Amino sulfonyl-based compounds, the preparation method therefor and use thereof

Patent metadata

Field	Value
Publication number	US-10093679-B2
Application number	US-201515509796-A
Country	US
Kind code	B2
Filing date	Sep 11, 2015
Priority date	Sep 12, 2014
Publication date	Oct 9, 2018
Grant date	Oct 9, 2018

Abstract

Disclosed are aminosulfonyl-based compounds represented by the general formula I or tautomers, enantiomers, racemates or pharmaceutically acceptable salts thereof, a method for preparing the same, pharmaceutical compositions and uses thereof. The compounds can be used to treat epilepsy, convulsions, obesity and the like.

First claim

What is claimed is:

1. An aminosulfonyl-based compound represented by formula I or a tautomer, enantiomer, racemate or pharmaceutically acceptable salt thereof,

wherein

Z is N—R 5 , O or CHR 5 ; when X is O and Y is N, Z is not O or CH 2 ;
m is an integer of 0 to 4;
n is a integer of 0 to 2;
p is an integer of 1 to 2;
R 1 s are each independently hydrogen, amino, halogen, trifluoromethyl, hydroxyl, nitro, nitrile, mercapto, carboxyl, aldehyde group, oxo(═O) group, thio(═S) group, C1˜C10 alkyl, C2˜C10 alkenyl, C2˜C10 alkynyl, C3˜C10 cycloalkyl, C1˜C10 alkoxyl, C1˜C10 alkylacyl, C1˜C10 alkoxyl carbonyl, C1˜C10 alkylacyloxy, —NR 6 R 7 , —CONR 6 R 7 , —OCONR 6 R 7 , C1˜C10 thioalkyl, sulfonic acid group, aminoformyl, sulfonyl, C6˜C10 aryl, 4-˜10-membered heterocyclic group containing 1˜4 heteroatoms selected from a group consisting of N, O and S, or 4-˜10-membered heteroaryl containing 1˜4 heteroatoms selected from a group consisting of N, O and S;
wherein the amino, C1˜C10 alkoxy, C1˜C10 alkyl, C1˜C10 alkyl acyl, C1˜C10 alkoxyl carbonyl, C1˜C10 alkyl acyloxy, sulfonyl, C6˜C10 aryl, 4-˜10-membered heterocyclic group containing 1˜4 heteroatoms selected from a group consisting of N, O and S, or 4-˜10-membered heteroaryl containing 1˜4 heteroatoms selected from a group consisting of N, O and S may be optionally substituted by one or more substituents selected from a group consisting of halogen, trifluoromethyl, hydroxyl, nitro, amino, cyano, carboxyl, aldehyde group, C1˜C10 alkyl, C1˜C10 alkoxyl, C1˜C10 alkylacyloxy, C1˜C10 alkoxyl carbonyl, C1˜C10 alkyl acyl, sulfonyl, C1˜C10 alkyl sufonyl, phenyl, and benzyl;
R 2 s are each independently hydrogen, amino, halogen, trifluoromethyl, hydroxyl, nitro, cyano, mercapto group, carboxyl, aldehyde group, C1˜C10 alkyl, C2˜C10 alkenyl, C2˜C10 alkynyl, C3˜C10 cycloalkyl, C1˜C10 alkoxyl, C1˜C10 alkyl acyl, C1˜C10 alkoxylcarbonyl, C1˜C10 alkyl acyloxy, —NR 6 R 7 , —CONR 6 R 7 , —OCONR 6 R 7 , C1˜C10 thioalkyl, sulfonic acid group, amino formyl, sulfonyl, C6˜C10 aryl, 4-˜10-membered heterocyclic group containing 1˜4 heteroatoms selected from a group consisting of N, O and S, or 4-˜10-membered heteroaryl containing 1˜4 heteroatoms selected from a group consisting of N, O and S;
wherein the amino, C1˜C10 alkoxy, C1˜C10 alkyl, C1˜C10 alkyl acyl, C1˜C10 alkoxyl carbonyl, C1˜C10 alkyl acyloxy, sulfonyl, C6˜C10 aryl, 4-˜10-membered heterocyclic group or 4-˜10-membered heteroaryl may be optionally substituted by one or more substituents selected from a group consisting of halogen, trifluoromethyl, hydroxyl, nitro, amino, cyano, carboxyl, aldehyde group, C1˜C10 alkyl, C1˜C10 alkoxyl, C1˜C10 alkyl acyloxy, C1˜C10 alkoyxl carbonyl, C1˜C10 alkyl acyl, sulfonyl, C1˜C10 alkyl sulfonyl, phenyl, and benzyl;
R 3 and R 4 are each independently hydrogen, amino, trofluoromethyl, hydroxyl, carboxyl, aldehyde group, amino, C1˜C10 alkyl, C2˜C10 alkenyl, C2˜C10 alkynyl, C3˜C10 cycloalkyl, C1˜C10 alkoxyl, C1˜C10 alkoxyl carbonyl, C1˜C10 alkyl acyl, C1˜C10 alkyl acyloxy, sulfonyl, C6˜C10 aryl, 4-˜10-membered heterocyclic group containing 1˜4 heteroatoms selected from a group consisting of N, O and S, or 4-˜10-membered heteroaryl containing 1˜4 heteroatoms selected from a group consisting of N, O and S;
wherein the amino, C1˜C10 alkyl, C1˜C10 alkoxy, C1˜C10 alkoxyl carbonyl, C1˜C10 alkyl acyl, C1˜C10 alkyl acyloxy, sulfonyl, C6˜C10 aryl, 4-˜10-membered heterocyclic group containing 1 to 4 heteroatoms selected from a group consisting of N, O and S, or 4-˜10-membered heteroaryl containing 1 to 4 heteroatoms selected from a group consisting of N, O and S may be optionally substituted by one or more substituents selected from a group consisting of halogen, trifluoromethyl, hydroxyl, nitro, amino, cyano, carboxyl, aldehyde group, C1˜C10 alkyl, C1˜C10 alkoxyl, C1˜C10 alkyl acyloxy, C1˜C10 alkoxyl carbonyl, C1˜C10 alkyl acyl, sulfonyl, C1˜C10 alkyl sulfonyl, phenyl and benzyl;
or R 3 and R 4 together with the N atom to which they are bonded form a 4- to 8-membered heterocyclic group or 4- to 8-membered heteroaryl containing 1 to 4 heteroatoms selected from a group consisting of N, S and O;
R 5 is H or C1˜C10 alkyl; and
R 6 and R 7 are each independently H or C1˜C10 alkyl, or R 6 and R 7 together with the N atom to which they are bonded form a 4-˜8-membered heterocyclic group containing 1˜4 heteroatoms selected from a group consisting of N, S and O, or form 4-˜8-membered heteroaryl containing 1˜4 heteroatoms selected from a group consisting of N, S and O.

2. The aminosulfonyl-based compound represented by formula I or a tautomer, enantiomer, racemate or a pharmaceutically acceptable salt thereof according to claim 1 , wherein,
Z is N—R 5 ;
m is 0, 1 or 2;
n is 0 or 1;
p is 1;
R 1 s are each independently hydrogen, halogen, trifluoromethyl, hydroxyl, nitro, cyano, mercapto, carboxyl, aldehyde group, C1˜C8 alkyl, C2˜C8 alkenyl, C2˜C8 alkynyl, C3˜C8 cycloakyl, C1˜C8 alkoxyl, C1˜C8 alkyl acyl, C1˜C8 alkoxy carbonyl, C1˜C8 alkyl acyloxy, —NR 6 R 7 , —CONR 6 R 7 , —OCONR 6 R 7 , C1˜C8 thioalkyl, sulfonamido, aminoformyl, sulfonyl, C1˜C8 alkylsulfonyl, C6˜C10 aryl, 4-˜10˜membered heterocyclic group or 4-˜10-membered heteroaryl containing 1˜3 heteroatoms selected from a group consisting of N, O and S;
R 2 s are each independently hydrogen, halogen, trifluoromethyl, hydroxyl, nitro, cyano, amino, mercapto, carboxyl, aldehyde group, C1˜C8 alkyl, C2˜C8 alkenyl, C2˜C8 alkynyl, C3˜C8 cycloakyl, C1˜C8 alkoxyl, C1˜C8 alkyl acyl, C1˜C8 alkoxy carbonyl, C1˜C8 alkyl acyloxy, —NR 6 R 7 , —CONR 6 R 7 , —OCONR 6 R 7 , C1˜C8 thioalkyl, sulfonic acid group, sulfonamido, aminoformyl, sulfonyl, C1˜C8 alkylsulfonyl, C6˜C10 aryl, 4-˜10˜membered heterocyclic group containing 1˜3 heteroatoms selected from a group consisting of N, O and S, or 4-˜10-membered heteroaryl containing 1˜3 heteroatoms selected from a group consisting of N, O and S;
R 3 and R 4 are each independently H or C1˜C8 alkyl or 5-˜6-membered heteroaryl;
or R 3 and R 4 together with the N atom to which they are bonded form a 5- to 7-membered heterocyclic group containing 1 to 3 heteroatoms selected from a group consisting of N, S and O or 5- to 7-membered heteroaryl containing 1 to 3 heteroatoms selected from a group consisting of N, S and O;
R 5 is H or C1˜C3 alkyl;
R 6 and R 7 are each independently H or C1˜C8 alkyl;
or R 6 and R 7 together with the N atom to which they are bonded form a 5- to 7-membered heterocyclic group or 5- to 7-membered heteroaryl containing 1 to 3 heteroatoms selected from a group consisting of N, S and O.

3. The aminosulfonyl-based compound represented by formula I or a tautomer, enantiomer, racemate or a pharmaceutically acceptable salt thereof according to claim 1 , wherein,
Z is N—R 5 ;
m is 0, 1 or 2;
n is 0 or 1;
p is 1;
R 1 is H, F, Cl, NO 2 , NH 2 , NHCOCH 3 or methoxyl;
R 2 is H or methyl;
R 3 and R 4 are each independently H, methyl, ethyl, or imidazolyl;
R 5 is H;
R 6 and R 7 are each independently H or methyl.

4. The aminosulfonyl-based compound represented by formula I or a tautomer, enantiomer, racemate or a pharmaceutically acceptable salt thereof according to claim 1 ,
wherein, the aminosulfonyl-based compound is selected from the group consisting of:

5. A method for preparing an aminosulfonyl-based compound represented by formula I,
wherein the aminosulfonyl-based

Assignees

• Suzhou Vigonvita Life Sciences Co Ltd
• Shanghai Inst Materia Medica Cas
• Topharman Shanghai Co Ltd
• Suzhou Vigonvita Life Sciences Co Ltd
• Topharman Shanghai Co Ltd

Inventors

• Shen Jingshan
• Liu Zheng
• Wang Zhen
• Tian Guanghui
• Li Jianfeng
• Yang Xiaojun

Classifications

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• A61P25/08

  Antiepileptics; Anticonvulsants · CPC title

• A61K31/428

  condensed with carbocyclic rings · CPC title

• C07D261/20 Primary

  condensed with carbocyclic rings or ring systems · CPC title

• C07D209/14

  Radicals substituted by nitrogen atoms, not forming part of a nitro radical · CPC title