Aminoalkylphenols, methods of using and making the same
View Patent ↗The present invention relates to Mannich base antimalarial aminoalkylphenol compounds and their use against protozoa of the genus Plasmodium , particularly emerging strains of drug-resistant Plasmodia. This invention further relates to compositions containing such compounds and a process for making the compounds. This and other aspects of the invention are realized upon review of the entire specification.
1. A pharmaceutical composition for the treatment of malaria, which comprises a compound of formula I:
or a pharmaceutically acceptable salt or enantiomer or diastereomer thereof, a second anti-malarial agent, and a pharmaceutically acceptable carrier;
wherein:
R 5 is hydrogen;
R 1a and R 1 independently are tert-butyl, halo, C 1-6 alkoxy, C 3-10 cycloalkyl, C 6-10 aryl, or trihalovinyl, wherein said aryl is optionally substituted with 1-3 groups of R a ;
each R 2 is hydrogen;
R 3 and R 3a are independently hydrogen, halo, C 1-6 alkyl, C 3-10 cycloalkyl, or C 6-10 aryl, wherein said aryl and alkyl are each optionally substituted with 1-3 groups of R a ;
R 4 is hydrogen;
R a represents C 1-6 alkoxy, C 1-6 alkyl, CF 3 , nitro, amino, cyano, C 1-6 alkylamino, or halogen; and
n represents 1-3.
2. A pharmaceutical composition according to claim 1 , wherein in the compound of formula I, or a pharmaceutically acceptable salt thereof, R 1a and R 1 independently are tert-butyl, 1,2,2-trichlorovinyl, or phenyl.
3. A pharmaceutical composition according to claim 1 , wherein in the compound of formula I, or a pharmaceutically acceptable salt thereof, n is 1.
4. A pharmaceutical composition according to claim 1 , wherein in the compound of formula I, or a pharmaceutically acceptable salt thereof, R 1a and R 1 independently are tert-butyl, 1,2,2-trichlorovinyl, or phenyl; and n is 1.
5. A pharmaceutical composition according to claim 4 , wherein in the compound of formula I or a pharmaceutically acceptable salt thereof, R 1a and R 1 are tert-butyl.
6. A pharmaceutical composition according to claim 5 , wherein the compound of formula I is 2-(aminomethyl)-3,5-di-tert-butylphenol or a pharmaceutically acceptable salt thereof.
7. A pharmaceutical composition according to claim 6 , wherein the compound of formula I is 2-(aminomethyl)-3,5-di-tert-butylphenol hydrochloride.
8. A pharmaceutical composition according to claim 1 , wherein the second anti-malarial agent is selected from the group consisting of Chloroquine, Fansidar, Amodiaquine, Quinine, Halofantrine, Mefloquine, Artemether/Artesunate and Malarone.
9. A pharmaceutical composition according to claim 6 , wherein the second anti-malarial agent is selected from the group consisting of Chloroquine, Fansidar, Amodiaquine, Quinine, Halofantrine, Mefloquine, Artemether/Artesunate and Malarone.
10. A pharmaceutical composition according to claim 7 , wherein the second anti-malarial agent is selected from the group consisting of Chloroquine, Fansidar, Amodiaquine, Quinine, Halofantrine, Mefloquine, Artemether/Artesunate and Malarone.