Tricyclic compound
The invention provides a method of activating PPAR γ and a method of treating or preventing a disease associated with PPAR γ by administering a tricyclic compound having a PPAR γ agonist activity, which is represented by the formula (I) wherein Z represents a single bond or the like, Y represents a hydrogen atom, lower alkyl optionally having substituent(s) or the like, X represents a hydrogen atom or the like, A represents aryl or the like, B and C are the same or different and each represents an aromatic carbocycle or the like, R 4 -R 9 are the same or different and each represents hydrogen or the like, V represents a single bond or the like, R 10 and R 11 are the same or different and each represents hydrogen or the like, or a pharmaceutically acceptable salt thereof or the like:
1. A tricyclic compound of formula (I)
wherein
represents the following formula c7
wherein
R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 , are the same or different and each is a hydrogen atom, halogen, hydroxy, lower alkoxy, or lower alkyl,
X B represents the following groups
wherein R B-3 is lower alkyl optionally having substituent(s) or aryl optionally having substituent(s),
A represents the following formula
wherein R C is a hydrogen atom, halogen, nitro, cyano, formyl, oxo, hydroxy, lower alkoxy optionally having substituent(s), lower alkanoyloxy optionally having substituent(s), lower alkyl optionally having substituent(s), lower alkenyl optionally having substituent(s), lower alkanoyl optionally having substituent(s), lower alkoxycarbonyl optionally having substituent(s), lower alkylsulfonylamino optionally having substituent(s), —NR F R G wherein R F and R G are the same or different and each is a hydrogen atom, lower alkyl optionally having substituent(s), lower alkanoyl optionally having substituent(s) or lower alkoxycarbonyl optionally having substituent(s), or R F and R G form, each together with the adjacent nitrogen atom, a nitrogen-containing heterocyclic group optionally having substituent(s), —CONR H R I wherein R H and R I are the same or different and each is a hydrogen atom, lower alkyl optionally having substituent(s), lower alkanoyl optionally having substituent(s) or lower alkoxycarbonyl optionally having substituent(s), or R H and R I , form, together with the adjacent nitrogen atom, a nitrogen-containing heterocyclic group optionally having substituent(s), aryl optionally having substituent(s), cycloalkyl optionally having substituent(s), an aromatic heterocyclic group optionally having substituent(s) or an aliphatic heterocyclic group optionally having substituent(s), R 1-2 is lower alkyl optionally having substituent(s), cycloalkyl optionally having substituent(s) or lower alkoxy optionally having substituent(s), R J is aryl optionally having substituent(s), an aromatic heterocyclic group optionally having substituent(s) (except benzimidazolyl group) or an aliphatic heterocyclic group optionally having substituent(s),
V represents a single bond, and
R 10 and R 11 are the same or different and each is a hydrogen atom or lower alkyl,
or a pharmaceutically acceptable salt thereof.
2. The tricyclic compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein
represents the following formula c17
wherein
R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are each as defined in claim 1 ,
X C is represented by the following group (b20)
and
R 1-2 is lower alkyl optionally having substituent(s) other than hydroxy.
3. The tricyclic compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein
is the following formula c19
wherein X E is the following group (b19)
R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are each as defined in claim 1 ,
R 1-2 is lower alkyl, and
R J is phenyl optionally having a fluorine atom as a substituent, thienyl, oxazolyl, oxadiazolyl or 5-methyloxazol-2-yl.
4. The tricyclic compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein
X B is the following formula (b20)
and
R 1-2 is lower alkyl.
5. A tricyclic compound of formula (I)
wherein
is a group selected from the group consisting of the following formula c4
wherein
R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are the same or different and each is a hydrogen atom, halogen, hydroxy, lower alkoxy, or lower alkyl,
X A represents any of the following formulas
wherein R B-1 is lower alkyl optionally having substituent(s) or cycloalkyl optionally having substituent(s), R B-2 is cycloalkyl optionally having substituent(s), R B is a hydrogen atom, lower alkyl optionally having substituent(s) or cycloalkyl optionally having substituent(s), and the broken line is absent or a single bond,
A represents the following formula
wherein R C is a hydrogen atom, halogen, nitro, cyano, formyl, oxo, hydroxy, lower alkoxy optionally having substituent(s), lower alkanoyloxy optionally having substituent(s), lower alkyl optionally having substituent(s), lower alkenyl optionally having substituent(s), lower alkanoyl optionally having substituent(s), lower alkoxycarbonyl optionally having substituent(s), lower alkylsulfonylamino optionally having substituent(s), —NR F R G wherein R F and R G are the same or different and each is a hydrogen atom, lower alkyl optionally having substituent(s), lower alkanoyl optionally having substituent(s) or lower alkoxycarbonyl optionally having substituent(s), or R F and R G form, each together with the adjacent nitrogen atom, a nitrogen-containing heterocyclic group optionally having substituent(s), —CONR H R I wherein R H and R I are the same or different and each is a hydrogen atom, lower alkyl optionally having substituent(s), lower alkanoyl optionally having substituent(s) or lower alkoxycarbonyl optionally having substituent(s), or R H and R I , form, together with the adjacent nitrogen atom, a nitrogen-containing heterocyclic group optionally having substituent(s), aryl optionally having substituent(s), cycloalkyl optionally having substituent(s), an aromatic heterocyclic group optionally having substituent(s) or an aliphatic heterocyclic group optionally having substituent(s), R 1-2 is lower alkyl optionally having substituent(s), cycloalkyl optionally having substituent(s) or lower alkoxy optionally having substituent(s), R J is aryl optionally having substituent(s), an aromatic heterocyclic group optionally having substituent(s) (except benzimidazolyl group) or an aliphatic heterocyclic group optionally having substituent(s),
V represents a single bond, and
R 10 and R 11 are the same or different and each is a hydrogen atom or lower alkyl,
or a pharmaceutically acceptable salt thereof.
6. A pharmaceutical composition comprising the tricyclic compound or the pharmaceutically acceptable salt thereof according to claim 1 , as an active ingredient.
7. A pharmaceutical composition comprising the tricyclic compound or the pharmaceutically acceptable salt thereof according to claim 5 , as an active ingredient.