The synthesis of 7-deazaguanines as potential inhibitors of guanosine triphosphate cyclohydrolase I

Gibson, Colin L.; Rosa, Salvatore La; Ohta, Kyuji; Boyle, Peter H.; Leurquin, Fabien; Lemaçon, Alexandra; Suckling, Colin J.

doi:10.1016/j.tet.2003.11.030

Cited by 31 publications

(17 citation statements)

References 37 publications

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“…Typically, due to the higher basicity of secondary amines, higher overall yields were obtained when, in a sequential synthesis, first the benzyl amine and second 1-methylpiperazine was coupled. Ether 17 and thioether 18 resulted from the reaction of 4-chloro-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine (17a) with benzyl alcohol, 47 and benzyl mercaptane, 48 respectively. Sodium hydride was needed to deprotonate the alcohol, whereas for thiol activation sodium hydroxide was sufficient.…”

Section: Chemistrymentioning

confidence: 99%

2,4-Diaminopyrimidines as histamine H4 receptor ligands—Scaffold optimization and pharmacological characterization

Sander

Kottke

Tanrıkulu

et al. 2009

Bioorganic & Medicinal Chemistry

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Section: Chemistrymentioning

confidence: 99%

2,4-Diaminopyrimidines as histamine H4 receptor ligands—Scaffold optimization and pharmacological characterization

Sander

Kottke

Tanrıkulu

et al. 2009

Bioorganic & Medicinal Chemistry

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“…Several mechanisms are also involved in their cytotoxic activities as being antifolate inhibitors of dihydrofolate reductases (Gangjee et al, 2008), tyrosine kinase c-Src or Lck inhibitors (Gibson et al, 2004;Hildick and Shaw, 1971), cyclindependent kinase (CDK) inhibitors (Grem, 1990;Schilsky, 1992), or adenosine receptor antagonists (Calderwood et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Antitumor activity of novel pyrrolo[2,3-d]pyrimidin-4-ones

Atapour-Mashhad

Tayarani‐Najaran

Davoodnia

et al. 2011

Drug and Chemical Toxicology

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Pyrrolo[2,3-d]pyrimidine is known to have a broad spectrum of biological activities, including antitumor activity. The cytotoxic properties of six novel pyrrolo[2,3-d]pyrimidin-4-ones in vitro were investigated on four different human cancer cell lines. Meanwhile, the role of apoptosis was explored. Malignant cells were cultured in RPMI medium and incubated with different concentrations. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using DAPI (4'-6-diamidino-2-phenylindole) and propidium iodide staining of DNA fragmentation by flow cytometry (sub-G1 peak). We have identified new analogs as a novel class of antiproliferative agents by a cell-based screening method. All compounds inhibited the growth of malignant cells in a dose-dependent manner. The IC₅₀ of compounds 4 and 5 as the two most potent analogs was determined as 122.4 and 106.7 μM in HeLa cells, respectively. Compounds 4 and 5 induced a sub-G1 peak in the flow-cytometry histogram of treated cells, compared to control, indicating that apoptotic cell death is involved in compound 4- and 5-induced toxicity. In conclusion, compounds 4 and 5 exert cytotoxic effects in different cancer cell lines in which apoptosis plays an important role. Thus, compounds 4 and 5 could be considered as potential chemotherapeutic agents.

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“…7b -e compounds were obtained by the reaction of aldehyde 5, with appropriate amines (Scheme 1) followed by the removal of trityl protection [37] were purified by recrystallization from the ethanol. Purification on a silica-gel column was performed before recrystallization, only if it was found necessary.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Activity of Novel 5‐Substituted Pyrrolo[2,3‐d]pyrimidine Analogues as pp60^c‐Src Tyrosine Kinase Inhibitors

Ölgen¹,

Isgor

Çoban

2008

Archiv der Pharmazie

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Therapy with receptor tyrosine kinase inhibitors provides an improved treatment option in a number of diseases such as cancer, myocardial infection, osteoporosis, stroke, and neurodegeneration. We have designed, synthesized, and evaluated a series of novel 2-amino-5-[(benzyl)imino]methyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidine-4-one 7a and 2-amino-5-[(substituted-benzyl)imino]methyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidine-4-one 7b-e derivatives as potential tyrosine kinase inhibitors. These compounds were synthesized by condensation reaction using 2-tritylamino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbaldehyde 5 and appropriate benzylamines followed by detritylation. Compounds were evaluated for their inhibitory activity toward tyrosine phosphorylation for the pp60c-Src tyrosine kinase. Compounds 7a, 7d, and 7e demonstrated potent inhibitory activities against pp60c-Src tyrosine kinase with IC50 values of 13.9, 34.5, and 78.4 microM, respectively. Dihalogenated compounds 7d and 7e have 3 to 7-times lower IC50 values than that of the parent compound 7a.

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The synthesis of 7-deazaguanines as potential inhibitors of guanosine triphosphate cyclohydrolase I

Cited by 31 publications

References 37 publications

2,4-Diaminopyrimidines as histamine H4 receptor ligands—Scaffold optimization and pharmacological characterization

2,4-Diaminopyrimidines as histamine H4 receptor ligands—Scaffold optimization and pharmacological characterization

Antitumor activity of novel pyrrolo[2,3-d]pyrimidin-4-ones

Synthesis and Activity of Novel 5‐Substituted Pyrrolo[2,3‐d]pyrimidine Analogues as pp60^c‐Src Tyrosine Kinase Inhibitors

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The synthesis of 7-deazaguanines as potential inhibitors of guanosine triphosphate cyclohydrolase I

Cited by 31 publications

References 37 publications

2,4-Diaminopyrimidines as histamine H4 receptor ligands—Scaffold optimization and pharmacological characterization

2,4-Diaminopyrimidines as histamine H4 receptor ligands—Scaffold optimization and pharmacological characterization

Antitumor activity of novel pyrrolo[2,3-d]pyrimidin-4-ones

Synthesis and Activity of Novel 5‐Substituted Pyrrolo[2,3‐d]pyrimidine Analogues as pp60c‐Src Tyrosine Kinase Inhibitors

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Synthesis and Activity of Novel 5‐Substituted Pyrrolo[2,3‐d]pyrimidine Analogues as pp60^c‐Src Tyrosine Kinase Inhibitors