KR950025022A - Substituted Amic Acid Derivatives - Google Patents

Abstract

A compound of formula (I) or a pharmaceutically acceptable salt or ester thereof:

[Wherein, And Are the same or different and each is an aryl group or a heteroaromatic ring group; A is C, which may have a substituent (s) selected from the group consisting of lower alkyl groups, hydroxyl groups, lower alkoxy groups, carboxyl groups, aryl groups and aralkyl groups _3-8 linear saturated or unsaturated aliphatic hydrocarbon group; Q represents a single bond or a group represented by the formula -CO-O-, -O-CO-, -CH 2 CH 2 -, -CH = CH-, -OCH 2 -, -SCH ₂ - -CH ₂ O- or -CH ₂ S- group, and ^{a; R 1, R 2, R} 3 and R ⁴ are the same or different, each represent a hydrogen atom, a halogen atom, a lower alkyl group, a hydroxyl group, a lower An aryl or heteroaromatic ring group which may have an alkoxy group or a substituent (s) selected from the group consisting of a halogen atom, a lower alkyl group and a lower alkoxy group; R ⁵ , R ⁶ and R ⁷ are the same or different and each is A hydrogen atom or a lower alkyl group; R ⁸ is a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group Or an aralkyl group; provided that when Q is a single bond,

Is not 4-chlorophenyl group at the same time]

Description

Substituted Amic Acid Derivatives

Since this is an open matter, no full text was included.

Claims (22)

A compound of formula (I) or a pharmaceutically acceptable salt or or ester thereof: [Wherein, And -Are the same or different and each is an aryl group or heteroaromatic ring group; A may have a substituent (s) selected from the group consisting of a lower alkyl group, a hydroxyl group, a lower alkoxy group, a carboxyl group, an aryl group and an aralkyl group ₃ ~ C ₈ straight-chain saturated or unsaturated aliphatic hydrocarbon group; Q represents a single bond or a group represented by the formula -CO-O-, -O-CO-, -CH 2 CH 2 -, -CH = CH-, -OCH 2 -, - SCH ₂ --CH ₂ O- or -CH ₂ S-; R ¹ , R ² , R ³ and R ⁴ are the same or different and each is a hydrogen atom, a halogen atom, a lower alkyl group, a hydroxyl group, Aryl or heteroaromatic ring groups which may have a lower alkoxy group or substituent (s) selected from the group consisting of halogen atoms, lower alkyl groups and lower alkoxy groups; R ⁵ , R ⁶ and R ⁷ are the same or different, respectively Is a hydrogen atom or a lower alkyl group; R ⁸ is a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group Or an aralkyl group; provided that when Q is a single bond, Is not 4-chlorophenyl group at the same time] A compound according to claim 1 which is a compound of formula (I-1): [In the above formula, And Are the same or different and each is an aryl group or heteroaromatic ring group; A may have a substituent (s) selected from the group consisting of lower alkali, hydroxyl group, lower alkoxy group, carboxyl group, aryl group and aralkale group C ₃ ~ ₈ straight chain saturated or unsaturated aliphatic hydrocarbon group; Q ¹ is a single bond, ^{and; R 1, R 2, R} 3 and R ⁴ are the same or different, each represent a hydrogen atom, a halogen atom, a lower alkyl group, a hydroxyl Aryl or heteroaromatic ring groups which may have a substituent (s) selected from the group consisting of a real group, a lower alkoxy group or a halogen atom, a lower alkyl group and a lower alkoxy group; R ⁵ , R ⁶ and R ⁷ are the same or different Each is a hydrogen atom or a lower alkyl group; R ⁸ is a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group or an aralkyl group; Is not 4-chlorophenyl group at the same time A compound according to claim 1 which is a compound of formula (I-2): [Wherein, And Are the same or different and each is an aryl group or heteroaromatic ring group; A may have a substituent (s) selected from the group consisting of lower alkyl groups, hydroxyl groups, lower alkoxy groups, carboxyl groups, aryl groups or aralkyl groups C3~8 in straight chain saturated or unsaturated aliphatic hydrocarbon group; Q ² is formula -CO-O0, -0-CO-, CH 2 CH 2 -, -CH = CH-, -OCH 2 -, -SCH 2 - - CH ₂ O— or —CH ₂ S— is a group; R ^1a , R ^2a , R ^3a and R ^4a are the same or different and each is a hydrogen atom, a halogen atom, a lower alkyl group, a hydroxyl group or a lower alkoxy group R ⁵ R ⁶ and R ⁷ are the same or different and each is a hydrogen atom or a lower alkyl group] A compound according to claim 1 which is a compound of formula (I-a): [Wherein,AndAre the same or different and each is an aryl group or heteroaromatic ring group; A may have a substituent (s) selected from the group consisting of lower alkyl groups, hydroxyl groups, lower alkoxy groups, carboxyl groups, aryl groups and aralkyl groups₃To₈Q is a single bond or a formula -CO-O-, -O-CO-, -CH₂CH₂-, -CH = CH-, -OCH₂-, -SCH₂--CH₂O- or -CH₂Is a group of S-;^One, R², R³And R⁴Are the same or different and each is an aryl which may have a substituent (s) selected from the group consisting of a hydrogen atom, a halogen atom, a lower alkyl group, a hydroxyl group, a lower alkoxy group, or a halogen atom, a lower alkyl group and a lower alkoxy group Heteroaromatic ring group; R^7aIs Lower alkyl group; R⁸Is a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group or an aralkyl group; provided that when Q is a single bond, Is not 4-chlorophenyl group at the same time] The compound according to claim 4, which is a compound of Formula (Ia ¹ ) or Formula (Ia ² ); [Wherein,AndAre the same or different and each is an aryl group or heteroaromatic ring group; A may have a substituent (s) selected from the group consisting of lower alkyl groups, hydroxyl groups, lower alkoxy groups, carboxyl groups, aryl groups and aralkyl groups₃To₈Q is a single bond or a formula -CO-O-, -O-CO-, -CH₂CH₂-, -CH = CH-, -OCH₂-, -SCH₂--CH₂O- or -CH₂Is a group of S-;^One, R², R³And R⁴Are the same or different and each is an aryl which may have a substituent (s) selected from the group consisting of a hydrogen atom, a halogen atom, a lower alkyl group, a hydroxyl group, a lower alkoxy group, or a halogen atom, a lower alkyl group and a lower alkoxy group Heteroaromatic ring group; R^7aIs Lower alkyl group; R⁸Is a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group or an aralkyl group; provided that when Q is a single bond, Is not 4-chlorophenyl group at the same time] [Wherein, A, Q, R ¹ , R ² , R ³ , R ⁴ , R ^7a , and R ⁸ are as defined above] The compound according to claim 4, which is a compound of the following formula (I-b). [Wherein, And Are the same or different and each is an aryl group or heteroaromatic ring group; A ^a is a formula-(CH ₂ ) _m -C (R ⁹ ) (R ¹⁰ )-(CH ₂ ) _n- (wherein R ⁹ is A hydrogen atom, a lower alkyl group, a hydroxyl group or a lower alkoxy group; R ¹⁰ is a hydrogen atom, a lower alkyl group, an aryl group, an aralkyl group or a carboxyl group; m is an integer of 1 to 3; n is an integer of 1 to 4 ) Or a group of the formula-(CH ₂ ) _q -CH = CH- (where q is an integer from 1 to 6); Q is a single bond or a formula -CO-O-, -O-CO-, _{-CH 2 CH 2 -, -CH =} CH, -OCH 2 -, -SCH 2, -CH 2 O- or a group of ^{_{-CH 2 S-; R 1, R}} 2, R 3 and R ⁴ are the same or Aryl or heteroaromatic ring groups which may be different and each may have a substituent (s) selected from the group consisting of a hydrogen atom, a halogen atom, a lower alkyl group, a hydroxyl group, a lower alkoxy group or a halogen atom, a lower alkyl group and a lower alkoxy group R ^7a is a lower alkyl group; R ⁸ is a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group or an aralkyl group; provided that when Q is a single bond Is not 4-chlorophenyl group at the same time] The compound of claim 6, wherein R ⁹ is a hydrogen atom or a hydroxyl group. The compound of claim 6, wherein R ¹⁰ is a lower alkyl group, a lower alkoxy group, or a carboxyl group. The compound of claim 6, wherein m and n are the same or different and each is 1 or 2. 7. The compound of claim 6, wherein q is 1 or 2. The formula according to claim 1, wherein The group of which is a group of the following formula: [Wherein, R ^1b and R ^2b are the same or different and each represents a substituent (s) selected from the group consisting of a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, or a halogen atom, a lower alkyl group and a lower alkoxy group Aryl or heteroaromatic ring group which may have The formula according to claim 11, wherein Of the formula Wherein R ^1c and R ^2c are the same or different and each is a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group. The formula according to claim 1, wherein This group is a compound of the formula: [Wherein, R ^3b is a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group; R ^4b is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, or a halogen atom, a lower alkyl group and a lower alkoxy group An aryl or heteroaromatic ring group which may have the substituent (s) selected] The method of claim 1 wherein, Q is formula -CO-O -, - O- CO-, -CH 2 CH 2 -, -CH = CH-, -OCH 2 -, -SCH 2 -, CH 2 O- or - A group of CH ₂ S-, Of the formula Wherein R ^3b and R ^4c are the same or different and each is a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group. A compound according to claim 1, wherein R ⁸ is a hydrogen atom, a lower alkyl group or an aralkyl group. The compound of claim 1, wherein R ⁸ is a hydrogen atom or a lower alkyl group. The compound of claim 1, wherein when Q is a single bond, R ⁸ is an aralkyl group. The compound of formula (II) is reacted with a carboxylic acid of formula (III) or a reactive derivative thereof to form a compound of formula (IV), wherein the protecting group is removed if necessary, wherein formula (I) Process for the preparation of compounds of or pharmaceutically acceptable salts or esters thereof: [Wherein,AndAre the same or different and each is an aryl group or heteroaromatic ring group; A is C, which may have a substituent (s) selected from the group consisting of lower alkyl group, hydroxyl group, lower alkoxy group, carboxyl group, aryl group and aralkyl group₃To₈Q is a single bond or a formula -CO-O-, -0-CO-, -CH₂CH₂-, -CH = CH-, -OCH₂-, -SCH₂--CH₂O- or -CH₂Is a group of S-;^One, R², R³And R⁴Are the same or different and each is an aryl which may have a substituent (s) selected from the group consisting of a hydrogen atom, a halogen atom, a lower alkyl group, a hydroxyl group, a lower alkoxy group, or a halogen atom, a lower alkyl group and a lower alkoxy group Heteroaromatic ring group; R⁵, R⁶And R⁷silver The same or different, each being a hydrogen atom or a lower alkyl group; R⁸Is a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group or an aralkyl group; provided that when Q is a single bond, Is not 4-chlorophenyl group at the same time] [Wherein, Q, R ⁵ , R ⁶ , R ⁷ and R ⁸ are as defined above; R ^1p , R ^2p , R ^3p and R ^4p are the same or different and each may be hydrogen atom, halogen atom, lower alkyl group, protected An aryl or heteroaromatic ring group which may have a substituent (s) selected from the group consisting of a hydroxyl group, a lower alkoxy group, or a halogen atom, a lower alkyl group and a lower alkoxy group; and when Q is a single bond, Is not 4-chlorophenyl group at the same time] [Wherein, A ^p is a lower alkyl group, a lower alkoxy group, an aryl group, an aralkyl group, and may be protected with hydroxyl and by optionally having substituent (s) selected from the group consisting of carboxyl group C ₃ ~ ₈ saturated linear or in that Unsaturated aliphatic hydrocarbon group; R ¹¹ is hydrogen atom or carboxyl-protecting group] [WhereinA^p, Q, R^1p, R^2p, R^3p, R^4p, R⁵, R⁶, R⁷, R⁸And R¹¹Is as defined above] A compound of formula (II ′) [Wherein, (Wherein R ^1c and R ^2c are the same or different and each is a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group) or a naphthyl group; Wherein R ^3b is a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group; R ^4b is selected from the group consisting of a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, or a halogen atom, a lower alkyl group and a lower alkoxy group Is an aryl or heteroaromatic ring group which may have substituent (s) provided that when Q is a single bond, R ^4b may have a substituent (s) selected from the group consisting of halogen atoms, lower alkyl groups and lower alkoxy groups Is an aryl or heteroaromatic ring group; Q is a single bond or a formula -CO-O-, -O-CO-, -CH ₂ CH _2- , -CH = CH-, -OCH _2- , -SCH _{Is a group of 2-} , CH ₂ O- or -CH ₂ S-; R ^7a is a lower alkyl group; R ₈ is a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group or an aralkyl group. A compound of formula (III-b ¹ ) or formula (III-b ² ): [Wherein R ¹² and R ¹³ are the same or different and each is a carboxyl-protecting group] [Wherein, R ¹² and R ¹³ are as defined above] Treating and / or treating hypercholesterolemia, hyperlipidemia, or atherosclerosis, which comprises an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or ester thereof, and a pharmaceutically acceptable carrier or diluent Prevention: [Wherein,AndAre the same or different and each is an aryl group or heteroaromatic ring group; A is C, which may have a substituent (s) selected from the group consisting of lower alkyl group, hydroxyl group, lower alkoxy group, carboxyl group, aryl group and aralkyl group₃To₈Q is a single bond or a formula -CO-O-, -O-CO-, -CH₂CH₂-, -CH = CH-, -OCH₂-, -SCH₂--CH₂O- or -CH₂Is a group of S-;^One, R², R³And R⁴Are the same or different and each is an aryl which may have a substituent (s) selected from the group consisting of a hydrogen atom, a halogen atom, a lower alkyl group, a hydroxyl group, a lower alkoxy group, or a halogen atom, a lower alkyl group and a lower alkoxy group Heteroaromatic ring group; R⁵, R⁶And R⁷silver The same or different, each being a hydrogen atom or a lower alkyl group; R⁸Is a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group or an aralkyl group; provided that when Q is a single bond, Is not 4-chlorophenyl group at the same time] A therapeutic and / or prophylactic agent for fungal infection diseases, characterized by containing an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or ester thereof and a pharmaceutically acceptable carrier or diluent: [Wherein,AndAre the same or different and each is an aryl group or heteroaromatic ring group; A is C, which may have a substituent (s) selected from the group consisting of lower alkyl group, hydroxyl group, lower alkoxy group, carboxyl group, aryl group and aralkyl group₃To₈Is a linear or unsaturated aliphatic hydrocarbon group; Q is a single bond or a formula -CO-0-, -O-CO-, -CH₂CH₂-, -CH = CH-, -OCH₂-, -SCH₂--CH₂O- or -CH₂Is a group of S-;^One, R², R³And R⁴Are the same or different and each is an aryl which may have a substituent (s) selected from the group consisting of a hydrogen atom, a halogen atom, a lower alkyl group, a hydroxyl group, a lower alkoxy group, or a halogen atom, a lower alkyl group and a lower alkoxy group Heteroaromatic ring group; R⁵R⁶And R⁷silver The same or different, each being a hydrogen atom or a lower alkyl group; R⁸Is a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group or an aralkyl group; provided that when Q is a single bond, Is not a 4-chlorophenyl group] ※ Note: The disclosure is based on the initial application.