Steroid derivatives, pharmaceutical compositions containing...

C - Chemistry – Metallurgy – 07 – J

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C07J 41/00 (2006.01) A61K 31/56 (2006.01) C07J 17/00 (2006.01) C07J 31/00 (2006.01) C07J 43/00 (2006.01) C07J 51/00 (2006.01)

Patent

CA 2185123

Compounds having a broad range of antimicrobial activity generally have a structure including a steroid nucleus with a cationic, preferably polyamine, side chain (X) and an anionic side chain (Y). The invention is also directed to compounds of formula (III), preferably where the steroid ring nucleus is saturated; the steroid ring substituent Z5 is a-H; one Z7 is .beta.-H and the other is .alpha.-H or .alpha.-OH; both substituents Z12 are hydrogen; X' is a polyamine side chain of the formula - NH(CH2)p-NH(CH2)q- N(R11)(R111) where p and q are each independently 3 or 4, and R II and R III are each independently hydrogen or methyl; R' is methyl; and Y' is (C1-C10)-alkyl substituted with a group such as -CO2H or -SO3H. Such compounds, as well as squalamine itself, have antiangiogenic activity and Na+/K+-- ATPase-inhibiting activity.

Des composés présentant une activité antimicrobienne étendue présentent généralement une structure comprenant un noyau stéroïde avec une chaîne latérale (X) cationique, de préférence polyamine, et une chaîne latérale (Y) anionique. L'invention concerne également des composés de formule (III), dans laquelle, de préférence, le noyau du cycle stéroïde est saturé; le substituant du cycle stéroïde Z5 représente alpha -H; un Z7 représente beta -H et l'autre alpha -H ou alpha -OH; les deux substituants Z12 représentent hydrogène; X' est une chaîne latérale polyamine de formule -NH-(CH2)p-NH -(CH2)q-N(R<II>)(R<III>) où p et q valent indépendamment 3 ou 4, et R<II> et R<III> représentent indépendamment hydrogène ou méthyle; R' représente méthyle; et Y' représente alkyle-(C1-C10) substitué avec un groupe tel que -CO2H ou -SO3H. Ces composés ainsi que la squalamine présentent une activité antiangiogénique et d'inhibition de la NA<+>/K<+>-ATPase.

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