Alkoxy compounds for disease treatment

Patent metadata

Field	Value
Publication number	US-10188615-B2
Application number	US-201715672031-A
Country	US
Kind code	B2
Filing date	Aug 8, 2017
Priority date	Oct 5, 2007
Publication date	Jan 29, 2019
Grant date	Jan 29, 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 alkoxyl derivative compounds and pharmaceutical compositions comprising these compounds. The subject compositions are useful for treating and preventing ophthalmic diseases and disorders, including age-related macular degeneration (AMD) and Stargardt's Disease.

First claim

We claim:

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)CH 2 NH 2 wherein R is H, CH 3 , or —OH and the second substituent is an optionally substituted alkoxy group, and wherein the optional third substituent is a halogen or —OH.

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

3. The method of claim 1 , wherein the optionally substituted alkoxy group is —OR′ wherein R′ is optionally substituted C 5 -C 15 alkyl, or optionally substituted carbocyclyalkyl.

4. The method of claim 1 , wherein the optionally substituted alkoxy group is —OCH 2 CR 16 R 17 R 18 , wherein R 17 and R 18 are optionally substituted C 1-4 alkyl, or are joined together to form an optionally substituted carbocyclic ring of 5, 6, 7, or 8 ring carbon atoms and R 18 is H or —OH.

5. The method of claim 4 , wherein R 17 and R 18 are joined together to form an optionally substituted carbocyclic ring of 5, 6, 7, or 8 ring carbon atoms and R 18 is H or —OH.

6. The method of claim 4 , wherein R 17 and R 18 are joined together to form a optionally substituted carbocyclic ring of 6 or 7 ring carbon atoms and R 8 is H or —OH.

7. The method of claim 1 , wherein the optionally substituted alkoxy group is (c-C 6 H 11 )CH 2 —O—.

Assignees

• Acucela Inc

Inventors

• Scott Ian L
• Kuksa Vladimir A
• Orme Mark W
• Little Jr Thomas L
• Gall Anna
• Hong Feng

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P27/06

  Antiglaucoma agents or miotics · CPC title

• A61P27/02

  Ophthalmic agents · CPC title