Tiazofurin

Tiazofurin
Clinical data
Other names	2-[(2R,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3-thiazole-4-carboxamide
ATC code	L01XX18 (WHO) ;
Identifiers
	IUPAC name (1R)-1-[4-(aminocarbonyl)-1,3-thiazol-2-yl]-1,4-anhydro-D-ribitol;
CAS Number	60084-10-8 ;
PubChem CID	457954;
ChemSpider	403014 ;
UNII	ULJ82834RE;
ChEMBL	ChEMBL108358 ;
CompTox Dashboard (EPA)	DTXSID00208827 ;
Chemical and physical data
Formula	C9H12N2O5S
Molar mass	260.26 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(c1nc(sc1)[C@@H]2O[C@@H]([C@@H](O)[C@H]2O)CO)N;
	InChI InChI=1S/C9H12N2O5S/c10-8(15)3-2-17-9(11-3)7-6(14)5(13)4(1-12)16-7/h2,4-7,12-14H,1H2,(H2,10,15)/t4-,5-,6-,7-/m1/s1 ; Key:FVRDYQYEVDDKCR-DBRKOABJSA-N ;
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Tiazofurin is a drug which acts as an inhibitor of the enzyme IMP dehydrogenase. Tiazofurin and its analogues were under investigation for potential use in the treatment of cancer,^[1] though side effects such as pleuropericarditis and a flu-like syndrome precluded further development. They also show antiviral effects and may be reevaluated as potential options in the treatment of newly emerging viral diseases.^[2]

Synthesis

The treatment of 1-O-Acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose [6974-32-9] (1) with trimethylsilyl cyanide gives 2,3,5-Tri-O-benzoyl-beta-D-ribofuranosyl cyanide [23316-67-8] (2). Treatment with hydrogen sulfide led to (2R,3R,4R,5R)-2-((Benzoyloxy)methyl)-5-carbamothioyltetrahydrofuran-3,4-diyl dibenzoate, PC10907289 (3). Cyclization with Ethyl bromopyruvate [70-23-5] (4) led to 2-(2,3,5-Tri-O-benzoyl-beta-D-ribofuranosyl)-4-thiazolecarboxylic Acid Ethyl Ester [60084-09-5] (5). Removal of the protecting groups with sodium methoxide afforded 2-beta-D-Ribofuranosyl-4-thiazolecarboxylic Acid Ethyl Ester [95936-53-1] (6). Amide-ester interchange by treatment with dry ammonia completed the synthesis of Tiazofurin (7).

References

^ Popsavin M, Torović L, Svircev M, et al. (2006). "Synthesis and antiproliferative activity of two new tiazofurin analogues with 2'-amido functionalities". Bioorg. Med. Chem. Lett. 16 (10): 2773–6. doi:10.1016/j.bmcl.2006.02.001. PMID 16495053.
^ De Clercq E (March 2016). "C-Nucleosides To Be Revisited". Journal of Medicinal Chemistry. 59 (6): 2301–11. doi:10.1021/acs.jmedchem.5b01157. PMID 26513594.
^ Eastland, G.; Tiazofurine. Drugs Fut 1985, 10, 4, 304.

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[1] Popsavin M, Torović L, Svircev M, et al. (2006). "Synthesis and antiproliferative activity of two new tiazofurin analogues with 2'-amido functionalities". Bioorg. Med. Chem. Lett. 16 (10): 2773–6. doi:10.1016/j.bmcl.2006.02.001. PMID 16495053.

[2] De Clercq E (March 2016). "C-Nucleosides To Be Revisited". Journal of Medicinal Chemistry. 59 (6): 2301–11. doi:10.1021/acs.jmedchem.5b01157. PMID 26513594.

[3] Eastland, G.; Tiazofurine. Drugs Fut 1985, 10, 4, 304.

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