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US 8,895,576 B2Granted
Methods of use of cyclopamine analogs
AssigneeInfinity Pharmaceuticals, Inc.
InventorsAlfredo C. Castro, Michael J. Grogan, Karen J. McGovern, Martin R. Tremblay
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Abstract
The invention provides methods for treating various conditions using derivatives of cyclopamine having the following formula:
Claims25
A method of treating cancer of the hematopoietic system comprising administering to a patient a therapeutically effective amount of a compound of the formula:
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 is H, alkyl, —OR, amino, sulfonamido, sulfamido, —OC(O)R5, —N(R5)C(O)R5 or a sugar;
- R2 is H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, nitrile, or heterocycloalkyl;
- or R1 and R2 taken together form ═O, ═S, ═N(OR), ═N(R), ═N(NR2), or ═C(R)2;
- R3 is H, alkyl, alkenyl, or alkynyl;
- R4 is H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, heteroaralkyl, haloalkyl, —OR, —C(O)R5, —CO2R5, —SO2R5, —C(O)N(R5)(R5), —[C(R)2]q—R5, —[(W)—N(R)C(O)]qR5, —[(W)—C(O)]qR5, —[(W)—C(O)O]qR5, —[(W)—OC(O)]qR5, —[(W)—SO2]qR5, —[(W)—N(R5)SO2]qR5, —[(W)—C(O)N(R5)]qR5, —[(W)—O]qR5, —[(W)—N(R)]qR5, —W—NR3+X− or —[(W)—S]qR5;
- wherein each W is, independently, a diradical;
- each q is independently for each occurrence 1, 2, 3, 4, 5, or 6;
- X− is a halide;
- each R5 is, independently, H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, heteroaralkyl or —[C(R)2]p—R6;
- wherein p is 0-6;
- or
- any two occurrences of R5 on the same substituent can be taken together to form a 4-8 membered optionally substituted ring which contains 0-3 heteroatoms selected from N, O, S, and P;
- each R6 is independently hydroxyl, —N(R)COR, —N(R)C(O)OR, —N(R)SO2(R), —C(O)N(R)2, —OC(O)N(R)(R), —SO2N(R)(R), —N(R)(R), —COOR, —C(O)N(OH)(R), —OS(O)2OR, —S(O)2OR, —OP(O)(OR)(OR), —NP(O)(OR)(OR), or —P(O)(OR)(OR);
- and
- each R is independently H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl or aralkyl;
- provided that when R2, R3, and R4 are H;
- R1 is not hydroxyl or a sugar;
- further
- provided that when R4 is hydroxyl, then R1 is not a sugar or hydroxyl;
- further
- provided that when R4 is hydroxyl, then R1 and R2 together are not C═O.
19 more elements
Dependencies are inferred from the claim text.