127592-40-9Relevant academic research and scientific papers
Inhibition of Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium avium by novel dideoxy nucleosides
Rai, Dinesh,Johar, Monika,Srivastav, Naveen C.,Manning, Tracey,Agrawal,Kunimoto, Dennis Y.,Kumar, Rakesh
, p. 4766 - 4774 (2008/03/12)
The prevalence of tuberculosis (TB) and mutidrug-resistant tuberculosis (MDR-TB) has been increasing, leading to serious infections, high mortality, and a global health threat. Here, we report the identification of a novel class of dideoxy nucleosides as potent and selective inhibitors of Mycobacterium bovis, Mycobacterium tuberculosis, and drug-resistant Mycobacterium tuberculosis. A series of 5-acetylenic derivatives of 2′,3′-dideoxyuridine (3-8) and 3′-fluoro-2′,3′-dideoxyuridine (22-27) were synthesized and tested for their antimycobacterial activity against M. bovis, M. tuberculosis, and M. avium. 2′,3′-Dideoxyuridine possessing 5-decynyl, 5-dodecynyl, 5-tridecynyl, and 5-tetradecynyl substituents (4-7) exhibited the highest antimycobacterial activity against all three mycobacteria. In contrast, in the 3′-fluoro-2′,3′-dideoxyuridine series, a 5-tetradecynyl analogue (26) displayed the most potent activity against these mycobacteria. Among other derivatives, 5-bromo-2′,3′-dideoxycytidine (11), 5-methyl-2′,3′-dideoxycytidine (12), and 5-chloro-4-thio-2′, 3′-dideoxyuridine (19) exhibited modest inhibition of M. bovis and M. tuberculosis. In the series of dideoxy derivatives of adenosine, guanosine, and purines, 2-amino-6-mercaptoethyl-9-(2,3-dideoxy-β-D-glyceropentofuranosyl) purine (32) and 2-amino-4-fluoro-7-(2,3-dideoxy-β-D-glyceropentofuranosyl) pyrrolo[2,3-d]-pyrimidine (35) were the most efficacious against M. bovis and M. tuberculosis, and M. avium, respectively.
Synthesis and Anti-HIV Evaluation of 2',3'-Dideoxyribo-5-chloropyrimidine Analogues: Reduced Toxicity of 5-Chlorinated 2',3'-Dideoxynucleosides
Aerschot, Arthur Van,Everaert, Dirk,Balzarini, Jan,Augustyns, Koen,Jie, Liu,at al.
, p. 1833 - 1839 (2007/10/02)
In view of the selective anti-HIV activity of 2',3'-dideoxy-3'-fluoro-5-chlorouridine (11), a series of eight 2',3'-dideoxy-5-chloropyrimidines were synthesized and evaluated for their inhibitory activity against human immunodeficiency virus type 1 (HIV-1) replication in MT-4 cells.A marked improvement in selectivity was noted for the 5-chlorouracil derivatives of 2,3-dideoxyribofuranose, 3-azido-2,3-dideoxyribofuranose, and 3-fluoro-2,3-dideoxyribofuranose, mainly due to decreased toxicity of the compounds for the host cells.While chlorination of 2',3'-dideoxycytidine remo ved the anti-HIV activity, introduction of chlorine at the C-5 position of 3'-fluoro-, 3'-azido- or 2',3'-didehydro-2',3'-dideoxycytidine led to reduced cytotoxicity with only slightly reduced anti-HIV activity.X-ray analysis showed compound 11 to have two molecules in the asymmetric unit with κ = -168.8(3) deg and -131.3(3) deg and P = 179(1) deg and 163(1) deg, respectively; thus revealing no close resemblance to 3'-azido-3'-deoxythymidine (AZT).
Analogs of pyrimidine nucleosides. 16. Racemic 2′,3′-dideoxynucleosides and their derivatives
Kaulinya,Liepin'sh,Lidak,Zhuk
, p. 85 - 93 (2007/10/02)
The chlorination of 2-halomethyltetrahydrofurans and acyl derivatives of tetrahydrofuryl alcohol wasstudied; mixtures of 2,5- and 2,2-disubstituted tetrahydrofurans are formed as a result of the reaction. 2,4-Bis(trimethylsilyl) derivatives of uracil, 5-substituted uracils, and cytosine are alkylated by the resulting mixtures of α-chloro ethers without separation, and mixtures of cis and transisomers of 1-(5-substituted-2-tetrahydrofuryl) and 1-(2-substituted-2-tetrahydrofuryl) derivatives of uracil, 5-substituted uracils, and cytosine are obtained. The reaction products were identified onthe basis of their PMR spectra.
