Design, Synthesis, and Evaluation of New Hybrid Derivatives of 5,6-Dihydro-4-pyrrolo[3,2,1-]quinolin-2(1)-one as Potential Dual Inhibitors of Blood Coagulation Factors Xa and XIa.

Cardiovascular diseases caused by blood coagulation system disorders are one of the leading causes of morbidity and mortality in the world. Research shows that blood clotting factors are involved in these thrombotic processes. Among them, factor Xa occupies a key position in the blood coagulation cascade.

Experimentally Validated Novel Factor XIIa Inhibitors Identified by Docking and Quantum Chemical Post-processing.

Antithrombotic agents based on factor XIIa inhibitors can become a new class of drugs to manage conditions associated with thrombosis. Herein, we report identification of two novel classes of factor XIIa inhibitors. The first one is triazolopyrimidine derivatives designed on the basis of the literature aminotriazole hit and identified using virtual screening of the focused library.

New Chemicals Suppressing SARS-CoV-2 Replication in Cell Culture.

Candidates to being inhibitors of the main protease (Mpro) of SARS-CoV-2 were selected from the database of Voronezh State University using molecular modeling. The database contained approximately 19,000 compounds represented by more than 41,000 ligand conformers. These ligands were docked into Mpro using the SOL docking program.

Synthesis of 4,5-Dihydro-1-[1,2]dithiolo[3,4-]quinoline-1-thione Derivatives and Their Application as Protein Kinase Inhibitors.

This study represents the design and synthesis of a new set of hybrid and chimeric derivatives of 4,5-dihydro-4,4-dimethyl-1H-[1,2]dithiolo[3,4-c]quinoline-1-thiones, the structure of which the tricyclic fragment linearly bound or/and condensed with another heterocyclic fragment. Using the PASS Online software, among the previously synthesized and new derivatives of 1,2-dithiolo[3,4-c]quinoline-1-thione we identified 12 substances with pleiotropic activity, including chemoprotective and antitumor activity. All the synthesized derivatives were screened for their inhibitory assessment against a number of kinases.

New Blood Coagulation Factor XIIa Inhibitors: Molecular Modeling, Synthesis, and Experimental Confirmation.

In the modern world, complications caused by disorders in the blood coagulation system are found in almost all areas of medicine. Thus, the development of new, more advanced drugs that can prevent pathological conditions without disrupting normal hemostasis is an urgent task. The blood coagulation factor XIIa is one of the most promising therapeutic targets for the development of anticoagulants based on its inhibitors.

Synthesis, Docking, and In Vitro Anticoagulant Activity Assay of Hybrid Derivatives of Pyrrolo[3,2,1-]Quinolin-2(1)-one as New Inhibitors of Factor Xa and Factor XIa.

Coagulation factor Xa and factor XIa are proven to be convenient and crucial protein targets for treatment for thrombotic disorders and thereby their inhibitors can serve as effective anticoagulant drugs. In the present work, we focused on the structure-activity relationships of derivatives of pyrrolo[3,2,1-]quinolin-2(1)-one and an evaluation of their activity against factor Xa and factor XIa. For this, docking-guided synthesis of nine compounds based on pyrrolo[3,2,1-]quinolin-2(1)-one was carried out.

A New Synthetic Route to Polyhydrogenated Pyrrolo[3,4-b]pyrroles by the Domino Reaction of 3-Bromopyrrole-2,5-Diones with Aminocrotonic Acid Esters.

A new synthetic approach to polyfunctional hexahydropyrrolo[3,4-]pyrroles was developed based on cyclization of N-arylbromomaleimides with aminocrotonic acid esters. A highly chemo- and stereoselective reaction is a Hantzsch-type domino process, involving the steps of initial nucleophilic C-addition or substitution and subsequent intramolecular nucleophilic addition without recyclyzation of imide cycle.