Aryl ethene derivative and pharmaceutical composition containing same as active ingredient

Patent metadata

Field	Value
Publication number	US-11285226-B2
Application number	US-201916677596-A
Country	US
Kind code	B2
Filing date	Nov 7, 2019
Priority date	Jun 27, 2016
Publication date	Mar 29, 2022
Grant date	Mar 29, 2022

Abstract

The present invention relates to an aryl ethene derivative, for inhibiting an estrogen-related receptor gamma (ERRγ) activity, a prodrug of same, a solvate of same, a stereoisomer of same or pharmaceutically acceptable salts of same, and a pharmaceutical composition containing same as an active ingredient.

First claim

The invention claimed is:

1. A method for treating thyroid cancer, comprising: the combined administration of a pharmaceutical composition comprising a compound represented by the following Chemical Formula 6 or a solvate, stereoisomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier with radioactive iodine to a subject in need thereof:

wherein
R 1 is (C3-C10)heterocycloalkyl or —O—(CH 2 ) m —R 11 ;
the heterocycloalkyl of R 1 is a monovalent radical of a non-aromatic heterocycle containing 1 to 4 heteroatoms selected from the group consisting of N, O and S, and is a saturated or unsaturated mono-, bi-, or spirocycle having a carbon atom or nitrogen atom in a ring as a binding site, and the heterocycloalkyl of R 1 may be further substituted by one or more selected from the group consisting of (C1-C10)alkyl, (C3-C10)cycloalkyl, (C2-C10)alkenyl, amidino, (C1-C10)alkoxycarbonyl, hydroxy(C1-C10)alkyl, and di(C1-C20)alkylamino(C1-C20)alkyl;
m is an integer of 1 to 3;
R 11 is selected from the following structures:

wherein R 31 and R 32 are independently of each other hydrogen, (C1-C10)alkyl, (C3-C10)cycloalkyl, (C2-C10)alkenyl, amidino, (C1-C10)alkoxycarbonyl, hydroxy(C1-C10)alkyl, or di(C1-C10)alkylamino(C1-C10)alkyl; and L is O or S;
wherein Ar is (C6-C12)aryl or (C3-C12)heteroaryl, in which the aryl or heteroaryl of Ar may be further substituted by one or more selected from the group consisting of hydroxy, halogen, (C1-C10)alkyl, halo(C1-C10)alkyl, (C1-C10)alkoxy, nitro, cyano, amino, (C1-C10)alkylsulfonylamino, (C3-C10)cycloalkylsulfonylamino, di((C1-C10)alkylsulfonyl)amino, (C1-C10)alkylcarbonyloxy, (C1-C10)alkylcarbonylamino, guanidino, (C1-C10)alkylsulfonyl, (C1-C10)alkylsulfonyloxy, halo(C1-C10)alkylsulfonyloxy, and (C3-C10)cycloalkylsulfonyloxy;
wherein the heteroaryl of Ar is a monovalent radical of a heteroaromatic ring which is an aryl group containing 1 to 4 heteroatoms selected from the group consisting of N, O and S as an aromatic ring backbone atom, and carbons as remaining aromatic ring backbone atoms;
and R 2 is hydroxy, fluoro, (C1-C10)alkylcarbonyloxy, or (C1-C10)alkylsulfonyloxy.

2. The method of claim 1 , wherein the thyroid cancer is analpastic thyroid cancer.

3. The method of claim 1 , wherein R 2 is hydroxy; and R 1 is heterocycloalkyl selected from the following structures:

wherein R 31 and R 32 are independently of each other hydrogen, (C1-C10)alkyl, (C3-C10)cycloalkyl, (C2-C10)alkenyl, amidino, (C1-C10)alkoxycarbonyl, hydroxy(C1-C10)alkyl, or di(C1-C10)alkylamino(C1-C10)alkyl; and L is O or S.

4. The method of claim 1 , wherein R 2 is hydroxy; R 1 is —O—(CH 2 ) m —R 11 ; m is an integer of 1 or 2.

5. The method of claim 1 , wherein the compound is selected from the following structures:

6. The method of claim 1 , wherein the compound is selected from the following structures:

Assignees

• Daegu Gyeongbuk Medical Innovation Found
• Kyungpook Nat Univ Hospital
• Kyungpook Nat Univ Ind Academic Coop Found

Inventors

• Hwang Sung Yeoun
• Cho Sung Jin
• Kim Jina
• Chin Jungwook
• Hwang Hayoung
• Lee In-Kyu
• Jeon Yong-Hyun
• Lee Jaetae
• Jeon Jae-Han
• Kim Sang Wook

Classifications

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• A61K31/403

  condensed with carbocyclic rings, e.g. carbazole · CPC title

• A61K31/397

  having four-membered rings, e.g. azetidine · CPC title

• A61K31/404

  Indoles, e.g. pindolol · CPC title

• C07D241/04

  having no double bonds between ring members or between ring members and non-ring members · CPC title