Substituted N-sulfonylaminobenzyl-2-phenoxyacetamide compounds as VR1 receptor agonists
申请人:Inoue Tadashi
公开号:US20060100460A1
公开(公告)日:2006-05-11
This invention provides a compound of the formula (I):
wherein R
1
represents a (C
1
-C
6
)alkyl group; R
2
represents a hydrogen atom, a halogen atom, a hydroxy group, a (C
1
-C
6
) alkyl group or a (C
1
-C
6
) alkoxy group; R
3
, R
4
, R
5
and R
6
each independently represents a hydrogen atom, a (C
1
-C
6
) alkyl, or a halogen atom; R
7
represents a hydrogen atom, a halogen atom, a hydroxy group, a (C
1
-C
6
) alkyl group optionally substituted with a piperidino group, a (C-
1
-C
6
)alkoxy group optionally substituted with a 3-7 membered cycloalkyl ring, a hydroxy(C
1
-C
6
)alkoxy group, a (C
1
-C
6
)alkoxy-(C
1
-C
6
)alkyl group, a (C
1
-C
6
)alkoxy-(C
1
-C
6
)alkoxy group, a halo (C
1
-C
6
)alkyl group, a (C
1
-C
6
)alkylthio group, a (C
1
-C
6
)alkylsulfinyl group or a (C
1
-C
6
)alkylsulfonyl group; R
5
represents a (C
1
-C
6
)alkyl group, a halo(C
1
-C
6
)alkyl group, a (C
1
-C
6
)alkoxy group, a hydroxy(C
1
-C
6
)alkoxy group, a (C
1
-C
6
)alkoxy-(C
1
-C
6
)alkyl group or a (C
1
-C
6
)alkoxy-(C
1
-C
6
)alkoxy group; or R
7
and R
8
, when adjacent to each other, taken together with the carbon atoms to which they are attached form a 5-8 membered carbocyclic or heterocyclic ring, wherein the carbocyclic ring or the heterocyclic ring is unsubstituted or substituted with one or more substituents selected from the group consisting of a hydroxy group, a (C
1
-C
6
)alkyl group, a (C
1
-C
6
)alkoxy group and a hydroxy(C
1
-C
6
)alkyl group; and R
9
represents a hydrogen atom or a halogen atom; or a pharmaceutically acceptable salt or solvate thereof.
These compounds are useful for the treatment of disease conditions caused by overactivation of VR1 receptor, such as pain or the like in mammalian. The present invention also provides a pharmaceutical composition comprising the compound of formula (I).
本发明提供了式(I)的化合物:
其中,R1代表(C1-C6)烷基;R2代表氢原子、卤素原子、羟基、(C1-C6)烷基或(C1-C6)烷氧基;R3、R4、R5和R6各自独立地代表氢原子、(C1-C6)烷基或卤素原子;R7代表氢原子、卤素原子、羟基、(C1-C6)烷基(可选地被哌啶基取代)、(C-1-C6)烷氧基(可选地被3-7个成员的环烷基取代)、羟基(C1-C6)烷氧基、(C1-C6)烷氧基-(C1-C6)烷基、(C1-C6)烷氧基-(C1-C6)烷氧基、卤代(C1-C6)烷基、(C1-C6)烷基硫基、(C1-C6)烷基亚砜基或(C1-C6)烷基磺酰基;R8代表(C1-C6)烷基、卤代(C1-C6)烷基、(C1-C6)烷氧基、羟基(C1-C6)烷氧基、(C1-C6)烷氧基-(C1-C6)烷基或(C1-C6)烷氧基-(C1-C6)烷氧基;或当R7和R8相邻时,它们与它们所连接的碳原子一起形成一个5-8个成员的碳环或杂环,其中该碳环或杂环未被取代或被选自羟基、(C1-C6)烷基、(C1-C6)烷氧基和羟基(C1-C6)烷基的一个或多个取代基取代;R9代表氢原子或卤素原子;或其药学上可接受的盐或溶剂。这些化合物对于治疗由VR1受体过度激活引起的疾病状况,如哺乳动物中的疼痛或类似症状,是有用的。本发明还提供了一种包含式(I)化合物的制药组合物。