Compounds for treating ophthalmic diseases and disorders

Patent metadata

Field	Value
Publication number	US-2016145198-A1
Application number	US-201514946721-A
Country	US
Kind code	A1
Filing date	Nov 19, 2015
Priority date	Oct 22, 2008
Publication date	May 26, 2016
Grant date	—

Abstract

Provided are compounds, pharmaceutical compositions thereof, and methods of treating ophthalmic diseases and disorders, such as age-related macular degeneration and Stargardt's Disease, using said compounds and compositions.

First claim

1 .- 98 . (canceled)

99 . A compound of Formula (I) or tautomer, stereoisomer, geometric isomer or a pharmaceutically acceptable salt or N-oxide thereof:

wherein,
Z is —C(R 9 )(R 10 )—C(R 1 )(R 2 )—;
G is selected from —N(R 42 )C(═O)—R 40 , or —N(R 42 )—C(R 42 )(R 42 )—R 40 ;
R 40 is selected from —C(R 16 )(R 17 )(R 18 );
each R 42 is hydrogen;
R 1 and R 2 are each independently selected from hydrogen, halogen, C 1 -C 5 alkyl; or R 1 and R 2 together form an oxo;
R 3 and R 4 are each hydrogen;
R 9 is OR 19 ;
R 10 is each is selected from hydrogen, halogen, C 1 -C 5 alkyl or —OR 19 ; or R 9 and R 10 form an oxo;
R 11 is hydrogen and R 12 is hydrogen, —CH 3 , or —C(═O)R 23 ;
R 23 is C 1 -C 5 alkyl;
R 19 and R 34 are each independently hydrogen or C 1 -C 5 alkyl;
R 16 and R 17 are each independently selected from hydrogen, C 1 -C 5 alkyl, or halo;
R 18 is selected from hydrogen, C 1 -C 5 alkyl, alkoxy, hydroxy, halo or fluoroalkyl;
each R 33 is independently selected from halogen, OR 34 , C 1 -C 5 alkyl, or fluoroalkyl; and n is 0, 1, or 2.

100 . The compound of claim 99 wherein,
G is selected from —N(R 42 )C(═O)—R 40 ; and R 10 is hydrogen.

101 . The compound of claim 99 wherein,
G is selected from —N(R 42 )C(═O)—R 40 ; and R 9 and R 10 form an oxo.

102 . The compound of claim 100 wherein,
R 11 and R 12 are each hydrogen; and n is 0.

103 . The compound of claim 101 wherein,
R 11 and R 12 are each hydrogen; and n is 0.

104 . The compound of claim 102 wherein,
R 16 and R 17 are each independently selected from hydrogen or C 1 -C 5 alkyl; and
R 18 is selected from hydrogen, C 1 -C 5 alkyl, alkoxy, or hydroxyl.

105 . The compound of claim 103 wherein,
R 16 and R 17 are each independently selected from hydrogen, C 1 -C 5 alkyl; and
R 18 is selected from hydrogen, C 1 -C 5 alkyl, alkoxy, or hydroxyl.

106 . The compound of claim 99 wherein,
G is selected from —N(R 42 )—C(R 42 )(R 42 )—R 40 ; and R 10 is hydrogen.

107 . The compound of claim 99 wherein,
G is selected from —N(R 42 )—C(R 42 )(R 42 )—R 40 ; and R 9 and R 10 form an oxo.

108 . The compound of claim 106 wherein,
R 11 and R 12 are each hydrogen; and n is 0.

109 . The compound of claim 100 wherein,
R 11 and R 12 are each hydrogen; and n is 0.

110 . The compound of claim 108 wherein,
R 11 and R 12 are each hydrogen; and n is 0.

111 . The compound of claim 109 wherein,
R 11 and R 12 are each hydrogen; and n is 0.

112 . The compound of claim 110 wherein,
R 16 and R 17 are each independently selected from hydrogen, —C 1 -C 5 alkyl; and
R 18 is selected from hydrogen, C 1 -C 5 alkyl, alkoxy, or hydroxyl.

113 . The compound of claim 111 wherein,
R 16 and R 17 are each independently selected from hydrogen, C 1 -C 5 alkyl; and
R 18 is selected from hydrogen, C 1 -C 5 alkyl, alkoxy, or hydroxyl.

114 . A compound chosen from:

115 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 99 or a tautomer, stereoisomer, geometric isomer, pharmaceutically acceptable salt, or N-oxide thereof.

116 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 114 or a tautomer, stereoisomer, geometric isomer, pharmaceutically acceptable salt, or N-oxide thereof.

Assignees

• Acucela Inc

Inventors

• Scott Ian L
• Kuksa Vladimir A
• Hong Feng
• Kubota Ryo
• Gage Jennifer

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• 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

• C07C2601/08

  the ring being saturated · 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