7223-50-9Relevant academic research and scientific papers
Magnetic chitosan nanocomposite: As a novel catalyst for the synthesis of new derivatives of N-sulfonylamidine and N-sulfonylimidate
Valizadeh, Sepideh,Ghasemi, Zarrin,Shahrisa, Aziz,Notash, Behrouz,Pirouzmand, Mahtab,Kabiri, Roya
, (2019)
This study reports the synthesis and characterization of a highly active catalyst based on chelated copper iodide on magnetic chitosan-salicylaldehyde Schiff base. This catalyst was successfully used for the three-component reaction of N-propargylphthalimide, tosylazide, and NH or OH containing nucleophiles to access new classes of N-sulfonylamidine or N-sulfonylimidate derivatives. The products, which were constructed via an in situ generated sulfonyl keteneimine intermediate, were obtained in good to excellent yields. Short reaction times, easy separation and reusability without significant loss of catalyst activity were found to be the notable features of this synthetic protocol.
New synthesis of trifluorinated amines from 1-bromopropargylic amines in superacid
Cantet, Anne-Céline,Carreyre, Hélène,Gesson, Jean-Pierre,Renoux, Brigitte,Jouannetaud, Marie-Paule
, p. 5547 - 5551 (2006)
Treatment of 1-bromopropargylic amines affords the corresponding 1,1,1-trifluoro in one step in HF-SbF5 medium. 1-Bromo-1,1-difluoro or 2-bromo-1,1,1-trifluoro derivatives could also be prepared, depending on the reaction conditions.
Synthesis, antitubercular evaluation and molecular docking studies of phthalimide bearing 1,2,3-triazoles
Phatak, Pramod S.,Bakale, Rajubai D.,Dhumal, Sambhaji T.,Dahiwade, Lalita K.,Choudhari, Prafulla B.,Siva Krishna, Vagolu,Sriram, Dharmarajan,Haval, Kishan P.
, p. 2017 - 2028 (2019)
In a search for safer and potent antitubercular agents, here a library of newly substituted dioxoisoindolinylmethyl-triazolyl-N-phenylacetamide derivatives (5a–l) has been synthesized via click chemistry approach. All synthesized compounds were evaluated for their antitubercular activity against Mycobacterium tuberculosis H37Rv (MTB). Among the screened compounds, 5d, 5e, 5h, and 5l showed good antitubercular activity. The compounds 5d and 5l have shown very effective antitubercular activity against Mycobacterium tuberculosis H37Rv (MTB) with MIC 12.5 μg/mL. All the newly synthesized compounds were thoroughly characterized by 1H NMR, 13C NMR, and HRMS spectral data. We further performed exploratory docking studies on the crystal structure of Mycobacterium tuberculosis enoyl reductase to demonstrate the mechanism of antitubercular activity.
Design of molecular hybrids of phthalimide-triazole agents with potent selective MCF-7/HepG2 cytotoxicity: Synthesis, EGFR inhibitory effect, and metabolic stability
Ihmaid, Saleh K.,Alraqa, Shaya Yahya,Aouad, Mohamed R.,Aljuhani, Ateyatallah,Elbadawy, Hossein M.,Salama, Samir A.,Rezki, Nadjet,Ahmed, Hany E.A.
, (2021)
This study reports an efficient and convenient click chemistry synthesis of a novel series of phthalimide scaffold linked to 1,2,3 triazole ring and terminal lipophilic fragments. Structures of newly synthesized compounds were well characterized by different spectroscopic tools. In vitro MTT cytotoxicity assay was performed comparing the cytotoxic effects of newly synthesized compounds to staurosporine using three different types: human liver cancer cell line (HepG2), Michigan cancer foundation-7 (MCF-7) and human colorectal carcinoma cell line (HCT116). The initial screening showed excellent to moderate anticancer activity for these newly synthesized compounds with high degree of cell line selectivity with micromolar (μM) half maximal inhibitory concentration (IC50) values against tumor cells. The SAR analysis of these derivatives confirmed the role of molecular fragments including phthalimide, linker, triazole, and terminal tails in correlation to activity. In addition, enzymatic inhibitory assay against wild type EGFR was performed for the most active compounds to get more details about their mechanism of action. In order to further explore their binding affinities, molecular docking simulation was studied against EGFR site. The results obtained from molecular docking study and those obtained from cytotoxic screening were correlated. One of the most prominent analogs is (6f) with terminal disubstituted ring and amide linker showed selective MCF-7 cytotoxicity profile with IC50 0.22 μM and 79 nM to EGFR target. Extensive structure activity relationship (SAR) analyses were also carried out. The pharmacokinetic profile of (6f) was studied showing good metabolic stability and long duration behavior. This design offered a potent selective anticancer phthalimide-triazole leads for further optimization in cancer drug discovery.
Direct Conversion of Primary Alcohols to 1,2-Amino Alcohols: Enantioselective Iridium-Catalyzed Carbonyl Reductive Coupling of Phthalimido-Allene via Hydrogen Auto-Transfer
Spielmann, Kim,Xiang, Ming,Schwartz, Leyah A.,Krische, Michael J.
, p. 14136 - 14141 (2019)
The first catalytic enantioselective carbonyl (α-amino)allylations are described. Phthalimido-allene 1 and primary alcohols 2a-2z, 2a′-2c′ engage in hydrogen auto-transfer-mediated carbonyl reductive coupling by way of (α-amino)allyliridium-aldehyde pairs to form vicinal amino alcohols 3a-3z, 3a′-3c′ with high levels of regio-, anti-diastereo-, and enantioselectivity. Reaction progress kinetic analysis and isotopic labeling studies corroborate a catalytic cycle involving turnover-limiting alcohol dehydrogenation followed by rapid allene hydrometalation.
One-pot enyne metathesis/Diels-Alder reaction for the construction of highly functionalized novel polycyclic aza-compounds
Ben-Othman, Raja,Othman, Mohamed,Coste, Servane,Decroix, Bernard
, p. 559 - 567 (2008)
Various tricyclic dienes were synthesized via enyne metathesis using the first generation Grubbs catalyst. The enyne metathesis proceeded smoothly in refluxing CH2Cl2 with a low catalyst loading (3.0 mol %), giving good yields (72-89%) of the tricyclic products 6 and 16. The resulting 1,3-dienes are suitable precursors of polycyclic structures via a Diels-Alder process. One-pot RCM/Diels-Alder reactions of the enyne products with dienophiles proceeded smoothly to afford polycyclic compounds as a single cycloadduct. The structures of the Diels-Alder adducts were determined by 1H NMR spectra and X-ray analysis. The cycloadducts were formed via the approach of the dienophiles towards the diene in endo mode.
Potent antiproliferative activity of bradykinin B2 receptor selective agonist FR-190997 and analogue structures thereof: A paradox resolved?
Rassias, Gerasimos,Leonardi, Sofia,Rigopoulou, Dionisia,Vachlioti, Eleanna,Afratis, Konstantinos,Piperigkou, Zoi,Koutsakis, Christos,Karamanos, Nikos K.,Gavras, Haralambos,Papaioannou, Dionissios
, (2020/11/12)
Βradykinin stimulation of B2 receptor is known to activate the oncogenic ERK pathway and overexpression of bradykinin receptors B1 and B2 has been reported to occur in glioma, colorectal and cervical cancers. B1R and B2R antagonists have been shown to reverse tumor proliferation and invasion. Paradoxically, B1R and B2R agonism has also been reported to elicit antiproliferative benefits. In order to complement the data accumulated to date with the natural substrate bradykinin and peptidic B2R antagonists, we decided to examine for the first time the response elicited by B2R stimulation in breast cancer lines with a non-peptidic small molecule B2R agonist. We synthesized and assessed the highly selective and potent B2R partial agonist FR-190997 in MCF-7 and MDA-MBA-231 breast cancer lines and found it possessed significant antiproliferative activity (IC50 2.14 and 0.08 μΜ, respectively). The modular nature of FR-190997 allowed us to conduct a focused SAR study and discover compound 10 which exhibits subnanomolar antiproliferative activity (IC 50 0.06 nΜ) in the TNBC MDA-MBA-231 cell line. This performance surpasses, in most cases by several orders of magnitude, those of established anticancer agents and FDA-approved breast cancer drugs. In line with the established literature we suggest that this remarkable activity precipitates from a dual mode of action involving agonist-induced receptor internalization/degradation combined with sequestration of functional intracellular B2 receptors and inhibition of the associated endosomal signaling. The latter mode may be realized by appropriate ligands regardless of B2R agonist/antagonist designation which only relates to membrane residing GCPRs. Under this prism the controversy over the antiproliferative effects of B2 agonists and antagonists is potentially neutralized.
Electroselective and Controlled Reduction of Cyclic Imides to Hydroxylactams and Lactams
Bai, Ya,Shi, Lingling,Zheng, Lianyou,Ning, Shulin,Che, Xin,Zhang, Zhuoqi,Xiang, Jinbao
supporting information, p. 2298 - 2302 (2021/04/05)
An efficient and practical electrochemical method for selective reduction of cyclic imides has been developed using a simple undivided cell with carbon electrodes at room temperature. The reaction provides a useful strategy for the rapid synthesis of hydroxylactams and lactams in a controllable manner, which is tuned by electric current and reaction time, and exhibits broad substrate scope and high functional group tolerance even to reduction-sensitive moieties. Initial mechanistic studies suggest that the approach heavily relies on the utilization of amines (e.g., i-Pr2NH), which are able to generate α-aminoalkyl radicals. This protocol provides an efficient route for the cleavage of C-O bonds under mild conditions with high chemoselectivity.
Discovery of fast-acting dual-stage antimalarial agents by profiling pyridylvinylquinoline chemical space via copper catalyzed azide-alkyne cycloadditions
Huang, Guang,Solano, Claribel Murillo,Melendez, Joel,Yu-Alfonzo, Sabrina,Boonhok, Rachasak,Min, Hui,Miao, Jun,Chakrabarti, Debopam,Yuan, Yu
supporting information, (2020/10/13)
To identity fast-acting, multistage antimalarial agents, a series of pyridylvinylquinoline-triazole analogues have been synthesized via CuAAC. Most of the compounds display significant inhibitory effect on the drug-resistant malarial Dd2 strain at low submicromolar concentrations. Among the tested analogues, compound 60 is the most potent molecule with an EC50 value of 0.04 ± 0.01 μM. Our current study indicates that compound 60 is a fast-acting antimalarial compound and it demonstrates stage specific action at the trophozoite phase in the P. falciparum asexual life cycle. In addition, compound 60 is active against both early and late stage P. falciparum gametocytes. From a mechanistic perspective, compound 60 shows good activity as an inhibitor of β-hematin formation. Collectively, our findings suggest that fast-acting agent 60 targets dual life stages of the malarial parasites and warrant further investigation of pyridylvinylquinoline hybrids as new antimalarials.
Radical Carbonyl Propargylation by Dual Catalysis
Huang, Huan-Ming,Bellotti, Peter,Daniliuc, Constantin G.,Glorius, Frank
supporting information, p. 2464 - 2471 (2020/12/07)
Carbonyl propargylation has been established as a valuable tool in the realm of carbon–carbon bond forming reactions. The 1,3-enyne moiety has been recognized as an alternative pronucleophile in the above transformation through an ionic mechanism. Herein, we report for the first time, the radical carbonyl propargylation through dual chromium/photoredox catalysis. A library of valuable homopropargylic alcohols bearing all-carbon quaternary centers could be obtained by a catalytic radical three-component coupling of 1,3-enynes, aldehydes and suitable radical precursors (41 examples). This redox-neutral multi-component reaction occurs under very mild conditions and shows high functional group tolerance. Remarkably, bench-stable, non-toxic, and inexpensive CrCl3 could be employed as a chromium source. Preliminary mechanistic investigations suggest a radical-polar crossover mechanism, which offers a complementary and novel approach towards the preparation of valuable synthetic architectures from simple chemicals.
