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, comprising injecting a compound of Formula (I):
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 N;
R 3 is optionally substituted heteroaryl; and
n is 0, 1, 2, 3, or 4.
2. The method of claim 1 , wherein the compound of Formula (I) is a compound of Formula (II) or Formula (III):
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 or a nitrogen protecting group; and
m is 0, 1, 2, 3, 4, or 5.
3. The method of claim 1 , wherein R 1 is CH 3 .
4. The method of claim 1 , wherein R 2 is
wherein p, q, s, and t are independently 0, 1, 2, 3, or 4.
5. The method of claim 1 , wherein X is a bond.
6. The method of claim 1 , wherein X is —C(═O)—.
7. The method of claim 1 , wherein n is 2.
8. The method of claim 1 , wherein n is 1.
9. The method of claim 2 , wherein at least one instance of R 4 is CH 3 .
10. The method of claim 2 , wherein at least one instance of R 4 is F.
11. The method of claim 2 , wherein at least one instance of R 4 is H.
12. The method of claim 2 , wherein R 5 is H.
13. The method of claim 4 , wherein R 2 is
14. The method of claim 4 , wherein R 2 is
15. The method of claim 4 , wherein R 2 is
16. The method of claim 1 , wherein the compound of Formula (I) is:
or a pharmaceutically acceptable salt thereof.
17. The method of claim 1 , wherein the compound, or pharmaceutically acceptable salt thereof, is in the form of a pharmaceutical composition.
18. The method of claim 1 , wherein the ocular disease is a growth factor-associated disorder.
19. The method of claim 18 , therein the growth factor is vascular endothelial growth factor.
20. The method of claim 1 , wherein the ocular disease is at the front of the eye of the subject.
21. The method of claim 20 , wherein the front of the eye 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 disorders, strabismus, and glaucoma.
22. The method of claim 1 , wherein the ocular disease is at the back of the eye of the subject.
23. The method of claim 22 , wherein the back of the eye ocular disease is intraocular melanoma, acute macular neuroretinopathy, Behcet's disease, choroidal neovascularization, uveitis, diabetic uveitis, histoplasmosis, an infection, macular degeneration, edema, multifocal choroiditis, ocular trauma which affects a posterior ocular site or location, ocular tumors, 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, posterior ocular conditions caused by or influenced by a photodynamic therapy, photocoagulation, radiation retinopathy, a epiretinal membrane disorder, branch retinal vein occlusion, anterior ischemic optic neuropathy, non-retinopathy diabetic retinal dysfunction, retinitis pigmentosa, retinoblastoma, and glaucoma.
24. The method of claim 1 , wherein the compound is injected intraocular, intrastromal, intravitreal, or intracameral.
25. The method of claim 1 , wherein the compound of Formula (I) is
or a pharmaceutically acceptable salt thereof.
26. The method of claim 1 , wherein the compound of Formula (I) is
or a pharmaceutically acceptable salt thereof.