9-membered fused ring derivative

Patent metadata

Field	Value
Publication number	US-10233156-B2
Application number	US-201615557992-A
Country	US
Kind code	B2
Filing date	Mar 30, 2016
Priority date	Mar 30, 2015
Publication date	Mar 19, 2019
Grant date	Mar 19, 2019

Abstract

The purpose of the present invention is to provide novel compounds having ACC2 selective inhibitory activity. In addition, the present invention provides a pharmaceutical composition comprising the compound.
A compound of Formula:

or its pharmaceutically acceptable salt,
wherein, R 1 is substituted or unsubstituted fused aromatic heterocyclyl represented by Formula:

wherein,
ring B is 5-membered ring, ring C is 6-membered ring;

ring A is substituted or unsubstituted non-aromatic carbocycle or the like;
—L 1 — is —O—(CR 6 R 7 )m— or the like;
—L 2 — is —O—(CR 6 R 7 )n— or the like;
each R 6 is independently hydrogen or the like;
each R 7 is independently hydrogen or the like;
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;
R 4 is substituted or unsubstituted alkylcarbonyl or the like.

First claim

The invention claimed is:

1. A compound of Formula (I):

or its pharmaceutically acceptable salt,
wherein
R 1 is substituted or unsubstituted benzimidazol;
ring A is substituted or unsubstituted non-aromatic heterocycle;
—L 1 — is —O—(CR 6 R 7 )m—, wherein the bond of left side is attached to R 1 , and the bond of right side is attached to ring A;
—L 2 — is (CR 6 R 7 )n—, wherein the bond of left side is attached to ring A, and the bond of right side is attached to the group represented by Formula:

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;
R 6 and R 7 on the same carbon atom may be taken together with the carbon atom to form 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;
R 4 is substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl, substituted or unsubstituted non-aromatic carbocyclylcarbonyl, substituted or unsubstituted aromatic carbocyclylcarbonyl, substituted or unsubstituted non-aromatic heterocyclylcarbonyl, substituted or unsubstituted aromatic heterocyclylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted non-aromatic carbocyclyloxycarbonyl, substituted or unsubstituted aromatic carbocyclyloxycarbonyl, substituted or unsubstituted non-aromatic heterocyclyloxycarbonyl, substituted or unsubstituted aromatic heterocyclyloxycarbonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfonyl, substituted or unsubstituted non-aromatic carbocyclylsulfonyl, substituted or unsubstituted aromatic carbocyclylsulfonyl, substituted or unsubstituted non-aromatic heterocyclylsulfonyl, substituted or unsubstituted aromatic heterocyclylsulfonyl or substituted or unsubstituted sulfamoyl.

2. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein R 1 is the group represented by Formula:

wherein
X 1 is C(R x1 );
X 2 is C(R x2 );
X 3 is C(R x3 );
X 4 is C(R x4 );
X 5 is N(R x5 );
X 6 is N;
each R x1 , R x2 , R x3 , R x4 , and R x5 is independently hydrogen, halogen, hydroxy, carboxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfonyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic carbocyclylsulfonyl, substituted or unsubstituted aromatic carbocyclylsulfonyl, substituted or unsubstituted non-aromatic heterocyclylsulfonyl, substituted or unsubstituted aromatic heterocyclylsulfonyl, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, or substituted or unsubstituted aromatic heterocyclyloxy.

3. The compound or its pharmaceutically acceptable salt according to claim 2 , wherein R 1 is the group represented by Formula:

wherein R x1 , R x2 , R x3 , R x4 and R x5 are the same as in claim 2 .

4. The compound or its pharmaceutically acceptable salt according to claim 3 , wherein R x1 is hydrogen, halogen or cyano; R x2 is hydrogen, halogen or cyano; R x3 is substituted or unsubstituted alkyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy or substituted or unsubstituted aromatic heterocyclyloxy; R x4 is hydrogen, halogen or cyano, and R x5 is substituted or unsubstituted alkyl.

5. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein the group represented by the formula —L 1 — ring A—L 2 — is a group selected from the group consisting of:

and
wherein
R 9 is halogen, cyano, hydroxy, carboxy, oxo, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy or substituted or unsubstituted amino;
p is an integer of 0 to 4; and
—L 1 — and —L 2 — are as defined in claim 1 .

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

7. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein n is 2.

8. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein R 4 is substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkylsulfonyl or substituted or unsubstituted sulfamoyl.

9. The compound or its pharmaceutically acceptable salt according to claim 8 , wherein R 4 is substituted or unsubstituted alkylcarbonyl.

10. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein Formula (I) is Formula (I′):

wherein R 1 , L 1 , ring A, L 2 , R 2 , R 3 and R 4 are as defined in claim 1 .

11. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein Formula (I) is Formula (I″):

wherein R 1 , L 1 , ring A, L 2 , R 2 , R 3 and R 4 are as defined in claim 1 .

12. A compound of Formula (I):

or its pharmaceutically acceptable salt,
wherein
R 1 is a gr

Assignees

• Shionogi & Co

Inventors

• Ohyabu Naoki
• Kurahashi Kana
• Nishiura Yuji
• Katou Manabu
• Miyazaki Keisuke
• Sasaki Yoshikazu
• Wada Toshihiro
• Iwatsu Masafumi

Classifications

• C07D471/04

  Ortho-condensed systems · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P9/12

  Antihypertensives · CPC title