Design, synthesis and biological evaluation of novel 2,4-diaminopyrimidine derivatives as potent antitumor agents

Hu, Gang; Wang, Chu; Xin, Xin; Li, Shuaikang; Li, Zefei; Zhao, Yanfang; Gong, Ping

doi:10.1039/c9nj02154j

Cited by 10 publications

(10 citation statements)

References 19 publications

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“…It was established further that the blockade of G2-M phase of cell cycle occurred by accumulation of the contents at S phase due to decrease in mitochondrial membrane potential making 2,4-diaminopyrimidine derivatives potential anticancer agents. 3a (IC 50 = 2.14 to 5.52 μM) and 3b (IC 50 = 1.98 to 4.27 μM) were most potent against the PC-3, A549, MCF-7, and HCT-116 cancer cell lines due to the variation of substitution on aromatic ring and terminal aniline on the pyrimidine moiety [6]. The induction of apoptosis was observed for cancer cell line K562 by novel anilino substituted pyrimidine sulfonamides.…”

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confidence: 96%

Pyrimidine: a review on anticancer activity with key emphasis on SAR

2021

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Background Cancer is a global health challenge, it impacts the quality of life and its treatment is associated with several side effects. Resistance of the cancer cells to the existing drugs has led to search for novel anticancer agents. Pyrimidine, a privileged scaffold, is part of living organisms and plays vital role in various biological procedures as well as in cancer pathogenesis. Due to resemblance in structure with the nucleotide base pair of DNA and RNA, it is recognized as valuable compound in the treatment of cancer. Main text Many novel pyrimidine derivatives have been designed and developed for their anticancer activity in the last few years. The present review aims to focus on the structure activity relationship (SAR) of pyrimidine derivatives as anticancer agent from the last decade. Conclusion This review intends to assist in the development of more potent and efficacious anticancer drugs with pyrimidine scaffold. Graphical abstract

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confidence: 96%

Pyrimidine: a review on anticancer activity with key emphasis on SAR

2021

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“…Polyamino-pyrimidines play a very important role in biological and pharmaceutical chemistry. 2,4-diamino-pyrimidine derivatives as potential antimalarial agents [17], SNSR4 antagonists [47], antitumor agents [48] and caspase-1 inhibitors [49]. This report focused on the method development for the synthesis of the latter class of compounds.…”

Section: Synthesis Of N-24-disubstitited Pyrimidinesmentioning

confidence: 99%

“…The first step was accomplished by reacting the 2,4-dichloro-5-fluoropyrimide with the mono-BOCylated metadiaminobenzene (46). The selective displacement of chloride at C4 by tert-butyl N-(3aminophenyl) carbamate (46) renders high ratio of regioselective synthon and yielded the intermediate (47), which was reacted with the second substrate at C2 by 4-(2methoxyethoxy)aniline (48). Due to the presence of tert-BOC (acid cleavable) as protecting group the two steps have be conducted under basic conditions.…”

Section: Pazopanib One Drug Different Synthetic Routesmentioning

confidence: 99%

Synthetic Approaches for Pharmacologically Active Decorated Six-Membered Diazines

Najajreh,

Awwad Khoury

2023

Strategies for the Synthesis of Heterocycles and Their Applications

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Diazine alkaloid (pyridazine, pyrimidine and pyrazine) scaffold, a widespread two-nitrogen containing compounds in nature (DNA, RNA, flavors, and fragrances), constitutes a central building block for wide range of pharmacological applications. Diazines are reported to exhibit antimetabolite (antifolate and), anticancer, antibacterial, antiallergic, tyrosine kinase, antimicrobial, calcium channel antagonistic, anti-inflammatory, analgesic, antihypertensive, antileishmanial, antituberculostatic, anticonvulsant, diuretic and potassium-sparing, to antiaggressive activities. Pyridazine (1,2-diazine), pyrimidine (1,3-diazine) and pyrazine (1,4-diazine) are found as mono-systems, fused or annulated in pharmaceutical, agrochemical or materials. These six-membered heterocyclic aromatic moieties defined as privileged scaffolds constitute diverse chemical structures and as such hold substantial interest for organic, medicinal and biological chemists. This chapter will focus on elaboration of the different synthetic approaches applied in preparing pharmacologically active decorated diazines with special care on pyrimidines (non-fused substituted forms) that are endowed with clinical applications. Synthetic approaches applied in preparing selected FDA approved drugs with pyrimidine as a central unit bearing different substituents will be intensively explored. Special attention will be given to novel synthetic methodologies that served molecules with improved druglikeness and ADME-Tox properties.

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“…synthesized novel 2,4-diaminopyrimidine derivatives possessing triazolopiperazine scaffolds 126 ( Fig. 28 ) and screened them against a panel of kinases (CDK4, JAK2, VEGFR2, PI3Kα and FLT3) and four tumor cell lines [ 120 ]. Among them, compound 126k exhibited most potent antitumor activities against A549, HCT-116, PC-3 and MCF-7 cell lines with IC 50 values of 2.14 μM, 3.59 μM, 5.52 μM and 3.69 μM, respectively.…”

Section: Biological Activities Of 124-triazole Derivativesmentioning

confidence: 99%

An insight on medicinal attributes of 1,2,4-triazoles

Aggarwal

Sumran²

2020

European Journal of Medicinal Chemistry

196

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The present review aims to summarize the pharmacological profile of 1,2,4-triazole, one of the emerging privileged scaffold, as antifungal, antibacterial, anticancer, anticonvulsant, antituberculosis, antiviral, antiparasitic, analgesic and anti-inflammatory agents, etc. along with structure-activity relationship. The comprehensive compilation of work carried out in the last decade on 1,2,4-triazole nucleus will provide inevitable scope for researchers for the advancement of novel potential drug candidates having better efficacy and selectivity.

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Design, synthesis and biological evaluation of novel 2,4-diaminopyrimidine derivatives as potent antitumor agents

Abstract: Two series of 2-aminopyrimidine derivatives possessing triazolopiperazine or 1,4,8-triazaspiro[4.5]decan-3-one scaffolds were designed, synthesized and evaluated for their biological activity.

Cited by 10 publications

References 19 publications

Pyrimidine: a review on anticancer activity with key emphasis on SAR

Pyrimidine: a review on anticancer activity with key emphasis on SAR

Synthetic Approaches for Pharmacologically Active Decorated Six-Membered Diazines

An insight on medicinal attributes of 1,2,4-triazoles

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