13451-79-1Relevant articles and documents
Rhodium(II)-Catalyzed Undirected and Selective C(sp2)-H Amination en Route to Benzoxazolones
Singh, Ritesh,Nagesh, Kommu,Parameshwar, Matam
, p. 6520 - 6524 (2016)
Rhodium(II) can effectively promote the activation and cyclization of arylcarbamate substrates to yield benzoxazolones via an intramolecular nitrene C-H insertion reaction. Investigation of the substrate scope shows that the reaction undergoes selective a
Molecular iodine-mediated domino reaction for the synthesis of benzamides, 2,2-Diazidobenzofuran-3(2H)-ones and benzoxazolones
Rajendar,Kant, Ruchir,Narender
, p. 3591 - 3596 (2013)
A simple and efficient domino protocol has been developed for the preparation of biologically important benzamides, 2,2-diazidobenzofuran-3(2H)- ones and benzoxazolones from various structurally and electronically divergent acetophenones and ortho-hydroxyacetophenones in the presence of molecular iodine, sodium azide and sodium bicarbonate at 100 °C in good to excellent yields. Copyright
Identification and characterization of benzo[d]oxazol-2(3H)-one derivatives as the first potent and selective small-molecule inhibitors of chromodomain protein CDYL
Yang, Lixin,Liu, Yongqing,Fan, Minghua,Zhu, Guiwang,Jin, Hongwei,Liang, Jing,Liu, Zhenming,Huang, Zhuo,Zhang, Liangren
, (2019)
Chemical probes of epigenetic ‘readers’ of histone post-translational modifications (PTMs) have become powerful tools for mechanistic and functional studies of their target proteins in physiology and pathology. However, only limited ‘reader’ probes have been developed, which restricted our understanding towards these macromolecules and their roles in cells or animals. Here, we reported a structure-guided approach to develop and characterize benzo [d]oxazol-2(3H)-one analogs as the first potent and selective small-molecule inhibitors of chromodomain Y-like (CDYL), a histone methyllysine reader protein. The binding conformation between the chromodomain of CDYL and the modified peptidomimetics was studied via molecular docking and dynamic simulations, facilitating subsequent virtual screening of tens of hits from Specs chemical library validated by SPR technique (KD values: from 271.1 μM to 5.4 μM). Further design and synthesis of 43 compounds helped to interpret the structure-activity relationship (SAR) that lead to the discovery of novel small-molecule inhibitors of CDYL. Compound D03 (KD: 0.5 μM) was discovered and showed excellent selectivity among other chromodomain proteins, including CDYL2 (>140 folds), CDY1 (no observed binding) and CBX7 (>32 folds). Moreover, we demonstrated that D03 engaged with endogenous CDYL in a dose-dependent manner, and perturbed the recruitment of CDYL onto chromatin, resulting in transcriptional derepression of its target genes. Finally, the results showed that D03 promoted the development and branching of neurodendrites by inhibiting CDYL in hippocampal and cortical cultured neurons. This study not only discovers the first selective small-molecule inhibitors of CDYL, but provids a new chemical tool to intervene the dynamic nature of bio-macromolecules involved in epigenetic mechanism.
Iron-Catalyzed Arene C-H Amidation Using Functionalized Hydroxyl Amines at Room Temperature
Prasanthi,Begum, Samiyara,Srivastava, Hemant Kumar,Tiwari, Sandip Kumar,Singh, Ritesh
, p. 8369 - 8375 (2018)
Herein, we report Fe(III)(TPP)Cl as an effective catalyst for promoting arene C-H amidation through intramolecular cyclization of N-tosyloxyarylcarbamate substrates. The reaction proceeds via nitrene (outer sphere pathway) C(sp2)-H i
Visible-Light-Induced Intramolecular C(sp2)-H Amination and Aziridination of Azidoformates via a Triplet Nitrene Pathway
Zhang, Yipin,Dong, Xunqing,Wu, Yanan,Li, Guigen,Lu, Hongjian
supporting information, p. 4838 - 4842 (2018/08/24)
Catalytic intramolecular C-H amination and aziridination reactions of o-allylphenyl azidoformates have been achieved under visible-light irradiation, providing a mild, clean, and efficient method for the synthesis of useful benzoxazolones and [5.1.0] bicyclic aziridines. Mechanistic studies suggest that a triplet nitrene acts as the reactive intermediate. The chemoselectivity of the reaction, with alkyl olefin aziridination ? electron deficient olefin aziridination ≈ C(sp2)-H amination ? C(sp3)-H amination was observed, which may be instructive in the development of an understanding of visible-light-induced triplet nitrene transformation reactions.
Benzo five-membered heterocyclic IDO1 (indoleamine 2,3-dioxygenase 1) inhibitor, preparation method thereof and application
-
Paragraph 0071; 0072; 0073; 0074; 0147; 0148; 0149; 0150, (2017/07/22)
The invention belongs to the field of medicines, and particularly relates to a benzo five-membered heterocyclic compound or pharmaceutically acceptable salt of the compound, a preparation method of the compound and an application of the compound serving as an IDO1 (indoleamine 2,3-dioxygenase 1) inhibitor. Experimental results indicate that the compound has a remarkable inhibiting effect on activity of IDO1, T cell proliferation can be effectively promoted, differentiation of initial T cells into regulatory T cells is inhibited, IDO1-mediated immune inhibition is reversed, and the compound can be used for treating related diseases with pathological features of an IDO1-mediated kynurenine metabolic pathway, wherein the related diseases include cancer, virus infection, neurodegenerative diseases, cataract, organ transplant rejection, depression and autoimmune diseases.
Discovery of potent IDO1 inhibitors derived from tryptophan using scaffold-hopping and structure-based design approaches
Zou, Yi,Wang, Yan,Wang, Fang,Luo, Minghao,Li, Yuezhen,Liu, Wen,Huang, Zhangjian,Zhang, Yihua,Guo, Wenjie,Xu, Qiang,Lai, Yisheng
, p. 199 - 211 (2017/07/03)
Indoleamine 2,3-dioxygenase 1 (IDO1) is frequently hijacked by tumors to escape the host immune response, and the enzyme is now firmly established as an attractive target for cancer immunotherapy. To identify novel IDO1 inhibitors suitable for drug development, a scaffold-hopping strategy combined with the average electrostatic potentials calculation was ultilized to design novel benzoxazolinone derivatives. Among these, compounds 7e, 7f and 9c exhibited the inhibitory potency in the low micromolar range and displayed negligible level of cytotoxicity against HeLa cells. Treatment with these three compounds promoted the proliferation of T lymphocyte and led to the dramatic decrease of regulatory T cells in the B16F1 cells and na?ve T cells co-culture system. Subsequent spectroscopic experiments suggested that these benzoxazolinones formed a coordinate bond with the heme iron to stabilize the complex. This study suggested that the benzoxazolinone was an interesting scaffold for discovering novel IDO1 inhibitors, and these compounds are attractive candidates for further development.
Selective: S -arylation of 2-oxazolidinethiones and selective N -arylation of 2-benzoxazolinones/2-benzimidazolinones
Sun, Chu-Han,Lu, Yi,Zhang, Qing,Lu, Rong,Bao, Lin-Qing,Shen, Mei-Hua,Xu, Hua-Dong
supporting information, p. 4058 - 4063 (2017/07/10)
There exist three possible patterns for the reaction of cyclic 2-oxazolidinethione and 2-benzoxazolidinethione with arynes, namely (a) S-arylation, (b) N-arylation, and (c) aryne insertion into the thiocarbonyl group (CS). Our studies demonstrate that S-arylation wins out affording S-aryl dihydrooxazoles. In contrast, for related reactions of cyclic 2-benzoxazolinone and 2-benzimidazolinone with arynes, it is found that N-arylation outcompetes O-arylation and aryne insertion into the CO group to give N-aryl 2-benzoxazolinones and N-aryl 2-benzimidazolinones.
Benzoxazolone Carboxamides as Potent Acid Ceramidase Inhibitors: Synthesis and Structure-Activity Relationship (SAR) Studies
Bach, Anders,Pizzirani, Daniela,Realini, Natalia,Vozella, Valentina,Russo, Debora,Penna, Ilaria,Melzig, Laurin,Scarpelli, Rita,Piomelli, Daniele
supporting information, p. 9258 - 9272 (2015/12/23)
Ceramides are lipid-derived intracellular messengers involved in the control of senescence, inflammation, and apoptosis. The cysteine amidase, acid ceramidase (AC), hydrolyzes these substances into sphingosine and fatty acid and, by doing so, regulates their signaling activity. AC inhibitors may be useful in the treatment of pathological conditions, such as cancer, in which ceramide levels are abnormally reduced. Here, we present a systematic SAR investigation of the benzoxazolone carboxamides, a recently described class of AC inhibitors that display high potency and systemic activity in mice. We examined a diverse series of substitutions on both benzoxazolone ring and carboxamide side chain. Several modifications enhanced potency and stability, and one key compound with a balanced activity-stability profile (14) was found to inhibit AC activity in mouse lungs and cerebral cortex after systemic administration. The results expand our arsenal of AC inhibitors, thereby facilitating the use of these compounds as pharmacological tools and their potential development as drug leads.
Optimization of N-benzyl-benzoxazol-2-ones as receptor antagonists of macrophage migration inhibitory factor (MIF)
Hare, Alissa A.,Leng, Lin,Gandavadi, Sunilkumar,Du, Xin,Cournia, Zoe,Bucala, Richard,Jorgensen, William L.
scheme or table, p. 5811 - 5814 (2010/12/20)
The cytokine MIF is involved in inflammation and cell proliferation via pathways initiated by its binding to the transmembrane receptor CD74. MIF also exhibits keto-enol tautomerase activity, believed to be vestigial in mammals. Starting from a 1 μM hit from virtual screening, substituted benzoxazol-2-ones have been discovered as antagonists with IC50 values as low as 7.5 nM in a tautomerase assay and 80 nM in a MIF-CD74 binding assay. Additional studies for one of the potent inhibitors demonstrated that it is not a covalent inhibitor of MIF and that it attenuates MIF-dependent ERK1/2 phosphorylation in human synovial fibroblasts.
