Iron binding agents
View Patent ↗Composition, article of manufacture for and method of treating malaria in a human having an infestation of Plasmodium protozoans are described. The method comprises administering a therapeutically-effective amount of a compound of formula (I) or (IV), i.e. sufficient quantity to reduce the population of Plasmodium . The composition of the invention is a compound of formula (I) or (IV) with a pharmaceutical excipient. The article of manufacture is the composition in combination with labeling for treating malaria. The substituents are detailed in the specification.
1. A pharmaceutical composition comprising an amount of a compound represented by formula (I) sufficient to reduce the population of Plasmodium in a human infested with Plasmodium protozoans and suffering from malaria, in combination with a pharmaceutically acceptable excipient, wherein formula (I) is
where:
R is OH, OR 7 , or N(OH)R 8 ;
R 1 is H, CH 3 or an available electron;
R 2 is H, CH 3 or an available electron;
R 3 is H, CH 3 or an available electron and together with either R 1 or R 2 when one is an available electron, forms a double bond with the R 1 /R 2 carbon;
R 4 is H, acyl of 1-4 carbons or alkyl of 1-4 carbons;
R 5 is H, OH, O-acyl of 1-4 carbons, O-alkyl of 1-4 carbons, or (CH 2 ) a (R 10 ) b (CH 2 ) a R 10 (CH 2 ) a (R 10 ) b X
R 6 is H, OH, alkyl of 1-6 carbons, a halogen, (CH 2 ) a (R 10 )(CH 2 ) r (R 10 )Y, or is C═C—C═C—, which, together with R 11 , when R 11 , is an available electron, forms a fused ring system as follows:
R 7 is alkyl of one to four carbons or optionally substituted benzyl;
R 8 is H, alkyl of one to four carbons, optionally substituted benzyl,
R 9 is H, alkyl of one to four carbons or optionally substituted benzyl;
R 10 is O or CH 2 ,
R 11 is H, OH, O-acyl of 1-4 carbons, O-alkyl of 1-4 carbons or an available electron;
A is N, CH or COH;
B is S, O, N, CH 2 or CH 2 S;
a is 2 or 3;
b is 0 or 1;
m is an integer from 1 to 8;
n is 0 or 1;
p is 0, 1 or 2;
r is 2 or 3;
wherein each of the substituents shown is defined above, or
a compound of formula (I) where the ring containing the B and N moieties is fully reduced and contains no double bonds, or a pharmaceutically acceptable salt of the compound represented by formula (I) or a stereoisomer of the compound or mixture of stereoisomers.
2. The composition of claim 1 , wherein B is S, and n and p are 0.
3. The composition of claim 2 , wherein
each of R 1 , R 2 and R 3 is H or CH 3 ,
each of R 5 and R 11 is H, OH, O-acyl of 1-4 carbons or O-alkyl of 1-4 carbons,
R 6 is H, OH, alkyl of 1-6 carbons or a halogen, and
R 7 is alkyl of 1-4 carbons.
4. The composition of claim 3 , wherein R 4 is H.
5. The composition of claim 2 , wherein R is N(OH)R 8 .
6. The composition of claim 5 , wherein R 8 is CH 3 .
7. The composition of claim 1 , wherein A is CH.
8. The composition of claim 7 , wherein B is S, and n and p each is 0.
9. The composition of claim 8 , wherein
each of R 1 , R 2 , R 3 , R 4 is H or CH 3 ,
each of R 5 and R 11 is H, OH, O-acyl of 1-4 carbons or O-alkyl of 1-4 carbons,
R 6 is H, OH, alkyl of 1-6 carbons or a halogen, and
R 7 is alkyl of 1-4 carbons.
10. The composition of claim 9 , wherein R 4 is H.
11. The composition of claim 9 , wherein each of R 1 , R 2 , R 3 , R 5 , and R 6 is H.
12. The composition of claim 9 , wherein R 11 is OH.
13. The composition of claim 12 , wherein each of R 1 , R 2 , R 3 , R 5 , and R 6 is H.
14. The composition of claim 10 , wherein R is N(OH)R 8 .
15. The composition of claim 14 , wherein R 11 is OH, and each of R 1 and R 2 is H.
16. The composition of claim 15 , wherein each of R 3 and R 5 is H.
17. The composition of claim 15 , wherein R 8 is CH 3 .