688317-00-2Relevant academic research and scientific papers
Discovery of Potent Succinate-Ubiquinone Oxidoreductase Inhibitors via Pharmacophore-linked Fragment Virtual Screening Approach
Xiong, Li,Zhu, Xiao-Lei,Gao, Hua-Wei,Fu, Yu,Hu, Sheng-Quan,Jiang, Li-Na,Yang, Wen-Chao,Yang, Guang-Fu
, p. 4830 - 4837 (2016/07/06)
Succinate-ubiquinone oxidoreductase (SQR) is an attractive target for fungicide discovery. Herein, we report the discovery of novel SQR inhibitors using a pharmacophore-linked fragment virtual screening approach, a new drug design method developed in our laboratory. Among newly designed compounds, compound 9s was identified as the most potent inhibitor with a Ki value of 34 nM against porcine SQR, displaying approximately 10-fold higher potency than that of the commercial control penthiopyrad. Further inhibitory kinetics studies revealed that compound 9s is a noncompetitive inhibitor with respect to the substrate cytochrome c and DCIP. Interestingly, compounds 8a, 9h, 9j, and 9k exhibited good in vivo preventive effects against Rhizoctonia solani. The results obtained from molecular modeling showed that the orientation of the R2 group had a significant effect on binding with the protein.
High-affinity thrombin receptor (PAR-1) ligands: A new generation of indole-based peptide mimetic antagonists with a basic amine at the C-terminus
Zhang, Han-Cheng,White, Kimberly B.,McComsey, David F.,Addo, Michael F.,Andrade-Gordon, Patricia,Derian, Claudia K.,Oksenberg, Donna,Maryanoff, Bruce E.
, p. 2199 - 2203 (2007/10/03)
A new generation of indole-based peptide mimetics, bearing a basic amine at the C-terminus, was developed by the agency of two complementary, multistep, trityl resin-based approaches. Thus, we obtained several high-affinity thrombin receptor (PAR-1) ligands, such as 32 and 34. Compounds 32 and 34 were found to bind to PAR-1 with excellent affinity (IC50=25 and 35 nM, respectively) and to effectively block platelet aggregation induced by SFLLRN-NH2 (TRAP-6) and α-thrombin.
