124737-24-2Relevant articles and documents
Discovery of ANA975: An oral prodrug of the TLR-7 agonist isatoribine
Xiang, Alan X.,Webber, Stephen E.,Kerr, Bradley M.,Rueden, Erik J.,Lennox, Joseph R.,Haley, Gregory J.,Wang, Tingmin,Ng, John S.,Herbert, Mark R.,Clark, David L.,Banh, Virginia N.,Li, Wei,Fletcher, Simon P.,Steffy, Kevin R.,Bartkowski, Darian M.,Kirkovsky, Leonid I.,Bauman, Lisa A.,Averett, Devron R.
, p. 635 - 640 (2007)
ANA975, a 5-amino-3-β-D-ribofuranosyl-3H-thiazolo[4,5-d]pyrimidin-2- one derivative, was synthesized in the search of an oral prodrug of isatoribine, a small molecule toll-like receptor 7 (TLR-7) agonist. Several strategies were studied to enable the kilogram-scale synthesis of ANA975. Three general total syntheses are described. In the phase I clinical study of ANA975 against hepatitis C virus (HCV), conversion to isatoribine in plasma was rapid and effective, delivering levels of isatoribine that have been shown to be clinically relevant. Copyright Taylor & Francis Group, LLC.
3-β-D-RIBOFURANOSYLTHIAZOLO[4,5-d]PYRIDIMINE NUCLEOSIDES AND USES THEREOF
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Page/Page column 79; 80, (2010/02/15)
The invention is directed to 3-?-D-ribofuranosylthiazolo[4,5-d]pyridimine nucleosides and pharmaceutical compositions containing such compounds that have immunomodulatory activity. The invention is also directed to the therapeutic or prophylactic use of such compounds and compositions, and to methods of treating diseases and disorders described herein, by administering effective amounts of such compounds.
Synthesis and antiviral activity of certain guanosine analogues in the thiazolo[4,5-d]pyrimidine ring system
Kini,Anderson,Sanghvi,Lewis,Smee,Revankar,Robins,Cottam
, p. 3006 - 3010 (2007/10/02)
Several sugar-modified nucleoside derivatives of the purine analogue 5-amino-3-β-D-ribofuranosylthiazolo[4,5-d]-pyrimidine-2,7-dione (1) were synthesized. Phosphorylation of 1 using POCl3 resulted in 5'-monophosphate 2, which was subsequently converted to 3',5'-cyclic phosphate 3, by reported methods. 5'-Sulfamoyl derivative 4 was synthesized by treatment of the 2,3-O-isopropylidene derivative of 1 with chlorosulfonamide followed by acid deprotection. Compounds 5-7, the 5'-deoxy, the tri-O-acetyl, and the 2'-deoxy derivatives of 1, respectively, were synthesized by glycosylation of 5-aminothiazolo[4,5-d]pyrimidine-2,7-dione, the aglycon of 1, with the appropriate sugar moieties, utilizing the Vorbruggen procedure. Oxidative cleavage of the C(2')-C(3') bond in 1 followed by reduction with sodium borohydride led to ''seco'' analogue 8. Nucleosides 2-8 were evaluated for antiviral activity in vivo against the Semliki Forest virus. The activity of compounds 2, 5, and 7 were similar to that of 1. Cyclic phosphate 3 was toxic at the high dose and weakly active at the lower dose. Compounds 4, 6, and 8 were inactive in this system.