5502-78-3Relevant articles and documents
Preparation of a methylated DNA standard, and its stability on storage
Osborne, Martin R.,Phillips, David H.
, p. 257 - 261 (2000)
Several methods are available for the determination of low levels of O6-methylguanine in DNA; this base arises after methylation by environmental carcinogens. The reliability of these assays is much improved by the use of a standard. We have prepared such a standard by treating calf thymus DNA with [3H-methyl]-N-methyl-N-nitrosourea. We characterized the methylated bases by hydrolysis of a sample to nucleosides, followed by liquid chromatography and liquid scintillation counting of the tritium content. The level of O6- methylguanine was 0.6 per one million nucleotides. This base is stable, and its level was unchanged after storage for 5 years at -20 °C. The methylated DNA also contained 7-methylguanine and 3-methyladenine, which are slowly cleaved from the DNA on standing. The half-life for loss of 7-methylguanine at neutral pH was estimated to be 70 h at 39 °C, 460 h at 22 °C, 3800 h at 10 °C, and about 4 years at -20 °C.
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.
HETEROCYCLIC GTP CYCLOHYDROLASE 1 INHIBITORS FOR THE TREATMENT OF PAIN
-
Page/Page column 54, (2011/04/19)
The present invention relates to the field of small molecule heterocyclic inhibitors of GTP cyclohydrolase (GCH-I), or a tautomer, prodrug, or pharmaceutically acceptable salt thereof. The invention also features pharmaceutical compositions of the compounds and the medical use of these compounds for the treatment or prevention of pain (e.g., inflammatory pain, nociceptive pain, functional pain, or neuropathic pain).
Universal Base
-
Page/Page column 5, (2010/03/02)
The present invention provides artificial universal base capable of base pairing nonspecifically with any of four kinds of natural nucleic acid bases (A, T, G, and C) without the function to specifically recognize pairing natural nucleic acid bases for base pair formation. Universal base capable of base paring nonspecifically with four kinds of natural nucleic acid bases, wherein the universal base has a structure represented by the following chemical formula: wherein R represents a monovalent group other than a hydrogen atom.
2-Amino-6-(1,2,4-triazol-4-yl)-purine: A useful intermediate in the synthesis of 9-alkylguanines
Alarcon,Martelli,Demeunynck,Lhomme
, p. 7211 - 7215 (2007/10/03)
2-Amino-6-(1,2,4-triazol-4-yl)purine, prepared from 2,6-diaminopurine, was regioselectively alkylated at position 9. Subsequent alkaline hydrolysis afforded 9-alkylguanines in high yield. (C) 2000 Elsevier Science Ltd.
New synthesis of 9-alkylguanines and their N2-substituted derivatives
Kochergin,Persanova,Aleksandrova
, p. 480 - 483 (2007/10/03)
A new method of synthesizing 9-alkyl guanines and their N2-substituted derivatives from 7-benzylguanine and its N2-substituted derivatives has been developed by quaternization with alkyl halides, dialkyl sulfates, or arenesulfonic acid esters, and subsequent removal of the benzyl protection by hydrogenation of the intermediate quaternary salts or of the betaines obtained from them. 1998 Plenum Publishing Corporation.
Process for the preparation of 9-substituted guanine derivatives
-
, (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.
