Alkoxy compounds for disease treatment

• US 9,458,088 B2
• Filed: 02/25/2015
• Issued: 10/04/2016
• Est. Priority Date: 10/05/2007
• Status: Expired due to Fees

• Current Assignee: Acucela Inc. (Kubota Pharmaceutical Holdings Co. Ltd.)
• Original Assignee: Acucela Inc. (Kubota Pharmaceutical Holdings Co. Ltd.)
• Inventors: Scott, Ian L., Kuksa, Vladimir A., Orme, Mark W., Little, Thomas L. Jr., Gall, Anna, Hong, Feng
• Primary Examiner(s): Valenrod, Yevegeny
• Assistant Examiner(s): Doletski, Blaine G
• Application Number:
  US14/631,763
• Publication Number:
  US 20150239825A1
• Time in Patent Office: 587 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/222 with compounds having aromatic groups, e.g. dipivefrine, ibopamine
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07C 215/20 the carbon skeleton being saturated and containing rings
• CPC Class Codes: C07C 217/20 by halogen atoms, by trihalomethyl, nitro or nitroso groups, or by singly-bound oxygen atoms
• CPC Class Codes: C07C 217/60 linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
• CPC Class Codes: C07C 217/62 linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
• CPC Class Codes: C07C 217/64 with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by singly-bound oxygen atoms
• CPC Class Codes: C07C 217/72 linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
• CPC Class Codes: C07C 217/84 the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom
• CPC Class Codes: C07C 225/16 and containing six-membered aromatic rings
• CPC Class Codes: C07C 229/38 having amino groups bound to acyclic carbon atoms and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
• CPC Class Codes: C07C 233/18 having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
• CPC Class Codes: C07C 235/08 : having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
• CPC Class Codes: C07C 251/86 : having doubly-bound carbon atoms of hydrazone groups bound to carbon atoms of six-membered aromatic rings
• CPC Class Codes: C07C 2601/02 : with a three-membered ring
• CPC Class Codes: C07C 2601/04 : with a four-membered ring
• CPC Class Codes: C07C 2601/08 : the ring being saturated
• CPC Class Codes: C07C 2601/14 : The ring being saturated
• CPC Class Codes: C07C 2601/18 : with a ring being at least seven-membered
• CPC Class Codes: C07C 2602/42 : the bicyclo ring system containing seven carbon atoms
• CPC Class Codes: C07C 279/08 : being further substituted by singly-bound oxygen atoms
• CPC Class Codes: C07C 309/06 : containing halogen atoms, or nitro or nitroso groups bound to the carbon skeleton
• CPC Class Codes: C07C 317/28 : with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
• CPC Class Codes: C07C 323/25 : the carbon skeleton being acyclic and saturated
• CPC Class Codes: C07C 323/33 : having at least one of the nitrogen atoms bound to a carbon atom of the same non-condensed six-membered aromatic ring
• CPC Class Codes: C07D 277/24 : Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 309/06 : Radicals substituted by oxygen atoms

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.

Claims

1. A compound of Formula (D) or tautomer, stereoisomer, or a pharmaceutically acceptable salt, or N-oxide thereof:

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 R¹⁴ and R¹⁵ is hydrogen.

4. The compound of claim 3, or tautomer, stereoisomer, or a pharmaceutically acceptable salt, or N-oxide thereof, wherein,

R³¹ and R³² are each independently hydrogen, or C₁-C₅ alkyl;

R¹⁶ and R¹⁷, together with the carbon atom to which they are attached, form a carbocyclyl; and

R¹⁸ is hydrogen, hydroxy, or alkoxy.

5. The compound of claim 1, or tautomer, stereoisomer, or a pharmaceutically acceptable salt, or N-oxide thereof, wherein R¹⁶ and R¹⁷, together with the carbon atom to which they are attached form cyclopentyl, cyclohexyl or cycloheptyl and R¹⁸ is hydrogen or hydroxy.

6. The compound of claim 3, or tautomer, stereoisomer, or a pharmaceutically acceptable salt, or N-oxide thereof, wherein, R³¹ and R³² are each independently selected from hydrogen, or C₁-C₅ alkyl;

and R¹⁸ is hydrogen, hydroxy or alkoxy.

7. The compound of claim 1, or tautomer, stereoisomer, or a pharmaceutically acceptable salt, or N-oxide thereof, wherein R¹⁶ and R¹⁷ are each C₁-C₁₃ alkyl.

8. The compound of claim 1, or tautomer, stereoisomer, or a pharmaceutically acceptable salt, or N-oxide thereof, wherein R¹⁶ and R¹⁷ are each independently selected from C₁-C₁₃ alkyl;

and R¹⁸ is hydrogen, or hydroxy.

9. The compound of claim 1, or tautomer, stereoisomer, or a pharmaceutically acceptable salt, or N-oxide thereof, wherein R¹⁶ and R¹⁷ are each independently selected from C₁-C₄ alkyl;

and R¹⁸ 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.