ²⁰ ) (where R ²⁰ is as defined above). The other of R ⁸ and R ⁹ is the same or different and is a hydrogen atom, a C _1-6 alkyl group, an optionally substituted C _6-14 aryl group or a hydroxy C _1-6 alkyl group. And D is the following formula:

[Where:
R ⁵ , R ⁶ and R ⁷ are the same or different and are a hydrogen atom, a C _1-6 alkyl group, a C _1-6 alkoxy group, a C _2-7 alkoxycarbonyl group, a carboxyl group, a halogen atom, a cyano group or a nitro group. , A halo C _1-6 alkyl group, a C _1-6 acyl group, a hydroxyl group, an amino group, a C _6-14 aryl group _optionally substituted by a substituent Z (wherein the substituent Z is as defined above) Or — (CH ₂ ) _r —CON (R ¹⁶ ) (R ¹⁷ ) (wherein R ¹⁶ and R ¹⁷ are the same or different and each represents a hydrogen atom, a C _1-6 alkyl group, or a haloC _1-6. An alkyl group, r is 0 or an integer of 1 to 3);
Ring C is a C _6-14 aryl group, a heterocyclic residue, or a C _3-7 cycloalkyl group, or ring C, R ⁷ and R ⁸ are taken together,

May be formed. Or a group represented by

(III) One of R ⁸ and R ⁹ is CON (R ¹⁸ ) (R ¹⁹ ) (R ¹⁸ and R ¹⁹ are as defined above) or COO (R ²⁰ ) (where R ²⁰ is as defined above) The other of R ⁸ and R ⁹ is the same or different and is a hydrogen atom, a C _1-6 alkyl group, an optionally substituted C _6-14 aryl group or a hydroxy C _1-6 alkyl group, and D is A C _1-6 alkyl group, a C _2-6 alkenyl group, a C _2-7 alkoxycarbonyl group, —N (R ⁴² ) —CO (R ⁴³ ) (where R ⁴² and R ⁴³ are as defined in (I) above) Is equivalent).

(IV) Each of R ⁸ and R ⁹ is a hydrogen atom, a C _1-6 alkyl group, an optionally substituted C _6-14 aryl group or a hydroxy C _1-6 alkyl group, and D is represented by the following formula:

Wherein R ⁵ , R ⁶ and R ⁷ have the same meaning as in (II) above;
Ring C is a C _6-14 aryl group, a C _7-15 arylcarbonylamino group, a C _{8-17 aralkylcarbonylamino} group, a C _3-7 cycloalkyl group or a C _7-16 aralkyl group, or ring C And R ⁷ and R ⁸ together

May be formed. ) Or a group represented by

(V) Each of R ⁸ and R ⁹ is a hydrogen atom, a C _1-6 alkyl group, an optionally substituted C _6-14 aryl group or a hydroxy C _1-6 alkyl group, and D is a C _1-6 An alkyl group, a C _2-6 alkenyl group, a C _2-7 alkoxycarbonyl group, or —N (R ⁴² ) —CO (R ⁴³ ) (where R ⁴² and R ⁴³ have the same meanings as in (I) above). The ester compound according to claim 1, or a pharmaceutically acceptable salt thereof.