Synthesis and antiviral activity of certain guanosine analogs in the thiazolo[4,5-d]pyrimidine ring system

Abstract

Several sugar-modified nucleoside derivatives of the purine analogue 5-amino-3-beta-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 C2'-C3' 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.

One-pot microwave-assisted synthesis of 2,5-bis(pyrazol-4-yl)[1,3]thiazolo[5,4-d][1,3]thiazoles from pyrazole-4-carbaldehydes and dithiooxamide

“…The 1 H, 13 C, 15 N NMR spectra were recorded on Bruker DPX-400 (400.13, 100.62 and 40.55 MHz, respectively) from solutions in (DMSO-d6) and СDСl3 relative to HMDS ( 1 Н, 13 The melting points were determined on a PolyTherm A micro hot stage. Starting dithiooxamide was taken from commercial suppliers and used without further purification.…”

“…This reaction is carried out in diverse solvents, 10,[31][32][33][34] or without solvent. 6,15,16,18 However, the harsh reaction conditions and duration of the process (24 h) lead to resinification and formation of the side products. The developed alternative approaches to the synthesis of diarylthiazolo [5,4-d]thiazoles such as treatment of 2,5-bis(acetylamino)thiazole with sodium thiocyanate in the presence of bromine followed by thermal cyclization, 35 acidcatalyzed reaction of 5-amino-2-aryl-4-mercaptothiazole with orthoether 36 and others 1 are of limited utility.…”

Significance of Thiazole-based Heterocycles for Bioactive Systems

“…Thiazolo [4,5-d]pyrimidine derivative 151 revealed in vivo activity towards a broad range of RNA and DNA viruses [114] and also had antitumor and antimetastatic activity [115]. The guanine analogs 152 exhibited potent in vitro activity against human cytomegalovirus (HCMV) [116].…”

A facile synthesis of novel thiazolo[4,5‐d]pyrimidin‐7‐ones

“…Thiazolo[4,5‐d]pyrimidines are widely recognized as pharmaceutically and biologically useful heterocycles because of their structural similarities to purine bases. As such, thiazolo[4,5‐d]pyrimidines have been found to possess anti‐HIV [1], anticancer [2], anti‐inflammatory [3], and antimicrobial activities [4, 5]. An important synthetic route for thiazolo[4,5‐d]pyrimidines in previous reports is the condensation reaction of 4‐aminothiazole‐5‐carboxylate and isothiocyanate.…”