Tricyclic compound and use thereof

Patent metadata

Field	Value
Publication number	US-9643946-B2
Application number	US-201414771049-A
Country	US
Kind code	B2
Filing date	Feb 28, 2014
Priority date	Feb 28, 2013
Publication date	May 9, 2017
Grant date	May 9, 2017

Abstract

The present invention relates to: a compound selected from the group consisting of a tricyclic compound having the structure of formula I, a pharmaceutically acceptable salt, an isomer, a solvate and a precursor thereof; and a use thereof. The compound effectively controls GPR40, and thus, can be effectively used for the prophylaxis or treatment of diseases associated with GPR40, for example, diabetes and many other diseases.

First claim

What is claimed is:

1. A compound selected from the group consisting of a tricyclic compound of Formula I, and a pharmaceutically acceptable salt, isomer, and solvate thereof:

wherein
V and W are each independently ═C(R 14 )—, or ═N—;
X is —CH 2 —, —O—, —O—CH 2 —O—, —S—, —C(═O)—, —S(═O)—, —S(═O) 2 —, or —NR 15 —;
Y is a C 1-6 alkylene;
Z is —O—, —S—, —C(═O)—, —S(═O)—, —S(═O) 2 —, or —NR 15 —;
Ar is one of the following substituents (a) to (c),

wherein A is —CH 2 —, —CF 2 —, —O—, —NR 15 —, —S—, —S(═O)—, —S(═O) 2 —, —C(═O)—, or —CH(OR 15 )—;
B is a C 1-3 alkylene;
R 1 is hydrogen, a halogen, hydroxy, amino, nitro, cyano, a C 1-6 alkyl, a C 1-10 alkoxy, a C 1-6 alkylthio, acyl, a C 1-6 alkylsulfonyloxy, a C 3-12 carbocyclyl, a C 3-12 carbocyclyloxy, a C 3-12 carbocyclylsulfonyloxy, a 5- to 14-membered heterocyclyl, a 5- to 14-membered heterocyclyloxy, or a 5- to 14-membered heterocyclylsulfonyloxy;
R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are each independently hydrogen, a halogen, amino, cyano, a C 1-6 alkyl, a C 1-6 alkoxy, a C 1-6 alkylthio, acyl, a C 3-12 carbocyclyl, or a 5- to 14-membered heterocyclyl;
R 8 is hydrogen, a halogen, hydroxy, amino, nitro, cyano, a C 1-6 alkyl, a C 1-6 alkoxy, or a C 1-6 alkylthio;
R 9 and R 10 are each independently hydrogen, a halogen, hydroxy, a C 1-6 alkyl, or a C 1-6 alkoxy;
R 11 is hydroxy, amino, or a C 1-6 alkoxy;
R 12 is hydrogen, a C 1-6 alkyl, a C 2-6 akenyl, a C 2-6 alkynyl, a C 1-6 alkoxy, a C 1-6 alkoxy-C 1-6 alkyl, a C 3-12 carbocyclyl, or a 5- to 14-membered heterocyclyl;
R 13 is hydrogen, or a C 1-6 alkyl;
R 14 is hydrogen, a halogen, amino, —CF 3 , nitro, cyano, a C 1-6 alkyl, a C 1-6 alkoxy, a C 1-6 alkylthio, acyl, a C 3-12 carbocyclyl, or a 5- to 14-membered heterocyclyl;
R 15 is hydrogen, or a C 1-6 alkyl; and
n, o, and p are each independently 0, 1, 2, or 3;
provided that the alkylene, the alkyl, the akenyl, the alkynyl, the alkoxy, the alkylthio, the amino, the acyl, the alkylsulfonyloxy, the carbocyclyl, the carbocyclyloxy, the carbocyclylsulfonyloxy, the heterocyclyl, the heterocyclyloxy, and the heterocyclylsulfonyloxy may each independently be substituted with at least one substituent selected from the group consisting of a 4- to 7-membered heterocyclyl (unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of hydroxy, a halogenated C 1-6 alkyl, and a C 1-6 alkoxy-carbonyl), a C 3-8 cycloalkyl, hydroxy, a C 1-6 alkoxy, a halogenated C 1-6 alkoxy, amino, a mono- or di-C 1-6 alkyl-amino, an N—C 1-6 alkyl-N—C 1-6 alkyl-carbonyl-amino, a C 7-16 aralkyloxy, a C 1-6 alkylthio, a C 1-6 alkylsulfinyl, a C 1-6 alkylsulfonyl, and a mono- or di-C 1-6 alkyl-phosphono; and
the heterocyclyl contains 1 to 4 heteroelements selected from the group consisting of N, O, S, S(═O), and S(═O) 2 .

2. The compound of claim 1 ,
wherein
V and W are each independently ═C(R 14 )—, or ═N—;
X is —CH 2 —, —O—, —O—CH 2 —O—, —S—, or —NR 15 —;
Y is a C 1-3 alkylene;
Z is —O—, —S—, or —NR 15 —, provided that Z is substituted at the 2 nd or 3 rd carbon atom of Ar;
Ar is one of the substituents (a) to (c);
A is —CH 2 —, —CF 2 —, —O—, or —NR 15 —;
B is a C 1-2 alkylene;
R 1 is hydrogen, a halogen, hydroxy, amino, nitro, cyano, a C 1-6 alkyl, a C 1-10 alkoxy, a C 1-6 alkylthio, acyl, a C 1-6 alkylsulfonyloxy, a C 3-12 carbocyclyl, a C 3-12 carbocyclyloxy, a C 3-12 carbocyclylsulfonyloxy, a 5- to 14-membered heterocyclyl, a 5- to 14-membered heterocyclyloxy, or a 5- to 14-membered heterocyclylsulfonyloxy;
R 2 is hydrogen, a halogen, amino, cyano, a C 1-6 alkyl, a C 1-6 alkoxy, a C 1-6 alkylthio, a C 3-12 carbocyclyl, or a 5- to 14-membered heterocyclyl;
R 3 , R 4 , R 5 , and R 6 are each independently hydrogen, a halogen, amino, a C 1-6 alkyl, or a C 1-6 alkoxy;
R 7 is hydrogen, a halogen, amino, cyano, a C 1-6 alkyl, a C 1-6 alkoxy, a C 1-6 alkylthio, a C 3-12 carbocyclyl, or a 5- to 14-membered heterocyclyl;
R 8 is hydrogen, a halogen, amino, a C 1-6 alkyl, or a C 1-6 alkoxy;
R 9 and R 10 are each independently hydrogen, a halogen, hydroxy, a C 1-6 alkyl, or a C 1-6 alkoxy;
R 11 is hydroxy, or a C 1-6 alkoxy;
R 12 is hydrogen, a C 1-6 alkyl, a C 2-6 akenyl, a C 2-6 alkynyl, a C 1-6 alkoxy, a C 1-6 alkoxy-C 1-6 alkyl, a C 3-12 carbocyclyl, or a 5- to 14-membered heterocyclyl;
R 13 is hydrogen, or a C 1-6 alkyl;
R 14 is hydrogen, a halogen, amino, —CF 3 , a C 1-6 alkyl, a C 1-6 alkoxy, acyl, a C 3-12 carbocyclyl, or a 5- to 14-membered heterocyclyl;
R 15 is hydrogen, or a C 1-6 alkyl; and
n, o, and p are each independently 0, 1, or 2;
provided that the alkylene, the alkyl, the alkynyl, the alkoxy, the alkylthio, the amino, the acyl, the alkylsulfonyloxy, the carbocyclyl, the carbocyclyloxy, the carbocyclylsulfonyloxy, the heterocyclyl, and the heterocyclyloxy may each independently substituted with at least one substituent selected from the group consisting of a 4- to 7-membered heterocyclyl (unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of hydroxy, a halogenated C 1-6 alkyl, and a C 1-6 alkoxy-carbonyl), a C 3-8 cycloalkyl, hydroxy, a C 1-6 alkoxy, a halogenated C 1-6 alkoxy, amino, a mono- or di-C 1-6 alkyl-amino, an N—C 1-6 alkyl-N—C 1-6 alkyl-carbonyl-amino, a C 7-16 aralkyloxy, a C 1-6 alkylthio, a C 1-6 alkylsulfinyl, a C 1-6 alkylsulfonyl, and a mono- or di-C 1-6 alkyl-phosphono; and
the heterocyclyl contains 1 to 4 heteroelements selected from the group consisting of N, O, S, S(═O), and S(═O) 2 .

3. The compound of claim 1 ,
wherein
V and W are each independently ═C(R 14 )—, or ═N—;
X is —CH 2 —, —O—CH 2 —O—, —O—, —S—, or —NR 15 —;
Y is a C 1-3 alkylene;
Z is —O—, —S—, or —NR 15 —, provided that Z is substituted at the 2 nd or 3 rd carbon atom of Ar;
Ar is one of the substituents (a) to (c);
A is —CH 2 —, —CF 2 —, —O—, or —NR 15 —;
B is a C 1-2 alkylene;
R 1 is hydrogen, a halogen, hydroxy, amino, a C 1-6 alkyl, a C 1-10 alkoxy, acyl, a C 1-6 alkylsulfonyloxy, a C 3-12 carbocyclyloxy, a 5- to 14-membered heterocyclyl, or a 5- to 14-membered heterocyclyloxy;
R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 are each independently hydrogen, a halogen, amino, a C 1-6 alkyl, or a C 1-6 alkoxy;
R 9 and R 10 are each independently hydrogen, or a halogen;
R 11 is hydroxy, or a C 1-6 alkoxy;
R 12 is hydrogen, a C 1-6 alkyl, a C 2-6 akenyl, a C 2-6 alkynyl, a C 1-6 alkoxy, a C 1-6 alkoxy-C 1-6 alkyl, a C 3-12 carbocyclyl, or a 5- to 14-membered heterocyclyl;
R 13 is hydrogen;
R 14 is hydrogen, a halogen, amino, a C 1-6 alkyl, a C 1-6 alkoxy, or acyl;
R 15 is hydrogen, methyl, ethyl, or isopropyl; and
n, o, and p are each independently 0, 1, or 2;
provided that the alkylene, the alkyl, the alkynyl, the alkoxy, the amino, the acyl, the alkylsulfonyloxy, the carbocyclyloxy, the heterocyclyl, and the heterocyclyloxy may each independently be substituted with at least one substituent selected from the group consisting of a 4- to 7-membered heterocyclyl (unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of hydroxy, a halogenated C 1-6 alkyl, and a C 1-6 alkoxy-carbonyl), a C 3-8 cycloalkyl, hydroxy, a C 1-6 alkoxy, a halogenated C 1-6 alkoxy, amino, a mono- or di-C 1-6 alkyl-amino, an N—C 1-6 alkyl-N—C 1-6 alkyl-carbonyl-amino, a C 7-16 aralky

Assignees

• Sk Chemicals Co Ltd

Inventors

• Lee Ju Young
• Lee Jeong A
• Ahn Jaeseung
• Ryu Je Ho
• Han Min-Young
• Yoo Taekyung
• Sa Joon Ho
• Kim Jae-Sun
• Seo Jeongmin

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P5/50

  for increasing or potentiating the activity of insulin · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title