- Structure-activity relationship (SAR) studies on the mutagenic properties of 2,7-diaminofluorene and 2,7-diaminocarbazole derivatives
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We discovered that 2,7-diaminofluorene or 2,7-diaminocarbazole moiety can be employed as a core structure of highly effective NS5A inhibitors that are connected through amide bonds to proline-valine-carbamate motifs. Amide bonds can be easily cleaved via various metabolic pathways upon administration into the body, and metabolites containing 2,7-diaminofluorene and 2,7-diaminocarbazole core structures have been known to be strong mutagens. To avoid the mutagenesis issue of these core structures, we examined various functional groups at the C9 or N9 position of 2,7-diaminofluorene or 2,7-diaminocarbazole, respectively, through the Ames test in TA98 and TA100 mutants of Salmonella typhimurium LT-2. We discovered that, through proper alkyl substitution at the C9 or N9 position, 2,7-diaminofluorene and 2,7-diaminocarbazole moieties can be successfully employed in drug discovery without necessarily causing mutagenicity problems.
- Kim, Byeong Wook,Lee, Hwa,Keum, Gyochang,Kim, B. Moon
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supporting information
(2020/11/27)
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- Azo dye, and preparation method and application thereof
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The invention discloses an azo dye represented by formula I shown in the specification, and a preparation method and application thereof. The azo dye provided by the invention has remarkably high dichroism, the solubility of the azo dye in a liquid crystal medium can reach 2 wt% or above, and when the azo dye is applied to a guest-host liquid crystal composition, a liquid crystal display device containing the guest-host liquid crystal composition can have higher contrast.
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Paragraph 0081-0083
(2021/06/12)
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- New convergent one pot synthesis of amino benzyl ethers bearing a nitrogen-containing bicycle
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We report herein a new convergent one pot method for the synthesis of amino benzyl ethers containing a bicyclic amine, derived from different substituted benzyl alcohols and bicyclic amino alcohols such as tropine, pseudotropine, and 3-quinuclidinol, using chlorotrimethylsilane and sodium iodide. In order to avoid the competitive reaction with the nitrogen atom, a solution of the separately prepared alkoxide of tropine, pseudotropine, and 3-quinuclidinol was added to the preformed substituted benzyl iodides and allowed to reflux at 90 °C for 15 h under nitrogen atmosphere. This method provides an efficient alternative of the preparation of amino benzyl ethers in organic synthesis with good yields in comparison with existed methods.
- López, Jhon J.,Pérez, Edwin G.
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p. 715 - 723
(2019/02/19)
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- CARBAZOLE COMPOUND HAVING ANTI-VIRUS ACTIVITY
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The present invention relates to a carbazole compound having anti-virus activity, and more particularly, to a novel compound selected from the group of consisting of a carbazole compound which shows excellent anti-proliferative efficacy against hepatitis C virus (HCV), a pharmaceutically acceptable salt thereof, a hydrate thereof, and an isomer thereof; an anti-virus pharmaceutical composition including the novel compound as an active ingredient; a pharmaceutical composition for preventing or treating liver diseases caused by hepatitis C virus; and a method of preparing the novel compound.
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Paragraph 0409; 0410; 0411; 0466; 0467
(2018/03/25)
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- Chemoselective and site-selective peptide and native protein modification enabled by aldehyde auto-oxidation
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We report a chemoselective and site-selective formylation of ?-amine in native proteins. The aldehyde auto-oxidation re-routing, regulated generation of formate, and reversible N-terminus protection drive the transformation. It labels a single ?-amine in a pool of its copies, other nucleophilic residues, and α-amine. The extension of the methodology leads to site-selective acylation.
- Purushottam, Landa,Adusumalli, Srinivasa Rao,Chilamari, Maheshwerreddy,Rai, Vishal
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supporting information
p. 959 - 962
(2017/01/17)
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- Highly efficient reduction of carbonyls, azides, and benzyl halides by NaBH4 in water catalyzed by PANF-immobilized quaternary ammonium salts
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A series of polyacrylonitrile fiber-supported quaternary ammonium salts (PANF-QAS) were prepared and applied to the catalytic reduction of aldehydes, ketones, azides, and benzyl halides in water using NaBH4 as the reducing reagent in a highly efficient, economic, and environmentally benign way. The structure-activity relationships were investigated, which showed that the catalysts made up of quaternary ammonium salts with longer alkyl chains, larger cationic radii and better lipophilicity speed up the reduction reaction to afford the products in excellent yield. Moreover, the optimized catalyst can be applied to the reduction of 1-naphthaldehyde in a continuous flow process with outstanding reactivity and recyclability.
- Du, Jianguo,Xu, Gang,Lin, Huikun,Wang, Guangwei,Tao, Minli,Zhang, Wenqin
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p. 2726 - 2735
(2016/05/24)
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- Expanded hexapyrrolohexaazacoronenes. Near-infrared absorbing chromophores with interrupted peripheral conjugation
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A family of azacoronenes containing up to two saturated bridges at the periphery was synthesized from substituted hexapyrrolylbenzenes using a two-step condensation-aromatization procedure. The introduction of peripheral bridges provides access to nonplanar, sterically crowded systems that display complex reactivity patterns, involving stereospecific aromatization of bridges and nucleophile additions. Despite the interrupted conjugation on the periphery, the new azacoronenes have easily accessible higher oxidation levels, and a quadruply charged species was chemically generated by reaction with SbCl5. These oxidized species show extensive π-electron conjugation and are efficient UV-vis-NIR absorbers, active up to ca. 2400 nm. Interruption of peripheral conjugation is shown to induce a tendency toward biradicaloid electron configurations in doubly oxidized species.
- Goka, Elzbieta,Chmielewski, Piotr J.,Lis, Tadeusz,Stpie, Marcin
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p. 16399 - 16410
(2015/02/05)
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- Synthesis and biological evaluation of pyridazinone analogues as potential cardiac positron emission tomography tracers
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A series of fluorinated pyridazinone derivatives with IC50 values ranging from 8 to 4000 nM for the mitochondrial complex 1 (MC1) have been prepared. Structure-activity relationship (SAR) assessment indicated preference of the fluorine label to be incorporated on an alkyl side chain rather than directly on the pyridazinone moiety. Tissue distribution studies of a series of analogues ([18F] 22-28) in Sprague-Dawley (SD) rats identified [ 18F]27 as the most promising radiotracer with high uptake in cardiac tissue (3.41%ID/g; 30 min post injection) in addition to favorable heart to nontarget organ distribution ratios. MicroPET images of SD rats and nonhuman primates after [18F]27 administration allowed easy assessment of the myocardium through 60 min with minimal lung or liver interference.
- Purohit, Ajay,Radeke, Heike,Azure, Michael,Hanson, Kelley,Benetti, Richard,Su, Fran,Yalamanchili, Padmaja,Yu, Ming,Hayes, Megan,Guaraldi, Mary,Kagan, Mikhail,Robinson, Simon,Casebier, David
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experimental part
p. 2954 - 2970
(2009/05/27)
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- Design, synthesis and antiproliferative activity of tripentones: A new series of antitubulin agents
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Structure-activity relationship studies of a new series of tripentones (thieno[2,3-b]pyrrolizin-8-ones), led us to prepare several derivatives with antiproliferative activities. The most promising 3-(3-hydroxy-4-methoxyphenyl)thieno[2,3-b]pyrrolizin-8-one 20 (leukemia L1210, IC50 = 15 nM) was shown to be a potent inhibitor of tubulin polymerization.
- Lisowski, Vincent,Enguehard, Cecile,Lancelot, Jean-Charles,Caignard, Daniel-Henri,Lambel, Stephanie,Leonce, Stephane,Pierre, Alain,Atassi, Ghanem,Renard, Pierre,Rault, Sylvain
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p. 2205 - 2208
(2007/10/03)
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- Substituent Effects on Chemosterilant Activity of 2,4-Di-tert-butyl-6-(4'-substituted benzyl)phenols in the House Fly (Musca domestica L.)
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A series of 2,4-di-tert-butyl-6-(4'-X-benzyl)phenols was prepared, analogous to the compound Jurd 2644 (X = OMe) in an attempt to establish a Hammett relationship between the 4'-substituent and the chemosterilant activity of the compounds after oral administration to adult Musca domestica.Fourteen compounds of this type were prepared, 12 of them new.Jurd 2419 (X = H) was found to be as active in our bioassay as Jurd 2644, as were four new compounds .All prevented successful reproduction at 30 mg/kg of diet.There was no correlation between Hammett ? and activity.Active compounds all had small substituents and molecular weights below 350.The activity seemed to be determined by the bulk of X rather than by its electronic properties. - Keywords: Reproduction; delayed toxicity; Jurd 2644
- Kochansky, Jan,Cohen, Charles F.,Lusby, William R.
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p. 2974 - 2980
(2007/10/03)
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- Molecular Recognition Directed Self-Assembly of Tubular Liquid Crystalline and Crystalline Supramolecular Architectures from Taper Shaped (15-Crown-5)methyl 3,4,5-Tris(p-alkyloxybenzyloxy)benzoates and (15-Crown-5-)methyl 3,4,5-Tris(p-dodecyloxy)benzoate
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The syntheses and characterization of a series of (15-crown-5-)methyl 3,4,5-tris(p-alkyloxybenzyloxy)benzoates with alkyl tails of four 25, six 26, and twelve 27 carbon atoms and of (15-crown-5-)methyl 3,4,5-tris(p-dodecyloxybenzoate) 28 are described.Complexation of the crown ether endo-receptor with NaCF3SO3 destabilizes the crystalline phase of 25, 26, 27 and 28 and induces for the case of 27 and 28 the self-assembly of a supramolecular cylindral channel-like architecture which displays a thermotropic hexagonal columnar (Φh) mesophase.Most remarkably, in the crystalline phase of the complexes of 27 with NaCF3SO3 the cylindrical structure of the Φh mesophase is maintained.Characterization of these supramolecular architectures was performed by a combination of differential scanning calorimetry (DSC), thermal optical polarized microscopy, X-ray scattering and molecular modelling.A model is proposed in which a stratum of the column is formed by six molecules of 27 and 28 with the crown ether receptors residing in the column centre and the alkyl tails radiating toward the column periphery. endo-Recognition generated via the (15-crown-5)methyl receptor upon complexation, and exo-recognition provided by the tapered 3,4,5-tris(p-dodecyloxybenzyloxy)benzoate and 3,4,5-tris(p-dodecyloxy)benzoate fragments of 27 and 28 provide the driving force for the self-assembly of this cylindrical supramolecule.
- Johansson, Gary,Percec, Virgil,Ungar, Goran,Abramic, Darija
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p. 447 - 460
(2007/10/02)
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