Compounds and methods for the treatment of parasitic diseases

Patent metadata

Field	Value
Publication number	US-11866441-B2
Application number	US-202117387639-A
Country	US
Kind code	B2
Filing date	Jul 28, 2021
Priority date	Mar 20, 2017
Publication date	Jan 9, 2024
Grant date	Jan 9, 2024

Abstract

Provided herein are compounds useful for the treatment of various parasitic diseases. These compounds, as well as pharmaceutically acceptable salts thereof may be formulated in pharmaceutical compostions, veterinary compositions and may be used in methods of treatment and/or prophylaxis of diseases spread by parasites, including malaria and cryptosporidiosis.

First claim

What is claimed is:

1. A compound having the structure:

R 1 is optionally substituted aryl or heteroaryl;
R 2 is optionally substituted alkoxy, cycloalkoxy or heterocyclyl;
R 3 is hydrogen, or —CH 2 —X;
R 4 and R 5 are independently hydrogen, —X, or —CH 2 —X, and at least one of R 4 and R 5 is not hydrogen;
—X is independently selected at each occurrence from —OH, —OR, —S(O)R, —S(O) 2 R, —N(R)—S(O) 2 R, —S(O) 2 —N(R)(R), —S(O) 2 —NHR, —N(R)—C(O)—R, —NH 2 , or —N(R)(R); and
R is independently at each occurrence an optionally substituted C 1 -C 12 alkyl;
or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 having the structure:

or pharmaceutically acceptable salts thereof.

3. The compound according to claim 1 having the structure:

or pharmaceutically acceptable salts thereof.

4. The compound according to claim 1 having the structure:

or pharmaceutically acceptable salts thereof.

5. The compound according to claim 1 , wherein R 4 and R 5 are the same functional group selected from —X or —CH 2 —X; or
pharmaceutically acceptable salts thereof.

6. The compound according to claim 1 , wherein R 5 is hydrogen and R 4 is —X, or —(CH 2 )—X; or
pharmaceutically acceptable salts thereof.

7. The compound according to claim 1 , wherein R 4 is hydrogen and R 5 is —X, or —(CH 2 )—X; or
pharmaceutically acceptable salts thereof.

8. The compound according to claim 1 , wherein —X in the group —X or —(CH 2 )—X of R 4 or R 5 is —OH, —NH 2 , or —N(R)(R); or
pharmaceutically acceptable salts thereof.

9. The compound according to claim 1 , wherein R 4 and R 5 are —OH; or
pharmaceutically acceptable salts thereof.

10. The compound according to claim 1 , wherein R 1 is phenyl, fluorophenyl, difluorophenyl, or pyridyl; or pharmaceutically acceptable salts thereof.

11. The compound according to claim 1 , wherein R 2 is C 1-4 linear or branched alkoxy; or
pharmaceutically acceptable salts thereof.

12. The compound according to claim 1 , wherein R 2 is methoxy; or
pharmaceutically acceptable salts thereof.

13. The compound according to claim 1 , wherein said compound is selected from the group consisting of

or
pharmaceutically acceptable salts thereof.

14. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 1 , or
a pharmaceutically acceptable salt thereof.

15. The pharmaceutical composition according to claim 14 , formulated as a veterinary composition, or
a pharmaceutically acceptable salt thereof.

16. A method of treatment or prophylaxis of malaria, drug resistant malaria, or cryptosporidiosis in a subject, comprising the step of administering to the subject an effective amount of a compound of claim 1 , or
a pharmaceutically acceptable salt thereof.

17. The method of claim 16 , wherein said parasitic disease is malaria or drug resistant malaria.

18. The method of claim 17 , wherein the liver of said subject is infected with a malaria-causing parasite and administration prevents spread of said infection from their liver.

19. A method of preventing the spread of Plasmodium infection, preventing the symptomatic stage of malaria, or preventing establishment of Plasmodium infection in a subject, comprising administering to the subject an effective amount of a compound of claim 1 , or
a pharmaceutically acceptable salt thereof.

Assignees

• Broad Inst Inc
• Harvard College

Inventors

• Comer Eamon
• Kato Nobutaka
• Morningstar Marshall
• Melillo Bruno

Classifications

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• A61P33/06

  Antimalarials · CPC title

• A61P33/00

  Antiparasitic agents · CPC title

• A61P33/02

  Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis · 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