Styrenyl derivative compounds for treating ophthalmic diseases and disorders

Patent metadata

Field	Value
Publication number	US-10201545-B2
Application number	US-201514631711-A
Country	US
Kind code	B2
Filing date	Feb 25, 2015
Priority date	Apr 20, 2007
Publication date	Feb 12, 2019
Grant date	Feb 12, 2019

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 method of modulating chromophore flux in a retinoid cycle comprising introducing into a subject a non-retinoid aromatic compound that inhibits 11-cis-retinol production with an IC 50 of about 0.1 micromolar or less when assayed in vitro, the assay consisting of a homogenate of HEK293 cell clone expressing recombinant human RPE65 and LRAT as the source of visual enzyme, exogenous all-trans-retinol in the amount of about 20 μM, recombinant human CRALBP in the amount of about 80 μg/mL, about 10 mM pH 7.2 phosphate buffer, about 0.5% BSA and about 1 mM NaPPi, and wherein the amount of assay reaction product 11-cis-retinol being determined by HPLC analysis following heptane extraction of the assay reaction mixture and wherein the non-retinoid aromatic compound consists of a benzene core that is substituted with a first substituent, a second substituent, and an optional third substituent, wherein the first and second substituents are attached to the benzene core in a meta-substitution configuration, wherein the first substituent is a group selected from —CH(OH)CH(R)CHNH 2 wherein R is H, CH 3 , or —OH and the second substituent is a substituted alkenyl, and wherein the optional third substituent is a halogen.

2. The method of claim 1 , wherein the R is H.

3. The method of claim 1 , wherein the substituted alkenyl is a 1,2-disubstituted alken-1-yl moiety.

4. The method of claim 3 , wherein the 1,2-disubstituted alken-1-yl is a 2-(cycloalkyl)-1-ethenyl moiety.

Assignees

• Acucela Inc

Inventors

• Scott Ian Leslie
• Kuksa 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

• A61P27/10

  for accommodation disorders, e.g. myopia · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title