Research advances in the study of anticoagulant active molecules / 药学学报

The incidence of thrombosis-induced cardiovascular diseases is increasing worldwide and poses a serious threat to human health. Three factors, slow speed of blood flow, hypercoagulable blood and vascular damage, have been considered to be causes of thrombosis. Antithrombotic drugs have been classified into three categories based on the mechanism of thrombosis, including anticoagulants, platelet inhibitors and fibrinolytics. The coagulation and anticoagulation systems have drawn increasing attention because of the important role they play in the process of thrombosis. Novel compounds with anticoagulant activity are now emerging, alleviating to some extent some of the problems associated with the clinical use of early approved thrombotic drugs, such as high bleeding risk, slow onset of action and narrow therapeutic windows. In this review, we initially describe the mechanisms of coagulation as well as thrombosis. Meanwhile, a wide range of bioactive compounds and potential antithrombotic candidates reported in recent years have been summarized. In addition, the structure-activity relationship of certain compounds has been discussed, expecting to facilitate the development of molecules with anticoagulant biological activity for the treatment of thrombotic diseases.

Applications and constructions of benzazepine scaffolds in drug molecular design / 药学学报

Benzazepine is a kind of fused ring structure, which is composed of nitrogen-containing seven-membered ring and benzene ring. The introduction of benzazepine scaffolds into compounds can not only adjust the physicochemical properties, maintain or enhance the biological activities of the compounds, but also improve the pharmacokinetic properties, increase the brain permeability, and reduce the toxicity of hERG of the compounds, which is one of the privileged scaffolds for rational design and structural optimization of drug molecules. Benzazepine scaffolds can be constructed by different synthetic methods such as Dickmann condensation reaction, Mitsunobu reaction, Pictet-Spengler reaction, CMD reaction, multicomponent reactions (MCRs), metal catalysis reactions and asymmetric catalysis etc., which play an important role in enriching the structure diversity of drug molecules.

Druggability enhancement by modification of physicochemical properties of drugs via crystal engineering / 药学学报

The solubility/dissolution, hygroscopicity and mechanical properties of drug candidates have a profound effect on oral bioavailability, processability and stability. The physicochemical properties of crystalline drug are closely related to inner crystal structure. Crystal engineering technologies, as strategies of altering the crystal structure and tailoring physicochemical properties at molecular level, possess the potential of enhancing the pharmaceutical performance of product. The current article reviewed the modification of drug solubility/dissolution, hygroscopicity and mechanical properties by crystal engineering technologies through polymorphic selection, amorphization/co-amorphization, as well as co-crystallization, which provided a reference for the applications of pharmaceutical crystallography in improving physicochemical properties and druggability.