1074-89-1Relevant academic research and scientific papers
An efficient synthesis of substituted cytosines and purines under focused microwave irradiation
Huang, Ling-Kuen,Cherng, Yen-Chih,Cheng, Yann-Ru,Jang, Jing-Pei,Chao, Yi-Ling,Cherng, Yie-Jia
, p. 5323 - 5327 (2007)
A rapid nucleophilic displacement reaction of 6-chloropurine, 2-amino-6-chloropurine and 5-bromocytosine with various nucleophiles under focused microwave irradiation is described. Using this method, the desired products were obtained with the yields up to 99% in?a?short reaction time.
9-Sulfonyl-9(H)-Purine Derivatives Inhibit HCV Replication Via their Degradation Species
Hu, Rong,Wang, Wan-Li,Xiao, Kun-Jie,Wang, Ning-Yu
, p. 36 - 45 (2021)
Cell-based screening of a privileged small molecule library led to the discovery of 9-sulfonyl-9(H)-purine as new scaffold for hepatitis C virus (HCV) inhibitors. Structure–activity relationship study with respect to the 2-, 6- and 9-positions in the purine core resulted in the identification of several active compounds with moderate potency against the HCV genotype 1b. Subsequent stability studies demonstrated that HCV inhibitors of this type were unstable in Dulbecco’s modified eagle medium (DMEM) and plasma, as well as glutathione-containing water, and their instability was closely related to their HCV inhibitory activity. A preliminary study of the mechanism of action showed that the sulfonamide bond at the 9-position of purine would be the primary degradation site and the resulting sulfonylation degradation species would mediate the anti-HCV activity of 9-sulfonyl-9(H)-purines. Results of this study demonstrated that 9-sulfonyl-9(H)-purine is an unstable scaffold for HCV inhibitors and further detailed analysis of the degradation species is needed to determine the main active components and direct target for this type of molecules.
5′-Noraristeromycin possessing a C-1′ cyclopentyl double bond: A new carbanucleoside structural prototype
Yin, Xue-Qiang,Schneller, Stewart W.
, p. 3451 - 3455 (2004)
Prior to this work only two examples of carbanucleosides possessing a C-1′/C-6′ double bond had been reported and they were minor derivatized side products arising during other targeted syntheses. To develop this structural feature into a new class of potential antiviral agents, the 5′-nor derivative of aristeromycin with such an olefinic structure (6) represents the first example. In this regard, treatment of (1′S,2′S, 3′S,4′R,5′S)-6-chloro-9-(2′,3′- isopropylidenedioxy-6′-oxabicyclo[3.1.0]hex-4′-yl)purine (7) with sodium methoxide yielded 6 via an E′2-like elimination pathway. A convenient way to the C-4′ epimer of 6 (that is, 17) also arose during these studies and is described. Antiviral analysis of 6 and 17 failed to produce any significant activity.
Gene therapy of cancer: activation of nucleoside prodrugs with e. colipurine nucleoside phosphorylase
Secrist III, John A.
, p. 745 - 757 (1999)
During the last few years, many gene therapy strategies have been developed for various disease targets. The development of anticancer gene therapy strategies to selectively generate cytotoxic nucleoside or nucleotide analogs is an attractive goal. One such approach involves the delivery of herpes simplex virus thymidine kinase followed by the acyclic nucleoside analog ganciclovir. We have developed another gene therapy methodology for the treatment of cancer that has several significant attributes. Specifically, our approach involves the delivery of E. coli purine nucleoside phosphorylase, followed by treatment with a relatively non-toxic nucleoside prodrug that is cleaved by the enzyme to a toxic compound. .This presentation describes the concept, details our search for suitable prodrugs, and summarizes the current biological data. Copyright
Synthesis and biological evaluation of new HIV-1 protease inhibitors with purine bases as P2-ligands
Zhu, Mei,Dong, Biao,Zhang, Guo-Ning,Wang, Ju-Xian,Cen, Shan,Wang, Yu-Cheng
, p. 1541 - 1545 (2019)
Introducing purine bases to P2-ligands might enhance the potency of Human Immunodeficiency Virus-1 (HIV-1) protease inhibitory because of the carbonyl and NH groups promoting the formation of extensive H-bonding interactions. In this work, thirty-three compounds are synthesized and evaluated, among which inhibitors 16a, 16f and 16j containing N-2-(6-substituted-9H-purin-9-yl)acetamide as the P2-ligands along with 4-methoxylphenylsulfonamide as the P2′-ligand, display potent inhibitory effect on the activity of HIV-1 protease with IC50 43 nM, 42 nM and 68 nM in vitro, respectively.
ACIDIC HYDROLYSIS OF 6-SUBSTITUTED 9-(2-DEOXY-β-D-ERYTHRO-PENTOFURANOSYL)PURINES AND THEIR 9-(1-ALKOXYETHYL) COUNTERPARTS: KINETICS AND MECHANISM.
Oivanen, Mikko,Loennberg, Harri,Zhou, Xiao-xiong,Chattopadhyaya, Jyoti
, p. 1133 - 1140 (1987)
The rate constants for the hydrolysis of several 6-substituted 9-(2-deoxy-β-D-erythro-pentofuranosyl)purines and 9-(1-alkoxyethyl)purines have been measured at different concentrations of oxonium ion.The effects that varying the polar nature of the alkoxy group exerts on the hydrolysis of unsubstituted 9-(1-alkoxyethyl)purines are interpreted to indicate that the reaction proceeds by a rate-limiting departure of the protonated base moiety with a concomitant formation of an alkoxyethyl oxocarbenium ion.The same mechanism is applied to the hydrolysis of 9-(2-deoxy-β-D-erythro-pentofuranosyl)purines by comparing the influences that 6-substituents have on the reactivity of these compounds and their 9-(1-alkoxyethyl) counterparts.No sign of anomerisation was detected, when the hydrolysis of 2'-deoxyadenosine was followed by 1H NMR spectroscopy.
Synthesis and Pharmacological Evaluation of Novel Non-nucleotide Purine Derivatives as P2X7 Antagonists for the Treatment of Neuroinflammation
Calzaferri, Francesco,Narros-Fernández, Paloma,De Pascual, Ricardo,De Diego, Antonio M.G.,Nicke, Annette,Egea, Javier,García, Antonio G.,De Los Ríos, Cristóbal
, p. 2272 - 2290 (2021)
The ATP-gated P2X7 purinergic receptor (P2X7) is involved in the pathogenesis of many neurodegenerative diseases (NDDs). Several P2X7 antagonists have been developed, though none of them reached clinical trials for this indication. In this work, we designed and synthesized novel blood-brain barrier (BBB)-permeable derivatives as potential P2X7 antagonists. They comprise purine or xanthine cores linked to an aryl group through different short spacers. Compounds were tested in YO-PRO-1 uptake assays and intracellular calcium dynamics in a human P2X7-expressing HEK293 cell line, two-electrode voltage-clamp recordings in Xenopus laevis oocytes, and in interleukin 1β release assays in mouse peritoneal macrophages. BBB permeability was assessed by parallel artificial membrane permeability assays and P-glycoprotein ATPase activity. Dichloroarylpurinylethanones featured a certain P2X7 blockade, being compound 6 (2-(6-chloro-9H-purin-9-yl)-1-(2,4-dichlorophenyl)ethan-1-one), named ITH15004, the most potent, selective, and BBB-permeable antagonist. Compound 6 can be considered as a first non-nucleotide purine hit for future drug optimizations.
Synthesis and cytotoxic activity of some new 2,6-substituted purines
Kode, Nageswara Rao,Phadtare, Shashikant
experimental part, p. 5840 - 5860 (2011/09/20)
A seriesof twenty four acyclic unsaturated 2,6-substututed purines 5a-20b were synthesized. These compounds were evaluated for cytotoxic activity against NCI-60 DTP human tumor cell line screen at 10?Mconcentration. N 9-[(Z)-4′-chloro-2′-butenyl-1′-yl]-2, 6-dichloropurine(5a), N9-[4′-chloro-2′-butynyl-1′- yl]-2,6-dichloropurine(10a), N9-[(E)-2′,3′-dibromo- 4′-chloro-2′-butenyl-1′-yl]-6-methoxypurine(14)and N 9-[4′-chloro-2′-butynyl-1′-yl]-6-(4-methoxyphenyl) -purine(19)exhibited highly potent cytotoxic activity with GI50 values in the 1-5 μM range for most human tumor cell lines. Other compounds exhibited moderate activity.
DEAMINATION, INVOLVING RING OPENING, IN REACTIONS OF 1-AMINOPURINIUM MESITYLENESULFONATES WITH METHANOLIC AMMONIA
Kos, N. J.,Jongejan, H.,van der Plas, H. C.
, p. 4841 - 4848 (2007/10/02)
On reaction of 1-aminopurinium mesitylenesulfonates with methanolic ammonia N-deamination occurs.For 1-amino-, 1-amino-8-(methylthio)-, 1-amino-8-phenyl-, 1-amino-2-methyl-, 1-amino-6-methyl- and 1-amino-8-phenyl-9-methylpurinium mesitylenesulfonate this reaction proceeds for at least 75percent via ring opening as shown by the isolation of 1-15N-labelled purines when 15N-labelled methanolic ammonia was used. 1-Amino-9-methylpurinium mesitylenesulfonate gave N-deamination without ring opening.The reaction of 1-amino-6-(methylthio)purinium mesitylenesulfonate with methanolic ammonia involves, besides deamination, partial substitution of the methylthio group; no ring opening is involved.However, ring opening followed by substitution occurs in the reaction of 1-amino-2-(methylthio)purinium mesitylenesulfonate; the reaction proceeds via an adduct at position 2.
PHOTOCHEMISTRY OF PURINE 3-OXIDES IN HYDROXYLIC SOLVENTS
Lam, Fuk L.,Parham, James C.
, p. 2371 - 2376 (2007/10/02)
UV irradiation of the potent oncogen hypoxanthine 3-oxide in aqueoous solution induces elimination of and rearrangement of the nitrogen-bound oxygen.The extent of each reaction shows a complex variation over the pH range 0-7.The variations in quantum yield for product formation are shown to result from the presence in the neutral molecule of tautomeric species with differing photochemistries that ionize in the excited state (pKa* ca. 3.5) just above the protonation pKa (1.2).The photochemical reactivity of each ionic and each tautomeric form was assigned by comparing the effect of pH changes between 0 and 11 on the quantum yields for formation of each photoproduct from hypoxanthine 3-oxide with those of two model compounds, 1-hydroxyhypoxanthine and 6-methoxypurine 3-oxide.Photoreduction of the 3-oxides occurs via the triplet state.This process has a relatively consistent low quantum yield (Φ=0.005 to 0.04) for most ionic and tautomeric forms of both purine 1-oxides and purine 3-oxides.Photorearrangement is a much more efficient process for purine 3-oxides (Φ=0.3) than for purine 1-oxides (Φ=0.04).
