111647-36-0Relevant articles and documents
Probing the binding requirements of modified nucleosides with the dna nuclease snm1a
Dürr, Eva-Maria,McGouran, Joanna F.
, (2021/06/21)
SNM1A is a nuclease that is implicated in DNA interstrand crosslink repair and, as such, its inhibition is of interest for overcoming resistance to chemotherapeutic crosslinking agents. However, the number and identity of the metal ion(s) in the active site of SNM1A are still unconfirmed, and only a limited number of inhibitors have been reported to date. Herein, we report the synthesis and evaluation of a family of malonate-based modified nucleosides to investigate the optimal positioning of metal-binding groups in nucleoside-derived inhibitors for SNM1A. These compounds include ester, carboxylate and hydroxamic acid malonate derivatives which were installed in the 5′-position or 3′-position of thymidine or as a linkage between two nucleosides. Evaluation as inhibitors of recombinant SNM1A showed that nine of the twelve compounds tested had an inhibitory effect at 1 mM concentration. The most potent compound contains a hydroxamic acid malonate group at the 5′-position. Overall, our studies advance the understanding of requirements for nucleoside-derived inhibitors for SNM1A and indicate that groups containing a negatively charged group in close proximity to a metal chelator, such as hydroxamic acid malonates, are promising structures in the design of inhibitors.
Synthesis, structure-activity relationship and antiviral activity of 3′-N,N-dimethylamino-2′,3′-dideoxythymidine and its prodrugs
Singh, Ramendra K.,Yadav, Dipti,Rai, Diwakar,Kumari, Garima,Pannecouque,De Clercq, Erik
experimental part, p. 3787 - 3793 (2010/09/15)
A probable NRTI molecule, viz. 3′-N,N-dimethylamino-2′, 3′-dideoxythymidine (4) and its 5′-O-carboxyl ester prodrugs - 5′-(N-α-BOC-l-phenylalanyl)-3′-N,N-dimethylamino-2′, 3′-dideoxythymidine (5), 5′-l-phenylalanyl-3′-N,N- dimethylamino-2′,3′-dideoxythymidine (6) and 5′-decanoyl- 3′-N,N-dimethylamino-2′,3′-dideoxythymidine (7) have been synthesized and screened against HIV, HSV-1 and 2, parainfluenza-3, vesicular stomatitis and several other viruses. The compound 6 showed good antiviral activity with EC50 value 0.03 μM (SI = 8) against VSV in Hela and HEL cell lines. However, the lead compound 4 and its derivatives 5, 6 and 7 showed no remarkable activity against HIV-1 and other viruses. Molecular docking studies with HIV-1 RT using DS 2.5 and pymol softwares have shown marked differences in the interaction patterns between the lead compound 4 and AZT. Synthesis, molecular modeling and antiviral/anti-HIV activity of 3′-N,N-dimethylamino-2′,3′-dideoxythymidine and its prodrugs have been described.
Nucleoside analog inhibitors of reverse transcriptase
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Page 10, (2008/06/13)
Compounds of formula (XXIII), or pharmaceutically acceptable salts or esters thereof, are inhibitors of reverse transcriptase: R4 is a nucleoside with Q substituting a 3′ hydroxyl group, and Q is a moiety of formulas (XXIV)-(XXXII):
