2327-45-9Relevant articles and documents
Design, synthesis and biological evaluation of second-generation benzoylpiperidine derivatives as reversible monoacylglycerol lipase (MAGL) inhibitors
Granchi, Carlotta,Bononi, Giulia,Ferrisi, Rebecca,Gori, Eleonora,Mantini, Giulia,Glasmacher, Sandra,Poli, Giulio,Palazzolo, Stefano,Caligiuri, Isabella,Rizzolio, Flavio,Canzonieri, Vincenzo,Perin, Tiziana,Gertsch, Jürg,Sodi, Andrea,Giovannetti, Elisa,Macchia, Marco,Minutolo, Filippo,Tuccinardi, Tiziano,Chicca, Andrea
, (2020/10/14)
An interesting enzyme of the endocannabinoid system is monoacylglycerol lipase (MAGL). This enzyme, which metabolizes the endocannabinoid 2-arachidonoylglycerol (2-AG), has attracted great interest due to its involvement in several physiological and pathological processes, such as cancer progression. Experimental evidences highlighted some drawbacks associated with the use of irreversible MAGL inhibitors in vivo, therefore the research field concerning reversible inhibitors is rapidly growing. In the present manuscript, the class of benzoylpiperidine-based MAGL inhibitors was further expanded and optimized. Enzymatic assays identified some compounds in the low nanomolar range and steered molecular dynamics simulations predicted the dissociation itinerary of one of the best compounds from the enzyme, confirming the observed structure-activity relationship. Biological evaluation, including assays in intact U937 cells and competitive activity-based protein profiling experiments in mouse brain membranes, confirmed the selectivity of the selected compounds for MAGL versus other components of the endocannabinoid system. An antiproliferative ability in a panel of cancer cell lines highlighted their potential as potential anticancer agents. Future studies on the potential use of these compounds in the clinical setting are also supported by the inhibition of cell growth observed both in cancer organoids derived from high grade serous ovarian cancer patients and in pancreatic ductal adenocarcinoma primary cells, which showed genetic and histological features very similar to the primary tumors.
Efficient synthesis of NIR emitting bis[2-(2′-hydroxylphenyl)benzoxazole] derivative and its potential for imaging applications
Wang, Junfeng,Baumann, Hannah,Bi, Xiaoman,Shriver, Leah P.,Zhang, Zhaoda,Pang, Yi
, (2020/01/25)
Unassymetric bis[2-(2′-hydroxyphenylbenzoxole)] bis(HBO) derivatives with a DPA functionality for zinc binding have been developed with an efficient synthetic route, using the retrosynthetic analysis. Comparison of bis(HBO) derivatives with different substitution patterns allows us to verify and optimize their unique fluorescence properties. Upon binding zinc cation, bis(HBO) derivatives give a large fluorescence turn-on in both visible (λem ≈ 536 nm) and near-infrared (NIR) window (λem ≈ 746 nm). The probes are readily excitable by a 488 nm laser, making this series of compounds a suitable imaging tool for in vitro and in vivo study on a confocal microscope. The application of zinc binding-induced fluorescence turn-on is successfully demonstrated in cellular environments and thrombus imaging.
BICYCLIC HETEROARYL SUBSTITUTED COMPOUNDS
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Page/Page column 563, (2018/03/25)
Disclosed are compounds of Formula (I) to (VIII): (I) (II) (III) (IV) (V) (VI) (VII) (VIII); or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or prodrug thereof, wherein R3 is a bicyclic heteroaryl group substituted with zero to 3 R3a; and R1, R2, R3a, R4, and n are defined herein. Also disclosed are methods of using such compounds as PAR4 inhibitors, and pharmaceutical compositions comprising such compounds. These compounds are useful in inhibiting or preventing platelet aggregation, and are useful for the treatment of a thromboembolic disorder or the primary prophylaxis of a thromboembolic disorder.
Preparation technology of 6-hydroxy-bentazone
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Paragraph 0087; 0088; 0119-0120; 0135-0136, (2017/08/28)
The invention discloses a preparation technology of 6-hydroxy-3-isopropyl-1H-benzo[c][1,2,6]thiadiazine-4(3H)-keto-2,2-dioxide. The preparation technology includes subjecting 5-chloro-2-nitrobenzoic acid serving as a raw material to hydrolysis reaction an
Concise Synthesis of Dictyoquinazol A via a Dimerisation-Cyclocondensation Sequence
Wangsahardja, Jonatan,Marcolin, Gabriella M.,Lizarme, Yuvixza,Morris, Jonathan C.,Hunter, Luke
supporting information, p. 1237 - 1240 (2016/05/10)
A two-step total synthesis of the neuroprotective alkaloid, dictyoquinazol A, has been achieved. The brevity of this synthesis was enabled by exploiting the hidden symmetry of the target molecule. Several structural analogues were also prepared using a similar strategy. These results provide a platform for future structure-activity relationship studies in the quest for a novel treatment for stroke.
Copper-catalyzed methyl esterification reactions via C-C bond cleavage
Zhu, Yan,Yan, Hong,Lu, Linhua,Liu, Defu,Rong, Guangwei,Mao, Jincheng
, p. 9898 - 9905 (2013/10/22)
The highly effective synthesis of methyl esters from benzylic alcohols, aldehydes, or acids via copper-catalyzed C-C cleavage from tert-butyl hydroperoxide is reported in this paper for the first time. Our protocol is easily accessible and practical, making it a possible supplement for the traditional way.
Discovery of novel Tricyclic full agonists for the G-protein-coupled niacin receptor 109A with minimized flushing in rats
Shen, Hong C.,Ding,Deng, Qiaolin,Wilsie, Larissa C.,Krsmanovic, Mihajlo L.,Taggart, Andrew K.,Carballo-Jane, Ester,Ren, Ning,Cai,Wu,Wu, Kenneth K.,Cheng, Kang,Chen, Qing,Wolff, Michael S.,Tong, Xinchun,Holt, Tom G.,Waters, M. Gerard,Hammond, Milton L.,Tata, James R.,Colletti, Steven L.
supporting information; experimental part, p. 2587 - 2602 (2010/01/15)
Tricyclic analogues were rationally designed as the high affinity niacin receptor G-protein-coupled receptor 109A (GPR109A) agonists by overlapping three lead structures. Various tricyclic anthranilide and cycloalkene carboxylic acid full agonists were di
COMPOUND HAVING TGF-BETA INHIBITORY ACTIVITY AND PHARMACEUTICAL COMPOSITION CONTAINING SAME
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Page/Page column 49, (2010/11/24)
The present invention provides compounds of formula (I) or compounds of formula (II) and pharmaceutically acceptable salts or solvates thereof. An objective of the present invention is to provide compounds having TGF2 inhibitory activity.
NIACIN RECEPTOR AGONISTS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT
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Page/Page column 35; 82-83, (2010/11/30)
The present invention relates to niacin receptor agonists of formula: (I); as well as pharmaceutically acceptable salts and solvates. The compounds are useful for treating dyslipidemias, and in particular, reducing serum LDL, VLDL and triglycerides, and raising HDL levels. Pharmaceutical compositions and methods of treatment are also included.
SUBSTITUTED TRIAZOLE DERIVATIVES AS OXYTOCIN ANTAGONISTS
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Page/Page column 30, (2010/02/15)
This invention relates to compounds of formula (I) with activity as oxytocin antagonists, uses thereof, processes for the preparation thereof and compositions containing said inhibitors. These inhibitors have utility in a variety of therapeutic areas including sexual dysfunction, particularly premature ejaculation (P.E.).