Substituted 4,6-dihydrospiro[[1,2,3]triazolo[4,5-b]pyridine-7,3′-indoline]-2′,5(3H)-dione analogues

Patent metadata

Field	Value
Publication number	US-11407752-B2
Application number	US-202016938886-A
Country	US
Kind code	B2
Filing date	Jul 24, 2020
Priority date	Jul 26, 2019
Publication date	Aug 9, 2022
Grant date	Aug 9, 2022

Abstract

A series of substituted 4,6-dihydrospiro[[1,2,3]triazolo[4,5-b]pyridine-7,3′-indoline]-2′,5(3H)-dione analogues, the use thereof and the preparation thereof.

First claim

We claim:

1. A compound of Formula (I)

wherein:
R 1 , R 2 are independently chosen from H, F, Cl, Br and CF 3 ;
R 3 is F, Cl or Br;
R 4 is F, Cl, Br, alkyl, alkenyl, alkynyl, alkoxy, hydroxyl, carboxyl, ester, acetal, amino, 5-membered cycle or heterocycle, or 6-membered cycle or heterocycle;
R 5 is H or alkyl;
X, Y are independently chosen from CH and N; and
linker is a 1-20 atom length carbon chain, wherein said chain optionally includes one or more ester bonds, amide bonds or oxygen atoms.

2. The compound according to claim 1 , wherein:
wherein X is CH, Y is CH, R 3 =Cl, and R 5 is H.

3. A compound according to Formula Ib, wherein:

wherein R 6 , R 7 are independently chosen from H and alkyl; or R 6 and R 7 taken together with the N atom to which they are attached to form a form 5-membered or 6-membered heterocycle ring; and
n is 1-10.

4. A compound according to formula Ic, wherein:

wherein R 8 , R 9 is independently chosen from H, alkyl, alkoxy, F, Cl, Br, CF 3 , hydroxyl, carboxyl, ester, cyano, amino, and nitro, or R 8 and R 9 taken together with the atoms to which they are attached form 5-membered or 6-membered fused ring;
X 1 , X 2 , X 3 are independently chosen from CH and N; and
n is 1-10.

5. A compound represented by

wherein R 10 is chosen from

and n is 1-10.

6. A compound represented by:

wherein R 11 is chosen from

and
linker is a 1-20 atom length carbon chain, wherein said chain optionally includes ester bonds, amide bonds or oxygen atoms.

7. A compound of Formula (II)

wherein X 4 , X 5 are independently chosen from F, Cl, Br and CF 3 ; and R 12 , R 13 are 1-20 atom length carbon chains, which is optionally substituted with one or more ester bonds, amide bonds or oxygen atoms; wherein said chain is tethered to a terminal group chosen from F, Cl, Br, alkyl, alkenyl, alkynyl, alkoxy, hydroxyl, carboxyl, ester, acetal, amino, 5-membered cycle or heterocycle, or 6-membered cycle and heterocycle.

8. The compound according to claim 1 , wherein said linker is a 7-20 atom length carbon chain, which is optionally substituted with one or more ester bonds, amide bonds or oxygen atoms; and
wherein R 4 is F, Cl, Br, alkyl, alkenyl, alkynyl, alkoxy, hydroxyl, carboxyl, ester, acetal, amino, 5-membered cycle or heterocycle, or 6-membered cycle or heterocycle.

9. The compound according to claim 1 , wherein
said linker is a 13-20 atom length carbon chain, which is optionally with substituted one or more ester bonds, amide bonds or oxygen atoms; and
wherein R 4 is F, Cl, Br, alkyl, alkenyl, alkynyl, alkoxy, hydroxyl, carboxyl, ester, acetal, amino, 5-membered cycle or heterocycle, or 6-membered cycle or heterocycle.

10. A method of treating dengue disease comprising administering an Dengue NS4B specific inhibitor to a subject having dengue disease, wherein the Dengue NS4B specific inhibitor is a compound of claim 1 .

11. The method of claim 10 , wherein the dengue disease is severe dengue disease, dengue hemorrhagic fever, or dengue shock syndrome.

12. The method of claim 10 , where in the dengue disease is caused by a dengue virus of serotype 1, 2, or 3.

13. The compound according to claim 2 , wherein said compound is:

14. The compound according to claim 3 , wherein said compound is:

wherein R 6 , R 7 are independently chosen from H and alkyl.

15. The compound according to claim 5 , wherein said compound is:

wherein R 10 is

and n is 1-10.

16. The compound according to claim 4 , wherein said compound is:

wherein R 8 , R 9 is H, alkyl, alkoxy, F, Cl, Br, CF 3 , hydroxy, carboxyl, ester, cyano, amino, and nitro.

Assignees

• Zhou Jia
• Shi Pei Yong
• Xu Jimin
• Xie Xuping
• Univ Texas

Inventors

• Zhou Jia
• Shi Pei-Yong
• Xu Jimin
• Xie Xuping

Classifications

• C07D471/20 Primary

  Spiro-condensed systems · CPC title

• A61P31/14 Primary

  for RNA viruses · CPC title

• C07D495/04

  Ortho-condensed systems · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title

• A61K31/438

  The ring being spiro-condensed with carbocyclic or heterocyclic ring systems · CPC title