Method of treating age-related macular degeneration

A method of treating or preventing age-related macular degeneration (AMD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of Formula II, or a pharmaceutically acceptable salt or ester thereof, or a pharmaceutical composition comprising the compound or pharmaceutically acceptable salt or ester thereof:

• Cy10-L10-Cy11-L11-W10 Formula II
• wherein:
• Cy10 and Cy11 are each independently an optionally substituted cycloalkyl ring (e.g., C3-7 cycloalkyl ring), an optionally substituted heterocyclic ring (e.g., 4-7 membered heterocyclic ring), an optionally substituted aryl ring (e.g., C6-10 aryl ring), an optionally substituted heteroaromatic ring (e.g., 5-10 membered heteroaromatic ring), or an optionally substituted ring structure comprising a cycloalkyl ring or heterocyclic ring, and an aryl or heteroaryl ring, wherein the ring structure can be a fused ring;
• L10 is null or a linker;
• L11 is null, an optionally substituted C1-6alkylene, an optionally substituted C1-6 heteroalkylene, an optionally substituted C2-6 alkenylene, an optionally substituted C2-6 alkynylene, an optionally substituted C3-6cycloalkylene, an optionally substituted arylene, an optionally substituted heteroarylene, or an optionally substituted 4-7 membered heterocyclylene;
• W10 is —OR1;
• —COOR1a;
• —OCOOR1a;
• —COR2;
• —NR3R4;
• —CONR3aR4a;
• —OCONR3bR4b;
• —SO2NR3cR4c;
• —OSO2NR3dR4d;
• —SR5;
• —SO2R5a;
• —OCOR2a;
• —OSO2R5a or
• wherein:
• R1 and R1a are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclyl;
• R3 and R4 are each independently hydrogen, —COR2b, —SO2R5b, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl optionally substituted C2-6 alkynyl, optionally substituted C3-6 cycloalkyl, optionally substituted phenyl, optionally substituted 5 or 6 membered heteroaryl, or optionally substituted 4-7 membered heterocyclyl, or R3 and R4 together with the atoms they are bound to form an optionally substituted 4-7 membered heterocyclyl;
• R2, R2a, R2b, R5, R5a, and R5b are each independently hydrogen, —OH, —NR3eR4e, an optionally substituted C1-6 alkyl, an optionally substituted C2-6 alkenyl an optionally substituted C2-6 alkynyl, an optionally substituted C1-6alkoxy, an optionally substituted C3-6 cycloalkyl, an optionally substituted C3-6 cycloalkoxy, an optionally substituted phenyl;
• an optionally substituted 5 or 6 membered heteroaryl;
• or an optionally substituted 4-7 membered heterocyclyl;
• and
• R3a, R3b, R3c, R3d, R3e, R4a, R4b, R4c, R4d, and R4e are each independently hydrogen, an optionally substituted C1-6 alkyl, an optionally substituted C2-6 alkenyl an optionally substituted C2-6 alkynyl, an optionally substituted C1-6alkoxy, an optionally substituted C3-6 cycloalkyl, an optionally substituted C3-6cycloalkoxy, an optionally substituted phenyl;
• an optionally substituted 5 or 6 membered heteroaryl;
• or an optionally substituted 4-7 membered heterocyclyl;
• or R3a and R4a, R3b and R4b, R3c and R4c, R3d and R4d, or R3e and R4e, together with the atoms they are bound to form an optionally substituted 4-7 membered heterocyclyl.

A method of treating or preventing age-related macular degeneration (AMD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of Formula III, or a pharmaceutically acceptable salt or ester thereof, or a pharmaceutical composition comprising the compound or pharmaceutically acceptable salt or ester thereof:

• Ar20-L20-W20 Formula III,
• wherein Ar20 is an optionally substituted aryl ring (e.g., C6-10 aryl ring), or an optionally substituted heteroaryl ring (e.g., 5-10 membered heteroaryl ring);
• L20 is null, an optionally substituted C1-6 alkylene, an optionally substituted C1-6 heteroalkylene, an optionally substituted C2-6 alkenylene, an optionally substituted C2-6 alkynylene, an optionally substituted C3-6cycloalkylene, an optionally substituted arylene, an optionally substituted heteroarylene, or an optionally substituted 4-7 membered heterocyclylene,
• W20 is —OR1;
• —COR2;
• —COOR1a;
• —OCOOR1a;
• —NR3R4;
• —CONR3aR4a;
• —OCONR3bR4b;
• —SO2NR3cR4c;
• —OSO2NR3dR4d;
• —SR5;
• —SO2R5a;
• —OCOR2a;
• —OSO2R5a;
• or
• wherein:
• R1 and R1a are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclyl;
• R3 and R4 are each independently hydrogen, —COR2b, —SO2R5b, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C3-6 cycloalkyl, optionally substituted phenyl, optionally substituted 5 or 6 membered heteroaryl, or optionally substituted 4-7 membered heterocyclyl, or R3 and R4 together with the atoms they are bound to form an optionally substituted 4-7 membered heterocyclyl;
• R2, R2a, R2b, R5, R5a, and R5b are each independently hydrogen, —OH, —NR3eR4e, an optionally substituted C1-6 alkyl, an optionally substituted C2-6 alkenyl, an optionally substituted C2-6 alkynyl, an optionally substituted C1-6alkoxy, an optionally substituted C3-6 cycloalkyl, an optionally substituted C3-6cycloalkoxy, an optionally substituted phenyl;
• an optionally substituted 5 or 6 membered heteroaryl;
• or an optionally substituted 4-7 membered heterocyclyl;
• and
• R3a, R3b, R3c, R3d, R3e, R4a, R4b, R4c, R4d, and R4e are each independently hydrogen, an optionally substituted C1-6 alkyl, an optionally substituted C2-6 alkenyl, an optionally substituted C2-6 alkynyl, an optionally substituted C1-6alkoxy, an optionally substituted C3-6 cycloalkyl, an optionally substituted C3-6cycloalkoxy, an optionally substituted phenyl;
• an optionally substituted 5 or 6 membered heteroaryl;
• or an optionally substituted 4-7 membered heterocyclyl;
• or R3a and R4a, R3b and R4b, R3c and R4c, R3d and R4d, or R3e and R4e, together with the atoms they are bound to form an optionally substituted 4-7 membered heterocyclyl.

A method of treating or preventing age-related macular degeneration (AMD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of Formula IV-1 or IV-2, or a pharmaceutically acceptable salt or ester thereof, or a pharmaceutical composition comprising the compound or pharmaceutically acceptable salt or ester thereof:

• wherein:
• R40 is hydrogen;
• —COR2;
• —COOR1a;
• —SO2R5a;
• optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclyl;
• R41 is —OR1;
• —OCOOR1a;
• —OCONR3bR4b;
• —OCOR2a;
• or —OSO2R5a;
• n is 0 or 1;
• R42, R43, and R44 are each independently hydrogen, —OR1, OCOR2a;
• or —OSO2R5a;
• L30 is null or methylene, W30 is —OR1;
• —COR2;
• —COOR1a;
• —OCOOR1a;
• —NR3R4;
• —CONR3aR4a;
• —OCONR3bR4b;
• —OSO2NR3dR4d;
• —OCOR2a;
• or —OSO2R5a
• wherein:
• R1 and R1a are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclyl;
• R3 and R4 are each independently hydrogen, —COR2b, —SO2R5b, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C3-6 cycloalkyl, optionally substituted phenyl, optionally substituted 5 or 6 membered heteroaryl, or optionally substituted 4-7 membered heterocyclyl, or R3 and R4 together with the atoms they are bound to form an optionally substituted 4-7 membered heterocyclyl;
• R2, R2a, R2b, R5, R5a, and R5b are each independently hydrogen, —OH, —NR3eR4e, an optionally substituted C1-6 alkyl, an optionally substituted C2-6 alkenyl, an optionally substituted C2-6 alkynyl, an optionally substituted C1-6alkoxy, an optionally substituted C3-6 cycloalkyl, an optionally substituted C3-6 cycloalkoxy, an optionally substituted phenyl;
• an optionally substituted 5 or 6 membered heteroaryl;
• or an optionally substituted 4-7 membered heterocyclyl;
• and
• R3a, R3b, R3c, R3d, R3e, R4a, R4b, R4c, R4d, and R4e are each independently hydrogen, an optionally substituted C1-6 alkyl, an optionally substituted C2-6 alkenyl an optionally substituted C2-6 alkynyl an optionally substituted C1-6alkoxy, an optionally substituted C3-6 cycloalkyl, an optionally substituted C3-6 cycloalkoxy, an optionally substituted phenyl;
• an optionally substituted 5 or 6 membered heteroaryl;
• or an optionally substituted 4-7 membered heterocyclyl;
• or R3a and R4a, R3b and R4b, R3c and R4c, R3d and R4d, or R3e and R4e, together with the atoms they are bound to form an optionally substituted 4-7 membered heterocyclyl.

A method of treating or preventing age-related macular degeneration (AMD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibiotic selected from Amikacin, Amoxicillin, Ampicillin, Arsphenamine, Azithromycin, Azlocillin, Aztreonam, Bacitracin, Capreomycin, Carbenicillin, Cefaclor, Cefadroxil, Cefalexin, Cefalotin, Cefamandole, Cefazolin, Cefdinir, Cefditoren, Cefixime, Cefoperazone, Cefotaxime, Cefoxitin, Cefpodoxime, Cefprozil, Ceftazidime, Ceftibuten, Ceftizoxime, Ceftriaxone, Cefuroxime, Chloramphenicol, Cilastatin, Clarithromycin, Clavulanate, Clindamycin, Clofazimine, Cloxacillin, Colistin, Cycloserine, Dalfopristin, Dapsone, Daptomycin, Dicloxacillin, Dirithromycin, Doripenem, Doxycycline, Erythromycin, Ethambutol, Ethionamide, Flucloxacillin, Fosfomycin, Furazolidone, Fusidic acid, Gentamicin, Imipenem, Isoniazid, Kanamycin, Lincomycin, Linezolid, Loracarbef, Mafenide, Meropenem, Methicillin, Metronidazole, Mezlocillin, Minocycline, Mupirocin, Nafcillin, Neomycin, Netilmicin, Nitrofurantoin, Oxacillin, Oxytetracycline, Paromomycin, Penicillin G, Penicillin V, Piperacillin, Platensimycin, Polymyxin B, Pyrazinamide, Quinupristin, Rapamycin, Rifabutin, Rifampicin, Rifampin, Rifapentine, Rifaximin, Roxithromycin, Silver sulfadiazine, Spectinomycin, Streptomycin, Sulbactam, Sulfacetamide, Sulfadiazine, Sulfamethizole, Sulfamethoxazole, Sulfanilimide, Sulfasalazine, Sulfisoxazole, Tazobactam, Teicoplanin, Telavancin, Telithromycin, Temocillin, Tetracycline, Thiamphenicol, Ticarcillin, Tigecycline, Tinidazole, Tobramycin, Trimethoprim, Troleandomycin Vancomycin, enoxacin, lomefloxacin, nalidixic acid, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, ofloxacin, norfloxacin, Cefotetan, Cefonicid, Cephradine, Cephapirin, Cephalothin, Cefinetazole, Cefotaxime, Moxalactam, Cefepime, Ceftaroline fosamil, Ceftobiprole, Dalbavancin, Demeclocycline, Metacycline, Ertapenem, Fidaxomicin, geldanamycin, herbimycin, Posizolid, Radezolid, Torezolid, Oritavancin, Spiramycin, Sulfadimethoxine, Sulfonamidochrysoidine, Gemifloxacin Nadifloxacin Trovafloxacin Grepafloxacin Sparfloxacin Temafloxacin, Teixobactin, Malacidins, and combinations thereof, or a pharmaceutically acceptable salt thereof.