14937-72-5Relevant academic research and scientific papers
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.
Synthetic method of nitric acid catalyzed hypoxanthine derivative
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Paragraph 0039-0040, (2021/10/11)
The invention discloses a synthetic method of a nitric acid catalytic hypoxanthine derivative, and belongs to the technical field of pharmaceutical chemistry. 6 - Chloropurine derivatives were mixed with a solvent, a catalytic amount of nitric acid heating reaction was added, and acid generated in the reaction was neutralized, and the solvent was removed under reduced pressure to obtain a hypoxanthine derivative. The hypoxanthine derivative obtained by the method is low in cost, high in purity and good in substrate adaptability; various impurities in a traditional method are removed; separation and purification are convenient; and the reliability of the quality of the hypoxanthine derivative is improved.
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.
Long-range heteronuclear coupling constants in 2,6-disubstituted purine derivatives
Prochazkova, Eliska,Cechova, Lucie,Jansa, Petr,Dracinsky, Martin
body text, p. 295 - 298 (2012/07/17)
Four- and five-bond heteronuclear J-couplings between the hydrogen H-8 and carbons C-6 and C-2 in a series of 7- and 9-benzyl substituted purine derivaties with variuous substituents in positions 2 and 6 were studied by coupled 13 C NMR and H,C
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
β-Diketo acids with purine nucleobase scaffolds: Novel, selective inhibitors of the strand transfer step of HIV integrase
Nair, Vasu,Uchil, Vinod,Neamati, Nouri
, p. 1920 - 1923 (2007/10/03)
The HIV pol gene encodes three viral enzymes that are required for its replication. While drug discovery involving the viral targets, reverse transcriptase and protease, has resulted in useful therapeutic agents, such efforts on HIV integrase have not produced a single FDA-approved drug. In the work focused on the discovery of inhibitors of HIV integrase, we have synthesized new β-diketo acids with purine nucleobase scaffolds that are potent inhibitors of the strand transfer steps of wild-type HIV-1 integrase.
Regioselective functionalization of guanine: Simple and practical synthesis of 7- and 9-alkylated guanines starting from guanosine
Kalayanov, Genadiy,Jaksa, Suzana,Scarcia, Tommaso,Kobe, Joze
, p. 2026 - 2034 (2007/10/03)
Reaction of N2-acetyl-9- and/or -7-benzylated guanines 8 and 12 with selected alkylating agents in 1-methyl-2-pyrrolidone at 120°C yielded the guaninium salts 9 and 13. The salts were consequently transformed by phase transfer hydrogenation into N7- and N9-isomers 10 and 14, respectively, in a highly regioselective manner. A convenient deoxygenation of both derivatives, achieved via the corresponding O6-arenesulfonates, into 2-aminopurine potential prodrugs was also established.
Low-temperature photosensitized oxidation of a guanosine derivative and formation of an imidazole ring-opened product
Sheu, Chimin,Kang, Ping,Khan, Saeed,Foote, Christopher S.
, p. 3905 - 3913 (2007/10/03)
An organic-soluble guanosine derivative, 2′,3′,5′-O-(tert-butyldimethylsilyl)guanosine (1), was prepared and its photosensitized oxidation was carried out in several solvents at various temperatures. Singlet oxygen is the reactive oxidizing agent responsi
1,4-Diazabicyclooctane (DABCO)-catalysed Hydrolysis and Alcoholysis Reactions of 2-Amino-9-benzyl-6-chloro-9H-purine
Linn, James A.,McLean, Ed W.,Kelley, James L.
, p. 913 - 914 (2007/10/02)
2-Amino-9-benzyl-6-chloro-9H-purine 1 is hydrolysed in refluxing water in the presence of 1,4-diazabicyclooctane (DABCO) to give 2-amino-9-benzyl-1,6-dihydro-6-oxo-9H-purine 3; however, 1 reacts with hydroxide ion at ambient temp., or an alcohol an
Process for the preparation of 9-substituted guanine derivatives
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, (2008/06/13)
A process for the preparation of 9-substituted quanine derivatives of general formula (I), in which R is C1 -C4 -alkyl optionally substituted with one or more hydroxy groups, or R is (α), benzyl, ribosyl, 2'-deoxyribosyl or (CH2)n -OR1 where n is 1 or 2, and R1 is CH2 CH2 OH or (β) or salts thereof, in which a 1-substituted5-(thiocarbamoyl)amino-1H-imidazole-4-carboxamide of general formula (III), where R has the same meaning as in formula (I), is cyclized: a) by treatment with a heavy metal salt of the group of Cu-, Ag-, Pb- and Hg-salts in an aqueous alkaline medium containing at least for equivalents of OH-ions at a temperature form about 0° C. to the reflux temperature, or b) by treatment with a peroxy compound in an aqueous alkaline medium at a temperature of about 0°-30° C., whereafter (I) is isolated by treatment with a acid and, if desired, is converted into a salt. The invention further comprises intermediates for use in the preparation of the above-mentioned compounds.
