13066-01-8Relevant articles and documents
Structural optimization and structure–activity relationship of 4-thiazolidinone derivatives as novel inhibitors of human dihydroorotate dehydrogenase
Zeng, Fanxun,Quan, Lina,Yang, Guantian,Qi, Tiantian,Zhang, Letian,Li, Shiliang,Li, Honglin,Zhu, Lili,Xu, Xiaoyong
, (2019/08/07)
Human dihydroorotate dehydrogenase (hDHODH), one of the attractive targets for the development of immunosuppressive drugs, is also a potential target of anticancer drugs and anti-leukemic drugs. The development of promising hDHODH inhibitors is in high demand. Based on the unique binding mode of our previous reported 4-thiazolidinone derivatives, via molecular docking method, three new series 4-thiazolidinone derivatives were designed and synthesized as hDHODH inhibitors. The preliminary structure–activity relationship was investigated. Compound 9 of biphenyl series and compound 37 of amide series displayed IC50 values of 1.32 μM and 1.45 μM, respectively. This research will provide valuable reference for the research of new structures of hDHODH inhibitors.
Discovery of 1,2,4-triazole-1,3-disulfonamides as dual inhibitors of mitochondrial complex II and complex III
Cheng, Hua,Shen, Yan-Qing,Pan, Xia-Yan,Hou, Yi-Ping,Wu, Qiong-You,Yang, Guang-Fu
, p. 7281 - 7292 (2015/09/02)
Respiratory chain succinate-ubiquinone oxidoreductase (SQR or complex II) and ubihydroquinone-cytochrome (cyt) c oxidoreductase (cyt bc1 or complex III) have been demonstrated as the promising targets of numerous antibiotics and fungicides. As a continuation of our research work on the development of new fungicides, a series of 1,2,4-triazole-1,3-disulfonamide derivatives with dual functions targeting both SQR and cyt bc1 were designed and synthesized by coupling diverse diphenyl ether moieties with triazolesulfonamide units. These newly synthesized compounds were characterized by elemental analyses, 1H NMR and ESI-MS spectrometry. The in vitro assay indicated that most of the synthesized compounds displayed good inhibition against porcine succinate-cytochrome reductase (SCR) with IC50 values ranging from 3.2 to 81.8 μM, revealing much higher activity than that of the commercial control amisulbrom whose IC50 value is 93.0 μM. Further evaluation against the respective SQR and cyt bc1 indicated that most compounds exhibited SQR-inhibiting activity as well as cyt bc1-inhibiting activity, but the inhibition potency against SQR is much higher than that against cyt bc1, showing that the SCR inhibition might be contributed greatly by the SQR inhibition. The further antibacterial evaluation against Xanthomonas oryzae pv. oryzae revealed that four compounds showed excellent potency at the concentration of 20 μg mL-1. In particular, compounds 6h and 6j exhibited much better antibacterial activity than the commercial control bismerthiazol in terms of their EC50. Impressively, 6j has an EC90 of 33.62 μg mL-1, more than 10-fold higher than that of bismerthiazol.
4-Substituted anilides as selective melatonin MT2 receptor agonists
Epperson, James R.,Deskus, Jeffrey A.,Gentile, Anthony J.,Iben, Lawrence G.,Ryan, Elaine,Sarbin, Nathan S.
, p. 1023 - 1026 (2007/10/03)
A series of 4-substituted anilides with human melatonergic affinity is reported. Butyramides 26, 39, 42, 52, 57, and 58 all demonstrated subnanomolar MT2 binding affinity and MT2 selectivity of at least 70-fold over the MT1 receptor. Compound 26 demonstrated full agonism at the MT2 receptor.