Synthesis and Anticoagulant Activity of New Ethylidene and Spiro Derivatives of Pyrrolo[3,2,1-ij]quinolin-2-ones

Novichikhina, N. P.; Skoptsova, A. A.; Shestakov, A. S.; Potapov, A. Yu.; Kosheleva, E. A.; Kozaderov, O. A.; Ledenyova, Irina V.; Подоплелова, Н. А.; Panteleev, Mikhail A.; Шихалиев, Х. С.

doi:10.1134/s1070428020090080

Cited by 15 publications

(7 citation statements)

References 33 publications

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“…The starting compound Ia,b, II was synthesized according to a published method [46,47]. Commercially available reagents from Lancaster were also used in the syntheses.…”

Section: Chemicalsmentioning

confidence: 99%

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

et al. 2022

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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. The initial stage of drug development is directly related to computational methods of searching for a lead compound. In this study, docking followed by quantum chemical calculations was used to search for noncovalent low-molecular-weight factor XIIa inhibitors in a focused library of druglike compounds. As a result of the study, four low-molecular-weight compounds were experimentally confirmed as factor XIIa inhibitors. Selectivity testing revealed that two of the identified factor XIIa inhibitors were selective over the coagulation factors Xa and XIa.

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“…The starting compound Ia,b, II was synthesized according to a published method [46,47]. Commercially available reagents from Lancaster were also used in the syntheses.…”

Section: Chemicalsmentioning

confidence: 99%

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

et al. 2022

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“…Prompted by all the above-mentioned, and our previous studies [ 55 , 56 , 57 , 58 , 59 , 60 ], we designed and synthesized, based on the hybridization approach, new methyl 2-(4-oxo-2-(2-(2-oxo-5,6-dihydro-4 H -pyrrolo[3,2,1- ij ]quinolin-1(2 H )-ylidene)hydrazineyl)thiazol-5(4H)-ylidene)acetates and studied their inhibitory properties against blood clotting factors Xa and XIa in vitro.…”

Section: Introductionmentioning

confidence: 96%

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

Skoptsova,

Geronikaki,

Novichikhina

et al. 2024

Molecules

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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. Another coagulation factor, XIa, is also a promising target because its inhibition can suppress thrombosis with a limited contribution to normal hemostasis. In this regard, the development of dual inhibitors as new generation anticoagulants is an urgent problem. Here we report the synthesis and evaluation of novel potential dual inhibitors of coagulation factors Xa and XIa. Based on the principles of molecular design, we selected a series of compounds that combine in their structure fragments of pyrrolo[3,2,1-ij]quinolin-2-one and thiazole, connected through a hydrazine linker. The production of new hybrid molecules was carried out using a two-stage method. The reaction of 5,6-dihydropyrrolo[3,2,1-ij]quinoline-1,2-diones with thiosemicarbazide gave the corresponding hydrazinocarbothioamides. The reaction of the latter with DMAD led to the target methyl 2-(4-oxo-2-(2-(2-oxo-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1(2H)-ylidene)hydrazineyl)thiazol-5(4H)-ylidene)acetates in high yields. In vitro testing of the synthesized molecules revealed that ten of them showed high inhibition values for both the coagulation factors Xa and XIa, and the IC50 value for some compounds was also assessed. The resulting structures were also tested for their ability to inhibit thrombin.

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“…Similarly, quinoline is found in various natural products. It is frequently utilised to explore a range of bioactive compounds with varying pharmacological properties like antifungal [17,18], anti-inflammatory [19,20], anticancer [21,22], antimicrobial [23,24], anticoagulant [25,26], antiviral [27,28], antimalarial [29,30], antitrypanosomal [30,31] etc. Due to the therapeutic efficacy of benzimidazole and quinoline scaffolds, medicinal chemists have been interested in developing hybrid analogues with enhanced potency by incorporating them, and molecular hybridisation technology has been employed to do so.…”

Section: Introductionmentioning

confidence: 99%

Current Development in the Synthesis of Benzimidazole-Quinoline Hybrid Analogues and Their Biological Applications

Khalifa,

Upadhyay,

Kumari

et al. 2023

Strategies for the Synthesis of Heterocycles and Their Applications

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Heterocyclic compounds have an essential role in many domains of medicinal chemistry. Many pharmaceutical industries use and investigate nitrogen-containing heterocycles because they are crucial in discovering and developing novel therapeutically active compounds. The benzimidazole moiety is a fundamental component of many heterocyclic scaffolds, which play an important role in producing a wide range of biological activities. Similarly, quinoline is also a versatile bicyclic heterocyclic scaffold with many medicinal applications. It is an essential scaffold for drug discovery leads, and it plays a significant role in medicinal chemistry and has biological activities similar to benzimidazole scaffolds. The present chapter discusses the quinoline-benzimidazole hybrids scaffolds and their potential pharmacological activities.

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Synthesis and Anticoagulant Activity of New Ethylidene and Spiro Derivatives of Pyrrolo[3,2,1-ij]quinolin-2-ones

Cited by 15 publications

References 33 publications

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

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

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

Current Development in the Synthesis of Benzimidazole-Quinoline Hybrid Analogues and Their Biological Applications

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