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, or a pharmaceutically acceptable salt thereof, having a structure of Formula (A):
wherein:
m is 0 or 1;
Z is —X—C(R 21 )(R 22 )—;
X is —S—, —S(═O)—, —S(═O) 2 —, —N(R 31 )—, —C(═N—NR 35 )—, or —C(═N—OR 35 )—;
Y is a bond, —C(R 27 )(R 28 )—, or —C(R 27 )(R 28 )—C(R 29 )(R 30 )—;
R 21 and R 22 are each independently selected from hydrogen, C 1 -C 5 alkyl, or fluoroalkyl;
R 3 and R 4 are hydrogen;
R 5 is alkyl, aryl, or carbocyclyl;
each R 6 is the same or different and independently hydrogen or C 1 -C 5 alkyl;
R 12 and R 13 are hydrogen;
each R 14 is the same or different and independently alkyl, halo, or —OCH 3 ;
each R 27 , R 28 , R 29 and R 30 are the same or different and independently hydrogen, alkyl or —OR 6 ; and
R 31 and R 35 are each independently hydrogen or C 1 -C 5 alkyl.
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is alkyl.
3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein m is 0.
4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein R 21 and R 22 are each independently hydrogen or C 1 -C 5 alkyl.
5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is aryl.
6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein m is 0.
7. The compound of claim 6 , or a pharmaceutically acceptable salt thereof, wherein R 21 and R 22 are each independently hydrogen or C 1 -C 5 alkyl.
8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is carbocyclyl.
9. The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein m is 0.
10. The compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein R 21 and R 22 are each independently hydrogen or C 1 -C 5 alkyl.
11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, chosen from:
3-amino-1-(3-(3-hydroxy-3-propylhex-1-ynyl)phenyl)propan-1-one oxime;
4-((3-(2-aminoethylamino)-phenyl)ethynyl)heptan-4-ol;
4-((3-(2-aminoethylthio)phenyl)ethynyl)heptan-4-ol;
4-((3-(2-aminoethylsulfinyl)phenyl)ethynyl)heptan-4-ol; or
4-((3-(2-aminoethylsulfonyl)phenyl)ethynyl)heptan-4-ol.
12. A pharmaceutical composition comprising a compound of Formula (A), or pharmaceutically acceptable salt thereof, as described in claim 1 , and a pharmaceutically acceptable excipient.
13. A pharmaceutical composition comprising a compound of claim 11 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.