Agonists of peroxisome proliferator-activated receptor alpha and methods of use
AssigneeThe Board of Regents of the University of Oklahoma
InventorsAdam Duerfeldt, Jian-xing Ma, Xiaozheng Dou, Dinesh Nath, Young-Hwa Shin
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Abstract
Benzyl derivative compounds having peroxisome proliferator-activated receptor α (PPARα) agonistic activity, compositions containing such compounds, and methods of their use in enhancing PPARα activity for treating diseases and/or conditions involving inflammation and/or angiogenesis, particularly ocular diseases and/or conditions such as but not limited to retinal inflammation, retinal neovascularization, retinal vascular leakage, retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, and diabetic macular edema are disclosed.
Claims13
A compound, comprising chemical structure II:
- wherein:
- k is 0;
- m is 1;
- n is 1;
- R1 is selected from the group consisting of COOH, OC(CH3)2COOH, B(OH)2, OCH2COOH, NHSO2CH3, SO2NH2, tetrazole, SC(CH3)2COOH, and salts thereof;
- R2 is selected from the group consisting of hydrogen (H), CH3, OCH3, F, difluoro, Br, dibromo, Cl, dichloro, I, diiodo, CF3, CBr3, CCl3, CI3, O-para-methoxybenzyl, and O-para-fluorobenzyl;
- R3 is selected from the group consisting of H, F, difluoro, Br, dibromo, Cl, dichloro, I, diiodo, CF3, CBr3, CCl3, CI3, NO2, CN, CH3, OCH3, O-para-methoxybenzyl, and O-para-fluorobenzyl;
- R4 is H or CH3;
- R5 is selected from the group consisting of H, F, Br, Cl, I, and CH3;
- and
- wherein the compound has PPARα agonistic activity, and with the proviso that
- when R1═COOH, at least one of R2-R5 is not H;
- when R1═COOH and R3═CH3, at least one of R2, R4, and R5 is not H;
- and
- when R2-R5═H, R1 is not tetrazole.
A method of increasing peroxisome proliferator-activated receptor α (PPARα) activity in a retinal cell, comprising:
- administering to the retinal cell a PPARα activity-enhancing amount of a compound comprising chemical structure II:
- wherein:
- k is 0;
- m is 1;
- n is 1;
- R1 is selected from the group consisting of COOH, OC(CH3)2COOH, B(OH)2, OCH2COOH, NHSO2CH3, SO2NH2, tetrazole, SC(CH3)2COOH, and salts thereof;
- R2 is selected from the group consisting of hydrogen (H), CH3, OCH3, F, difluoro, Br, dibromo, Cl, dichloro, I, diiodo, CF3, CBr3, CCl3, CI3, O-para-methoxybenzyl, and O-para-fluorobenzyl;
- R3 is selected from the group consisting of H, F, difluoro, Br, dibromo, Cl, dichloro, I, diiodo, CF3, CBr3, CCl3, CI3, NO2, CN, CH3, OCH3, O-para-methoxybenzyl, and O-para-fluorobenzyl;
- R4 is H or CH3;
- R5 is selected from the group consisting of H, F, Br, Cl, I, and CH3;
- and
- wherein the compound has PPARα agonistic activity.
A method of treating a disorder or condition in a subject by causing an increase in peroxisome proliferator-activated receptor α (PPARα) activity, comprising:
- administering to a subject in need of such therapy, a therapeutic amount of a compound comprising chemical structure II:
- wherein:
- k is 0;
- m is 1;
- n is 1;
- R1 is selected from the group consisting of COOH, OC(CH3)2COOH, B(OH)2, OCH2COOH, NHSO2CH3, SO2NH2, tetrazole, SC(CH3)2COOH, and salts thereof;
- R2 is selected from the group consisting of hydrogen (H), CH3, OCH3, F, difluoro, Br, dibromo, Cl, dichloro, I, diiodo, CF3, CBr3, CCl3, CI3, O-para-methoxybenzyl, and O-para-fluorobenzyl;
- R3 is selected from the group consisting of H, F, difluoro, Br, dibromo, Cl, dichloro, I, diiodo, CF3, CBr3, CCl3, CI3, NO2, CN, CH3, OCH3, O-para-methoxybenzyl, and O-para-fluorobenzyl;
- R4 is H or CH3;
- R5 is selected from the group consisting of H, F, Br, Cl, I, and CH3;
- and
- wherein the compound has PPARα agonistic activity.
Dependencies are inferred from the claim text.