Small molecule regulators of steroid receptor coactivators and methods of use thereof
AssigneeBaylor College of Medicine
InventorsBert W. O'Malley, David Michael Lonard, Jin Wang, Jianming Xu, Jianwei Chen
Life of this patent
Estimating the term…
Abstract
Small molecule regulators of steroid receptor coactivator (SRC) family proteins are provided, as well as methods for their use in treating or preventing SRC-related diseases. The SRC-related diseases can include cancer, metabolic disorders, human immunodeficiency virus, neurodegenerative disorders, and/or inflammatory diseases. Also provided are methods for regulating SRC family proteins in a cell.
Claims44
A compound of the following formula:
- or a pharmaceutically acceptable salt or prodrug thereof, wherein:
- X is a substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
- R1, R4, R5, R6, and R7 are each independently selected from hydrogen, halogen, cyano, trifluoromethyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl;
- and
- R2 and R3 are each independently selected from hydrogen, substituted or unsubstituted alkyl, and substituted or unsubstituted aryl,
- wherein when X is a pyridine or a pyrimidine, (1) the pyridine or the pyrimidine is substituted, (2) at least one of R4, R5, R6, and R7 is other than hydrogen, or (3) R1 is other than hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted cycloalkyl.
A compound of the following formula:
- or a pharmaceutically acceptable salt or prodrug thereof, wherein:
- X is a substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
- R1, R4, R5, R6, and R7 are each independently selected from hydrogen, halogen, cyano, trifluoromethyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl;
- and
- R2 is hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted aryl.
A compound of the following formula:
- or a pharmaceutically acceptable salt or prodrug thereof, wherein:
- X is a substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
- R1, R5, R6, and R7 are each independently selected from hydrogen, halogen, cyano, trifluoromethyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl;
- and
- R2 is hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted aryl.
A compound of the following formula:
- or a pharmaceutically acceptable salt or prodrug thereof, wherein:
- X is a substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
- and
- R1, R5, R6, and R7 are each independently selected from hydrogen, halogen, cyano, trifluoromethyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl.
A compound of the following formula:
- or a pharmaceutically acceptable salt or prodrug thereof, wherein:
- X is a substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
- R1, R5, and R6 are each independently selected from hydrogen, halogen, cyano, trifluoromethyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl;
- and
- R2, R3, and R4 are each independently selected from hydrogen, substituted or unsubstituted alkyl, and substituted or unsubstituted aryl.
A compound of the following formula:
- or a pharmaceutically acceptable salt or prodrug thereof, wherein:
- X is a substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
- R1, R5, and R6 are each independently selected from hydrogen, halogen, cyano, trifluoromethyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl;
- and
- R3 and R4 are each independently selected from hydrogen, cyano, substituted or unsubstituted alkyl, and substituted or unsubstituted aryl.
A compound of the following formula:
- or a pharmaceutically acceptable salt or prodrug thereof, wherein:
- X is a substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
- R1, R4, R5, R6, and R7 are each independently selected from hydrogen, halogen, cyano, trifluoromethyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl;
- and
- R2 and R3 are each independently selected from hydrogen, substituted or unsubstituted alkyl, and substituted or unsubstituted aryl.
A compound of the following formula:
- or a pharmaceutically acceptable salt or prodrug thereof, wherein:
- X is a substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
- R1, R4, R5, R6, and R7 are each independently selected from hydrogen, halogen, cyano, trifluoromethyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl;
- and
- R3 is hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted aryl.
A compound of the following formula:
- or a pharmaceutically acceptable salt or prodrug thereof, wherein:
- X is a substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
- R1, R4, R5, R6, and R7 are each independently selected from hydrogen, halogen, cyano, trifluoromethyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl;
- and
- R3 is hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted aryl.
A compound of the following formula:
- or a pharmaceutically acceptable salt or prodrug thereof, wherein:
- X is a substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
- R1, R2, and R3 are each independently selected from hydrogen, substituted or unsubstituted alkyl, and substituted or unsubstituted aryl;
- and
- R4, R5, R6, and R7 are each independently selected from hydrogen, halogen, cyano, trifluoromethyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl.
A compound of the following formula:
- or a pharmaceutically acceptable salt or prodrug thereof, wherein:
- X is a substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
- R1, R2, and R3 are each independently selected from hydrogen, substituted or unsubstituted alkyl, and substituted or unsubstituted aryl;
- and
- R4, R5, R6, and R7 are each independently selected from hydrogen, halogen, cyano, trifluoromethyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl.
A compound of the following formula:
- or a pharmaceutically acceptable salt or prodrug thereof, wherein:
- X is a substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
- R1, R4, R5, R6, and R7 are each independently selected from hydrogen, halogen, cyano, trifluoromethyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl;
- and
- R3 is hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted aryl.
A compound of the following formula:
- or a pharmaceutically acceptable salt or prodrug thereof, wherein:
- X is a substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
- R2 and R3 are each independently selected from hydrogen, substituted or unsubstituted alkyl, and substituted or unsubstituted aryl;
- and
- R4, R5, R6, and R7 are each independently selected from hydrogen, halogen, cyano, trifluoromethyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl.
A compound of the following formula:
- or a pharmaceutically acceptable salt or prodrug thereof, wherein:
- X is a substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
- R3 is hydrogen, substituted or unsubstituted alkyl, and substituted or unsubstituted aryl;
- and
- R4, R5, R6, and R7 are each independently selected from hydrogen, halogen, cyano, trifluoromethyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl.
A method of treating a metabolic disorder, human immunodeficiency virus, a neurodegenerative disorder, or an inflammatory disease in a subject, comprising:
- administering to the subject an effective amount of a compound of the following formula:
- or a pharmaceutically acceptable salt or prodrug thereof, wherein:
- Y1 and Y2 are each independently selected from CH and N;
- and
- R1, R2, and R3 are each independently selected from hydrogen and substituted or unsubstituted alkyl,
- wherein at least one of Y1 and Y2 is N.
A method of regulating a steroid receptor coactivator protein in a cell, comprising:
- contacting a cell with an effective amount of a compound of the following formula:
- or a pharmaceutically acceptable salt or prodrug thereof, wherein:
- Y1 and Y2 are each independently selected from CH and N;
- and
- R1, R2, and R3 are each independently selected from hydrogen and substituted or unsubstituted alkyl,
- wherein at least one of Y1 and Y2 is N.
A compound of the following formula:
- or a pharmaceutically acceptable salt or prodrug thereof, wherein:
- is a single bond or a double bond;
- X and Y are each independently selected from the group consisting of substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, and substituted or unsubstituted alkynyl;
- A1 is B, CR, CRR′, N, NR, O, or S;
- A2 is BR, CRR′, NR, O, or S;
- R and R′ are each independently selected from hydrogen, halogen, cyano, trifluoromethyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl;
- and
- R1 is hydrogen, halogen, cyano, trifluoromethyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocycloalkyl,
- wherein if X is pyridine, is a double bond, A1 is N, A2 is NH, and R1 is methyl, then Y is not unsubstituted benzimidazole or N-methyl-benzimidazole.
Dependencies are inferred from the claim text.