- Stereoselective total synthesis of (S)- and (R)-nuciferine using benzyne chemistry
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Total syntheses of (S)- and (R)-nuciferine were accomplished through approach involving diastereoselective reaction between a chiral dihydroisoquinoline enamide and 2-(trimethylsilyl)phenyl trifluoromethanesulfonate promoted by CsF, affording a separable mixture of diastereoisomers, which provided (S)- and (R)-nuciferine via simple and efficient transformations.
- Casagrande, Gleison A.,Deflon, Victor M.,Martins, Gabriel R.,Oliveira-Silva, Diogo,Perecim, Givago P.,Pinto, Leandro M. C.,Raminelli, Cristiano
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- Synthesis, docking and in vitro evaluation of L-proline derived 1,3-diketones possessing anti-cancer and anti-inflammatory activities
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Unsymmetrical 1,3-diketones with potential anti-cancer as well as anti-inflammatory activities were synthesized via direct coupling reaction between ketones and N-acyl benzotriazoles, based on soft enolisation under mild conditions and characterized by 1H,13C NMR, IR and HRMS. Molecular docking of the synthesized compounds (5a-5j) with the enzymes PTK6 (breast cancer cell), COX-1 and COX-2 (inflammation and pain) revealed 5j to be the potent compound. It was found to inhibit several important mitogen activated protein kinases, preferentially p38β with a binding energy of ?11.2 kcal/mol. During in vitro studies for MTT cytotoxicity assay using breast cancer cell line (MDA-MB-231) and HRBC assay for anti-inflammatory studies, the compound 5j exhibited anti-cancer activity with IC50 = 3.4 μM and 94.7% stabilization respectively. Thus the synthesized compounds (5a-5j) with more drug likeliness and high GI values as proved by the Swiss ADME online portal, can be effective in inhibiting breast cancer cells and the associated inflammation.
- Porchezhiyan,Kalaivani,Shobana,Noorjahan
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- Synthesis, characterization, in silico and in vitro evaluations of symmetrical 1,3-Diketones
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1,3-Dicarbonyl compounds have gained significant importance since they are abundantly available in the natural products and possess myriad biological activities. The new symmetrical 1,3-diketones bearing L-proline, 2-methyl-5-iodobenzoic acid, piperidine-3-carboxylic acid and naphthalene-1-acetic acid moieties were synthesized by coupling reaction of appropriate ketone with N-acyl triazole in the presence of MgBr2·Et2O and DIPEA. The chemical structure of the compounds were confirmed from the spectral data such as 1H, 13C NMR, FT-IR and HRMS. Molecular docking studies were carried out for all the compounds with tumor associated protein tyrosine kinase-6 (PTK6) and inflammatory protein cyclooxygenase-2 (COX2). The in vitro evaluation was carried out using breast cancer cell lines (MTT assay) and HRBC stabilization assays. During in silico studies, the ki values obtained against PTK6 and COX2 for (5a-d) compounds were in the range (-7.5 to -10.6) and (-7.6 to -9.8) kcal/mol, respectively. The compound 5d was selected for MTT assay, since it exhibited the highest binding affinity (-10.6 kcal/mol) against PTK6 and gave IC50 - 2.4 μg/mL against breast cancer cell lines. The HRBC stabilization of all the compounds (5a-5d) were in the range (59.28-93.4) %, with highest stabilization value by 5d, which also displayed higher binding affinity with -7.6 kcal/mol towards COX2. Thus, the synthesized symmetrical 1,3-diketones with suitable functionality can be both anticancer and anti-inflammatory agents.
- Porchezhiyan,Kalaivani,Shobana,Noorjahan
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p. 853 - 864
(2020/03/24)
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- Access to Optically Pure Benzosultams by Superelectrophilic Activation
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Through superacid activation, N-(arenesulfonyl)-aminoalcohols derived from readily available ephedrines or amino acids undergo an intramolecular Friedel-Crafts reaction to afford enantiopure benzosultams bearing two adjacent stereocenters in high yields with fully controlled diastereoselectivity. Low-temperature NMR spectroscopy demonstrated the crucial role played by the conformationally restricted chiral dicationic intermediates.
- Michelet, Bastien,Castelli, Ugo,Appert, Emeline,Boucher, Maude,Vitse, Kassandra,Marrot, Jér?me,Guillard, Jér?me,Martin-Mingot, Agnès,Thibaudeau, Sébastien
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p. 4944 - 4948
(2020/07/14)
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- New carboxamides bearing benzenesulphonamides: Synthesis, molecular docking and pharmacological properties
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Ten new derivatives of benzenesulphonamide bearing carboxamide functionality were synthesized and investigated for their in vitro antimicrobial, antioxidant and in vivo anti-inflammatory activities. Compound 9d inhibited carrageenan induced rat-paw oedema
- Eze, Florence Uchenna,Okoro, Uchechukwu Chris,Ugwu, David Izuchukwu,Okafor, Sunday N.
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- TRICYCLIC COMPOUND FOR BROMODOMAIN-CONTAINING PROTEIN INHIBITOR AND PREPARATION, PHARMACEUTICAL COMPOSITION, AND APPLICATION THEREOF
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The present applicationpresent application relates to a compound represented by Formula (III) or a pharmaceutically acceptable salt, solvent compound, active metabolite, crystal polymorph, ester, isomer, or prodrug thereof. The application further provides a pharmaceutical composition comprising the compound represented by Formula (III) and a use thereof for preparing a bromodomain inhibitor for preventing or treating various diseases, such as inflammation and cancer, related to the bromodomain.
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Paragraph 0208; 0209
(2019/01/04)
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- Synthesis, characterization and in vitro antitrypanosomal activities of new carboxamides bearing quinoline moiety
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The reported toxicities of current antitrypanosomal drugs and the emergence of drug resistant trypanosomes underscore the need for the development of new antitrypanosomal agents. We report herein the synthesis and antitrypanosomal activity of 24 new amide derivatives of 3-aminoquinoline, bearing substituted benzenesulphonamide. Nine of the new derivatives showed comparable antitrypanosomal activities at IC50 range of 1–6 nM (melarsoprol 5 nM). Compound 11n and 11v are more promising antitrypanosomal agents with IC50 1.0 nM than the rest of the reported derivatives. The novel compounds showed satisfactory predicted physico-chemical properties including oral bioavailability, permeability and transport properties.
- Ugwu, David Izuchukwu,Okoro, Uchechukwu Chris,Mishra, Narendra Kumar
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- Synthesis of proline derived benzenesulfonamides: A potent anti-Trypanosoma brucei gambiense agent
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Thousands of death in Africa and other developing nations are still attributed to trypanosomiasis. Excessive sleep has been associated with increased inflammation. We report herein, the synthesis, antitrypanosomal and anti-inflammatory activities of eight
- Ugwu, David I.,Okoro, Uchechukwu C.,Mishra, Narendra K.
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supporting information
p. 110 - 116
(2018/05/24)
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- Novel anti-inflammatory and analgesic agents: synthesis, molecular docking and in vivo studies
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Twelve new derivatives of benzothiazole bearing benzenesulphonamide and carboxamide were synthesised and investigated for their in vivo anti-inflammatory, analgesic and ulcerogenic activities. Molecular docking showed an excellent binding interaction of t
- Ugwu, David Izuchukwu,Okoro, Uchechukwu Christopher,Ukoha, Pius Onyeoziri,Okafor, Sunday N.,Gupta, Astha
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p. 405 - 415
(2018/03/21)
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- Synthesis, characterization, molecular docking and in?vitro antimalarial properties of new carboxamides bearing sulphonamide
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Sulphonamides and carboxamides have shown large number of pharmacological properties against different types of diseases among which is malaria. Twenty four new carboxamide derivatives bearing benzenesulphonamoyl alkanamides were synthesized and investigated for their in silico and in?vitro antimalarial and antioxidant properties. The substituted benzenesulphonyl chlorides (1a-c) were treated with various amino acids (2a-h) to obtain the benzenesulphonamoyl alkanamides (3a-x) which were subsequently treated with benzoyl chloride to obtain the N-benzoylated derivatives (5a-f, i-n and q-v). Further reactions of the N-benzoylated derivatives or proline derivatives with 4-aminoacetophenone (6) using boric acid as a catalyst gave the sulphonamide carboxamide derivatives (7a-x) in excellent yields. The in?vitro antimalarial studies showed that all synthesized compounds had antimalarial property. Compound 7k, 7c, 7l, 7s, and 7j had mean MIC value of 0.02, 0.03, 0.05, 0.06 and 0.08?μM respectively comparable with chloroquine 0.06?μM. Compound 7c was the most potent antioxidant agent with IC50 value of 0.045?mM comparable with 0.34?mM for ascorbic acid. In addition to the successful synthesis of the target molecules using boric acid catalysis, the compounds were found to have antimalarial and antioxidant activities comparable with known antimalarial and antioxidant drugs. The class of compounds reported herein have the potential of reducing oxidative stress arising from malaria parasite and chemotherapeutic agent used in the treatment of malaria.
- Ugwu,Okoro,Ukoha,Okafor,Ibezim,Kumar
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p. 349 - 369
(2017/05/04)
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- Exceptionally Stable and Efficient Solid Supported Hoveyda-Type Catalyst
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The ammonium tagged Hoveyda-type catalyst bearing sterically enlarged N-heterocyclic carbene ligand was synthesized and supported on SBA-15. The obtained heterogeneous olefin metathesis catalyst forms unprecedentedly stable Ru-methylidenes and provides products of ring-closing and cross metathesis with turnover numbers (TONs) up to 35 000 and turnover frequencies (TOFs) up to 1590 min-1. The catalyst proved to be truly recyclable and effective in a continuous flow mode.
- Skowerski, Krzysztof,Pastva, Jakub,Czarnocki, Stefan J.,Janoscova, Jana
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supporting information
p. 872 - 877
(2015/07/27)
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- High-Performance Isocyanide Scavengers for Use in Low-Waste Purification of Olefin Metathesis Products
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Three isocyanides containing a tertiary nitrogen atom were investigated for use as small-molecule ruthenium scavenging agents in the workup of olefin metathesis reactions. The proposed compounds are odorless, easy to obtain, and highly effective in removi
- Szczepaniak, Grzegorz,Urbaniak, Katarzyna,Wierzbicka, Celina,Kosiński, Krzysztof,Skowerski, Krzysztof,Grela, Karol
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p. 4139 - 4148
(2015/12/30)
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- The effect of hydrogen bond on Br?nsted acid-catalyzed intramolecular hydroamination of unfunctionalized olefins
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The catalytic activity of benzoic acid could be increased by introducing a hydrogen bond donor group at the ortho-position. Preliminary DFT calculation indicated that the activation of CC double bond was realized by the action of both the carboxyl group and the hydrogen bond donor. The amino group was brought to the activated CC bond by the interaction between the carboxyl oxygen and amino proton. This interaction also increased the nucleophilicity of the amino group. Thus, in the presence of 20 mol % of 2-(trifluoromethanesulfonamido)benzoic acid, intramolecular hydroamination of unfunctionalized olefins gave the corresponding products in up to 95% isolated yields.
- Li, Ting-Ting,Liu, Gong-Qing,Wang, Yu-Mei,Cui, Bin,Sun, Hui,Li, Yue-Ming
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supporting information
p. 7003 - 7009
(2015/08/19)
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- Enantiomeric resolution of [(2,2-diphenyl-1,3-dioxolan-4-yl)methyl](2-phenoxyethyl)amine, a potent α1 and 5-HT1A receptor ligand: An in vitro and computational study
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In this paper, the enantiomers of (±)-1, previously studied as α1 and 5-HT1A ligands, were prepared both by resolution of the racemate and asymmetric synthesis. The enantiomeric purity and absolute configuration were determined by me
- Franchini, Silvia,Baraldi, Annamaria,Sorbi, Claudia,Pellati, Federica,Cichero, Elena,Battisti, Umberto M.,Angeli, Piero,Cilia, Antonio,Brasili, Livio
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p. 677 - 690
(2015/04/27)
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- Synthesis, enantiomeric separation and docking studies of spiropiperidine analogues as ligands of the nociceptin/orphanin FQ receptor
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A series of triazospirodecanone derivatives were synthesized as potential NOP ligands. 8-(Chroman-4-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one (4) and its 5-fluoro analogue (18) proved to be active as agonists with EC50 values in the submicromolar range. Single enantiomers of compound 4 were separated and tested as NOP agonists; the eutomer R-(+)-4 showed a pEC 50 of 7.34. Finally docking studies were performed on the NOP receptor to identify the most significant stereospecific interactions.
- Battisti, Umberto M.,Corrado, Sandra,Sorbi, Claudia,Cornia, Andrea,Tait, Annalisa,Malfacini, Davide,Cerlesi, Maria Camilla,Calò, Girolamo,Brasili, Livio
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p. 973 - 983
(2014/07/08)
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- Does an axial propeller shape on a dirhodium(III,III) core affect equatorial ligand chirality?
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The dirhodium(III,III) tetrakis(1-aza-2-cyclooctanoate) framework, which exists solely in a propeller conformation, has been prepared with nonidentical apical aryl ligands. The presence of these nonidentical ligands on the propeller conformation was expec
- Doyle, Michael P.,Shabashov, Dmitry,Zhou, Lei,Zavalij, Peter Y.,Welch, Christopher,Pirzada, Zainab
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experimental part
p. 3619 - 3627
(2011/09/20)
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- Synthesis of constrained peptidomimetics containing 2-oxo-1,3-oxazolidine- 4-carboxylic acids
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Sulfonyl peptides containing a serine or threonine residue undergo cyclization with bis(succinimidyl) carbonate (DSC) and diisopropylethylamine (DIPEA) to give peptides with a 2-oxo-1,3-oxazolidine-4-carboxylate (Oxd) group, either in solution or in the solid phase. The position of the serine or threonine residue in the sequence is relatively unimportant. Under the same conditions, the corresponding Fmoc- or Boc-peptides gave dehydration products, in agreement to previous studies. The protocol constitutes a valuable approach to the preparation of oxazolidinone-containing peptides, which are a recently emerging class of constrained peptidomimetics. As a representative example, an Oxd analogue of the endogenous opioid peptide endomorphin-1, characterized by an all-trans conformation, was readily prepared.
- Gentilucci, Luca,Tolomelli, Alessandra,De Marco, Rossella,Tomasini, Claudia,Feddersen, Soeren
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body text
p. 4925 - 4930
(2011/10/31)
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- Oxidative desulfurization-fluorination of thioethers. Application for the synthesis of fluorinated nitrogen containing building blocks
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An oxidative desulfurization-fluorination protocol has been used to synthesize (2S)-2-(difluoromethyl)-N-tosylpyrrolidine (6a) and (2S)-2-(trifluoromethyl)-N-tosylpyrrolidine (7a) from the (2S)-prolinol-derived (2S)-2-(4-chlorophenylthiomethyl)-N-tosylpyr
- Hugenberg, Verena,Froehlich, Roland,Haufe, Guenter
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scheme or table
p. 5682 - 5691
(2011/02/18)
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- Allylation of aldehydes and imines: Promoted by reuseable polymer-supported sulfonamide of N-glycine
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A allylation of aldehydes and imines (generated in situ from aldehydes and amines) with allyltributyltin promoted by recoverable and reusable the polymer-supported sulfonamide of N-glycine has been developed. Good to high yields were obtained in various cases. Most of the SnBu3 residue can be recovered as Bu3SnCl. Highly stereoselective synthesis of N-Boc-(2S,3S)-3-hydroxy-2-phenylpiperidine 7 was achieved by using the P4a-mediated allylation of Boc-L-phenylglycinal as a key step.
- Li, Gui-Long,Zhao, Gang
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p. 633 - 636
(2007/10/03)
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- Simple derivatives of natural amino acids as chiral ligands in the catalytic asymmetric addition of phenylacetylene to aldehydes
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Optically active propargylic alcohols are important chiral building blocks in asymmetric synthesis, and asymmetric addition of terminal alkynes to aldehydes is one of the most important and interesting procedures by which to prepare these chiral building
- Han, Zhi-Jian,Wang, Rui,Zhou, Yi-Feng,Liu, Lei
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p. 934 - 938
(2007/10/03)
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- The photochemistry of N-p-toluenesulfonyl peptides: The peptide bond as an electron donor
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The scope of photobiological processes that involve absorbers within a protein matrix may be limited by the vulnerability of the peptide group to attack by highly reactive redox centers consequent upon electronic excitation. We have explored the nature of this vulnerability by undertaking comprehensive product analyses of aqueous photolysates of 12 N-p-toluene-sulfonyl peptides with systematically selected structures. The results indicate that degradation includes a major pathway that is initiated by intramolecular electron transfer in which the peptide bond serves as electron donor, and the data support the likelihood' of a relay process in dipeptide derivatives.
- Hill, Roger R.,Moore, Sharon A.,Roberts, David R.
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p. 1439 - 1446
(2008/02/01)
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- Biphenyl derivatives and drug composition
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A biphenyl derivative represented by the following general formula (1) and a pharmaceutically acceptable salt thereof: [In the formula (1), A represents a single bond, —CH2—, —CO—, —CS— or —SO2—; B represents a single bond or —CH2—; R1represents a hydrogen atom, —OH, —NR11R12(wherein R11and R12each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms), —OCOCH3, or a halogen atom; R2represents a hydrogen atom or R1and R2form a group ═O together; R3represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; provided that in the formula, the absolute configuration of the position a may be either R or S]. The compound of the present invention has considerably high safety and efficacy and is useful as, in particular, a vasopressin receptor antagonist.
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- Preparation of both enantiomers of 1-allyl-1,2,3,4-tetrahydro-β-carboline using allyltin reagents and a chiral auxiliary derived from L-proline
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β-Carboline, which had an acyl group derived from L-proline at the 9-position, reacted with allyltributyltin and 2,2,2-trichloroethyl chloroformate to afford an 1-allyl-1,2-dihydro-β-carboline derivative in a diastereoselective manner. The chiral acyl group at N-9 was readily eliminated by aqueous alkali to give a corresponding carboxylic acid. The formed 1-allyl-1,2-dihydro-β-carboline was transformed via two reduction steps to 1-allyl-1,2,3,4-tetrahydro-β-carboline in high ee. When the allylation was carried out using tetraallyltin instead of allyltributyltin, the stereoselectivity was reversed, and the antipode of the allyl adduct was obtained in high yield and ee in the presence of tin(IV) tetraiodide. Thus, it was found that both enantiomers of 1-allyl-β-carboline were obtained in good enantioselectivities by the use of the same chiral auxiliary.
- Itoh, Takashi,Matsuya, Y?ji,Enomoto, Yasuko,Ohsawa, Akio
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p. 7277 - 7289
(2007/10/03)
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- An efficient synthesis of functionalized helicenes
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[5]- and [6]helicenebisquinones can be prepared easily and in quantity by combining enol ethers of 1,4 diacetylbenzene or 2,7-diacetylnaphthalene with p-benzoquinone. Similar diethenyl aromatics that either have no ether functions or have them attached to the double bonds, but to the aromatic rings, give the corresponding helicenes in only low yields and low purities. [6]Helicenebisquinone 11c is resolved into its enantiomers. An X-ray diffraction analysis of the adduct of one of these enantiomers and L-prolinol shows the absolute stereochemistry of 11c and the regiochemistry with which the amine adds to the quinone.
- Katz, Thomas J.,Liu, Longbin,Willmore, Nikolaos D.,Fox, Joseph M.,Rheingold, Arnold L.,Shi, Shuhao,Nuckolls, Colin,Rickman, Barry H.
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p. 10054 - 10063
(2007/10/03)
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