Patent ID: 6432970
Filing Date: 2002-08-13
Classification: A61K

Abstract:
A method for inhibiting activation of a hedgehog-patched pathway in a patient diagnosed with a hyperproliferative disorder, comprising administering to the patient a composition comprising a purified hedgehog antagonist in a sufficient amount to reduce the activation of the hedgehog-patched pathway in a cell of the patient, wherein the antagonist is a steroidal alkaloid having a structure represented in the general formula (I), or unsaturated forms thereof and/or nor- or homo-derivatives thereof: wherein, as valence permits,R2, R3, R4, and R5, represent one or more substitutions to the ring to which each is attached, for each occurrence, independently represent hydrogen, halogens, alkyls, alkenyls, alkynyls, aryls, hydroxyl, =O, =S, alkoxyl, silyloxy, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, carboxamides, anhydrides, silyls, ethers, thioethers, alkylsulfonyls, arylsulfonyls, selenoethers, ketones, aldehydes, esters, or â€”(CH2)mâ€”R8; R6, R7, and Râ€²7, independently for each occurrence, are absent or represent hydrogens, halogens, alkyls, alkenyls, alkynyls, aryls, hydroxyl, =O, =S, alkoxyl, silyloxy, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, carboxamides, anhydrides, silyls, ethers, thioethers, alkylsulfonyls, arylsulfonyls, selenoethers, ketones, aldehydes, esters, or â€”(CH2)mâ€”R8, or R6 and R7, or R7 and Râ€²7, taken together form a ring or polycyclic ring, with the proviso that at least one of R6, R7, or Râ€²7 is present and includes a primary or secondary amine; R8 represents an aryl, a cycloalkyl, a cycloaklenyl, a heterocycle, or a polycycle; and m is an integer in the range 0 to 8 inclusive.