Regulators of the hedgehog pathway, compositions and uses related thereto

A compound represented in the general formula (II), or unsaturated forms thereof and/or seco-, nor- or homo-derivatives thereof:

• wherein, as valence and stability permit,
• R2 and R3, independently for each occurrence, represent one or more substitutions to the ring to which each is attached, selected from 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, sugar, carbamate, carbonate, or (CH2)m—R8;
• R4 and R5, independently for each occurrence, are absent or represent one or more substitutions to the ring to which each is attached, selected from 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, sugar, carbamate, carbonate, or —(CH2)m—R8;
• R6, R7, and R′7, are absent or represent, independently, halogen, alkyl, alkenyl, alkynyl, aryl, hydroxyl, ═O, ═S, alkoxyl, silyloxy, amino, nitro, thiol, amine, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, ether, thioether, alkylsulfonyl, arylsulfonyl, selenoether, ketone, aldehyde, ester, or —(CH2)m—R8,
• R7, or R7 and R′7, taken together, form a substituted or unsubstituted ring or polycycle, which includes a tertiary amine in the atoms which make up the ring, wherein, if the ring is formed by R7 and R′7, the tertiary amine contained therein is substituted by an alkyl substituted with a group selected from aryl, aralkyl, heteroaryl, heteroaralkyl, amide, acylamino, carbonyl, ester, carbamate, urea, ketone, sulfonamide, carbocyclyl, heterocyclyl, polycyclyl, ether, halogen, alkenyl, and alkynyl;
• R8 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle, or a polycycle;
• X represents O or S;
• and
• m is an integer in the range 0 to 8 inclusive;
• or a pharmaceutically acceptable salt thereof.

A compound represented in the general formula (III), or unsaturated forms thereof and/or seco-, nor- or homo-derivatives thereof:

• wherein, as valence and stability permit,
• R2 and R3, independently for each occurrence, represent one or more substitutions to the ring to which each is attached, selected from 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, sugar, carbamate, carbonate, or —(CH2)m—R8;
• R4 and R5, independently for each occurrence, are absent or represent one or more substitutions to the ring to which each is attached, selected from 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, sugar, carbamate, carbonate, or —(CH2)m—R8;
• R8 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle, or a polycycle;
• B represents a monocyclic or polycyclic group;
• T represents an alkyl, an aminoalkyl, a carboxyl, an ester, an amide, ether or amine linkage of 1–10 bond lengths;
• T′ is absent, or represents an alkyl, an aminoalkyl, a carboxyl, an ester, an amide, ether or amine linkage of 1–3 bond lengths, wherein if T and T′ are both present, T and T′ taken together with the ring B form a covalently closed ring of 5–8 ring atoms;
• R9 is absent or, independently for each occurrence, represents one or more substitutions to the ring to which it is attached, selected from halogen, alkyl, alkenyl, alkynyl, aryl, hydroxyl, ═O, ═S, alkoxyl, silyloxy, amino, nitro, thiol, amine, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, ether, thioether, alkylsulfonyl, arylsulfonyl, selenoether, ketone, aldehyde, ester, or —(CH2)m—R8;
• and
• n and m are, independently, zero, 1 or 2;
• with the proviso that T, T′, and B, taken together, include at least one tertiary amine;
• wherein the tertiary amine is substituted by an alkyl substituted with a group selected from aryl, aralkyl, heteroaryl, heteroaralkyl, amide, acylamino, carbonyl, ester, carbamate, urea, ketone, sulfonamide, carbocyclyl, heterocyclyl, polycyclyl, ether, halogen, alkenyl, and alkynyl;
• or a pharmaceutically acceptable salt thereof.

A compound represented in the general formula (IV), or unsaturated forms thereof and/or seco-, nor- or homo-derivatives thereof:

• wherein, as valence and stability permit,
• R2 and R3, independently for each occurrence, represent one or more substitutions to the ring to which each is attached, selected from 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 —(CH2)m—R8;
• R4 and R5, independently for each occurrence, are absent or represent one or more substitutions to the ring to which each is attached, selected from 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, sugar, carbamate, carbonate, or —(CH2)m—R8;
• R6 is absent or represents, independently, halogen, alkyl, alkenyl, alkynyl, aryl, hydroxyl, ═O, ═S, alkoxyl, silyloxy, amino, nitro, thiol, amine, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, ether, thioether, alkylsulfonyl, arylsulfonyl, selenoether, ketone, aldehyde, ester, or —(CH2)m—R8;
• R8 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle, or a polycycle;
• R9 is, independently for each occurrence, represents one or more substitutions to the ring to which it is attached, selected from halogen, alkyl, alkenyl, alkynyl, aryl, hydroxyl, ═O, ═S, alkoxyl, silyloxy, amino, nitro, thiol, amine, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, ether, thioether, alkylsulfonyl, arylsulfonyl, selenoether, ketone, aldehyde, ester, or —(CH2)m—R8;
• R22 is absent or represents an alkyl, an alkoxyl or —OH;
• and
• m is an integer in the range 0 to 8 inclusive,
• wherein at least one occurrence of R9 is bound to N, thereby forming a tertiary amine, and this occurrence of R9 is an alkyl substituted with a group selected from aryl, aralkyl, heteroaryl, heteroaralkyl, amide, acylamino, carbonyl, ester, carbamate, urea, ketone, sulfonamide, carbocyclyl, heterocyclyl, polycyclyl, ether, halogen, alkenyl, and alkynyl;
• or a pharmaceutically acceptable salt thereof.

A compound represented in the general formula (V) or unsaturated forms thereof and/or seco-, nor- or homo-derivatives thereof:

• wherein, as valence and stability permit,
• R2 and R3, independently for each occurrence, represent one or more substitutions to the ring to which each is attached, selected from 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 —(CH2)m—R8;
• R4 is absent or represents one or more substitutions to the ring to which each is attached, selected from 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, sugar, carbamate, carbonate, or —(CH2)m—R8;
• R6 is absent or represents halogen, alkyl, alkenyl, alkynyl, aryl, hydroxyl, ═O, ═S, alkoxyl, silyloxy, amino, nitro, thiol, amine, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, ether, thioether, alkylsulfonyl, arylsulfonyl, selenoether, ketone, aldehyde, ester, or —(CH2)m—R8;
• R8 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle, or a polycycle;
• R9 is, independently for each occurrence, represents one or more substitutions to the ring to which it is attached, selected from halogen, alkyl, alkenyl, alkynyl, aryl, hydroxyl, ═O, ═S, alkoxyl, silyloxy, amino, nitro, thiol, amine, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, ether, thioether, alkylsulfonyl, arylsulfonyl, selenoether, ketone, aldehyde, ester, or —(CH2)m—R8;
• and
• m is an integer in the range 0 to 8 inclusive,
• wherein at least one occurrence of R9 is attached to N, thereby forming a tertiary amine, and this occurrence of R9 is an alkyl substituted with a group selected from aryl, aralkyl, heteroaryl, heteroaralkyl, amide, acylamino, carbonyl, ester, carbamate, urea, ketone, sulfonamide, carbocyclyl, heterocyclyl, polycyclyl, ketone, ether, halogen, alkenyl, and alkynyl;
• or a pharmaceutically acceptable salt thereof.