Synthesis and antitumor activity of halogen-substituted 4-(3,3-dimethyl-1-triazeno)quinolines

Abstract

Halogenated 4-(3,3-dimethyl-1-triazeno)quinolines were synthesized as potential antitumor agents on the basis of the biochemical pharmacological properties of existing triazenes, their structural-activity relationships, and the high melanin binding of chloroquine and iodoquine in vivo and in vitro. They were synthesized by diazotization of appropriate halogen-substituted 4-aminoquinolines in fluoboric acid at -5 degrees C followed by coupling with dimethylamine. Among these new compounds, 8-chloro-4-(3,3-dimethyl-1-triazeno)quinoline produces significant antitumor activity against both P-388 and L1210 murine leukemias. Although only marginally active or inactive against P-388, the other chloro, bromo, or iodo analogues show activity against L1210 comparable to that of dacarbazine (DIC). However, none of these compounds is active against B-16 melanoma. Compared with DIC these new agents demonstrate a higher in vitro affinity for melanin; however, this affinity is apparently not correlated with their antitumor activity.

Synthesis and evaluation of a 125I-labeled iminodihydroquinoline-derived tracer for imaging of voltage-gated sodium channels

“…The non-radioactive iodinated compound 10 (Scheme 1) was synthesized following the pathway described by Lin and Loo 22 for the preparation of the key intermediate 4-chloro-7-iodoquinoline ( 8 ). The reaction of 3-iodoaniline ( 3 ) with diethyl ethoxymethylenemalonate ( 4 ) gave the acrylate 5 , which was converted to hydroxyquinoline 6 upon heating in diphenyl ether at 250 °C.…”

Design and synthesis of a novel pre-column derivatization reagent with a 6-methoxy-4-quinolone moiety for fluorescence and tandem mass spectrometric detection and its application to chiral amino acid analysis

“…1. 6-MOQ was prepared according to the reported methods (Gold-Jacobs reaction) [28,29], and 6-MOQ-EtOH, 6-MOQ-AcOH and 6-MOQ-EtNH 2 were synthesized as shown in 2.2.1-2.2.6. Fig.…”

“…Synthesis of the reagents and chemicals 2.2.1. Synthesis of 1-(2-hydroxyethyl)-6-methoxyquinolin-4(1H)-one (6-MOQ-EtOH) 6-MOQ was synthesized from p-anisidine in four steps according to previously reported methods with some modifications [28,29]. A mixture of 6-MOQ (525 mg, 3.0 mmol), KOH (107 mg, 1.91 mmol), and ethylene carbonate (798 mg, 9.0 mmol) in DMF (5 mL) was heated at 130 • C for 12 h. The reaction mixture was evaporated, then purified by column chromatography over silica gel with a gradient of CHCl 3 :MeOH (from 20:1 to 10:1) to obtain a colorless powder (yield; 75.3%, 496 mg).…”

Structural and photophysical properties of novel dual fluorescent compounds, 1‐aryl‐substituted 6‐methoxy‐4‐quinolones

“…6MOQ was prepared in four steps, starting from the commercially available p-anisidine, according to previously reported methods (12)(13)(14). To investigate the structural and photophysical properties of 1-aryl-substituted 6MOQs, we selected the substituted benzenes having various electron-accepting capabilities as the electron acceptor moieties.…”