Synthesis and biological evaluation of 6H-pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5(6H)-ones as antimitotic agents and inhibitors of tubulin polymerization

Meng, Tao; Wang, Wei; Zhang, Zhixiang; Ma, Li; Zhang, Yongliang; Miao, Ze‐Hong; Shen, Jingkang

doi:10.1016/j.bmc.2013.12.004

Cited by 25 publications

(4 citation statements)

References 22 publications

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“…The best compound is built around the para-substituted phenyl-imidazo-[1,2-a]pyrazine scaffold and a small library of 29 compounds was synthesized for SAR optimizing, resulting in lead compound 102 (Scheme 40). In continuation of Shen et al [206] another HeLa cytotoxic series of 6H-pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5(6H)-ones was reported by the same research group [87] In this report the tetracyclic profile was maintained, however the alkynyl moiety was replaced with a carboxylic acid (phthaldehydic acid) which direct reacts with the secondary amine, formed in the GBB-3CR (Scheme 41).…”

Section: Similar Imidazo[21-c][124]triazoles Derivatives Were Repomentioning

confidence: 71%

The Groebke‐Blackburn‐Bienaymé Reaction

2019

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Imidazo[1,2‐a]pyridine is a well‐known scaffold in many marketed drugs, such as Zolpidem, Minodronic acid, Miroprofen and DS‐1 and it also serves as a broadly applied pharmacophore in drug discovery. The scaffold revoked a wave of interest when Groebke, Blackburn and Bienaymé reported independently a new three component reaction resulting in compounds with the imidazo[1,2‐a]‐heterocycles as a core structure. During the course of two decades the Groebke Blackburn Bienaymé (GBB‐3CR) reaction has emerged as a very important multicomponent reaction (MCR), resulting in over a hundred patents and a great number of publications in various fields of interest. Now two compounds derived from GBB‐3CR chemistry received FDA approval. To celebrate the first 20 years of GBB‐chemistry, we present an overview of the chemistry of the GBB‐3CR, including an analysis of each of the three starting material classes, solvents and catalysts. Additionally, a list of patents and their applications and a more in‐depth summary of the biological targets that were addressed, including structural biology analysis, is given.

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Section: Similar Imidazo[21-c][124]triazoles Derivatives Were Repomentioning

confidence: 71%

The Groebke‐Blackburn‐Bienaymé Reaction

2019

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“…Both 3,4-dihydroquinolin-2(1 H )-one and sulfonic chloride were chlorosulfonated to obtain intermediate A . Moreover, 3,4,5-trimethoxyaniline and different substituted aldehydes were subjected to the Schiff’s base reaction to obtain different intermediates B [ 21 , 22 , 23 ]. Subsequently, intermediate B was reduced to obtain C .…”

Section: Resultsmentioning

confidence: 99%

“…In addition, the sulfonamide tubulin inhibitor ABT-751 ( Figure 1 ), which also acts on the colchicine site, has strong proliferation inhibitory activity [ 19 ]. Moreover, there are many small molecular compounds with diverse structures, such as quinolinones that target the binding site of colchicine, which show excellent anti-tumor activity and block tumor vasculature in vivo and in vitro, showing good application prospects [ 21 ]. These interesting studies have stimulated our interest, so we envisioned putting these effective fragments together, hoping to obtain a series of tubulin inhibitors ( Figure 2 ).…”

Section: Introductionmentioning

confidence: 99%

Discovery of Novel 3,4-Dihydro-2(1H)-Quinolinone Sulfonamide Derivatives as New Tubulin Polymerization Inhibitors with Anti-Cancer Activity

Gong

2022

Molecules

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In this paper, a small series of novel quinoline sulfonamide derivatives was synthesized, and their structure of the target compounds were confirmed by 1H NMR and MS. The screening of the news target compounds’ in vitro cytotoxic activities against tumor cell lines by the MTT method was performed. Among them, compound D13 (N-(4-methoxybenzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-6-sulfonamide exhibited the strongest inhibitory effect on the proliferation of HeLa (IC50: 1.34 μM), and this value correlated well with the inhibitory activities of the compound against tubulin polymerization (IC50: 6.74 μM). In summary, a new type of quinoline-sulfonamide derivative with tubulin polymerization inhibitory activity was discovered, and it can be used as a lead compound for further modification.

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“…The compounds containing an imidazo[1,2- a ]pyridine (IP) scaffold, such as necopidem, saripidem, and zolpidem, have attracted much attention due to their biological activities . We wonder if we can directly functionalize the C–H bonds in imidazo[1,2- a ]pyridines to obtain a class of hybrid structures of coumarin derivatives through lactonization with CO 2 .…”

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confidence: 99%