Synthesis and Cytokine Modulation Properties of Pyrrolo[2,3-<i>d</i>]-4-pyrimidone Nucleosides

Wang, Guangyi; Tam, Robert C.; Gunić, Esmir; Du, Jinfa; Bard, Josie; Pai, Bharati

doi:10.1021/jm000035+

Cited by 23 publications

(12 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further investigation of 281c showed that it also stimulates IL-5 (type 2) and inhibits IL-2 and tumor necrosis factor alpha (TNFα) (type 1). 114 Seela and co-workers demonstrated that aminopyrrolo[2,3d]pyrimidines 288 and 289 (Scheme 57) are strongly fluorescent nucleosides. To investigate the influence of substituents on the alkyne, several compounds 289 were synthesized.…”

Section: Nucleosidesmentioning

confidence: 99%

See 1 more Smart Citation

Synthetic Entries to and Biological Activity of Pyrrolopyrimidines

et al. 2015

View full text Add to dashboard Cite

This review summarizes recent literature (2000-2015) on the synthesis and pharmaceutical properties of pyrrolopyrimidines. These modified pyrimidine bases, fused to a pyrrole ring, and their corresponding nucleosides display a broad applicability in medicinal chemistry. This overview is divided into three main sections, according to the respective isomers: pyrrolo[2,3-d]pyrimidines, pyrrolo[3,2-d]pyrimidines, and pyrrolo[3,4-d]pyrimidines. Each section contains a description of common retro-synthetic strategies, with particular attention for newly reported synthetic entries to the scaffold. Next, the synthetic strategies and the ways in which the scaffolds can be further modified are exemplified according to the biological properties of the obtained products.

show abstract

Section: Nucleosidesmentioning

confidence: 99%

“…Compounds 281d and 283c , on the other hand, behave as IL-4 stimulants but not as IFNγ suppressants. Further investigation of 281c showed that it also stimulates IL-5 (type 2) and inhibits IL-2 and tumor necrosis factor alpha (TNFα) (type 1) …”

Section: Pyrrolo[23-d]pyrimidinementioning

confidence: 99%

Synthetic Entries to and Biological Activity of Pyrrolopyrimidines

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Considering the identical chemical properties of L-and D-nucleosides and their precursors, the protocols developed for the 7-deazapurine D-nucleoside synthesis can be also employed for the preparation of the L-enantiomers. L-Toyocamycin 161 was prepared by the same procedure as used for D-toyocamycin described by Bobek et al [63] except that the L-ribofuranose 158 was employed [101]. The Scheme (42).…”

Section: -Deazapurine β-L-ribonucleosidesmentioning

confidence: 99%

Progress in 7-Deazapurine - Pyrrolo[2,3-d]pyrimidine - Ribonucleoside Synthesis

Seela¹,

Peng

2006

CTMC

View full text Add to dashboard Cite

This review reports on the synthesis of 7-deazapurine ribonucleosides, including C-nucleosides, 2'-C-methyl derivatives and L-enantiomers. It covers the various aspects of convergent nucleoside synthesis such as the Schiff base procedure, the fusion reaction, the metal salt procedures, the Silyl-Hilbert-Johnson reaction, and the nucleobase anion glycosylation. The review discusses the scope and limitations of glycosylation reactions performed on 7-deazapurines. Peracylated ribose derivatives were now employed in the glycosylation, which overcome difficulties reported earlier.

show abstract

“…1b The use of the Vilsmeyer salt for anomeric chlorination 17 is a new, convenient method that proved very useful for the preparation of certain 1-chlororibosyl analogues. 6a The triacetate 10 was prepared from 8a by modification of a known method 18 and was used for the glycosylation of a pyrazolopyrimidine base.…”

Section: Chemistrymentioning

confidence: 99%

“…Stirring was continued at room temperature for 8 h, the solvent evaporated, and then the residue dissolved in a mixture of ether and water. The layers were separated and the ether layer washed with water and brine, dried (MgSO 4), and evaporated to provide 6.2 g (83%) of 5-deoxyribose-1,2,3-triacetate 18 (10) as a mixture of 1-R and 1-β isomers which were used without further purification: TLC Rf ) 0.73 (major) and 0.65 (minor) (1:1 hexane/EtOAc).…”

Section: -Amino-1-(5-deoxy-23-o-isopropylidenyl-β-d-ribofuranosyl)-3-...mentioning

confidence: 99%

Adenosine Kinase Inhibitors. 6. Synthesis, Water Solubility, and Antinociceptive Activity of 5-Phenyl-7-(5-deoxy-β-d-ribofuranosyl)pyrrolo[2,3-d]pyrimidines Substituted at C4 with Glycinamides and Related Compounds

et al. 2005

View full text Add to dashboard Cite

4-(Phenylamino)-5-phenyl-7-(5-deoxy-beta-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine 1 and related compounds known as "diaryltubercidin" analogues are potent inhibitors of adenosine kinase (AK) and are orally active in animal models of pain such as the rat formalin paw model (GP3269 ED50= 6.4 mg/kg). However, the utility of this compound class is limited by poor water solubility that can be attributed to the high energy of crystallization caused by stacking of the parallel C4 and C5 aryl rings in the solid state (compound 1 and GP3269 each with pH 7.4 solubility <0.05 microg/mL). To increase water solubility, the hydrophobic C4-phenylamino substituent was replaced with a more hydrophilic group, glycinamide. This modification resulted in improved water solubility while retaining AK inhibition potency. Analogues were studied where changes in the glycinamide moiety were combined with changes to the base and sugar. A lead compound, 4-N-(N-cyclopropylcarbamoylmethyl)amino-5-phenyl-7-(5-deoxy-beta-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine (16c) (IC50= 3 nM and water solubility = 32 +/- 9 microg/mL at pH 7.4), was further characterized in biological assays. Compound 16c exhibited strong oral efficacy in the rat formalin paw model (ED50 of 2.5 mg/kg). In the most advanced assay, 16c was found to inhibit bradykinin-induced licking in marmoset monkeys with an ED50 estimated at 0.9 mg/kg without producing evidence of side effects such as ataxia, sedation, and emesis at this dose. However, lethal toxicity in the rat formalin paw model occurred with high doses of 16c, and further work on this series was discontinued.

show abstract

Synthesis and Cytokine Modulation Properties of Pyrrolo[2,3-d]-4-pyrimidone Nucleosides

Cited by 23 publications

References 37 publications

Synthetic Entries to and Biological Activity of Pyrrolopyrimidines

Synthetic Entries to and Biological Activity of Pyrrolopyrimidines

Progress in 7-Deazapurine - Pyrrolo[2,3-d]pyrimidine - Ribonucleoside Synthesis

Adenosine Kinase Inhibitors. 6. Synthesis, Water Solubility, and Antinociceptive Activity of 5-Phenyl-7-(5-deoxy-β-d-ribofuranosyl)pyrrolo[2,3-d]pyrimidines Substituted at C4 with Glycinamides and Related Compounds

Contact Info

Product

Resources

About