Alkynyl phenyl derivative compounds for treating ophthalmic diseases and disorders
Provided are alkynyl phenyl derivative compounds, pharmaceutical compositions thereof, and methods of treating ophthalmic diseases and disorders, such as age-related macular degeneration and Stargardt's Disease, using said compounds and compositions.
1. A compound having the structure of Formula (F):
as a pharmaceutically acceptable salt, or stereoisomer, thereof, wherein:
m is 0, 1, 2 or 3;
R 21 and R 22 are each independently hydrogen, C 1 -C 5 alkyl or fluoroalkyl;
R 3 and R 4 are each hydrogen;
each R 6 is the same or different and independently hydrogen or C 1 -C 5 alkyl;
R 9 is alkyl;
R 12 and R 13 are the same or different and independently hydrogen, alkyl or —C(═O)R 9 ;
each R 14 is the same or different and independently alkyl, halo, fluoroalkyl or —OR 6 ; and
R 16 , R 17 and R 18 are each the same or different and independently hydrogen, alkyl, —OR 6 , carbocyclyl or aryl.
2. The compound of claim 1 wherein each of R 12 and R 13 is hydrogen.
3. The compound of claim 2 wherein each of R 21 , and R 22 is independently hydrogen or C 1 -C 5 alkyl.
4. The compound of claim 3 wherein m is 0.
5. The compound of claim 4 wherein each of R 16 , R 17 and R 18 is independently hydrogen, alkyl or —OR 6 , wherein each R 6 is independently hydrogen or C 1 -C 5 alkyl.
6. The compound of claim 4 wherein each of R 16 , R 17 and R 18 is independently hydrogen, alkyl or aryl.
7. The compound of either claim 5 or claim 6 wherein the compound is selected from:
4-((3-(2-aminoethoxy)phenyl)ethynyl)heptan-4-ol;
1-(3-(2-aminoethoxy)phenyl)-3-ethylpent-1-yn-3-ol;
1-(3-(2-aminoethoxy)phenyl)-3-isopropyl-4-methylpent-1-yn-3-ol;
5-((3-(2-aminoethoxy)phenyl)ethynyl)nonan-5-ol;
4-(3-(2-aminoethoxy)phenyl)-2-methylbut-3-yn-2-ol;
2-(3-(hept-1-ynyl)phenoxy)ethanamine;
4-(3-(2-aminoethoxy)phenyl)but-3-yn-1-ol;
2-(3-(3-phenylprop-1-ynyl)phenoxy)ethanamine;
2-(3-(4-methylpent-1-ynyl)phenoxy)ethanamine;
6-(3-(2-aminoethoxy)phenyl)hex-5-yn-1-ol;
2-(3-(3-ethylpent-1-ynyl)phenoxy)propan-1-amine;
2-(3-(3-propylhex-1-ynyl)phenoxy)propan-1-amine;
1-(3-(2-aminoethoxy)phenyl)-3-ethylpent-1-yn-3-ol;
4-((3-(1-aminopropan-2-yloxy)phenyl)ethynyl)heptan-4-ol;
2-(3-(3-ethylpent-1-ynyl)phenoxy)ethanamine; and
2-(3-(3-propylhex-1-ynyl)phenoxy)ethanamine.
8. A compound selected from:
4-((3-(2-aminoethoxy)phenynethynyl)-heptan-4-ol;
1-(3-(2-aminoethoxy)phenyl)-3-ethylpent-1-yn-3-ol;
1-(3-(2-aminoethoxy)phenyl)-3-isopropyl-4-methylpent-1-yn-3-ol;
5-((3-(2-aminaethoxy)phenyl)ethynyl)-nonan-5-ol;
4-(3-(2-aminoethoxy)phenyl)-2-methylbut-3-yn-2-ol;
2-(3-(4-methylpent-1-ynyl)phenoxy)ethanamine;
6-(3-(2-aminoethoxy)phenyl)hex-5-yn-1-ol;
2-(3-(3-phenylprop-1-ynyl)phenoxy)ethanamine;
4-(3-(2-aminoethoxy)phenyl)but-3-yn-1-ol;
2-(3-(hept-1-ynyl)phenoxy)ethanamine;
2-(3-(3-cyclopentylprop-1-ynyl)nhenoxy)ethanamine;
2-(3-(4-phenylbut-1-ynyl)phenoxy)ethanamine;
5-(3-(2-aminoethoxy)phenyl)pent-4-yn-1-ol;
2-(3-(hex-1-ynyl)phenoxy)ethanamine;
2-(3-(3-methoxyprop-1-ynyl)phenoxy)ethanamine;
1-(3-(2-aminoethoxy)phenyl)hex-1-yn-3-ol;
1-(3-(2-aminoethoxy)phenyl)-3-methylhex-1-yn-3-ol;
1-(3-(2-aminoethoxy)phenyl)-4-methylpent-1-yn-3-ol;
2-(3-(4-methoxybut-1-ynyl)phenoxy)ethanamine;
5-(3-(2-aminoethoxy)-phenyl)-N-methylpent-4-ynamnide;
5-(3-(2-aminoethoxy)phenyl)-N,N-dimethylpent-4-ynamide;
5-(3-(2-aminoethoxy)phenyl)pent-4-ynamide; and
2-(3-(5-methoxypent-1-ynyl)phenoxy)ethanamine.
9. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of any one of claims 1 - 8 .