Janus kinase (JAK) is a non receptor tyrosine protein kinase, which has attracted wide attention and JAK inhibitors are mainly used to screen therapeutic drugs for hematological diseases, tumors, rheumatoid arthritis (RA) and psoriasis. Filgotinib is an oral small molecule JAK inhibitor which is currently at the clinical stage to treat Crohn's disease (CD) and rheumatoid arthritis. In this study, we designed novel triazolopyridine derivatives A1-A4 using Filgotinib as the lead compound, then replaced cyclopropane with trifluoromethane and replaced triazolopyridine with imidazopyrazine to get B1-B4 by isosteric principle of bioelectronics. These compounds were prepared in this work, and the corresponding effects against JAK1, JAK2 and JAK3 were assessed. The results indicated that B2 had stronger inhibitory effect on JAK1 and JAK3. A1 and A2 showed a good inhibitory effect on JAK1. Molecular docking results showed that compounds A1, A2 and B2 bind well to protein binding sites. These compounds can supply leading compounds for developing rheumatoid arthritis and Crohn's drugs.

Bicyclic phloroglucinol is a phenolic compound which mainly exist in Dryopteris fragrans (L.) Schott with antiinflammatory, antithrombotic, antifungal and antitumor activity. Although a series of anticancer agents target various tumors under clinical trials, different limitations hinder their clinical development and novel targeting chemical agents are required. Herein, we have made a number of modifications around the scaffold of the phloroglucinol. The results of antitumor activities reveal that compound A5 against A549 cells and compound A3 against HepG2 and McF‐7 cells were best with a degree of concentration dependence, which stronger than that of positive control 5‐FU, and compound A3 and A5 display lower cytotoxicity to normal cells. The molecule docking studies indicate protein Bcl‐xl and Mcl‐12 may be a potential target of these compounds. In general, A3 and A5 with potent binding affinity and good efficacy have the potential to develop into antitumor lead compounds which also deserve further study.

A series of imidazopyrazine derivatives were synthesized, and evaluated for their anti‐inflammatory activity in vitro and in vivo using RAW264.7 cells model and Zebrafish Traumatic Infection Inflammation model. The results in vitro showed that the compounds had significant inhibitory effect on inflammatory factor interleukin 6 (IL6), and N‐ (3 ‐( 4‐ ((1,1‐dioxidothiomorpholino) methyl)phenyl) imidazo [1,5‐a] pyrazin‐6‐yl) cyclopropanecarboxamide A1 the best activity, which was significantly different from that of the lipopolysaccharide (LPS) control group (P<0.03). The experiment of anti‐inflammatory activity in vivo indicated that compound A1 showed obvious aggregation inhibitory activity on inflammatory effector cells which was significantly different from that in the tail‐cutting control group (P<0.03). When the concentration of the compound was 160 μg/mL, the inhibitory activity of compound A1 was better than that of dexamethasone positive control group (P<0.05). This study could supply some anti‐inflammatory leading structure and possible mechanism for studying and developing new anti‐inflammatory agents.

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