Inactivators of toxoplasma gondii ornithine aminotransferase for treating toxoplasmosis and malaria

Patent metadata

Field	Value
Publication number	US-11207283-B2
Application number	US-202016836870-A
Country	US
Kind code	B2
Filing date	Mar 31, 2020
Priority date	Oct 10, 2016
Publication date	Dec 28, 2021
Grant date	Dec 28, 2021

Abstract

Disclosed are methods, compounds, and compositions for treating infection by an Apicomplexan parasite that include administering a compound that selectively inactivates ornithine aminotransferase of the Apicomplexan parasite. Specifically, the methods, compounds, compounds may be utilized for treating infection by Toxoplasma gondii and toxoplasmosis and for treating infection by Plasmodium falciparum and malaria. The compounds disclosed herein are observed to selectively inactivate Toxoplasma gondii ornithine aminotransferase (TgOAT) relative to human OAT and relative to human γ-aminobutyric aminotransferase (GABA-AT).

First claim

We claim:

1. A compound having a formula:

wherein:
m is 1-6;
n is 0-6; and
R 2 , R 3 and R 4 may be the same or different and are selected from hydrogen, halo, and C1-C6 alkyl which may be straight chain or branched and may be substituted at one or more positions with halo.

2. A pharmaceutical composition comprising the compound of claim 1 together with a pharmaceutical carrier or excipient.

3. The compound of claim 1 , wherein the compound has a formula:

4. The compound of claim 1 , wherein the compound has a formula:

5. The compound of claim 1 , wherein the compound has a formula:

6. A compound having a formula:

wherein:
R 2 , R 3 and R 4 may be the same or different and are selected from hydrogen, halo, and C1-C6 alkyl which may be straight chain or branched and may be substituted at one or more positions with halo.

7. A pharmaceutical composition comprising the compound of claim 6 together with a pharmaceutical carrier or excipient.

8. A method for treating a subject infected with an Apicomplexan parasite, the method comprising administering to the subject an effective amount of the compound of claim 6 that selectively inactivates ornithine aminotransferase of the Apicomplexan parasite.

9. A compound having a formula:

10. A pharmaceutical composition comprising the compound of claim 9 together with a pharmaceutical carrier or excipient.

11. A method for treating a subject infected with an Apicomplexan parasite, the method comprising administering to the subject an effective amount of the compound of claim 9 that selectively inactivates ornithine aminotransferase of the Apicomplexan parasite.

Assignees

• Univ Northwestern
• Univ Chicago

Inventors

• Silverman Richard B
• Le Hoang V
• Mcleod Rima L
• Hawker Dustin D

Classifications

• C12Y206/01013

  Ornithine aminotransferase (2.6.1.13) · CPC title

• A61K31/196 Primary

  the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil · CPC title

• A61K31/03

  aromatic · CPC title

• A61K31/381

  having five-membered rings · CPC title

• A61K31/035

  having aliphatic unsaturation · CPC title