1-({4-[(3-methylphenyl)amino]pyridin-3-yl}sulfonyl)-3-(propan-2-yl)urea

• ChemBase ID: 99
• Molecular Formular: C16H20N4O3S
• Molecular Mass: 348.42
• Monoisotopic Mass: 348.12561152
• SMILES: S(=O)(=O)(NC(=O)NC(C)C)c1c(Nc2cc(ccc2)C)ccnc1
• Canonical SMILES: CC(NC(=O)NS(=O)(=O)c1cnccc1Nc1cccc(c1)C)C
• InChI: InChI=1S/C16H20N4O3S/c1-11(2)18-16(21)20-24(22,23)15-10-17-8-7-14(15)19-13-6-4-5-12(3)9-13/h4-11H,1-3H3,(H,17,19)(H2,18,20,21)
• InChIKey: NGBFQHCMQULJNZ-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 1-({4-[(3-methylphenyl)amino]pyridin-3-yl}sulfonyl)-3-(propan-2-yl)urea
• IUPAC Traditional name: torsemide; torasemide
• Brand Name: Demadex; Luprac
• Synonyms: N-[[(1-Methylethyl)amino]carbonyl]-4-[(3-methylphenyl)amino]-3-pyridinesulfonamide; Torsemide; AC-4464; BM-02015; JDL-464; Luplac; Toradiur; Torem; Torasemide; Unat; Torasemida [INN-Spanish]; Torasemidum [INN-Latin]; Torsemide; Torasemide; Demadex; Torsemide

Database IDs

• CAS Number: 56211-40-6
• MDL Number: MFCD00866166
• PubChem SID: 160963562; 46504760
• PubChem CID: 41781

CALCULATED PROPERTIES

JChem

• Acid pKa: 5.9225373
• H Acceptors: 5
• H Donor: 3
• LogD (pH = 5.5): 1.8233185
• LogD (pH = 7.4): 1.118939
• Log P: 1.8639036
• Molar Refractivity: 91.8931 cm^3
• Polarizability: 35.803543 Å^3
• Polar Surface Area: 100.19 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.76
• LOG S: -3.77
• Solubility (Water): 5.96e-02 g/l

PROPERTIES

Physical Property

• Solubility: DMSO; DMSO: soluble18 mg/mL; H2O: insoluble; Methanol; Water soluble
• Apperance: solid; White Solid
• Melting Point: 163-164°C
• Hydrophobicity(logP): 2.3

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• RTECS: UT7938000
• European Hazard Symbols: Irritant (Xi)
• German water hazard class: 2
• Risk Statements: 36
• Safety Statements: 26
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H319
• GHS Precautionary statements: P305 + P351 + P338
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Gloves

Product Information

• Purity: ≥98% (HPLC)
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C16H20N4O3S

DETAILS

DrugBank - DB00214

• Drug Groups: approved
• Description: Torasemide (rINN) or torsemide (USAN) is a pyridine-sulfonylurea type loop diuretic mainly used in the management of edema associated with congestive heart failure. It is also used at low doses for the management of hypertension. It is marketed under the brand name Demadex. [Wikipedia]
• Indication: For the treatment of edema associated with congestive heart failure, renal disease, or hepatic disease. Also for the treatment of hypertension alone or in combination with other antihypertensive agents.
• Pharmacology: Torasemide (INN) or torsemide (USAN) is a novel loop diuretic belonging to pridine sulphonyl urea. It differs form other thiazide diuretics in that a double ring system is incorporated into its structure. Like thiazides, loop diuretics must be secreted into the tubular fluid by proximal tubule cells. In the thick ascending loop Na+ and Cl- reabsorption is accomplished by a Na^+/K^+/2Cl^- symporter. The thick ascending limb has a high reabsorptive capacity and is responsible for reabsorbing 25% of the filtered load of Na^+. The loop diuretics act by blocking this symporter. Because of the large absorptive capacity and the amount of Na^+ delivered to the ascending limb, loop diuretics have a profound diuretic action. In addition, more distal nephron segments do not have the reabsorptive capacity to compensate for this increased load. The osmotic gradient for water reabsorption is also reduced resulting in an increase in the amount of water excreted.
• Toxicity: Symptoms of overdose include dehydration, hypovolemia, hypotension, hyponatremia, hypokalemia, hypochloremic alkalosis, and hemoconcentration. Oral LD₅₀ in rat is 5 g/kg, and intravenous LD₅₀ in rat is 500 mg/kg.
• Affected Organisms: Humans and other mammals
• Biotransformation: Metabolized via the hepatic CYP2C8 to 5 metabolites. The major metabolite, M5, is pharmacologically inactive. There are 2 minor metabolites, M1, possessing one-tenth the activity of torasemide, and M3, equal in activity to torasemide. Overall, torasemide appears to account for 80% of the total diuretic activity, while metabolites M1 and M3 account for 9% and 11%, respectively.
• Absorption: Rapidly absorbed following oral administration. Absolute bioavailability is 80%. Food has no effect on absorption.
• Half Life: 3.5 hours
• Protein Binding: > 99%
• Elimination: Torsemide is cleared from the circulation by both hepatic metabolism (approximately 80% of total clearance) and excretion into the urine (approximately 20% of total clearance in patients with normal renal function).
• Distribution: * 12 to 15 L [normal adults or in patients with mild to moderate renal failure or congestive heart failure]
• References: Dunn CJ, Fitton A, Brogden RN: Torasemide. An update of its pharmacological properties and therapeutic efficacy. Drugs. 1995 Jan;49(1):121-42. [Pubmed] ; FDA approved new drug bulletin: torsemide (Demadex), trimetrexate glucuronate (neuTrexin). RN. 1994 May;57(5):53-6. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth

Selleck Chemicals - S1698

Research Area: Cardiovascular Disease
Biological Activity:
Torsemide(Demadex) is a pyridine-sulfonyl urea type loop diuretic with an IC50 of 2.7 ± 0.17 µM.  [1] It was mainly used in the management of edema associated with congestive heart failure. It is also used at low doses for the management of hypertension. [2]

Sigma Aldrich - T3202

Biochem/physiol Actions
Torsemide is a loop diuretic of the pyridine-sulfonylurea class with antialdosteronergic properties and inhibitor of the Na+/K+/2Cl- carrier system.

Toronto Research Chemicals - T548750

Used as a diuretic.

REFERENCES

• Dunn CJ, Fitton A, Brogden RN: Torasemide. An update of its pharmacological properties and therapeutic efficacy. Drugs. 1995 Jan;49(1):121-42. Pubmed
• FDA approved new drug bulletin: torsemide (Demadex), trimetrexate glucuronate (neuTrexin). RN. 1994 May;57(5):53-6. Pubmed
• http://en.wikipedia.org/wiki/Torasemide
• Lesne, M., et al.: In. J. Clin. Pharmacol. Ther. Toxicol., 20, 382 (1982)
• Brater, D.C., et al.: Clin. Pharmacol. Ther., 42, 187 (1982)