Tricyclic compound

Patent metadata

Field	Value
Publication number	US-9475805-B2
Application number	US-201514721680-A
Country	US
Kind code	B2
Filing date	May 26, 2015
Priority date	Aug 6, 2008
Publication date	Oct 25, 2016
Grant date	Oct 25, 2016

Abstract

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:

First claim

The invention claimed is:

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 1

Assignees

• Kyowa Hakko Kirin Co Ltd

Inventors

• Yanagisawa Arata
• Uehara Keiji
• Matsubara Masahiro
• Ueno Kimihisa
• Suzuki Michihiko
• Kuboyama Takeshi
• Yamamoto Keisuke
• Tamura Tomohiro

Classifications

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title