Styrenyl derivative compounds for treating ophthalmic diseases and disorders

Patent metadata

Field	Value
Publication number	US-9314467-B2
Application number	US-201514630889-A
Country	US
Kind code	B2
Filing date	Feb 25, 2015
Priority date	Apr 20, 2007
Publication date	Apr 19, 2016
Grant date	Apr 19, 2016

Abstract

The present invention relates generally to compositions and methods for treating neurodegenerative diseases and disorders, particularly ophthalmic diseases and disorders. Provided herein are styrenyl derivative compounds, including but not limited to stilbene derivative compounds, and compositions comprising these compounds, that are useful for treating and preventing ophthalmic diseases and disorders, including age-related macular degeneration (AMD) and Stargardt's Disease.

First claim

What is claimed is:

1. A compound, or the pharmaceutically acceptable salt thereof, having a structure of Formula (A):

wherein:
R 1 and R 2 are hydrogen;
R 3 , R 4 , R 5 and R 6 are each the same or different and independently hydrogen, halogen, —OR 12 , alkyl or fluoroalkyl;
R 7 and R 8 are hydrogen;
R 9 is hydrogen;
R 10 is hydrogen;
R 11 is 5, 6-, or 7-member cycloalkyl;
each R 12 is independently selected from hydrogen or alkyl;
Z is W—Y, wherein
W is —C(R 14 )(R 15 )—;
Y is —C(R 16 )(R 17 )—;
R 14 and R 15 are each the same or different and independently hydrogen, halogen, alkyl, fluoroalkyl, —OR 12 , or —NR 18 R 19 ; or R 14 and R 15 together form an oxo;
R 16 and R 17 are each the same or different and independently hydrogen, halogen, alkyl, fluoroalkyl, —OR 12 , or —NR 18 R 19 ; or R 16 and R 17 together form an oxo; and
each R 18 and R 19 is independently selected from hydrogen or alkyl.

2. The compound of claim 1 , or the pharmaceutically acceptable salt thereof, wherein R 11 is cyclohexyl.

3. The compound of claim 1 , or the pharmaceutically acceptable salt thereof, wherein R 14 , R 15 , R 16 and R 17 are each independently hydrogen, halogen, alkyl, fluoroalkyl, —OR 12 , or —NR 18 R 19 , wherein each R 12 is independently hydrogen or alkyl.

4. The compound of claim 1 , or the pharmaceutically acceptable salt thereof, wherein R 3 , R 4 , R 5 and R 6 are each the same or different and independently hydrogen, halogen, —OR 12 , or alkyl.

5. The compound of claim 1 , or the pharmaceutically acceptable salt thereof, selected from:
(E)-3-(3-(2-cyclohexylvinyl)phenyl)propan-1-amine;
(E)-1-(3-(3-amino-1-hydroxypropyl)styryl)cyclohexanol;
(E)-1-(3-((1R,2R)-3-amino-1-hydroxy-2-methylpropyl)styryl)cyclohexanol;
(E)-1-(3-(3-amino-1-hydroxypropyl)-5-fluorostyryl)cyclohexanol;
(E)-1-(3-(3-amino-1-hydroxypropyl)-2-fluorostyryl)cyclohexanol;
(1S,2S)-3-amino-1-(3-((E)-2-(1-hydroxycyclohexyl)vinyl)phenyl)propane-1,2-diol;
(1R,2R)-3-amino-1-(3-((E)-2-(1-hydroxycyclohexyl)vinyl)phenyl)propane-1,2-diol;
(E)-1-(5-(3-amino-1-hydroxypropyl)-2-methoxystyryl)cyclohexanol;
(E)-1-(3-(3-amino-1-hydroxypropyl)-4-chlorostyryl)cyclohexanol;
(E)-1-(3-(3-amino-1-hydroxypropyl)-4-methylstyryl)cyclohexanol;
(E)-1-(3-(3-amino-1-hydroxypropyl)-5-methylstyryl)cyclohexanol;
(1S,2R)-3-amino-1-(3-((E)-2-(1-hydroxycyclohexyl)vinyl)phenyl)-propane-1,2-diol;
(E)-2-(3-(3-amino-1-hydroxypropyl)styryl)cyclohexanol;
(E)-1-(5-(3-amino-1-hydroxypropyl)-2-fluorostyryl)cyclohexanol;
(E)-1-(3-(3-amino-1-hydroxypropyl)-5-methoxystyryl)cyclohexanol;
(E)-1-(3-(3-amino-1-hydroxypropyl)-4-fluorostyryl)cyclohexanol;
(1R,2S)-3-amino-1-(3-((E)-2-(1-hydroxycyclohexyl)vinyl)phenyl)propane-1,2-diol;
(E)-1-(3-(3-amino-1-hydroxypropyl)-5-chlorostyryl)cyclohexanol; and
(E)-1-(3-(3-amino-1-hydroxypropyl)-2-methoxystyryl)cyclohexanol;
or the pharmaceutically acceptable salt thereof.

6. A compound selected from:
(E/Z)-3-(3-(2,6-dimethylstyryl)phenyl)prop-2-en-1-amine;
(E)-3-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)prop-2-yn-1-amine; and
(E)-2-fluoro-3-(3-((E)-2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)prop-2-en-1-amine;
or the pharmaceutically acceptable salt thereof.

7. A compound having a structure described by
(E)-4-(3-(3-amino-1-hydroxypropyl)styryl)heptan-4-ol;
or the pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition comprising a compound of Formula (A), or a pharmaceutically acceptable salt thereof, as described in claim 1 , and a pharmaceutically acceptable excipient.

9. A pharmaceutical composition comprising a compound of claim 5 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

10. A pharmaceutical composition comprising a compound of claim 6 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

11. A pharmaceutical composition comprising a compound of claim 7 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

Assignees

• Acucela Inc

Inventors

• Scott Ian Leslie
• Kuska Vladimir Aleksandrovich
• Gall Anna
• Orme Mark W
• Gage Jennifer
• Little Jr Thomas L
• Jiang Qin
• Rossiter Lana Michele
• Mcgee Jr Kevin F
• Kubota Ryo

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/4453

  only substituted in position 1, e.g. propipocaine, diperodon · CPC title

• C07C215/42

  having amino groups or hydroxy groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton · CPC title

• C07C217/48

  the carbon skeleton being unsaturated and containing rings · CPC title