Glucopyranosyl derivatives and their uses

Patent metadata

Field	Value
Publication number	US-12324812-B2
Application number	US-202017624963-A
Country	US
Kind code	B2
Filing date	Jul 9, 2020
Priority date	Jul 10, 2019
Publication date	Jun 10, 2025
Grant date	Jun 10, 2025

Abstract

At present relates to a glucopyranosyl derivative and application thereof. In particular, relates to a glucopyranosyl derivative as a sodium-dependent glucose transporters1 (SGLT1) inhibitor, and a pharmaceutically acceptable salt or a stereoisomer thereof, and further relates to a pharmaceutical composition containing the derivative. Further relating to uses of the compound and pharmaceutical composition thereof in the preparation of drugs for the treatment of diabetes and diabetes-related diseases.

First claim

What is claimed is:

1. A compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a pharmaceutically acceptable salt, a dimer, or a trimer thereof,

wherein,
Y is —(CH 2 ) q —, —O—, —NH—, —S—, —S (═O)— or —S (═O) 2 —; q is 0, 1, 2 or 3;
L is C 1-6 alkylene or C 1-6 alkenylene, wherein the L is unsubstituted or substituted with 1, 2 or 3 R y ;
R 1 is H, deuterium, F, Cl, Br, I, —OH, —CN, —NO 2 , —NH 2 , —SH, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 1-6 alkylamino, C 1-6 alkylthio, cyano C 1-6 alkyl, amino C 1-6 alkyl, hydroxy C 1-6 alkyl or C 3-6 cycloalkyl;
each of R 5 and R 6 is independently H, deuterium, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 5-6 membered heterocyclyl, C 6-10 aryl or 5-6 membered heteroaryl; or R 5 , R 6 together with the nitrogen atom they are attached to, form a 5-6 membered heterocyclic ring or a 5-6 membered heteroaromatic ring;
R 4 is F, Cl, Br, I, OH, CN, NO 2 , NH 2 , —SH, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 1-6 alkylthio, C 1-6 alkylamino, hydroxy C 1-6 alkyl, cyano C 1-6 alkyl, amino C 1-6 alkyl, C 3-6 cycloalkyl, 5-6 membered heterocyclyl, C 6-10 aryl or 5-6 membered heteroaryl, wherein each of the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 1-6 alkylthio, C 1-6 alkylamino, hydroxy C 1-6 alkyl, cyano C 1-6 alkyl, amino C 1-6 alkyl, C 3-6 cycloalkyl, 5-6 membered heterocyclyl, C 6-10 aryl or 5-6 membered heteroaryl is independently unsubstituted or substituted with 1, 2 or 3 R x ;
each of R 2 and R 3 is independently H, deuterium, F, Cl, Br, I, OH, CN, NO 2 , NH 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 1-6 alkylamino, C 1-6 alkylthio, hydroxy C 1-6 alkyl, cyano C 1-6 alkyl, or amino C 1-6 alkyl;
or R 2 , R 3 together with

they are attached to, form

wherein the bond to the R 2 group is identified by *, and the bond to the R 3 group is identified by **;
each of R 7 and R 8 is independently H, deuterium, F, Cl, Br, I, OH, CN, NO 2 , NH 2 , —SH, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl or 5-8 membered heteroaryl, wherein each of the C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl or 5-8 membered heteroaryl is independently unsubstituted or substituted with 1, 2 or 3 R w ;
or R 7 , R 8 and the carbon atom to which they are attached form a C 3-8 carbocyclic ring or a 3-8 membered heterocyclic ring, wherein each of the C 3-8 carbocyclic ring and 3-8 membered heterocyclic ring is independently unsubstituted or substituted with 1, 2 or 3 R w ;
each R x , R y , and R w is independently deuterium, F, Cl, Br, I, CN, NO 2 , OH, NH 2 , —SH, ═O, —C (═O) OH, —C(═O)NH 2 , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylamino or C 1-6 haloalkoxy;
wherein, the compound does not include

2. The compound of claim 1 having Formula (II),

3. The compound of claim 1 , wherein L is —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH(CH 3 )CH 2 —, —CH 2 (CH 2 ) 2 CH 2 —, —C(CH 3 ) 2 CH 2 —, —CH 2 (CH 2 ) 3 CH 2 —, —CH 2 (CH 2 ) 4 CH 2 —, —CH═CH—, —CH═CHCH 2 —, —CH 2 CH═CH—, —CH═CHCH 2 CH 2 —, —CH 2 CH═CHCH 2 — or —CH 2 CH 2 CH═CH—, wherein the L is unsubstituted or substituted with 1, 2 or 3 R y .

4. The compound of claim 1 , wherein R 1 is H, deuterium, F, Cl, Br, I, —OH, —CN, —NO 2 , —NH 2 , —SH, methyl, ethyl, n-propyl, isopropyl, vinyl, ethynyl, methoxy, ethoxy, monofluoromethyl, difluoromethyl, trifluoromethyl, trifluoromethoxy, methylamino, ethyl amino, cyanomethyl, aminomethyl, hydroxymethyl, hydroxyethyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;
each of R 5 and R 6 is independently H, deuterium, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, vinyl, ethynyl, monofluoromethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 5-6 membered heterocyclyl, phenyl or 5-6 membered heteroaryl; or R 5 , R 6 together with the nitrogen atom they are attached to, form a 5-6 membered heterocyclic ring or a 5-6 membered heteroaromatic ring.

5. The compound of claim 1 , wherein R 4 is F, Cl, Br, I, OH, CN, NO 2 , NH 2 , —SH, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 1-4 haloalkoxy, C 1-4 alkylthio, C 1-4 alkylamino, hydroxy C 1-4 alkyl, cyano C 1-4 alkyl, amino C 1-4 alkyl, C 3-6 cycloalkyl, 5-6 membered heterocyclyl, C 6-10 aryl or 5-6 membered heteroaryl, wherein each of the C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 1-4 haloalkoxy, C 1-4 alkylthio, C 1-4 alkylamino, hydroxy C 1-4 alkyl, cyano C 1-4 alkyl, amino C 1-4 alkyl, C 3-6 cycloalkyl, 5-6 membered heterocyclyl, C 6-10 aryl or 5-6 membered heteroaryl is independently unsubstituted or substituted with 1, 2 or 3 R x .

6. The compound of claim 1 , wherein R 4 is F, Cl, Br, I, OH, CN, NO 2 , NH 2 , —SH, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, vinyl, ethynyl, 1-propynyl, propargyl, methoxy, ethoxy, monofluoromethyl, difluoromethyl, trifluoromethyl, trifluoromethoxy, methylthio, ethylthio, methylamino, hydroxymethyl, hydroxyethyl, cyanomethyl, aminomethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 5-6 membered heterocyclyl, phenyl or 5-6 membered heteroaryl, wherein each of the methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, vinyl, ethynyl, 1-propynyl, propargyl, methoxy, ethoxy, monofluoromethyl, difluoromethyl, trifluoromethyl, trifluoromethoxy, methylthio, ethylthio, methylamino, hydroxymethyl, hydroxyethyl, cyanomethyl, aminomethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 5-6 membered heterocyclyl, phenyl or 5-6 membered heteroaryl is independently unsubstituted or substituted with 1, 2 or 3 R x .

7. The compound of claim 1 , wherein each of R 7 and R 8 is independently H, deuterium, F, Cl, Br, I, OH, CN, NO 2 , NH 2 , —SH, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylamino, C 1-4 haloalkyl, C 1-4 haloalkoxy, C 3-6 cycloalkyl, 5-6 membered heterocyclyl, C 6-10 aryl or 5-6 membered heteroaryl; wherein each of the C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylamino, C 1-4 haloalkyl, C 1-4 haloalkoxy, C 3-6 cycloalkyl, 5-6 membered heterocyclyl, C 6-10 aryl or 5-6 membered heteroaryl is independently unsubstituted or substituted with 1, 2 or 3 R w ;
or R 7 , R 8 and the carbon atom to which they are attached form a C 3-7 carbocyclic ring or a 5-6 membered heterocyclic ring, wherein each of the C 3-7 carbocyclic ring and 5-6 membered heterocyclic ring is independently unsubstituted or substituted with 1, 2 or 3 R w .

8. The compound of claim 1 , wherein each of R 7 and R 8 is independently H, deuterium, F, Cl, Br, I, OH, CN, NO 2 , NH 2 , —SH, methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, methoxy, ethoxy, methylamino, mo

Assignees

• Sunshine Lake Pharma Co Ltd

Inventors

• Gu Zheng
• Wu Wuyong
• Kang Panpan
• Wang Weihua
• Liu Jianyu
• Deng xinshan

Classifications

• C07H17/04

  Heterocyclic radicals containing only oxygen as ring hetero atoms · CPC title

• C07D309/10 Primary

  Oxygen atoms · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/351

  not condensed with another ring · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title