81917-06-8Relevant academic research and scientific papers
Discovery and Characterization of 1 H-1,2,3-Triazole Derivatives as Novel Prostanoid EP4 Receptor Antagonists for Cancer Immunotherapy
Yang, Jun-Jie,Yu, Wei-Wei,Hu, Long-Long,Liu, Wen-Juan,Lin, Xian-Hua,Wang, Wei,Zhang, Qiansen,Wang, Pei-Li,Tang, Shuo-Wen,Wang, Xin,Liu, Mingyao,Lu, Weiqiang,Zhang, Han-Kun
, p. 569 - 590 (2020/02/05)
The prostanoid EP4 receptor is one of the key receptors associated with inflammatory mediator PGE2-elicited immunosuppression in the tumor microenvironment. Blockade of EP4 signaling to enhance immunity-mediated tumor elimination has recently emerged as a promising strategy for cancer immunotherapy. In our efforts to discover novel subtype-selective EP4 antagonists, we designed and synthesized a class of 1H-1,2,3-triazole-based ligands that display low nanomolar antagonism activity toward the human EP4 receptor and excellent subtype selectivity. The most promising compound 59 exhibits single-digit nanomolar potency in the EP4 calcium flux and cAMP-response element reporter assays and effectively suppresses the expression of multiple immunosuppression-related genes in macrophage cells. On the basis of its favorable ADMET properties, compound 59 was chosen for further in vivo biological evaluation. Oral administration of compound 59 significantly inhibited tumor growth in the mouse CT26 colon carcinoma model accompanied by enhanced infiltration of cytotoxic T lymphocytes in the tumor tissue.
Regioselective synthesis of 4-fluoro-1,5-disubstituted-1,2,3-triazoles from synthetic surrogates of α-fluoroalkynes
Jana, Sampad,Adhikari, Sweta,Cox, Michael R.,Roy, Sudeshna
supporting information, p. 1871 - 1874 (2020/02/20)
α-Fluoroalkynes are elusive molecules due to their instability and inaccessibility. Here, we show that α-fluoronitroalkenes can serve as synthetic surrogates of α-fluoroalkynes in [3+2] cycloaddition reactions with organic azides facilitated by a catalytic amount of trifluoroacetic acid (TFA). This work provides the first regioselective method to access 4-fluoro-1,5-disubstituted-1,2,3-triazoles.
P-benzoquinone diazide core skeleton derivative as well as preparation method and application thereof
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Paragraph 0046; 0156-0160, (2020/03/17)
The invention relates to a p-benzoquinone diazide core skeleton derivative and a preparation method and application, thereof, belongs to. the field of organic chemistry, and can effectively treat-ovarian-ovarian cancer-carcinoma STAT3-ovarian, cancer-ATG4
1,2,3-Triazolium-Based Cationic Amphipathic Peptoid Oligomers Mimicking Antimicrobial Helical Peptides
Shyam, Radhe,Charbonnel, Nicolas,Job, Aurélie,Blavignac, Christelle,Forestier, Christiane,Taillefumier, Claude,Faure, Sophie
supporting information, p. 1513 - 1516 (2018/07/31)
Amphipathic cationic peptoids (N-substituted glycine oligomers) represent a promising class of antimicrobial peptide mimics. The aim of this study is to explore the potential of the triazolium group as a cationic moiety and helix inducer to develop potent antimicrobial helical peptoids. Herein we report the first solid-phase synthesis of peptoid oligomers incorporating 1,2,3-triazolium-type side chains and their evaluation against Escherichia coli, Enterococcus faecalis, and Staphylococcus aureus. Several triazolium-based oligomers, even of short length, selectively kill bacteria over mammalian cells. SEM visualization of S. aureus cells treated with a dodecamer and a hexamer reveals severe cell membrane damage and suggests that the longer oligomer acts by pore formation.
Copper-Catalyzed Decarboxylative/Click Cascade Reaction: Regioselective Assembly of 5-Selenotriazole Anticancer Agents
Cui, Fei-Hu,Chen, Jing,Mo, Zu-Yu,Su, Shi-Xia,Chen, Yan-Yan,Ma, Xian-Li,Tang, Hai-Tao,Wang, Heng-Shan,Pan, Ying-Ming,Xu, Yan-Li
supporting information, p. 925 - 929 (2018/02/22)
A simple and efficient Cu-catalyzed decarboxylative/click reaction for the preparation of 1,4-disubstituted 5-arylselanyl-1,2,3-triazoles from propiolic acids, diselenides, and azides has been developed. The mechanistic study revealed that the intermolecular AAC reaction of an alkynyl selenium intermediate occurred. The resulting multisubstituted 5-seleno-1,2,3-triazoles were tested for in vitro anticancer activity by MTT assay, and compounds 4f, 4h, and 4p showed potent cancer cell-growth inhibition activities.
Development of new scaffolds as reversible tissue transglutaminase inhibitors, with improved potency or resistance to glutathione addition
Apperley, Kim Y. P.,Roy, Isabelle,Saucier, Vincent,Brunet-Filion, Nicholas,Piscopo, Sara-Pier,Pardin, Christophe,De Francesco, élise,Hao, Catherine,Keillor, Jeffrey W.
supporting information, p. 338 - 345 (2017/03/08)
Previous studies within our group have yielded a class of cinnamoyl-based competitive reversible inhibitors for tissue transglutaminase (TG2), with Ki values as low as 1.0 μM (compound CP4d). However, due to the electrophilic nature of their al
A cuprous catalytic phenmethyl nitrine with styrene synthesis of 2, 5 - disubstituted-oxazole
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Paragraph 0047, (2017/08/25)
The invention discloses a preparation method for synthesizing 2,5-disubstituted oxazoles from benzyl azide and styrene under the catalysis of sub copper. The method comprises the following steps of (1) preparing a substituent azide; (2) reacting azide with styrene to prepare a product. According to the method, the raw materials are simple, reaction conditions are moderate, and the method has high application value, and is suitable for industrial production.
Synthesis, Antibacterial, and Anticancer Evaluation of Novel Spiramycin-Like Conjugates Containing C(5) Triazole Arm
Klich, Katarzyna,Pyta, Krystian,Kubicka, Marcelina M.,Ruszkowski, Piotr,Celewicz, Lech,Gajecka, Marzena,Przybylski, Piotr
, p. 7963 - 7973 (2016/09/23)
Huisgen cycloaddition allowed obtaining of novel triazole-bridged antibiotics (6-16) with the reconstructed C(5) arm of spiramycin. 1H-1H NOESY couplings indicated the structure of novel derivatives in solution and demonstrated that
Synthesis and Evaluation of a Library of Trifunctional Scaffold-Derived Compounds as Modulators of the Insulin Receptor
Fabre, Benjamin,Pícha, Jan,Vaněk, Václav,Selicharová, Irena,Chrudinová, Martina,Collinsová, Michaela,?áková, Lenka,Budě?ínsky, Milo?,Jirá?ek, Ji?í
supporting information, p. 710 - 722 (2016/12/22)
We designed a combinatorial library of trifunctional scaffold-derived compounds, which were derivatized with 30 different in-house-made azides. The compounds were proposed to mimic insulin receptor (IR)-binding epitopes in the insulin molecule and bind to and activate this receptor. This work has enabled us to test our synthetic and biological methodology and to prove its robustness and reliability for the solid-phase synthesis and testing of combinatorial libraries of the trifunctional scaffold-derived compounds. Our effort resulted in the discovery of two compounds, which were able to weakly induce the autophosphorylation of IR and weakly bind to this receptor at a 0.1 mM concentration. Despite these modest biological results, which well document the well-known difficulty in modulating protein-protein interactions, this study represents a unique example of targeting the IR with a set of nonpeptide compounds that were specifically designed and synthesized for this purpose. We believe that this work can open new perspectives for the development of next-generation insulin mimetics based on the scaffold structure.
Manganese-catalyzed late-stage aliphatic C-H azidation
Huang, Xiongyi,Bergsten, Tova M.,Groves, John T.
supporting information, p. 5300 - 5303 (2015/05/13)
We report a manganese-catalyzed aliphatic C-H azidation reaction that can efficiently convert secondary, tertiary, and benzylic C-H bonds to the corresponding azides. The method utilizes aqueous sodium azide solution as the azide source and can be performed under air. Besides its operational simplicity, the potential of this method for late-stage functionalization has been demonstrated by successful azidation of various bioactive molecules with yields up to 74%, including the important drugs pregabalin, memantine, and the antimalarial artemisinin. Azidation of celestolide with a chiral manganese salen catalyst afforded the azide product in 70% ee, representing a Mn-catalyzed enantioselective aliphatic C-H azidation reaction. Considering the versatile roles of organic azides in modern chemistry and the ubiquity of aliphatic C-H bonds in organic molecules, we envision that this Mn-azidation method will find wide application in organic synthesis, drug discovery, and chemical biology.
