328552-90-5Relevant articles and documents
Design and synthesis of novel diosgenin-triazole hybrids targeting inflammation as potential neuroprotective agents
Huang, Yi,Huang, Weiwei,Yang, Guixiang,Wang, Rui,Ma, Lei
supporting information, (2021/05/21)
Alzheimer's disease is a progressive neurodegenerative disease, and its incidence is expected to increase as the global population ages. Recent studies provide increasing evidence that inflammation plays a key role in the pathogenesis and progression of AD. Diosgenin, an active ingredient in Dioscorea nipponica Makino, is a promising bioactive lead compound in the treatment of Alzheimer's disease, which exhibited anti-inflammatory activity. To search for more efficient anti-Alzheimer agents, a series of novel diosgenin-triazolyl hybrids were designed, synthesized, and their neuroprotective effects against oxygen-glucose deprivation-induced neurotoxicity and LPS-induced NO production were evaluated. Most of these new hybrids displayed better activities than DIO. In particular, the promising compound L6 not only demonstrated an excellent neuroprotective effect but also showed the best anti-inflammatory activity. The structure-activity relationship study illustrated that the introduction of benzyl or phenyl triazole did improve the activity, and the introduction of benzyl triazole was better than that of phenyl triazole. The results we obtained showed that the diosgenin skeleton could be a promising structural template for the development of new anti-Alzheimer drug candidates, and compound L6 has the potential to be an important lead compound for further research.
NOVEL DIBENZOOXAPHOSPHININE OXIDE DERIVATIVE COMPOUNDS AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING DEGENERATIVE DISEASE COMPRISING THE SAME AS AN ACTIVE INGREDIENT
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Paragraph 0153-0156, (2021/03/23)
The present invention relates to a novel dibenzooxininin oxide derivative compound having various nitrogen-containing substituents introduced at 6-position of a dibenzooxaphosphorin oxide mononuclear, and to the use thereof. The present invention relates to a pharmaceutical composition for preventing or treating degenerative diseases and a health supplement food composition for preventing or treating degenerative diseases, comprising the dibenzooxaphosphorin oxide derivative compound of the present invention.
Identification of highly potent and selective Cdc25 protein phosphatases inhibitors from miniaturization click-chemistry-based combinatorial libraries
Jing, Lanlan,Wu, Gaochan,Hao, Xia,Olotu, Fisayo A.,Kang, Dongwei,Chen, Chin Ho,Lee, Kuo-Hsiung,Soliman, Mahmoud E.S.,Liu, Xinyong,Song, Yuning,Zhan, Peng
, (2019/09/19)
Cell division cycle 25 (Cdc25) protein phosphatases play key roles in the transition between the cell cycle phases and their association with various cancers has been widely proven, which makes them ideal targets for anti-cancer treatment. Though several Cdc25 inhibitors have been developed, most of them displayed low activity and poor subtype selectivity. Therefore, it is extremely important to discover novel small molecule inhibitors with potent activities and significant selectivity for Cdc25 subtypes, not only served as drugs to treat cancer but also to probe its mechanism in transitions. In this study, miniaturized parallel click chemistry synthesis via CuAAC reaction followed by in situ biological screening were used to discover selective Cdc25 inhibitors. The bioassay results showed that compound M2N12 proved to be the most potent Cdc25 inhibitor, which also act as a highly selective Cdc25C inhibitor and was about 9-fold potent than that of NSC 663284. Moreover, M2N12 showed remarkable anti-growth activity against the KB-VIN cell line, equivalent to that of PXL and NSC 663284. An all-atom molecular dynamics (MD) simulation approach was further employed to probe the significant selectivity of M2N12 for Cdc25C relative to its structural homologs Cdc25A and Cdc25B. Overall, above results make M2N12 a promising lead compound for further investigation and structural modification.
Novel leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry
Cao, Jiangying,Ma, Chunhua,Zang, Jie,Gao, Shuai,Gao, Qianwen,Kong, Xiujie,Yan, Yugang,Liang, Xuewu,Ding, Qin'ge,Zhao, Chunlong,Wang, Binghe,Xu, Wenfang,Zhang, Yingjie
, p. 3145 - 3157 (2018/06/01)
The over-expression of aminopeptidase N on diverse malignant cells is associated with the tumor angiogenesis and metastasis. In this report, one new series of leucine ureido derivatives containing the triazole moiety was designed, synthesized and evaluated as APN inhibitors. Among them, compound 13v showed the best APN inhibition with an IC50 value of 0.089 ± 0.007 μM, which was two orders of magnitude lower than that of bestatin (IC50 = 9.4 ± 0.5 μM). Compound 13v also showed dose-dependent anti-angiogenesis activities. Even at the lower concentration (10 μM), compound 13v presented similar anti-angiogenesis activity compared with bestatin at 100 μM in both the human umbilical vein endothelial cells (HUVECs) capillary tube formation assay and the rat thoracic aorta rings test. Moreover, compared with bestatin, 13v exhibited comparable, if not better in vivo anti-metastasis activity in a mouse H22 pulmonary metastasis model.
Sustainable organophosphorus-catalysed Staudinger reduction
Lenstra, Danny C.,Lenting, Peter E.,Mecinovi?, Jasmin
supporting information, p. 4418 - 4422 (2018/10/17)
A highly efficient and sustainable catalytic Staudinger reduction for the conversion of organic azides to amines in excellent yields has been developed. The reaction displays excellent functional group tolerance to functionalities that are otherwise prone to reduction, such as sulfones, esters, amides, ketones, nitriles, alkenes, and benzyl ethers. The green nature of the reaction is exemplified by the use of PMHS, CPME, and a lack of column chromatography.
Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus
Tian, Ye,Liu, Zhaoqiang,Liu, Jinghan,Huang, Boshi,Kang, Dongwei,Zhang, Heng,De Clercq, Erik,Daelemans, Dirk,Pannecouque, Christophe,Lee, Kuo-Hsiung,Chen, Chin-Ho,Zhan, Peng,Liu, Xinyong
, p. 339 - 350 (2018/04/10)
Inspired by our previous efforts on the modifications of diarylpyrimidines as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTI) and reported crystallography study, novel diarylnicotinamide derivatives were designed with a “triazole tail” occupying the entrance channel in the NNRTI binding pocket of the reverse transcriptase to afford additional interactions. The newly designed compounds were then synthesized and evaluated for their anti-HIV activities in MT-4 cells. All the compounds showed excellent to good activity against wild-type HIV-1 strain with EC50 of 0.02–1.77 μM. Evaluations of selected compounds against more drug-resistant strains showed these compounds had advantage of inhibiting E138K mutant virus which is a key drug-resistant mutant to the new generation of NNRTIs. Among this series, propionitrile (3b2, EC50(IIIB) = 0.020 μM, EC50(E138K) = 0.015 μM, CC50 = 40.15 μM), pyrrolidin-1-ylmethanone (3b8, EC50(IIIB) = 0.020 μM, EC50(E138K) = 0.014 μM, CC50 = 58.09 μM) and morpholinomethanone (3b9, EC50(IIIB) = 0.020 μM, EC50(E138K) = 0.027 μM, CC50 = 180.90 μM) derivatives are the three most promising compounds which are equally potent to the marketed drug Etravirine against E138K mutant strain but with much lower cytotoxicity. Furthermore, detailed SAR, inhibitory activity against RT and docking study of the representative compounds are also discussed.
Discovery of phenylalanine derivatives as potent HIV-1 capsid inhibitors from click chemistry-based compound library
Wu, Gaochan,Zalloum, Waleed A.,Meuser, Megan E.,Jing, Lanlan,Kang, Dongwei,Chen, Chin-Ho,Tian, Ye,Zhang, Fangfang,Cocklin, Simon,Lee, Kuo-Hsiung,Liu, Xinyong,Zhan, Peng
, p. 478 - 492 (2018/09/25)
The HIV-1 capsid (CA) protein plays essential roles in both early and late stages of HIV-1 replication and is considered an important, clinically unexploited therapeutic target. As such, small drug-like molecules that inhibit this critical HIV-1 protein h
Steering Siglec–Sialic Acid Interactions on Living Cells using Bioorthogonal Chemistry
Büll, Christian,Heise, Torben,van Hilten, Niek,Pijnenborg, Johan F. A.,Bloemendal, Victor R. L. J.,Gerrits, Lotte,Kers-Rebel, Esther D.,Ritschel, Tina,den Brok, Martijn H.,Adema, Gosse J.,Boltje, Thomas J.
supporting information, p. 3309 - 3313 (2017/03/17)
Sialic acid sugars that terminate cell-surface glycans form the ligands for the sialic acid binding immunoglobulin-like lectin (Siglec) family, which are immunomodulatory receptors expressed by immune cells. Interactions between sialic acid and Siglecs regulate the immune system, and aberrations contribute to pathologies like autoimmunity and cancer. Sialic acid/Siglec interactions between living cells are difficult to study owing to a lack of specific tools. Here, we report a glycoengineering approach to remodel the sialic acids of living cells and their binding to Siglecs. Using bioorthogonal chemistry, a library of cells with more than sixty different sialic acid modifications was generated that showed dramatically increased binding toward the different Siglec family members. Rational design reduced cross-reactivity and led to the discovery of three selective Siglec-5/14 ligands. Furthermore, glycoengineered cells carrying sialic acid ligands for Siglec-3 dampened the activation of Siglec-3+ monocytic cells through the NF-κB and IRF pathways.
2-IMIDAZOLYL-PYRIMIDINE SCAFFOLDS AS POTENT AND SELECTIVE INHIBITORS OF NEURONAL NITRIC OXIDE SYNTHASE
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Paragraph 0031, (2016/01/25)
Imidazolyl-pyrimidine and related compounds, as can utilize heme-iron coordination in the selective inhibition of neuronal nitric oxide synthase.
Application of the Huisgen cycloaddition and ‘click’ reaction toward various 1,2,3-triazoles as HIV non-nucleoside reverse transcriptase inhibitors
Pribut, Nicole,Veale, Clinton G.L.,Basson, Adriaan E.,van Otterlo, Willem A.L.,Pelly, Stephen C.
supporting information, p. 3700 - 3704 (2016/07/21)
The development of novel anti-HIV agents remains an important medicinal chemistry challenge given that no cure for the disease is imminent, and the continued use of current NNRTIs inevitably leads to problems associated with resistance. Inspired by the pyrazole-containing NNRTI lersivirine (LSV), we embarked upon a study to establish whether 1,2,3-triazole heterocycles could be used as a new scaffold for the creation of novel NNRTIs. An especially attractive feature of triazoles used for this purpose is the versatility in accessing variously functionalised systems using either the thermally regulated Huisgen cycloaddition, or the related ‘click’ reaction. Employing three alternative forms of these reactions, we were able to synthesise a range of triazole compounds and evaluate their efficacy in a phenotypic HIV assay. To our astonishment, even compounds closely mimicking LSV were only moderately effective against HIV.
