473907-59-4Relevant articles and documents
Synthesis and vasorelaxing evaluation of α-methylidene-γ-butyrolactone bearing quinolin-2(1H)-one and 3,4-dihydroquinolin-2(1H)-one derivatives
Wang, Tai-Chi,Zhao, Yue-Ling,Kuo, Daih-Huang
, p. 909 - 914 (2001)
The main objective of this investigation was to explore the vasorelaxing structure-activity relationships of α-methylidene-γ-butyrolactone bearing quinolin-2(1H)-ones and their 3,4-dihydro derivatives. These target compounds were synthesised in two steps starting from aryl-OH which was treated with a bromomethyl ketone followed by a Reformatsky-type condensation. Quinolin-2(1H)-one α-methylidene-γ-butyrolactones exhibited less vasorelaxing activity than their 3,4-dihydro counterparts. Compounds with a methyl or a phenyl group at the C(γ) of the lactone were more vasorelaxant than the C(γ)-fluorophenyl derivatives in the 3,4-dihydroquinolin-2(1H)-one series. When comparing the positional isomers, α-methylidene-γ-butyrolactone substituted at the 7-position of the 3,4-dihydroquinolin-2(1H)-ones were more active than their 6-substituted counterparts, which in turn were more active than the 8-substituted derivatives. The vasorelaxing effect of these 3,4-dihydroquinolin-2(1H)-ones was proved to be dose dependent. Among them, 7-[(2,3,4,5-tetrahydro-4-methylidene-5-oxo-2-phenyfuran-2-yl)methoxy]- quinolin-2(1H)-one (10b) was the most potent with an IC50 of 9.2 μM on the KCl-induced vasoconstriction of pig coronary arteries.
