4369-55-5Relevant academic research and scientific papers
Gramine-based structure optimization to enhance anti-gastric cancer activity
Zhang, Xin-Hui,Guo, Qian,Wang, Heng-Ying,Li, Yi-Han,Khamis, Mussa Yussuf,Ma, Li-Ying,Wang, Bo,Liu, Hong-Min
, (2021/01/07)
Gramine is a natural indole alkaloid with a wide range of biological activities, but its anti-gastric cancer activity is poor. Herein, a pharmacophore fusion strategy was adopted to design and synthesize a new series of indole-azole hybrids on the structural basis of gramine. Based on our previous studies, different nitrogen-containing five-membered heterocyclic rings and terminal alkyne group were introduced into the indole-based scaffold to investigate their effect on improving the anti-gastric cancer activity of gramine derivatives. Structure-activity relationship (SAR) studies highlighted the role played by terminal alkyne in enhancing the inhibitory effect, and compound 16h displayed the best antiproliferative activity against gastric cancer MGC803 cells with IC50 value of 3.74 μM. Further investigations displayed compound 16h could induce mitochondria-mediated apoptosis, and caused cell cycle arrest at G2/M phase. Besides, compound 16h could inhibit the metastasis ability of MGC803 cells. Our studies may provide a new strategy for structural optimization of gramine to enhance anti-gastric cancer activity, and provide a potential candidate for the treatment of gastric cancer.
An enantioselective aza-Friedel-Crafts reaction of 5-aminoisoxazoles with isatin-derived: N -Boc ketimines
Liu, Hui,Yan, Yingkun,Li, Min,Zhang, Xiaomei
supporting information, p. 3820 - 3824 (2021/05/14)
By employing a chiral phosphoric acid as a catalyst, an enantioselective aza-Friedel-Crafts reaction of 5-aminoisoxazoles with isatin-derived N-Boc ketimines was realized. The reaction provided a wide variety of novel 3-isoxazole 3-amino-oxindoles with good yields (up to 99%) and moderate to good enantioselectivities (up to 99%). The absolute configuration of one product was assigned by X-ray crystal structural analysis and a plausible reaction mechanism was proposed. In addition, a scale-up reaction was performed successfully. Finally, one product was subjected to Suzuki-Miyaura coupling with phenylboronic acid to afford the product in a moderate yield without erosion of the enantioselectivity. This journal is
Identification of diphenylalkylisoxazol-5-amine scaffold as novel activator of cardiac myosin
Boggu, Pulla Reddy,Venkateswararao, Eeda,Manickam, Manoj,Sharma, Niti,Kang, Jong Seong,Jung, Sang-Hun
, (2020/09/16)
To identify novel potent cardiac myosin activator, a series of diphenylalkylisoxazol-5-amine compounds 4–7 have been synthesized and evaluated for cardiac myosin ATPase activation. Among the 37 compounds, 4a (CMA at 10 μM = 81.6%), 4w (CMA at 10 μM = 71.2%) and 6b (CMA at 10 μM = 67.4%) showed potent cardiac myosin activation at a single concentration of 10 μM. These results suggested that the introduction of the amino-isoxazole ring as a bioisostere for urea group is acceptable for the cardiac myosin activation. Additional structure–activity relationship (SAR) studies were conducted. Para substitution (-Cl, –OCH3, -SO2N(CH3)2) to the phenyl rings or replacement of a phenyl ring with a heterocycle (pyridine, piperidine and tetrahydropyran) appeared to attenuate cardiac myosin activation at 10 μM. Additional hydrogen bonding acceptor next to the amino group of the isoxazoles did not enhance the activity. The potent isoxazole compounds showed selectivity for cardiac myosin activation over skeletal and smooth muscle myosin, and therefore these potent and selective isoxazole compounds could be considered as a new series of cardiac myosin ATPase activators for the treatment of systolic heart failure.
In Situ Generated Magnesium Cyanide as an Efficient Reagent for Nucleophilic Cyanation of Nitrosoalkenes and Parent Nitronates
Ushakov, Pavel Yu.,Tabolin, Andrey A.,Ioffe, Sema L.,Sukhorukov, Alexey Yu.
supporting information, p. 1888 - 1892 (2019/01/30)
In situ generated magnesium cyanide [NaCN/Mg(ClO4)2] is suggested as a convenient, readily available, non-volatile and organic-soluble reagent for hydrocyanation reactions. It was successfully used for nucleophilic cyanation of nitrosoalkenes, nitronates, as well as other typical π-electrophiles, such as imines, α,β-unsaturated ketones, alkylidenemalonates and azoalkenes.
Reactions of 5-Aminoisoxazoles with α-Diazocarbonyl Compounds: Wolff Rearrangement vs N-H Insertion
Ge, Yun,Sun, Wangbin,Chen, Yang,Huang, Yulin,Liu, Zhuang,Jiang, Yaojia,Loh, Teck-Peng
, p. 2676 - 2688 (2019/02/26)
A highly chemoselective reaction between 5-aminoisoxazoles and α-diazocarbonyl compounds has been described. Both Wolff rearrangement and N-H insertion products can be obtained selectively by the judicious choice of reaction conditions. In the case of the
Copper-catalyzed direct cyanation of terminal alkynes with benzoyl cyanide
Du, Yan,Li, Zheng
supporting information, p. 4622 - 4625 (2018/11/27)
Copper-catalyzed direct cyanation of terminal alkynes is achieved using less toxic, stable and easy to handle benzoyl cyanide as a cyanide source and air as an oxidant. This protocol provides a good alternative to the preparation of 3-arylpropiolonitriles
Hoveyda-Grubbs II Catalyst: A Useful Catalyst for One-Pot Visible-Light-Promoted Ring Contraction and Olefin Metathesis Reactions
Ge, Yun,Sun, Wangbin,Pei, Bingbing,Ding, Jia,Jiang, Yaojia,Loh, Teck-Peng
supporting information, p. 2774 - 2777 (2018/05/22)
A one-pot reaction to synthesize functionalized 2H-azirines through visible-light-mediated ring contraction and olefin metathesis of isoxazoles is described. Hoveyda-Grubbs II catalyst was found to function as a photocatalyst for these transformations, al
Human carbonic anhydrase inhibitory profile of mono- and bis-sulfonamides synthesized via a direct sulfochlorination of 3- and 4-(hetero)arylisoxazol-5-amine scaffolds
Krasavin, Mikhail,Korsakov, Mikhail,Zvonaryova, Zhanna,Semyonychev, Evgenii,Tuccinardi, Tiziano,Kalinin, Stanislav,Tan?, Muhammet,Supuran, Claudiu T.
, p. 1914 - 1925 (2017/03/08)
Three distinct series of isoxazole-based primary mono- and bis-sulfonamides have been synthesized via direct sulfochlorination, each of them delivering nanomolar inhibitors of human carbonic anhydrase. Certain pronounced SAR trends have been established a
Difluoromethylthiolation of Phenols and Related Compounds with a HF2CSO2Na/Ph2PCl/Me3SiCl System
Huang, Zhongyan,Matsubara, Okiya,Jia, Shichong,Tokunaga, Etsuko,Shibata, Norio
supporting information, p. 934 - 937 (2017/02/26)
A novel HF2CSO2Na/Ph2PCl/Me3SiCl system is disclosed for the late-stage direct difluoromethylthiolation of Csp2 and Csp3 nucleophiles. Difluoromethylthiolation of phenols and naphthols proceeded nicely under this system to regioselectively provide corresponding SCF2H compounds in good yields. Other substrates such as indoles, pyrroles, pyrazoles, enamines, ketones, and β-keto esters were also transformed to corresponding SCF2H products in good yields. The late-stage direct difluoromethylthiolation of a number of natural products and pharmaceutically attractive molecules was also achieved.
WNT PATHWAY MODULATORS
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Paragraph 0197; 0198; 0206; 0207, (2015/07/07)
The present invention relates to dihydropyrazolo[l,5-a]pyrimidine compounds of formula I, defined herein, as WNT pathways modulators, processes for making them, and pharmaceutical compositions comprising them. Methods of treatment of conditions mediated by WNT pathway signalling including cancer, fibrosis, stem cell and diabetic retinopathy, rheumatoid arthritis, psoriasis and myocardial infarction, comprising the compounds of formula I are also provided.
