MTOR PATHWAY INHIBITORS FOR TREATING OCULAR DISORDERS

摘要

Diseases and conditions associated with tissues of the body, including but not limited to tissues in the eye, can be effectively treated, prevented, inhibited, onset delayed, or regression caused by administering therapeutic agents to those tissues. Described herein are ophthalmic formulations that deliver a variety of therapeutic agents, including but not limited to rapamycin (sirolimus), analogs thereof (rapalogs) or other mTOR inhibitors, to a subject for an extended period of time. The ophthalmic formulations may be placed in an aqueous medium of a subject, including but not limited to intraocular or periocular administration, or placement proximate to a site of a disease or condition to be treated in a subject. A method may be used to administer a therapeutic agent to treat or prevent age-related macular degeneration, macular edema, diabetic retinopathy, uveitis, dry eye, or a hyperpermeability disease in a subject.

主权项

1. A method for treating an ocular condition in a human subject, comprising administering to an eye of the human subject a volume of an ophthalmic formulation comprising an amount of a mTOR pathway inhibitor effective for treating the ocular condition in the human subject, wherein the mTOR pathway inhibitor is selected from the group consisting of AZD8055, BEZ235, BGT226, curcumin, farnesylthioslicyclic acid, INK128, LY294002, RGDS-conjugated LY294002, MKC-1, OSI-027, P2281, palomid 529 (P529), PI-103, PP242, PP30, QLT-0447, TAE226, TOP216, torin1, wortmannin, XL-765, EXEL-2044, EXEL-3885, EXEL-4431, EXEL-7518, YM-58483, compound 23, compound 401, PF04691502, ZSTK474, AZD6482, BKM120, CAL-101, CAL-120, CAL-263, GCS-0941, GSK-1059615, LY317615, PX-866, SF2626, WX-037, XL147, A-443654, AEZS-126, AEZS-127, AR-12, AR-42, AT13148, EZN-4150, GSK60-693, GSK1720070, KRX-0401, MK2206, SR13668, VQD-002, NV-128, GDC-0941, KU-006374, WAY-600, WYE-687, WYE-354, biolimus a9, myolimus, novolimus, ABI-009, 5-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[5,6-e]pyrimidin-7-yl]-2-methoxy-N-methylbenzamide; 4-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[5,6-e]pyrimidin-7-yl]aniline; 6-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[5,6-e]pyrimidin-7-yl]-1H-indazol-3-amine; 8-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[5,6-e]pyrimidin-7-yl]-1,2,3,4-tetrahydro-1,4-benzodiazepin-5-one; 5-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[5,6-e]pyrimidin-7-yl]-2-methoxy-N-methylbenzamide; 5-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[5,6-e]pyrimidin-7-yl]pyridin-2-amine; N-[3-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[5,6-e]pyrimidin-7-yl]phenyl]methanesulfonamide; 3-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[5,6-e]pyrimidin-7-yl]aniline; 5-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[6,5-d]pyrimidin-7-yl]-2-ethoxybenzamide; 5-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[5,6-e]pyrimidin-7-yl]-2-(difluoromethoxy)-N-methylbenzamide; 5-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[5,6-e]pyrimidin-7-yl]-1H-indazol-3-amine; [5-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[5,6-e]pyrimidin-7-yl]-2-methoxyphenyl]methanol; N-[[4-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[5,6-e]pyrimidin-7-yl]phenyl]methyl]methanesulfonamide; 5-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[5,6-e]pyrimidin-7-yl]-1,3-dihydroindol-2-one; 6-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[5,6-e]pyrimidin-7-yl]-1,3-dihydroindol-2-one; 3-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[5,6-e]pyrimidin-7-yl]-N-methylbenzamide; 5-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[5,6-e]pyrimidin-7-yl]-2-(difluoromethoxy)benzamide; 6-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[5,6-e]pyrimidin-7-yl]-2,3-dihydroisoindol-1-one; [5-[2-(2,6-dimethylmorpholin-4-yl)-4-morpholin-4-ylpyrido[6,5-d]pyrimidin-7-yl]-2-methoxyphenyl]methanol; and [2-methoxy-5-[2-(3-methylmorpholin-4-yl)-4-morpholin-4-ylpyrido [6,5-d]pyrimidin-7-yl]phenyl]methanol, and pharmaceutically acceptable salts and esters thereof.