Discovery and SAR study of c-Met kinase inhibitors bearing an 3-amino-benzo[d]isoxazole or 3-aminoindazole scaffold

Jiang, Xiaolong; Liu, Hongyan; Song, Zilan; Xia, Peng; Ji, Yinchun; Yao, Qizheng; Geng, Meiyu; Ai, Jing; Zhang, Ao

doi:10.1016/j.bmc.2014.12.002

Cited by 16 publications

(8 citation statements)

References 43 publications

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“…10) was investigated, and the SIRT1 IC 50 values were 35.25 and 37.36 µM, respectively. 3-amino-benzo[d]isoxazole based compounds were synthesized by Jiang et al (2015) and evaluated for their tyrosine kinase c-Met inhibitory activity. This tyrosine kinase c-Met is a receptor for hepatocyte growth factor.…”

Section: Biological Activitiesmentioning

confidence: 99%

The synthetic and therapeutic expedition of isoxazole and its analogs

2018

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Isoxazole, constituting an important family of five-membered heterocycles with one oxygen atom and one nitrogen atom at adjacent positions is of immense importance because of its wide spectrum of biological activities and therapeutic potential. It is, therefore, of prime importance that the development of new synthetic strategies and designing of new isoxazole derivatives should be based on the most recent knowledge emerging from the latest research. This review is an endeavor to highlight the progress in the chemistry and biological activity of isoxazole derivatives which could provide a low-height flying bird's eye view of isoxazole derivatives to the medicinal chemists for the development of clinically viable drugs using this information.

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Section: Biological Activitiesmentioning

confidence: 99%

The synthetic and therapeutic expedition of isoxazole and its analogs

2018

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“…For the hinge‐binding quinoline moiety, modifications have primarily been made at the 7‐position, these frequently being groups intended to increase solubility . With other heterocycles as hinge‐binders, substituents known to participate in more direct interactions with the enzyme have been explored, exemplified with amines, anilines, and nitrogen containing heterocycles in Figure . Molecules containing such variations have been shown to have strong interactions with the c‐Met active site, made possible by the formation of additional hydrogen bonds.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis and biological evaluation of 6‐substituted quinolines derived from cabozantinib as c‐Met inhibitors

Lien

Pettersen

Haugen

et al. 2019

Archiv der Pharmazie

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Based on the cabozantinib scaffold, novel c-Met inhibitors were rationalized from the limited knowledge of structure-activity relationships for the quinoline 6-position. Emphasis was given to modifications capable of engaging in additional polar interactions with the c-Met active site. In addition, ortho-fluorinations of the terminal benzene ring were explored. Fifteen new molecules were synthesized and evaluated in a c-Met enzymatic binding assay. A wide range of substituents were tolerated in the quinoline 6-position, while the ortho-fluorinations performed were shown to give considerable reductions in the c-Met binding affinity. The antiproliferative effects of the compounds were evaluated in the NCI60 cancer cell line panel. Most notably, compounds 15b and 18b were able to inhibit cell proliferation more efficiently than cabozantinib in leukemia, CNS, and breast cancer cell lines. The in vitro data agreed well with the in silico docking results, where additional hydrogen bonding was identified in the enzymatic pocket for the para-amino substituted 15b and 18b.

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“…In recent years compounds containing benzo [d]isoxazole scaffold attracts many researchers due to their pharmacological activities. Benzo [d]isoxazole and their derivatives are associated with antitubercular 1 , antimycobacterial 2 , anti-inflammatory 3 , antidiabetic 4 and c-Met kinase inhibitor 5 6 , cathepsin L inhibitors 7 , metallo-β -lactamase inhibitors 8 etc activities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antibacterial Screening of 1-(2-(2-Chlorophenyl)-2-(4-(6-Fluorobenzo[d]isoxazol-3-Yl)piperidin-1-Yl) Containing 1,3,4-Thiadiazole, 1,2,4-Triazole and 1,3,4-Oxadiazole Derivatives

Deshmukh¹,

Akolkar²,

Karale³

2019

Int. Res. J. Pharm.

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A series of novel 1,3,4-thiadiazole, 1,2,4-triazole and 1,3,4-oxadiazole have been synthesized from 1-(2-(2-chlorophenyl)-2-(4-(6fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)acetyl)-4-phenyl thiosemicarbazide 6 and their antimicrobial activities were reported. Compounds 6b, 6c, 9a, 9b, 9d and 9e have shown moderate activity towards Bacillus Subtilis and Escherichia Coli bacterial species. The structure of synthesized compounds was confirmed by spectral analysis.

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Discovery and SAR study of c-Met kinase inhibitors bearing an 3-amino-benzo[d]isoxazole or 3-aminoindazole scaffold

Cited by 16 publications

References 43 publications

The synthetic and therapeutic expedition of isoxazole and its analogs

The synthetic and therapeutic expedition of isoxazole and its analogs

Design, synthesis and biological evaluation of 6‐substituted quinolines derived from cabozantinib as c‐Met inhibitors

Synthesis and Antibacterial Screening of 1-(2-(2-Chlorophenyl)-2-(4-(6-Fluorobenzo[d]isoxazol-3-Yl)piperidin-1-Yl) Containing 1,3,4-Thiadiazole, 1,2,4-Triazole and 1,3,4-Oxadiazole Derivatives

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