90924-12-2Relevant academic research and scientific papers
Quinazoline derivatives preparation method and use thereof
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Paragraph 0075; 0080-0082, (2019/04/02)
The invention discloses a quinazoline derivative shown in formula (I) which is described in the specification and a salt thereof. In the formula, Z represents -NH- and -O-, R1 and R2 represent C1-3 alkoxy groups or hydrogen, R3 is selected from the group consisting of 4-fluoro-, 4-chloro-, 2-chloro-, 4-bromo-, 2, 4-dichloro-, 4-methyl, 4-methoxy, hydrogen, 4-trifluoromethyl and 2,4-dimethoxy. The invention relates to a preparation method and application of the compound shown in the formula (I) and the salt thereof. The compound or the salt thereof has strong inhibitory activity on colorectal cancer cell strains HCT-116, human lung cancer cell strains A549 and breast cancer cell strains MCF-7. The compound has wide spectrum antitumor activity and can be used as a drug or lead compound for treatment of diseases like tumors and cancers.
Synthesis and SAR of new isoxazole-triazole bis-heterocyclic compounds as analogues of natural lignans with antiparasitic activity
Zimmermann, Lara A.,de Moraes, Milene H.,da Rosa, Rafael,de Melo, Eduardo B.,Paula, Fávero R.,Schenkel, Eloir P.,Steindel, Mario,Bernardes, Lílian S.C.
, p. 4850 - 4862 (2018/09/11)
Despite the impressive scientific and technological advances of recent decades, no effective treatment is currently available for Chagas disease. Our research group has been studying the design and synthesis of analogues of natural lignans aiming to identify compounds with antiparasitic activity. This article reports the synthesis of 42 novel bis-heterocyclic derivatives and the structure-activity relationship study conducted based on results of biological assays against Trypanosoma cruzi amastigotes. Thirty-seven compounds were active, and eight of them had GI50 values lower than 100 μM (GI50 88.4–12.2 μM). A qualitative structure activity relationship study using three dimensional descriptors was carried out and showed a correlation between growth inhibitory potency and the presence of bulky hydrophobic groups located at rings A and D of the compounds. Compound 3-(3,4-dimethoxyphenyl)-5-((4-(4-pentylphenyl)-1H-1,2,3-triazol-1-yl)methyl)isoxazole (31) was the most active in the series (GI50 12.2 μM), showing, in vitro, low toxicity and potency similar to benznidazole (GI50 10.2 μM). These results suggest that this compound can be a promising scaffold for the design of new trypanocidal compounds.
Ferrocene derivatives, preparation method and use thereof
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Paragraph 0076; 0077; 0081-0083, (2018/10/11)
The invention discloses ferrocene derivatives as shown in a formula I in the specification and salts thereof, wherein Z is O or NH; R is selected from hydrogen, fluorine, chlorine, bromine, methyl, methoxyl and trifluoromethyl; n is an integer ranging fro
Discovery of Farnesoid X Receptor Antagonists Based on a Library of Oleanolic Acid 3-O-Esters through Diverse Substituent Design and Molecular Docking Methods
Wang, Shao-Rong,Xu, Tingting,Deng, Kai,Wong, Chi-Wai,Liu, Jinsong,Fang, Wei-Shuo
, (2017/06/08)
The pentacyclic triterpene oleanolic acid (OA, 1) with known farnesoid X receptor (FXR) modulatory activity was modified at its C-3 position to find new FXR-interacting agents. A diverse substitution library of OA derivatives was constructed in silico through a 2D fingerprint similarity cluster strategy. With further docking analysis, four top-scored OA 3-O-ester derivatives were selected for synthesis. The bioassay results indicated that all four compounds 3 inhibited chenodeoxycholic acid (CDCA)-induced FXR transactivation in a concentration-dependent mode. Among them 3b and 3d are more active than the parent compound OA. A molecular simulation study was performed to attempt to explain the structure-Activity relationship (SAR) and the antagonistic action. To the best of our knowledge, this is the first report on semi-synthetic pentacyclic triterpenoids with FXR-modulatory activities.
Design and synthesis of a new series of 3,5-disubstituted isoxazoles active against Trypanosoma cruzi and Leishmania amazonensis
da Rosa, Rafael,de Moraes, Milene H?ehr,Zimmermann, Lara Almida,Schenkel, Eloir Paulo,Steindel, Mario,Bernardes, Lílian Sibelle Campos
, p. 25 - 35 (2017/02/05)
Chagas disease and leishmaniasis are neglected tropical diseases (NTDs) endemic in developing countries. Although there are drugs available for their treatment, efforts on finding new efficacious therapies are continuous. The natural lignans grandisin (1)
Synthesis and in vitro biological evaluation of novel coumarin derivatives containing isoxazole moieties on melanin synthesis in B16 cells and inhibition on bacteria
Pang, Guang Xian,Niu, Chao,Mamat, Nuramina,Aisa, Haji Akber
supporting information, p. 2674 - 2677 (2017/05/29)
A novel series of coumarin derivatives 6a–o, bearing isoxazole moieties were designed and synthesized. After that, they were evaluated for melanin synthesis in murine B16 cells and inhibitory effect on the growth of CA (Candida albicans), EC (Escherichia coli), SA (Staphylococcus aureus). It was found that eleven compounds (6b–f, 6j–o) showed a better activity on melanin synthesis than positive control (8-MOP). Among them, compounds 6d (242%) and 6f (390%), with nearly 1.6 and 2.6-fold potency compared with 8-MOP (149%) respectively, were recognized as the most promising candidate hits for further pharmacological study of anti-vitiligo. Seven halogen substituted compounds exhibited moderate antimicrobial activity against CA. It is interesting that 6e–f and 6l–m, which had two halogens on the benzene showed a comparable activity with Amphotericin B against CA. The evaluation of melanin synthesis in B16 cells and inhibitory effect on bacteria of above structurally diverse derivatives had also led to an outline of structure-activity relationship.
Ultrasonic-assisted synthesis of 1,4-disubstituted 1,2,3-triazoles via various terminal acetylenes and azide and their quorum sensing inhibition
Zhang, Da-wei,Zhang, Yu-min,Li, Jing,Zhao, Tian-qi,Gu, Qiang,Lin, Feng
, p. 343 - 353 (2016/12/23)
An efficient synthesis of 1,4-disubstituted 1,2,3-triazole derivatives was studied. 1,4-Disubstituted 1,2,3-triazoles containing isoxazole and thymidine structures were synthesized in 84–96% yields starting from various terminal isoxazole ether alkynes and β-thymidine azide derivatives via a 1,3-dispolar cycloaddition using copper acetate, sodium ascorbate as the catalyst under ultrasonic assisted condition. All the target compounds were characterized by HRMS, FT-IR, 1H NMR and 13C NMR spectroscopy. Furthermore, the quorum sensing inhibitory activities of synthesized compounds were evaluated with Chromobacterium violaceum (C. Violaceum CV026) based on their inhibition of violacein production, with compound C10-HSL as a positive control. The compounds 8a, 8c and 8f exhibited considerable levels of inhibitory activity against violacein production, and IC50 values were 217?±?19, 223?±?20 and 42.8?±?4.5?μM, respectively, which highlighted the potential of these compounds as lead structures for further research towards the development of novel QS inhibitors.
Cu(I) catalyzed microwave assisted telescopic synthesis of 3,5-disubstituted isoxazoles in green media
Meena,Maiti, Barnali,Chanda, Kaushik
, p. 5514 - 5517 (2016/11/19)
A facile and efficient microwave assisted telescopic synthesis of diverse isoxazoles was reported in green reaction medium. Initially, N-hydroxyl imidoyl chlorides were reacted with substituted alkynes in aqueous medium using 2 mol% of [Cu(phen)(PPh3
Thiophene [2, 3 - d] pyrimidine derivatives, their preparation and use thereof
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Paragraph 0118; 0119; 0120, (2017/02/17)
The invention provides a thiophene [2, 3-d] pyrimidine derivative containing isoxazole heterocycle shown by formula (I) or a pharmaceutically accepted salt thereof, wherein R1 and R2 are respectively selected from hydrogen, C1-6 alkyl, C1-6 alkoxy, haloge
A rapid and efficient solvent-free microwave-assisted synthesis of pyrazolone derivatives containing substituted isoxazole ring
Zhang, Dawei,Zhang, Yumin,Zhao, Tianqi,Li, Jing,Hou, Yaya,Gu, Qiang
, p. 2979 - 2987 (2016/05/19)
An efficient synthesis of 4-substituted pyrazolone derivatives was developed. 4-Substituted pyrazolone derivatives were synthesized in 78-97% yields starting from various 3-substituted isoxazole-5-carbaldehydes, ethyl acetoacetate and hydrazine under micr
