Use of cymanquine compounds as antimalarial agents

Patent metadata

Field	Value
Publication number	US-10512652-B2
Application number	US-201615745938-A
Country	US
Kind code	B2
Filing date	Jul 20, 2016
Priority date	Jul 20, 2015
Publication date	Dec 24, 2019
Grant date	Dec 24, 2019

Abstract

Organometallic compounds comprising a chloroquinoline moiety for use in the prophylaxis and treatment of malaria. The compounds can be manganese or rhenium complexes of a ligand comprising a chloroquinoline moiety.

First claim

What is claimed is:

1. A method of treatment of malaria comprising administering to an individual who has been diagnosed with and/or is suffering from malaria comprising administering to the individual a therapeutically effective amount of a composition comprising one of more compounds of the following formula:

wherein:
M is Mn or Re,
L is a neutral, two-electron donor ligand,
R 1 is an amine-substituted alkyl group,
R 2 is H, (CH 2 ) n CH 3 , wherein n is 0 or any integer from 1 to 20, OMe, OEt, OPh, Ph, CHO, COMe, COPh, CH 2 OH, CO 2 H, CO 2 Me, CO 2 Et, CH 2 Ph, NH 2 , NMe 2 , NEt 2 , C 6 H 4 Me, C 6 H 4 OMe, NH 2 COMe, F, Cl, Br, or I; and
E is a linker moiety connecting the cyclopentadienyl moiety with the chloroquinoline moiety, wherein E is —NH(CH 2 ) n —, —NH(CH 2 ) n NH—, or —NH(CH 2 ) n NH(CH 2 )— and n is an integer from 1 to 10.

2. The method of claim 1 , wherein R 1 is (CH 2 ) n NR 3 R 4 , wherein n is an integer from 1 to 20 and R 3 and R 4 are independently H or an C 1 -C x alkyl group, wherein x is an integer from 2 to 20.

3. The method of claim 1 , wherein L is —CO, a phosphine, a phosphite, an aryl amine, or a carbene.

4. The method of claim 3 , wherein the phosphine is a water-soluble phosphine.

5. The method of claim 3 , wherein the phosphine is alkyl phosphine, aryl phosphine, or alkyl aryl phosphine.

6. The method of claim 3 , wherein the aryl amine is pyridine.

7. The method of claim 1 , wherein a second CO ligand is replaced by a two-electron donor.

8. The method of claim 1 , wherein M is Mn.

9. The method of claim 1 , wherein the compound has the following structure:

10. The method of claim 1 , wherein the compound has the following structure:

11. The method of claim 3 , wherein M is Mn.

12. A kit comprising one or more containers or packaging having a compound of claim 1 , and instructions for use for treatment of malaria.

13. The kit of claim 12 , wherein the kit comprises a plurality of individualized sealed packets, each individual packet representing a dose of the composition for a single use.

Assignees

• Univ Of Vermont And State Agricultural College
• Univ Drexel

Inventors

• Geiger William E
• Lam Kevin
• Bergman Lawrence W

Classifications

• A61K31/555 Primary

  containing heavy metals, e.g. hemin, hematin, melarsoprol · CPC title

• A61P33/06

  Antimalarials · CPC title

• Y02A50/411

  Cross-Sectional Technologies · mapped topic

• 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