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US 10,519,098 B2Granted
Aromatic derivatives as anti-malarial
AssigneeCouncil of Scientific and Industrial Research
InventorsAsish Kumar Bhattacharya, Eswar Kumar Aratikatla, Kumkum Srivastava, Ashan Manhas
Life of this patent
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Abstract
The present invention discloses anti-malarial compound of formula (I) Formula (I) wherein, X is selected from O or NH; R1, R2, R3, R4 and R5 is selected from H or OMe or CH3, —CH2—O—CH2— or —CH═CH—CH═CH—; Y is selected from O or NH and R6, R7 is selected from the following compounds: or pharmaceutically acceptable salts thereof, process for preparation and a pharmaceutical composition containing the same.
Claims8
A compound of formula (I)
- wherein, X is selected from O and NH;
- R1, R2, R3, R4 and R5 is selected from H, CH3, and OMe, or R1 and R2 or R2 and R3 or R3 and R4 or R4 and R5 may be combined to form a 5 or 6 membered saturated or unsaturated ring optionally having one or more hetero atoms;
- Y is selected from O and NH and
- R6, R7 is selected from
- and a pharmaceutically acceptable salt thereof
- with the proviso that when R6 is
- then X is NH, and TBS refers to Tert-butyldimethyl silyl;
- and
- wherein said compound is selected from
- (R)-2-cinnamamido-1-(3,4-dimethoxyphenyl)ethylcinnamate,
- (S)-1-(3,4-dimethoxyphenyl)ethane-1,2-diyl(2E,2′E)-bis(3-phenylacrylate),
- (R)-1-(3,4-dimethoxyphenyl)ethane-1,2-diyl(2E,2′E)-bis(3-phenylacrylate),
- (S)-2-cinnamamido-1-(3,4,5-trimethoxyphenyl) ethyl cinnamate,
- (R)-2-cinnamamido-1-(3,4,5-trimethoxyphenyl)ethyl cinnamate,
- (S)-1-(3,4,5-trimethoxyphenyl)ethane-1,2-diyl (2E,2′E)-bis(3-phenylacrylate),
- (R)-1-(3,4,5-trimethoxyphenyl)ethane-1,2-diyl(2E,2′E)-bis(3-phenylacrylate),
- (S)-2-cinnamamido-1-(2-methoxyphenyl)ethylcinnamate,
- (R)-2-cinnamamido-1-(2-methoxyphenyl)ethylcinnamate,
- (S)-1-(2-methoxyphenyl)ethane-1,2-diyl(2E,2′E)-bis(3-phenylacrylate),
- (R)-1-(2-methoxyphenyl)ethane-1,2-diyl(2E,2′E)-bis(3-phenylacrylate),
- (S)-2-cinnamamido-1-(3-methoxyphenyl)ethyl cinnamate,
- (R)-2-cinnamamido-1-(3-methoxyphenyl)ethylcinnamate,
- (S)-1-(3-methoxyphenyl)ethane-1,2-diyl (2E,2′E)-bis(3-phenylacrylate),
- (R)-1-(3-methoxyphenyl)ethane-1,2-diyl(2E,2′E)-bis(3-phenylacrylate),
- (S)-2-cinnamamido-1-(4-methoxyphenyl)ethyl cinnamate,
- (R)-2-cinnamamido-1-(4-methoxyphenyl)ethylcinnamate,
- (S)-1-(4-methoxyphenyl)ethane-1,2-diyl (2E,2′E)-bis(3-phenylacrylate),
- (R)-1-(4-methoxyphenyl)ethane-1,2-diyl(2E,2′E)-bis(3-phenylacrylate),
- (S)-2-cinnamamido-1-(2,3-dimethoxyphenyl)ethyl cinnamate,
- (R)-2-cinnamamido-1-(2,3-dimethoxyphenyl)ethyl cinnamate,
- (S)-1-(2,3-dimethoxyphenyl)ethane-1,2-diyl(2E,2′E)-bis(3-phenylacrylate),
- (R)-1-(2,3-dimethoxyphenyl)ethane-1,2-diyl(2E,2′E)-bis(3-phenylacrylate),
- (S)-2-cinnamamido-1-phenylethyl cinnamate,
- (R)-2-cinnamamido-1-phenylethyl cinnamate,
- (S)-1-phenylethane-1,2-diyl(2E,2′E)-bis(3-phenylacrylate),
- (R)-1-phenylethane-1,2-diyl (2E,2′E)-bis(3-phenylacrylate),
- (S)-2-cinnamamido-1-(p-tolyl)ethyl cinnamate,
- (R)-2-cinnamamido-1-(p-tolyl)ethylcinnamate,
- (S)-1-(p-tolyl)ethane-1,2-diyl (2E,2′E)-bis(3-phenylacrylate),
- (R)-1-(p-tolyl)ethane-1,2-diyl(2E,2′E)-bis(3-phenylacrylate),
- (S)-1-(benzo[d][1,3]dioxol-5-yl)-2-cinnamamidoethylcinnamate,
- (R)-1-(benzo[d][1,3]dioxol-5-yl)-2-cinnamamidoethylcinnamate,
- (S)-1-(benzo[d][1,3]dioxol-5-yl)ethane-1,2-diyl(2E,2′E)-bis(3-phenylacrylate),
- (R)-1-(benzo[d][1,3]dioxol-5-yl)ethane-1,2-diyl (2E,2′E)-bis(3-phenylacrylate),
- (S)-1-(benzo[d][1,3]dioxol-4-yl)ethane-1,2-diyl (2E,2′E)-bis(3-phenylacrylate),
- (R)-1-(benzo[d][1,3]dioxol-4-yl)ethane-1,2-diyl (2E,2′E)-bis(3-phenylacrylate),
- (S)-2-benzamido-1-(3,4-dimethoxyphenyl)ethyl benzoate,
- (R)-2-benzamido-1-(3,4-dimethoxyphenyl)ethyl benzoate,
- (S)-1-(3,4-dimethoxyphenyl)-2-((E)-3-(3,4,5-trimethoxyphenyl)acrylamido)ethyl(E)-3-(3,4,5-trimethoxyphenyl)acrylate,
- (R)-1-(3,4-dimethoxyphenyl)-2-((E)-3-(3,4,5-trimethoxyphenyl)acrylamido)ethyl(E)-3-(3,4,5-trimethoxyphenyl)acrylate,
- (S)-1-(3,4-dimethoxyphenyl)-2-(3-phenylpropanamido)ethyl-3-phenylpropanoate,
- (R)-1-(3,4-dimethoxyphenyl)-2-(3-phenylpropanamido)ethyl-3-phenylpropanoate,
- (S)-2-butyramido-1-(3,4-dimethoxyphenyl)ethylbutyrate,
- (S)-2-((E)-3-(2-((tert-butyldimethylsilyl)oxy)phenyl)acrylamido)-1-(3,4-dimethoxyphenyl)ethyl(E)-3-(2-((tert-butyldimethylsilyl)oxy)phenyl)acrylate;
- (S)-2-((E)-3-(3-((tert-butyldimethylsilyl)oxy)phenyl)acrylamido)-1-(3,4-dimethoxyphenyl)ethyl(E)-3-(3-((tert-butyldimethylsilyl)oxy)phenyl)acrylate,
- (S)-2-((E)-3-(4-((tert-butyldimethylsilyl)oxy)phenyl)acrylamido)-1-(3,4-dimethoxy phenyl)ethyl(E)-3-(4-((tert-butyldimethylsilyl)oxy)phenyl)acrylate,
- (S)-2-cinnamamido-1-(3,4-dimethoxyphenyl)ethyl3-phenylpropanoate,
- (S)-1-(3,4-dimethoxyphenyl)-2-(3-phenylpropanamido)ethylcinnamate,
- (S)-2-butyramido-1-(3,4-dimethoxyphenyl)ethylcinnamate,
- (S)-2-cinnamamido-1-(3,4-dimethoxyphenyl)ethyl butyrate,
- (S)-1-(naphthalen-2-yl)ethane-1,2-diyl (2E,2′E)-bis(3-phenylacrylate),
- (R)-1-(naphthalen-2-yl)ethane-1,2-diyl (2E,2′E)-bis(3-phenylacrylate),
- (S)-2-cinnamamido-2-(3,4-dimethoxyphenyl)ethylcinnamate,
- (S)-1-(3,4-dimethoxyphenyl)ethane-1,2-diyl(2E,2′E)-bis(3-(3,4,5-trimethoxyphenyl)acrylate),
- (S)-1-(3,4,5-trimethoxyphenyl)ethane-1,2-diyl(2E,2′E)-bis(3-(3,4,5-trimethoxyphenyl)acrylate), and
- (S)-1-(3,4,5-trimethoxyphenyl)-2-((E)-3-(3,4,5-trimethoxyphenyl)acrylamido)ethyl(E)-3-(3,4,5-trimethoxyphenyl)acrylate.
63 more elements
A process for the preparation of compounds of formula (I)
- wherein, X is selected from O and NH;
- R1, R2, R3, R4 and R5 is selected from H, CH3, and OMe, or
- R1 and R2 or R2 and R3 or R3 and R4 or R4 and R5 may be combined to form a 5 or 6 membered saturated or unsaturated ring optionally having one or more hetero atoms;
- Y is selected from O and NH and
- R6, R7 is selected from
- and a pharmaceutically acceptable salt thereof
- with the proviso that when R6 is
- then X is NH, and TBS refers to Tert-butyldimethyl silyl
- wherein said process comprises the steps of:
- a) subjecting the styrene compound of formula B
- to dihydroxylation at 0° C. for the period ranging from 6 to 24 h to obtain the diol compound of formula C
- b) subjecting the diol compound of formula C of step (a) to monotosylation at 0° C. for the period ranging from 3 to 4 h to obtain the monotosylated compound of formula D
- c) treating the monotosylated compound of formula D of step (b) with sodium azide to obtain the azido alcohol of formula E
- d) reducing the azido alcohol of formula E of step (c) with anhydrous MeOH and palladium on carbon to furnish the amino alcohol of formula F
- e) coupling the amino alcohol of formula F of step (d) or diol compound of formula C of step (a) with carboxylic acid in presence of DCC (N,N′-dicyclohexylcarbodiimide) and DMAP (4-Dimethylaminopyridine) to obtain the compound of formula I.
12 more elements
Dependencies are inferred from the claim text.