US 7,888,337 B2 · Synthesis of oseltamivir containing phosphonate congeners with anti-influenza activity

Abstract

Novel phosphonate compounds are described. The compounds have activity as neuraminidase inhibitors against wild-type and H274Y mutant of H1N1 and H5N1 viruses. The present disclosure also provides an enantioselective synthetic route to known neuraminidase inhibitors oseltamivir and the anti-flu drug Tamiflu®, as well as novel phosphonate compounds, via D-xylose. Another efficient and flexible synthesis of Tamiflu and the highly potent neuraminidase inhibitor Tamiphosphor was also achieved in 11 steps and >20% overall yields from the readily available fermentation product (1S-cis)-3-bromo-3,5 -cyclohexadiene-1,2-diol. Most of the reaction intermediates were obtained as crystals without tedious purification procedures. The key transformations include an initial regio- and stereoselective bromoamidation of a bromoarene cis-dihydrodiol, as well as the final palladium-catalyzed carbonylation and phosphonylation.

Claims26

Dependent claims

A composition comprising:

a therapeutically effective amount of formula I:
wherein A is PO(OR)(OR′), where R and R′ are independently selected from H, C1-C6 alkyl, aryl, and X, X being a cationic counterion selected from the group consisting of ammonium, methyl ammonium, dimethylammonium, trimethylammonium, tetramethylammonium, ethanol-ammonium, dicyclohexylammonium, guanidinium, ethylenediammonium cation, lithium cation, sodium cation, potassium cation, cesium cation, beryllium cation, magnesium cation, calcium cation, and zinc cation;
and R1 is NH2, NH3+H2PO4−, or NH(C═NH)NH2;
and
a pharmaceutical carrier.

2 more elements

Dependencies are inferred from the claim text.

Synthesis of oseltamivir containing phosphonate congeners with anti-influenza activity

Life of this patent

Synthesis of oseltamivir containing phosphonate congeners with anti-influenza activity

Life of this patent

Abstract

Claims26