582-33-2Relevant articles and documents
Pleuromutilin derivative with 1, 3, 4-oxadiazole side chain and preparation and application thereof
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Paragraph 0055-0056; 0070; 0090; 0092; 0095; 0103, (2021/07/24)
The invention belongs to the field of medicinal chemistry, and particularly relates to a pleuromutilin derivative with a 1, 3, 4-oxadiazole side chain and preparation and application thereof The pleuromutilin derivative with the 1, 3, 4-oxadiazole side chain is a compound shown in a formula 2 or a pharmaceutically acceptable salt thereof, and a solvent compound, an enantiomer, a diastereoisomer and a tautomer of the compound shown in the formula 2 or the pharmaceutically acceptable salt thereof or a mixture of the solvent compound, the enantiomer, the diastereoisomer and the tautomer in any proportion, including a racemic mixture. The pleuromutilin derivative has good antibacterial activity, is especially suitable for being used as a novel antibacterial agent for systemic system infection of animals or human beings, and has good water solubility.
Half-Sandwich Ruthenium Complexes of Amide-Phosphine Based Ligands: H-Bonding Cavity Assisted Binding and Reduction of Nitro-substrates
Pachisia, Sanya,Kishan, Ram,Yadav, Samanta,Gupta, Rajeev
, p. 2009 - 2022 (2021/02/06)
We present synthesis and characterization of two half-sandwich Ru(II) complexes supported with amide-phosphine based ligands. These complexes presented a pyridine-2,6-dicarboxamide based pincer cavity, decorated with hydrogen bonds, that participated in the binding of nitro-substrates closer to the Ru(II) centers, which is further supported with binding and docking studies. These ruthenium complexes functioned as the noteworthy catalysts for the borohydride mediated reduction of assorted nitro-substrates. Mechanistic studies not only confirmed the intermediacy of [Ru-H] in the reduction but also asserted the involvement of several organic intermediates during the course of the catalysis. A similar Ru(II) complex that lacked pyridine-2,6-dicarboxamide based pincer cavity substantiated its unique role both in the substrate binding and the subsequent catalysis.
Synthesis and biological evaluation of 2,5-diaryl-1,3,4-oxadiazole derivatives as novel Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) inhibitors
Meng, Xiang-Dong,Gao, Li-Xin,Wang, Zhi-Jia,Feng, Bo,Zhang, Chun,Satheeshkumar, Rajendran,Li, Jia,Zhu, Yun-Long,Zhou, Yu-Bo,Wang, Wen-Long
, (2021/10/04)
The Src homology-2 domain containing-protein tyrosine phosphatase-2 (SHP2) is a convergent node for oncogenic cell-signaling cascades including the PD-L1/PD-1 pathway. As an oncoprotein as well as a potential immunomodulator, SHP2 has now emerged as an attractive target for novel anti-cancer agents. Although significant progress has been made in identifying chemotypes of SHP2 inhibitors, these specific compounds might not be clinically useful to inhibit frequently encountered mutated SHP2 variants. Consequently, it is highly desirable to develop chemically different SHP2 inhibitors sensitive to SHP2 mutants. This work developed a new type of SHP2 inhibitors with 2,5-diaryl-1,3,4-oxadiazole scaffold. The representative compound 6l exhibited SHP2 inhibitory activity with IC50 of 2.73 ± 0.20 μM, showed about 1.56-fold, 5.26-fold, and 7.36-fold selectivity for SHP2 over SHP1, PTP1B and TCPTP respectively. Further investigations confirmed that 6l behaved as mixed-type inhibitor sensitive to leukemia cell TF-1 and inhibited SHP2 mediated cell signaling and proliferation. Molecular dynamics simulation provided more detailed information on the binding modes of compounds and SHP2 protein. These preliminary results could provide a possible opportunity for the development of novel SHP2 inhibitors sensitive to SHP2 mutants with optimal potency and improved pharmacological properties.