- Structure and biological evaluation of (E)-5-bromo-2-methoxy-4-((phenylimino)methyl)phenol derivatives as antibacterial agents
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Three (E)-5-bromo-2-methoxy-4-((phenylimino)methyl)phenol derivatives (1-3) are synthesized and characterized by elemental analysis and single-crystal X-ray diffraction. The antibacterial activities of compounds 1-3 against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Staphylococcus aureus are evaluated by the MTT method.
- Zhou,Ma,Yuan,Han,Liu,Zhu
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Read Online
- Convergent First Total Synthesis of Melovinone: A Densely Substituted 3-Methoxy-4-quinolone Isolated from Melochia tomentosa L
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The first total synthesis of melovinone, a nonrutaceous 3-methoxy-4-quinolone alkaloid isolated from Melochia tomentosa L., is reported. The target was acquired in a convergent fashion through the Suzuki-Miyaura cross-coupling reaction between an ortho-nitrobenzoic acid acetonyl ester derivative prepared from vanillin and potassium 5-phenyl-1-pentyltrifluoroborate, obtained from β-phenethyl bromide. The coupling was followed by a chemoselective reduction of the nitro group and a microwave-Assisted and AcOH-promoted cyclization with rearrangement of the resulting acetonyl anthranilate. This afforded a pseudane intermediate, which was selectively methylated on the 3-OH. The synthetic pathway enabled to reach the objective in 11 steps and 18% overall yield. The 1 H NMR spectra of the synthetic and natural product were in full agreement.
- Aguilar, Abel A. Arroyo,Kaufman, Teodoro S.,Larghi, Enrique L.,Ledesma, Gabriela N.,Tirloni, Bárbara
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p. 4253 - 4262
(2019/11/14)
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- BORON-CONTAINING SMALL MOLECULES
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Compounds, pharmaceutical formulations, and methods of treating bacterial infections are disclosed.
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Paragraph 0304
(2017/09/19)
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- cGAS ANTAGONIST COMPOUNDS
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Disclosed are novel compounds of Formula (I) that are cGAS antagonists, methods of preparation of the compounds, pharmaceutical compositions comprising the compounds, and their use in medical therapy.
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Paragraph 0400
(2017/11/06)
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- Exploring the formation and recognition of an important G-quadruplex in a HIF1α promoter and its transcriptional inhibition by a benzo[c]phenanthridine derivative
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Four putative G-quadruplex sequences (PGSs) in the HIF1α promoter and the 5′UTR were evaluated for their G-quadruplex-forming potential using ESI-MS, CD, FRET, DMS footprinting, and a polymerase stop assay. An important G-quadruplex (S1) has been proven to inhibit HIF1α transcription by blocking AP2 binding. A benzo[c]phenanthridine derivative was found to target the S1 G-quadruplex and induce its conformational conversion from antiparallel to parallel orientation. The transcriptional suppression of HIF1α by this compound was demonstrated using western blotting, Q-RT-PCR, luciferase assay, and ChIP. Our new findings provided a novel strategy for HIF1α regulation and potential insight for cancer therapy.
- Chen, Han,Long, Haitao,Cui, Xiaojie,Zhou, Jiang,Xu, Ming,Yuan, Gu
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supporting information
p. 2583 - 2591
(2014/03/21)
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- Discovery and gram-scale synthesis of BMS-593214, a potent, selective FVIIa inhibitor
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A 6-amidinotetrahydroquinoline screening hit was driven to a structurally novel, potent, and selective FVIIa inhibitor through a combination of library synthesis and rational design. An efficient gram-scale synthesis of the active enantiomer BMS-593214 was developed, which required significant optimization of the key Povarov annulation. Importantly, BMS-593214 showed antithrombotic efficacy in a rabbit arterial thrombosis model. A crystal structure of BMS-593214 bound to FVIIa highlights key contacts with Asp 189, Lys 192, and the S2 pocket.
- Priestley, E. Scott,De Lucca, Indawati,Zhou, Jinglan,Zhou, Jiacheng,Saiah, Eddine,Stanton, Robert,Robinson, Leslie,Luettgen, Joseph M.,Wei, Anzhi,Wen, Xiao,Knabb, Robert M.,Wong, Pancras C.,Wexler, Ruth R.
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supporting information
p. 2432 - 2435
(2013/05/09)
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- A new method for induced fit docking (genius) and its application to virtual screening of novel HCV NS3-4A protease inhibitors
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Hepatitis C virus (HCV) is an etiologic agent of chronic liver disease, and approximately 170 million people worldwide are infected with the virus. HCV NS3-4A serine protease is essential for the replication of this virus, and thus has been investigated as an attractive target for anti-HCV drugs. In this study, we developed our new induced-fit docking program (genius), and applied it to the discovery of a new class of NS3-4A protease inhibitors (IC50 = 1-10 μM including high selectivity index). The new inhibitors thus identified were modified, based on the docking models, and revealed preliminary structure-activity relationships. Moreover, the genius in silico screening performance was validated by using an enrichment factor. We believe our designed scaffold could contribute to the improvement of HCV chemotherapy.
- Takaya, Daisuke,Yamashita, Atsuya,Kamijo, Kazue,Gomi, Junko,Ito, Masahiko,Maekawa, Shinya,Enomoto, Nobuyuki,Sakamoto, Naoya,Watanabe, Yoshiaki,Arai, Ryoichi,Umeyama, Hideaki,Honma, Teruki,Matsumoto, Takehisa,Yokoyama, Shigeyuki
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experimental part
p. 6892 - 6905
(2011/12/16)
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- Tetrahydroquinoline derivatives as antithrombotic agents
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This invention relates generally to tetracyclic tetrahydroquinoline compounds, and analogues thereof, and pharmaceutically acceptable salt forms thereof, which are selective inhibitors of serine protease enzymes, especially factor VIIa; pharmaceutical compositions containing the same; and methods of using the same as anticoagulant agents for modulation of the coagulation cascade.
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- Stereochemistry and Mechanisms of the 3-Carboxymuconate Fungal Pathway in Neurospora SY4a
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The cyclisation of cis,cis-3-carboxymuconic acid 2, catalysed by cycloisomerase enzyme of Neurospora crassa SY4a, has been shown to occur by syn addition of the 1-carboxy group to the 4,5-double bond to give (S)-(-)-carboxymuconolactone 3.Thus, the absolute configuration of the lactone 3 was determined by ozonolysis to give (S)-malic(L-malic) acid.Furthermore, incubation of trisodium cis,cis-3-carboxy-5-deuteriomuconate 9 then ozonolysis of the derived lactone 28 gave (2S,3S)-3-deuteriomalic acid 29.This evidence for syn addition was confirmed by a complementary incubation of undedeuteriated 3-carboxymuconate in deuterium oxide, giving the lactone 31 and hence (2S,3R)-3-deuteriomalic acid 32. The degradation of 3-carboxymuconolactone 3 by multifunctional enzyme complex of Neurospora, to give 3-oxoadipic acid 5, has been studied with the deuteriated trisodium muconates 27, 14 and 20.The overall transformation has been found to involve an intramolecular, suprafacial 1,3-shift of hydrogen (or deuterium) from C-4 in the lactone to C-5 in the oxoadipic acid.The location and stereochemistry of deuterium in the oxoadipic acids 44 and 45 were esteblished by conversion of these acids into the optically active 2-deuteriosuccinic acids 46 and 47, respectively.The 1,3-shift provides compelling eveidence for the formation of the enol lactone 4 as an enzyme-bound intermediate.Successive enzymic hydrolysis and decarboxylation would then complete the biosynthesis of 3-oxoadipic acid 5.
- Hill, Robert A.,Kirby, Gordon W.,O'Loughlin Gary J.,Robins, David J.
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p. 1967 - 1972
(2007/10/02)
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