124493-84-1Relevant academic research and scientific papers
3′-Bromo analogues of pyrimidine nucleosides as a new class of potent inhibitors of mycobacterium tuberculosis
Shakya, Neeraj,Srivastav, Naveen C.,Desroches, Nancy,Agrawal, Babita,Kunimoto, Dennis Y.,Kumar, Rakesh
experimental part, p. 4130 - 4140 (2010/09/04)
Tuberculosis (TB) is a major health problem worldwide. We herein report a new class of pyrimidine nucleosides as potent inhibitors of Mycobacterium tuberculosis (M. tuberculosis). Various 2′- or 3′-halogeno derivatives of pyrimidine nucleosides containing uracil, 5-fluorouracil, and thymine bases were synthesized and evaluated for antimycobacterial activities. Among the compounds tested, 3′-bromo-3′-deoxy- arabinofuranosylthymine (33) was the most effective antituberculosis agent in the in vitro assays against wild-type M. tuberculosis strain (H37Ra) (MIC 50 = 1 μg/mL) as well as drug-resistant (H37Rv) (rifampicin-resistant and isoniazid-resistant) strains of M. tuberculosis (MIC50 = 1-2 μg/mL). Compound 33 also inhibited intracellular M. tuberculosis in a human monocytic cell line infected with H37Ra, demonstrating higher activity against intramacrophagic mycobacteria (80% reduction at 10 μg/mL concentration) than extracellular mycobacteria (75% reduction at 10 μg/mL concentration). In contrast, pyrimidine nucleosides possessing 5-fluorouracil base were weak inhibitors of M. tuberculosis. No cytotoxicity was found up to the highest concentration of compounds tested (CC50 > 100-200 μg/mL) against a human cell line. Overall, these encouraging results substantiate the potential of this new class of compounds as promising antituberculosis agents.
Synthesis and anti-HIV activity of 4′-cyano-2′,3′ -didehydro-3′-deoxythymidine
Haraguchi, Kazuhiro,Itoh, Yoshiharu,Takeda, Shingo,Honma, Yosuke,Tanaka, Hiromichi,Nitanda, Takao,Baba, Masanori,Dutschman, Ginger E.,Cheng, Yung-Chi
, p. 647 - 654 (2007/10/03)
A new anti-HIV agent 4′-cyano-2′,3′-didehydro-3′ -deoxythymidine (9) was synthesized by allylic substitution of the 3′,4′-unsaturated nucleoside 14, having a leaving group at the 2′-position, with cyanotrimethylsilane in the presence of SnCl4. Evaluation
1-(3'-fluoro-2',3'-dideoxy-β-D-ribofuranosyl)-5-substituted pyrimidine nucleosides
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, (2008/06/13)
A 2',3'-deoxy-3'-fluoro-pyrimidine nucleoside having the formula: STR1 wherein R1 is OH or NH2 ; R2 is CF3, CH2 CH2 CH3, STR2 CH2 OCH3, CH2 SCH3, CH=CH2 CH=CH--CH3, C CH, C C--CH3 or CH2 --C CH; or a pharmaceutically acceptable salt thereof. These nucleoside analogs exhibit antiviral activity against HIV.
Synthesis of 2′,3′-didehydro-2′,3′-dideoxynucleosides by reaction of 5′-protected nucleoside 2′,3′-dimesylates with telluride dianion: A general route from cis vicinal diols to olefins
Clive, Derrick L. J.,Wickens, Philip L.,Sgarbi, Paulo W. M.
, p. 7426 - 7437 (2007/10/03)
2′,3′-Dimesylates of 5′-protected nucleosides are converted into the corresponding 2′,3′-didehydro2′,3′-dideoxy compounds by treatment with telluride dianion in the form of the sodium or lithium salt. The method is well-suited to the preparation of unsaturated nucleosides that can be converted into compounds that are believed to be useful in the treatment of AIDS. The deoxygenation is general for vicinal dimesylates that have, or may adopt, a synperiplanar conformation. With straight chain compounds the reaction is stereospecific. In some cases, similar, but slower, deoxygenations can be performed with selenide dianion.
Deoxygenation of cis vicinal diols to make didehydro dideoxy nucleosidies and synthetic intermediates
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, (2008/06/13)
Cis vicinal diols are converted to olefins using tellurides or selenide reagents. The diol is reacted to convert the hydroxyl groups into good leaving groups for nucleophilic substitution. Alkyl and aryl sulfonate groups such as mesylate or tosylate are p
Fluorinated sugar analogues of potential anti-HIV-1 nucleosides
Huang,Chen,Wang,Kim,Warshaw,Armstrong,Zhu,Chou,Watanabe,Matulic-Adamic,Su,Fox,Polsky,Baron,Gold,Hardy,Zuckerman
, p. 1640 - 1646 (2007/10/02)
In order to obtain agents with therapeutic indices superior to those of AZT, FLT, or D4T, several analogues of anti-HIV-1 nucleosides were synthesized. These include 2',3'-dideoxy-2',3'-difluoro-5-methyluridine (13), its arabino analogue 19, arabino-5-met
