Androgen receptor regulation by small molecule enantiomers
AssigneeUniversity of Southern California
InventorsCharles E. McKenna, David B. Agus
Life of this patent
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Abstract
Herein is reported a class of chiral compounds with paradoxical effects on the androgen receptor (AR). The (R)-enantiomers behave like classical anti-androgens while the (S)-enantiomers activate AR signaling. In castration-resistant prostate cancer, the change during the course of therapy to growth in the presence of AR targeted therapeutics, a harbinger of progression to lethal disease, is commonly attributed to acquired mutations of the AR-ligand binding domain. This is the first report of an antagonist-agonist duality solely due to structural enantiomerism, without any modification to the AR binding site.
Claims15
A method for the treatment of an endocrine disorder or a hormonal disorder in a subject in need thereof by administering to the subject an effective amount of a compound of Formula I:
- or
- a salt thereof;
- wherein
- G1 is NHRA or OH;
- G2 is H or OH;
- RA is —C(═O)heteroaryl, —C(═O)(C1-C6)alkyl, —S(═O)2(C1-C6)alkyl, or —C(═O)heterocycloalkyl, wherein RA is substituted or unsubstituted with substituents;
- R1 is H, halo, or —(C1-C6)alkyl;
- and
- R3 is CF3 or halo.
A compound represented by Formula IA:
- the enantiomer and/or a salt thereof;
- wherein
- R1 is H, F, methyl, or ethyl;
- and
- R2 is H, —C(═O)CH3, or —C(OH)CH3.
Dependencies are inferred from the claim text.