51077-01-1Relevant articles and documents
Stereoselective total synthesis of (S)- and (R)-nuciferine using benzyne chemistry
Casagrande, Gleison A.,Deflon, Victor M.,Martins, Gabriel R.,Oliveira-Silva, Diogo,Perecim, Givago P.,Pinto, Leandro M. C.,Raminelli, Cristiano
, (2020/08/13)
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.
Synthesis, docking and in vitro evaluation of L-proline derived 1,3-diketones possessing anti-cancer and anti-inflammatory activities
Porchezhiyan,Kalaivani,Shobana,Noorjahan
, (2020/01/31)
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.
Synthesis, characterization, in silico and in vitro evaluations of symmetrical 1,3-Diketones
Porchezhiyan,Kalaivani,Shobana,Noorjahan
, p. 853 - 864 (2020/03/24)
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.
Access to Optically Pure Benzosultams by Superelectrophilic Activation
Michelet, Bastien,Castelli, Ugo,Appert, Emeline,Boucher, Maude,Vitse, Kassandra,Marrot, Jér?me,Guillard, Jér?me,Martin-Mingot, Agnès,Thibaudeau, Sébastien
, p. 4944 - 4948 (2020/07/14)
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.
New carboxamides bearing benzenesulphonamides: Synthesis, molecular docking and pharmacological properties
Eze, Florence Uchenna,Okoro, Uchechukwu Chris,Ugwu, David Izuchukwu,Okafor, Sunday N.
, (2019/09/18)
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
TRICYCLIC COMPOUND FOR BROMODOMAIN-CONTAINING PROTEIN INHIBITOR AND PREPARATION, PHARMACEUTICAL COMPOSITION, AND APPLICATION THEREOF
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Paragraph 0208; 0209, (2019/01/04)
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.
Synthesis, characterization and in vitro antitrypanosomal activities of new carboxamides bearing quinoline moiety
Ugwu, David Izuchukwu,Okoro, Uchechukwu Chris,Mishra, Narendra Kumar
, (2018/01/17)
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.
Synthesis of proline derived benzenesulfonamides: A potent anti-Trypanosoma brucei gambiense agent
Ugwu, David I.,Okoro, Uchechukwu C.,Mishra, Narendra K.
supporting information, p. 110 - 116 (2018/05/24)
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
Novel anti-inflammatory and analgesic agents: synthesis, molecular docking and in vivo studies
Ugwu, David Izuchukwu,Okoro, Uchechukwu Christopher,Ukoha, Pius Onyeoziri,Okafor, Sunday N.,Gupta, Astha
, p. 405 - 415 (2018/03/21)
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
Synthesis, characterization, molecular docking and in?vitro antimalarial properties of new carboxamides bearing sulphonamide
Ugwu,Okoro,Ukoha,Okafor,Ibezim,Kumar
, p. 349 - 369 (2017/05/04)
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.
