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Thrombosis is the leading cause of illness and mortality worldwide, posing a serious risk to human health and life. Because antithrombotic drugs can prevent the beginning and progression of thrombotic disorders, they are essential in the management of thrombotic diseases. The substantial side effects and unsatisfactory efficacy of present antithrombotic drugs stimulate the search for novel, effective, and safer antithrombotic therapies. Natural and synthetic coumarins have been shown to have antithrombotic action, specifically anticoagulation, and antiplatelet aggregation. In particular, coumarin-based medications like warfarin, phenprocoumon, and cloricromen have long been used to treat thrombosis in clinical settings. The favored structure for creating novel antithrombotic medications with diverse modes of action is coumarin, which has low toxicity. The goal of the current review is to consolidate recent findings on the development of coumarins as antithrombotic agents, with a focus on the connection between these compounds' chemical compositions and therapeutic potency. It aims to offer promising suggestions for the identification of new coumarin compounds with potent antithrombotic properties. [ABSTRACT FROM AUTHOR]

Novel dihydro-5H-furo[2,3-d]thiazolo[3,2-a]pyrimidin-5-ones (3a–r) and 6H-furo[2,3-d][1,3,4]thiadiazolo[3,2-a]pyrimidin-8(7H)-ones (3s–v) were designed and obtained from radical cyclizations between 7-hydroxy-5H-thiazolo[3,2-a]pyrimidin-5-one derivatives (1a–d) and 7-hydroxy-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one (1e) with various alkenes (2a–h) mediated by Mn(OAc)3. Obtained compounds were characterized with 1H NMR, 13C NMR, 19F NMR, FTIR and HRMS techniques. In vitro AChE inhibitory results of these compounds show that compounds (3i–p) are the most active AChEI's (AChE inhibitor) with IC50 values between 0.15 and 15.16 µM. Also, ligand protein interactions of two most active compounds (3i and 3j) were investigated by molecular docking studies. Furthermore, druglikeness and ADME analyses of 3i–p were performed. All tested compounds showed satisfactory druglike characteristics. [ABSTRACT FROM AUTHOR]

Based on the cholinergic hypothesis of the reported compound, N-(4-(4-methoxy-phenyl)thiazol-2-yl)-3-(pyrrolidin-1-yl)propionamide, which had a good inhibitory activity to acetylcholinesterase (AChE), the new 4-methoxy-phenylthiazole-2-amine derivatives as AChE inhibitors (AChEIs) have been designed and synthesized in this study. Their chemical structures were confirmed by proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, mass spectrometry, and infrared. Furthermore, their inhibitory activities against AChE in vitro were also tested by Ellman spectrophotometry, and the inhibitory activity test results showed that most of the compounds of 4-methoxy-phenylthiazole-2-amine derivatives had a certain AChE inhibitory activity in vitro, and the IC50 (half-maximal inhibitory concentration) value of compound 5g was 5.84 μmol/L, which was higher than that of the reference compound, rivastigmine. Moreover, it had almost no inhibitory effect on butyrylcholinesterase. In addition, compound 5g was subjected to enzyme inhibition kinetics experiments, and the result of Lineweaver–Burk's V−1–[S]−1 double-reciprocal plot showed that the acting type of compound 5g was mixed inhibition type. Furthermore, the AChE inhibitory activity mechanism of compound 5g was explored by the conformational analysis and molecular docking, which was based on the principle of the four-point pharmacophore model necessary for AChE inhibition. Finally, in silico molecular property and ADMET (absorption, distribution, metabolism, excretion, and toxicity) of the synthesized compounds were predicted by using Molinspiration and PreADMET online servers, respectively. It can be concluded that the lead AChEI compound 5g presented satisfactory drug-like characteristics and ADME properties. [ABSTRACT FROM AUTHOR]