Therapeutic compounds and uses thereof
Described herein are compounds of Formula (I)-(III), pharmaceutically acceptable salts thereof, 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. Methods of using the compounds or pharmaceutical compositions thereof for treating and/or preventing diseases are also provided.
1. A method of treating an ocular disease in an eye of a subject in need thereof, comprising injecting a compound to the eye, wherein the compound is:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is H or optionally substituted C 1-6 alkyl;
R 2 is optionally substituted bicyclic heterocyclyl having 1 or 2 heteroatoms;
X is a bond, O, or —C(═O)—;
Y is CH;
R 3 is optionally substituted heteroaryl; and
n is 0, 1, 2, 3, or 4.
2. The method of claim 1 , wherein the ocular disease is a vascular endothelial growth factor-associated disorder.
3. The method of claim 1 , wherein the ocular disease is post-surgical inflammation, uveitis, an infection, aphakia, pseudophakia, astigmatism, blepharospasm, cataract, a conjunctival disease, conjunctivitis, a corneal disease, corneal ulcer, a dry eye syndrome, an eyelid disease, a lacrimal apparatus disease, lacrimal duct obstruction, myopia, presbyopia, a pupil disorder, corneal neovascularization, a refractive disorder, strabismus, glaucoma, intraocular melanoma, acute macular neuroretinopathy, Behcet's disease, choroidal neovascularization, diabetic uveitis, histoplasmosis, macular degeneration, edema, multifocal choroiditis, ocular trauma which affects a posterior ocular site or location, an ocular tumor, a retinal disorder, diabetic retinopathy, proliferative vitreoretinopathy (PVR), retinal arterial occlusive disease, retinal detachment, uveitic retinal disease, sympathetic opthalmia, Vogt Koyanagi-Harada (VKH) syndrome, uveal diffusion, a posterior ocular condition caused by or influenced by an ocular laser treatment, a posterior ocular condition caused by or influenced by a photodynamic therapy, photocoagulation, radiation retinopathy, an epiretinal membrane disorder, branch retinal vein occlusion, anterior ischemic optic neuropathy, non-retinopathy diabetic retinal dysfunction, retinitis pigmentosa, or retinoblastoma.
4. The method of claim 1 , wherein the compound is injected by intraocular, intrastromal, intravitreal, or intracameral injection.
5. The method of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof,
wherein:
each instance of R 4 is independently H, optionally substituted C 1-6 alkyl, F, Cl, Br, I, CN, OH, or alkoxy;
R 5 is H; and
m is 0, 1, 2, 3, 4, or 5.
6. The method of claim 5 , wherein at least one instance of R 4 is CH 3 , F, or H.
7. The method of claim 1 , wherein R 2 is
8. The method of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
9. The method of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof,
wherein:
each instance of R 4 is independently H, optionally substituted C 1-6 alkyl, F, Cl, Br, I, CN, OH, or alkoxy;
R 5 is H; and
m is 0, 1, 2, 3, 4, or 5.