Analogs of biologically active, naturally occurring polyamines, pharmaceutical compositions and methods of treatment

摘要

Polyamines having the formula: chemistry chemdraw filechemistry mol file;or a salt thereof with a pharmaceutically acceptable acid wherein: ;R₁-R₆ may be the same or different and are alkyl, aryl, aryl alkyl, cycloalkyl, optionally having an alkyl chain interrupted by at least one etheric oxygen atom, or hydrogen; ;N¹, N², N³ and N⁴ 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; ;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 polyamines: ;(i) are capable of uptake by a target cell upon administration thereof to a human or non-human animal; and ;(ii) upon uptake by the target cell, competitively bind via an electrostatic interaction between the positively charged nitrogen atoms to substantially the same biological counter-anions as the intracellular natural polyamines in the target cell; ;the polyamines, upon binding to the biological counter-anion in the cell, function in a manner biologically different than the intracellular polyamines, the polyamines not occurring in nature; as well as pharmaceutical compositions embodying the polyamines and methods of treating patients requiring anti-neoplastic therapy.