289061-22-9Relevant academic research and scientific papers
Discovery of secondary sulphonamides as IDO1 inhibitors with potent antitumour effects in vivo
Ge, Shushan,Guo, Wenjie,Hu, Yue,Lai, Yisheng,Li, Yuezhen,Liu, Wen,Ma, Xuewei,Wang, Fang,Wang, Yan,Xu, Qiang,Zheng, Yingbo,Zhong, Haiqing,Zou, Yi
, p. 1240 - 1257 (2020/06/18)
Indoleamine 2,3-dioxygenase 1 (IDO1) as a key rate-limiting enzyme in the kynurenine pathway of tryptophan metabolism plays an important role in tumour immune escape. Herein, a variety of secondary sulphonamides were synthesised and evaluated in the HeLa cell-based IDO1/kynurenine assay, leading to the identification of new IDO1 inhibitors. Among them, compounds 5d, 5l and 8g exhibited the strongest inhibitory effect with significantly improved activity over the hit compound BS-1. The in vitro results showed that these compounds could restore the T cell proliferation and inhibit the differentiation of na?ve CD4+ T cell into highly immunosuppressive FoxP3+ regulatory T (Treg) cell without affecting the viability of HeLa cells and the expression of IDO1 protein. Importantly, the pharmacodynamic assay showed that compound 5d possessed potent antitumour effect in both CT26 and B16F1 tumours bearing immunocompetent mice but not in immunodeficient mice. Functionally, subsequent experiments demonstrated that compound 5d could effectively inhibit tumour cell proliferation, induce apoptosis, up-regulate the expression of IFN-γ and granzyme B, and suppress FoxP3+ Treg cell differentiation, thereby activate the immune system. Thus, compound 5d could be a potential and efficacious agent for further evaluation.
SULFONAMIDO COMPOUNDS THAT ANTAGONISE THE VANILLOID TRPV1 RECEPTOR
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Page/Page column 14, (2008/06/13)
The invention relates to sulfonamido derivatives of formula (I) wherein R1-R7 are as defined in the description. Compounds (I) antagonize the 10 vanilloid receptor and can be used for the preparation of medicaments for the treatment of inflammatory states.
