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US 8,299,307 B2Granted
Alkynyl phenyl derivative compounds for treating ophthalmic diseases and disorders
AssigneeAcucela Inc.
InventorsIan Leslie Scott, Vladimir Aleksandrovich Kuksa, Mark W Orme, Thomas Little, Anna Gall, Jennifer Gage, Feng Hong
Life of this patent
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Abstract
Provided are alkynyl phenyl derivative 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.
Claims52
A compound having a structure of Formula (A):
- as a tautomer or a mixture of tautomers, or as a pharmaceutically acceptable salt, stereoisomer, or geometric isomer thereof, wherein:
- m is 0, 1, 2 or 3;
- Z is —C(R23)(R24)—C(R1)(R2)—;
- Y is a bond, —C(R27)(R28)—, or —C(R27)(R28)—C(R29)(R30)—;
- R1 and R2 are each independently selected from hydrogen, halogen, C1-C5 alkyl, fluoroalkyl, —OR6 or —NR7R8;
- or R1 and R2 together form an oxo;
- R23 and R24 are each independently selected from hydrogen, halogen, C1-C5 alkyl, fluoroalkyl, —OR6, —NR7R8;
- or R23 and R24 together form an oxo;
- or optionally, R23 and an adjacent R1 together form a direct bond to provide a double bond;
- R3 and R4 are hydrogen;
- or R3 and R4 together form an imino;
- R5 is alkyl, heteroalkyl, alkenyl, heteroalkenyl, aryl, carbocyclyl, heteroaryl or heterocyclyl;
- each R6 is the same or different and independently hydrogen or C1-C5 alkyl;
- each R7 and each R8 are each the same or different and independently hydrogen, alkyl, carbocyclyl, heteroalkyl, heterocycloalkyl, aryl, heteroaryl, —C(═O)R9, SO2R9, CO2R9, SO2NH2, SO2NHR9 or SO2N(R9)2;
- or R7 and R8, together with the nitrogen atom to which they are attached, form an N-heterocyclyl;
- each R9 is the same or different and each is independently methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, C5-C8 alkyl, alkenyl, aryl, carbocyclyl, heteroaryl or heterocyclyl;
- R12 and R13 are the same or different and independently hydrogen, heteroalkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, —C(═O)R9, SO2R9, CO2R9, SO2NH2, SO2NHR9 or SO2N(R9)2;
- each R14 is the same or different and independently alkyl, halo, fluoroalkyl or —OR6;
- each R27, R28, and R29 are the same or different and independently hydrogen, alkyl or —OR6;
- and
- R30 is hydrogen or C1-C5 alkyl.
18 more elements
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of any of the preceeding claims.
Dependencies are inferred from the claim text.