2,3,4,6-tetra-substituted benzene-1,5-diamine derivatives, preparation method therefor and medicinal use thereof

Inventors: Jiong Lan (Shanghai, CN); Yunzhou Jin (Shanghai, CN); Fusheng Zhou (Shanghai, CN); Qi He (Shanghai, CN); Xiangyu He (Shanghai, CN); Qiang Lv (Shanghai, CN)

Assignees: SHANGHAI HAIYAN PHARMACEUTICAL TECHNOLOGY CO., LTD.; YANGTZE RIVER PHARMACEUTICAL GROUP CO., LTD.

C07D471/04 A61K31/16 A61K31/505 A61K31/506 A61K31/55 A61K45/06 C07C211/51 C07C211/54 C07D239/02 C07D401/12 C07D401/14 C07D403/12

View Patent ↗

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US 9,879,008
App. No.: 15/303,475
Granted: Jan 30, 2018
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

The present invention relates to 2,3,4,6-tetra-substituted benzene-1,5-diamine derivatives, a preparation method therefor and a medicinal use thereof. Specifically, disclosed are compounds of formula (I) or pharmaceutically acceptable salts, stereoisomers, solvates or prodrugs, preparation method therefor and application thereof. Definition of each group in the formula can be found in the specification for details.

Claims (77)

1. A compound of formula (VI), or a pharmaceutically acceptable salt, a solvate, a stereoisomer or a prodrug thereof:

wherein,

Z 2 is CR 10 , R 10 is a hydrogen, hydroxy, NO 2 , fluorine, chlorine, —NH 2 , —N(CH 3 ) 2 , C 1-3 alkyl, cyclopropyl, cyclopropyloxy, C 1-3 alkoxy, —CHO, —COCH 3 , —CO-phenyl, phenyl, —CONH 2 , —CON(CH 3 ) 2 , —C(O)OCH 3 , —OC(O)CH 3 , —SO 2 CH 3 , —SO 2 -phenyl or t-butyloxycarbonyl; wherein each of alkyl, cyclopropyl, alkoxy and phenyl is unsubstituted or substituted with 1-3 substituents selected from the group consisting of fluorine, chlorine, nitro, phenyl, methyl, methoxy, cyclopropyl, cyclopropyloxy, —CONH 2 , —CON(CH 3 ) 2 , —C(O)OCH 3 , —CHO, —OC(O)CH 3 , —SO 2 CH 3 , —SO 2 -phenyl, and —CO-phenyl;

X is NH, N(C 1-3 alkyl), O or S;

m 3 is 0 or 1;

R 0 is a hydrogen, hydroxy, C 1-3 alkyl, cyclopropyl, —CHO, —COC 1-3 alkyl, —CO— phenyl, phenyl, —CONH 2 , —CON(CH 3 ) 2 , —C(O)OCH 3 , —SO 2 C 1-3 alkyl, —SO 2 -phenyl, —S(O)C 1-3 alkyl, —S(O)-phenyl, or t-butyloxycarbonyl; wherein, each of alkyl and phenyl is unsubstituted or substituted with 1-3 substituent selected from the group consisting of fluorine, chlorine, hydroxy, NO 2 , phenyl, methyl, methoxy, cyclopropyl, cyclopropyloxy, —CONH 2 , —CON(CH 3 ) 2 , —C(O)OCH 3 , —CHO, —OC(O)CH 3 , —SO 2 CH 3 , —SO 2 -phenyl, —CO-phenyl; or R 0 is selected from: pyridyl,

each of n 3 and n 4 is independently 0, 1, 2 or 3, and n 3 and n 4 are not 0 simultaneously;

R 1 is a hydrogen;

R 2 is methoxy;

each of R 3 and R 5 are independently a hydrogen;

R 4 is a group selected from

each of R 6 and R 7 is independently a hydrogen.

2. The compound of claim 1 , or a pharmaceutically acceptable salt, a solvate, a stereoisomer or a prodrug thereof, wherein, the compound of formula (I) is selected from the group consisting of

3. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, a solvate, a stereoisomer or a prodrug thereof; and a pharmaceutically acceptable carrier.

4. The compound of claim 1 , wherein R 0 is a hydrogen, C 1-3 alkyl, —COC 1-3 alkyl, —CO-phenyl, —SO 2 C 1-3 alkyl, —SO 2 -phenyl, or t-butyloxycarbonyl; wherein each of alkyl and phenyl is unsubstituted or substituted with 1-3 substituents selected from the group consisting of fluorine, chlorine, methyl.

5. The compound of claim 1 , wherein R 0 is C 1-3 alkyl, —COC 1-3 alkyl, or —SO 2 C 1-3 alkyl; wherein, the alkyl is unsubstituted or substituted with 1 substituent selected from the group consisting of fluorine and chlorine.

6. The compound of claim 1 , wherein R 0 is C 1-3 alkyl substituted by one fluorine, —COC 1-3 alkyl or —SO 2 C 1-3 alkyl.

7. The compound of claim 1 , wherein n 3 is 1, 2 or 3; n 4 is 1 or 2.

8. The compound of claim 1 , wherein n 3 is 1; n 4 is 1.

9. The compound of claim 1 , wherein in the compound of formula (VI),

(i) Z 2 is CR 10 , R 10 is trifluoromethyl, fluorine or chlorine;

m 3 is 0; n 3 is 1; n 4 is 1;

X is NH, O or S;

R 0 is a hydrogen, C 1-3 alkyl, —COC 1-3 alkyl, —CO-phenyl, —SO 2 C 1-3 alkyl, —SO 2 -phenyl, or t-butyloxycarbonyl; wherein each of alkyl and phenyl is unsubstituted or substituted with 1-3 substituents selected from the group consisting of fluorine, chlorine and methyl;