Bisphenol derivatives and their use as androgen receptor activity modulators
AssigneesProvincial Health Services Authority, The University of British Columbia
InventorsRaymond John ANDERSEN, Marianne Dorothy SADAR, Kunzhong JIAN, Nasrin R. MAWJI, Jun WANG, Carmen Adriana BANUELOS, Yu-Chi YANG
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Abstract
Compounds having a structure of Formula I: or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R1, R2, R3, R11a, R11b, R11c, R11d, and X, are as defined herein, are provided. Uses of such compounds for modulating androgen receptor activity, imaging diagnostics in cancer and therapeutics, and methods for treatment of subjects in need thereof, including prostate cancer are also provided.
Claims67
A compound having the following structure (I):
- or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein:
- X is —S(O)n— or —C(R8R9)—;
- R1 is H, hydroxyl or —OC(═O)R13;
- R2 is hydroxyl or —OC(═O)R13;
- R3 is halo, —OH, —OR4;
- —OC(═O)R13, —NH2, —NHC(═O)R13, —N(C(═O)R13)2, —NHS(O)nR5, —N(C(═O)R13)(S(O)nR5), —N(C1-C6 alkyl)(S(O)nR5), —S(O)nR5, —N3, aryl, carbocyclyl, heteroaryl or heterocyclyl which are optionally substituted with one or more R6;
- R4 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, carbocyclyl, heteroaryl or heterocyclyl which are optionally substituted with one or more R6;
- R5 is each independently C1-C6 alkyl or aryl which are optionally substituted with one or more R6;
- R6 is each independently selected from the group consisting of H, F, Cl, Br, I, 123I, hydroxyl, oxo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C6-C12 aryl, wherein each R6 is optionally substituted with one or more of halogen, 123I, 18F, hydroxyl, —OS(O)2-aryl, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl;
- R8 and R9 are each independently H or C1-C6 alkyl;
- R11a, R11b, R11c and R11d are each independently H, methyl, F, Cl, Br, I, or 123I;
- R13 is C1-C6 alkyl;
- and
- n is 0, 1, or 2;
- wherein at least one of R11a, R11b, R11c and R11d is methyl F, Cl, Br, I, or 123I.
A compound having the following structure (II):
- or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein:
- R1 is H, —OH or —OC(═O)R13;
- R2 is —OH or —OC(═O)R13;
- R3 is halo, —OH, —OR4, —OC(═O)R13, —NH2, NHC(═O)R13, —N(C(═O)R13)2, —NHS(O)nR5, —N(C1-C6 alkyl)S(O)nR5, —N(C(═O)R13)(S(O)nR5), —S(O)nR5, —N3, aryl, carbocyclyl, heteroaryl or heterocyclyl which are optionally substituted with one or more R6;
- R4 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, carbocyclyl, heteroaryl or heterocyclyl which are optionally substituted with one or more R6;
- R5 is each independently C1-C6 alkyl or aryl which are optionally substituted with one or more R6;
- R6 is each independently selected from the group consisting of H, F, Cl, Br, I, 123I, hydroxyl, oxo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C6-C12 aryl, wherein each R6 is optionally substituted with one or more of halogen, 123I, 18F, hydroxyl, —OS(O)2-aryl, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl;
- and
- n is 0, 1, or 2.
Dependencies are inferred from the claim text.