The 3-D conformational shape of N-naphthyl-cyclopenta[d]pyrimidines affects their potency as microtubule targeting agents and their antitumor activity

Xiang, Weidong; Quadery, Tasdique M.; Hamel, Ernest; Luckett-Chastain, Lerin R.; Ihnat, Michael A.; Mooberry, Susan L.; Gangjee, Aleem

doi:10.1016/j.bmc.2020.115887

Cited by 5 publications

(2 citation statements)

References 34 publications

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“…The monomethylated aniline, 5-methoxy- N -methylnaphthalen-2-amine ( 26 ), was synthesized over three steps from 6-aminonaphthalen-1-ol ( 23 ) ( Scheme 2 ) [ 48 ]. Boc protection of 23 in THF at r.t. yielded tert-butyl(5-hydroxyaphthalen-2-yl)carbamate ( 24 ) in 84% yield, followed by methylation with methyl iodide and sodium hydride to provide 25 .…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines as Microtubule Targeting Agents

et al. 2022

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A series of eleven 4-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines were designed and synthesized and their biological activities were evaluated. Synthesis involved the Gewald reaction to synthesize ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ring, and SNAr reactions. Compound 4 was 1.6- and ~7-fold more potent than the lead compound 1 in cell proliferation and microtubule depolymerization assays, respectively. Compounds 4, 5 and 7 showed the most potent antiproliferative effects (IC50 values < 40 nM), while compounds 6, 8, 10, 12 and 13 had lower antiproliferative potencies (IC50 values of 53–125 nM). Additionally, compounds 4–8, 10 and 12–13 circumvented Pgp and βIII-tubulin mediated drug resistance, mechanisms that diminish the clinical efficacy of paclitaxel (PTX). In the NCI-60 cell line panel, compound 4 exhibited an average GI50 of ~10 nM in the 40 most sensitive cell lines. Compound 4 demonstrated statistically significant antitumor effects in a murine MDA-MB-435 xenograft model.

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Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines as Microtubule Targeting Agents

et al. 2022

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“…7 Therefore, it is used as a key intermediate to synthesize pyridines, pyrimidines, thiophenes, pyridazines, pyrazoles, and their analogs. [8][9][10] The biological significance of these compounds arises from their various pharmaceutical activities in neurological disorders, 11 as receptor antagonists, 12,13 kinase inhibitors, 14 tubulin inhibitors, 15 antitumor, 16 and for anticancer activity. 17 In view of the aforementioned facts, we have reported the synthesis of some new substituted pyrimidines and their potential biological activity using malonitrile dimmer as precursor.…”

Section: Introductionmentioning

confidence: 99%

Efficient access to some new pyrimidine derivatives and their antimicrobial evaluation

El-mahdy

Farouk

2021

Journal of Heterocyclic Chem

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1-[4-(3-Hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl]eth anone (1) was used as a precursor for heterocyclic synthesis. Condensation of compound 1 with monochloroacetic acid and benzaldehyde gave thiazolopyrimidine 2 which in turn underwent cyclization with malononitrile dimmer to afford malononitrile derivative 3. Also, the reaction of compound 1 with benzaldehyde under a basic condition produced chalcone 4. Chalcone 4 can be used as a key intermediate for further preparation of heterocyclic compounds. In addition, compound 1 was allowed to react with malononitrile dimmer and/or ethyl chloroacetate to give pyrimidines 8 and 9, respectively.Alkylation of compound 8 with ethyl chloroacetate afforded S-alkylated product 10 which was treated with hydrazine hydrate to yield the hydrazino derivative 11. Alternative synthesis of compound 10 was taken place through reaction of compound 9 with malononitrile dimmer. The biological activity of the synthesized compounds was investigated. Compounds 1, 4, 5, and 8 recorded high activities against Gram positive bacteria (S. aureus). Structures of the new synthesized compounds were elucidated by elemental analysis and spectral data.

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Novel pyrazolo[4,3-d]pyrimidine microtubule targeting agents (MTAs): Synthesis, structure–activity relationship, in vitro and in vivo evaluation as antitumor agents

Islam

Quadery

Bai

et al. 2021

Bioorganic & Medicinal Chemistry Letters

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The 3-D conformational shape of N-naphthyl-cyclopenta[d]pyrimidines affects their potency as microtubule targeting agents and their antitumor activity

Cited by 5 publications

References 34 publications

Design, Synthesis, and Biological Evaluation of 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines as Microtubule Targeting Agents

Design, Synthesis, and Biological Evaluation of 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines as Microtubule Targeting Agents

Efficient access to some new pyrimidine derivatives and their antimicrobial evaluation

Novel pyrazolo[4,3-d]pyrimidine microtubule targeting agents (MTAs): Synthesis, structure–activity relationship, in vitro and in vivo evaluation as antitumor agents

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