Chlorthalidone

Base Information

• Chemical Name: Chlorthalidone
• CAS No.: 77-36-1
• Molecular Formula: C14H11ClN2O4S
• Molecular Weight: 338.771
• Hs Code.: 2935904000
• European Community (EC) Number: 201-022-5
• NSC Number: 756692,69200
• UNII: Q0MQD1073Q
• DSSTox Substance ID: DTXSID4022812
• Nikkaji Number: J1.476A
• Wikipedia: Chlortalidone
• Wikidata: Q425289
• NCI Thesaurus Code: C47449
• RXCUI: 2409
• Pharos Ligand ID: 7ZZX3JGF5TZJ
• Metabolomics Workbench ID: 42697
• ChEMBL ID: CHEMBL1055
• Mol file: 77-36-1.mol

Synonyms:Chlorphthalidolone;Chlortalidone;Chlorthalidone;Hygroton;Oxodoline;Phthalamudine;Thalitone

Chemical Property of Chlorthalidone

Chemical Property:

• Appearance/Colour: white solid
• Melting Point: 265-267 °C (dec.)
• Refractive Index: 1.694
• PKA: pKa 9.4 (Uncertain)
• PSA: 117.87000
• Density: 1.601 g/cm³
• LogP: 3.03410
• Storage Temp.: 2-8°C
• Solubility.: DMSO: soluble5mg/mL, clear (warmed)
• Water Solubility.: 0.12g/L(25 oC)
• XLogP3: 0.9
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 2
• Exact Mass: 338.0128057
• Heavy Atom Count: 22
• Complexity: 564

Purity/Quality:

99% ^*data from raw suppliers

Chlorthalidone ^*data from reagent suppliers

Safty Information:

• Safety Statements: 22-24/25

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1=CC=C2C(=C1)C(=O)NC2(C3=CC(=C(C=C3)Cl)S(=O)(=O)N)O
• Recent ClinicalTrials: Chlorthalidone in Chronic Kidney Disease
• Recent EU Clinical Trials: Diuretic Treatment in Acute Heart Failure with Volume Overload Guided by Serial Spot Urine Sodium Assessment
• Uses: Chlorthalidone is used as a diuretic; antihypertensive. Antihypertensive Agents,Diuretics,Sodium Chloride Symporter Inhibitors In terms of activity, chlorothalidone is very similar to benzothiadiazide (21.3.13) and is used as an independent drug or in combination with other antihypertensive agents for lowering arterial blood pressure, and also as an adjuvant drug for treating edema caused by cardiac insufficiency and renal irregularities, including nephrotic syndrome.
• Clinical Use: Chlorthalidone has a long duration of action (48–72 hours). Although quinethazone and metolazone are administered daily, chlorthalidone may be administered in doses of 25 to 100 mg three times a week. When chlorthalidone is formulated with the excipient povidone, the product, Thalitone, has greater bioavailability (>90%) and reaches peak plasma concentrations in a shorter time compared with its other products. Similar to the quinazolinones, it also is extensively bound to carbonic anhydrase in the erythrocytes.
• Drug interactions: Potentially hazardous interactions with other drugs Analgesics: increased risk of nephrotoxicity with NSAIDs; antagonism of diuretic effect.Anti-arrhythmics: hypokalaemia leads to increased cardiac toxicity; effects of lidocaine and mexiletine antagonised. Antibacterials: avoid administration with lymecycline. Antidepressants: increased risk of hypokalaemia with reboxetine; enhanced hypotensive effect with MAOIs; increased risk of postural hypotension with tricyclics. Antiepileptics: increased risk of hyponatraemia with carbamazepine. Antifungals: increased risk of hypokalaemia with amphotericin. Antihypertensives: enhanced hypotensive effect; increased risk of first dose hypotension with postsynaptic alpha-blockers like prazosin; hypokalaemia increases risk of ventricular arrhythmias with sotalol. Antipsychotics: hypokalaemia increases risk of ventricular arrhythmias with amisulpride; enhanced hypotensive effect with phenothiazines; hypokalaemia increases risk of ventricular arrhythmias with pimozide - avoid. Atomoxetine: hypokalaemia increases risk of ventricular arrhythmias. Cardiac glycosides: increased toxicity if hypokalaemia occurs. Ciclosporin: increased risk of nephrotoxicity and hypomagnesaemia. Cytotoxics: increased risk of ventricular arrhythmias due to hypokalaemia with arsenic trioxide; increased risk of nephrotoxicity and ototoxicity with platinum compounds. Lithium excretion reduced, increased toxicity.

Technology Process of Chlorthalidone

There total 10 articles about Chlorthalidone which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 76.0%

3-(3'-sulfamyl-4'-chlorophenyl)phthalimidine (82875-49-8) → chlorthalidon (77-36-1)

Guidance literature:

With dihydrogen peroxide; sodium hydroxide; In water; at 0 - 26 ℃;

Reference yield:

4-(4-chlorophenyl)-1H-2,3-benzoxazin-1-one (2224-83-1) → chlorthalidon (77-36-1)

Guidance literature:

Multi-step reaction with 4 steps

1.1: zinc; acetic acid / 70 - 75 °C

2.1: chlorosulfonic acid / 0 - 80 °C

2.2: 2 h / 75 - 80 °C

3.1: ammonium hydroxide / acetone; water / 0 - 5 °C

4.1: dihydrogen peroxide; sodium hydroxide / water / 0 - 26 °C

With chlorosulfonic acid; ammonium hydroxide; dihydrogen peroxide; acetic acid; sodium hydroxide; zinc; In water; acetone;

Reference yield:

2-(4-chlorobenzoyl)benzoic acid (85-56-3) → chlorthalidon (77-36-1)

Guidance literature:

Multi-step reaction with 5 steps

1.1: sodium hydroxide; hydroxylamine hydrochloride / methanol / 25 - 65 °C

2.1: zinc; acetic acid / 70 - 75 °C

3.1: chlorosulfonic acid / 0 - 80 °C

3.2: 2 h / 75 - 80 °C

4.1: ammonium hydroxide / acetone; water / 0 - 5 °C

5.1: dihydrogen peroxide; sodium hydroxide / water / 0 - 26 °C

With chlorosulfonic acid; ammonium hydroxide; hydroxylamine hydrochloride; dihydrogen peroxide; acetic acid; sodium hydroxide; zinc; In methanol; water; acetone;

upstream raw materials:

(-)-Chlortalidon

chloroform

2-chloro-5-(1-chloro-3-oxo-phthalan-1-yl)-benzenesulfonyl chloride

ammonia

Downstream raw materials:

Chlortalidon-methylether

(+)-Chlortalidon

(-)-Chlortalidon

2-(4-chloro-3-sulfamoyl-benzoyl)-benzoic acid

Refernces

• 1、 -. "NOVEL POLYMORPH OF 3-HYDROXY-3-(3’-SULFAMYL-4’-CHLOROPHENYL)PHTHALIMIDINE". Page/Page column 16. . Retrieved 2008/06/13.
• 2、 -. "2,3-dihydrobenzofuran-5-sulfonamide derivatives useful as antihypertensive diuretic agents". . . Retrieved 2008/06/13.