Pyrrolo[2,3-d]Pyrimidine Nucleosides: Synthesis and Antitumor Activity of 7-Substituted 7-Deaza-2′-Deoxyadenosines

Seela, Frank; Zulauf, Matthias; Chen, Shih-Fong

doi:10.1080/15257770008033006

Cited by 7 publications

(7 citation statements)

References 32 publications

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“…In both cases, the duplex stability was only marginally affected. The same result has been found for the corresponding oligomer duplex containing 8-aza-7-deaza-2'-deoxyadenosine (c7z8A, = A: ; 16.28, Table 6 ) [35].…”

Section: S-d(a-a-a-za-a-za-a-za-a-a-a-a)-y (33)supporting

confidence: 82%

8‐Azaadenosine and Its 2′‐Deoxyribonucleoside: Synthesis and oligonucleotide base‐pair stability

Seela

Münster

Lüchner

et al. 1998

Helvetica Chimica Acta

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The synthesis of 8-azaadenosine (la; z8A) has been performed by SnCI,-catalyzed glycosylation of X-azaadeninc (4) with I ,2,3.5-tetra-O-acetyl-/7-~-rihofuranose (5). followed by the separation of the regioisomers 6 and 7 and subsequent deacetylation. The ribonucleoside la as well as its 2.'-deoxy derivative Ib (z8AA,) wcrc converted into oligonucleotide building blocks ~ the phosphonate 2 as well as the phosphoramidites 3 and 19. They were uscd to preparc the oligoribonucleotide (z*A-U), and oligodeoxyribonucleotides. The T, values and the thermodynamic data of duplex formation of the modified duplexes showed no significant changes compared to those containing A, or A residues. This indicates that the stereoelectronic effect of the 8-azaadenine base which was found for the monomeric nucleoside has only a minor influence on the duplex stability.

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Section: S-d(a-a-a-za-a-za-a-za-a-a-a-a)-y (33)supporting

confidence: 82%

8‐Azaadenosine and Its 2′‐Deoxyribonucleoside: Synthesis and oligonucleotide base‐pair stability

Seela

Münster

Lüchner

et al. 1998

Helvetica Chimica Acta

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“…Compounds 12bα , 12c , and 12d show good selectivity toward cancer cell lines and are nontoxic to fibroblasts as compared to toxic tubercidin. These rather surprising results are interesting because in the previous examples of tubercidin, 37 7-substituted 8 or fused deazapurine nucleosides, 13 , 14 the ribonucleosides were always more active whereas 2′-deoxytubercidin 38 was inactive. This suggests that the mode of action of this class of nucleosides will probably be different from the previously reported tubercidin or tricyclic thieno-, furo-, and pyrrolo-fused 7-deazapurine ribonucleosides that become phosphorylated and incorporated to DNA causing DNA damage and apoptosis.…”

Section: Resultsmentioning

confidence: 78%

“…Table 3 summarizes the cytotoxic activities of compounds in the MTS assay in comparison with known parent compounds: strongly and nonselectively cytotoxic tubercidin (7-deazaadenosine) 37 and 2′-deoxytubercidin (2′-deoxy-7-deazaadenosine). 38 …”

Section: Resultsmentioning

confidence: 99%

Synthesis of Polycyclic Hetero-Fused 7-Deazapurine Heterocycles and Nucleosides through C–H Dibenzothiophenation and Negishi Coupling

et al. 2022

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A new approach for synthesizing polycyclic heterofused 7-deazapurine heterocycles and the corresponding nucleosides was developed based on C–H functionalization of diverse (hetero)aromatics with dibenzothiophene-S-oxide followed by the Negishi cross-cooupling with bis(4,6-dichloropyrimidin-5-yl)zinc. This cross-coupling afforded a series of (het)aryl-pyrimidines that were converted to fused deazapurine heterocycles through azidation and thermal cyclization. The fused heterocycles were glycosylated to the corresponding 2′-deoxy- and ribonucleosides, and a series of derivatives were prepared by nucleophilic substitutions at position 4. Four series of new polycyclic thieno-fused 7-deazapurine nucleosides were synthesized using this strategy. Most of the deoxyribonucleosides showed good cytotoxic activity, especially for the CCRF-CEM cell line. Phenyl- and thienyl-substituted thieno-fused 7-deazapurine nucleosides were fluorescent, and the former one was converted to 2′-deoxyribonucleoside triphosphate for enzymatic synthesis of labeled oligonucleotides.

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“…Even though many sugar‐modified analogs of naturally occurring 7‐deazapurine nucleosides (e.g. deoxynucleosides, ara ‐, and xylo ‐diastereomers) were synthesized, modification of the sugar moiety typically led to a decrease in cytotoxic activity . Therefore, nucleobase‐modified derivatives and compounds combining nucleobase and sugar modifications attracted more attention.…”

Section: Cytotoxic Nucleosidesmentioning

confidence: 99%

“…deoxynucleosides, ara-, and xylo-diastereomers) were synthesized, modification of the sugar moiety typically led to a decrease in cytotoxic activity. 13,14,[30][31][32][33] Therefore, nucleobase-modified derivatives and compounds combining nucleobase and sugar modifications attracted more attention. 7-Halogenated tubercidins (6a-d) 34 differ in their cytotoxic activity depending on the nature of the halogen (Fig.…”

Section: Synthetic Nucleosides With C7 and C8 Substituentsmentioning

confidence: 99%

Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides

Perlíková

Hocek

2017

Medicinal Research Reviews

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Abstract7‐Deazapurine (pyrrolo[2,3‐d]pyrimidine) nucleosides are important analogues of biogenic purine nucleosides with diverse biological activities. Replacement of the N7 atom with a carbon atom makes the five‐membered ring more electron rich and brings a possibility of attaching additional substituents at the C7 position. This often leads to derivatives with increased base‐pairing in DNA or RNA or better binding to enzymes. Several types of 7‐deazapurine nucleosides with potent cytostatic or cytotoxic effects have been identified. The most promising are 7‐hetaryl‐7‐deazaadenosines, which are activated in cancer cells by phosphorylation and get incorporated both to RNA (causing inhibition of proteosynthesis) and to DNA (causing DNA damage). Mechanism of action of other types of cytostatic nucleosides, 6‐hetaryl‐7‐deazapurine and thieno‐fused deazapurine ribonucleosides, is not yet known. Many 7‐deazaadenosine derivatives are potent inhibitors of adenosine kinases. Many types of sugar‐modified derivatives of 7‐deazapurine nucleosides are also strong antivirals. Most important are 2′‐C‐methylribo‐ or 2′‐C‐methyl‐2′‐fluororibonucleosides with anti‐HCV activities (several compounds underwent clinical trials). Some underexplored areas of potential interest are also outlined.

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Pyrrolo[2,3-d]Pyrimidine Nucleosides: Synthesis and Antitumor Activity of 7-Substituted 7-Deaza-2′-Deoxyadenosines

Cited by 7 publications

References 32 publications

8‐Azaadenosine and Its 2′‐Deoxyribonucleoside: Synthesis and oligonucleotide base‐pair stability

8‐Azaadenosine and Its 2′‐Deoxyribonucleoside: Synthesis and oligonucleotide base‐pair stability

Synthesis of Polycyclic Hetero-Fused 7-Deazapurine Heterocycles and Nucleosides through C–H Dibenzothiophenation and Negishi Coupling

Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides

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