Preparation of pyrazolo[3,4-B]pyridines as antimalarials

Patent metadata

Field	Value
Publication number	US-11578071-B2
Application number	US-202017063498-A
Country	US
Kind code	B2
Filing date	Oct 5, 2020
Priority date	Oct 4, 2019
Publication date	Feb 14, 2023
Grant date	Feb 14, 2023

Abstract

The present invention relates to pyrazolo[3,4-b]pyridine compounds. The present invention further relates to methods for inhibiting Plasmodium comprising contacting Plasmodium with pyrazolo[3,4-b]pyridine compounds described herein. Also described herein are methods of treating malaria comprising administering pyrazolo[3,4-b]pyridine compounds to a subject in need thereof.

First claim

The invention claimed is:

1. A compound of the following formula:

wherein R 1 -R 5 is H, hydroxyl, halo, haloalkyl, alkoxy haloalkoxy, carboxyl, alkoxycarbonyl, lower alkyl, sulfonyl, alkylsulfonyl, amino, imino, nitro, cyano, or alkynyl;
R 6 is alkyl, unsubstituted or substituted cycloalkyl, substituted or unsubstituted aryl excluding phenyl, or substituted or unsubstituted heteroaryl;
R 7 is alkyl excluding methyl; or R 7 is unsubstituted or substituted cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 8 -R 12 is H, OH, alkyl, alkoxy, halo, haloalkyl, alkoxy, branched or unbranched alkyl, haloalkyl, halo, cyano, nitro, sulfonyl, alkylsulfonyl, or heterocycloalkyl;
R 13 is cyano, nitro, imino, or alkynyl; and
R 10 may optionally form a 5 or 6 membered substituted or unsubstituted heterocycle with R 11 .

2. The compound of claim 1 of the following formula:

wherein R 1 -R 5 is H, hydroxyl, halo, haloalkyl, alkoxy haloalkoxy, carboxyl, alkoxycarbonyl, lower alkyl, sulfonyl, alkylsulfonyl, amino, imino, nitro, cyano, or alkynyl;
R 6 is alkyl, unsubstituted or substituted cycloalkyl, substituted or unsubstituted aryl excluding phenyl, or substituted or unsubstituted heteroaryl;
R 7 is alkyl excluding methyl; or R 7 is unsubstituted or substituted cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 8 -R 12 is H, OH, alkyl, alkoxy, halo, haloalkyl, alkoxy, branched or unbranched alkyl, haloalkyl, halo, cyano, nitro, sulfonyl, alkylsulfonyl, or heterocycloalkyl; and
R 10 may optionally form a 5 or 6 membered substituted or unsubstituted heterocycle with R 11 .

3. The compound of claim 2 , wherein
R 1 -R 5 is H, hydroxyl, halo, haloalkyl, alkoxy haloalkoxy, carboxyl, alkoxycarbonyl, lower alkyl, sulfonyl, alkylsulfonyl, amino, imino, nitro, cyano, or alkynyl;
R 6 is methyl;
R 7 is phenyl;
R 8 -R 9 is H;
R 10 is lower alkyl; and
R 11 -R 12 is H.

4. The compound of claim 3 selected from:

5. The compound of claim 2 , wherein
R 1 is OH;
R 2 -R 5 is H;
R 6 is lower alkyl;
R 7 is phenyl;
R 8 -R 12 is H, OH, alkyl, alkoxy, halo, haloalkyl, alkoxy, branched or unbranched alkyl, haloalkyl, halo, cyano, nitro, sulfonyl, alkylsulfonyl, or heterocycloalkyl; and
R 10 may optionally form a 5 or 6 membered substituted or unsubstituted heterocycle with R 11 .

6. The compound of claim 5 , selected from

7. The compound of claim 2 , wherein
R 1 is OH;
R 2 -R 5 is H;
R 6 is alkyl, unsubstituted or substituted cycloalkyl, substituted or unsubstituted aryl excluding phenyl, or substituted or unsubstituted heteroaryl;
R 7 is alkyl excluding methyl; or R 7 is unsubstituted or substituted cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 8 -R 9 is H;
R 10 is lower alkyl; and
R 11 -R 12 is H.

8. The compound of claim 7 selected from:

9. A pharmaceutical composition, comprising a compound of the following formula:

wherein R 1 -R 5 is H, hydroxyl, halo, haloalkyl, alkoxy haloalkoxy, carboxyl, alkoxycarbonyl, lower alkyl, sulfonyl, alkylsulfonyl, amino, imino, nitro, cyano, or alkynyl;
R 6 is alkyl, unsubstituted or substituted cycloalkyl, substituted or unsubstituted aryl excluding phenyl, or substituted or unsubstituted heteroaryl;
R 7 is alkyl excluding methyl; or R 7 is unsubstituted or substituted cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 8 -R 12 is H, OH, alkyl, alkoxy, halo, haloalkyl, alkoxy, branched or unbranched alkyl, haloalkyl, halo, cyano, nitro, sulfonyl, alkylsulfonyl, or heterocycloalkyl;
R 13 is cyano, nitro, imino, or alkynyl; and
R 10 may optionally form a 5 or 6 membered substituted or unsubstituted heterocycle with R 11 ; and
a pharmaceutically acceptable carrier.

10. A method for inhibiting the growth of Plasmodium comprising administering to cells infected with Plasmodium the compound of claim 1 .

11. The method of claim 10 , wherein the Plasmodium is Plasmodium falciparum.

12. The method of claim 10 , wherein the Plasmodium is drug resistant.

13. The method of claim 12 , wherein the Plasmodium is atovaquone-resistant.

14. The method of claim 10 , wherein the cells are in a subject.

15. The method of claim 14 , wherein the subject is a human.

Assignees

• Univ Kentucky Res Found
• Cal Poly Corp

Inventors

• Eagon Scott Charles
• Guy Rodney Kiplin
• Hammill Jared T

Classifications

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• C07D231/56 Primary

  Benzopyrazoles; Hydrogenated benzopyrazoles · 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