- Boron-Promoted Ether Interchange Reaction: Synthesis of Alkyl Nitroaromatic Ethers from Methoxynitroarenes
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The first protocol for boron-promoted ether interchange reaction of methoxynitroarenes was described. A series of methoxynitroarenes and alcohols, including primary, secondary, as well as tertiary alcohols were reacted smoothly in moderate to good yields under the optimized reaction conditions. This protocol constitutes an operationally simple and scalable strategy for the synthesis of alkyl nitroaromatic ethers. Moreover, the new reactivity of boron reagents was discovered.
- Liu, Zhenwei,Luan, Nannan,Lu, Hongtao,Liang, Apeng,Li, Jingya,Zou, Dapeng,Wu, Yangjie,Wu, Yusheng
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p. 702 - 707
(2020/02/11)
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- Discovery of new ATP-competitive inhibitors of human DNA topoisomerase IIα through screening of bacterial topoisomerase inhibitors
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Human DNA topoisomerase II is one of the major targets in anticancer therapy, however ATP-competitive inhibitors of this target have not yet reached their full potential. ATPase domain of human DNA topoisomerase II belongs to the GHKL ATPase superfamily and shares a very high 3D structural similarity with other superfamily members, including bacterial topoisomerases. In this work we report the discovery of a new chemotype of ATP-competitive inhibitors of human DNA topoisomerase IIα that were discovered through screening of in-house library of ATP-competitive inhibitors of bacterial DNA gyrase and topoisomerase IV. Systematic screening of this library provided us with 20 hit compounds. 1,2,4-Substituted N-phenylpyrrolamides were selected for a further exploration which resulted in 13 new analogues, including 52 with potent activity in relaxation assay (IC50 = 3.2 μM) and ATPase assay (IC50 = 0.43 μM). Cytotoxic activity of all hits was determined in MCF-7 cancer cell line and the most potent compounds, 16 and 20, showed an IC50 value of 8.7 and 8.2 μM, respectively.
- Baran?oková, Michaela,Durcik, Martina,Gramec Skledar, Darja,Ila?, Janez,Kikelj, Danijel,Peterlin Ma?i?, Lucija,Skok, ?iga,Toma?i?, Tihomir,Zega, Anamarija,Zidar, Nace
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- Modulators of the nuclear hormone receptor ROR
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The invention provides small molecule modulators of retinoic acid receptor-related orphan receptors such as RORα, RORβ, or RORγ, of formula with the variable atoms as defined herein and R1 comprising a hydroxyl- or alkoxyl-substituted fluoroalkyl group. Compounds of the invention can be effective modulators at concentrations ineffective to act on LXR receptors, or on other nuclear receptors, or other biological targets. Methods of modulation the RORs and methods of treating metabolic disorders, immune disorders, cancer, and CNS disorders wherein modulation of an ROR is medically indicated are also provided.
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Page/Page column 160
(2017/03/28)
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- QUINAZOLINONE-BASED ONCOGENIC-RAS-SELECTIVE LETHAL COMPOUNDS AND THEIR USE
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The present invention provides, inter alia, compounds having the structure (1) compositions containing such compounds are also provided. Methods for using such compounds or compositions for treating or ameliorating the effects of a cancer having a cell that harbors an oncogenic RAS mutation, for modulating a lipoxygenase in a ferroptosis cell death pathway, and for depleting reduced glutathione (GSH) in a cell harboring an oncogenic RAS mutation are further provided.
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Paragraph 0157; 0160
(2014/02/15)
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- Synthesis of aryl ethers from aromatic carboxylic acids
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A silver/copper bimetallic catalyst system promotes the decarboxylative Chan-Evans-Lam alkoxylation of ortho-substituted aromatic carboxylate salts with tetraalkyl orthosilicates or triaryl borates. Non-ortho-substituted carboxylates are alkoxylated via an ortho-C-H-alkoxylation with concomitant cleavage of the carboxylate directing group via protodecarboxylation. This way, meta-substituted carboxylates are converted into para-substituted alkoxyarenes and vice versa. The combined processes provide a convenient synthetic entry to the important class of aromatic ethers from widely available carboxylic acids.
- Bhadra, Sukalyan,Dzik, Wojciech I.,Goossen, Lukas J.
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supporting information
p. 2387 - 2390
(2013/09/23)
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- Decarboxylative etherification of aromatic carboxylic acids
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Decarboxylative Chan-Evans-Lam-type couplings are presented as a new strategy for the regiospecific construction of diaryl and alkyl aryl ethers starting from easily available aromatic carboxylic acids. They allow converting various aromatic carboxylate salts into the corresponding aryl ethers by reaction with alkyl orthosilicates or aryl borates, under aerobic conditions in the presence of silver carbonate as the decarboxylation catalyst and copper acetate as the cross-coupling catalyst.
- Bhadra, Sukalyan,Dzik, Wojciech I.,Goossen, Lukas J.
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p. 9938 - 9941
(2012/08/08)
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- Exploration of the structure-activity relationship of the diaryl anilide class of ligands for translocator protein - Potential novel positron emitting tomography imaging agents
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A series of novel ligands based on the diaryl anilide (DAA) class of translocator protein (TSPO) ligands was synthesised and evaluated as potential positron emitting tomography (PET) ligands for imaging TPSO in vivo. Fluorine-18 labelling of the molecules was achieved using direct radiolabelling or synthon based labelling approaches. Several of the ligands prepared have promising profiles as potential TSPO PET imaging ligands and will be evaluated further as potential clinical imaging agents.
- Wadsworth, Harry,Jones, Paul A.,Chau, Wai-Fung,Durrant, Clare,Morisson-Iveson, Veronique,Passmore, Joanna,O'Shea, Dennis,Wynn, Duncan,Khan, Imtiaz,Black, Andrew,Avory, Michelle,Trigg, William
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p. 5795 - 5800,6
(2020/07/30)
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- A molecular balance for measuring aliphatic CH-π interactions
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A series of conformationally flexible bicyclic N-arylimides were employed as molecular balances to study the weak aliphatic CH-π interaction between alkyl and arene groups. The formation of intramolecular CH-π interactions in the folded conformers was characterized by X-ray crystallography. The strengths of the interactions were characterized in CDCl3 by the changes in the folded/unfolded ratios, as measured by 1H NMR. The CH-π interaction between a methyl group and an aromatic surface was ~1.0 kcal/mol and was easily disrupted or masked by conformational entropy and repulsive steric interactions.
- Carroll, William R.,Zhao, Chen,Smith, Mark D.,Pellechia, Perry J.,Shimizu, Ken D.
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supporting information; experimental part
p. 4320 - 4323
(2011/10/05)
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- NOVEL USE OF THIENOPYRIMIDINES
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The present invention relates to the use of thienopyrimidine compounds for the production of pharmaceutical compositions for the treatment of inflammatory diseases.
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Page/Page column 36
(2010/11/27)
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- Iodine-mediated cyclisation of thiobenzamides to produce benzothiazoles and benzoxazoles
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Synthesis of benzothiazoles by reaction of iodine with thiobenzamides, which do not possess an ortho alkoxy or ester group, is described. The unlikely synthesis of benzoxazoles from reaction of 2-alkoxythiobenzamides with iodine is also reported.
- Downer-Riley, Nadale K.,Jackson, Yvette A.
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p. 10276 - 10281
(2008/02/13)
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- Structure-activity relationships in the binding of chemically derivatized CD4 to gp120 from human immunodeficiency virus
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The first step in HIV infection is the binding of the envelope glycoprotein gp120 to the host cell receptor CD4. An interfacial "Phe43 cavity" in gp120, adjacent to residue Phe43 of gp120-bound CD4, has been suggested as a potential target for therapeutic intervention. We designed a CD4 mutant (D1D2F43C) for site-specific coupling of compounds for screening against the cavity. Altogether, 81 cysteine-reactive compounds were designed, synthesized, and tested. Eight derivatives exceeded the affinity of native D1D2 for gp120. Structure-activity relationships (SAR) for derivatized CD4 binding to gp120 revealed significant plasticity of the Phe43 cavity and a narrow entrance. The primary contacts for compound recognition inside the cavity were found to be van der Waals interactions, whereas hydrophilic interactions were detected in the entrance. This first SAR on ligand binding to an interior cavity of gp120 may provide a starting point for structure-based assembly of small molecules targeting gp120-CD4 interaction.
- Xie, Hui,Ng, Danny,Savinov, Sergey N.,Dey, Barna,Kwong, Peter D.,Wyatt, Richard,Smith III, Amos B.,Hendrickson, Wayne A.
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p. 4898 - 4908
(2008/03/11)
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- THIENOPYRIMIDINES FOR PHARMACEUTICAL COMPOSITIONS
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The present invention relates to novel pharmaceutical compositions of general formula (I) comprising thienopyrimidine compounds. Moreover, the present invention relates to the use of the thienopyrimidine compounds of the invention for the production of pharmaceutical compositions for the prophylaxis and/or treatment of diseases which can be influenced by the inhibition of the kinase activity of Mnk1 and/or Mnk2 (Mnk2a or Mnk2b) and/or variants thereof.
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Page/Page column 52
(2010/11/25)
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- Aryl piperidine amides
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The invention provides novel GlyT2 inhibiting compounds useful in modulating, treating, or preventing: anxiolytic disorders; a condition requiring treatment of injured mammalian nerve tissue; a condition amenable to treatment through administration of a neurotrophic factor; a neurological disorder; or obesity; an obesity-related disorder.
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Page/Page column 13
(2010/02/11)
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- Acetamides and benzamides that are useful in treating sexual dysfunction
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The present invention relates to the use of compounds of formula (I) for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction.
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- Inhibitors of the glycine transporter type-2 (GlyT-2): synthesis and biological activity of benzoylpiperidine derivatives.
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A series of benzoylpiperidine analogs related to 4a was prepared, and their ability to inhibit the uptake of [(14)C]-glycine in COS7 cells transfected with human glycine transporter type-2 (GlyT-2) was evaluated. Small structural changes to the benzoylpiperidine region of the molecule led to a significant decrease in GlyT-2 inhibitory activity. In contrast, the distal aryl ring was more tolerant to functional group modifications and could accommodate a variety of substitutes at the C-2 or C-3 positions. Comparable activities to 4a were obtained by replacing the anilino nitrogen with an ether linkage 27 or by exchanging the isopropoxy ether moiety with an isopropyl amino group 15. A distinct preference for a 2-carbon tether (n=1) was observed relative to the corresponding 3-carbon homolog (n=2).
- Wolin, Ronald L,Santillan Jr., Alejandro,Tang, Liu,Huang, Charles,Jiang, Xiaoxia,Lovenberg, Timothy W
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p. 4511 - 4532
(2007/10/03)
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- Acetamides and benzamides that are useful in treating sexual dysfunction
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The present invention relates to the use of compounds of formula (I) for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction.
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- Competition between Radical and Nonradical Reactions of Halonitrobenzenes in Alkaline Alcoholic Solutions
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The study of the reactivity of monohalonitrobenzenes in 2-propanol solutions of potassium 2-propoxide has led to the identification of three distinct reaction paths: (a) hydro dehalogenation to nitrobenzene, (b) alkoxy dehalogenation via the SNAr mechanism, and (c) nitro reduction to azoxy and anilino derivatives via nitroso intermediates.With the exception of 2- and 4-fluoronitrobenzene, radical processes c or a are faster than the SNAr reaction.The radical processes proceed via a common intermediate, the radical anion *-, which can undergo unimolecular fragmentation to nitroaryl radical and X- (path a, favored for X = 2-I, 2-Br), or reduction to the dianion 2-, the direct precursor of the nitroso intermediate XC6H4NO (path c).In the presence of oxyen, an effective oxidant of the radical-anion intermediate, the SNAr reaction prevails for the activated ortho and para substrates.Cation-anion interactions are also major consequence in determining the course of reaction.Ion pairing favors nitro reduction, whereas it slows both the SNAr and the hydro dehalogenation reactions.
- Arca, Vittorio,Paradisi, Cristina,Scorrano, Gianfranco
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p. 3617 - 3621
(2007/10/02)
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- The synthesis of anilines or azoxybenzenes from the reduction of nitrobenzenes in basic alcoholic media
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Reduction of substituted nitrobenzenes in alkaline alcoholic solutions affords, depending on the experimental conditions used, either anilines or azoxybenzenes in good yields.In the presence of a methylketone, such as acetophenone, the reaction of nitroarenes with aqueous KOH in 2-propanol provides the corresponding anilines in high yields (80-90 percent).On the other hand, when the reaction is carried out in the CH3OH/toluene/KOH system, in the absence of methylketones, the azoxyderivatives are isolated in 70-90 percent yield.
- Prato, Maurizio,Quintily, Ugo,Scapol, Lucia,Scorrano, Gianfranco
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