UREA DERIVATIVES AND USES THEREOF

摘要

The present invention provides novel compounds of any one of Formulae (I)-(III), and pharmaceutical compositions thereof. Also provided are particles (e.g., nanoparticles) comprising compounds of Formula (I)-(III) and pharmaceutical compositions thereof that are mucus penetrating. The invention also provides methods and kits for using the inventive compounds, and pharmaceutical compositions thereof, for treating and/or preventing diseases associated with abnormal or pathological angiogenesis and/or aberrant signaling of a growth factor (e.g., vascular endothelial growth factor (VEGF)), such as proliferative diseases (e.g., cancers, benign neoplasms, inflammatory diseases, autoimmune diseases) and ocular diseases (e.g., macular degeneration, glaucoma, diabetic retinopathy, retinoblastoma, edema, uveitis, dry eye, blepharitis, and post-surgical inflammation) in a subject in need thereof.;

主权项

1. A compound of Formula (I): or a pharmaceutically acceptable salt thereof; wherein:
XC is CH, N, or NH;XD is CH, N, or NH;each instance of RA is independently hydrogen, halogen, 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, —ORA1, —N(RA1)2, —SRA1, —CN, —SCN, —C(═NRA1)RA1, —C(═NRA1)ORA1, —C(═NRA1)N(RA1)2, —C(═O)RA1, —C(═O)ORA1, —C(═O)N(RA1)2, —NO2, —NRA1C(═O)RA1, —NRA1C(═O)ORA1, —NRA1C(═O)N(RA1)2, —OC(═O)RA1, —OC(═O)ORA1, or —OC(═O)N(RA1)2, or two instances of RA are joined to form substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;each instance of RA1 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 RA1 are joined to form substituted or unsubstituted heterocyclyl;Ring Z is substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;each instance of RB is independently hydrogen, halogen, 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, —ORB1, —N(RB1)2, —SRB1, —CN, —SCN, —C(═NRB1)RB1, —C(═NRB1)ORB1, —C(═NRB1)N(RB1)2, —C(═O)RB1, —C(═O)ORB1, —C(═O)N(RB1)2, —NO2, —NRB1C(═O)RB1, —NRB1C(═O)ORB1, —NRB1C(═O)N(RB1)2, —OC(═O)RB1, —OC(═O)ORB1, or —OC(═O)N(RB1)2, or two instances of RB are joined to form substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;each instance of RB1 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 RB1 are joined to form substituted or unsubstituted heterocyclyl;RC is substituted or unsubstituted alkyl, a nitrogen protecting group, or of the formula: Ring C is substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;each instance of RC1 is independently hydrogen, halogen, 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, —ORC1a, —N(RC1a)2, —SRC1a, —CN, —SCN, —C(═NRC1a)RC1a, —C(═NRC1a)ORC1a, —C(═NRC1a)N(RC1a)2, —C(═O)RC1a, —C(═O)ORC1a, —C(═O)N(RC1a)2, —NO2, —NRC1aC(═O)RC1a, —NRC1aC(═O)ORC1a, —NRC1aC(═O)N(RC1a)2, —OC(═O)RC1a, —OC(═O)ORC1a, —OC(═O)N(RC1a)2, or a nitrogen protecting group when attached to a nitrogen atom, or two instances of RC1 are joined to form substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; 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 instances of RC1a are joined to form substituted or unsubstituted heterocyclyl; RD is hydrogen, substituted or unsubstituted C1-6 alkyl, or a nitrogen protecting group; RE is hydrogen, substituted or unsubstituted C1-6 alkyl, or a nitrogen protecting group; a is 0, 1, 2, or 3; b is 0, 1, 2, 3, or 4; and c is 0, 1, 2, 3, 4, or 5.