Patent ID: 6274630
Filing Date: 2001-08-14
Classification: A61K,A61P

Abstract:
A method for the inhibition or prevention of the intracellular biosynthesis of Elf5A comprising administering to a human or non-human mammal in need thereof an amount of a polyamine sufficient to deplete the supply of intracellular spermidine required for Elf5A biosynthesis, but insufficient to substantially affect polyamine homeostasis, said polyamine having one of the formulae: ##STR7##wherein: R.sub.1 and R.sub.6 may be the same or different and are H, alkyl or aralkyl having from 1 to 12 carbon atoms, provided that, in formula (I), R.sub.1 and R.sub.6 are not H;R.sub.2 -R.sub.5 may be the same or different and are H, R.sub.1 or R.sub.6 ;R.sub.7 is H, alkyl, aryl or aralkyl having from 1 to 12 carbon atoms;m is an integer from 3 to 6, inclusive;n is an integer from 3 to 6, inclusive;v, w, x, y and z may be the same or different and are integers from 3 to 10, inclusive; ##STR8##or its stereoisomers wherein:R.sub.8 -R.sub.13 may be the same or different and are alkyl, branched alkyl, aryl, arylalkyl, cycloalkyl, optionally having an alkyl chain interrupted by at least one etheric oxygen atom, or hydrogen;N.sup.1, N.sup.2, N.sup.3 and N.sup.4 are nitrogen atoms capable of protonation at physiological pH's;a and b may be the same or different and are integers from 1 to 4, with the proviso that one, but not both, of a and b may be 0;A, B and C may be the same or different and are bridging groups which effectively maintain the distance between the nitrogen atoms such that the polyamine:(i) is capable of uptake by a target cell upon administration of the polyamine to a human or non-human mammal or is capable of binding to at least one polyamine site of a receptor located within or on the surface of a cell upon administration of the polyamine to a human or non-human mammal; and(ii) upon uptake by the target cell, competitively binds via an electrostatic interaction between the positively charged nitrogen atoms to biological counter-anions;the polyamine, upon binding to the biological counter-anion in the cell, functions in a manner substantially biologically different than the intracellular polyamines; andfurther wherein at least one of said bridging groups A, B and C may contain at least one --CH(OH)-- group which is not alpha- to either of the nitrogen atoms; or(V) a salt thereof with a pharmaceutically acceptable acid.