Synthesis, in vitro and in vivo evaluation of 3-arylisoquinolinamines as potent antitumor agents

Yang, Suhui; Van, Hue Thi My; Le, Thanh Nguyen; Khadka, Daulat Bikram; Cho, Suk Hee; Lee, Kyung‐Tae; Chung, Hwa‐Jin; Lee, Sang Kook; Ahn, Changwoo; Lee, Young Bok; Cho, Won‐Jea

doi:10.1016/j.bmcl.2010.06.132

Cited by 27 publications

(6 citation statements)

References 17 publications

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“…After establishing the reaction with sulfur nucleophiles, we became interested in exploring the scope of chemistry with nitrogen nucleophiles such as amines (primary and secondary amines) due to their prevalence in medicinal chemistry . We selected morpholine (a secondary amine) as the nucleophile for the optimization of the reaction conditions (Table ).…”

Section: Resultsmentioning

confidence: 99%

Pd-Catalyzed One-Pot Stepwise Synthesis of Benzo[b][1,6]naphthyridines from 2-Chloroquinoline-3-carbonitriles Using Sulfur and Amines As Nucleophiles

2017

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A palladium-catalyzed one-pot stepwise coupling-annulation reaction of 2-chloroqunoline-3-carbonitriles enabled the direct synthesis of sulfur-substituted benzo[b][1,6]naphthyridines via multiple bond formation. The reaction provided an unusual mode for cyclization as sodium sulfide, a soft nucleophile, preferred to attack on the carbon of the nitrile group rather than on the C-C triple bond. The developed chemistry was extended with the secondary amines as nucleophiles to afford nitrogen-substituted benzo[b][1,6]naphythyridines while primary amines afforded hydroamination products . The hydromination products were transformed to benzo[b][1,6]naphthyridones via a base-mediated cyclization reaction. The developed protocol features inexpensive and easily synthesizable starting materials, easy operations, and a high efficiency and tolerance to a broad range of substrates.

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Section: Resultsmentioning

confidence: 99%

Pd-Catalyzed One-Pot Stepwise Synthesis of Benzo[b][1,6]naphthyridines from 2-Chloroquinoline-3-carbonitriles Using Sulfur and Amines As Nucleophiles

2017

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“…Isoquinolone derivatives were synthesized as described previously [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. The structure of newly synthesized compounds 7– 10 and 21 was confirmed by 300 MHz (Varian Unity Plus 300 MHz; Varian Inc., Palo Alto, CA, USA) and 400 MHz (Bruker Ascend 400 MHz; Bruker Daltonik, Bremen, Germany) nuclear magnetic resonance (NMR) spectrometry.…”

Section: Methodsmentioning

confidence: 99%

“…These products were characterized by 1 H NMR (Supplementary Figures S1 to S5). The remaining compounds, 4, 5, 6, 11, 12, 20, and 23, were also synthesized according to Scheme 1 and our previous reports [15][16][17][18][19].…”

Section: Synthesis Of Isoquinolone Derivativesmentioning

confidence: 99%

“…For an in depth SAR analysis, we focused on synthesizing additional dimethoxy derivatives of phenylisoquinolone, starting from compound 1 (Table 2). The ethyl group at the 2′ position of R 2 in compound 1 was replaced by ethylene (18) and hydroxyethyl (19) groups. As expected, compound 18 had properties very similar to those of compound 1, i.e., it was active but highly toxic, with a CC50 value of 40.3 µM.…”

Section: Structure-activity Relationship: Dimethoxy Isoquinolone Derivativesmentioning

confidence: 99%

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Antiviral Activity of Isoquinolone Derivatives against Influenza Viruses and Their Cytotoxicity

Jang

Han

et al. 2021

Pharmaceuticals

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Influenza viruses are one of the major causative agents for human respiratory infections. Currently, vaccines and antivirals approved for preventing and treating viral infections are available. However, limited protection efficacy and frequent emergence of drug-resistant viruses stand for a need for the development of antivirals with different chemical skeletons from existing drugs. Screening of a chemical library identified an isoquinolone compound (1) as a hit with 50% effective concentrations (EC50s) between 0.2 and 0.6 µM against the influenza A and B viruses. However, it exhibited severe cytotoxic effects with a 50% cytotoxic concentration (CC50) of 39.0 µM in canine kidney epithelial cells. To address this cytotoxic issue, we synthesized an additional 22 chemical derivatives. Through structure-activity, as well as structure-cytotoxicity relationship studies, we discovered compound 21 that has higher EC50 values ranging from 9.9 to 18.5 µM, but greatly alleviated cytotoxicity with a CC50 value over 300 µM. Mode-of-action and cell type-dependent antiviral experiments indicated that it targets viral polymerase activity and functions also in human cells. Here, we present a new class of viral polymerase inhibitors with a core skeleton of isoquinolone, of which antiviral activity could be better improved through following design and synthesis of its derivatives for drug development.

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“…Finally, we found that trifluoroacetic acid was useful to remove the PMB group on the C-1 position to afford the desired 3-aryl-1-isoquinolinamines 6 in moderate yield as shown in Scheme 1. The free amines were then treated with concentrated HCl in acetone to give the HCl salt forms of the amines 6 [9].…”

Section: Chemistrymentioning

confidence: 99%

Development of 3-aryl-1-isoquinolinamines as potent antitumor agents based on CoMFA

Yang

Van

et al. 2010

European Journal of Medicinal Chemistry

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Synthesis, in vitro and in vivo evaluation of 3-arylisoquinolinamines as potent antitumor agents

Cited by 27 publications

References 17 publications

Pd-Catalyzed One-Pot Stepwise Synthesis of Benzo[b][1,6]naphthyridines from 2-Chloroquinoline-3-carbonitriles Using Sulfur and Amines As Nucleophiles

Pd-Catalyzed One-Pot Stepwise Synthesis of Benzo[b][1,6]naphthyridines from 2-Chloroquinoline-3-carbonitriles Using Sulfur and Amines As Nucleophiles

Antiviral Activity of Isoquinolone Derivatives against Influenza Viruses and Their Cytotoxicity

Development of 3-aryl-1-isoquinolinamines as potent antitumor agents based on CoMFA

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