发明公开
EP2459548A1 DÉRIVÉS D'URÉE DE TETRAHYDROQUINOXALINE, LEUR PRÉPARATION ET LEUR APPLICATION EN THÉRAPEUTIQUE
有权
DÉRIVÉSD'URÉEDE TETRAHYDROQUINOXALINE，LEURPRÉPARATIONET LEUR APPLICATION ENTHÉRAPEUTIQUE
- 专利标题： DÉRIVÉS D'URÉE DE TETRAHYDROQUINOXALINE, LEUR PRÉPARATION ET LEUR APPLICATION EN THÉRAPEUTIQUE
- 专利标题（英）： Tetrahydroquinoxaline urea derivatives, preparation thereof, and therapeutic use thereof
- 专利标题（中）： DÉRIVÉSD'URÉEDE TETRAHYDROQUINOXALINE，LEURPRÉPARATIONET LEUR APPLICATION ENTHÉRAPEUTIQUE
-
申请号： EP10752089.2申请日： 2010-07-23
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公开(公告)号： EP2459548A1公开(公告)日： 2012-06-06
- 发明人: CRESPIN, Olivier , NICOLAI, Eric , VENIER, Olivier
- 申请人： SANOFI
- 申请人地址： 54 rue La Boétie 75008 Paris FR
- 专利权人： SANOFI
- 当前专利权人： SANOFI
- 当前专利权人地址： 54 rue La Boétie 75008 Paris FR
- 代理机构： Böhm, Brigitte
- 优先权： FR0903685 20090727
- 国际公布： WO2011012800 20110203
- 主分类号： C07D401/10
- IPC分类号： C07D401/10 ; C07D401/12 ; A61K31/495 ; A61P3/00
摘要：
The invention relates to compounds of formula (I), where: A is a bond, an oxygen atom, or an O-CH
2 - group; Ar
1 is a phenyl or heteroaryl group; Ar
2 is a phenyl, heteroaryl, or heterocycloalkyl group; R
1a,b,c and
R2a,b,c are a hydrogen or halogen atom, or an alkyl, cycloalkyl, or alkyl-cycloalkyl group optionally substituted by one or more halogen atoms, or an -OR
5 (hydroxy or alkoxy), hydroxy-alkyl, alkoxy-alkyl, alkoxy-alkoxy, halogenoalkyl, -O-halogenoalkyl, oxo, -CO-alkyl, -CO-alkyl-NR
6 R
7 , -CO-halogenoalkyl, -COOR
5 , alkyl-COOR
5 , -O-alkyl-COOR
5 , -SO
2 -alkyl, -SO
2 -cycloalkyl, -SO
2 -alkyl-cycloalkyl, -SO
2 -alkyl-OR
5 , -SO
2 -alkyl-COOR
5 , -SO
2 -alkyl-NR
6 R
7 , -SO
2 -halogenoalkyl, alkyl-SO
2 -alkyl, -SO
2 -NR
6 R
7 , -SO
2 -alkyl-O-alkyl-OR
5 , -CONR
6 R
7 , -alkyl-CONR
6 R
7 , or O-alkyl-NR
6 R
7 group, or further R
1a , R
1b , and R
1c are bonded to R
2a , R
2b , R
2c , respectively, as well as to the carbon atom having same, and are O-alkyl-O-; R
3 is a hydrogen atom or an alkyl group; R
4 is a CONR
6 R
7 group, a hydroxyalkyl group substituted by a halogenoalkyl group, or an alkyl-NH-SO
2 -alkyl, NH-SO
2 -alkyl, -O-SO
2 -NR
6 R
7 , -alkyl-CO-NR
6 R
7 , -O-alkyl-CO-NR
6 R
7 , -alkyl-NR
6 R
7 , -O-CO-NR
6 R
7 , -alkyl-heteroaryl, a heteroaryl group optionally substituted by an alkyl, alkoxy-imino, or CO-NH-NH-CO-alkyl group, with the proviso that R
4 is in the cis position when it is the CONR
6 R
7 group and that R
6 and R
7 are each hydrogen, or an alkyl or alkyl-phenyl group; R
5 is hydrogen, an alkyl group, or alkyl-phenyl; R
6 and R
7 , identical or different, are each a hydrogen atom, an alkyl group, alkoxy, or an alkyl-phenyl group; and R
8 is a hydrogen atom or an SO
2 -alkyl group, or a group of formula B-Het, where B can be absent or be a bond, an oxygen atom, or a CO- or SO
2 -(CH
2 )
n group, with n being equal to 0, 1, or 2, and where Het is a heteroaryl or heterocycloaryl optionally substituted by the alkyl, -SO
2 -alkyl, and -COOR
5 groups. The invention also relates to a method for preparing same to the therapeutic use thereof.
2 - group; Ar
1 is a phenyl or heteroaryl group; Ar
2 is a phenyl, heteroaryl, or heterocycloalkyl group; R
1a,b,c and
R2a,b,c are a hydrogen or halogen atom, or an alkyl, cycloalkyl, or alkyl-cycloalkyl group optionally substituted by one or more halogen atoms, or an -OR
5 (hydroxy or alkoxy), hydroxy-alkyl, alkoxy-alkyl, alkoxy-alkoxy, halogenoalkyl, -O-halogenoalkyl, oxo, -CO-alkyl, -CO-alkyl-NR
6 R
7 , -CO-halogenoalkyl, -COOR
5 , alkyl-COOR
5 , -O-alkyl-COOR
5 , -SO
2 -alkyl, -SO
2 -cycloalkyl, -SO
2 -alkyl-cycloalkyl, -SO
2 -alkyl-OR
5 , -SO
2 -alkyl-COOR
5 , -SO
2 -alkyl-NR
6 R
7 , -SO
2 -halogenoalkyl, alkyl-SO
2 -alkyl, -SO
2 -NR
6 R
7 , -SO
2 -alkyl-O-alkyl-OR
5 , -CONR
6 R
7 , -alkyl-CONR
6 R
7 , or O-alkyl-NR
6 R
7 group, or further R
1a , R
1b , and R
1c are bonded to R
2a , R
2b , R
2c , respectively, as well as to the carbon atom having same, and are O-alkyl-O-; R
3 is a hydrogen atom or an alkyl group; R
4 is a CONR
6 R
7 group, a hydroxyalkyl group substituted by a halogenoalkyl group, or an alkyl-NH-SO
2 -alkyl, NH-SO
2 -alkyl, -O-SO
2 -NR
6 R
7 , -alkyl-CO-NR
6 R
7 , -O-alkyl-CO-NR
6 R
7 , -alkyl-NR
6 R
7 , -O-CO-NR
6 R
7 , -alkyl-heteroaryl, a heteroaryl group optionally substituted by an alkyl, alkoxy-imino, or CO-NH-NH-CO-alkyl group, with the proviso that R
4 is in the cis position when it is the CONR
6 R
7 group and that R
6 and R
7 are each hydrogen, or an alkyl or alkyl-phenyl group; R
5 is hydrogen, an alkyl group, or alkyl-phenyl; R
6 and R
7 , identical or different, are each a hydrogen atom, an alkyl group, alkoxy, or an alkyl-phenyl group; and R
8 is a hydrogen atom or an SO
2 -alkyl group, or a group of formula B-Het, where B can be absent or be a bond, an oxygen atom, or a CO- or SO
2 -(CH
2 )
n group, with n being equal to 0, 1, or 2, and where Het is a heteroaryl or heterocycloaryl optionally substituted by the alkyl, -SO
2 -alkyl, and -COOR
5 groups. The invention also relates to a method for preparing same to the therapeutic use thereof.
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