76620-00-3Relevant academic research and scientific papers
The discovery, design and synthesis of potent agonists of adenylyl cyclase type 2 by virtual screening combining biological evaluation
Li, Shanshan,Song, Gao,Wang, Liang-Liang,Weng, Zhiying,Xu, Guowei,Yang, Weimin,Yang, Yanming,Yang, Yaqing,Zhang, Jiajun,Zuo, Zhili
supporting information, (2020/02/27)
Adenylate cyclases (ACs), play a critical role in the conversion of adenosine triphosphate (ATP) into the second messenger cyclic adenosine monophosphate (cAMP). Studies have indicated that adenylyl cyclase type 2 (AC2) is potential drug target for many diseases, however, up to now, there is no AC2-selective agonist reported. In this research, docking-based virtual screening with the combination of cell-based biological assays have been performed for discovering novel potent and selective AC2 agonists. Virtual screening disclosed a novel hit compound 8 as an AC2 agonist with EC50 value of 8.10 μM on recombinant human hAC2 + HEK293 cells. The SAR (structure activity relationship) based on the derivatives of compound 8 was further explored on recombinant AC2 cells and compound 73 was found to be the most active agonist with the EC50 of 90 nM, which is 160-fold more potent than the reported agonist Forskolin and could selectively activate AC2 to inhibit the expression of Interleukin-6. The discovery of a new class of AC2-selective agonists would provide a novel chemical probe to study the physiological function of AC2.
Synthesis and Evaluation of Novel Spiro[oxindole-isoxazolidine] Derivatives as Potent Antioxidants
Kaur, Manpreet,Singh, Baldev,Singh, Baljit,Arjuna, Anania
, p. 1348 - 1354 (2017/03/27)
The antioxidant activity of isatin derivatives can be described with the presence of enolic hydroxyl group at the second position of the ring because of the keto-enol tautomerism between NH and C O groups of indolone moiety. The reducing ability of the tested compounds was evaluated by their interaction with the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) at various concentrations. Novel spiro[oxindole-isoxazolidine] derivatives (4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i) have been synthesized by 1,3-dipolar cycloaddition reactions of variously substituted maleimides (1) with isatin ketonitrone (3) and tested for their in vitro antioxidant potency in the DPPH assay. All the synthesized compounds have been identified as potent in vitro antioxidants.
DABCO-catalyzed [3+2] cycloaddition reactions of azomethine imines with N-aryl maleimides: Facile access to dinitrogen-fused heterocycles
Jia, Qianfa,Chen, Lei,Yang, Gongming,Wang, Jian,Wei, Jia,Du, Zhiyun
, p. 7150 - 7153 (2015/12/12)
DABCO-catalyzed [3+2] cycloaddition of azomethine imines with maleimides has been developed. This method could efficiently furnish dinitrogen-fused tetracyclic heterocycles in high levels of regioselectivity and with good yields.
Synthesis and in vitro evaluation of N-substituted maleimide derivatives as selective monoglyceride lipase inhibitors
Matuszak, Nicolas,Muccioli, Giulio G.,Labar, Geoffray,Lambert, Didier M.
experimental part, p. 7410 - 7420 (2010/04/30)
The endocannabinoid 2-arachidonoylglycerol (2-AG) plays a major role in many physiological processes, and its action is quickly terminated via enzymatic hydrolysis catalyzed by monoglyceride lipase (MGL). Regulating its endogenous level could offer therapeutic opportunities; however, few selective MGL inhibitors have been described so far. Here, we describe the synthesis of N-substituted maleimides and their pharmacological evaluation on the recombinant human fatty acid amide hydrolase (FAAH) and on the purified human MGL. A few N-arylmaleimides were previously described (Saario, S. M.; Salo, O. M.; Nevalainen, T.; Poso, A.; Laitinen, J. T.; Jarvinen, T.; Niemi, R. Characterization of the Sulfhydryl-Sensitive Site in the Enzyme Responsible for Hydrolysis of 2-Arachidonoylglycerol in Rat Cerebellar Membranes. Chem. Biol. 2005, 12, 649-656) as MGL inhibitors, and along these lines, we present a new set of maleimide derivatives that showed low micromolar IC50 and high selectivity toward MGL vs FAAH. Then, structure-activity relationships have been investigated and, for instance, 1-biphenyl-4-ylmethylmaleimide inhibits MGL with an IC50 value of 790 nM. Furthermore, rapid dilution experiments reveal that these compounds act as irreversible inhibitors. In conclusion, N-substituted maleimides constitute a promising class of potent and selective MGL inhibitors.
Access to indoles via Diels-Alder reactions of 2-vinylpyrroles with maleimides
Noland, Wayland E.,Lanzatella, Nicholas P.,Venkatraman, Lakshmanan,Anderson, Nicholas F.,Gullickson, Glen C.
experimental part, p. 1154 - 1176 (2010/03/04)
(Chemical Equation Presented) Variously substituted 2-vinylpyrroles underwent an endo-addition [4+2] cycloaddition reaction with maleimides followed by a spontaneous highly diastereoselective (93-98% de) isomerization to give tetrahydroindoles in moderate to excellent yield. Treatment with activated MnO2 in refluxing toluene provided the corresponding indoles in moderate to good yield. This highly convergent methodology for formation of indoles is versatile and the starting materials are conveniently prepared.
Process for preparation of N-substituted maleimides
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, (2008/06/13)
N-substituted maleimide represented by formula (2): STR1 is produced from N-substituted maleamic acid monoester represented by formula (1): STR2 in the presence of an acid catalyst by elmination of an alcohol from the monoester. The above N-substituted maleamic acid monoester represented by formula (1) is produced by esterification of N-substituted maleamic acid represented by formula (3): STR3 with an alcohol R2 -OH in the represence of an acid catalyst.
