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编号: 82
• 分子式: C24H27NO5S
• 平均质量: 441.53988
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: 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传统名: troglitazone
• 商标名: Noscal; Prelay; Rezulin; Romglizone; Resulin; Romozin
• 别名: (±)-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

登记号

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

理论计算性质

JChem

• Acid pKa: 6.613558
• 质子受体: 5
• 质子供体: 2
• LogD (pH = 5.5): 5.463373
• LogD (pH = 7.4): 4.6721177
• Log P: 5.4952044
• 摩尔折射率: 120.9914 cm^3
• 极化性: 46.61733 Å^3
• 极化表面积: 84.86 Å^2
• 可自由旋转的化学键: 5
• 里宾斯基五规则: false

ALOGPS 2.1

• Log P: 4.16
• LOG S: -5.56
• 溶解度: 1.21e-03 g/l

分子性质

理化性质

• 溶解度: DMSO; DMSO: soluble20 mg/mL; Methanol
• 外观: White Solid; white to yellow solid
• 熔点: 184-186°C
• 疏水性(logP): 3.6

安全信息

• 保存条件: -20°C Freezer
• RTECS编号: XJ5813130
• 德国WGK号: 2
• 个人保护装置: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter

药理学性质

• 相关基因信息: human ... PPARA(5465), PPARG(5468)

产品相关信息

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

详细说明

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• Drug Groups: withdrawn
• Description: Troglitazone was withdrawn in 2000 due to risk of hepatotoxicity. It was superseded by pioglitazone and rosiglitazone.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.

参考文献

• 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)