14937-72-5Relevant articles and documents
Mitsunobu coupling of nucleobases and alcohols: An efficient, practical synthesis for novel nonsugar carbon nucleosides
Lu, Weibing,Sengupta, Sujata,Petersen, Jeffrey L.,Akhmedov, Novruz G.,Shi, Xiaodong
, p. 5012 - 5015 (2007)
(Chemical Equation Presented) A simple facile synthesis of substituted purine derivatives has been developed by using Mitsunobu conditions for an alcohol and a respective nucleobase. A wide range of alcohols produces good to excellent yield (>90%). The resulting purine analogues show good regioselectivity with N-9 substitution as the dominant products in most of the cases. Application of diastereospecific alcohols reveals a complete inversion of the carbon stereogenic center giving a single diastereomer. More than two dozen novel nucleobase derivatives have been prepared in high yield.
The discovery of purine-based agents targeting triple-negative breast cancer and the αB-crystallin/VEGF protein–protein interaction
Fosu-Mensah, Nelly A.,Jiang, Wen,Brancale, Andrea,Cai, Jun,Westwell, Andrew D.
, p. 182 - 202 (2019/01/04)
Oestrogen receptor-negative breast cancer, particularly subtypes such as triple-negative breast cancer (TNBC, around 10–15% of cases), are characterised by poor long-term survival, poor response to therapy and early progression to metastasis. Purine-based compounds represent a privileged scaffold in anticancer drug design, with several clinically approved and experimental agents in clinical development comprising a purine core structure. In this study, a series of new purine-based compounds were synthesised; seven of the new analogues were found to significantly reduce the in vitro viability of TNBC cell lines (MDA-MB-231 and MDA-MB-436) with IC50 values of ≤50 μM. In previous work, we have proposed a new concept for targeting angiogenesis driving TNBC progression, by disrupting the protein–protein interaction between the molecular chaperone αB-crystallin (CRYAB) and VEGF. Since previous clinical studies applying anti-VEGF therapy to TNBC patients have met with limited success, we were interested to test our most promising purine analogues against CRYAB/VEGF, using a custom-designed cell-based CRYAB/VEGF165 interaction assay platform. Analogues 4e and 4f significantly reduced the interaction between CRYAB/VEGF165, and compound 4e (100 μM) was also found to decrease the levels of soluble VEGF expressed by MDA-MB-231 cells by 40%. In conclusion, these promising early activity profiles warrant further investigation to validate this concept.
Concise access to N9-mono-, N2-mono- and N2,N9-di-substituted guanines via efficient Mitsunobu reactions
Fletcher, Steven,Shahani, Vijay M.,Lough, Alan J.,Gunning, Patrick T.
experimental part, p. 4621 - 4632 (2010/07/06)
Guanine poses several problems to the synthetic chemist owing to its polyfunctional nature and poor solubility. Over the past few decades, synthetic guanines have found applications as anti-cancer and anti-viral agents. Coupled with the ever-growing inter
