Reivindicaciones
WHAT IS CLAIMED IS: 1. A method of reducing intraocular pressure in a subject in need thereof, said method comprising: administering to said subject an indole derivative in an amount effective to reduce intraocular pressure, wherein said indole derivative is a compound of Formula I: <img class="EMIRef" id="fab8a2f0-8f0a-4c57-861a-b4070ad74fdb-IMG00280001" /> wherein: n 0, 1, 2, 3,4, or 5 ; m=0orl ; Ri and R2 are each independently H, substituted or unsubstituted linear-, branchedor cyclo-alkyl,-alkenyl,-alkynyl,-aryl,-aralkyl,-aralkenyl,-aralkynyl, R6 (CO)-, F, OR5, or either Ri or R2 is R6R7N (CO)-; or Ri and R2 when taken together is oxo; or a substituted or unsubstituted carbocycle, or heterocycle of 4,5,6, or 7 members; R3 and R4 are each independently H, substituted or unsubstituted linear-, branchedor cyclo-alkyl,-alkenyl,-alkynyl,-aryl,-aralkyl,-aralkenyl,-aralkynyl, R6 (CO)-, or R3 and R4 when taken together is oxo; or a substituted or unsubstituted carbocycle or a heterocycle of 4, 5, 6, or 7 members ; or R2 and R4 when taken together represent a substituted or unsubstituted carbocycle or heterocycle of 4,5,6, or 7 members; A = halogen, N02, CN or R5-X1-; B = halogen, N02, CN or R5-Xl-; when B is in position on 4 of indole, and when B is not equal to halogen, NO2, CN or H, then B taken together with RI, or R3, or Zi, represent a substituted or unsubstituted carbocyclic or heterocyclic ring of 5,6, or 7 members; when B is not equal to halogen, NO2, CN or H, and when B is in position 7 of the indole, then B optionally taken together with E represent a substituted or unsubstituted heterocyclic ring of 5,6, or 7 members; Xi = O, S, NR9,-CF2-,-CH2-,-CH2CH2-,-CH2CH2CH2-, or absent; R5 = H, substituted or unsubstituted linear-, branched-or cyclo-alkyl,-alkenyl,alkynyl,-aryl,-aralkyl,-aralkenyl,-aralkynyl, R6R7N(CO)-, R6 (CO)-, R80 (CO)-, R8S (O) 2- , R8S (O)-, R80S (0) 2-, R8OS (O)-, R6R7NS (0) 2-, R6R7NP (O) (ORg)-, R8P (O) (ORg)-, R6 and R7 are independently H, substituted or unsubstituted linear-, branched-or cyclo-alkyl,-alkenyl,-alkynyl,-aryl,-aralkyl,-aralkenyl,-aralkynyl or heterocyclic ring; when taken together, NR6R7 represent a substituted or unsubstituted ring of 3,4,5,6, or 7 members; R8 = substituted or unsubstituted linear-, branched-or cyclo-alkyl,-alkenyl,alkynyl,-aryl,-aralkyl,-aralkenyl,-aralkynyl, heterocyclic ring or CF3- ; Rg = H, substituted or unsubstituted linear-, branched-or cyclo-alkyl,-alkenyl,alkynyl,-aryl,-aralkyl,-aralkenyl,-aralkynyl ; when taken together, R6 and Rg represent a ring of 5,6, or 7 members; E = H, substituted or unsubstituted linear-, branched-or cyclo-alkyl,-alkenyl,alkynyl,-aryl,-aralkyl,-aralkenyl,-aralkynyl, R80 (CO)-, R8S (O) 2-, or OR6 ; or E = R6 (CO)-, provided that when Z1 = NR10R11, R10 is H; or E = R6 (CO)-, provided that when Zl = OR5, R5 is not H, alkyl, aryl, or aralkyl ; or E = R6R7N (CO)-, provided that when Z1 = NR10R11, R10 is H; or E = R6R7N (CO)-, provided that when Z1 = OR5, Rs is not H, alkyl, aryl, or aralkyl ; D1 = halogen, NO2, CN or R5-X1-; when D1 = R5-Xl-, D1 and E when taken together represent a substituted or unsubstituted heterocyclic ring of 4,5,6, or 7 members; when D1 = R5 - X1 -, D1 and Ri when taken together represent a substituted or unsubstituted carbocyclic or heterocyclic ring of 5,6, or 7 members; when D1 = R5 - X1 -, D, and R3 when taken together represent a substituted or unsubstituted carbocyclic or heterocyclic ring of 5, 6, or 7 members; when D, = R5 - X1 -, D, and Z1 when taken together represent a substituted or unsubstituted heterocyclic ring of 5,6, or 7 members; Z1 = OR5 NR10R11; Zl and R1 when taken together represent a substituted or unsubstituted heterocycle of 4,5,6, or 7 members; Rio = H, substituted or unsubstituted linear-, branched-or cycloalkyl,-alkenyl,-alkynyl,-aryl,-aralkyl,-aralkenyl,-aralkynyl, heterocycle, R6R7N (CO)-, R6 (CO)-, R80 (CO)-, R8S (O) 2-, R80S (O) 2-, R6R7NS (O) 2-, CF3- ; and Ru = NR6R7 (CO)-, R6 (CO)-, R80 (CO)-, RgS (O) 2-, R8OS(O)2-, R6R7NS(O)2-; provided that when n = 1, m = 0, R5 = CH3, Xi = O, B = D1 = E =R3= R4 = H, then Z is not -NHAc. 2. 2. The method according to Claim 1, wherein said indole is a compound of Formula II : <img class="EMIRef" id="fab8a2f0-8f0a-4c57-861a-b4070ad74fdb-IMG00300001" /> wherein Rlo and R'10 each independently is H, (un)substituted linear-, branched-or cyclo-alkyl,-alkenyl,-alkynyl,-aryl,-aralkyl,-aralkenyl,-aralkynyl, heterocycle, R6R7N (CO)-, R6 (CO)-, RsO (CO)-, R8S (O) 2-, R80S (O) 2-, R6R7NS (O) 2-, CF3- ; wherein Z2 and Z3 are independently R6R7N(CO)-, R6 (CO)-, R80 (CO)-, R8S (O) 2-, R80S (0) 2-, R6R7NS(O)2-; or each unit Z2-N-R10, and Z3-N-R10 independently represent a ring of 4-7 members. 3. 3. The method according to Claim 1, wherein said indole is a compound of Formula m <img class="EMIRef" id="fab8a2f0-8f0a-4c57-861a-b4070ad74fdb-IMG00310001" /> wherein D1 is halogen, NO2, CN, or Rs-Xi, or alternately D1 forms a ring with R6, or alternately D1 and R6 are absent and the carbonyl participates in a ring bridging the two positions. 4. 4. The method according to Claim 3 wherein B = D1 = E = H. 5. 5. The method according to Claim 1, wherein said indole is a compound of Formula IV: Formula IV <img class="EMIRef" id="fab8a2f0-8f0a-4c57-861a-b4070ad74fdb-IMG00310002" /> D2 = H, substituted or unsubstituted linear-, branched-or cyclo-alkyl, halogen, substituted or unsubstituted phenyl, or substituted or unsubstituted arylalkyl ; provided when R5 = R6 = CH3, then D2 is not equal to H. 6. 6. The method according to Claim 5 wherein R5 = C1-C4 alkyl, acetyl, formyl or CF3 ; R6 = H, Cl-C4 alkyl, or CF3; provided when R5. = CH3, then R6 is not CH3. 7. 7. The method according to Claim 1, wherein said compound is administered in an amount effective to achieve a concentration thereof on the ocular surface of said subject of from about 10-l2M to 10-3M. 8. 8. The method according to Claim 1, wherein said compound is 5methoxycarbonylamino-N-acetyltryptamine. 9. 9. The method according to Claim 1, wherein said indole is selected from the group of compounds consisting of N- [2- (5-Dimethylamino-1H-indol-3-yl)-ethyl]- acetamide, {3-[2-(2-Hydroxy-benzylamino)-ethyl]-lH-indol-5-yl}-carbamic acid methyl ester, [3- (2-Acetylamino-ethyl)-2-phenyl-lH-indol-5-yl]-carbamic acid methyl ester, [3- (2Acetylamino-ethyl)-l-methyl-lH-indol-5-yl]-carbamic acid methyl ester, [3- (3- Acetylamino-propyl)-lH-indol-5-yl]-carbamic acid methyl ester, [3- (3- Benzenesulfonylamino-propyl)-lH-indol-5-yl]-carbamic acid methyl ester, N- [2- (5- Ureido-lH-indol-3-yl)-ethyl]-acetamide, [3- (2-Propionylamino-ethyl)-lH-indol-5-yl]- carbamic acid methyl ester, N-[2-(5-Methoxyvarbonylamino-lH-indol-3-yl)-ethyl]- succinamic acid, [3-(2-Acetylamino-ethyl)-lH-indol-5-yl]-carbamic acid allyl ester, [3- (2- Acetylamino-ethyl)-lH-indol-5-yl]-carbamic acid 3-hydroxy-propyl ester, [3- (2Acetylamino-ethyl)-lH-indol-5-yl]-carbamic acid 2,3-dihydroxy-allyl ester, and N- [3- (2Acetylamino-ethyl)-lH-indol-5-yl]-acetamide, [3-(2-Acetylamino-ethyl)-2-bromo-1H- indol-5-yl]-carbamic acid methyl ester, [3-(2-Acetylamino-ethyl)-2-methyl-1H-indol-5-yl]carbamic acid methyl ester, [3-(2-Acetylamino-ethyl)-l-benzyl-lH-indol-5-yl]-carbamic acid methyl ester, (l-Oxo-2, 3,4,9-tetrahydro-lH-ss-carbolin-6-yl)-carbamic acid methyl ester, and [3- (2-Acetylamino-ethyl)-4- (l-methoxy-ethyl)-l-methyl-lH-indol-5-yl]carbamic acid methyl ester. 10. 10. The method according to Claim 1, wherein said indole derivative of Formula I is administered to a subject in need of treatment, to treat a condition selected from the group consisting of ocular hypertension and glaucoma, in and amount effective to treat said condition. 11. 11. The method according to Claim 10, wherein said glaucoma is primary glaucoma. 12. 12. The method according to Claim 11, wherein said primary glaucoma is selected from the group consisting of narrow-angle, acute congestive glaucoma; wideangle, chronic simple glaucoma; and secondary glaucoma. 13. 13. The method according to Claim 12, wherein said indole derivative is coadministered with therapeutic and adjunctive agents used to manage narrow angle, acute congestive glaucoma, selected from the group consisting of : anticholinesterase inhibitors, carbonic anhydrase inhibitors, prostaglandin analogues, and osmotic agents. 14. 14. The method according to of Claim 13, wherein said anticholinesterase inhibitor is salicylate or pilocarpine nitrate; said carbonic anhydrase inhibitor is acetazolamide; said prostaglandin analogue is Xalatan or Lumigan; and said osmotic agent is mannitol or glycerin. 15. 15. The method according to Claim 1, wherein said indole is co-administered with therapeutic agents used to manage wide angle, chronic simple glaucoma, and is selected from the group consisting of parasympathomimetic agents, short-acting anticholinesterase agents, long-acting anticholinesterase agents, alpha-adrenergic agonists, beta-adrenergic antagonists, sympathomimetic agents, and prostaglandin analogues. 16. 16. The method according to Claim 15, wherein said parasympathomimetic agent is pilocarpine nitrate; said short-acting anticholinesterase inhibitor is physostigmine salicylate; said long-acting anticholinesterase inhibitor is demecarium bromide, echothiophate iodide or isofluorophate; said beta adrenergic antagonist is timolol maleate ; said sympathomimetic agent is epinephrine or phenylephrine; and said prostaglandin analogue is latanoprost or Lumigan. 17. 17. The method according to Claim 12, wherein said indole derivative is coadministered with therapeutic agents used to manage secondary glaucoma, and selected from the group consisting of : parasympathomimetic agents, short-acting anticholinesterase agents, long-acting anticholinesterase agents, beta-adrenergic antagonists, sympathomimetic agents, and prostaglandin analogues. 18. 18. The method according to Claim 17, wherein said parasympathomimetic agent is pilocarpine nitrate; said short-acting anticholinesterase inhibitor is physostigmine salicylate; said long-acting anticholinesterase inhibitor is demecarium bromide, echothiophate iodide or isofluorophate; said beta adrenergic antagonist is timolol maleate; said sympathomimetic agents is epinephrine or phenylephrine; and said prostaglandin analogue is latanoprost or Lumigan. 19. 19. The method according to Claim 1, wherein said indole derivative is administered in a sterile preparation comprising said compound or pharmaceutically acceptable salts thereof together with a pharmaceutically acceptable vehicle or carrier therefor. 20. 20. The method according to Claim 19, wherein said pharmaceutically acceptable carrier is a physiologically compatible vehicle selected from the group consisting of aqueous electrolyte solutions, polyethers, polyvinyls, polymers of acrylic acid, lanolin, and glucosaminoglycans, whereby said formulation enhances outflow of fluid from the eye and thereby reduces intraocular pressure. 21. 21. The method according to Claim 1, wherein said method of administering said compound is selected from the group consisting of; a) topical administration via a carrier vehicle selected from a group consisting of, drops of liquid, liquid wash, gels, ointments, sprays and liposomes ; b) infusion to said ocular surface via a device selected from a group consisting of, a pump-catheter system, a continuous or selective release device, and a contact lens; and c) systemic administration. 22. 22. The method according to Claim 22, wherein said systemic administration of said indole is accomplished by administering an intra-operative instillation of a gel, cream, powder, foam, crystals, liposomes, spray or liquid suspension form of said compound, such that a therapeutically effective amount of said compound contacts the ocular tissues of said subject via systemic absorption and circulation. 23. 23. The method according to Claim 1, wherein said indole derivative is used to reduce adverse side effects of drugs used to treat glaucoma, comprising the step of : administering said indole derivative with a drug selected from the group consisting of : demecarium, echothiophate and isofluorophate. 24. A composition of matter selected from the group of compounds consisting of : [3- (2- acetylamino-ethyl)-2-methyl-lH-indol-5-yl]-carbamic acid methyl ester; [3- (2acetylamino-ethyl)-2-phenyl-1H-indol-5-yl]-carbamic acid methyl ester; [3- (3-acetylamino- prop-l-yl)-lH-indol-5-yl]-carbamic acid methyl ester; N- [2- (5-methoxycarbonylamino-lH- indol-3-yl)-ethyl]-succinamic acid; [3- (2-acetylamino-ethyl)-lH-indol-5-yl]-carbamic acid allyl ester; [3- (2-acetylamino-ethyl)-lH-indol-5-yl]-carbamic acid 3-hydroxy-prop-1-yl ester; [3-(2-acetylamino-ethyl)-lH-indol-5-yl]-carbamic acid 2,3-dihydroxy-allyl ester; [3- (2-acetylamino-ethyl)-4- (l-methoxy-ethyl)-1-methyl-lH-indol-5-yl]-carbamic acid methyl ester N- [3- (2-acetylamino-ethyl)-lH-indol-5-yl]-acetamide ; [3- (2-acetylamino- ethyl)-l-benzyl-lH-indol-5-yl]-carbamic acid methyl ester; and (1-oxo-2, 3,4,9-tetrahydro1H-p-carbolin-6-yl)-carbamic acid methyl ester.
