Design, Synthesis, and In Vitro and In Silico Study of New Hybrid 1-(2-(4-Arylthiazol-2-yl)hydrazineylidene)-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-2-ones as Factor Xa and Factor XIa Inhibitors

To develop efficient and structurally novel anticoagulants, a library of new hybrid molecules—(Z)-1-(2-(4-arylthiazol-2-yl)hydrazineylidene)-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-2-ones—was designed and synthesized through a two-step approach. The reaction of pyrrolo[3,2,1-ij]quinoline-1,2-diones with thiosemicarbazide produced thiosemicarbazones, which were subsequently reacted with α-bromoacetophenones. The structure of the resulting compounds was determined by HPLC-HRMS-ESI analysis, 1H NMR spectroscopy, and 13C NMR spectroscopy. X-ray diffraction analysis unambiguously confirmed the structure of the resulting substances. The synthesized compounds were tested for their anticoagulant activity in vitro. Among the tested derivatives, two substances have a dual effect and exhibit 98–100% inhibitory ability against blood coagulation factors Xa and XIa at 30 μM. IC50 values were also evaluated for these compounds. The results obtained show the high potential of the synthesized derivatives in the development of new multitarget anticoagulant drugs. The docking studies confirmed the experimental results.