6-dithio-substituted-2′-deoxyguanosine compound, preparation method thereof and use thereof

Patent metadata

Field	Value
Publication number	US-11247994-B2
Application number	US-202117149747-A
Country	US
Kind code	B2
Filing date	Jan 15, 2021
Priority date	Aug 30, 2018
Publication date	Feb 15, 2022
Grant date	Feb 15, 2022

Abstract

The present invention provides a 6-dithio-substituted-2′-deoxyguanosine compound and a preparation method thereof and use thereof in anti-tumor drugs. According to the present invention, a series of brand-new thioredoxin-1 (Trx-1) inhibitors are designed and synthesized by using 2′-deoxyguanosine as a structure mother nucleus. The compound according to the present invention is a structure of formula I, and Trx-1 activity inhibition testing is performed on the type of compounds, showing apparent inhibitory activity. It is indicated from in vitro and vivo researches that these compounds show significant anti-tumor effects on multiple types of tumors, can be applied to drugs for tumors related to human body cell proliferation, and provide a new path for the research of anticancer drugs.

First claim

What is claimed is:

1. A method of treating colon cancer, comprising administering to a subject in need thereof a composition comprising a 6-dithio-substituted-2′-deoxyguanosine compound of formula I:

wherein R is C1-8 alkyl, C1-8 fluoroalkyl, C1-8 chloroalkyl, C1-8 hydroxyalkyl, C1-8 ketoalkyl, —(C1-4 alkyl) R1, —(C1-4 alkyl) NH 2 , —(C1-4 alkyl) NH (C1-4 alkyl), phenyl selectively substituted by R2, a 5-membered aromatic ring selectively substituted with R2, C3-6 cycloalkyl selectively substituted with R2, or a 5 to 6-membered heteroaromatic ring containing at least one nitrogen and selectively substituted with R2;
R1 is phenyl, phenyl selectively substituted with —F, —Cl, —OH, —NH 2 , —C1-4 alkyl, —OCH 3 , —CONH 2 or —CONHCH 3 , or a 5 to 6-membered heteroaromatic ring containing at least one nitrogen atom and selectively substituted with R2; and
R2 is C1-4 alkyl, —CN, —OH, —OMe, —NH 2 , —NHMe, —N(CH 3 ) 2 , —F, —CF 3 , —CO(C1-4 alkyl), —COCH 2 CH 2 OH, or —CONHCH 3 .

2. The method according to claim 1 , wherein the 6-dithio-substituted-2′-deoxyguanosine compound is a compound having a structure selected from the group consisting of:

Assignees

• Univ Zhejiang

Inventors

• Yu Lushan
• Zeng Su
• Zhang Yang

Classifications

• C07D473/24 Primary

  one nitrogen and one sulfur atom · CPC title

• C07H1/00

  Processes for the preparation of sugar derivatives · CPC title

• A61P35/02

  specific for leukemia · CPC title

• C07H19/173 Primary

  with 2-deoxyribosyl as the saccharide radical · CPC title

• A61P35/00

  Antineoplastic agents · CPC title