Jinan Asia Pharma Tech Co., Ltd.

Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunomodulatory enzyme associated with tumor immune evasion, making it a promising target for cancer therapy. This study aimed to identify novel holo-IDO1 inhibitors with distinct structural scaffolds. A series of theophylline derivatives containing 1,2,3-triazole groups were designed and synthesized through the condensation of theophylline acetic acid and 4-aminophenylacetylene. Among the synthesized compounds, 3c and 3e exhibited the most potent inhibitory effects in IDO1 enzymatic activity assays. Molecular docking and affinity prediction analyses provided insights into the binding affinities and mechanisms of action of the lead compounds. Our findings suggest that theophylline derivatives are promising holo-IDO1 inhibitors, warranting further development for potential therapeutic applications.

To explore potential indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors, we designed a series of compounds incorporating urea and 1,2,3-triazole structures. IDO1 enzymatic activity experiments with the synthesized compounds were used to verify their molecular-level activity; for instance, the half maximal inhibitory concentration value of compound 3c was 0.07 μM. Our research has yielded a series of novel IDO1 inhibitors which may be beneficial in the development of drugs targeting IDO1 for cancer treatment.

Based on 2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione as a raw material, a series of novel pomalidomide linked with diphenylcarbamide derivatives were synthesized through several step reactions of substitution, click reaction, and addition reaction. The structures of these compounds were confirmed by 1 H NMR, 13 C NMR, and MS. We discovered that some of the compounds are capable of suppressing indoleamine pyrrole-2,3-dioxygenase-1 activities in in vitro experiments, in which the inhibitory activity of 5b reached the level of benefits.