Amino-functionalized 1,2,4-trioxanes useful as antimalarial agents and process for preparation thereof
AssigneeCouncil of Scientific and Industrial Research
InventorsChndan Singh, Heetika Malik, Sunil Puri
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Abstract
The present invention relates to a novel series of antimalarial amino functionalized 1,2,4-trioxane analogues of formula 4 wherein Ar represents aryl groups such as phenyl, 4-biphenyl, 4-chlorophenyl, 4-methoxyphenyl, 4-methylphenyl and R represents phenyl, 4-methoxyphenyl, 4-chlorophenyl, 3,5-dichlorophenyl, 4-acetylaminophenyl, 1-naphthyl, 2-biphenyl, 4-biphenyl, 2-fluorene, 4-fluorophenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl and 4-trifluoromethylphenyl and the like.
Claims14
A substituted amino functionalized 1,2,4-trioxane of formula 4
- wherein Ar represents aryl groups selected from the groups consisting of phenyl, 4-biphenyl, 4-chlorophenyl, 4-methoxyphenyl and 4-methylphenyl and R represents phenyl, 4-methoxyphenyl, 4-chlorophenyl, 3,5-dichlorophenyl, 4-acetylaminophenyl, 1-naphthyl, 2-biphenyl, 4-biphenyl, 2-fluorene, 4-fluorophenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl and 4-trifluoromethylphenyl.
Compound of formula 4 with structural formula 4aa-4ai shown below:
Compound of formula 4 with structural formula 4ba-4bi shown below:
Compound of formula 4 with structural formula 4ca-4cp shown below:
Compound of formula 4 with structural formula 4da-4dn shown below:
Compound of formula 4 with structural formula 4ea-4eo shown below:
Method for the preparation of a substitute amino functionalize-1,2,4-trioxane of formula 4
- wherein Ar represents aryl groups selected from the groups consisting of phenyl 4-biphenyl, 4-chlorophenyl, 4-methoxyphenyl and 4-methylphenyl and R represents phenyl, 4-methoxyphenyl, 4-chlorophenyl, 3,5-dichlorophenyl, 4-acetylaminophenyl, 1-naphthyl, 2-biphenyl, 4-biphenyl, 2-fluorene, 4-fluorophenyl 2-trifluoromethylphenyl, 3-trifluoromethylphenyl and 4-trifluoromethylphenyl, the process comprising reacting a keto trioxane of formula 3
- with an aromatic me in the presence of NaBH(OAc)3 in CH2Cl2 to furnish amino functionalized 1,2,4-trioxanes of formula 4.
A method for the preparation of substituted amino functionalized-1,2,4-trioxanes of formula 4
- wherein Ar is an aryl group selected from the group consisting of phenyl, 4-biphenyl, 4-chlorophenyl, 4-methoxyphenyl and 4-methylphenyl and R represents phenyl, 4-methoxyphenyl, 4-chlorophenyl 3,5-dichlorophenyl, 4-acetylaminophenyl, 1-naphthyl, 2-biphenyl % 4-biphenyl, 2-fluorene, 4-fluorophenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl and 4-trifluoromethylphenyl, the method comprising:
- (i) photooxygenating an allylic alcohol of formula 1 by passing oxygen gas or air in a solution of the alcohol in an organic solvent and in the presence of a dye and a light source which provides visible light, for a period of 4 b, to obtain a β-hydroxyhydroperoxide of formula 2
- (ii) reacting the hydroperoxides of formula 2 in situ with 1,4-cyclohexanedione in the presence of an acid catalyst to give a trioxane of formula 3;
- reacting the keto trioxane of formula 3 with an aromatic amine in the presence of NaBH(OAc)3 in CH2Cl2 to obtain amino functionalized 1,2,4-trioxane of formula 4.
A method of treating a subject having malaria, comprising administering to the subject a pharmaceutically effective amount of a composition containing substituted amino functionalized-1,2,4-trioxanes of formula 4,
- wherein Ar represents aryl groups selected from the groups consisting of phenyl, 4-biphenyl, 4-chlorophenyl, 4-methoxyphenyl and 4-methylphenyl and R represents phenyl, 4-methoxyphenyl, 4-chlorophenyl, 3,5-dichlorophenyl, 4-acetylaminophenyl, 1-naphthyl, 2-biphenyl, 4-biphenyl, 2-fluorene, 4-fluorophenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl and 4-trifluoromethylphenyl and a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.