75650-38-3Relevant academic research and scientific papers
Design and optimisation of a small-molecule TLR2/4 antagonist for anti-tumour therapy
Chen, Hekai,Kong, Jun,Li, Tian,Xu, Qun,Yin, Hang,Zhang, Liwei
supporting information, p. 1771 - 1779 (2021/11/19)
In anti-tumour therapy, the toll-like receptor 2/4 (TLR2/4) signalling pathway has been a double-edged sword. TLR2/4 agonists are commonly considered adjuvants for immune stimulation, whereas TLR2/4 antagonists demonstrate more feasibility for anti-tumour therapy under specific chronic inflammatory situations. In individuals with cancer retaliatory proliferation and metastasis after surgery, blocking the TLR2/4 signalling pathway may produce favourable prognosis for patients. Therefore, here, we developed a small-molecule co-inhibitor that targets the TLR2/4 signalling pathway. After high-throughput screening of a compound library containing 14 400 small molecules, followed by hit-to-lead structural optimisation, we finally obtained the compound TX-33, which has effective inhibitory properties against the TLR2/4 signalling pathways. This compound was found to significantly inhibit multiple pro-inflammatory cytokines released by RAW264.7 cells. This was followed by TX-33 demonstrating promising efficacy in subsequent anti-tumour experiments. The current results provide a novel understanding of the role of TLR2/4 in cancer and a novel strategy for anti-tumour therapy.
Cobalt-Catalyzed Radical Hydroamination of Alkenes with N-Fluorobenzenesulfonimides
Lv, Guowei,Meng, Qi,Qin, Tao,Xiong, Tao,Zhang, Ge,Zhang, Qian
supporting information, p. 25949 - 25957 (2021/11/01)
An efficient and general radical hydroamination of alkenes using Co(salen) as catalyst, N-fluorobenzenesulfonimide (NFSI) and its analogues as both nitrogen source and oxidant was successfully disclosed. A variety of alkenes, including aliphatic alkenes, styrenes, α, β-unsaturated esters, amides, acids, as well as enones, were all compatible to provide desired amination products. Mechanistic experiments suggest that the reaction underwent a metal-hydride-mediated hydrogen atom transfer (HAT) with alkene, followed by a pivotal catalyst controlled SN2-like pathway between in situ generated organocobalt(IV) species and nitrogen-based nucleophiles. Moreover, by virtue of modified chiral cobalt(II)-salen catalyst, an unprecedented asymmetric version was also achieved with good to excellent level of enantiocontrol. This novel asymmetric radical C?N bond construction opens a new door for the challenging asymmetric radical hydrofunctionalization.
Light-Mediated Difluoromethylthiolation of Aldehydes with a Hydrogen Atom Transfer Photocatalyst
Dong, Jianyang,Yue, Fuyang,Wang, Xiaochen,Song, Hongjian,Liu, Yuxiu,Wang, Qingmin
supporting information, p. 8272 - 8277 (2020/11/03)
A mild general method for difluoromethylthiolation of aldehydes with PhSO2SCF2H and a decatungstate photocatalyst under redox-neutral conditions has been developed. This reaction is highly efficient, scalable, and oxidant-free. The broad substrate scope and excellent functional group tolerance of the reaction make it suitable for generating libraries of difluoromethyl thioesters. We demonstrated the utility and sustainability of the method by synthesizing several structurally complex difluoromethyl thioesters.
Deoxygenative Deuteration of Carboxylic Acids with D2O
Zhang, Muliang,Yuan, Xiang-Ai,Zhu, Chengjian,Xie, Jin
supporting information, p. 312 - 316 (2018/11/25)
We report a general, practical, and scalable means of preparing deuterated aldehydes from aromatic and aliphatic carboxylic acids with D2O as an inexpensive deuterium source. The use of Ph3P as an O-atom transfer reagent can facilitate the deoxygenation of aromatic acids, while Ph2POEt is a better O-atom transfer reagent for aliphatic acids. The highly precise deoxygenation of complex carboxylic acids makes this protocol promising for late-stage deoxygenative deuteration of natural product derivatives and pharmaceutical compounds.
Formamide catalyzed activation of carboxylic acids-versatile and cost-efficient amidation and esterification
Huy, Peter H.,Mbouhom, Christelle
, p. 7399 - 7406 (2019/08/20)
A novel, broadly applicable method for amide C-N and ester C-O bond formation is presented based on formylpyrrolidine (FPyr) as a Lewis base catalyst. Herein, trichlorotriazine (TCT), which is the most cost-efficient reagent for OH-group activation, was employed in amounts of ≤40 mol% with respect to the starting material (100 mol%). The new approach is distinguished by excellent cost-efficiency, waste-balance (E-factor down to 3) and scalability (up to >80 g). Moreover, high levels of functional group compatibility, which includes acid-labile acetals and silyl ethers, are demonstrated and even peptide C-N bonds can be formed. In comparison to reported amidation procedures using TCT, yields are considerably improved (for instance from 26 to 91%) and esterification is facilitated for the first time in synthetically useful yields. These significant enhancements are rationalized by activation by means of acid chlorides instead of less electrophilic acid anhydride intermediates.
β-Selective Reductive Coupling of Alkenylpyridines with Aldehydes and Imines via Synergistic Lewis Acid/Photoredox Catalysis
Lee, Katarzyna N.,Lei, Zhen,Ngai, Ming-Yu
supporting information, p. 5003 - 5006 (2017/05/04)
Umpolung (polarity reversal) strategies of aldehydes and imines have dramatically expanded the scope of carbonyl and iminyl chemistry by facilitating reactions with non-nucleophilic reagents. Herein, we report the first visible light photoredox-catalyzed β-selective reductive coupling of alkenylpyridines with carbonyl or iminyl derivatives with the aid of a Lewis acid co-catalyst. Our process tolerates complex molecular scaffolds (e.g., sugar, natural product, and peptide derivatives) and is applicable to the preparation of compounds containing a broad range of heterocyclic moieties. Mechanistic investigations indicate that the key step involves single-electron-transfer reduction of aldehydes or imines followed by the addition of resulting ketyl or α-aminoalkyl radicals to Lewis acid-activated alkenylpyridines.
BICYCLIC HYDROXAMIC ACIDS USEFUL AS INHIBITORS OF MAMMALIAN HISTONE DEACETYLASE ACTIVITY
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Page/Page column 125, (2017/07/14)
A compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof. The compound is an inhibitor of a histone deacetylase, and as such is useful in terepy, e.g. in the treatment of autoimmune disorders, mental disorders, neurodegenerative disorders, and hyperproliferative disorders.
Ruthenium-Catalyzed Difluoroalkylation of 8-Aminoquinoline Amides at the C5-Position
Chen, Changpeng,Zeng, Runsheng,Zhang, Jingyu,Zhao, Yingsheng
supporting information, p. 6947 - 6950 (2017/12/26)
A ruthenium-catalyzed highly selective difluoromethylation of 8-aminoquinoline amides at the C5 position has been developed. It tolerates a broad range of functional groups, providing the corresponding difluoromethylated products in moderate to good yields. Preliminary experimental results indicate that the tricoordinate ruthenium intermediate is the key factor in achieving the C5-position selectivity.
Facile access to new C-glycosides and C-glycoside scaffolds incorporating functionalised aromatic moieties
Redpath, Philip,Ness, Kerry A.,Rousseau, Joanne,Macdonald, Simon J.F.,Migaud, Marie E.
, p. 25 - 34 (2015/02/05)
The tandem ene/intramolecular Sakurai cyclisation (IMSC) reaction has been successfully applied to the synthesis of a range of C-glycosides, with key intermediates offering opportunities for functionalisation of the glycon moiety. To demonstrate the versatility of the approach to access the 2-deoxy-C-glycoside series, we synthesised diastereomerically pure C-glucoside and galactoside derivatives incorporating functionalised aromatic, heteroaromatic and bicyclic aromatic moieties, in addition to the C-homologue of (±)-β-2-deoxy-glucose 6-phosphate.
Facile access to new C-glycosides and C-glycoside scaffolds incorporating functionalised aromatic moieties
Redpath, Philip,Ness, Kerry A.,Rousseau, Joanne,Macdonald, Simon J.F.,Migaud, Marie E.
, p. 25 - 34 (2015/02/19)
The tandem ene/intramolecular Sakurai cyclisation (IMSC) reaction has been successfully applied to the synthesis of a range of C-glycosides, with key intermediates offering opportunities for functionalisation of the glycon moiety. To demonstrate the versatility of the approach to access the 2-deoxy-C-glycoside series, we synthesised diastereomerically pure C-glucoside and galactoside derivatives incorporating functionalised aromatic, heteroaromatic and bicyclic aromatic moieties, in addition to the C-homologue of (±)-β-2-deoxy-glucose 6-phosphate.
