Chlorthalidone

Title: Chlorthalidone
CAS Registry Number: 77-36-1
CAS Name: 2-Chloro-5-(2,3-dihydro-1-hydroxy-3-oxo-1H-isoindol-1-yl)benzenesulfonamide
Additional Names: 2-chloro-5-(1-hydroxy-3-oxo-1-isoindolinyl)benzenesulfonamide; 3-hydroxy-3-(4-chloro-3-sulfamylphenyl)phthalimidine; 2-chloro-5-(3-hydroxy-1-oxoisoindolin-3-yl)benzenesulfonamide; 1-oxo-3-(3-sulfamyl-4-chlorophenyl)-3-hydroxyisoindoline; 3-(4¢-chloro-3¢-sulfamoylphenyl)-3-hydroxyphthalimidine; 1-keto-3-(3¢-sulfamyl-4¢-chlorophenyl)-3-hydroxyisoindoline; chlorphthalidolone; phthalamudine; phthalamodine
Manufacturers' Codes: G-33182
Trademarks: Higroton (Novartis); Hydro-long (Sanorania); Hygroton (Novartis); Thalitone (Boehringer, Ing.)
Molecular Formula: C14H11ClN2O4S
Molecular Weight: 338.77
Percent Composition: C 49.64%, H 3.27%, Cl 10.47%, N 8.27%, O 18.89%, S 9.47%
Literature References: Prepn: Graf et al., Helv. Chim. Acta 42, 1085 (1959); US 3055904 (1962 to Geigy). Activity and side effects: Holtmeier et al., Med. Welt 1967, 1384; Zsoter et al., J. Pharmacol. Exp. Ther. 180, 723 (1972). Metabolism: Beisenherz et al., Arch. Int. Pharmacodyn. Ther. 161, 76 (1966). Comprehensive description: J. M. Singer et al., Anal. Profiles Drug Subs. 14, 1-36 (1985).
Properties: Crystals from 50% acetic acid, dec 224-226°. mp range may extend from 218 to 264° on slow heating. Can form a monohydrate. uv max (methanol): <220 nm. Soly in water: 12 mg/100 ml (20°); 27 mg/100 ml (37°); in 0.1N Na2CO3: 577 mg/100 ml (20°); 990 mg/100 ml (37°). More sol in aq solns of NaOH. Soluble in warm ethanol; slightly sol in ether.
Melting point: mp range may extend from 218 to 264° on slow heating
Absorption maximum: uv max (methanol): <220 nm
Therap-Cat: Diuretic; antihypertensive.
Therap-Cat-Vet: Diuretic.
Keywords: Antihypertensive; Thiazides and Analogs; Diuretic; Thiazides and Analogs.
Chlorthenoxazin(e) Chlorthion? Chlorzoxazone Cholane Cholanic Acid

Chlortalidone
Chlortalidone.svg
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Systematic (IUPAC) name
(RS)-2-chloro-5-(1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)benzene-1-sulfonamide
Clinical data
Trade names Hygroton, Tenoretic
AHFS/Drugs.com Consumer Drug Information
MedlinePlus a682342
Pregnancy cat. C (Au), B (U.S.)
Legal status POM (UK)
Routes Oral
Pharmacokinetic data
Protein binding 75%
Half-life 40 hours
Excretion Renal
Identifiers
CAS number 77-36-1 YesY
ATC code C03BA04
PubChem CID 2732
DrugBank DB00310
ChemSpider 2631 YesY
UNII Q0MQD1073Q YesY
KEGG D00272 YesY
ChEBI CHEBI:3654 YesY
ChEMBL CHEMBL1055 YesY
Chemical data
Formula C14H11ClN2O4S 
Mol. mass 338.766 g/mol
 YesY (what is this?)  (verify)

Chlortalidone (INN/BAN) or chlorthalidone (USAN) is a diuretic drug used to treat hypertension, originally marketed as Hygroton in the USA. It is described as a thiazide diuretic (or, rather, a thiazide-like diuretic because it acts similarly to the thiazides but does not contain the benzothiadiazine molecular structure). Compared with other medications of the thiazide class, chlortalidone has the longest duration of action but a similar diuretic effect at maximal therapeutic doses. It is often used in the management of hypertension and edema.

Unlike loop diuretics, chlortalidone efficacy is diminished in patients with certain renal diseases (e.g. chronic renal disease). A clinical trial (ALLHAT) in 2002 compared chlortalidone to doxazosin in the treatment of high-risk hypertensive patients. In this study, only chlortalidone significantly reduced the risk of combined cardiovascular disease events, especially heart failure, when compared with drugs such as doxazosin.[1] Chlortalidone was approved by the FDA in 1960. The ALLHAT study conclusions showed that there was no significant difference in all-cause mortality, fatal heart disease, or non-fatal myocardial infarction when chlortalidone was compared with lisinopril or amlodipine but did show decrease rates of heart failure after 6 years when compared with amlodipine and decreased rates of cerebrovascular disease after 6 years when compared with lisinopril leading the study conclusions to say that thiazide-type diuretics are preferred first-step in antihypertensive therapy.