480439-89-2Relevant articles and documents
Getting DNA and RNA out of the dark with 2CNqA: A bright adenine analogue and interbase FRET donor
Del Nogal, Anna Wypijewska,Füchtbauer, Anders F.,Bood, Mattias,Nilsson, Jesper R.,Wranne, Moa S.,Sarangamath, Sangamesh,Pfeiffer, Pauline,Rajan, Vinoth Sundar,El-Sagheer, Afaf H.,Dahlén, Anders,Brown, Tom,Gr?tli, Morten,Marcus Wilhelmsson
, p. 7640 - 7652 (2020)
With the central role of nucleic acids there is a need for development of fluorophores that facilitate the visualization of processes involving nucleic acids without perturbing their natural properties and behaviour. Here, we incorporate a new analogue of adenine, 2CNqA, into both DNA and RNA, and evaluate its nucleobase-mimicking and internal fluorophore capacities. We find that 2CNqA displays excellent photophysical properties in both nucleic acids, is highly specific for thymine/uracil, and maintains and slightly stabilises the canonical conformations of DNA and RNA duplexes. Moreover, the 2CNqA fluorophore has a quantum yield in single-stranded and duplex DNA ranging from 10% to 44% and 22% to 32%, respectively, and a slightly lower one (average 12%) inside duplex RNA. In combination with a comparatively strong molar absorptivity for this class of compounds, the resulting brightness of 2CNqA inside double-stranded DNA is the highest reported for a fluorescent base analogue. The high, relatively sequence-independent quantum yield in duplexes makes 2CNqA promising as a nucleic acid label and as an interbase F?rster resonance energy transfer (FRET) donor. Finally, we report its excellent spectral overlap with the interbase FRET acceptors qAnitro and tCnitro, and demonstrate that these FRET pairs enable conformation studies of DNA and RNA.
Synthetic method of Jjar mycin
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Paragraph 0004; 0009-0010; 0014-0015, (2021/05/29)
The invention relates to a synthetic method of jjar mycin. The technical problems of long steps and high cost of the existing synthesis method are mainly solved. The synthesis method comprises the following synthesis steps: generating a compound 1 from 4-
NOVEL 6-SUBSTITUTED 7-DEAZAPURINES AND CORRESPONDING NUCLEOSIDES AS MEDICAMENTS
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Page/Page column 49, (2021/08/27)
The present invention relates to the synthesis of 6-substituted 7-deazapurines and their corresponding nucleosides by coupling aryl or alkyl Grignard reagents with halogenated purine nucleosides in the presence of iron or an iron/copper mixture such as Fe(acac)3/Cul. The present invention also relates to pharmaceutical compositions comprising said compounds and the use of said pharmaceutical compositions to treat or prevent viral infections.
C6–O-alkylated 7-deazainosine nucleoside analogues: Discovery of potent and selective anti-sleeping sickness agents
Hulpia, Fabian,Bouton, Jakob,Campagnaro, Gustavo D.,Alfayez, Ibrahim A.,Mabille, Dorien,Maes, Louis,de Koning, Harry P.,Caljon, Guy,Van Calenbergh, Serge
, (2020/01/13)
African trypanosomiasis, a deadly infectious disease caused by the protozoan Trypanosoma brucei spp., is spread to new hosts by bites of infected tsetse flies. Currently approved therapies all have their specific drawbacks, prompting a search for novel th
Synthesis of 7-trifluoromethyl-7-deazapurine ribonucleoside analogs and their monophosphate prodrugs
Cho, Jong Hyun,Bassit, Leda C.,Amblard, Franck,Schinazi, Raymond F.
, p. 671 - 687 (2019/11/03)
Novel 7-trifluoromethyl-7-deazapurine ribonucleoside analogs (13a-c) and their Protides (15a-c) were successfully synthesized from ribolactol or 1-α-bromo-ribose derivatives using Silyl-Hilbert-Johnson or nucleobase-anion substitution reactions followed by key aromatic trifluoromethyl substitution. Newly prepared compounds were evaluated against a panel of RNA viruses, including HCV, Ebola or Zika viruses.
Tumor immunity compound and application thereof
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Paragraph 0384-0389, (2020/07/14)
Disclosed are a tumor immunity compound and an application thereof. The invention discloses a compound as shown in the formula (I), optical isomers thereof, and pharmaceutically acceptable salts thereof, and an application of the compound as an STING agonist.
Iron/Copper Co-Catalyzed Cross-Coupling Reaction for the Synthesis of 6-Substituted 7-Deazapurines and the Corresponding Nucleosides
Daelemans, Dirk,Herdewijn, Piet,Li, Qingfeng,Persoons, Leentje
, (2020/01/03)
An efficient access to 6-substituted 7-deazapurine and the corresponding nucleosides by coupling aryl or alkyl Grignard reagents and halogenated purine nucleosides in the presence of Fe(acac)3/CuI is described. A series of 6-substituted 7-deazapurines and the corresponding nucleosides were obtained in medium to good yields. For the synthesis of modified nucleosides that will be the subject of biological testing, we propose to use iron-catalyzed instead of palladium-catalyzed reaction. The synthesized compounds were tested for their antiproliferative activity. The cytotoxicity study of compounds 11a-q shows that by modifying the 6-position of 7-deazapurine ribonucleosides, the compounds may become selective for certain cancer cell lines.
Synthesis and evaluation of analogs of 5′-(((Z)-4-amino-2-butenyl)methylamino)-5′-deoxyadenosine (MDL 73811, or AbeAdo) – An inhibitor of S-adenosylmethionine decarboxylase with antitrypanosomal activity
Brockway, Anthony J.,Volkov, Oleg A.,Cosner, Casey C.,MacMillan, Karen S.,Wring, Stephen A.,Richardson, Thomas E.,Peel, Michael,Phillips, Margaret A.,De Brabander, Jef K.
supporting information, p. 5433 - 5440 (2017/10/06)
We describe our efforts to improve the pharmacokinetic properties of a mechanism-based suicide inhibitor of the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (AdoMetDC), essential for the survival of the eukaryotic parasite Trypanosoma brucei responsible for Human African Trypanosomiasis (HAT). The lead compound, 5′-(((Z)-4-amino-2-butenyl)methylamino)-5′-deoxyadenosine (1, also known as MDL 73811, or AbeAdo), has curative efficacy at a low dosage in a hemolymphatic model of HAT but displayed no demonstrable effect in a mouse model of the CNS stage of HAT due to poor blood–brain barrier permeation. Therefore, we prepared and evaluated an extensive set of analogs with modifications in the aminobutenyl side chain, the 5′-amine, the ribose, and the purine fragments. Although we gained valuable structure–activity insights from this comprehensive dataset, we did not gain traction on improving the prospects for CNS penetration while retaining the potent antiparasitic activity and metabolic stability of the lead compound 1.
6-methyl 7-position-denitrified purine nucleoside compounds and application thereof
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, (2017/09/02)
The invention discloses6-methyl 7-position-denitrified purine nucleoside compounds and an application thereof and belongs to the field of medicinal chemistry. The 6-methyl 7-position-denitrified purine nucleoside compounds or pharmaceutically acceptable salts of the compounds having characteristics of a structure shown as formula I are a kind of novel-structured compounds designed and synthesized according to protein structure characteristics of RNA virus polymerase, and the compounds can inhibit RNA viruses, thereby being capable of serving as potential drugs for preventing and treating infection of RNA viruses such as HCV (hepatitis c virus), influenza virus, HRV (rhinovirus), RSV, Ebola virus, DENV (Dengue virus), enterovirus and the like.
Design and synthesis of fluorescent 7-deazaadenosine nucleosides containing π-extended diarylacetylene motifs
De Ornellas, Sara,Slattery, John M.,Edkins, Robert M.,Beeby, Andrew,Baumann, Christoph G.,Fairlamb, Ian J. S.
supporting information, p. 68 - 72 (2015/02/02)
C-modified 7-deazaadenosines containing a diphenylacetylene moiety have been synthesised using cross-coupling approaches. The C-modified nucleosides exhibit remarkable fluorescence properties, including high quantum yields. Solvatochromic studies show a n