6924-68-1Relevant articles and documents
Synthesis, Configurational Assignment, and Conformational Analysis of β-Hydroxy Sulfoxides, Bioisosteres of Oxisuran Metabolites, and Their O-Methyl Derivatives
Alvarez-Ibarra, C.,Cuervo-Rodriguez, R.,Fernandez-Monreal, M. C.,Ruiz, M. P.
, p. 7284 - 7291 (1994)
Synthesis, configurational assignment, and conformational analysis of diastereomers of 2-(methylsulfinyl)-1-(2-quinolyl)ethanol, 3a, 2-(methylsulfinyl)-1-(1-isoquinolyl)ethanol, 3b, 2-(methylsulfinyl)-1-(2-pyrazyl)ethanol, 3c, and their O-methyl derivatives 4a-c are reported.The configurational assignment and conformational analysis of the two diastereoisomers of β-hydroxy sulfoxides and β-methoxy sulfoxides have been carried out from the observed vicinal coupling constants using the molecular mechanics force field (MMX) and the Altona relationship as fundamental tools.The conformational equilibrium is explained in terms of polar and steric factors.Of significant importance was the role of intramolecular hydrogen bonding in the RS/SR isomers of β-hydroxy sulfoxides.
Novel pyrazine based anti-tubercular agents: Design, synthesis, biological evaluation and in silico studies
Abdel-Aziz, Marwa M.,Abdel-Ghany, Yasser S.,El-Hawash, Soad A.,Elzahhar, Perihan A.,Hassan, Nayera W.,Ismail, Azza,Nassra, Rasha,Saudi, Manal N.,Sriram, Dharmarajan
, (2020)
TB continues to be a leading health threat despite the availability of powerful anti-TB drugs. We report herein the design and synthesis of various hybrid molecules comprising pyrazine scaffold and various formerly identified anti-mycobacterial moieties. Thirty-one compounds were screened in vitro for their activity against Mycobacterium tuberculosis H37Rv strain using MABA assay. The results revealed that six compounds (8a, 8b, 8c, 8d, 14b and 18) displayed significant activity against Mtb with MIC values ≤6.25 μg/ml versus 6.25 μg/ml for pyrazinamide. The most active compounds were then assessed for their in vitro cytotoxicity against PBMC normal cell line using MTT assay and showed SI > 200. Several in silico studies have been carried out for target fishing of the novel compounds such as shape-based similarity, pharmacophore mapping and inverse docking. Based on this multi-step target fishing study, we suggest that pantothenate synthetase could be the possible target responsible for the action of these compounds. The most active compounds were then successfully docked into the active site of pantothenate synthetase enzyme with favorable binding interactions. In addition, in silico prediction of physicochemical, ADMET and drug-like properties were also determined indicating that compounds 8b, 8c and 8d are promising candidates for the development of new anti-TB agents with enhanced activity and better safety profile.
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.
ATF6 INHIBITORS AND USES THEREOF
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Paragraph 0517, (2019/10/29)
Compounds as inhibitors of Activating Transcription Factor 6 (ATF6) are provided. The compounds may find use as therapeutic agents for the treatment of diseases or disorders mediated by ATF6 and may find particular use in the treatment of viral infections, neurodegenerative diseases, vascular diseases, or cancer.
