1501-27-5Relevant articles and documents
New compounds for a good old class: Synthesis of two Β-lactam bearing cephalosporins and their evaluation with a multidisciplinary approach
Vigliotta, Giovanni,Giordano, Deborah,Verdino, Anna,Caputo, Ivana,Martucciello, Stefania,Soriente, Annunziata,Marabotti, Anna,De Rosa, Margherita
supporting information, (2020/01/22)
Antimicrobial resistance is spreading massively in the world and is becoming one of the main health threats of the 21st century. One of the possible strategies to overcome this problem is to modify the known classes of antibiotics in a rational way, with the aim of tuning their efficacy. In this paper, we present the synthesis and the evaluation of the biological activity of a series of two β-lactam bearing cephalosporin derivatives, in which an additional isolated azetidinone ring, bearing different substituents, is joined to the classical cephalosporanic nucleus by a chain of variable length. A computational approach has been also applied in order to predict the molecular interactions between some representative derivatives and selected penicillin-binding proteins, the natural targets of β-lactam antibiotics. All these derivatives are active against Gram-positive bacteria, with MIC100 comparable or even better than that of the reference antibiotic ceftriaxone, and show no or very low cytotoxic activity on different cell lines. Overall, these molecules appear to be able to exert their activity in particular against microorganisms belonging to some of the species more involved in the development of multidrug resistance.
PYRIDAZINE DERIVATIVES AS SMARCA2/4 DEGRADERS
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Page/Page column 91-92, (2019/11/12)
The present invention provides pyridazine derivatives of formula (I), which are therapeutically useful as SMARCA2/4 degraders. These compounds are useful in the treatment and/or prevention of diseases or disorders dependent upon SMARCA2/4 in a mammal. The present invention also provides preparation of the compounds and pharmaceutical compositions comprising at least one of the pyridazine derivatives of formula (I) or a pharmaceutically acceptable salt, or a stereoisomer thereof.
Novel photochemical reactions of carbocyclic diazodiketones without elimination of nitrogen – a suitable way to N-hydrazonation of C–H-bonds
Rodina, Liudmila L.,Azarova, Xenia V.,Medvedev, Jury J.,Semenok, Dmitrij V.,Nikolaev, Valerij A.
, p. 2250 - 2258 (2018/09/14)
The sensitized photoexcitation of 2-diazocyclopentane-1,3-diones in the presence of THF leads to the insertion of the terminal N-atom of the diazo group into the α-С–Н bond of THF, producing the associated N-alkylhydrazones in yields of up to 63–71%. Further irradiation of hydrazones derived from furan-fused tricyclic diazocyclopentanediones culminates in the cycloelimination of furans to yield 2-N-(alkyl)hydrazone of cyclopentene-1,2,3-trione. By contrast, the direct photolysis of carbocyclic diazodiketones gives only Wolff rearrangement products with up to 90–97% yield.
Intracellular delivery of chemical probes using a glutathione-responsive traceless tag
Aoyama, Eriko,Fuchida, Hirokazu,Oshikawa, Yuji,Uchinomiya, Shohei,Ojida, Akio
supporting information, p. 7715 - 7718 (2016/07/06)
A new glutathione (GSH)-responsive traceless tag that facilitates intracellular delivery of small molecule chemical probes has been developed.
Computer-aided identification of new histone deacetylase 6 selective inhibitor with anti-sepsis activity
Yoo, Jakyung,Kim, So-Jin,Son, Dohyun,Seo, Heewon,Baek, Seung Yeop,Maeng, Cheol-Young,Lee, Changsik,Kim, In Su,Jung, Young Hoon,Lee, Sun-Mee,Park, Hyun-Ju
, p. 126 - 135 (2016/04/19)
Histone deacetylase (HDAC) inhibitors have been recognized as promising approaches to the treatment of various human diseases including cancer, inflammation, neurodegenerative diseases, and metabolic disorders. Several pan-HDAC inhibitors are currently approved only as anticancer drugs. Interestingly, SAHA (vorinostat), one of clinically available pan-HDAC inhibitors, shows an anti-inflammatory effect at concentrations lower than those required for inhibition of tumor cell growth. It was also reported that HDAC6 selective inhibitor tubastatin A has anti-inflammatory and anti-rheumatic effect. In our efforts to develop novel HDAC inhibitors, we rationally designed various HDAC inhibitors based on the structures of two hit compounds identified by virtual screening of chemical database. Among them, 9a ((E)-N-hydroxy-4-(2-styrylthiazol-4-yl)butanamide) was identified as a HDAC6 selective inhibitor (IC50 values of 0.199 μM for HDAC6 versus 13.8 μM for HDAC1), and it did not show significant cytotoxicity against HeLa cells. In vivo biological evaluation of 9a was conducted on a lipopolysaccharide (LPS)-induced mouse model of sepsis. The compound 9a significantly improved 40% survival rate (P = 0.0483), and suppressed the LPS-induced increase of TNF-α and IL-6 mRNA expression in the liver of mice. Our study identified novel HDAC6 selective inhibitor 9a, which may serve as a potential lead for the development of anti-inflammatory or anti-sepsis agents.
NMR-based molecular ruler for determining the depth of intercalants within the lipid bilayer. Part III: Studies on keto esters and acids
Afri, Michal,Alexenberg, Carmit,Aped, Pinchas,Bodner, Efrat,Cohen, Sarit,Ejgenburg, Michal,Eliyahu, Shlomi,Gilinsky-Sharon, Pessia,Harel, Yifat,Naqqash, Miriam E.,Porat, Hani,Ranz, Ayala,Frimer, Aryeh A.
, p. 105 - 118 (2015/02/19)
The development of "molecular rulers" would allow one to quantitatively locate the penetration depth of intercalants within lipid bilayers. To this end, an attempt was made to correlate the 13C NMR chemical shift of polarizable "reporter" carbons (e.g., carbonyls) of intercalants within DMPC liposomal bilayers - with the polarity it experiences, and with its Angstrom distance from the interface. This requires families of molecules with two "reporter carbons" separated by a known distance, residing at various depths/polarities within the bilayer. For this purpose, two homologous series of dicarbonyl compounds, methyl n-oxooctadecanoates and the corresponding n-oxooctadecanoic acids (n = 4-16), were synthesized. To assist in assignment and detection several homologs in each system were prepared 13C-enriched in both carbonyls. Within each family, the number of carbons and functional groups remains the same, with the only difference being the location of the second ketone carbonyl along the fatty acid chain. Surprisingly, the head groups within each family are not anchored near the lipid-water interface, nor are they even all located at the same depth. Nevertheless, using an iterative best fit analysis of the data points enables one to obtain an exponential curve. The latter gives substantial insight into the correlation between polarity (measured in terms of the Reichardt polarity parameter, ET(30)) and penetration depth into the liposomal bilayer. Still missing from this curve are data points in the moderate polarity range.
Insights into soluble guanylyl cyclase activation derived from improved heme-mimetics
Von Wantoch Rekowski, Margarete,Kumar, Vijay,Zhou, Zongmin,Moschner, Johann,Marazioti, Antonia,Bantzi, Marina,Spyroulias, Georgios A.,Van Den Akker, Focco,Giannis, Athanassios,Papapetropoulos, Andreas
supporting information, p. 8948 - 8952 (2013/12/04)
Recently, the structure of BAY 58-2667 bound to the Nostoc sp. H-NOX domain was published. On the basis of this structural information, we designed BAY 58-2667 derivatives and tested their effects on soluble guanylyl cyclase (sGC) activity. Derivative 20 activated sGC 4.8-fold more than BAY 58-2667. Co-crystallization of 20 with the Ns H-NOX domain revealed that the increased conformational distortion at the C-terminal region of αF helix containing 110-114 residues contributes to the higher activation triggered by 20.
INDAZOLE COMPOUNDS
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Page/Page column 29, (2012/03/26)
Indazole compounds, processes for their preparation, pharmaceutical compositions containing such compounds and their use in therapy.
Design, synthesis and preliminary bioactivity studies of 1,3,4-thiadiazole hydroxamic acid derivatives as novel histone deacetylase inhibitors
Guan, Peng,Sun, Feng'E,Hou, Xuben,Wang, Feng,Yi, Fan,Xu, Wenfang,Fang, Hao
experimental part, p. 3865 - 3872 (2012/08/27)
Histone deacetylase (HDAC) inhibitors have emerged as a new class of anticancer agents, targeting the biological processes including cell cycle, apoptosis and differentiation. In the present study, a series of 1,3,4-thiadiazole based hydroxamic acids were developed as potent HDAC inhibitors. Some of them showed good inhibitory activity in HDAC enzyme assay and potent growth inhibition in some tumor cell lines. Among them, compound 6i (IC50 = 0.089 μM), exhibited better inhibitory effect compared with SAHA (IC50 = 0.15 μM).
Synthesis and biological evaluation of Ezetimibe analogs as possible cholesterol absorption inhibitors
Wang, Yubin,Haiqian,Huang, Wenlong,Zhang, Huibin,Zhou, Jinpei
scheme or table, p. 500 - 505 (2012/05/19)
In order to investigate the SAR of Ezetimibe analogs for cholesterol absorption inhibitions, amide group and electron-deficient pyridine ring were introduced to the C-(3) carbon chain of Ezetimibe. Eight new derivatives of the 2- azetidinone cholesterol absorption inhibitors have been synthesized, and all of them were enantiomerically pure. All the new compounds were evaluated for their activity to inhibit cholesterol absorption in hamsters, and most of them showed comparable effects in lowering the levels of total cholesterol in the serum.
