DIAMINOPYRIMIDINE BENZENESULFONE DERIVATIVES AND USES THEREOF

摘要

The present invention provides compounds of Formula (II) (e.g., compounds of Formula (I)), and pharmaceutically compositions thereof. Compounds of Formula (II) are believed to be binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.;

主权项

1. A compound of Formula (II): or pharmaceutically acceptable salt thereof; wherein:
R1 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, or a nitrogen protecting group when attached to a nitrogen atom;R2 is 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, —ORD1, —N(RD1)2, —SRD1, —CN, —SCN, —C(═NRD1)RD1, —C(═NRD1)ORD1, —C(═NRD1)N(RD1)2, —C(═O)RD1, —C(═O)ORD1, —C(═O)N(RD1)2, —NO2, —NRD1C(═O)RD1, —NRD1C(═O)ORD1, —NRD1C(═O)N(RD1)2, —OC(═O)RD1, —OC(═O)ORD1, or —OC(═O)N(RD1)2, wherein 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 RD1 groups are joined to form a substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring;R3 and R4 are each independently 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, or a nitrogen protecting group; or R3 and R4 groups are joined to form an substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring;each instance of R5 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, or substituted or unsubstituted heteroaryl;each instance of R6 is independently 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, —ORB1a, —N(RB1a)2, —SRB1a, —CN, —SCN, —C(═NRB1a)RB1a, —C(═NRB1a)ORB1a, —C(═NRB1a)N(RB1a)2, —C(═O)RB1a, —C(═O)ORB1a, —C(═O)N(RB1a)2, —NO2, —NRB1aC(═O)RB1a, —NRB1aC(═O)ORB1a, —NRB1aC(═O)N(RB1a)2, —OC(═O)RB1a, —OC(═O)ORB1a, or —OC(═O)N(RB1a)2;q is 0, 1, 2, 3, or 4;A is ═N— or ═C(R2)—;each instance of RB1 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, —ORB1a, —N(RB1a)2, —SRB1a, —CN, —SCN, —C(═NRB1a)RB1a, —C(═NRB1a)ORB1a, —C(═NRB1a)N(RB1a)2, —C(═O)RB1a, —C(═O)ORB1a, —C(═O)N(RB1a)2, —NO2, —NRB1aC(═O)RB1a, —NRB1aC(═O)ORB1a, —NRB1aC(═O)N(RB1a)2, —OC(═O)RB1a, —OC(═O)ORB1a, or —OC(═O)N(RB1a)2;each instance of RB1a 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 RB1a groups are joined to form a substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring;p is 0 or an integer between 1 and 4, inclusive;n is 0, 1, 2, 3, 4, 5, or 6;L1, L2, and L4 are each independently a bond, L3 is Ra1 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, or a nitrogen protecting group; andeach instance of Rc1 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, —ORc1a, —N(Rc1a)2, —SRc1a, —CN, —C(═O)Rc1a, —C(═O)ORc1a, —C(═O)N(Rc1a)2, —NRc1aC(═O)Rc1a, —NRc1aC(═O)ORc1a, —NRc1aC(═O)N(Rc1a)2, —OC(═O)Rc1a, or —OC(═O)N(Rc1a)2, wherein each instance of Rc1a 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 Rc1a groups are joined to form a substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring.