Synthesis and in Vitro Antitumor Activity of a Novel Series of 2-Pyrazoline Derivatives Bearing the 4-Aryloxy-7-chloroquinoline Fragment

摘要

A new series of NH-pyrazoline derivatives >6 was synthesized by cyclocondensation reaction of novel [(7-chloroquinolin-4-yl)oxy]chalcones >5 with hydrazine hydrate. The treatment of pyrazolines >6 with acetic anhydride or formic acid yielded the N-acetyl- or N-formylpyrazoline derivatives >7–>8, respectively. These novel 2-pyrazoline derivatives >6–>8 were evaluated by the U.S. National Cancer Institute (NCI). Compounds >7b,>d,>f and >8c,>f showed remarkable antitumor activity against 58 cancer cell lines, with the most important GI50 values from in vitro assays ranging from 0.48 to 1.66 μM. The 2-pyrazoline derivatives bearing the 4-aryloxy-7-chloroquinoline fragment are thus considered to be useful leads for the rational design of new antitumor agents.