# US 2017/0283385 A1 · Proxisome Proliferator Activated Receptor (PPAR) Compounds and Methods of Using the Same > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2017/0283385 A1 - Document ID: US20170283385A1 - Status: Published application - Kind: A1 - Application number: 15/593,750 - Filed: 2017-05-12 - Published: 2017-10-05 - Earliest claimed: 2013-03-14 - Assignees: The University of Toledo - Applicants: The University of Toledo - Inventors: Bruce E. Heck; Dong Hyun Kim; Paul Erhardt; Brian Kress - Web page: https://patentgrep.com/patent/US20170283385A1 ## CPC - C07D 277/24: Radicals substituted by oxygen atoms - A61K 31/426: 1,3-Thiazoles - A61K 31/5575: having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - C07D 277/22: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms - C07D 277/28: Radicals substituted by nitrogen atoms - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract Peroxisome proliferator activated receptor (PPAR) compounds, and methods of using the same for treating bone fractures, treating osteoporosis and/or metabolic bone diseases, and inducing osteogenesis and/or chondrogenesis, are disclosed. ## Claims ### Claim 1 A method of treating bone fractures, comprising: administering an effective amount of a pharmaceutical composition to a mammalian patient in need thereof, the pharmaceutical composition comprising a peroxisome proliferator activated receptor (PPAR) compound in an amount sufficient to prompt stem cells in the patient to contribute toward repair of the fracture, and a pharmaceutically acceptable carrier, excipient, diluent or adjuvant; wherein the PPAR compound has a chemical structure of Formula I: wherein: X is O; R is CH═CHR3, and R3 is carboxylic acid; R1 is para-CF3; and R2 is meta-H, or R1 is meta-CF3; and R2 is para-H; and salts, isomers, solvates, hydrates, polymorphs, and prodrugs thereof. ### Claim 2 (depends on 1) The method of claim 1, wherein the mammalian patient is a human. ### Claim 3 (depends on 2) The method of claim 2, wherein the administration is by surgical implantation including allograft bone, bone substitutes or bone scaffold matrices, or by localized injection of liquid or gel formulations or delivery systems to or near the fracture. ### Claim 4 (depends on 2) The method of claim 2, wherein the administration is by an intravenous, intramuscular or subcutaneous injection of liquid or gel formulations or delivery systems. ### Claim 5 A method of treating bone fractures, the method comprising: administering induced stem cells to a mammalian patient in need thereof; the induced stem cells derived from incubating stem cells with a pharmaceutical composition comprising a peroxisome proliferator activated receptor (PPAR) compound and a pharmaceutically acceptable carrier, excipient, diluent or adjuvant; wherein the PPAR compound has a chemical structure of Formula I: wherein: X is O; R is CH═CHR3, R3 is a carboxylic acid; R1 is para-CF3 and R2 is meta-H; or R1 is meta-CF3 and R2 is para-H; and salts, isomers, solvates, hydrates, polymorphs and prodrugs thereof. ### Claim 6 (depends on 5) The method of claim 5, wherein the mammalian patient is a human and the stem cells are either harvested from the same patient or supplied from another mammalian donor. ### Claim 7 (depends on 6) The method of claim 6, wherein the administration is by surgical implantation including allograft bone, bone substitutes or bone scaffold matrices, or by localized injection of liquid or gel formulations or delivery systems to or near the fracture. ### Claim 8 (depends on 6) The method of claim 6, wherein the administration is by an intravenous injection of liquid or gel formulations or delivery systems. ### Claim 9 A method of treating osteoporosis or metabolic bone disease, the method comprising: administering an effective amount of a pharmaceutical composition to a human patient in need thereof; the pharmaceutical composition comprising a peroxisome proliferator activated receptor (PPAR) compound in an amount sufficient to prompt stem cells in the patient to contribute toward improving bone density, and a pharmaceutically acceptable carrier, excipient, diluent or adjuvant; wherein the PPAR compound has a chemical structure of Formula I: wherein: X is O; R is CH═CHR3, R3 is a carboxylic acid; R1 is para-CF3 and R2 is meta-H; or R1 is meta-CF3 and R2 is para-H; and salts, isomers, solvates, hydrates, polymorphs and prodrugs thereof. ### Claim 10 (depends on 9) The method of claim 9, wherein the administration is by an intravenous, intramuscular or subcutaneous injection of liquid or gel formulations or delivery systems. ### Claim 11 (depends on 9) The method of claim 9, wherein the administration is by the oral route. ### Claim 12 A method of treating osteoporosis or metabolic bone disease, the method comprising administering induced stem cells to a human patient in need thereof; the induced stem cells derived from incubating stem cells with a pharmaceutical composition comprising a peroxisome proliferator activated receptor (PPAR) compound and a pharmaceutically acceptable carrier, excipient, diluent or adjuvant; wherein the PPAR compound has a chemical structure of Formula I: wherein X is O; R is CH═CHR3, R3 is a carboxylic acid; R1 is para-CF3 and R2 is meta-H; or R1 is meta-CF3 and R2 is para-H; and salts, isomers, solvates, hydrates, polymorphs and prodrugs thereof. ### Claim 13 (depends on 12) The method of claim 12, wherein the stem cells are either harvested from the same patient or supplied from another mammalian donor. ### Claim 14 (depends on 13) The method of claim 13, wherein the administration is by an intravenous, intramuscular or subcutaneous injection of liquid or gel formulations or delivery systems. ### Claim 15 A method of inducing osteogenesis or chondrogenesis, comprising: treating mammalian stem cells by administering an effective amount of a peroxisome proliferator activated receptor (PPAR) compound whereby the mammalian stem cells differentiate into an osteocyte cell of osteoblast lineage, or into a chondrocyte cell of chrondroblast lineage, and a pharmaceutically acceptable carrier, excipient, diluent, or adjuvant; wherein the PPAR compound has a chemical structure of Formula I: wherein X is O; R is CH═CHR3, R3 is a carboxylic acid; R1 is para-CF3 and R2 is meta-H; or R1 is meta-CF3 and R2 is para-H; and salts, isomers, solvates, hydrates, polymorphs and prodrugs thereof. ### Claim 16 (depends on 15) The method of claim 15, wherein the stem cells are present in a human patient in need of therapy for osteoarthritis, cartilage disorder, bone fracture, osteoporosis, metabolic bone disease, avascular necrosis, or concurrent with skeletal surgery. ### Claim 17 (depends on 16) The method of claim 16, wherein the administration is by surgical implantation including allograft bone, bone substitutes or bone scaffold matrices, or by localized injection of liquid or gel formulations or delivery systems to or near the fracture or site of skeletal surgery. ### Claim 18 (depends on 16) The method of claim 16, wherein the administration is by an intravenous, intramuscular or subcutaneous injection of liquid or gel formulations or delivery systems. ### Claim 19 (depends on 16) The method of claim 16, wherein the administration is by the oral route. ### Claim 20 (depends on 15) The method of claim 15, wherein the stem cells are present in a culture media after either being harvested from a human patient or another mammal; and wherein after treatment are administered to a human patient as a therapy for osteoarthritis, bone fracture, osteoporosis, metabolic bone disease, avascular necrosis or concurrent with skeletal surgery. ### Claim 21 (depends on 20) The method of claim 20, wherein the administration to human patients is by either surgical implantation including allograft bone, bone substitutes or bone scaffold matrices, or by localized, intravenous, intramuscular or subcutaneous injection of liquid or gel formulations or delivery systems. ### Claim 22 (depends on 16) The method of claim 16, wherein the cartilage disorder is one or more of: injury to articular cartilage; osteoarthritis; costochondritis; herniation; achondroplasia; relapsing polychondritis; benign or non-cancerous chondroma; and, malignant or cancerous chondrosarcoma. ### Claim 23 A compound comprising a structural Formula II: wherein R is OCH2R3, CH═CHR3, or (CH2)nR3 where n is 0, 1, 2 or 3, and R3 is carboxylic acid, phosphonic acid, sulfonic acid, an acidic sulfonamide, or pharmacophoric mimics thereof; R1 is H, CH3 or CF3; R2 is H, alkyl, substituted alkyl, or halogen; and R3 is H, alkyl, substituted alkyl, or halogen; provided that when R is OCH2CO2H, (i) either R1 is not para-CF3 or R2 is not H, and (ii) either R1 is not meta-CH3 or R2 is not para-tert-butyl; and salts, isomers, stereoisomers, enantiomers, racemates, solvates, hydrates, polymorphs, and prodrugs thereof. ### Claim 24 (depends on 23) The compound in claim 23, wherein: R is CH═CHCO2H; R1 is para-CF3 and R2 is meta-H; R1 is meta-CF3 and R2 is para-H; and, R3 is H, CH3 or CF3. ### Claim 25 (depends on 24) The compound in claim 24, wherein: R1 is para-CF3 and R2 is meta-H; R1 is meta-CF3 and R2 is para-H; and, R3 is H. ### Claim 26 (depends on 25) A pharmaceutical composition comprising: a compound of claim 25; and one or more of a pharmaceutically acceptable carrier, excipient, diluent or adjuvant.