Nephronin: a series of compounds for treatment of infectious...

C - Chemistry – Metallurgy – 07 – C

Patent

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C07C 69/003 (2006.01) A61K 31/20 (2006.01) A61K 31/22 (2006.01) A61K 31/225 (2006.01) A61K 31/23 (2006.01) A61K 31/66 (2006.01) A61K 31/70 (2006.01) A61P 31/12 (2006.01) A61P 31/18 (2006.01) A61P 31/22 (2006.01) C07C 69/007 (2006.01) C07C 69/02 (2006.01) C07C 69/608 (2006.01) C07C 69/675 (2006.01) C07C 69/704 (2006.01) C07C 69/74 (2006.01) C07C 69/75 (2006.01) C07C 69/757 (2006.01) C07C 233/46 (2006.01) C07C 305/08 (2006.01) C07C 305/10 (2006.01) C07F 9/08 (2006.01) C07F 9/09 (2006.01)

Patent

CA 2355840

The present invention provides a non-proteinaceous compound isolatable from the urine of patients suffering from steroid responsive nephrotic syndrome. The compound has the following characterising features; (i) a molecular weight less than 1 KDa; (ii) binds specifically to heparin and heparan sulphate but not other glycosaminoglycans; and (iii) inhibits LPS induced production of TNF- .alpha. and/or IL-1.alpha.. The present invention also provides a compound of general formula: (I) in which l, m and n may be the same or different and integers of 0 to 10; and X is R-CO-O-, R-O-PO2-O-, R-O-SO2-O-, R-CO-NH-, R-CO- , R-O- or monosaccharide or oligosaccharide including amide substituted saccharides; in which R is a saturated, unsaturated, branched or cyclic carbon chain of up to 32 carbon atoms which optionally contains one or more hydroxyl groups, carbonyl groups, carboxylic acids groups, amino groups, phosphate groups or sulphate groups or combination thereof; and pharmaceutically acceptable salts and derivatives thereof.

L'invention concerne un composé non protéinique, que l'on peut isoler à partir de l'urine de patients souffrant d'un syndrome néphrotique sensible aux stéroïdes, et qui possède les caractéristiques suivantes: (i) un poids moléculaire inférieur à 1 KDa; (ii) une liaison spécifique à l'héparine et au sulfate d'héparane, mais pas à d'autres glycosaminoglycannes; et (iii) une inhibition de la production de TNF-.alpha. et/ou IL-1.alpha. induite par un lipopolysaccharide. L'invention concerne également un composé correspondant à la formule générale: (I) dans laquelle l, m et n peuvent être semblables ou différents et représenter des nombres entiers compris entre 0 et 10, X représente R-CO-O-, R-O-PO¿2?-O-, R-O-SO¿2?-O-, R-CO-NH-, R-CO-, R-O- ou un monosaccharide ou un oligosaccharide, notamment des saccharides à substitution amide, et R représente une chaîne carbone, saturée, insaturée, ramifiée ou cyclique, possédant jusqu'à 32 atomes de carbone et contenant éventuellement un ou plusieurs des groupes suivants: hydroxyle, carbonyle, acide carboxylique, amino, phosphate ou sulfate, ou des combinaisons de ces groupes. L'invention concerne également des sels et dérivés de ce composé, acceptables sur le plan pharmacologique.

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