5-({4-[(6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2-yl)methoxy]phenyl}methyl)-1,3-thiazolidine-2,4-dione

• ChemBase ID: 82
• Molecular Formular: C24H27NO5S
• Molecular Mass: 441.53988
• Monoisotopic Mass: 441.16099397
• SMILES: S1C(Cc2ccc(OCC3(Oc4c(CC3)c(c(O)c(c4C)C)C)C)cc2)C(=O)NC1=O
• Canonical SMILES: O=C1NC(=O)C(S1)Cc1ccc(cc1)OCC1(C)CCc2c(O1)c(C)c(c(c2C)O)C
• InChI: InChI=1S/C24H27NO5S/c1-13-14(2)21-18(15(3)20(13)26)9-10-24(4,30-21)12-29-17-7-5-16(6-8-17)11-19-22(27)25-23(28)31-19/h5-8,19,26H,9-12H2,1-4H3,(H,25,27,28)
• InChIKey: GXPHKUHSUJUWKP-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 5-({4-[(6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2-yl)methoxy]phenyl}methyl)-1,3-thiazolidine-2,4-dione
• IUPAC Traditional name: troglitazone
• Brand Name: Noscal; Prelay; Rezulin; Romglizone; Resulin; Romozin
• Synonyms: (±)-5-[4-[(6-Hydroxy-2,5,7,8-tetramethylchroman-2-yl)methoxy]benzyl]-2,4-thiazolidinedione; CS-045; Troglitazone; 5-[[4-[(3,4-Dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)methoxy]phenyl]methyl]-2,4-thiazolidinedione; CI 991; CS 045; Depotox; GR 92132X; Noscal; Rezulin; Romglizone; Troglitazone

Database IDs

• CAS Number: 97322-87-7
• MDL Number: MFCD00878416
• PubChem SID: 160963545; 24724629; 46504655
• PubChem CID: 5591

CALCULATED PROPERTIES

JChem

• Acid pKa: 6.613558
• H Acceptors: 5
• H Donor: 2
• LogD (pH = 5.5): 5.463373
• LogD (pH = 7.4): 4.6721177
• Log P: 5.4952044
• Molar Refractivity: 120.9914 cm^3
• Polarizability: 46.61733 Å^3
• Polar Surface Area: 84.86 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 4.16
• LOG S: -5.56
• Solubility (Water): 1.21e-03 g/l

PROPERTIES

Physical Property

• Solubility: DMSO; DMSO: soluble20 mg/mL; Methanol
• Apperance: White Solid; white to yellow solid
• Melting Point: 184-186°C
• Hydrophobicity(logP): 3.6

Safety Information

• Storage Condition: -20°C Freezer
• RTECS: XJ5813130
• German water hazard class: 2
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter

Pharmacology Properties

• Gene Information: human ... PPARA(5465), PPARG(5468)

Product Information

• Purity: ≥98% (HPLC)
• Empirical Formula (Hill Notation): C24H27NO5S

DETAILS

DrugBank - DB00197

• Drug Groups: withdrawn
• Description: Troglitazone was withdrawn in 2000 due to risk of hepatotoxicity. It was superseded by pioglitazone and rosiglitazone.
• Indication: For the treatment of Type II diabetes mellitus. It is used alone or in combination with a sulfonylurea, metformin, or insulin as an adjunct to diet and exercise.
• Pharmacology: Troglitazone is an oral antihyperglycemic agent which acts primarily by decreasing insulin resistance. Troglitazone is used in the management of type II diabetes (noninsulin-dependent diabetes mellitus (NIDDM) also known as adult-onset diabetes). It improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis. Troglitazone is not chemically or functionally related to either the sulfonylureas, the biguanides, or the g-glucosidase inhibitors. Troglitazone may be used concomitantly with a sulfonylurea or insulin to improve glycemic control.
• Affected Organisms: Humans and other mammals
• Biotransformation: A sulfate conjugate metabolite (Metabolite 1) and a quinone metabolite (Metabolite 3) have been detected in the plasma of healthy males. A glucuronide conjugate (Metabolite 2) has been detected in the urine and also in negligible amounts in the plasma. In healthy volunteers and in patients with type 2 diabetes, the steady-state concentration of Metabolite 1 is six to seven times that of troglitazone and Metabolite 3. In in vivo drug interaction studies, troglitazone has been shown to induce cytochrome P450 CYP3A4 at clinically relevant doses.
• Absorption: Absorbed rapidly. Food increases the extent of absorption by 30% to 85%.
• Half Life: 16-34 hours
• Protein Binding: > 99% (primarily to serum albumin)
• References: Aljada A, Garg R, Ghanim H, Mohanty P, Hamouda W, Assian E, Dandona P: Nuclear factor-kappaB suppressive and inhibitor-kappaB stimulatory effects of troglitazone in obese patients with type 2 diabetes: evidence of an antiinflammatory action? J Clin Endocrinol Metab. 2001 Jul;86(7):3250-6. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Sigma Aldrich - T2573

Biochem/physiol Actions
PPARγ agonist; anti-diabetic thiazolidinedione (TZD) with anti-inflammatory and anti-tumor activity; induces apoptosis via a p53 pathway.

Toronto Research Chemicals - T892500

Troglitazone is an an oral hypoglycemic agent which improves insulin sensitivity and decreases hepatic glucose production. Antidiabetic.

REFERENCES

• Aljada A, Garg R, Ghanim H, Mohanty P, Hamouda W, Assian E, Dandona P: Nuclear factor-kappaB suppressive and inhibitor-kappaB stimulatory effects of troglitazone in obese patients with type 2 diabetes: evidence of an antiinflammatory action? J Clin Endocrinol Metab. 2001 Jul;86(7):3250-6. Pubmed
• Ciaraldi, T.P., et al.: Metabolism, 39, 1056 (1990)
• Kuzuya, T., et al.: Diabetes Res. Clin. Pract., 11, 147 (1990)
• Kellerer, M., et al.: Diabetes, 43, 447 (1990)