Myc modulators and uses thereof
AssigneeMassachusetts Institute of Technology
InventorsAngela N. Koehler, Eric Stefan, Francisco Caballero
Life of this patent
Estimating the term…
Abstract
The present disclosure provides compounds of Formula (I-a), Formula (I), and Formula (II). The compounds described herein may be Myc modulators (e.g., Myc inhibitors) and may be useful in treating in a subject in need thereof diseases associated with Myc and proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including a compound described herein.
Claims94
A compound of Formula (I-a):
- or a pharmaceutically acceptable salt thereof, wherein:
- each instance of RA is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —ORa, —N(Ra)2, —SRa, —CN, —SCN, —C(═NRa)Ra, —C(═NRa)ORa, —C(═NRa)N(Ra)2, —C(═O)Ra, —C(═O)ORa, —C(═O)N(Ra)2, —NO2, —N(Ra)C(═O)Ra, —N(Ra)C(═O)ORa, —N(Ra)C(═O)N(Ra)2, —N(Ra)S(═O)Ra, —N(Ra)S(═O)ORa, —N(Ra)S(═O)N(Ra)2, —N(Ra)S(═O)2Ra, —N(Ra)S(═O)2ORa, —N(Ra)S(═O)2N(Ra)2, —OC(═O)Ra, —OC(═O)ORa, or —OC(═O)N(Ra)2, or two instances of RA are joined to form a substituted or unsubstituted, carbocyclic ring, substituted or unsubstituted, heterocyclic ring, substituted or unsubstituted, aryl ring, or substituted or unsubstituted, heteroaryl ring;
- k is 0, 1, 2, or 3;
- L is —N—, —O—, —S—, or a bond;
- Xa is —NRB—, —O—, or —S—;
- Wa is —C(RA)═, or —N═;
- RB is hydrogen, substituted or unsubstituted C1-6 alkyl, or a nitrogen protecting group;
- RD is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —ORd1, —N(Rd1)2, —NO2, —NRd1C(═O)Rd1, —NRd1C(═O)ORd1, —NRd1C(═O)N(Rd1)2, —OC(═O)Rd1, —OC(═O)ORd1, —OC(═O)N(Rd1)2, —C(═O)Rd1, —C(═O)ORd1, —C(═O)N(Rd1)2, —CH2N(Rd1)2, or —CH2ORd1;
- each instance of Ra is independently hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of Ra are joined to form a substituted or unsubstituted carbocyclyl ring, substituted or unsubstituted, heterocyclic ring, substituted or unsubstituted aryl ring, or substituted or unsubstituted, heteroaryl ring;
- each instance of Rd1 is independently hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of Rd1 are joined to form a substituted or unsubstituted carbocyclyl ring, substituted or unsubstituted, heterocyclic ring, substituted or unsubstituted aryl ring, or substituted or unsubstituted, heteroaryl ring;
- and
- Ring A is a substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.
A compound of Formula (II):
- or a pharmaceutically acceptable salt thereof, wherein:
- the double bond labeled with “a” is in the (E)- or (Z)-configuration;
- RC is hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —C(═O)Ra, —C(═O)ORa, —C(═O)N(Ra)2, or a nitrogen protecting group;
- each instance of Ra is independently hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of Ra are joined to form a substituted or unsubstituted, heterocyclic ring, or substituted or unsubstituted, heteroaryl ring;
- and
- RE is a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl.
A method of treating a disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of any one of claims 1-69, or a pharmaceutical composition of claim 70 or 72, wherein the disease is associated with Myc.
The method of 81, wherein the disease is lung cancer, cervical cancer, breast cancer, or colorectal cancer.
The method of 81, wherein the disease is ovarian cancer, pancreatic cancer, gastric cancer, or uterine cancer.
The method of 81, wherein the disease is hematological malignancy.
The method of 81, wherein the disease is lymphoma.
Dependencies are inferred from the claim text.