Sonic hedgehog modulators

A method of treating Gorlin syndrome, medulloblastoma, basal cell carcinoma, or pancreatic cancer in a subject suffering therefrom, the method comprising administering to the subject a therapeutically effective amount of a compound of formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• designates a single or double bond;
• X1 is —O—;
• X2 is —NR—;
• Y1, Y2, and Y3 are each ═O;
• Z is —NR4R5 or —OR5;
• T is a covalent bond or a bivalent C1-12 saturated or unsaturated, straight or branched, aliphatic chain;
• j is 1;
• k is 1;
• m is an integer from 0 to 2, inclusive;
• n is an integer from 0 to 2, inclusive;
• each occurrence of R1 is independently hydrogen, halogen, —CN, —SCN, —NO2, —CO2R, —SOR, —SO2R, —NR2, —OR, —SR, or an optionally substituted group selected from the group consisting of —C(═O)-alkyl, —C(═O)-alkenyl, —C(═O)-alkynyl, —C(═O)-aryl, —C(═O)-carbocyclic, —C(═O)-heterocyclic, —C(═O)-(aromatic heterocyclic), C1-12 aliphatic, C1-12 heteroaliphatic, C7-15 arylalkyl, C3-15 heteroarylalkyl, 6-10-membered aryl, 5-10-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and 4-7-membered heterocyclyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• or
• two R1 groups may be taken together with their intervening atoms to form a 3-8-membered ring;
• or
• when X2 is —NR—, R1 and the R of —NR— may be taken together with their intervening atoms to form a 3-8-membered ring;
• each occurrence of R2 is independently hydrogen, halogen, —CN, —SCN, —NO2, —CO2R, —SOR, —SO2R, —NR2, —OR, —SR, or an optionally substituted group selected from the group consisting of —C(═O)-alkyl, —C(═O)-alkenyl, —C(═O)-alkynyl, —C(═O)-aryl, —C(═O)-carbocyclic, —C(═O)-heterocyclic, —C(═O)-(aromatic heterocyclic), C1-12 aliphatic, C1-12 heteroaliphatic, C7-15 arylalkyl, C3-15 heteroarylalkyl, 6-10-membered aryl, 5-10-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and 4-7-membered heterocyclyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• or
• two R2 groups may be taken together with their intervening atoms to form a 3-8-membered ring;
• R3 is hydrogen, halogen, —CN, —SCN, —NO2, —CO2R, —SOR, —SO2R, —NR2, —OR, —SR, or an optionally substituted group selected from the group consisting of —C(═O)-alkyl, —C(═O)-alkenyl, —C(═O)-alkynyl, —C(═O)-aryl, —C(═O)-carbocyclic, —C(═O)-heterocyclic, —C(═O)-(aromatic heterocyclic), C1-12 aliphatic, C1-12 heteroaliphatic, C7-15 arylalkyl, C3-15 heteroarylalkyl, 6-10-membered aryl, 5-10-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and 4-7-membered heterocyclyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• R4 is hydrogen;
• R5 is hydrogen or —C(R6)3;
• each occurrence of R6 is independently hydrogen, halogen, —CN, —SCN, —NO2, —CO2R, —SOR, —SO2R, —NR2, —OR, —SR, or an optionally substituted group selected from the group consisting of —C(═O)-alkyl, —C(═O)-alkenyl, —C(═O)-alkynyl, —C(═O)-aryl, —C(═O)-carbocyclic, —C(═O)-heterocyclic, —C(═O)-(aromatic heterocyclic), C1-12 aliphatic, C1-12 heteroaliphatic, C7-15 arylalkyl, C3-15 heteroarylalkyl, 6-10-membered aryl, 5-10-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and 4-7-membered heterocyclyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• or
• two occurrences of R6 may be taken together with their intervening atoms to form a 3-8-membered ring;
• and
• each R is independently hydrogen, a protecting group, —C(═O)-alkyl, —C(═O)-alkenyl, —C(═O)-alkynyl, —C(═O)-aryl, —C(═O)-carbocyclic, —C(═O)-heterocyclic, —C(═O)-(aromatic heterocyclic), C7-15 arylalkyl moiety, C1-12 aliphatic moiety, 6-10-membered aryl moiety, 5-10-membered heteroaryl moiety having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or C1-12 heteroaliphatic moiety;
• or:
• two R on the same nitrogen atom may be taken with the nitrogen to form a 4-7-membered heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• wherein when a group is substituted, the group is substituted with one or more substituents independently selected from the group consisting of aliphatic, heteroaliphatic, aryl, heteroaryl, arylalkyl, heteroarylalkyl, alkoxy, aryloxy, heteroalkoxy, heteroaryloxy, alkylthio, arylthio, heteroalkylthio, heteroarylthio, —F, —Cl, —Br, —I, —OH, —NO2, —CN, —CF3, —CH2CF3, —CHCl2, —CH2OH, —CH2CH2OH, —CH2NH2, —CH2SO2CH3, —C(O)Rx1, —CO2(Rx1), —CON(Rx1)2, —OC(O)Rx1, —OCO2Rx1, —OCON(Rx1)2, —N(Rx1)2, —S(O)2Rx1, and —NRx1(CO)Rx1, wherein each occurrence of Rx1 is independently selected from the group consisting of aliphatic, heteroaliphatic, aryl, heteroaryl, arylalkyl, and heteroarylalkyl.