1-(4-methylbenzenesulfonyl)-3-{octahydrocyclopenta[c]pyrrol-2-yl}urea

• ChemBase ID: 991
• Molecular Formular: C15H21N3O3S
• Molecular Mass: 323.41054
• Monoisotopic Mass: 323.13036255
• SMILES: S(=O)(=O)(NC(=O)NN1CC2C(CCC2)C1)c1ccc(cc1)C
• Canonical SMILES: O=C(NS(=O)(=O)c1ccc(cc1)C)NN1CC2C(C1)CCC2
• InChI: InChI=1S/C15H21N3O3S/c1-11-5-7-14(8-6-11)22(20,21)17-15(19)16-18-9-12-3-2-4-13(12)10-18/h5-8,12-13H,2-4,9-10H2,1H3,(H2,16,17,19)
• InChIKey: BOVGTQGAOIONJV-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 1-(4-methylbenzenesulfonyl)-3-{octahydrocyclopenta[c]pyrrol-2-yl}urea
• IUPAC Traditional name: 3-{hexahydro-1H-cyclopenta[c]pyrrol-2-yl}-1-(4-methylbenzenesulfonyl)urea; gliclazide; 1-(4-methylbenzenesulfonyl)-3-{octahydrocyclopenta[c]pyrrol-2-yl}urea
• Brand Name: Diamicron; Glimicron; Nordialex; Diamicron MR; Mylan-Gliclazide; PMS-Gliclazide
• Synonyms: N-[[(Hexahydrocylopenta[c]pyrrol-2(1H)-yl]amino]carbonyl]-4-methylbenzenesulfonamide; Glimicron; Nordialex; S-1702; 1-(3-Azabicyclo(3.3.0)oct-3-yl)-3-(p-tolylsulfonyl)urea; 1-(Hexahydrocyclopenta(c)pyrrol-2(1H)-yl)-3-(p-tolylsulfonyl)urea; Gliclazida [INN-Spanish]; Gliclazidum [INN-Latin]; N-(4-Methylbenzenesulfonyl)-N'-(3-azabicyclo(3.3.0)oct-3-yl)urea; Gliclazide; Diamicron; 1-(3-Azabicyclo[3.3.0]oct-3-yl)-3-p-tolylsulphonylurea; Gliclazide; N-((hexahydrocyclopenta[c]pyrrol-2(1H)-yl)carbamoyl)-4-methylbenzenesulfonamide; Diabrezide; Glyclazide; Unava

Database IDs

• CAS Number: 21187-98-4
• EC Number: 244-260-5
• MDL Number: MFCD00409893
• PubChem SID: 46505475; 160964454; 24895090
• PubChem CID: 3475

CALCULATED PROPERTIES

JChem

• Acid pKa: 4.070456
• H Acceptors: 4
• H Donor: 2
• LogD (pH = 5.5): 0.89702356
• LogD (pH = 7.4): 0.7922661
• Log P: 1.733641
• Molar Refractivity: 83.8761 cm^3
• Polarizability: 33.30756 Å^3
• Polar Surface Area: 78.51 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.52
• LOG S: -3.23
• Solubility (Water): 1.90e-01 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; methylene chloride: soluble
• Apperance: white powder; White Solid
• Melting Point: 163-169 °C(lit.); 164-166°C
• Hydrophobicity(logP): 2.6

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• RTECS: YT4500000
• German water hazard class: 2
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter

Pharmacology Properties

• Gene Information: human ... KCNJ1(3758)
• Mechanism of Action: Appears to enhance glucose stimulated insulin secretion at a submaximally stimulating blood-glucose level

Product Information

• Purity: ≥98%
• Salt Data: Free Base
• Application(s): Antidiabetic; Oral antihyperglycaemic agent
• Empirical Formula (Hill Notation): C15H21N3O3S

DETAILS

DrugBank - DB01120

• Drug Groups: approved
• Description: Gliclazide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It belongs to the sulfonylurea class of insulin secretagogues, which act by stimulating β cells of the pancreas to release insulin. Sulfonylureas increase both basal insulin secretion and meal-stimulated insulin release. Medications in this class differ in their dose, rate of absorption, duration of action, route of elimination and binding site on their target pancreatic β cell receptor. Sulfonylureas also increase peripheral glucose utilization, decrease hepatic gluconeogenesis and may increase the number and sensitivity of insulin receptors. Sulfonylureas are associated with weight gain, though less so than insulin. Due to their mechanism of action, sulfonylureas may cause hypoglycemia and require consistent food intake to decrease this risk. The risk of hypoglycemia is increased in elderly, debilitated and malnourished individuals. Gliclazide has been shown to decrease fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels (reflective of the last 8-10 weeks of glucose control). Gliclazide is extensively metabolized by the liver; its metabolites are excreted in both urine (60-70%) and feces (10-20%).
• Indication: For the treatment of NIDDM in conjunction with diet and exercise.
• Pharmacology: Gliclazide is a second generation sulphonylurea which acts as a hypoglycemic agent. It stimulates β cells of the islet of Langerhans in the pancreas to release insulin. It also enhances peripheral insulin sensitivity. Overall, it potentiates insulin release and improves insulin dynamics.
• Toxicity: LD₅₀=3000 mg/kg (orally in mice). Gliclazide and its metabolites may accumulate in those with severe hepatic and/or renal dysfunction. Symptoms of hypoglycemia include: dizziness, lack of energy, drowsiness, headache and sweating.
• Affected Organisms: Humans and other mammals
• Biotransformation: Extensively metabolized in the liver. Less than 1% of the orally administered dose appears unchanged in the urine. Metabolites include oxidized and hydroxylated derivates, as well as glucuronic acid conjugates.
• Absorption: Rapidly and well absorbed but may have wide inter- and intra-individual variability. Peak plasma concentrations occur within 4-6 hours of oral administration.
• Half Life: 10.4 hours. Duration of action is 10-24 hours.
• Protein Binding: 94%, highly bound to plasma proteins
• Elimination: Metabolites and conjugates are eliminated primarily by the kidneys (60-70%) and also in the feces (10-20%).
• External Links: Wikipedia

Selleck Chemicals - S2601

Research Area: Metabolic Disease
Biological Activity:
Gliclazide (Diamicron) is a whole-cell beta-cell ATP-sensitive potassium currents blocker with an IC50 of 184 ± 30 nM. Gliclazide (Diamicron) binds to sulfonylurea receptors on the surface of the Beta islet cells found in the pancreas. This binding effectively closes the K+ ion channels. This decreases the efflux of potassium from the cell which leads to the depolarization of the cell. This causes voltage dependent Ca2+ ion channels to open increasing the Ca2+ influx. The calcium can then bind to and activate calmodulin which in turn leads to exocystosis of insulin vesicles leading to insulin release. Gliclazide is used for control of hyperglycemia in gliclazide-responsive diabetes mellitus of stable, mild, non-ketosis prone, maturity-onset or adult type. Gliclazide (Diamicron) is used when diabetes cannot be controlled by proper dietary management and exercise or when insulin therapy is not appropriate. [1][2][3]References on Gliclazide (Diamicron)[1] Diabetologia. , 2001 Aug, 44(8):1019-25[2] http://en.wikipedia.org/wiki/Gliclazide, , [3] Diabetes., 2009 Oct, 58(10):2419-24

Sigma Aldrich - G2167

Application
Used in the treatment of non-insulin dependent diabetes mellitus (NIDDM).
Biochem/physiol Actions
Oxidative modification of low-density lipoprotein (LDL) plays an important role in vascular dysfunction associated with diabetes mellitus. Gliclazide is a second-generation sulfonylurea with free-radical-scavenging activity. Incubation of human aortic smooth muscle cell (HASMC) with native human LDL (100 μg/mL) in the presence of increasing concentrations of gliclazide (1 to 10 μg/mL) resulted in a dose-dependent decrease in HASMC-mediated LDL oxidation. Exposure of HASMCs to gliclazide (1 to 10 μg/mL) and native LDL (100 μg/mL) also led to a dose-dependent decrease in oxidized LDL-induced human monocyte adhesion to HASMCs. In addition, incubation of HASMCs with gliclazide dramatically reduced the ability of oxidized LDL to stimulate the proliferation of these cells. Finally, treatment of HASMCs with gliclazide resulted in a marked decrease in oxidatively modified LDL-induced monocyte chemoattractant protein (MCP)-1 and human heat shock protein 70 (HSP 70) expression, both at the gene and protein levels. These results show that gliclazide, at concentrations in the therapeutic range (5 to 10 μg/mL), is effective in vitro in reducing vascular smooth muscle cell (VSMC) dysfunction induced by oxidatively modified LDL. Administration of gliclazide to type 2 diabetic patients could form part of the strategy for the prevention and management of diabetic cardiovascular diseases

Toronto Research Chemicals - G409875

A sulfonylurea hypoglycemic agent. Used as an antidiabetic.

REFERENCES

• Hamming KS et al. Diabetes. 2009 Oct;58(10):2419-24.
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