JP2010526152A5 - - Google Patents

Claims (33)

  [[3- (2-Amino-1,2-dioxoethyl) -2-ethyl-1- (phenylmethyl) -1H-indol-4-yl] oxy] for the manufacture of a medicament for the treatment of dyslipidemia Use of acetic acid or a pharmaceutically acceptable salt, polymorph, co-crystal, solvate or prodrug derivative thereof.   The use according to claim 1, wherein the administration of the medicament results in one or more of a decrease in cholesterol levels, a decrease in triglyceride levels and an increase in HDL levels.   [[3- (2-Amino-1,2-dioxoethyl) -2-ethyl-1- (phenylmethyl) -1H-indol-4-yl] oxy] acetic acid for the manufacture of a medicament for reducing cholesterol levels or Use of a pharmaceutically acceptable salt, polymorph, co-crystal, solvate or prodrug derivative thereof.   4. The method of claim 2 or 3, wherein administration of the medicament reduces one or more of total cholesterol level, non-HDL cholesterol level, LDL level, LDL particle level, small LDL particle level, oxidized LDL level and apolipoprotein B level. Use of description.   4. Use according to claim 2 or 3, wherein administration of said medicament increases LDL particle size.   Use according to claim 2 or 3, wherein administration of said medicament increases the HDL / LDL ratio.   [[3- (2-Amino-1,2-dioxoethyl) -2-ethyl-1- (phenylmethyl) -1H-indol-4-yl] oxy] for the manufacture of a medicament for the treatment of visceral fat syndrome Use of acetic acid or a pharmaceutically acceptable salt, polymorph, co-crystal, solvate or prodrug derivative thereof.   The prodrug derivatives are [[3- (2-amino-1,2-dioxoethyl) -2-ethyl-1- (phenylmethyl) -1H-indol-4-yl] oxy] acetic acid methyl ester and ((3 8. A 2, 8, or 7 selected from-(2-amino-1,2-dioxoethyl) -2-methyl-1- (phenylmethyl) -1H-indol-4-yl) oxy) acetic acid N-morpholinoethyl ester Use as described in. Administration of said medicament, use of claim 2, 3, or 7 to reduce the levels of one or more inflammatory markers selected from the sPLA _2, CRP and IL-6.   The use according to claim 2, 3 or 7, wherein the pharmaceutical is administered once a day, twice a day or twice a day.   [[3- (2-Amino-1,2-dioxoethyl) -2-ethyl-1- (phenylmethyl) -1H-indol-4-yl] oxy] acetic acid or a pharmaceutically acceptable salt or polymorph thereof , A co-crystal, solvate or prodrug derivative and one or more statins.   The one or more statins are selected from atorvastatin, cerivastatin, fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin and pharmaceutically acceptable salts, solvates, stereoisomers or prodrug derivatives thereof The composition of claim 11.   12. The composition of claim 11, wherein the composition further comprises one or more of ezetimibe, amlodipine, CP-529414, APA-01, sustained release niacin, MK-0524A, fenofibrate and TAK-457. .   Prodrug derivatives are [[3- (2-amino-1,2-dioxoethyl) -2-ethyl-1- (phenylmethyl) -1H-indol-4-yl] oxy] acetic acid methyl ester and ((3- 12. A composition according to claim 11 selected from (2-amino-1,2-dioxoethyl) -2-methyl-1- (phenylmethyl) -1H-indol-4-yl) oxy) acetic acid N-morpholinoethyl ester. .   12. The composition of claim 11, further comprising one or more pharmaceutically acceptable carriers.   [[3- (2-Amino-1,2-dioxoethyl) -2-ethyl-1- (phenylmethyl) for the manufacture of a medicament for the treatment of dyslipidemia, administered in combination with one or more statins -1H-indol-4-yl] oxy] acetic acid or a pharmaceutically acceptable salt, polymorph, co-crystal, solvate or prodrug derivative thereof.   17. Use according to claim 16, wherein administration of the medicament in combination with one or more statins results in a decrease in cholesterol levels, a decrease in triglyceride levels and an increase in HDL levels.   [[3- (2-Amino-1,2-dioxoethyl) -2-ethyl-1- (phenylmethyl) -1H for the manufacture of a medicament for reducing cholesterol levels, administered in combination with one or more statins -Indol-4-yl] oxy] acetic acid or a pharmaceutically acceptable salt, polymorph, co-crystal, solvate or prodrug derivative thereof.   Administration of the medicament in combination with one or more statins is one of total cholesterol level, non-HDL cholesterol level, LDL level, LDL particle level, small LDL particle level, oxidized LDL level and apolipoprotein B level 19. Use according to claim 17 or 18, which reduces the above.   19. Use according to claim 17 or 18, wherein administration of the medicament in combination with one or more statins increases LDL particle size.   19. Use according to claim 17 or 18, wherein administration of the medicament in combination with one or more statins increases the HDL / LDL ratio.   [[3- (2-Amino-1,2-dioxoethyl) -2-ethyl for the manufacture of a medicament for the treatment of cardiovascular diseases or diseases associated with cardiovascular diseases, administered in combination with one or more statins -1- (Phenylmethyl) -1H-indol-4-yl] oxy] acetic acid or a pharmaceutically acceptable salt, polymorph, co-crystal, solvate or prodrug derivative thereof.   Cardiovascular disease is atherosclerosis, coronary artery disease, coronary heart disease, disease associated with coronary artery disease or coronary heart disease, cerebrovascular disease, disease associated with cerebrovascular disease, peripheral vascular disease, disease associated with peripheral vascular disease 23. Use according to claim 22, selected from: aneurysm, vasculitis, venous thrombosis, diabetes and visceral fat syndrome.   24. Use according to claim 23, wherein the cardiovascular disease is selected from atherosclerosis, angina pectoris, myocardial infarction, transient cerebral ischemic attack and stroke.   [[3- (2-Amino-1,2-dioxoethyl) -2-ethyl-1- (phenylmethyl) for the manufacture of a medicament for the treatment of visceral fat syndrome, administered in combination with one or more statins -1H-indol-4-yl] oxy] acetic acid or a pharmaceutically acceptable salt, polymorph, co-crystal, solvate or prodrug derivative thereof. Administration of the pharmaceutical in combination with one or more statins or statins composite agent, claims to reduce the level of one or more inflammatory markers selected from the sPLA _2, CRP and IL-6 16, 18, 22 or 25. Use according to 25.   [[3- (2-Amino-1,2-dioxoethyl) -2-ethyl-1- (phenylmethyl) -1H-indole-4-one for the manufacture of a medicament to increase the efficacy of one or more statins [Il] oxy] acetic acid or a pharmaceutically acceptable salt, polymorph, co-crystal, solvate or prodrug derivative thereof.   Prodrug derivatives are [[3- (2-amino-1,2-dioxoethyl) -2-ethyl-1- (phenylmethyl) -1H-indol-4-yl] oxy] acetic acid methyl ester and ((3- (16) 18, 18, 22, selected from (2-amino-1,2-dioxoethyl) -2-methyl-1- (phenylmethyl) -1H-indol-4-yl) oxy) acetic acid N-morpholinoethyl ester Use according to 25 or 27.   The one or more statins are selected from atorvastatin, cerivastatin, fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin and pharmaceutically acceptable salts, solvates, stereoisomers or prodrug derivatives thereof 28. Use according to claim 16, 18, 22, 25 or 27.   28. Use according to claim 16, 18, 22, 25 or 27, wherein the medicament is administered simultaneously with one or more statins.   The use according to claim 30, wherein the medicament is administered in the same formulation as the one or more statins.   28. Use according to claim 16, 18, 22, 25 or 27, wherein the medicament is administered sequentially with one or more statins.   28. Use according to claim 16, 18, 22, 25 or 27, wherein the medicament is administered once a day, twice a day or twice a day or more.