A group of new amidrazone compounds that include a quinoline component was produced through the reaction of hydrazonyl chloride, derived from 6-aminoquinoline, with appropriate secondary cyclic amines. The new compounds were confirmed through 1H-NMR, 13C-NMR, FTIR, and HRMS, and further verified by single-crystal X-ray diffraction. The antitumor potential of the synthesized compounds was tested against lung cancer (A549) and breast cancer (MCF-7) cell lines. Among the compounds, the ethyl carboxylate and o-hydroxy phenyl piperazine derivatives (10d and 10g) exhibited the strongest activity against both cell lines, with IC50 values of 43.1 and 59.1 μM for the lung and breast cancer cell lines, respectively. Moreover, the most potent compounds were subsequently docked into the c-Abl kinase binding site (PDB code: 1IEP) as a possible anticancer mechanism. In-silico ADMET study shows acceptable pharmacokinetic properties, and the toxicity profile for the most potent compounds is non-carcinogenic.

Model α-chloro-β-nitrothieno[2,3-c]pyridazines incorporating N1-(aryl) entity appended with ortho-methoxycarbonyl or trifluoromethyl group were prepared via intramolecular cyclization of their respective N-arylhydrazone precursors. Interaction of these substrates with N′-(p-fluorophenyl)benzothiohydrazide, in the presence of NEt₃, furnished the respective 1,3,4-thiadiazoline–pyridazine thiolate hybrids that were S-methylated to produce the corresponding “sulfanyl” derivatives. Their structures were deduced from spectral data, and confirmed by single-crystal X-ray diffraction.

Fourteen isoindigos were synthesized; four inhibit FLT3 at nanomolar concentrations, 3 being the best dual inhibitor (243 nM wild-type, 121 nM D835Y), 8 the best on wild-type FLT3 at 180 nM, and both with stable binding over 1 µs of simulation.