Dataset Information

Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent c-Met/ALK Multikinase Inhibitory Activities.

ABSTRACT: By repurposing a typical dopamine D1/D5 receptor agonist motif, C1-substituted-N3-benzazepine or benzazecine, into the classical RTK inhibitor 2,4-diaminopyrimidine skeleton, a series of new 2,4-diarylaminopyrimidine analogues (DAAPalogues) were developed. Compounds 7 and 8a were identified possessing high potency against both c-Met and ALK kinases. Compound 8a displayed appreciable antitumor efficacy at the dose of 1 mg/kg in the ALK-driven BF3/EML4-ALK xenograft mice model.

SUBMITTER: Liu Z

PROVIDER: S-EPMC4027579 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent c-Met/ALK Multikinase Inhibitory Activities.

Liu Zhiqing Z Ai Jing J Peng Xia X Song Zilan Z Wu Kui K Zhang Jing J Yao Qizheng Q Chen Yi Y Ji Yinchun Y Yang Yanhong Y Geng Meiyu M Zhang Ao A

ACS medicinal chemistry letters 20140208 4

By repurposing a typical dopamine D1/D5 receptor agonist motif, C1-substituted-N3-benzazepine or benzazecine, into the classical RTK inhibitor 2,4-diaminopyrimidine skeleton, a series of new 2,4-diarylaminopyrimidine analogues (DAAPalogues) were developed. Compounds 7 and 8a were identified possessing high potency against both c-Met and ALK kinases. Compound 8a displayed appreciable antitumor efficacy at the dose of 1 mg/kg in the ALK-driven BF3/EML4-ALK xenograft mice model. ...[more]

PMID: 24900831

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Project description:Nucleoside analogues are among the most successful bioactive classes of druglike compounds in pharmaceutical chemistry as they are well-known for their numerous effective bioactivities in humans, especially as antiviral and anticancer agents. Coronavirus disease 2019 (COVID-19) is still untreatable, with its causing virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continuing to wreak havoc on the ground everywhere. This complicated international situation urged all concerned scientists, including medicinal chemists and drug discoverers, to search for a potent anti-COVID-19 drug. Cordycepin (3'-deoxyadenosine) is a known natural adenosine analogue of fungal origin, which could also be synthetically produced. This bioactive phytochemical compound is characterized by several proven strong pharmacological actions that may effectively contribute to the comprehensive treatment of COVID-19, with the antiviral activities being the leading ones. Some new studies predicted the possible inhibitory affinities of cordycepin against the principal SARS-CoV-2 protein targets (e.g., SARS-CoV-2 spike (S) protein, main protease (Mpro) enzyme, and RNA-dependent RNA polymerase (RdRp) enzyme) based on the computational approach. Interestingly, the current research showed, for the first time, that cordycepin is able to potently inhibit the multiplication of the new resistant strains of SARS-CoV-2 with a very minute in vitro anti-SARS-CoV-2 EC50 of about 2 μM, edging over both remdesivir and its active metabolite GS-441524. The ideal pharmacophoric features of the cordycepin molecule render it a typical inhibitor of SARS-CoV-2 replication, with its flexible structure open for most types of derivatization in the future. Briefly, the current findings further support and suggest the repurposing possibility of cordycepin against COVID-19 and greatly encourage us to confidently and rapidly begin its preclinical/clinical evaluations for the comprehensive treatment of COVID-19.

Dataset Information

Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent c-Met/ALK Multikinase Inhibitory Activities.

Publications

Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent c-Met/ALK Multikinase Inhibitory Activities.

Similar Datasets

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