Glucoside derivative that acts as SGLT1 inhibitor and application thereof

Patent metadata

Field	Value
Publication number	US-12258367-B2
Application number	US-202017599308-A
Country	US
Kind code	B2
Filing date	Mar 30, 2020
Priority date	Mar 29, 2019
Publication date	Mar 25, 2025
Grant date	Mar 25, 2025

Abstract

A glucoside derivative that acts as an SGLT1 inhibitor and an application thereof in the preparation of a drug for SGLT1 related diseases. Specifically disclosed is a compound represented by formula (II), a tautomer thereof or a pharmaceutically acceptable composition thereof.

First claim

What is claimed is:

1. A compound represented by formula (II), or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof,

wherein
R 1 is selected from H, F, Cl, Br, I, OH, NH 2 , CN, C 1-6 alkyl and C 1-6 alkoxy, wherein the C 1-6 alkyl and C 1-6 alkoxy are optionally substituted with 1, 2, or 3 R a ;

R 2 is selected from F, Cl, Br, I, OH, NH 2 and C 1-3 alkylamino;
R 3 , R 4 and R 5 are each independently selected from H, F, Cl, Br, I, OH, NH 2 , CN, and C 1-3 alkyl optionally substituted with 1, 2, or 3 R b ;
L is selected from single bond, —O—, —S—, —C(R c ) 2 —, and —N(R d )—;
m is selected from 0, 1, and 2;
n is selected from 1, 2, and 3;
R a , R b and R c are each independently selected from F, Cl, Br, I, OH, NH 2 and CH 3 ;
R d is selected from H and CH 3 .

2. The compound, or stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 1 , wherein R 1 is selected from H, F, Cl, Br, I, OH, NH 2 , CN, CH 3 , CH 2 CH 3 , and —OCH 3 , wherein the CH 3 , CH 2 CH 3 , and —OCH 3 are optionally substituted with 1, 2, or 3 R a .

3. The compound, or stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 2 , wherein R 1 is selected from H, F, Cl, Br, I, OH, NH 2 , CN, CH 3 , CH 2 F, CHF 2 , CF 3 , CH 2 CH 3 , and —OCH 3 .

4. The compound, or stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 1 , wherein R 2 is selected from F, Cl, Br, I, OH, NH 2 , NH(CH 3 ), and N(CH 3 ) 2 .

5. The compound, or stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 1 , wherein R 3 , R 4 and R 5 are each independently selected from H, F, Cl, Br, I, OH, NH 2 , CN, and CH 3 optionally substituted with 1, 2, or 3 R b .

6. The compound, or stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 5 , wherein R 3 , R 4 and R 5 are each independently selected from H, F, Cl, Br, I, OH, NH 2 , CN, CH 3 , CH 2 F, CHF 2 , and CF 3 .

7. The compound, or stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 1 , wherein L is selected from single bond, —O—, and —S—.

8. The compound, or stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 1 , wherein moiety

is selected from

9. The compound, or stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 1 , wherein moiety

is selected from

10. The compound, or stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is selected from the group consisting of:

wherein
R 1 , R 2 , R 3 , R 4 , R 5 , and L are as defined in claim 1 .

11. The compound, or stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 10 , wherein the compound is selected from the group consisting of:

wherein
R 2 is selected from the group consisting of F, Cl, Br, I, OH, NH 2 , NH(CH 3 ), and N(CH 3 ) 2 ;
R 1 , R 3 , R 4 , R 5 , and L are as defined in claim 10 .

12. The compound, or stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 11 , wherein the compound is selected from the group consisting of:

wherein
R 1 , R 2 , R 3 , R 4 , and R 5 are as defined in claim 11 .

13. The compound represented by the following formula, or stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:

14. The compound, or stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 13 , wherein the compound is selected from the group consisting of:

15. A pharmaceutical composition comprising a therapeutically effective amount of the compound, or stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 1 as an active ingredient, and pharmaceutically acceptable carrier(s).

16. A method of treating disease associated with SGLT1 in a subject in need thereof, comprising administering to the subject the compound, or stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 1 , wherein the disease associated with SGLT1 is diabetes or obesity.

17. A method of treating a disease associated with SGLT1 in a subject in need thereof, comprising administering to the subject the composition according to claim 15 , wherein the disease associated with SGLT1 is diabetes or obesity.

Assignees

• Medshine Discovery Inc

Inventors

• Li Yi
• Yu Tao
• Mao Qinghua
• Wu Chengde
• Chen Shuhui

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P3/04 Primary

  Anorexiants; Antiobesity agents · CPC title

• C07H15/14

  attached to a sulfur, selenium or tellurium atom of a saccharide radical · CPC title

• C07D405/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07H15/26 Primary

  Acyclic or carbocyclic radicals, substituted by hetero rings · CPC title