Wang Xiaoyu

Bio: Wang Xiaoyu is an academic researcher from Guangzhou Medical University. The author has contributed to research in topics: Quantitative structure–activity relationship & Alkyl. The author has an hindex of 1, co-authored 2 publications receiving 1 citations.

3D-QSAR modeling of Phosphodiesterase-5 inhibitors: evaluation and comparison of the receptor- and ligand-based alignments

Abstract: Phosphodiesterase-5 (PDE5) inhibitors can be used as clinical agents for the treatment of erectile dysfunction and pulmonary hypertension. A series of aryl-chromeno-pyrrol derivatives were previously identified as PDE5 inhibitors in our lab. Herein, these molecules were subjected to 3D-QSAR analysis with CoMFA and CoMSIA methods to gain deeper insight into the structural requirements for their bioactivities. Receptor- and ligand-based alignment were used and compared to find the alignment-related factors that affect the accuracy of QSAR models. The receptor-based CoMFA and CoMSIA models, which were generated by superimposing the docking conformations directly in the protein binding site, gave more significant results for 38 training set compounds and 5 test set molecules. Comparison of the two alignments revealed that spatial arrangement of the ligands is the principal factor in determining the reliability of the 3D-QSAR models. Detailed analysis of the receptor-based CoMSIA-SE contour maps provided much helpful information to improve the bioactivities of aryl-chromeno-pyrrol analogs as PDE5 inhibitors.

Dihydropyranopyrazole compound, as well as preparation method and application thereof

Abstract: The invention discloses a dihydropyranopyrazole compound, as well as a preparation method and application thereof. The compound has a structure as shown in formula (I) or a salt acceptable pharmaceutically, wherein R1 is selected from hydrogen, C1-6 linear alkyl, C1-6 cycloalkyl, C1-6 halogenated alkyl, cyclic or linear C1-6 alkoxy, substituted or unsubstituted phenyl, and substituted or unsubstituted 2-pyridyl; R2 is selected from C1-10 alkyl, C1-10 halogenated alkyl, aryl substituted C1-6 alkyl or C3-12 alkyl containing cycloalkyl; R3, R4, R5, R6 and R7 are separately selected from hydrogen,halogen, hydroxy, nitro, substituted or unsubstituted C1-6 alkyl, and substituted or unsubstituted C1-6 alkoxy. The dihydropyranopyrazole compound disclosed by the invention has a novel structure, iseasy to prepare, can inhibit AKR1C3 remarkably and is even better than positive control drug meclofenamic acid; the dihydropyranopyrazole compound can be used as an AKR1C3 inhibitor, and can be prepared into drugs for AKR1C3 related diseases, in particular to drugs for prostate cancer. The formula (I) is shown in the description.

Therapeutic Potential of Phosphodiesterase Inhibitors against Neurodegeneration: The Perspective of the Medicinal Chemist.

Abstract: Increasing human life expectancy prompts the development of novel remedies for cognitive decline: 44 million people worldwide are affected by dementia, and this number is predicted to triple by 2050. Acetylcholinesterase and N-methyl-d-aspartate receptors represent the targets of currently available drugs for Alzheimer's disease, which are characterized by limited efficacy. Thus, the search for therapeutic agents with alternative or combined mechanisms of action is wide open. Since variations in 3',5'-cyclic adenosine monophosphate, 3',5'-cyclic guanosine monophosphate, and/or nitric oxide levels interfere with downstream pathways involved in memory processes, evidence supporting the potential of phosphodiesterase (PDE) inhibitors in contrasting neurodegeneration should be critically considered. For the preparation of this Review, more than 140 scientific papers were retrieved by searching PubMed and Scopus databases. A systematic approach was adopted when overviewing the different PDE isoforms, taking into account details on brain localization, downstream molecular mechanisms, and inhibitors currently under study, according to available in vitro and in vivo data. In the context of drug repurposing, a section focusing on PDE5 was introduced. Original computational studies were performed to rationalize the emerging evidence that suggests the role of PDE5 inhibitors as multi-target agents against neurodegeneration. Moreover, since such compounds must cross the blood-brain barrier and reach inhibitory concentrations in the central nervous system to exert their therapeutic activity, physicochemical parameters were analyzed and discussed. Taken together, literature and computational data suggest that some PDE5 inhibitors, such as tadalafil, represent promising candidates.