5748-41-4Relevant articles and documents
Improving the metabolic stability of antifungal compounds based on a scaffold hopping strategy: Design, synthesis, and structure-activity relationship studies of dihydrooxazole derivatives
Cheng, Maosheng,Su, Xin,Sun, Nannan,Sun, Yin,Tian, Linfeng,Yin, Wenbo,Zhang, Chu,Zhao, Dongmei,Zhao, Liyu,Zhao, Shizhen,Zheng, Yang
, (2021/08/07)
L-amino alcohol derivatives exhibited high antifungal activity, but the metabolic stability of human liver microsomes in vitro was poor, and the half-life of optimal compound 5 was less than 5 min. To improve the metabolic properties of the compounds, the scaffold hopping strategy was adopted and a series of antifungal compounds with a dihydrooxazole scaffold was designed and synthesized. Compounds A33-A38 substituted with 4-phenyl group on dihydrooxazole ring exhibited excellent antifungal activities against C. albicans, C. tropicalis and C. krusei, with MIC values in the range of 0.03–0.25 μg/mL. In addition, the metabolic stability of compounds A33 and A34 in human liver microsomes in vitro was improved significantly, with the half-life greater than 145 min and the half-life of 59.1 min, respectively. Moreover, pharmacokinetic studies in SD rats showed that A33 exhibited favourable pharmacokinetic properties, with a bioavailability of 77.69%, and half-life (intravenous administration) of 9.35 h, indicating that A33 is worthy of further study.
Mimics of Pincer Ligands: An Accessible Phosphine-Free N-(Pyrimidin-2-yl)-1,2-azole-3-carboxamide Framework for Binuclear Pd(II) Complexes and High-Turnover Catalysis in Water
Bumagin, Nikolay A.,Dikusar, Evgenij A.,Ivashkevich, Ludmila S.,Kletskov, Alexey V.,Kolesnik, Iryna A.,Lyakhov, Alexander S.,Petkevich, Sergey K.,Potkin, Vladimir I.
supporting information, (2020/08/12)
We report for the first time cyclic phosphine-free "head to tail"N,N,N pincer-like (pincer complexes mimicking) N-(pyrimidin-2-yl)-1,2-azole-3-carboxamide Pd(II) complexes with deprotonated amide groups as high-turnover catalysts (TON up to 106, TOF up to 1.2 × 107 h-1) for cross-coupling reactions on the background of up to quantitative yields under Green Chemistry conditions. The potency of the described catalyst family representatives was demonstrated in Suzuki-Miyaura, Mizoroki-Heck, and Sonogashira reactions on industrially practical examples. Corresponding ligands could be synthesized based on readily available reagents through simple chemical transformations. Within the complex structures, a highly unusual 1,3,5,7-tetraza-2,6-dipalladocane frame could be observed.
Combating fluconazole-resistant fungi with novel β-azole-phenylacetone derivatives
Zhao, Liyu,Sun, Nannan,Tian, Linfeng,Sun, Yin,Chen, Yixuan,Wang, Xinran,Zhao, Shizhen,Su, Xin,Zhao, Dongmei,Cheng, Maosheng
, (2019/09/19)
A series of β-azole-phenylacetone derivatives with novel structures were designed and synthesized to combat the increasing incidence of susceptible fungal infections and drug-resistant fungal infections. The antifungal activity of the synthesized compounds was assessed against five susceptible strains and five fluconazole-resistant strains. Antifungal activity tests showed that most of the compounds exhibited excellent antifungal activities against five pathogenic strains with MIC values in the range of 0.03–1 μg/mL. Compounds with R1 = 3-F substituted and 15o and 15ae exhibited moderate antifungal activities against fluconazole-resistant strains 17# and CaR with MIC values in the range of 1–8 μg/mL. Compounds with R1 = H or 2-F (such as 15a, 15o, 15p) displayed moderate to good antifungal activity against fluconazole-resistant strains 632, 901 and 904 with MIC values in the range of 0.125–4 μg/mL. Notably, 15o and 15ae exhibited antifungal activity against five susceptible strains and five fluconazole-resistant strains. Preliminary mechanistic studies showed that the potent antifungal activity of compound 15ae stemmed from inhibition of C. albicans CYP51. Compounds 15o, 15z and 15ae were nearly nontoxic to mammalian A549 cells.
