US 2021/0228529 A1 · PHARMACEUTICAL COMPOSITIONS FOR TREATING BREAST CANCERS AND METHODS OF USES THEREOF

Abstract

This invention relates to the treatment of breast cancer in a subject, and the subject can be either a male or female subject. Including methods of: treating metastatic breast cancer; refractory breast cancer; AR-positive breast cancer; AR-positive refractory breast cancer; AR-positive metastatic breast cancer; AR-positive and ER-positive breast cancer; triple negative breast cancer; advanced breast cancer; breast cancer that has failed selective estrogen receptor modulator (SERM) (tamoxifen, toremifene, raloxifene), gonadotropin-releasing hormone (GnRH) agonist (goserelin), aromatase inhibitor (AI) (letrozole, anastrozole, exemestane), cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor (palbociclib (Ibrance), ribociclib (Kisqali), lerociclib, abemaciclib (Vorzenio), trilaciclib, lerociclib), mTOR inhibitor (everolimus), trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), alpelisib (Piqray) (an inhibitor of phosphatidylinositol-3-kinase subunit alpha (PI3Kα)), lapatinib, neratinib (Nerlynx), olaparib (Lynparza) (an inhibitor of the enzyme poly ADP ribose polymerase (PARP)), bevacizumab (Avastin), and/or fulvestrant treatments; metastasis in a subject suffering from breast cancer; HER2 -positive; treating a subject suffering from ER mutant expressing breast cancer and/or treating breast cancer in a subject, by first determining the 18F-16β-fluoro-5α-dihydrotestosterone (18F-DHT) tumor uptake and identifying said subject as having AR-positive breast cancer based on 18F-DHT tumor uptake, comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound and a cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor.

Claims32

Dependent claims

A pharmaceutical composition comprising a selective androgen receptor modulator (SARM) compound and a cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor, wherein said SARM compound is represented by a structure of formula I:

wherein
X is a bond, O, CH2, NH, S, Se, PR, NO, or NR;
G is O or S;
T is OH, OR, —NHCOCH3, or NHCOR;
R is alkyl, haloalkyl, dihaloalkyl, trihaloalkyl, CH2F, CHF2, CF3, CF2CF3, aryl, phenyl, halogen, alkenyl, or OH;
R1 is CH3, CH2F, CHF2, CF3, CH2CH3, or CF2CF3;
R2 is H, F, Cl, Br, I, CH3, CF3, OH, CN, NO2, NHCOCH3, NHCOCF3, NHCOR, alkyl, arylalkyl, OR, NH2, NHR, N(R)2, or SR;
R3 is H, F, Cl, Br, I, CN, NO2, COR, COOH, CONHR, CF3, Sn(R)3, or R3 together with the benzene ring to which it is attached forms a fused ring system represented by the structure:
Z is NO2, CN, COR, COOH, or CONHR;
Y is CF3, F, Br, Cl, I, CN, or Sn(R)3;
Q is CN, alkyl, halogen, N(R)2, NHCOCH3, NHCOCF3, NHCOR, NHCONHR, NHCOOR, OCONHR, CONHR, NHCSCH3, NHCSCF3, NHCSR, NHSO2CH3, NHSO2R, OR, COR, OCOR, OSO2R, SO2R, or SR;
or Q together with the benzene ring to which it is attached is a fused ring system represented by structure A, B or C:
n is an integer of 1-4;
and
m is an integer of 1-3, or
an optical isomer, a racemic mixture, a pharmaceutically acceptable salt, a pharmaceutical product, a hydrate, an N-oxide, or a crystal thereof.

13 more elements

Dependencies are inferred from the claim text.

Pharmaceutical compositions for treating breast cancers and methods of uses thereof

Life of this patent

Pharmaceutical compositions for treating breast cancers and methods of uses thereof

Life of this patent

Abstract

Claims32