- A minimalistic approach to develop new anti-apicomplexa polyamines analogs
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The development of new chemical entities against the major diseases caused by parasites is highly desired. A library of thirty diamines analogs following a minimalist approach and supported by chemoinformatics tools have been prepared and evaluated agains
- Panozzo-Zénere, Esteban A.,Porta, Exequiel O.J.,Arrizabalaga, Gustavo,Fargnoli, Lucía,Khan, Shabana I.,Tekwani, Babu L.,Labadie, Guillermo R.
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p. 866 - 880
(2017/12/13)
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- Novel bis-arylalkylamines as myeloperoxidase inhibitors: Design, synthesis, and structure-activity relationship study
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Human myeloperoxidase (MPO) plays an important role in innate immunity but also aggravates tissue damage by oxidation of biomolecules at sites of inflammation. As a result from a recent high-throughput virtual screening approach for MPO inhibitors, bis-2,2′-[(dihydro-1,3(2H,4H) pyrimidinediyl)bis(methylene)]phenol was detected as a promising lead compound for inhibition of the MPO-typical two-electron oxidation of chloride to hypochlorous acid (IC50= 0.5 μM). In the present pharmacomodulation study, 37 derivatives of this lead compound were designed and synthesized driven by comprehensive docking studies and the impact on the chlorination activity of MPO. We describe the structural requirements for optimum (i) binding to the heme periphery and (ii) inhibition capacity. Finally, the best three inhibitors (bis-arylalkylamine derivatives) were probed for interaction with the MPO redox intermediates Compound I and Compound II. Determined apparent bimolecular rate constants together with determination of reduction potential and nucleophilicity of the selected compounds allowed us to propose a mechanism of inhibition. The best inhibitor was found to promote the accumulation of inactive form of MPO-Compound II and has IC50= 54 nM, demonstrating the successful approach of the drug design. Due to the similarity of ligand interactions between MPO and serotonine transporter, the selectivity of this inhibitor was also tested on the serotonin transporter providing a selectivity index of 14 (KiSERT/IC50MPO).
- Aldib, Iyas,Gelbcke, Michel,Soubhye, Jalal,Prévost, Martine,Furtmüller, Paul G.,Obinger, Christian,Elfving, Betina,Alard, Ibaa Chikh,Roos, Goedele,Delporte, Cédric,Berger, Gilles,Dufour, Damien,Zouaoui Boudjeltia, Karim,Nève, Jean,Dufrasne, Francois,Van Antwerpen, Pierre
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supporting information
p. 746 - 762
(2016/08/18)
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- Synthesis and investigation of new cyclic haloamidinium salts
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The presented work describes the synthesis of new six- and seven-membered haloamidinium salts and their reaction with different metals. The isolated metal complexes were tested in a catalytic reaction. Two different synthetic routes were applied to prepare five different salts. Chloroamidinium salts were very water-sensitive in comparison to their corresponding bromoamidinium salts. Hence, the preparation of the less sensitive bromoamidinium salts was higher prioritized. The formed salts were converted with metal sources to N-heterocyclic carbene (NHC) metal complexes through an oxidative insertion into the C-X bond. This type of formation is less examined for the synthesis of extended NHC metal complexes. Pd(PPh3)4 and cobalt powder were applied as metal sources, whereby two palladium complexes were isolated, characterized, and their crystal and molecular structures determined. The palladium complexes were investigated in the Suzuki-Miyaura reaction and showed promising catalytic activity.
- Rais, Eduard,Fl?rke, Ulrich,Wilhelm, René
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p. 667 - 676
(2016/07/06)
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- Thiol activated prodrugs of sulfur dioxide (SO2) as MRSA inhibitors
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Drug resistant infections are becoming common worldwide and new strategies for drug development are necessary. Here, we report the synthesis and evaluation of 2,4-dinitrophenylsulfonamides, which are donors of sulfur dioxide (SO2), a reactive sulfur species, as methicillin-resistant Staphylococcus aureus (MRSA) inhibitors. N-(3-Methoxyphenyl)-2,4-dinitro-N-(prop-2-yn-1-yl)benzenesulfonamide (5e) was found to have excellent in vitro MRSA inhibitory potency. This compound is cell permeable and treatment of MRSA cells with 5e depleted intracellular thiols and enhanced oxidative species both results consistent with a mechanism involving thiol activation to produce SO2.
- Pardeshi, Kundansingh A.,Malwal, Satish R.,Banerjee, Ankita,Lahiri, Surobhi,Rangarajan, Radha,Chakrapani, Harinath
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p. 2694 - 2697
(2015/06/08)
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- INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kirl.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.
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Page/Page column 48; 49
(2014/07/08)
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- Synthesis and evaluation of hexahydropyrimidines and diamines as novel hepatitis C virus inhibitors
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In order to identify novel anti-hepatitis C virus (HCV) agents we devised cell-based strategies and screened phenotypically small molecule chemical libraries with infectious HCV particles, and identified a hit compound (1) containing a hexahydropyrimidine (HHP) core. During our cell-based SAR study, we observed a conversion of HHP 1 into a linear diamine (6), which is the active component in inhibiting HCV and exhibited comparable antiviral activity to the cyclic HHP 1. In addition, we engaged into the biological characterization of HHP and demonstrated that HHP does not interfere with HCV RNA replication, but with entry and release of viral particles. Here we report the results of the preliminary SAR and mechanism of action studies with HHP.
- Hwang, Jong Yeon,Kim, Hee-Young,Jo, Suyeon,Park, Eunjung,Choi, Jihyun,Kong, Sunju,Park, Dong-Sik,Heo, Ja Myung,Lee, Jong Seok,Ko, Yoonae,Choi, Inhee,Cechetto, Jonathan,Kim, Jaeseung,Lee, Jinhwa,No, Zaesung,Windisch, Marc Peter
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p. 315 - 325
(2013/11/19)
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- The effect of the nitrogen non-bonding electron pair on the NMR and X-ray in 1,3-diazaheterocycles
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The effect of the nitrogen nonbonding electron pair on the 1JC,H values of 1,3-diazaheterocycles was analyzed and compared to 1,5-diazabiciclo[3.2.1]octanes, which have a restricted conformation. The 1JC,H values were measured by observing the 13C satellites in the 1H NMR spectra and then determining the 1H-coupled 13C NMR spectra. The 1JC,H values are 10 Hz larger when the α-hydrogen is synperiplanar rather than antiperiplanar to the nonbonding electron pair on the nitrogen, which serves as experimental evidence of the orbital n N→σC,Hap interactions. In addition, the homoanomeric effect from the interactions of the nitrogen lone pair with the antibonding orbital of the equatorial hydrogen, which was in the β position, was discussed (nN→σC(β),H eq).
- Garcías-Morales, Cesar,Martínez-Salas, Selene H.,Ariza-Castolo, Armando
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supporting information; experimental part
p. 3310 - 3315
(2012/08/08)
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- Synthesis and antikinetoplastid activity of a series of N,N×-substituted diamines
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A series of 25 N,N×-substituted diamines were prepared by controlled reductive amination of free aliphatic diamines with different substituted benzaldehydes. The library was screened in vitro for antiparasitic activity on the causative agents of human Afr
- Caminos, Andrea P.,Panozzo-Zenere, Esteban A.,Wilkinson, Shane R.,Tekwani, Babu L.,Labadie, Guillermo R.
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supporting information; experimental part
p. 1712 - 1715
(2012/04/10)
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- Reversible aminal formation: Controlling the evaporation of bioactive volatiles by dynamic combinatorial/covalent chemistry
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Dynamic mixtures generated by reversible aminal formation efficiently prolong the duration of evaporation of bioactive volatile aldehydes. Secondary diamines used for the generation of dynamic mixtures are obtained by treatment of primary diamines with carbonyl compounds and reduction of the diimines with NaBH4. The reversibilities of the reactions were demonstrated by NMR measurements in buffered aqueous solutions. Kinetic rate constants and equilibrium constants for the formation and hydrolysis of aminals were determined. The performance of dynamic mixtures as delivery systems for perfumery ingredients was tested after deposition onto cotton, and the long-lastingness of fragrance evaporation was investigated by dynamic headspace analysis against a reference sample. The simplicity of the concept together with its excellent performance makes this delivery system highly interesting for applied perfumery. Reversible aminal formation might also be successfully applicable to dynamic combinatorial/covalent chemistry for screening of pharmaceutically or catalytically active ligands and receptors. The evaporation of bioactive volatiles that are emitted from flowers to attract insects and that are used as fragrances in our everyday life is limited in time. Dynamic mixtures obtained by reversible aminal formation of suitably designed diamines with volatile aldehydes prolong the perception of these compounds in functional perfumery.
- Buchsnee Levrand, Barbara,Godin, Guillaume,Trachsel, Alain,De Saint Laumer, Jean-Yves,Lehn, Jean-Marie,Herrmann, Andreas
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supporting information; experimental part
p. 681 - 695
(2011/03/22)
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- Reversible formation of aminals: A new strategy to control the release of bioactive volatiles from dynamic mixtures
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Dynamic mixtures generated by reversible aminal formation of fragrance aldehydes with N,N′-dibenzyl alkyldiamines in aqueous systems were found to be suitable delivery systems for the controlled release of bioactive volatiles. The Royal Society of Chemistry 2010.
- Godin, Guillaume,Levrand, Barbara,Trachsel, Alain,Lehn, Jean-Marie,Herrmann, Andreas
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body text
p. 3125 - 3127
(2010/08/21)
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- CYTOCHROME P450 OXIDASE INHIBITORS AND USES THEREOF
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The present invention features compounds of formula I or pharmaceutically acceptable salts, solvates or prodrugs thereof, and methods of using the same to inhibit the metabolizing activities of CYP enzymes. The present invention also features methods of using these compounds, salts, solvates or prodrugs to improve the pharmacokinetics of drugs that are metabolized by CYP enzymes.
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Page/Page column 109
(2008/06/13)
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- CONTROLLED RELEASE OF ACTIVE ALDEHYDES AND KETONES FROM EQUILIBRATED DYNAMIC MIXTURES
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The present invention concerns a dynamic mixture obtained by combining, in the presence of water, at least one diamine derivative, comprising at least one benzylamine moiety, with at least one active aldehyde or ketone. The invention's mixture is capable of releasing in a controlled and prolonged manner said active compound, in particular perfuming ingredients, in the surrounding environment.
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Page/Page column 26
(2008/12/07)
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- MODULATORS OF PHARMACOKINETIC PROPERTIES OF THERAPEUTICS
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The present application provides for a compound of Formula I, or a pharmaceutically acceptable salt, solvate, and/or ester thereof, compositions containing such compounds, therapeutic methods that include the administration of such compounds, and therapeutic methods and include the administration of such compounds with at least one additional therapeutic agent.
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Page/Page column 294
(2008/06/13)
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- A concise entry into nonsymmetrical alkyl polyamines
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(Chemical Equation Presented) The synthesis of nonsymmetrical polyamines (PAs) has, up to now, been problematic due to lengthy synthetic procedures, lack of regioselectivity, and very poor atom economy. An innovative synthetic protocol for nonsymmetrical
- Pirali, Tracey,Callipari, Grazia,Ercolano, Emanuela,Genazzani, Armando A.,Giovenzana, Giovanni Battista,Tron, Gian Cesare
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supporting information; experimental part
p. 4199 - 4202
(2009/05/30)
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- Double dearomatization of bis(diphenviphosphinamides) through anionic cyclization. A facile route of accessing multifunctional systems with antitumor properties
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(Chemical Equation Presented) The sequential one-pot double dearomatization of bis(N-benzyl-P,P-diphenylphosphinamides) via anionic cyclization is described for the first time. Protonation and alkylation of the dearomatized dianions provide bis(tetrahydro
- Ruiz-Gomez, Gloria,Iglesias, Maria Jose,Serrano-Ruiz, Manuel,Garcia-Granda, Santiago,Francesch, Andres,Lopez-Ortiz, Fernando,Cuevas, Carmen
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p. 3790 - 3799
(2008/02/02)
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- BICYCLIC PIPERAZINE COMPOUND AND USE THEREOF
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The present invention provides a compound represented by the formula: wherein R1 is an acyl group, R2 is a hydrocarbon group which may be substituted or the like, R3 is a hydrocarbon group which may be substituted or the like, R4 is a hydrocarbon group which may be substituted or the like, n is from 0 to 4, and X is an oxygen atom, a sulfur atom or the like, or a salt thereof. The invention also provides a compound which has a TGR23 antagonist activity and thus is useful for prevention and treatment of cancer.
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Page/Page column 59
(2010/11/08)
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- Bis-heteronucleophilic michael addition to divinyl sulfone: A new efficient access to macrocycles
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The Michael addition of bis(nitrogen or sulfur) nucleophiles to divinyl sulfone provides the corresponding macrocyclic adducts in good yields. The structures of some new macrocyclic sulfones are established by X-ray crystallographic analysis and NMR spectroscopy. The subsequent cleavage of benzyl or tosyl groups yields the unprotected macrocyclic sulfones. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Teyssot, Marie-Laure,Fayolle, Martine,Philouze, Christian,Dupuy, Claude
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- Novel cationic amphiphiles
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A cationic amphiphile for facilitating transport of a biologically active molecule into a cell has the structure A-F-D, in which A is a lipid anchor, D is a head group, and F is a spacer group having the structure described herein. A method for facilitating transport of a biologically active molecule into a cell comprises preparing a lipid mixture comprising a cationic amphiphile having structure A-F-D, preparing a lipoplex by contacting the lipid mixture with a biologically active molecule; and contacting the lipoplex with a cell, thereby facilitating transport of the biologically active molecule into the cell.
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Page/Page column 42, 15-16
(2010/02/06)
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- Synthesis, antiinflammatory and analgesic activity of new hexahydropyrimidine derivatives
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A number of potentially active hexahydropyrimidine derivatives of pharmaceutical interest have been synthesized. Various diSchiff's bases prepared by reacting different aromatic aldehydes with 1,3-diaminopropane were suitably reduced to give their tetrahy
- Khan,Gupta
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p. 377 - 383
(2007/10/03)
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- Synthesis of platinum complexes from N-benzyl-1,3-propanediamine derivatives, potential antineoplastic agents
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This work describes the synthesis of seven new platinum complexes having N-benzyl 1,3-propanediamine derivatives as ligands. They were prepared by the reaction of K2[PtCl4] with the appropriate ligand in water. These complexes are an
- De Almeida, Mauro Vieira,Fontes, Ana Paula Soares,Berg, Richard Nilton,Cesar, Eloi Teixeira,Felicio, Emanoel De Castro Antunes,De Souza Filho, Jose Dias
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p. 405 - 411
(2007/10/03)
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- Chiral phosphinamides: New catalysts for the asymmetric reduction of ketones by borane
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We have identified a new class of catalysts for the asymmetric reduction of prochiral ketones by borane. Key to the architecture of effective catalysts is an N-P=O structural unit which may be part of a phosphinamide, phosphonamide or a related structure.
- Burns, Barry,King, N. Paul,Tye, Heather,Studley, John R.,Gamble, Mark,Wills, Martin
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p. 1027 - 1038
(2007/10/03)
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- Synthesis of a new type of N2S2 tetradentate ligand
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Synthesis of a new type of N2S2 tetradentate ligand 3 possessing the bis-(hydrazonothioamide) structure based on condensation of the dihydrazines 8 with an α-ketoester is described.
- Charrier, Jean-Damien,Reliquet, Alain,Meslin, Jean-Claude
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p. 8645 - 8646
(2007/10/03)
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- Studies on antiamoebic compounds: Part IV - Synthesis of hexahydopyrimidines and tetrahydroimidazoles
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Several compounds containing o-alkylaminomethylenephenolic group (Mannich group) incorporating heterocycles such as hexahydropyrimidines and tetrahydroimidazoles have been synthesiszed.Compound 18 has been found to be active against hepatic amoebiasis.Effect of substituents on the conformations of hexahydropyrimidines is discussed.
- Kalyanam, N,Parthasarathy, P C,Ananthan, L,Manjunatha, S G,Likhate, M A
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p. 243 - 247
(2007/10/02)
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- Carbanion-Accelerated Claisen Rearrangements. 8. Phosphonamide Anion-Stabilizing Groups
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The utility of various phosphonamide groups has been examined in the context of the carbanion-accelerated Claisen rearrangement (CACR).An extensive survey has identified the N,N'-dibenzyl-1,3,2-diazaphospholidine group 11 to be optimal in the ease of construction of the CACR precursors and the facility and stereoselectivity of the rearrangement.Using n-butyllithium as the base, the phosphonamides rearranged readily at -20 deg C with complete regioselectivity and in good yield (74-79percent).The phosphonates also showed a high level of diastereoselectivity (>95percent de) but the yield from the (Z)-2-butenyl precursor (anti product) was only 45percent.A chiral N,N'-dibenzyl-1,3,2-diazaphospholidine 12 derived from trans-1,2-cyclohexanediamine was examined.Although the CACR proceeded very cleanly (71-85percent) and with high internal selectivity (94percent de), the relative asymmetric induction was poor (16-20percent de).This was also the case for a chiral N,N'-dibenzyl-1,3,2-diazaphosphorinane 15 derived from (R,R)-1,3-diphenyl-1,3-propanediamine and N,N'-dibenzyl-1,3,2-diazaphosphepine 16 derived from 6,6'-dimethyl-2,2'-diaminobiphenyl.The characteristic features of the CACR were compared with the aryl sulfone and phosphonate versions.
- Denmark, Scott E.,Stadler, Heinz,Dorow, Roberta L.,Kim, Jung-Ho
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p. 5063 - 5079
(2007/10/02)
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- Syntheses of a Series of Linear Pentaamines with Three and Four Methylene Chain Intervals
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Ten kinds of linear pentaamines with various combinations of 3 or 4 methylene chain intervals were synthesized.The methods were tentatively classified into two, leading to symmetrical and unsymmetrical pentaamines, all of which were prepared by succesive alkylation of secondary amino derivatives of benzylamine with N-(3-bromopropyl or 4-bromobutyl)phthalimide in the presence of KF-Celite, coupled with the purification of the phthaloyl compounds by silica gel column chromatography.Protecting benzyl and phthaloyl groups were removed by usual methods.The carbon-13 nuclear magnetic resonance (13C-NMR) spectra ot the ten pentaamines were recorded in D2O as fully protonated forms, and a comparative analysis of their spectra allowed the complete assignment of all 13C chemical shifts.Keywords-polyamine; pentaamine; benzylamine; N-(3-bromopropyl)phthalimide; N-(4-bromobutyl)phthalimide; alkylation; potassium fluoride-Celite; 13C-NMR spectrum
- Niitsu, Masaru,Samejima, Keijiro
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p. 1032 - 1038
(2007/10/02)
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