Qun Hao

Synthesis and anti-hypercholesterolemic evaluations of calcium salts of 4-substituted quinoline-based mevalonic acid.

A series of calcium (3R,5S,6E)‐7‐[4,6,7,8‐substituted‐quinoline‐3‐yl]‐3,5‐dihydroxy‐hept‐6‐enoates was synthesized from the lactones, and the anti‐hypercholesterolemic evaluation in quails was presented in this report. It was found that most of the compounds significantly decreased levels of total cholesterol and low‐density lipoprotein. 2e showed better hypolipidemic effect than atorvastatin, and 2d and 2j exhibited comparable efficacy to atorvastatin. These three compounds were selected as the hypocholesterolemic candidates for further evaluation.

Synthesis of phenylpyridine derivatives and their biological evaluation toward dipeptidyl peptidase-4

A novel series of pyridine-based derivatives was synthesized and evaluated for their inhibitory activity against dipeptidyl peptidase-4 (DPP4). 5-Aminomethyl-6-(2,4-dichlorophenyl)-4-[(1H-1,2,4-triazol-1-yl)methyl]pyridine-2-carboxylic acid was identified as a potent (IC50 0.57 nM) and selective DPP4 inhibitor (DPP8/DPP4 = 238). A docking study of this compound revealed a hydrogen-bonding interaction with the Arg125 residue of the enzyme providing a potential target residue for further structural optimization.

ALKYLATION OF 2-(2,4-DICHLOROPHENYL)-3-CYANO-6-METHYL-4-(1 H -1,2,4-TRIAZOL-1-YL)METHYLPYRIDINE AT THE METHYLENE GROUP

The reactivity of the 1-triazolyl- and 1-imidazolyl-substituted methylene groups at position 4 of pyridine ring toward alkyl halides is described. Nitrogen heterocycles attached to the methylene group, as well as a 3-cyano group effectively promoted the alkylation, offering a convenient method for constructing structurally diverse molecules that may present pharmaceutical interest.

Design, synthesis and biological evaluation of novel 3-substituted pyrazolopyrimidine derivatives as potent Bruton's tyrosine kinase (BTK) inhibitors

A series of 3-substituted pyrazolopyrimidine derivatives as BTK inhibitors were designed by structure-based drug design and they were synthesized, evaluated by enzyme-based assay and anti-proliferation against Ramos and Raji cells. Most of them displayed good inhibitory activities against both BTK and B-cell lymphoblastic leukemia lines in vitro. Among them, compound 8a exhibited excellent potency (IC50 = 7.95 nM against BTK enzyme, 8.91 μM against Ramos cells and 1.80 μM against Raji cells), with a better hydrophilicity (ClogP = 3.33). These explorations provided new clues to discover 3-substituted pyrazolopyrimidine derivatives as novel anti-tumor agents.