Alkylene derivatives

Patent metadata

Field	Value
Publication number	US-10150728-B2
Application number	US-201415029031-A
Country	US
Kind code	B2
Filing date	Oct 17, 2014
Priority date	Oct 17, 2013
Publication date	Dec 11, 2018
Grant date	Dec 11, 2018

Abstract

The object of the present invention is to provide novel compounds having ACC2 inhibiting activity. In addition, the object of the present invention is to provide a pharmaceutical composition comprising the compound.
A compound of formula (I):

wherein R 1 is substituted or unsubstituted fused aromatic heterocyclyl etc.,

ring A is substituted or unsubstituted non-aromatic carbocycle etc.,
-L 1 - is —O—(CR 6 R 7 )m- etc.,
-L 2 - is —O—(CR 6 R 7 )n- etc.,
each R 6 and R 7 are independently hydrogen, halogen etc.,
R 2 is substituted or unsubstituted alkyl,
R 3 is hydrogen or substituted or unsubstituted alkyl,
R 4 is substituted or unsubstituted alkylcarbonyl etc.

First claim

The invention claimed is:

1. A compound of Formula (I):

or its pharmaceutically acceptable salt,
wherein
R 1 is substituted or unsubstituted benzoxazole, substituted or unsubstituted benzothiazole, substituted or unsubstituted phenyl, substituted or unsubstituted 1H-imidazo[4,5-c]pyridine, substituted or unsubstituted benzimidazole, substituted or unsubstituted quinazoline, substituted or unsubstituted indazole, substituted or unsubstituted 1H-imidazo[4,5-b]pyridine, substituted or unsubstituted thiazolo[4,5-c]pyridine, substituted or unsubstituted oxazolo[4,5-c]pyridine, substituted or unsubstituted 2,6-naphthyridine, or substituted or unsubstituted thiazolo[5,4-b]pyridine,
ring A is substituted or unsubstituted cyclohexane, substituted or unsubstituted cyclobutane, substituted or unsubstituted tetrahydropyran, or substituted or unsubstituted 1,3-dioxane,
-L 1 - is —O—(CR 6 R 7 )m-,
-L 2 - is —O—(CR 6 R 7 )n-, —(CR 6 R 7 )n- or —C(═O)—(CR 6 R 7 )n-,
each R 6 is independently hydrogen, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl or substituted or unsubstituted alkynyl,
each R 7 is independently hydrogen, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl or substituted or unsubstituted alkynyl,
or R 6 and R 7 on the same carbon atom may be taken together with the carbon atom to form a ring,
or R 2 is taken together with either R 6 or R 7 to form a ring,
each m is independently an integer of 0, 1, 2 or 3,
each n is independently an integer of 1, 2 or 3,
R 2 is substituted or unsubstituted alkyl,
R 3 is hydrogen or substituted or unsubstituted alkyl, and
R 4 is substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, or substituted or unsubstituted carbamoyl.

2. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein ring A is substituted or unsubstituted cyclobutane, substituted or unsubstituted cyclohexane, or substituted or unsubstituted 1,3-dioxane.

3. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein R 1 is substituted or unsubstituted benzoxazole, or substituted or unsubstituted benzothiazole.

4. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein R 1 is substituted or unsubstituted benzothiazole, substituted or unsubstituted benzoxazole, substituted or unsubstituted benzoimidazole, substituted or unsubstituted indazole, or substituted or unsubstituted quinazoline.

5. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein R 4 is substituted or unsubstituted alkylcarbonyl.

6. The compound or its pharmaceutically acceptable salt according to claim 5 , wherein R 4 is methylcarbonyl.

7. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein R 4 is substituted or unsubstituted carbamoyl.

8. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein m is 0.

9. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein -L 2 - is —O—(CR 6 R 7 )n-.

10. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein n is 1.

11. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein -L 2 - is —O—(CR 6 7 )—, and R 2 is taken together with either R 6 or R 7 to form ring.

12. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein -L 1 - is —O—(CR 6 R 7 )m-, and -L 2 - is —O—(CR 6 R 7 )n- or —(CR 6 R 7 )n-.

13. A pharmaceutical composition, which comprises the compound or its pharmaceutically acceptable salt according to claim 1 , and a pharmaceutically acceptable additive.

14. A method for treatment of obesity and/or diabetes comprising administering an effective amount of the compound or its pharmaceutically acceptable salt according to claim 1 to a patient in need thereof.

15. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein ring A is substituted or unsubstituted 1,3-dioxane.

16. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein R 1 is substituted or unsubstituted benzimidazole.

17. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein R 1 is substituted or unsubstituted benzimidazole; ring A is substituted or unsubstituted 1,3-dioxane; and m is 0.

18. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein R 1 is substituted benzimidazole.

19. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein R 6 and R 7 are hydrogen.

Assignees

• Shionogi & Co

Inventors

• Kobayashi Naotake
• Asahi Kentarou
• Tomida Yutaka
• Ohdan Masahide
• Fumoto Masataka
• Sasaki Yoshikazu
• Kurahashi Kana
• Inoue Takatsugu
• Urabe Tomomi
• Nishiura Yuji
• Iwatsu Masafumi
• Miyazaki Keisuke
• Ohyabu Naoki
• Wada Toshihiro
• Katou Manabu

Classifications

• A61P43/00

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

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• C07D261/20

  condensed with carbocyclic rings or ring systems · CPC title

• C07D277/20

  having two or three double bonds between ring members or between ring members and non-ring members · CPC title