Alkoxy compounds for disease treatment

A method of inhibiting degeneration of a retinal cell in a retina comprising contacting the retina with a compound of Formula (F) or tautomer, A stereoisomer, geometric isomer or a pharmaceutically acceptable salt, salt or N-oxide thereof:

• wherein,
• Z is a bond, —C(R1)(R2)—, —C(R9)(R10)—C(R1)(R2)—, —X—C(R31)(R32)—, —C(R9)(R10)—C(R1)(R2)—C(R36)(R37)— or —X—C(R31)(R32)—C(R1)(R2)—;
• 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;
• R31 and R32 are each independently selected from hydrogen, C1-C5 alkyl, or fluoroalkyl;
• R36 and R37 are each independently selected from hydrogen, halogen, C1-C5 alkyl, fluoroalkyl, —OR6 or —NR7R8;
• or R36 and R37 together form an oxo;
• or optionally, R36 and R1 together form a direct bond to provide a double bond;
• or optionally, R36 and R1 together form a direct bond, and R37 and R2 together form a direct bond to provide a triple bond;
• R3 and R4 are each independently selected from hydrogen, alkyl, alkenyl, fluoroalkyl, aryl, heteroaryl, carbocyclyl or C-attached heterocyclyl;
• or R3 and R4 together with the carbon atom to which they are attached, form a carbocyclyl or heterocyclyl;
• or R3 and R4 together form an imino;
• R5 is C5-C15 alkyl, carbocyclyalkyl, arylalkyl, heteroaryl alkyl or heterocyclylalkyl;
• R7 and R8 are each independently selected from hydrogen, alkyl, carbocyclyl, heterocyclyl, —C(═O)R13, SO2R13, CO2R13 or SO2NR24R25;
• or R7 and R8 together with the nitrogen atom to which they are attached, form an N-heterocyclyl;
• X is —O—, —S—, —S(═O)—, —S(═O)2—, —N(R30)—, —C(═O)—, —C(═CH2)—, —C(═N—NR35)—, or —C(═N—OR35)—;
• R9 and R10 are each independently selected from hydrogen, halogen, alkyl, fluoroalkyl, —OR19, —NR20R21 or carbocyclyl;
• or R9 and R10 form an oxo;
• or optionally, R9 and R1 together form a direct bond to provide a double bond;
• or optionally, R9 and R1 together form a direct bond, and R10 and R2 together form a direct bond to provide a triple bond;
• R11 and R12 are hydrogen;
• each R13, R22 and R23 is independently selected from alkyl, heteroalkyl, alkenyl, aryl, aralkyl, carbocyclyl, heteroaryl or heterocyclyl;
• R6, R19, R30, R34 and R35 are each independently hydrogen or alkyl;
• R20 and R21 are each independently selected from hydrogen, alkyl, carbocyclyl, heterocyclyl, —C(═O)R22, SO2R22, CO2R22 or SO2NR26R27;
• or R20 and R21 together with the nitrogen atom to which they are attached, form an N-heterocyclyl;
• and
• each R24, R25, R26, R27, R28 and R29 is independently selected from hydrogen, alkyl, alkenyl, fluoroalkyl, aryl, heteroaryl, carbocyclyl or heterocyclyl;
• each R33 is independently selected from halogen, OR34, alkyl, or fluoroalkyl;
• and n is 0, 1, 2, 3, or 4;
• and wherein the degeneration results from lipofuscin accumulation.

A method of reducing lipofuscin pigment accumulation in a retina of a subject in need thereof comprising administering to the subject a compound of Formula (F), or tautomer, stereoisomer, geometric isomer or a pharmaceutically acceptable salt or N-oxide thereof:

• wherein,
• Z is a bond, —C(R1)(R2)—, —C(R9)(R10)—C(R1)(R2)—, —X—C(R31)(R32)—, —C(R9)(R10)—C(R1)(R2)—C(R36)(R37)— or —X—C(R31)(R32)—C(R1)(R2)—;
• 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;
• R31 and R32 are each independently selected from hydrogen, C1-C5 alkyl, or fluoroalkyl;
• R36 and R37 are each independently selected from hydrogen, halogen, C1-C5 alkyl, fluoroalkyl, —OR6 or —NR7R8;
• or R36 and R37 together form an oxo;
• or optionally, R36 and R1 together form a direct bond to provide a double bond;
• or optionally, R36 and R1 together form a direct bond, and R37 and R2 together form a direct bond to provide a triple bond;
• R3 and R4 are each independently selected from hydrogen, alkyl, alkenyl, fluoroalkyl, aryl, heteroaryl, carbocyclyl or C-attached heterocyclyl;
• or R3 and R4 together with the carbon atom to which they are attached, form a carbocyclyl or heterocyclyl;
• or R3 and R4 together form an imino;
• R5 is C5-C15 alkyl, carbocyclyalkyl, arylalkyl, heteroaryl alkyl or heterocyclylalkyl;
• R7 and R8 are each independently selected from hydrogen, alkyl, carbocyclyl, heterocyclyl, —C(═O)R13, SO2R13, CO2R13 or SO2NR24R25;
• or R7 and R8 together with the nitrogen atom to which they are attached, form an N-heterocyclyl;
• X is —O—, —S—, —S(═O)—, —S(═O)2—, —N(R30)—, —C(═O)—, —C(═CH2)—, —C(═N—NR35)—, or —C(═N—OR35)—;
• R9 and R10 are each independently selected from hydrogen, halogen, alkyl, fluoroalkyl, —OR19, —NR20R21 or carbocyclyl;
• or R9 and R10 form an oxo;
• or optionally, R9 and R1 together form a direct bond to provide a double bond;
• or optionally, R9 and R1 together form a direct bond, and R10 and R2 together form a direct bond to provide a triple bond;
• R11 and R12 are hydrogen;
• each R13, R22 and R23 is independently selected from alkyl, heteroalkyl, alkenyl, aryl, aralkyl, carbocyclyl, heteroaryl or heterocyclyl;
• R6, R19, R30, R34 and R35 are each independently hydrogen or alkyl;
• R20 and R21 are each independently selected from hydrogen, alkyl, carbocyclyl, heterocyclyl, —C(═O)R22, SO2R22, CO2R22 or SO2NR26R27;
• or R20 and R21 together with the nitrogen atom to which they are attached, form an N-heterocyclyl;
• and
• each R24, R25, R26, R27, R28 and R29 is independently selected from hydrogen, alkyl, alkenyl, fluoroalkyl, aryl, heteroaryl, carbocyclyl or heterocyclyl;
• each R33 is independently selected from halogen, OR34, alkyl, or fluoroalkyl;
• and n is 0, 1, 2, 3, or 4.