SULFUR-LINKED COMPOUNDS FOR TREATING OPTHALMIC DISEASES AND DISORDERSProvided are sulphur-linked 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.A compound of Formula (I) or tautomer, stereoisomer, geometric isomer or a pharmaceutically acceptable solvate, hydrate, salt, JV-oxide or prodrug thereof:Formula (I) wherein,Z is a bond, -C(R1XR2)-, -C(R9XR10K(R1XR2)-, -X-C(R31)(R32)-, -C(R9)(R10)-C(R1)(R2)-C(R36)(R37)-, -X-C(R31XR32J-C(R1XR2)- or -C(R38)(R39)-X-C(R31)(R32)-;Y is -SO2NR40-, -S-C(RI4)(R15)-, *S(=O)-C(RI4)(R15)-, or -S(=O)2-C(R14)(R15)-;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, R32, R38 and R39 are each independently selected from hydrogen, Ci-C5 alkyl, or fluoroalkyl;R40 is selected from hydrogen, alky], alkenyl, alkynyl, aryl, aralkyl, carbocyclyl, heteroaryl or C-attached hctcrocyclyl; or R40 and R5, together with the nitrogen atom to which they are attached, form a heterocycle; each R14 and R15 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, carbocyclyl, heteroaryl or C-attached heterocyclyl; or R14 and R15 together with the carbon atom to which they are attached, form a carbocyclyl or heterocyclyl; or optionally, R5 and either one R14 or R15, together with the carbon atom to which they are attached, form a carbocycle or heterocycle;R36 and R37 are each independently selected from hydrogen, halogen, C1-C5 alkyl, fluoroalkyl, -OR5 or -NR7R8; or R36 and R37 together form an oxo; or optionally, R3fi 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; R3 is C2-C]5 alkyl, carbocyclyalkyl, arylalkyl, heteroarylalkyl or heterocyclylalkyl; each R7 and R8 are 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 λf-heterocyclyl;X is -O-, -S-, -S(=O)-, -S(=O)2-, -N(R30)-, -C(=O)-, -C(=CH2)-, -C(=N-NR35)-, or -C(=N-ORJ5)-; R9 and R10 are each independently selected from hydrogen, halogen, alkyl, fluoroalkyl, -OR6, -NR7R8 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 each independently selected from hydrogen, alkyl, carbocyclyl, -C(=O)RB, SO2R13, CO2R13 or SO2NR24R25; or R1 ' and R12, together with the nitrogen atom to which they are attached, form an N- heterocyclyl; each R13 is independently selected from alkyl, alkenyl, aryl, aralkyl, carbocyclyl, heteroaryl or heterocyclyl; each R6, R30, R34 and R35 is independently hydrogen or alkyl; each R24 and R2S 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. The compound of claim 1 having the structure of Formula (Ia) Formula (Ia) wherein, Z is -C(R9XR10K(R1XR2)- or -O-C(R3l)(R32)-;Y is -SO2NR40-, -S-C(R14XR15K -S(=O)-C(RI4)(R1S)-, or -S(=0)2-C(R14)(R15)-;R1 and R2 are each independently selected from hydrogen, halogen, Ci-C5 alkyl, fluoroalkyl, -OR6 or- NR7R8; or R1 and R2 together form an oxo;R31 and R32 are each independently selected from hydrogen, CpC5 alkyl, or fluoroalkyl;R3 and R4 are each independently selected from hydrogen or alkyl; or R3 and R4 together form an imino;R5 is C2-Ci5 alkyl or carbocyclyalkyl;R7 and R8 are each independently selected from hydrogen, alkyl, carbocyclyl or -C(=O)R13; or R7 and R8, together with the nitrogen atom to which they are attached, form an ΛT-heterocyclyl;R9 and R10 are each independently selected from hydrogen, halogen, alkyl, fluoroalkyl, -OR6, -NR7R8 or carbocyclyl; or R9 and R10 together form an oxo;R11 and R12 are each independently selected from hydrogen, alkyl, carbocyclyl or -C(=O)R13; or R11 andR12, together with the nitrogen atom to which they are attached, form an Λf-heterocyclyl; each R13 is independently selected from alkyl, alkenyl, aryl, aralkyl, carbocyclyl, heteroaryl or heterocyclyl; each R6 and R34 are independently hydrogen or alkyl; each R33 is independently selected from halogen, -OR34, alkyl, or fluoroalkyl; and n is O, 1, 2, 3, or 4. The compound of claim 2 having the structure of Formula (Ib): Formula (Ib) wherein,Y is -S-C(R14J(R15)-, -S(=O)-C(Rl4)(R15)-, or -S(=O)2-C(R14)(R15)-;R1 and R2 are each independently selected from hydrogen, halogen, Q-C5 alkyl, fluoroalkyl, -OR6 or - NR7R8; or R1 and R2 together form an oxo; R3 and R4 are each independently selected from h...
안과 질환 및 장애 치료를 위한 황-연결 화합물황-연결 화합물, 이의 약학 조성물, 및 상기 화합물 및 조성물을 사용하는 노인성 황반 변성 및 스타가르트병과 같은 안과 질환 및 장애의 치료 방법이 제공된다.하기 화학식 (Ⅰ) 의 화합물 또는 이의 호변이성질체, 입체이성질체, 기하 이성질체 또는 이의 약학적으로 허용가능한 용매화물, 수화물, 염, N-옥시드 또는 전구약물:화학식 (Ⅰ)(식 중,Z 는 결합, -C(R1)(R2)-, -C(R9)(R10)-C(R1)(R2)-, -X-C(R31)(R32)-, -C(R9)(R10)-C(R1)(R2)-C(R36)(R37)-, -X-C(R31)(R32)-C(R1)(R2)- 또는 -C(R38)(R39)-X-C(R31)(R32)- 이고;Y 는 -SO2NR40-, -S-C(R14)(R15)-, -S(=O)-C(R14)(R15)- 또는 -S(=O)2-C(R14)(R15)- 이고;R1 및 R2 는 각각 독립적으로 수소, 할로겐, C1-C5 알킬, 플루오로알킬, -OR6 또는 -NR7R8 로부터 선택되거나; R1 및 R2 는 함께 옥소를 형성하고;R31, R32, R38 및 R39 는 각각 독립적으로 수소, C1-C5 알킬 또는 플루오로알킬로부터 선택되고;R40 은 수소, 알킬, 알케닐, 알키닐, 아릴, 아르알킬, 카르보시클릴, 헤테로아릴 또는 C-부착 헤테로시클릴로부터 선택되거나; R40 및 R5 는, 이들이 부착되어 있는 질소 원자와 함께 헤테로사이클을 형성하고;각각의 R14 및 R15 는 독립적으로 수소, 알킬, 알케닐, 알키닐, 아릴, 아르알킬, 카르보시클릴, 헤테로아릴 또는 C-부착 헤테로시클릴로부터 선택되거나; R14 및 R15 는 이들이 부착되어 있는 탄소 원자와 함께 카르보시클릴 또는 헤테로시클릴을 형성하거나; 임의로는, R5 와 R14 또는 R15 중 하나는, 이들이 부착되어 있는 탄소 원자와 함께 카르보사이클 또는 헤테로사이클을 형성하고;R36 및 R37 은 각각 독립적으로 수소, 할로겐, C1-C5 알킬, 플루오로알킬, -OR6 또는 -NR7R8 로부터 선택되거나; R36 및 R37 은 함께 옥소를 형성하거나; 임의로는, R36 및 R1 은 함께 직접 결합을 형성하여 이중 결합을 제공하거나; 임의로는, R36 및 R1 은 함께 직접 결합을 형성하고, R37 및 R2 는 함께 직접 결합을 형성하여 삼중 결합을 제공하고;R3 및 R4 는 각각 독립적으로 수소, 알킬, 알케닐, 플루오로알킬, 아릴, 헤테로아릴, 카르보시클릴 또는 C-부착 헤테로시클릴로부터 선택되거나; R3 및 R4 는 이들이 부착되어 있는 탄소 원자와 함께 카르보시클릴 또는 헤테로시클릴을 형성하거나; R3 및 R4 는 함께 이미노를 형성하고;R5 는 C2-C15 알킬, 카르보시클릴알킬, 아릴알킬, 헤테로아릴알킬 또는 헤테로시클릴알킬이고;각각의 R7 및 R8 은 독립적으로 수소, 알킬, 카르보시클릴, 헤테로시클릴, -C(=O)R13, SO2R13, CO2R13 또는 SO2NR24R25 로부터 선택되거나; R7 및 R8 은 이들이 부착되어 있는 질소 원자와 함께 N-헤테로시클릴을 형성하고;X 는 -O-, -S-, -S(=O)-, -S(=O)2-, -N(R30)-, -C(=O)-, -C(=CH2)-, -C(=N-NR35)- 또는 -C(=N-OR35)- 이고;R9 및 R10 은 각각 독립적으로 수소, 할로겐, 알킬, 플루오로알킬, -OR6, -NR7R8 또는 카르보시클릴로부터 선택되거나; R9 및 R10 은 옥소를 형성하거나; 임의로는, R9 및 R1 은 함께 직접 결합을 형성하여 이중 결합을 제공하거나; 임의로는, R9 및 R1 은 함께 직접 결합을 형성하고, R10 및 R2 는 함께 직접 결합을 형성하여 삼중 결합을 제공하고; R11 및 R12 는 각각 독립적으로 수소, 알킬, 카르보시클릴, -C(=O)R13, SO2R13, CO2R13 또는 SO2NR24R25 로부터 선택되거나; R11 및 R12 는, 이들이 부착되어 있는 질소 원자와 함께 N-헤테로시클릴을 형성하고;각각의 R13 은 독립적으로 알킬, 알케닐, 아릴, 아르알킬, 카르보시클릴, 헤테로아릴 또는 헤테로시클릴로부터 선택되고;각각의 R6, R30, R34 및 R35 는 독립적으로 수소 또는 알킬이고;각각의 R24 및 R25 는 독립적으로 수소, 알킬, 알케닐, 플루오로알킬, 아릴, 헤테로아릴, 카르보시클릴 또는 헤테로시클릴로부터 선택되고;각각의 R33 은 독립적으로 할로겐, OR34, 알킬 또는 플루오로알킬로부터 선택되며; n 은 0, 1, 2, 3 또는 4 임).