- Conjugation of aminoadamantanes by copper-catalyzed alkyne-azide 1,3-dipolar cycloaddition
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Four variants of conjugation of aminoadamantanes with 1,2,3-triazole- and ditriazolecontaining spacers by copper-catalyzed alkyne-azide 1,3-dipolar cycloaddition of azido- and propargyl-containing aminoadamantanes were suggested.
- Sokolov,Aksinenko, A. Yu.,Epishina,Goreva
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Read Online
- De novo Design of SARS-CoV-2 Main Protease Inhibitors
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The COVID-19 pandemic prompted many scientists to investigate remedies against SARS-CoV-2 and related viruses that are likely to appear in the future. As the main protease of the virus, M Pro, is highly conserved among coronaviruses, it has emerged as a prime target for developing inhibitors. Using a combination of virtual screening and molecular modeling, we identified small molecules that were easily accessible and could be quickly diversified. Biochemical assays confirmed a class of pyridones as low micromolar noncovalent inhibitors of the viral main protease.
- Fischer, Christian,Vep?ek, Nynke A.,Peitsinis, Zisis,Rühmann, Klaus-Peter,Yang, Chao,Spradlin, Jessica N.,Dovala, Dustin,Nomura, Daniel K.,Zhang, Yingkai,Trauner, Dirk
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supporting information
p. 458 - 463
(2021/10/16)
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- Novel selective ido1 inhibitors with isoxazolo[5,4-d]pyrimidin-4(5h)-one scaffold
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Indoleamine 2,3-dioxygenase 1 (IDO1) is a promising target in immunomodulation of several pathological conditions, especially cancers. Here we present the synthesis of a series of IDO1 inhibitors with the novel isoxazolo[5,4-d]pyrimidin-4(5H)-one scaffold. A focused library was prepared using a 6-or 7-step synthetic procedure to allow a systematic investigation of the structure-activity relationships of the described scaffold. Chemistry-driven modifications lead us to the discovery of our best-in-class inhibitors possessing p-trifluoromethyl (23), p-cyclohexyl (32), or p-methoxycarbonyl (20, 39) substituted aniline moieties with IC50 values in the low micromolar range. In addition to hIDO1, compounds were tested for their inhibition of indoleamine 2,3-dioxygenase 2 and tryptophan dioxygenase, and found to be selective for hIDO1. Our results thus demon-strate a successful study on IDO1-selective isoxazolo[5,4-d]pyrimidin-4(5H)-one inhibitors, defining promising chemical probes with a novel scaffold for further development of potent small-molecule immunomodulators.
- ?vajger, Urban,Bratkovi?, Toma?,Dol?ak, Ana,Gobec, Stanislav,Mlinari?, Larisa,Ogorevc, Eva,Sova, Matej
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- Application of acetyl amantadine piperazine (piperidine) compound as cerebral neuroprotective agent
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The present invention discloses an application of acetamantadine piperazine (piperidine) compound as cerebral neuroprotective agent. The structure of the acetamantadine piperazine (piperidine) compound is novel, and the application of the acetamantadine p
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Paragraph 0071-0074
(2019/12/08)
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- Discovery of a Small-Molecule Inhibitor of Interleukin 15: Pharmacophore-Based Virtual Screening and Hit Optimization
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Interleukin (IL)-15 is a pleiotropic cytokine, which is structurally close to IL-2 and shares with it the IL-2 β and γ receptor (R) subunits. By promoting the activation and proliferation of NK, NK-T, and CD8+ T cells, IL-15 plays important roles in innate and adaptative immunity. Moreover, the association of high levels of IL-15 expression with inflammatory and autoimmune diseases has led to the development of various antagonistic approaches targeting IL-15. This study is an original approach aimed at discovering small-molecule inhibitors impeding IL-15/IL-15R interaction. A pharmacophore and docking-based virtual screening of compound libraries led to the selection of 240 high-scoring compounds, 36 of which were found to bind IL-15, to inhibit the binding of IL-15 to the IL-2Rβ chain or the proliferation of IL-15-dependent cells or both. One of them was selected as a hit and optimized by a structure-activity relationship approach, leading to the first small-molecule IL-15 inhibitor with sub-micromolar activity.
- Quéméner, Agnès,Maillasson, Mike,Arzel, Laurence,Sicard, Benoit,Vomiandry, Romy,Mortier, Erwan,Dubreuil, Didier,Jacques, Yannick,Lebreton, Jacques,Mathé-Allainmat, Monique
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supporting information
p. 6249 - 6272
(2017/08/02)
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- Indium-Triflate-Catalyzed Ritter Reaction in Liquid Sulfur Dioxide
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The use of liquid sulfur dioxide as a reaction solvent facilitates the Ritter reaction between alcohols and nitriles. In(OTf)3 was found to be a viable catalyst for this transformation. The newly developed catalytic conditions for the Ritter reaction were successfully applied to the synthesis of various amides, which were formed in good to excellent yields. The catalytic activation of secondary alcohols for Ritter reactions in liquid sulfur dioxide was also found to be effective.
- Posevins, Daniels,Suta, Krista,Turks, Maris
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supporting information
p. 1414 - 1419
(2016/03/19)
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- Adamantanedicarboxylic deriv.
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PROBLEM TO BE SOLVED: To provide an adamantane derivative which can be used as a novel resist material, especially a photoresist material in which acids are controlled by incorporating a unit or a structure capable of controlling acids into a monomer or a polymer.SOLUTION: An adamantane derivative represented by the formula (1), where Rrepresents a hydrogen atom, a fluorine atom, a methyl group or a trifluoromethyl group, X represents a group selected from -O-, -NH-, -N(C(=O)R)-, Rto Reach represents a hydrogen atom, an alkyl group or an alkyl group substituted with a hydroxyl group or an ester group, Rand Rmay connect each other to form a ring, n represents an integer of 1 to 3, and asterisk represents a bond position, is provided.
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Paragraph 0057
(2018/03/31)
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- Homologation of isocyanates with lithium carbenoids: A straightforward access to α-halomethyl- and α,α-dihalomethylamides
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Treatment of widely available isocyanates with monohalolithium and dihalolithium carbenoids provides a valuable protocol for the one-pot preparation of α-halo- and α,α-dihaloacetamide derivatives. While monohalolithium carbenoids can be prepared by a smoo
- Pace, Vittorio,Castoldi, Laura,Mamuye, Ashenafi Damtew,Holzer, Wolfgang
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p. 2897 - 2909
(2015/01/16)
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- Addition of lithium carbenoids to isocyanates: A direct access to synthetically useful N-substituted 2-haloacetamides
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The addition of lithium carbenoids to isocyanates provides a versatile access to N-substituted 2-haloacetamides: the reaction tolerates the presence of variously functionalized substituents on the nitrogen atom, including sterically demanding ones and reactive halogens. No erosion of the enantiopurity was observed in the case of optically active isocyanates. One of the substrates prepared has been employed in Charette's type chemoselective addition of a Grignard reagent to access an α-chloroketone.
- Pace, Vittorio,Castoldi, Laura,Holzer, Wolfgang
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supporting information
p. 8383 - 8385
(2013/09/23)
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- Reusable and highly active supported copper(i)-NHC catalysts for Click chemistry
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Immobilised [Cu(NHC)] catalysts are reported for the preparation of 1,2,3-triazoles. In addition to showing outstanding catalytic activity, the catalyst systems are easy to prepare and can be recycled many times.
- Collinson, John-Michael,Wilton-Ely, James D. E. T.,Diez-Gonzalez, Silvia
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supporting information
p. 11358 - 11360
(2013/12/04)
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- KINASE INHIBITORS
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Methods of inhibiting kinases using kinase inhibitors having olefin moieties are disclosed.
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Paragraph 0455; 0456
(2013/03/26)
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- Discovery of N-(1-adamantyl)-2-(4-alkylpiperazin-1-yl)acetamide derivatives as T-type calcium channel (Cav3.2) inhibitors
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Chemical evolution of a HTS-based fragment hit resulted in the identification of N-(1-adamantyl)-2-[4-(2-tetrahydropyran-4-ylethyl)piperazin-1- yl]acetamide, a novel, selective T-type calcium channel (Cav3.2) inhibitor with in vivo antihypertensive effect in rats.
- Giordanetto, Fabrizio,Knerr, Laurent,Selmi, Nidhal,Llins, Antonio,Lindqvist, Anders,Wang, Qing-Dong,Sthlberg, Pernilla,Thorstensson, Fredrik,Ullah, Victoria,Nilsson, Kristina,O'Mahony, Gavin,Hoegberg, Got,Lindhardt, Emma,Strand, Annika,Duker, Goeran
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scheme or table
p. 5557 - 5561
(2011/10/12)
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- Synthesis and evaluation of SQ109 analogues as potential anti-tuberculosis candidates
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As part of an ongoing project to develop highly potent anti-tuberculosis therapeutics, six SQ109 derivatives were synthesized and screened in vitro for their anti-tuberculosis activity against the ATCC strain H37Rv and the extensively drug-resistant clinical strain XDR 173. Compound 16 with an extended alkene chain was the most active against both strains of Mycobacterium tuberculosis within a MIC range of 0.5-0.25 μM. Compound 12 and SQ109 were potent within a MIC range of 1-0.5 μM, whilst compound 18 displayed an activity within the MIC range of 0.5-2 μM against both Mycobacterium tuberculosis strains.
- Onajole, Oluseye K.,Govender, Patrick,Helden, Paul D. van,Kruger, Hendrik G.,Maguire, Glenn E.M.,Wiid, Ian,Govender, Thavendran
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scheme or table
p. 2075 - 2079
(2010/06/19)
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- Process for the preparation of adamantanamines
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The present invention concerns a process for the manufacture of an adamantanamine of formula wherein R, R' and X are as defined in the claims, which comprises (i) reacting a compound of formula with thiourea; (ii) subjecting the resulting compound of formula to an acid treatment and (iii) isolating the resulting adamantanamine or a hydrohalogenide thereof. According to the process of the invention, valuable pharmaceuticals are obtainable, such as Memantine hydrochloride (R,R' = methyl), an uncompetitive NMDA(N-methyl-D-aspartate) receptor antagonist used as a new treatment for Alzheimer's disease, or Amantadine hydrochloride (R,R' = hydrogen) used as an antiviral or in the treatment of Parkinson's disease.
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Page/Page column 7
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF ADAMANTANAMINES
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The invention relates to a process for preparing certain adamantanamines, of formula (IV) wherein R, R' are each methyl and X is halogen, to intermediates used in the process, and to processes for preparing such intermediates.
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Page/Page column 14
(2010/11/28)
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- NOVEL COMPOUNDS OF SUBSTITUTED AND UNSUBSTITUTED ADAMANTYL AMIDES
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The present invention relates to compounds with the formula (I) or a pharmaceutically acceptable salt thereof: The invention also relates to pharmaceutical compositions comprising the compounds of formula (I) and methods of treating a condition that is mediated by the modulation of 11-?-hsd-1, the method comprising administering to a mammal an effective amount of a compound of formula (I).
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Page/Page column 36
(2008/06/13)
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- Modular synthesis of heterocyclic carbene precursors
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A series of N-heterocyclic carbene precursors, containing an imidazoline or tetrahydropyrimidine framework, were prepared from ω-chloroalkanoyl chlorides. The sequential attachment of nitrogen nucleophiles and subsequent ring closure gave, depending on the reagents used, either the desired dihydroimidazolium and tetrahydropyrimidinium salts or their parent heterocycles. In this latter case, the second substituent was introduced in an alkylation step. The preparation of carbene precursors bearing chiral or bulky substituents was achieved with comparable efficiency.
- Paczal, Attila,Benyei, Attila C.,Kotschy, Andras
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p. 5969 - 5979
(2007/10/03)
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- Cinchona-alkaloid-based catalysts, and asymmetric alcoholysis of cyclic anhydrides using them
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One aspect of the present invention relates to cinchona-alkaloid-based catalysts. A second aspect of the invention relates to a method of preparing a derivatized cinchona alkaloid catalyst by reacting a cinchona-alkaloid with base and a compound that has a suitable leaving group. Another aspect of the present invention relates to a method of preparing a chiral, non-racemic compound from a prochiral cyclic anhydride or a meso cyclic anhydride, comprising the step of: reacting a prochiral cyclic anhydride or a meso cyclic anhydride with a nucleophile in the presence of a catalyst; wherein said prochiral cyclic anhydride or meso cyclic anhydride comprises an internal plane of symmetry or point of symmetry or both; thereby producing a chiral, non-racemic compound; wherein said catalyst is a derivatized cinchona-alkaloid. Yet another aspect of the present invention relates to a method of kinetic resolution, comprising the step of: reacting a racemic cyclic anhydride with an alcohol in the presence of a derivatized cinchona-alkaloid catalyst.
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Page/Page column 28
(2008/06/13)
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- COMPOUNDS OF THE FORMU;A R1-X-Y-Z-NR2R3 AS ABCA-1 ELEVATING AGENTS AGAINST CAD OR ATHEROSCLEROSIS
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The present invention provides compounds that elevate cellular expression of the ABCA-1 gene, promoting cholesterol efflux from cells and increasing HDL levels in the plasma of a mammal, in particular humans. The compounds are useful for treating coronary
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- A practical synthesis of tert-alkylamines via the ritter reaction with chloroacetonitrile
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Ritter reaction of tertiary alcohols with chloroacetonitrile and subsequent cleavage of chloroacetyl group in the resulting chloroacetamide with thiourea is an efficient procedure for synthesis of tert-alkylamines.
- Jirgensons,Kauss,Kalvinsh,Gold
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p. 1709 - 1712
(2007/10/03)
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- Adamantylation and adamantylalkylation of amides, nitriles, and ureas in trifluoroacetic acid
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A new preparative procedure was developed for N-adamantylation of carboxylic acids amides and ureas, and C5-adamantylation of barbituric acid in trifluoroacetic acid medium with tertiary adamantanols and 1-adamantylalkanols. The reaction of 2-adamantanols and secondary 1-adamantylalkanols with nitriles was for the first time used in the preparation of W-(2-adamantyl)-and N-(1-adamantylalkyl)amides.
- Shokova,Musulu, Tasula,Luzikov,Kovalev
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p. 844 - 856
(2007/10/03)
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- Adamantylation and adamantylalkylation of amides, nitriles and ureas in trifluoroacetic acid
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A new preparative method for N-adamantylation of carboxylic acid amides, ureas and for C5-adamantylation of barbituric acid in trifluoroacetic acid (TFA) is proposed. Tertiary 1-adamantanols and 1-(1-adamantyl)alkanols were used as adamantylating agents. The reaction of 1-(1-adamantyl)alkanols with nitriles in TFA solution was employed for the first time for the preparation of N-[1-(1-adamantyl)alkyl]amides.
- Shokova, Elvira,Mousoulou, Tasoulla,Luzikov, Yurij,Kovalev, Vladimir
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p. 1034 - 1040
(2007/10/03)
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- Thiolupinine and some derivatives of pharmacological interest
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The (quinolizidin-1α-yl)methanthiol (thiolupinine) was prepared and, utilizing the thiol group reactivity, several S-substituted derivatives were obtained among which was a group of 3-](lupinilthio)methyl]indoles. Eight of the prepared compounds were subjected to a broad pharmacological screening that evidentiated for many of them good level of the following activities in vivo and in vitro: antiarrhythmic, local anesthetic, negative chronotropic on isolated atria, calcium antagonism on ileum and atria, inhibition of spontaneous contraction of isolated trachea, inhibition of guinea pig ileum contractions induced by angiotensin I and II, bradykinin and cholecystokinin, inhibition of platelet aggregation induced by PAF and ADP. Single compounds were remarkable for additional antagonistic activities: 4 against P1-purine receptor, 8 against substance P, 12 against methacholine and 13 strongly inhibited arachidonate induced platelet aggregation. Very peculiar was the ability of compound 6 to protect mice from PAF induced mortality.
- Novelli,Sparatore
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p. 1021 - 1049
(2007/10/02)
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- DERIVATIVES OF ADAMANTANE. II. USE OF TRIFLUOROACETIC ACID IN THE RITTER REACTION
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For the case of 1-substituted adamantanes it was possible to realize the synthesis of amides by the Ritter reaction with high yields using trifluoroacetic acid as catalyst and solvent.This makes it possible to realize the process in a homogenous phase and to remove the excess of the nitrile and the excess of the acid itself from the reaction mass by hydrolysis of the intermediate immonium comples.On account of the mild conditions labile nitriles and aminonitriles, in particular, can be used in the reaction.
- Plakhotnik, V.M.,Kovtun, V.Yu.,Yashunskii, V.G.
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p. 867 - 871
(2007/10/02)
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