Biphenyl compounds for use in treating malaria and other parasitic disorders

Patent metadata

Field	Value
Publication number	US-9499471-B2
Application number	US-201214343431-A
Country	US
Kind code	B2
Filing date	Sep 10, 2012
Priority date	Sep 8, 2011
Publication date	Nov 22, 2016
Grant date	Nov 22, 2016

Abstract

The present invention relates to a compound of formula (I)

as defined herein.

First claim

The invention claimed is:

1. A method of treating or preventing a disease caused by a parasite of the group of Apicomplexa, comprising administering at least one compound of formula (V)

wherein
R 1 and R 2 are
aryl(C 1 -C 4 )alkyl, heteroaryl(C 1 -C 4 )alkyl or (C 1 -C 4 )alkoxyphenyl(C 1 -C 4 )alkyl;
R 3 and R 4 are independently selected from OH, OCH 3 , COOH, and phenylalkyl; or
R 3 and R 4 together with
(i) CO— 0 form a 6-membered lactone ring;
(ii) O—C(A)(B)—O form a 7-membered acetal or ketal ring; or
(iii) O—CH(A)-CH(B)—O or O—(CH 2 ) n —O form a ring with two ether oxygens, n being 1, 2, 3 or 4;
wherein A and B are independently selected from hydrogen, (C 1 -C 4 )alkyl, and (C 1 -C 4 ) alkenyl;

X 1 —Y 1 —Z 1 and X 2 —Y 2 —Z 2 are independently selected from CH 2 —CO—O, NH—CNH—NH, CH 2 —CO—NH, CH 2 —CNH—O, CH 2 —CNH—NH and CH 2 —CO; and
R 5 , R 6 , R 7 , R 8 , R 9 and R 10 are H;
wherein the aryl and heteroaryl moieties comprise one or two rings, each ring containing 5 or 6 atoms and wherein heteroaryl moieties comprise at least one heteroatom selected from N, 0 , and S.

2. The method of claim 1 , wherein said disease and said parasite, respectively, are
(a) Plasmodium and malaria;
(b) Toxoplasma gondii and toxoplasmosis;
(c) Eimeria and coccidiosis;
(d) Isospora and isosporiasiscoccidiosis;
(e) Babesia and babesiosis;
(f) Cyclospora and cyclosporiasis;
(g) Cryptosporidium and cryptosporidiosis;
(h) Theileria and theileriosis;
(i) Neospora and neosporosis;
(j) SarcocystisHoareosporidium and sarcocystiosis.

3. The method of claim 2 , wherein said parasite is Plasmodium falciparum.

4. The method of claim 1 , wherein the at least one compound is a compound of formula (II), (IIIa), (IIIb), (IIIc), (IIId), or (IV):

wherein R is R 1 .

5. The method of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

6. The method of claim 1 , wherein R 1 and R 2 are each independently selected from aryl(C 1 )alkyl, heteroaryl(C 1 )alkyl, and (C 1 )alkoxyphenyl(C 1 )alkyl.

7. The method of claim 1 , wherein R 1 and R 2 are each independently selected from benzyl and (C 1 -C 4 )alkoxyphenylmethyl.

8. The method of claim 1 , wherein R 3 and R 4 are each independently selected from OH and OCH 3 .

9. The method of claim 1 , wherein X 1 —Y 1 —Z 1 and X 2 —Y 2 —Z 2 are each CH 2 —CO—O.

10. The method of claim 1 , wherein R 3 is OH and R 4 is COOH.

11. The method of claim 1 , wherein R 3 is COOH and R 4 is OH.

12. The method of claim 1 , wherein A is allyl.

13. The method of claim 1 , wherein B is allyl.

14. The method of claim 1 , wherein A is methyl or ethyl and B is hydrogen.

15. The method of claim 1 , wherein B is methyl or ethyl and A is hydrogen.

16. The method of claim 4 , wherein R is CH 3 or CH 2 C 6 H 5 .

Assignees

• Manstein Dietmar
• Preller Matthias
• Furch Marcus
• Kalesse Markus
• Diaz-Gomez Nina
• Medizinische Hochschule Hannover

Inventors

• Manstein Dietmar
• Preller Matthias
• Furch Marcus
• Kalesse Markus
• Diaz-Gomez Nina

Classifications

• C07C69/734

  Ethers · CPC title

• C07D213/30

  Oxygen atoms · CPC title

• C07D295/205

  Radicals derived from carbonic acid · CPC title

• C07C69/616 Primary

  polycyclic · CPC title

• C07C257/06

  having carbon atoms of imino-carboxyl groups bound to hydrogen atoms, to acyclic carbon atoms, or to carbon atoms of rings other than six-membered aromatic rings · CPC title