- Total synthesis of (-)-flustramine B via one-pot intramolecular ullmann coupling and claisen rearrangement
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Total synthesis of (-)-flustramine B was achieved via one-pot intramolecular Ullmann coupling and Claisen rearrangement. A striking feature of this method of synthesis is that the sequential intramolecular Ullmann coupling and Claisen rearrangement reactions proceeds with concomitant deprotection of the methoxymethyl (MOM) group to afford spirocyclic oxindole with perfect asymmetric transmission in good overall yield.
- Hirano, Tomohiro,Iwakiri, Kanako,Miyamoto, Hiroshi,Nakazaki, Atsuo,Kobayashi, Susumu
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- Synthetic Analogues of the Snail Toxin 6-Bromo-2-mercaptotryptamine Dimer (BrMT) Reveal That Lipid Bilayer Perturbation Does Not Underlie Its Modulation of Voltage-Gated Potassium Channels
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Drugs do not act solely by canonical ligand-receptor binding interactions. Amphiphilic drugs partition into membranes, thereby perturbing bulk lipid bilayer properties and possibly altering the function of membrane proteins. Distinguishing membrane perturbation from more direct protein-ligand interactions is an ongoing challenge in chemical biology. Herein, we present one strategy for doing so, using dimeric 6-bromo-2-mercaptotryptamine (BrMT) and synthetic analogues. BrMT is a chemically unstable marine snail toxin that has unique effects on voltage-gated K+ channel proteins, making it an attractive medicinal chemistry lead. BrMT is amphiphilic and perturbs lipid bilayers, raising the question of whether its action against K+ channels is merely a manifestation of membrane perturbation. To determine whether medicinal chemistry approaches to improve BrMT might be viable, we synthesized BrMT and 11 analogues and determined their activities in parallel assays measuring K+ channel activity and lipid bilayer properties. Structure-activity relationships were determined for modulation of the Kv1.4 channel, bilayer partitioning, and bilayer perturbation. Neither membrane partitioning nor bilayer perturbation correlates with K+ channel modulation. We conclude that BrMT's membrane interactions are not critical for its inhibition of Kv1.4 activation. Further, we found that alkyl or ether linkages can replace the chemically labile disulfide bond in the BrMT pharmacophore, and we identified additional regions of the scaffold that are amenable to chemical modification. Our work demonstrates a strategy for determining if drugs act by specific interactions or bilayer-dependent mechanisms, and chemically stable modulators of Kv1 channels are reported.
- Dockendorff, Chris,Gandhi, Disha M.,Kimball, Ian H.,Eum, Kenneth S.,Rusinova, Radda,Ingólfsson, Helgi I.,Kapoor, Ruchi,Peyear, Thasin,Dodge, Matthew W.,Martin, Stephen F.,Aldrich, Richard W.,Andersen, Olaf S.,Sack, Jon T.
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- Synthesis of indoloquinolines: An intramolecular cyclization leading to advanced perophoramidine-relevant intermediates
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The bioactive natural product perophoramidine has proved a challenging synthetic target. An alternative route to its indolo[2,3-b]quinolone core structure involving a N-chlorosuccinimde-mediated intramolecular cyclization reaction is reported. Attempts to progress towards the natural product are also discussed with an unexpected deep-seated rearrangement of the core structure occurring during an attempted iodoetherification reaction. X-ray crystallographic analysis provides important analytical confirmation of assigned structures.
- Cordes, David B.,Johnston, Craig A.,Lebl, Tomas,Slawin, Alexandra M. Z.,Westwood, Nicholas J.
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supporting information
(2021/10/12)
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- Novel compound and organic light emitting device comprising the same
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The present invention provides: a novel compound each comprising an amino group at both ends of a molecule; and an organic light emitting device comprising the same. When the compound of chemical formula 1 of the present invention is applied to the organic light emitting device, it is possible to improve efficiency, lower driving voltage, and improve lifespan characteristics of the organic light emitting device.COPYRIGHT KIPO 2020
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Paragraph 0392; 0397-0399
(2020/05/26)
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- Synergy effect of electronic characteristics and spatial configurations of electron donors on photovoltaic performance of organic dyes
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Considering the key role of electron donors to the intramolecular charge transfer of organic dyes, molecular arrangement and electron processes in dye-sensitized solar cells, four organic dyes (LI-133-136) were designed and synthesized with indolo[3,2-b]indole (IDID) as the main electron donor and various aromatics as the assistant ones. The broad light response was achieved by the strong electron-donating ability of IDID with a planar structure, and with the aid of the electron-rich property of carbazole and triphenylamine. Moreover, the twisted configuration and large size of triphenylamine on the head of dye LI-136 can be beneficial to suppressing dye aggregation and electron recombination, contributing to the improved photovoltaic performance. With the systematic investigation of their photophysical and electrochemical impedance properties, together with theoretical calculations, the electronic characteristics of IDID and the spatial configuration of triphenylamine were highlighted as a synergy effect on the photovoltaic performance, affording an efficient strategy to simultaneously enhance the light-harvesting property and suppress the charge recombination.
- Chang, Kai,Han, Hongwei,Li, Qianqian,Li, Sheng,Li, Zhen,Liao, Qiuyan,Liu, Siwei,Wang, Jinfeng
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p. 14453 - 14461
(2020/11/09)
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- Novel compound and organic light emitting device comprising the same
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The present invention provides a novel compound containing amino groups at both ends of a molecule and an organic light emitting device having the novel compound. The present invention also provides the organic light emitting device comprising: a first electrode; a second electrode facing the first electrode; and at least one organic material layer provided between the first electrode and the second electrode.COPYRIGHT KIPO 2019
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Paragraph 0395; 0400-0402
(2019/01/31)
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- Discovery of Marinoquinolines as Potent and Fast-Acting Plasmodium falciparum Inhibitors with in Vivo Activity
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We report the discovery of marinoquinoline (3H-pyrrolo[2,3-c]quinoline) derivatives as new chemotypes with antiplasmodial activity. We evaluated their inhibitory activities against P. falciparum and conducted a structure-activity relationship study, focusing on improving their potency and maintaining low cytotoxicity. Next, we devised quantitative structure-activity relationship (QSAR) models, which we prospectively validated, to discover new analogues with enhanced potency. The most potent compound, 50 (IC503d7 = 39 nM; IC50K1 = 41 nM), is a fast-acting inhibitor with dual-stage (blood and liver) activity. The compound showed considerable selectivity (SI > 6410), an additive effect when administered in combination with artesunate, excellent tolerability in mice (all mice survived after an oral treatment with a 1000 mg/kg dose), and oral efficacy at 50 mg/kg in a mouse model of P. berghei malaria (62% reduction in parasitemia on day 5 postinfection); thus, compound 50 was considered a lead compound for the discovery of new antimalarial agents.
- Aguiar, Anna Caroline Campos,Panciera, Michele,Simao Dos Santos, Eric Francisco,Singh, Maneesh Kumar,Garcia, Mariana Lopes,De Souza, Guilherme Eduardo,Nakabashi, Myna,Costa, José Luiz,Garcia, Célia R.S.,Oliva, Glaucius,Correia, Carlos Roque Duarte,Guido, Rafael Victorio Carvalho
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p. 5547 - 5568
(2018/06/18)
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- BENZODIAZEPINES AS BROMODOMAIN INHIBITORS
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The present invention provides novel benzodiazepine derivatives of Formula I or pharmaceutically acceptable derivatives, polymorphs, salts or prodrugs thereof. Said compounds have potential as bromodomain (BRD) inhibitors.
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Page/Page column 62; 71
(2017/02/28)
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- A new regiospecific synthesis method of 1H-pyrazolo[3,4-b]quinoxalines – Potential materials for organic optoelectronic devices, and a revision of an old scheme
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A series of 6-substituted-1,3-diphenyl-1H-pyrazolo[3,4-b]quinoxalines were prepared using a new synthetic pathway: reductive cyclization of appropriate 5-(o-nitrophenyl)-pyrazoles with ferrous oxalate or triphenylphosphine. The main advantage of this procedure is that, contrary to the older protocols of pyrazolo[3,4-b]quinoxaline synthesis, this method allows for a substituent to be introduced to the carbocyclic ring without the formation of isomers. The pyrazole ring can also be modified to some extent. Furthermore, we propose a new mechanism for the oldest reported pyrazolo[3,4-b]quinoxaline synthesis, based on the condensation between o-phenylenediamine and 3,4-pyrazolin-5-diones.
- Danel, Andrzej,Wojtasik, Katarzyna,Szlachcic, Pawe?,Gryl, Marlena,Stadnicka, Katarzyna
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p. 5072 - 5081
(2017/07/28)
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- Palladium-Catalyzed Incorporation of Two C1 Building Blocks: The Reaction of Atmospheric CO2 and Isocyanides with 2-Iodoanilines Leading to the Synthesis of Quinazoline-2,4(1H,3H)-diones
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A Pd-catalyzed insertion and cycloaddition of CO2 and isocyanide into 2-iodoanilines under atmospheric pressure has been developed and affords quinazoline-2,4(1H,3H)-diones through the formation of new C-C, C-O, and C-N bonds under mild conditions. This reaction provides a new and practical method not only for the construction of quinazoline-2,4(1H,3H)-diones but also for the efficient utilization of carbon dioxide.
- Xu, Pei,Wang, Fei,Wei, Tian-Qi,Yin, Ling,Wang, Shun-Yi,Ji, Shun-Jun
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supporting information
p. 4484 - 4487
(2017/09/11)
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- Stereoselective synthesis of spirocyclic oxindoles based on a one-pot Ullmann coupling/Claisen rearrangement and its application to the synthesis of a hexahydropyrrolo[2,3-b]indole alkaloid
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An efficient and convenient approach to the synthesis of spirocyclic oxindoles from iodoindoles has been developed. The most striking feature of this approach is that the sequential intramolecular Ullmann coupling and Claisen rearrangement proceeds in a one-pot manner to afford 3-spiro-2-oxindoles in good yield with excellent diastereoselectivity. Application of this one-pot reaction to chiral non-racemic tertiary alcohol substrates resulted in complete chirality transfer to the spirocyclic quaternary carbon. Using this method, asymmetric total synthesis of (-)-debromoflustramine B was accomplished.
- Miyamoto, Hiroshi,Hirano, Tomohiro,Okawa, Yoichiro,Nakazaki, Atsuo,Kobayashi, Susumu
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supporting information
p. 9481 - 9493
(2013/10/08)
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- First synthesis of 3,6′- and 3,7′-biquinoline derivatives
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The preparation of new 3,6′- and 3,7′-biquinoline derivatives was achieved by microwave-assisted Suzuki cross-coupling between N-protected 6- or 7-bromoquinolin-2(lH)-ones and quino-lin-3-ylboronic acid. Moreover, a new synthesis of 7-bromoquino-lin-2(lH)-one leading solely to the 7-substituted isomer was carried out. Thieme Stuttgart.
- Broch, Sidonie,Anizon, Fabrice,Moreau, Pascale
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body text
p. 2039 - 2044
(2009/04/03)
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- Orthogonally Functionalized Oligomers for Controlled Self-Assembly
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The synthesis of molecules terminated with complementary thiol-protecting groups is described. The target compounds contain functionalities on one end known to form self-assembled monolayers on metal surfaces while at the other end an intact thioacetate is present whereby self-assembly may again occur after an in situ deprotection. Self-assembly data is reported for selected compounds to assess their efficacy in surface adhesion.
- Flatt, Austen K.,Yao, Yuxing,Maya, Francisco,Tour, James M.
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p. 1752 - 1755
(2007/10/03)
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- Condensed Heteroaromatic Ring Systems. XII. Synthesis of Indole Derivatives from Ethyl 2-Bromocarbanilates
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The palladium-catalyzed reaction of ethyl 2-bromocarbanilate with trimethylsilylacetylene yielded ethyl 2-(trimethylsilylethynyl)carbanilate, which was treated with sodium ethoxide to give indole.The carbanilates having a methyl or a bromo substituent were similarly transformed to corresponding indole derivatives.Furthermore, pyrrolo- and Pyrrolopyridines were synthesized by this method.Keywords---palladium-catalyzed reaction; trimethylsilylacetylene; ethyl 2-halocarbanilate; ethyl 2-halopyridinecarbamate; ethyl 2-(trimethylsilylethynyl)carbanylate; ethyl o-(trimethylsilylethynyl)pyridinecarbamate;indole;pyrrolopyridine
- Sakamoto, Takao,Kondo, Yoshinori,Iwashita, Shigeki,Yamanaka, Hiroshi
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p. 1823 - 1828
(2007/10/02)
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