624-84-0Relevant articles and documents
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Blackburn,Jencks
, p. 2638 (1968)
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Heavy-atom isotope effects on the hydrazinolysis of methyl formate
Marlier, John F.,Haptonstall, Brandy A.,Johnson, Amanda J.,Sacksteder, Katherine A.
, p. 8838 - 8842 (1997)
The carbonyl carbon, carbonyl oxygen, and nitrogen nucleophile isotope effects were measured for the hydrazinolysis of methyl formate at pH 8 and 10. At pH 8, where breakdown of a tetrahedral intermediate to products is rate-determining, the carbonyl carbon isotope effect is k12/k13 = 1.038, the carbonyl oxygen isotope effect is k16/k18 = 1.003, and the nitrogen nucleophile isotope effect is k14/k15 = 0.990. The isotope effects at pH 8 are consistent with a late transition state, which greatly resembles the hydrazide product. At pH 10, where formation of a tetrahedral intermediate is rate-determining, the carbonyl carbon isotope effect is k12/k13 = 1.020, the carbonyl oxygen isotope effect is k16/k18 = 1.004, and the nitrogen nucleophile isotope effect is k14/k15 = 0.9917. These isotope effects are best rationalized in terms of a concerted general base catalyzed nucleophilic attack of hydrazine on methyl formate as the rate-determining step.
Design, synthesis, in vitro and in vivo evaluation against MRSA and molecular docking studies of novel pleuromutilin derivatives bearing 1, 3, 4-oxadiazole linker
Liu, Jie,Zhang, Guang-Yu,Zhang, Zhe,Li, Bo,Chai, Fei,Wang, Qi,Zhou, Zi-Dan,Xu, Ling-Ling,Wang, Shou-Kai,Jin, Zhen,Tang, You-Zhi
, (2021/05/17)
A class of pleuromutilin derivatives containing 1, 3, 4-oxadiazole were designed and synthesized as potential antibacterial agents against Methicillin-resistant staphylococcus aureus (MRSA). The ultrasound-assisted reaction was proposed as a green chemistry method to synthesize 1, 3, 4-oxadiazole derivatives (intermediates 85–110). Among these pleuromutilin derivatives, compound 133 was found to be the strongest antibacterial derivative against MRSA (MIC = 0.125 μg/mL). Furthermore, the result of the time-kill curves displayed that compound 133 could inhibit the growth of MRSA in vitro quickly (- 4.36 log10 CFU/mL reduction). Then, compound 133 (- 1.82 log10 CFU/mL) displayed superior in vivo antibacterial efficacy than tiamulin (- 0.82 log10 CFU/mL) in reducing MRSA load in mice thigh model. Besides, compound 133 exhibited low cytotoxicity to RAW 264.7 cells. Molecular docking studies revealed that compound 133 was successfully localized in the binding pocket of 50S ribosomal subunit (ΔGb = -10.50 kcal/mol). The results indicated that these pleuromutilin derivatives containing 1, 3, 4-oxadiazole might be further developed into novel antibiotics against MRSA.
Process for the Preparation of Triazole Antifungal Drug, Its Intermediates and Polymorphs Thereof
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Paragraph 0335, (2014/12/09)
A process for the preparation of 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)tetrahydro-5-(1H-1,2,4-triazol-1-ylmethyl)-3-furanyl]methoxy]phenyl]-1-piperazinyl]phenyl]-2-[(1S,2S)-1-ethyl-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one compound of formula-1, its intermediates and polymorphs thereof. (I)