- Novel non-nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase. 6. 2-Indol-3-yl- and 2-azaindol-3-yl- dipyridodiazepinones
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Modification of the non-nucleoside inhibitor of HIV-1 reverse transcriptase nevirapine (Viramune) by incorporation of a 2-indolyl substituent confers activity against several mutant forms of the enzyme.
- Kelly,McNeil,Rose,David,Shih,Grob
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Read Online
- Synthesis of selenium-containing biindolyls and their Diels–Alder reaction toward the synthesis of heteroannulated [a]- and [c]-carbazoles
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We reported the first syntheses of 2- and 3-(2-(benzo[b]selenophen-2-yl)-indoles and their Diels–Alder reactions to furnish six unique annulated benzoselenphene carbazoles. This facile route can be used to synthesize selenium-containing biindolyl derivati
- Wang, Ruei-Yu,Kao, Wei-Ting,Shih, Tzenge-Lien
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- INDOLE DERIVATIVES AND USES THEREOF FOR TREATING A CANCER
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The present invention relates to indole derivatives of formula (I') as CK2 inhibitor and pharmaceutical compositions comprising the same. The present invention further relates to the use of such compounds of formula (I) for use for preventing and/or treating a cancer.
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- Tricepyridinium-inspired QACs yield potent antimicrobials and provide insight into QAC resistance
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Quaternary ammonium compounds (QACs) comprise a large class of surfactants, consumer products, and disinfectants. The recently-isolated QAC natural product tricepyridinium bromide displays potent inhibitory activity against S. aureus but due to its unique structure, its mechanism of action remains unclear. A concise synthetic route to access tricepyridinium analogs was thus designed and four N-alkyl compounds were generated in addition to the natural product. Biological analysis of these compounds revealed that they display remarkable selectivity towards clinically-relevant Gram-positive bacteria exceeding that of commercially-available QACs such as cetylpyridinium chloride (CPC) and benzalkonium chloride (BAC) while having little to no hemolytic activity. Molecular modeling studies revealed that tricepyridinium and shorter-chain N-alkyl analogs may preferentially bind to the QacR transcription factor leading to potential activation of the QAC resistance pathway found in MRSA; however, our newly synthesized analogs are able to overcome this liability.
- Garrison, Michelle A.,Mahoney, Andrew R.,Wuest, William M.
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p. 463 - 466
(2020/10/19)
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- Small-molecule anti-HIV-1 agents based on HIV-1 capsid proteins
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The capsid of human immunodeficiency virus type 1 (HIV-1) is a shell that encloses viral RNA and is highly conserved among many strains of the virus. It forms a conical structure by assembling oligomers of capsid (CA) proteins. CA dysfunction is expected to be an important target of suppression of HIV-1 replication, and it is important to understand a new mechanism that could lead to the CA dysfunction. A drug targeting CA however, has not been developed to date. Hydrophobic interactions between two CA molecules via Trp184/Met185 in CA were recently reported to be important for stabilization of the multimeric structure of CA. In the present study, a small molecule designed by in silico screening as a dipeptide mimic of Trp184 and Met185 in the interaction site, was synthesized and its significant anti-HIV-1 activity was confirmed. Structure activity relationship (SAR) studies of its derivatives were performed and provided results that are expected to be useful in the future design and development of novel anti-HIV agents targeting CA.
- Kobayakawa, Takuya,Yokoyama, Masaru,Tsuji, Kohei,Fujino, Masayuki,Kurakami, Masaki,Boku, Sayaka,Nakayama, Miyuki,Kaneko, Moemi,Ohashi, Nami,Kotani, Osamu,Murakami, Tsutomu,Sato, Hironori,Tamamura, Hirokazu
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- H-bonding vs Protonation of Alkynes in Regioselective Hydroamination Reactions: A Glimpse into the Reactivity of Arylogous Ynolethers and Ynamines
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In this paper is described the competition and transition between hydrogen bonding and protonation of alkynes connected, on one side, to various aromatic rings and to chiral amino ester appendages on the other side. While the first mode of activation indu
- Abe, Masahiro,Jean, Alexandre,Blanchet, Jér?me,Rouden, Jacques,Maddaluno, Jacques,De Paolis, Micha?l
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p. 15448 - 15475
(2019/11/29)
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- Total Synthesis of Spirotryprostatins through Organomediated Intramolecular Umpolung Cyclization
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Cyclodipeptide 2,5-diketopiperazines (DKP) are privileged structural units present in drugs and natural alkaloids. This work reports a new method for the synthesis of biologically important DKP scaffolds based on an intramolecular nucleophilic α-addition of general amides towards an alkynamide system. The utility of this umpolung cyclization mediated by trimethyl phosphine and l-glutamic acid is highlighted by its application to the concise total syntheses of 6-methoxyspirotryprostatin B (the first total synthesis), spirotryprostatin A, and spirotryprostatin B.
- Xi, Yong-Kai,Zhang, Hongbin,Li, Rui-Xi,Kang, Shi-Yuan,Li, Jin,Li, Yan
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p. 3005 - 3009
(2019/02/07)
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- BENZYLAMINE COMPOUND, AND PHARMACEUTICAL COMPOSITION AND ANTI-HIV AGENT THEREOF
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PROBLEM TO BE SOLVED: To provide: a novel benzylamine compound; and a pharmaceutical composition and an anti-HIV agent that are suitable for suppression of HIV activity. SOLUTION: The benzylamine compound is represented by the general formula (1) in the figure. In the general formula (1), R1 represents a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group; A represents an oxygen atom or sulfur atom; R2 represents a substituted or unsubstituted alkyl group; and n represents an integer from 1 to 10. SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT
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- Aerobic, Metal-Free, and Catalytic Dehydrogenative Coupling of Heterocycles: En Route to Hedgehog Signaling Pathway Inhibitors
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The nitrosonium ion-catalyzed dehydrogenative coupling of heteroarenes under mild reaction conditions is reported. The developed method utilizes ambient molecular oxygen as a terminal oxidant, and only water is produced as byproduct. Dehydrogenative coupl
- Bering, Luis,Paulussen, Felix M.,Antonchick, Andrey P.
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p. 1978 - 1981
(2018/04/16)
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- SELECTIVE ALPHA-7 NICOTINIC RECEPTOR AGONISTS AND METHODS FOR MAKING AND USING THEM
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In alternative embodiments, provided are selective agonists having a high affinity for the alpha7 nicotinic acetylcholine receptor (α7 nAChR), assays for selectivity of nicotinic receptor subtype and ligand-gated ion channel subtype based on receptor occupation and response, behavioral assessments for reversing cognitive impairment after scopolamine treatment, enhancing memory retention over time, pharmaceutical compositions and formulations and devices comprising them, and methods for making and using them, including characterizing and efficiently assaying them for receptor subtype selectivity. In alternative embodiments, provided are substituted anti 1,2,3-triazoles compounds with high affinity, and selective binding, for the alpha7 nicotine acetylcholine receptor (α7 nAChR), as exemplified by 5-(1-(2-(Piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND1”), 5-((quinuclid-3-yl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND8”) and 3-(4-hydroxyphenyl-1,2,3-triazol-1-yl) quinuclidine (“QND8”). In alternative embodiments, provided are products of manufacture such as pumps, devices, syringes and the like comprising a compound, pharmaceutical composition or formulation as provided herein.
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- Pyrimidine derivatives Anaplastic lymphoma kinase inhibitors
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The invention belongs to the field of a medical technology and specifically relates to a pyrimidine derivative type anaplastic lymphoma kinase inhibitor as shown in the general formula (I) or its stereisomer, or its pharmaceutically acceptable salt, ester or solvate, wherein R1, R2, R3, R4, R5 and A ring are as defined in the specification. The invention also relates to a preparation method of the compounds, a pharmaceutic preparation and a pharmaceutical composition containing the compounds and an application of the compound or its stereisomer, or its pharmaceutically acceptable salt, ester or solvate in the preparation of medicines for treating and/or preventing diseases related to anaplastic lymphoma kinase-mediated cancer.
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- PYRROLE DERIVATIVES
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Provided herein are compounds of the formula (I) : as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful
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- Total Synthesis of Oridamycins A and B
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(Chemical Equation Presented) The total synthesis of both oridamycin A and oridamycin B was accomplished starting from a common synthetic intermediate readily prepared from geranyl acetate. The sequence utilizes an oxidative radical cyclization to construct the trans-decalin ring system, setting three of four contiguous stereocenters in one operation. The carbazole nucleus was forged through a one-pot process entailing acid-promoted dehydration followed by 6π-electrocyclization/aromatization.
- Trotta, Adam H.
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supporting information
p. 3358 - 3361
(2015/07/15)
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- Asymmetric synthesis of 1-heteroaryl-1-arylalkyl tertiary alcohols and 1-pyridyl-1-arylethanes by lithiation-borylation methodology
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The synthesis of highly enantioenriched α-heterocyclic tertiary alcohols has been achieved via lithiation-borylation of a configurationally stable lithiated carbamate and heterocyclic pinacol boronic esters followed by oxidation. Protodeboronation of the α-heterocyclic tertiary boronic esters using TBAF·3H2O or CsF gave highly enantioenriched 1-pyridyl-1-arylethanes in high er.
- Watson, Charlotte G.,Aggarwal, Varinder K.
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p. 1346 - 1349
(2013/05/09)
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- One-pot synthesis of camalexins and 3,3′-biindoles by the Masuda borylation-Suzuki arylation (MBSA) sequence
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The Masuda borylation/Suzuki arylation (MBSA) sequence starting from N-protected 3-iodoindoles has successfully been extended to the coupling of five-membered heterocycles and indoles in the arylation step, which could not be achieved with previously developed MBSA methods. By this approach the one-pot nature of the method as well as the use of a simple catalyst system has been retained. The applicability of the method has been demonstrated by the facile synthesis of camalexins and 3,3′-biindoles, compounds of special interest due to their pronounced antifungal, antimicrobial and cytotoxic activities. The Masuda borylation/Suzuki arylation sequence furnishes in a concise one-pot manner camalexins and 3,3′-biindoles, compounds that show pronounced antifungal, antimicrobial, and cytotoxic activities. Copyright
- Tasch, Boris O. A.,Antovic, Dragutin,Merkul, Eugen,Mueller, Thomas J. J.
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p. 4564 - 4569
(2013/07/26)
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- Total synthesis of spirobacillene A
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The first total synthesis of spirobacillene A, an indole alkaloid isolated from Lysinibacillus fusiformis, is reported. A Lewis acid mediated spirocyclization of an anisole derivative onto a tethered ynone was used as a key step, drawing inspiration from
- Unsworth, William P.,Cuthbertson, James D.,Taylor, Richard J. K.
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p. 3306 - 3309
(2013/07/26)
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- Masuda borylation-Suzuki coupling (MBSC) sequence of vinylhalides and its application in a one-pot synthesis of 3,4-biarylpyrazoles
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The Masuda borylation-Suzuki coupling (MBSC) sequence was successfully extended to the challenging coupling of vinylhalides with various (hetero)arylhalides using sterically hindered phosphane ligands. Starting from (hetero)arylhalides and α-bromocinnamaldehyde, the sequentially Pd-catalyzed process selectively furnishes α,β-substituted cinnamaldehydes without affecting the reactivity of the Michael system. These intermediates were implemented as entries into a novel synthesis of 3,4-diaryl 1H-pyrazoles in the fashion of a three-step one-pot procedure consisting of a Masuda borylation-Suzuki coupling and subsequent Michael addition- cyclocondensation-elimination sequence. The Royal Society of Chemistry.
- Tasch, Boris O. A.,Bensch, Lisa,Antovic, Dragutin,Müller, Thomas J. J.
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p. 6113 - 6118
(2013/09/12)
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- An acid-promoted novel skeletal rearrangement initiated by intramolecular ipso-Friedel-Crafts-type addition to 3-alkylidene indolenium cations
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An acid-promoted novel skeletal rearrangement is described. Using trifluoroacetic acid as the acid promoter, an intramolecular ipso-Friedel-Crafts-type addition of phenols to 3-alkylidene indolenium cations, formation of iminium cations through rearomatization of the spirocyclohexadienone units, and intramolecular Pictet-Spengler reaction proceeded sequentially, producing tricyclic indole derivatives.
- Yokosaka, Takuya,Nemoto, Tetsuhiro,Hamada, Yasumasa
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p. 5431 - 5433
(2012/07/03)
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- Rapid preparation of triazolyl substituted NH-heterocyclic kinase inhibitors via one-pot Sonogashira coupling-TMS-deprotection-CuAAC sequence
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The one-pot, three-component Sonogashira coupling-TMS-deprotection-CuAAC ("click") sequence is the key reaction for the rapid synthesis of triazolyl substituted N-Boc protected NH-heterocycles, such as indole, indazole, 4-, 5-, 6-, and 7-azaindoles, 4,7-diazaindole, 7-deazapurines, pyrrole, pyrazole, and imidazole. Subsequently, the protective group was readily removed to give the corresponding triazolyl derivatives of these tremendously important NH-heterocycles. All compounds have been tested in a broad panel of kinase assays. Several compounds, 8f, 8h, 8k, and 8l, have been shown to inhibit the kinase PDK1, a target with high oncology relevance, and thus they are promising lead structures for the development of more active derivatives. The X-ray structure analysis of compound 8f in complex with PDK1 has revealed the detailed binding mode of the molecule in the kinase. The Royal Society of Chemistry 2011.
- Merkul, Eugen,Klukas, Fabian,Dorsch, Dieter,Graedler, Ulrich,Greiner, Hartmut E.,Mueller, Thomas J. J.
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p. 5129 - 5136
(2011/09/13)
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- One-pot synthesis of diazine-bridged bisindoles and concise synthesis of the marine alkaloid hyrtinadine A
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Diazine-bridged bisindoles are readily obtained from N-Bocprotected 3-iodoindoles and 3-iodo-7-azaindole in a pseudo three-component reaction involving a one-pot Masuda borylation-Suzuki arylation sequence. Some of the title com-pounds display promising c
- Tasch, Boris O. A.,Merkul, Eugen,Mueller, Thomas J. J.
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p. 4532 - 4535
(2011/10/03)
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- Alkyne-aldehyde reductive C-C coupling through ruthenium-catalyzed transfer hydrogenation: Direct regio- and stereoselective carbonyl vinylation to form trisubstituted allylic alcohols in the absence of premetallated reagents
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Nonsymmetric 1,2-disubstituted alkynes engage in reductive coupling to a variety of aldehydes under the conditions of ruthenium-catalyzed transfer hydrogenation by employing formic acid as the terminal reductant and delivering the products of carbonyl vinylation with good to excellent levels of regioselectivity and with complete control of olefin stereochemistry. As revealed in an assessment of the ruthenium counterion, iodide plays an essential role in directing the regioselectivity of C-C bond formation. Isotopic labeling studies corroborate reversible catalytic propargyl C-H oxidative addition in advance of the C-C coupling, and demonstrate that the C-C coupling products do not experience reversible dehydrogenation by way of enone intermediates. This transfer hydrogenation protocol enables carbonyl vinylation in the absence of stoichiometric metallic reagents. Fun with formate: Under the conditions of ruthenium-catalyzed transfer hydrogenation employing formic acid as the terminal reductant, nonsymmetric 1,2-disubstituted alkynes engage in reductive coupling to aldehydes, delivering the products of carbonyl vinylation with good to excellent levels of regioselectivity and with complete control of the olefin stereochemistry (see scheme). Copyright
- Leung, Joyce C.,Patman, Ryan L.,Sam, Brannon,Krische, Michael J.
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p. 12437 - 12443
(2011/12/04)
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- Divergent regioselectivity in the synthesis of trisubstituted allylic alcohols by nickel- and ruthenium-catalyzed alkyne hydrohydroxymethylation with formaldehyde
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Stoichiometric metals banned: Nonsymmetrically disubstituted alkynes were converted into primary trisubstituted allylic alcohols upon exposure to paraformaldehyde in the presence of nickel or ruthenium catalysts, which exhibit complementary regioselectivity and complete stereoselectivity in the absence of exogenous reducing agents (see scheme). Copyright
- Bausch, Cory C.,Patman, Ryan L.,Breit, Bernhard,Krische, Michael J.
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supporting information; experimental part
p. 5687 - 5690
(2011/08/06)
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- Amino-zinc-ene-enolate cyclization: A short access to cis-3-substituted prolino-homotryptophane derivatives
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(Chemical Equation Presented) Proline chimeras are useful tools for medicinal chemistry and/or biological applications. The asymmetric synthesis of cis-3-substituted prolines can be easily achieved via amino-zinc-ene-enolate cyclization followed by transm
- Mothes, Celine,Lavielle, Solange,Karoyan, Philippe
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p. 6706 - 6710
(2008/12/22)
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- Rapid route to 3,4-substituted indoles via a directed ortho metalation-retro-Mannich sequence.
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[reaction: see text] In the presence of NXS (X = Br, I, Cl), gramine derivatives 1, derived by combined directed ortho metalation (DoM)-cross-coupling sequences, rapidly undergo retro-Mannich fragmentation (2) to afford 3-halo indoles 3 in 37-88% yields.
- Chauder, Brian,Larkin, Andrew,Snieckus, Victor
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p. 815 - 817
(2007/10/03)
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- Hydroboration and Suzuki-Miyaura coupling reactions with the electronically modulated variant of an ynamine: The synthesis of (E)-β-arylenamides
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The first hydroboration of an 1-alkynylamide - the electronically modulated variant of an ynamine - is described. This hydroboration in combination with a Suzuki-Miyaura cross-coupling reaction with aryl bromides or aryl iodides allows a flexible synthesis of (E)-β-arylenamides and 3-(2'-amidovinyl)indoles with high degree of molecular diversity. (C) 2000 Elsevier Science Ltd.
- Witulski, Bernhard,Buschmann, Nicole,Bergstr??er, Uwe
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p. 8473 - 8480
(2007/10/03)
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- A mild and effective iodination method using iodine in the presence of bis-(trifluoroacetoxy)iodobenzene
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Herein is described a mild and effective iodination method using bis(trifluoroacetoxy)iodobenzene iodine as reagent to be applied to electron deficient heterocyclic systems (protected indoles coumarin...). Moreover, sensitive protecting groups such as acetyl and tert butyldimethylsilyl were found to be stable under the new iodination reaction conditions.
- Benhida, Rachid,Blanchard, Pierre,Fourrey, Jean-Louis
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p. 6849 - 6852
(2007/10/03)
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