Troglitazone

Base Information

• Chemical Name: Troglitazone
• CAS No.: 97322-87-7
• Molecular Formula: C24H27NO5S
• Molecular Weight: 441.548
• Hs Code.: 29145090
• DSSTox Substance ID: DTXSID8023719
• Nikkaji Number: J996.467C
• Wikipedia: Troglitazone
• Wikidata: Q7844989
• NCI Thesaurus Code: C1522
• Pharos Ligand ID: ZZZKMSXJFFQN
• Metabolomics Workbench ID: 53499
• ChEMBL ID: CHEMBL408
• Mol file: 97322-87-7.mol

Synonyms:5-(4-((6-Hydroxy-2,5,7,8-tetramethylchroman-2-yl-methoxy)benzyl)-2,4-thiazolidinedione) - T;CS 045;CS-045;CS045;Prelay;Rezulin;troglitazone

Chemical Property of Troglitazone

Chemical Property:

• Appearance/Colour: crystalline solid
• Melting Point: 184-186 °C
• Boiling Point: 657 °C at 760 mmHg
• PKA: 6.34±0.50(Predicted)
• Flash Point: 351.2 °C
• PSA: 110.16000
• Density: 1.266 g/cm³
• LogP: 4.70300
• Storage Temp.: Store at -20°C
• Solubility.: DMSO: 20 mg/mL
• XLogP3: 5.1
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 5
• Exact Mass: 441.16099414
• Heavy Atom Count: 31
• Complexity: 681

Purity/Quality:

99% ^*data from raw suppliers

Troglitazone ^*data from reagent suppliers

Safty Information:

• Safety Statements: 22-24/25

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Hypoglycemic Agents
• Canonical SMILES: CC1=C(C2=C(CCC(O2)(C)COC3=CC=C(C=C3)CC4C(=O)NC(=O)S4)C(=C1O)C)C
• Recent ClinicalTrials: Troglitazone in Treating Patients With Liposarcoma
• Description: Rezulin was launched in Japan, the UK (subseqently withdrawn) and the US for treatment of type Ⅱ diabetes. Two approaches, four steps and six steps, converge on 6-acetoxy-2-(4-aminophenoxymethyl)-2,5,7,8-tetramethylchroman which can be elaborated in two steps to Rezulin. It is the first of a new class of thiazolidenediones for NIDDM that reduces glucose concentrations without effecting insulin secretion. It binds to peroxisome proliferator-activated receptor gamma (PPARγ) thus activating this nuclear receptor which then influences carbohydrate metabolism. This is accomplished by increasing insulin sensitivity by upregulating glucose transporter (Glut1 and/or Glut4) expression without affecting the number or affinity of insulin receptors. There is also an increase in hepatic glycogen synthase activity which enhances glucose utilization and a reduction in hepatic gluconeogenesis by inhibiting fructose-1 ,&bisphosphatase. Pancreatic islet cell destruction is prevented. It reduces serum triglycerides because PPARγ causes fibroblasts to differentiate into adipocytes and does not activate RARα. It has a half-life of 9 h and is metabolized into three compounds having no activity.
• Uses: Troglitazone is an an oral hypoglycemic agent which improves insulin sensitivity and decreases hepatic glucose production. Antidiabetic. antidiabetic;peroxisome proliferator-activated receptors activator Troglitazone is a TZD which was approved for the treatment of insulin resistance and hyperglycemia in Type II diabetes, under the trade name Resulin?, but was withdrawn from the market due to hepatotoxicity. Troglitazone is a potent and selective PPARγ agonist. The EC50 values for transactivation of human and mouse PPARγ in a cell-based assay are 0.55 and 0.78 μM, respectively. In the same assay system, no activation of PPARα and PPARδ was observed at concentrations up to 10 μM. Troglitazone binds to the PPARγ ligand-binding domain (LBD) but fails to induce interaction of the PPARγ LBD with the transcriptional coactivators SRC-1, TIF2, AIB1, p300, or TRAP220. Troglitazone also induces cell cycle arrest and apoptosis in several cancer cell lines with an EC50 of 10 μM.

Technology Process of Troglitazone

There total 26 articles about Troglitazone which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 84.0%

5-[4-(6-hydroxy-2,5,7,8-tetramethylchroman-2-yl-methoxy)benzylidene]-2,4-thiazolidinedione → Troglitazone (97322-87-7)

Guidance literature:

With sodium tetrahydroborate; dimethylaminoacetic acid; sodium hydroxide; In tetrahydrofuran; water; at 20 ℃;

DOI:10.1016/j.bmcl.2004.02.087

Reference yield: 70.0%

5-[4-(6-benzyloxy-2,5,7,8-tetramethyl-chroman-2-ylmethoxy)-benzyl]-thiazolidine-2,4-dione (199441-78-6) → Troglitazone (97322-87-7)

Guidance literature:

With hydrogenchloride; acetic acid; at 70 - 80 ℃;

DOI:10.1021/jm9805541

Reference yield:

2-methoxy-ethanol (109-86-4,95507-80-5) + Ethyl 3-<4-<(6-acetoxy-2,5,7,8-tetramethylchroman-2-yl)methoxy>phenyl>-2-chloropropionate (97322-68-4) → Troglitazone (97322-87-7)

Guidance literature:

With hydrogenchloride; thiourea; In sulfolane;

upstream raw materials:

thiourea

Ethyl 3-<4-<(6-acetoxy-2,5,7,8-tetramethylchroman-2-yl)methoxy>phenyl>-2-chloropropionate

Troglitazone glucuronide

5-[4-(6-benzyloxy-2,5,7,8-tetramethyl-chroman-2-ylmethoxy)-benzyl]-thiazolidine-2,4-dione

Downstream raw materials:

methyl 2,3,4-tri-O-acetyl-1-O-<2-<4-<2,4-dioxothiazolidin-5-ylmethyl>phenoxymethyl>-2,5,7,8-tetramethylchroman-6-yl>-β-D-glucopyranuronate

5-[4-(6-butyryloxy-2,5,7,8-tetramethylchroman-2-ylmethoxy)benzyl]thiazolidine-2,4-dione

5-[4-(6-benzoyloxy-2,5,7,8-tetramethylchroman-2-ylmethoxy)benzyl]thiazolidine-2,4-dione

5-[4-(2,5,7,8-tetramethyl-6-nicotinoyloxychroman-2-ylmethoxy)benzyl]thiazolidine-2,4-dione

Refernces

• 1、 -. "Methods for predicting the response to statins". . . Retrieved 2011/10/13.
• 2、 Fan, Yun-Hua,Chen, Han,Natarajan, Amarnath,Guo, Yuhong,Harbinski, Fred,Iyasere, Julia,Christ, William,Aktas, Huseyin,Halperin, Jose A.. "Structure-activity requirements for the antiproliferative effect of troglitazone derivatives mediated by depletion of intracellular calcium". . p. 2547 - 2550. Retrieved 2007/10/03.