115509-32-5Relevant articles and documents
Design, Synthesis, and Anti-RNA Virus Activity of 6′-Fluorinated-Aristeromycin Analogues
Yoon, Ji-Seong,Kim, Gyudong,Jarhad, Dnyandev B.,Kim, Hong-Rae,Shin, Young-Sup,Qu, Shuhao,Sahu, Pramod K.,Kim, Hea Ok,Lee, Hyuk Woo,Wang, Su Bin,Kong, Yun Jeong,Chang, Tong-Shin,Ogando, Natacha S.,Kovacikova, Kristina,Snijder, Eric J.,Posthuma, Clara C.,Van Hemert, Martijn J.,Jeong, Lak Shin
, p. 6346 - 6362 (2019)
The 6′-fluorinated aristeromycins were designed as dual-target antiviral compounds aimed at inhibiting both the viral RNA-dependent RNA polymerase (RdRp) and the host cell S-adenosyl-l-homocysteine (SAH) hydrolase, which would indirectly target capping of viral RNA. The introduction of a fluorine at the 6′-position enhanced the inhibition of SAH hydrolase and the activity against RNA viruses. The adenosine and N6-methyladenosine analogues 2a-e showed potent inhibition against SAH hydrolase, while only the adenosine derivatives 2a-c exhibited potent antiviral activity against all tested RNA viruses such as Middle East respiratory syndrome-coronavirus (MERS-CoV), severe acute respiratory syndrome-coronavirus, chikungunya virus, and/or Zika virus. 6′,6′-Difluoroaristeromycin (2c) showed the strongest antiviral effect for MERS-CoV, with a ～2.5 log reduction in infectious progeny titer in viral load reduction assay. The phosphoramidate prodrug 3a also demonstrated potent broad-spectrum antiviral activity, possibly by inhibiting the viral RdRp. This study shows that 6′-fluorinated aristeromycins can serve as starting points for the development of broad-spectrum antiviral agents that target RNA viruses.
Asymmetric Synthesis of (-)-6′-β-Fluoro-aristeromycin via Stereoselective Electrophilic Fluorination
Kim, Gyudong,Yoon, Ji-Seong,Jarhad, Dnyandev B.,Shin, Young Sup,Majik, Mahesh S.,Mulamoottil, Varughese A.,Hou, Xiyan,Qu, Shuhao,Park, Jiyong,Baik, Mu-Hyun,Jeong, Lak Shin
, p. 5732 - 5735 (2017/11/10)
(-)-6′-β-Fluoro-aristeromycin (2), a potent inhibitor of S-adenosylhomocysteine (AdoHcy) hydrolase, has been synthesized via stereoselective electrophilic fluorination followed by a purine base build-up approach. Interestingly, purine base condensation using a cyclic sulfate resulted in a synthesis of (+)-5′-β-fluoro-isoaristeromycin (2a). Computational analysis indicates that the fluorine atom controlled the regioselectivity of the purine base substitution.
Chiral syntheses of 6′-β-fluoroaristeromycin, 6′-β-fluoro-5′-noraristeromycin and aristeromycin
Yin, Xue-Qiang,Schneller, Stewart W.
, p. 7535 - 7538 (2007/10/03)
Carbocyclic nucleosides substituted at the C-6′ position are receiving increasing attention. Chiral synthetic accessibility to the biologically promising 6′-β-fluoroaristeromycin is lacking. Its preparation and that of the 5′-nor analogue are described. A
Synthesis and Antiviral Evaluation of 6'-Substituted Aristeromycins: Potential Mechanism-Based Inhibitors of S-Adenosylhomocysteine Hydrolase
Madhavan, G. V. Bindu,McGee, Danny P. C.,Rydzewski, Robert M.,Boehme, Richard,Martin, John C.,Prisbe, Ernest J.
, p. 1798 - 1804 (2007/10/02)
New carboxylic adenosine analogues substituted at the 6'-position with fluorine, hydroxyl, methylene, of hydroxymethyl have been synthesized as potential mechanism-based inhibitors of S-adenosylhomocysteine (AdoHcy) hydrolase.The synthetic routes began wi
Purinyl or pyrimidinyl substituted hydroxycyclopentane compounds useful as antivirals
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, (2008/06/13)
Novel 4-substituted-5-hydroxymethyl-1,2-cyclopentanediols or 1-cyclopentanol substituted at the 3-position by various heterocyclic groups are useful as antiviral agents.
