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US 12,545,653 B2Granted
Compound as PPAR agonist and application thereof
AssigneeUSA Elixiria Biotech Inc.
InventorsLihai Zhang, Min Hu
Life of this patent
Estimating the term…
Abstract
The present invention provides compounds as PPAR agonists and their application, involving a new class of peroxisome proliferator-activated receptor (PPAR) gamma receptor agonist, which can inhibit the production of mitochondrial reactive oxygen species, and most of which can readily cross the blood-brain barrier. The present invention also includes pharmaceutical uses of the compounds.
Claims18
A method in therapeutically treating a peroxisome proliferator-activated receptor gamma (PPARγ) activity-dependent disease comprising administering a PPARγ agonist of formula (I) or pharmaceutically acceptable salts, solvates, or prodrugs thereof:
- wherein:
- sum of nitrogen and oxygen (referred as “(N+O)”) in the formula (I) together with all its substituents is limited to 1, 2 or 3;
- the formula (I) and all its substituents do not contain diacety, or α-hydroxy ketone, thiazolidinedione, oxazolidinedione or sulfonyl;
- RA-RB is
- wherein RA is the carbonyl containing cyclic ring in the structure (A);
- RB is the phenyl in the structure (A), and RB is optionally substituted by 0 to 3 Rb;
- R is connected to the RA-RB with the carbon atom on the phenyl only at position 1 or 2 as a connecting position;
- R is C4-6 alkyl, or C4-6 alkenyl;
- RC is phenyl, thiophene, 1H-pyrrole, pyridyl, furan, or 1,3-thiazole, optionally substituted by 0, 1, 2, 3 Rc;
- wherein following groups are excluded from formula (I), Rb, and Rc:
- quaternary ammonium, carboxyl, carboxylate, thiazolidinedione, phosphono, phosphate, sulfino, sulfo, carbothioic S-acid, carbothioic O-acid, carbodithioic acid, sulfhydryl when the pKa in water is lower than 7.4, or amine when the pKa in water is higher than 7.4;
- the molecular weight of the formula (I) is less than 400 Dalton;
- the molecular weight of Rb or Rc is less than 200 Dalton;
- and the number of carbons in Rb or Rc is no more than 10;
- if RC is phenyl, 1H-pyrrole or thiophene, Rb, and Rc can be independently selected from hydroxyl, hydrogen, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-10 aryl, halo, halogenated C1-8 alkyl, halogenated C1-6 alkoxy, amine when the pKa in water is not higher than 7.4, imine, nitrile, isonitrile, pyridyl, C1-6 alkylthio, C1-6 alkoxy, C1-6 alkoxyl C1-6 alkyl, sulfhydryl when the pKa in water is not lower than 7.4, sulfide, disulfide, carbonothioyl, carbodithio, thiocyanate, thionoester, borinate, borino, phosphino, or combination thereof as long as the total (N+O) in all Rb, and Rc together is 0 or 1;
- if RC is pyridyl, furan, or 1,3-thiazole, Rb, and Rc can be independently selected from hydrogen, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-10 aryl, halo, halogenated C1-8 alkyl, sulfhydryl when the pKa in water is not lower than 7.4, sulfide, disulfide, carbonothioyl, carbodithio, borinate, borino, phosphino, and combinations thereof as long as the combinations thereof are not containing any nitrogen or oxygen;
- and wherein any alkyl or alkenyl groups thereof can be linear or branched.
14 more elements
A method in therapeutically treating a peroxisome proliferator-activated receptor gamma (PPARγ) activity-dependent disease comprising administering a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a PPARγ agonist of formula (I) or pharmaceutically acceptable salts, solvates, or prodrugs thereof:
- wherein:
- sum of nitrogen and oxygen (referred as “(N+O)”) in the formula (I) together with all its substituents is limited to 1, 2 or 3;
- the formula (I) and all its substituents do not contain diacety, or α-hydroxy ketone, thiazolidinedione, oxazolidinedione or sulfonyl;
- RA—RB is
- wherein RA is the carbonyl containing cyclic ring in the structure (A);
- RB is the phenyl in the structure (A), and RB is optionally substituted by 0 to 3 Rb;
- R is connected to the RA-RB with the carbon atom on the phenyl only at position 1 or 2 as a connecting position;
- R is C4-6 alkyl, or C4-6 alkenyl;
- RC is phenyl, thiophene, 1H-pyrrole, pyridyl, furan, or 1,3-thiazole, optionally substituted by 0, 1, 2, 3 Rc;
- Wherein following groups are excluded from formula (I), Rb, and Rc:
- quaternary ammonium, carboxyl, carboxylate, thiazolidinedione, phosphono, phosphate, sulfino, sulfo, carbothioic S-acid, carbothioic O-acid, carbodithioic acid, sulfhydryl when the pKa in water is lower than 7.4, or amine when the pKa in water is higher than 7.4;
- the molecular weight of the formula (I) is less than 400 Dalton;
- the molecular weight of Rb or Rc is less than 200 Dalton;
- and the number of carbons in Rb or Rc is no more than 10;
- if RC is phenyl, 1H-pyrrole or thiophene, Rb, and Rc can be independently selected from hydroxyl, hydrogen, C1-6 alkyl, C2-3 alkenyl, C2-3 alkynyl, C3-10 aryl, halo, halogenated C1-3 alkyl, halogenated C1-6 alkoxy, amine when the pKa in water is not higher than 7.4, imine, nitrile, isonitrile, pyridyl, C1-6 alkylthio, C1-6 alkoxy, C1-6 alkoxyl C1-6 alkyl, sulfhydryl when the pKa in water is not lower than 7.4, sulfide, disulfide, carbonothioyl, carbodithio, thiocyanate, thionoester, borinate, borino, phosphino, or combination thereof as long as the total (N+O) in all Rb, and Rc together is 0 or 1;
- if RC is pyridyl, furan, or 1,3-thiazole, Rb, and Rc can be independently selected from hydrogen, C1-6 alkyl, C2-3 alkenyl, C2-3 alkynyl, C3-10 aryl, halo, halogenated C1-3 alkyl, sulfhydryl when the pKa in water is not lower than 7.4, sulfide, disulfide, carbonothioyl, carbodithio, borinate, borino, phosphino, and combinations thereof as long as the combinations thereof are not containing any nitrogen or oxygen;
- and wherein any alkyl or alkenyl groups thereof can be linear or branched.
14 more elements
Dependencies are inferred from the claim text.