6-chloro-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazine-7-sulfonamide

• ChemBase ID: 758
• Molecular Formular: C7H6ClN3O4S2
• Molecular Mass: 295.72324
• Monoisotopic Mass: 294.94882537
• SMILES: Clc1c(S(=O)(=O)N)cc2S(=O)(=O)N=CNc2c1
• Canonical SMILES: Clc1cc2NC=NS(=O)(=O)c2cc1S(=O)(=O)N
• InChI: InChI=1S/C7H6ClN3O4S2/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5/h1-3H,(H,10,11)(H2,9,12,13)
• InChIKey: JBMKAUGHUNFTOL-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 6-chloro-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazine-7-sulfonamide; 6-chloro-1,1-dioxo-4H-1λ^6,2,4-benzothiadiazine-7-sulfonamide
• IUPAC Traditional name: chlorothiazide; microzide
• Brand Name: Aldoclor; Alurene; Chloriazid; Chlorosal; Chlorurit; Chlotride; Chlrosal; Clotride; Diupres; Diuresal; Diuril; Diuril Boluses; Diurilix; Diurite; Diutrid; Esidrix; Flumen; Hydro-D; Hydrodiuril; Microzide; Minzil; Neo-Dema; Oretic; Salisan; Salunil; Saluretil; Saluric; Sk-Chlorothiazide; Thiazide; Urinex; Warduzide; Yadalan; Zide
• Synonyms: 6-Chloro-7-sulfamyl-1,2,4-benzothiadiazine-1,1-dioxide; 6-Chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide; Chlotride; Diuril; Saluric; Urinex; Chlorothiazid; Chlorthiazide; Chlortiazid; Chlorothiazide

Database IDs

• CAS Number: 58-94-6
• PubChem SID: 46507032; 160964221
• PubChem CID: 2720
• CHEBI ID: 3640
• ATC CODE: C03AA04
• CHEMBL: 842
• Chemspider ID: 2619
• DrugBank ID: DB00880
• KEGG ID: D00519
• Unique Ingredient Identifier: 77W477J15H
• Wikipedia Title: Chlorothiazide
• Medline Plus: a682341

CALCULATED PROPERTIES

JChem

• Acid pKa: 9.1031065
• H Acceptors: 6
• H Donor: 2
• LogD (pH = 5.5): -0.44231102
• LogD (pH = 7.4): -0.44985485
• Log P: -0.4421815
• Molar Refractivity: 62.5082 cm^3
• Polarizability: 24.935616 Å^3
• Polar Surface Area: 118.69 Å^2
• Rotatable Bonds: 1
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 0.41
• LOG S: -2.87
• Solubility (Water): 3.98e-01 g/l

PROPERTIES

Physical Property

• Solubility: 266 mg/L; Dimethyl Sulfoxide
• Apperance: White to Off-White Solid
• Melting Point: 300°C (dec.)
• Hydrophobicity(logP): -0.5

Safety Information

• Storage Condition: Refrigerator

Pharmacology Properties

• Admin Routes: Oral
• Excretion: Renal
• Half Life: 45 to 120 minutes
• Metabolism: Nil
• Legal Status: Rx-only (US)
• Pregnancy Category: C (US)

DETAILS

DrugBank - DB00880

• Drug Groups: approved
• Description: A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p812)
• Indication: Chlorothiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. It is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension.
• Pharmacology: Like other thiazides, chlorothiazide promotes water loss from the body (diuretics). It inhibits Na^+/Cl^- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. Chlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic efficacy. Chlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate. After oral doses, 10-15 percent of the dose is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.
• Toxicity: Oral, rat LD₅₀: > 10 g/kg. Signs of overdose include those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered hypokalemia may accentuate cardiac arrhythmias.
• Affected Organisms: Humans and other mammals
• Biotransformation: Chlorothiazide is not metabolized but is eliminated rapidly by the kidney.
• Absorption: Rapidly absorbed following oral administration.
• Half Life: 45-120 minutes
• Protein Binding: Approximately 40% bound to plasma proteins.
• Elimination: Chlorothiazide is not metabolized but is eliminated rapidly by the kidney. After oral doses, 10 to 15 percent of the dose is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.
• External Links: Wikipedia; RxList; Drugs.com

Toronto Research Chemicals - C380000

Diuretic; antihypertensive.

REFERENCES

• Brittain, H.G., et al.: Anal. Profiles Drug Subs., 18, 33 (1989)
• Yoshida, F., et al.: J. Med. Chem., 43, 2575 (1989)
• Luan, F., et al.: Chem. Res. Toxicol., 18, 198 (1989)
• Si, H., et al.: Bioorg. Med. Chem., 14, 4834 (1989)