Alkoxy compounds for disease treatment

Patent metadata

Field	Value
Publication number	US-9458088-B2
Application number	US-201514631763-A
Country	US
Kind code	B2
Filing date	Feb 25, 2015
Priority date	Oct 5, 2007
Publication date	Oct 4, 2016
Grant date	Oct 4, 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 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 compound of Formula (D) or tautomer, stereoisomer, or a pharmaceutically acceptable salt, or N-oxide thereof:

wherein,
R 31 and R 32 are each independently selected from hydrogen, C 1 -C 5 alkyl, or fluoroalkyl;
R 3 and R 4 are each hydrogen; or R 3 and R 4 together form an imino;
R 11 and R 12 are each hydrogen or —C(═O)R 23 ;
R 23 is selected from alkyl, alkenyl, aryl, carbocyclyl, heteroaryl or heterocyclyl;
R 14 and R 15 are each independently selected from hydrogen or alkyl;
R 16 and R 17 are each independently selected from C 1 -C 13 alkyl, or fluoroalkyl;
or R 16 and R 17 , together with the carbon atom to which they are attached, form a carbocyclyl;
R 18 is selected from a hydrogen, alkyl, alkoxy, hydroxy, halo or fluoroalkyl;
R 34 is hydrogen or alkyl; and
each R 33 is independently selected from halogen, OR 34 , alkyl, or fluoroalkyl; and n is 0, 1, or 2; with the provision that the group C(R 14 )(R 15 )—C(R 16 )(R 17 )(R 18 ) is not an unsubstituted normal alkyl.

2. The compound of claim 1 , or tautomer, stereoisomer, or a pharmaceutically acceptable salt, or N-oxide thereof, wherein n is 0.

3. The compound of claim 2 , or tautomer, stereoisomer, or a pharmaceutically acceptable salt, or N-oxide thereof, wherein each R 14 and R 15 is hydrogen.

4. The compound of claim 3 , or tautomer, stereoisomer, or a pharmaceutically acceptable salt, or N-oxide thereof, wherein,
R 31 and R 32 are each independently hydrogen, or C 1 -C 5 alkyl;
R 16 and R 17 , together with the carbon atom to which they are attached, form a carbocyclyl; and
R 18 is hydrogen, hydroxy, or alkoxy.

5. The compound of claim 1 , or tautomer, stereoisomer, or a pharmaceutically acceptable salt, or N-oxide thereof, wherein R 16 and R 17 , together with the carbon atom to which they are attached form cyclopentyl, cyclohexyl or cycloheptyl and R 18 is hydrogen or hydroxy.

6. The compound of claim 3 , or tautomer, stereoisomer, or a pharmaceutically acceptable salt, or N-oxide thereof, wherein, R 31 and R 32 are each independently selected from hydrogen, or C 1 -C 5 alkyl; and R 18 is hydrogen, hydroxy or alkoxy.

7. The compound of claim 1 , or tautomer, stereoisomer, or a pharmaceutically acceptable salt, or N-oxide thereof, wherein R 16 and R 17 are each C 1 -C 13 alkyl.

8. The compound of claim 1 , or tautomer, stereoisomer, or a pharmaceutically acceptable salt, or N-oxide thereof, wherein R 16 and R 17 are each independently selected from C 1 -C 13 alkyl; and R 18 is hydrogen, or hydroxy.

9. The compound of claim 1 , or tautomer, stereoisomer, or a pharmaceutically acceptable salt, or N-oxide thereof, wherein R 16 and R 17 are each independently selected from C 1 -C 4 alkyl; and R 18 is hydrogen, or hydroxy.

10. The compound of claim 1 , or tautomer, stereoisomer, or a pharmaceutically acceptable salt, or N-oxide thereof, selected from the group consisting of:

11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 , or tautomer, stereoisomer, or a pharmaceutically acceptable salt, or N-oxide thereof.

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

• A61P27/02

  Ophthalmic agents · CPC title

• A61P27/00

  Drugs for disorders of the senses · CPC title