Glucopyranosyl derivative and use thereof

Patent metadata

Field	Value
Publication number	US-11186602-B2
Application number	US-201916965438-A
Country	US
Kind code	B2
Filing date	Jan 29, 2019
Priority date	Jan 31, 2018
Publication date	Nov 30, 2021
Grant date	Nov 30, 2021

Abstract

A glucopyranosyl derivative is used as an inhibitor of sodium-dependent glucose transporters (SGLTs), particularly being used as an inhibitor of sodium-dependent glucose transporter-1 (SGLT1), and a pharmaceutically acceptable salt or stereoisomer thereof, further relating to a pharmaceutical composition containing the derivative. The compound and a pharmaceutical composition is used thereof in the preparation of a drug for treating diabetes and diabetes-related diseases.

First claim

The invention 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,
L is —(CR a R b ) q —, —CH═CH—(CR a R b ) p —, —O—(CR a R b ) p —, —NH—(CR a R b ) p —, —S—(CR a R b ) p —, —S(═O)—(CR a R b ) p — or —S(═O) 2 —(CR a R b ) p —;
q is 1, 2, 3, 4, 5 or 6;
p is 0, 1, 2, 3, 4, 5 or 6;
each R a and R b is independently H, D, F, Cl, Br, I, CN, NO 2 , OH, NH 2 , —C(═O) OH, —SH, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-6 membered heterocyclyl; or, R a and R b together with the carbon atom to which they are attached, form a C 3-6 carbocycle or a 3-6 membered heterocycle;
R 1 is H, D, 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 hydroxyalkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 1-6 alkylamino, C 1-6 alkylthio, C 3-6 cycloalkyl or C 3-6 cycloalkyl-C 1-4 alkylene, wherein each of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 1-6 alkylamino, C 1-6 alkylthio, C 3-6 cycloalkyl and C 3-6 cycloalkyl-C 1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents, and the substituent is independently selected from D, F, Cl, Br, I, CN, NO 2 , OH, NH 2 , —C(═O) OH, —SH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylamino or C 1-6 haloalkoxy;
each of R 2 and R 3 is independently H, D, CN, OH, NH 2 , —SH, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-6 cycloalkyl or 3-6 membered heterocyclyl, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-6 cycloalkyl and 3-6 membered heterocyclyl is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents, and the substituent is independently selected from D, F, Cl, Br, I, CN, NO 2 , OH, NH 2 , —C(═O) OH, —SH, ═O, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylamino or C 1-6 haloalkoxy;
or, R 2 and R 3 together with the carbon atom to which they are attached, form carbonyl,
or, R 2 and R 3 together with the carbon atom to which they are attached, form a C 3-6 carbocycle or a 3-6 membered heterocycle, wherein each of C 3-6 carbocycle and 3-6 membered heterocycle is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents, and the substituent is independently selected from D, F, Cl, Br, I, CN, NO 2 , OH, NH 2 , —C(═O) OH, —SH, ═O, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylamino or C 1-6 haloalkoxy;
R 4 is H, D, —OR 4a or —SR 4b ;
each of R 4a and R 4b is independently H, D, C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 alkylene, 5-6 membered heterocyclyl, (5-6 membered heterocyclyl)-C 1-4 alkylene, C 6-10 aryl, C 6-10 aryl-C 1-4 alkylene, 5-6 membered heteroaryl or (5-6 membered heteroaryl)-C 1-4 alkylene, wherein each C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 alkylene, 5-6 membered heterocyclyl, (5-6 membered heterocyclyl)-C 1-4 alkylene, C 6-10 aryl, C 6-10 aryl-C 1-4 alkylene, 5-6 membered heteroaryl and (5-6 membered heteroaryl)-C 1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents, and the substituent is independently selected from D, F, Cl, Br, I, CN, NO 2 , OH, NH 2 , —C(═O) OH, —SH, ═O, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylamino or C 1-6 haloalkoxy;
each R 10 is independently H, D, F, Cl, Br, I, OH, CN, NO 2 , NH 2 , C 1-6 alkyl or C 1-6 alkoxy;
R 5 is H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-8 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl or 5-8 membered heteroaryl, wherein each of C 1-6 alkyl, C 1-6 haloalkyl, C 3-8 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl and 5-8 membered heteroaryl is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents, and the substituent is independently selected from D, F, Cl, Br, I, CN, NO 2 , OH, NH 2 , ═O, —C(═O) OH, —C(═O) NH 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 5-6 membered heterocyclyl, C 6-10 aryl or 5-6 membered heteroaryl;
each of R 6 and R 7 is independently H, D, F, Cl, Br, I, CN, NO 2 , OH, NH 2 , 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 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 and 5-8 membered heteroaryl is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents, and the substituent is independently selected from D, F, Cl, Br, I, CN, NO 2 , OH, NH 2 , ═O, —C(═O) OH, —C(═O) NH 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 5-6 membered heterocyclyl, C 6-10 aryl or 5-6 membered heteroaryl;
or, R 6 and R 7 together with the carbon atom to which they are attached, form a C 3-8 carbocycle, a 3-8 membered heterocycle, a C 6-10 aromatic ring or a 5-8 membered heteroaromatic ring, wherein each of C 3-8 carbocycle, 3-8 membered heterocycle, C 6-10 aromatic ring and 5-8 membered heteroaromatic ring is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents, and the substituent is independently selected from D, F, Cl, Br, I, CN, NO 2 , OH, NH 2 , ═O, —C(═O) OH, —C(═O) NH 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylamino or C 1-6 haloalkoxy;
or R 5 and R 6 together with the atom to which they are attached, or R 5 and R 7 together with the atom to which they are attached, form a 3-8 membered heterocycle or a 5-8 membered heteroaromatic ring, wherein each 3-8 membered heterocycle and 5-8 membered heteroaromatic ring is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents, and the substituent is independently selected from D, F, Cl, Br, I, CN, NO 2 , OH, NH 2 , ═O, —C(═O) OH, —C(═O) NH 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylamino or C 1-6 haloalkoxy;
each of R 8 and R 9 is independently H, D, R e O—C 1-4 alkylene, R d R c N—C 1-4 alkylene, C 1-8 alkyl, C 1-6 haloalkyl, C 3-8 cycloalkyl, C 3-8 cycloalkyl-C 1-4 alkylene, 3-8 membered heterocyclyl, (3-8 membered heterocyclyl) —C 1-4 alkylene, C 6-10 aryl, C 6-10 aryl-C 1-4 alkylene, 5-8 membered heteroaryl or (5-8 membered heteroaryl)-C 1-4 alkylene, wherein each C 1-8 alkyl, C 1-6 haloalkyl, C 3-8 cycloalkyl, C 3-8 cycloalkyl-C 1-4 alkylene, 3-8 membered heterocyclyl, (3-8 membered heterocyclyl) —C 1-4 alkylene, C 6-10 aryl, C 6-10 aryl-C 1-4 alkylene, 5-8 membered heteroaryl and (5-8 membered heteroaryl)-C 1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents, and the substituent is independently selected from D, F, Cl, Br, I, CN, NO 2 , ═O, —OR e , —NR c R d , —C(═O) OR e , —C(═O) NHR f , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylamino or C 1-6 haloalkoxy;
or, R 8 and R 9 together with the nitrogen atom to which they are attached, form a 3-8 membered heterocycle or a 5-8 membered heteroaromatic ring, wherein each of 3-8 membered heterocycle and 5-8 membered heteroaromatic ring is indepe

Assignees

• Sunshine Lake Pharma Co Ltd

Inventors

• Gu Zheng
• Wu Wuyong
• Kang Panpan
• Qu Tong
• Zhang Zongyuan
• Huang Weiming
• Wu Tianyun
• Zhang Yingjun

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• C07H3/10 Primary

  Anhydrosugars, e.g. epoxides · CPC title

• C07D493/08

  Bridged systems · CPC title

• C07H9/04 Primary

  Cyclic acetals · CPC title