Synthesis of 4,4-Disubstituted 3-Methylidenechroman-2-ones as Potent Anticancer Agents.
ChemMedChem
; 12(8): 599-605, 2017 04 20.
Article
em En
| MEDLINE
| ID: mdl-28258688
ABSTRACT
The synthesis of a new library of 4,4-disubstituted 3-methylidene-3,4-dihydro-2H-chroman-2-ones applying Horner-Wadsworth-Emmons methodology for the construction of an exo-methylidene moiety is reported. Corresponding 3-diethoxyphosphorylchroman-2-ones were synthesized in a three-step reaction sequence consisting of O-methylation of ethyl 2-diethoxyphosphoryl-3-oxoalkanoates, followed by reaction of the obtained 2-diethoxyphosphoryl-3-methoxy-2-alkenoates with phenols or 1-naphthol. The resulting 3-diethoxyphosphorylochromen-2-ones proved to be effective Michael acceptors in reactions with various Grignard reagents. Preliminary biological evaluations showed that many of the synthesized 3-methylidenechroman-2-ones possess very high cytotoxic activity against NALM-6 and HL-60 cancer cell lines (IC50 <1.0â
µm) as well as high activity against the MCF-7 cancer cell line (IC50 <10â
µm). Furthermore, two of the highly active 3-methylidenechroman-2-ones with geminal methyl and ethyl substituents at positionâ
4 showed promising therapeutic indexes of 10 and 13 in tests against human umbilical vein endothelial cells (HUVECs).
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MEDLINE
Assunto principal:
Cumarínicos
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article