Benzofuran analogue as NS4B inhibitor

Patent metadata

Field	Value
Publication number	US-10100027-B2
Application number	US-201515514389-A
Country	US
Kind code	B2
Filing date	Sep 23, 2015
Priority date	Sep 26, 2014
Publication date	Oct 16, 2018
Grant date	Oct 16, 2018

Abstract

Provided is a benzofuran analog having a structure represented by formula (I) and used as an NS4B inhibitor, or a pharmaceutically acceptable salt of the benzofuran analog. The benzofuran analog has anti-hepatitis C virus activity.

First claim

What is claimed is:

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof,

wherein,
L 1 is —C(═O)—;
the moiety

L 2 is a bond;
R 3 is selected from the group consisting of

each of T 31-33 is N;
each of D 31-35 is dependently selected from the group consisting of —[C(R d1 )(R d2 )] 0-2 —, —C(═O)—, —C(═O)N(R d3 )—, —N(R d4 )—, —C(═NR d5 )—, —S(═O) 2 N(R d6 )—, —S(═O)N(R d7 )—, —O—, —S—, —C(═O)O—, —C(═S)—, —S(═O)— and —S(═O) 2 —;
R 31 is selected from the group consisting of H, F, Cl, Br, I, CN, OH, SH, NH 2 , CHO, COOH, and C(═O)NH 2 , or selected from the group consisting of a C 1-10 alkyl or heteroalkyl optionally substituted by R 01 , a C 3-10 cyclohydrocarbyl, a C 1-10 alkyl or heteroalkyl substituted by a C 3-10 cyclohydrocarbyl;
or, there is another linking bond (CH 2 ) 1-3 between T 31 and D 31 , D 33 and D 34 , T 33 and D 35 ;
each of R 11-12 , R d1 , R d2 is independently selected from the group consisting of H, F, Cl, Br, I, CN, OH, SH, NH 2 , CHO, COOH, C(═O)NH 2 , or selected from the group, optionally substituted by none, one, two or three of R 01 , consisting of a C 1-10 alkyl or heteroalkyl, a C 3-10 cyclohydrocarbyl, a C 1-10 alkyl or heteroalkyl substituted by a C 3-10 cyclohydrocarbyl;
R 01 is selected from the group consisting of F, Cl, Br, I, CN, OH, SH, NH 2 , and R 02 ;
R 02 is selected from the group consisting of a C 1-10 alkyl, a C 1-10 alkylamino, a alkyl)amino, a C 1-10 alkoxyl, a C 1-10 alkanoyl, a C 1-10 alkoxycarbonyl, a C 1-10 alkylsulfonyl, a C 1-10 alkylsulfinyl, a C 3-10 cycloalkyl, a C 3-10 cycloalkylamino, a C 3-10 heterocycloalkylamino, a C 3-10 cycloalkoxyl, a C 3-10 cycloalkanoyl, a C 3-10 cycloalkoxycarbonyl, a C 3-10 cycloalkylsulfonyl, and a C 3-10 cycloalkylsulfinyl;
the “hetero” represents a heteroatom or a heteroatomic group, which is selected from the group consisting of —C(═O)N(R d3 )—, —N(R d4 )—, —C(═NR d5 )—, —S(═O) 2 N(R d6 ) − , —S(═O)N(R d7 )—, —O—, —S—, —C(═O)O—, —C(═O)—, —C(═S)—, —S(═O)—, —S(═O) 2 — and —N(R d8 )C(═O)N(R d9 )—;
each of R d3-d9 is independently selected from the group consisting of H, OH, NH 2 , and R 02 ;
R 02 is optionally substituted by R 001 ;
R 001 is selected from the group consisting of F, Cl, Br, I, CN, OH, N(CH 3 ) 2 , NH(CH 3 ), NH 2 , CHO, COOH, C(═O)NH 2 , trihalomethyl, dihalomethyl, monohalomethyl, aminomethyl, hydroxymethyl, methyl, methylamino, formyl, methoxycarbonyl, methylsulfonyl, and methylsulfinyl;
the number of R 01 , R 001 , the heteroatom or the heteroatomic group is independently selected from the group consisting of 0, 1, 2 and 3.

2. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the moiety

is selected from

each of R 101-103 is independently selected from the group consisting of H, F, Cl, Br, I, CN, OH, SH, NH 2 , CHO, COOH, C(═O)NH 2 , or selected from the group, optionally substituted by none, one, two or three of R 01 , consisting of a C 1-10 alkyl or heteroalkyl, a C 3-10 cyclohydrocarbyl, and a C 1-10 alkyl or heteroalkyl substituted by a C 3-10 cyclohydrocarbyl, R 01 is defined as claim 1 .

3. The compound or the pharmaceutically acceptable salt thereof according to claim 2 , wherein each of R 101-103 is independently selected from the group consisting of F, Cl, Br, —CF 3 , —CHF 2 , CN, Me, ethyl, propyl, cyclopropyl and iso-propyl.

4. The compound or the pharmaceutically acceptable salt thereof according to claim 2 , wherein the moiety

is selected from the group consisting of

5. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein each of D 31-35 is dependently selected from the group consisting of —C(═O)—, —O—, methylene, —N(CH 3 )—, —CH(OH)—, and —CF 2 —; R 31 is selected from the group consisting of H, methyl, ethyl, n-propyl, and iso-propyl.

6. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R 3 is selected from the group consisting of

7. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , which is selected from the group consisting of

Assignees

• Changzhou Yinsheng Pharmaceutical Co Ltd
• Univ Sichuan

Inventors

• Zhang Yang
• Fu Zhifei
• Wang Jianfei
• Li Jian
• Chen Shuhui
• Wei Yuquan
• Yu Luoting
• Tao Xin

Classifications

• A61P31/12

  Antivirals · CPC title

• A61P43/00

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

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D307/85 Primary

  attached in position 2 · CPC title

• A61K31/343

  condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone · CPC title