Synthesis of Novel Diverse Methoxybenzenes‐substituted 2 H /4 H ‐chromene Derivatives in the Presence of InBr 3 (5 mol%) and their Cytotoxic Activity
A series of novel 2‐(trifluoromethyl)‐2 H /4 H ‐chromene‐3‐carboxylate isomers 3 and 4 functionalized with diverse methoxybenzenes 2 at position 4 in compound 3 and position 2 in compound 4 were prepared in different proportions by nucleophilic substitution on ethyl 2‐hydroxy‐2‐(trifluoromethyl)‐2 H...
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Published in | Journal of heterocyclic chemistry Vol. 54; no. 6; pp. 3607 - 3617 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.11.2017
|
Online Access | Get full text |
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Summary: | A series of novel 2‐(trifluoromethyl)‐2
H
/4
H
‐chromene‐3‐carboxylate isomers
3
and
4
functionalized with diverse methoxybenzenes
2
at position 4 in compound
3
and position 2 in compound
4
were prepared in different proportions by nucleophilic substitution on ethyl 2‐hydroxy‐2‐(trifluoromethyl)‐2
H
‐chromene‐3‐carboxylate
1
in single step promoted by Indium (III) bromide (5 mol%) a Lewis acid. Regiospecific isomers
3k
,
3l
,
3m
, and
3n
prepared by using sterically bulk 1,3,5‐trimethoxy benzene substrate
2e
in this reaction. Further, isomers
3a
and
4a
independently on reaction with amines, only compound
3a
could give Michael addition products
5a–c
. All the compounds
3a–n
,
4a–j
, and
5a–c
were screened for cytotoxic activity against four human cancer cell lines and found to show high activity at micromolar concentration. The compounds
4h
and
5a–c
showed promising cytotoxic activity against the tested cancer cell lines. Further, these compounds
4h
and
5a–c
were docked with protein (1SA0) on colchicine‐binding site of β tubulin suggesting that tubulin inhibition could be the possible mechanism of action for these compounds. |
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ISSN: | 0022-152X 1943-5193 |
DOI: | 10.1002/jhet.2987 |