58-94-6 Usage
Uses
Used in Pharmaceutical Industry:
Chlorothiazide is used as a diuretic and antihypertensive agent for treating arterial hypertension, edematous syndromes of various origins, congestive effects in cardiovascular insufficiency, nephrosis, nephritis, and toxicosis. It is especially recommended for hypertonic illnesses and can also lower intraocular pressure in certain cases.
Originator
Diuril,Merck Sharp and,US,1957
Manufacturing Process
(A) m-Chloroaniline (64 g, 0.5 mol) was added dropwise with stirring to 375
ml of chlorosulfonic acid in a 3-liter round bottom, 3-necked flask cooled in an
ice bath. Sodium chloride (350 g) was added portionwise over a period of 1 to2 hours and the mixture then heated gradually in an oil bath to 150°C. After 3
hours at 150° to 160°C, the flask was cooled thoroughly in an ice bath and
the contents treated with a liter of cold water. The product was extracted with
ether and the extract washed with water and dried over sodium sulfate.
After removal of ether on the steam bath, the residual 5-chloroaniline-2,4-
disulfonyl chloride, which may be crystallized from benzene-hexane MP 130°
to 132°C, was cooled in an ice bath and treated with 150 ml of 28%
ammonium hydroxide in a 2-liter Erlenmeyer flask. The mixture was heated
on the steam bath for 1 hour, cooled and the product collected on the filter,
washed with water and dried. Upon crystallization from dilute alcohol 5-
chloro-2,4-disulfamylaniline was obtained as colorless needles, MP 251° to
252°C.
(B) A solution of 88 g of 5-chloro-2,4-disulfamylaniline in 1.1 liters of 88%
formic acid was heated under reflux for 2 hours. After removal of 200 ml of
solvent by distillation, one liter of water was added and the product collected,
washed with water and dried. Crystallization from dilute alcohol afforded 6-
chloro-7-sulfamyl-1,2,4-benzothiadiazine-1,1-dioxide as colorless needles, MP
342.5° to 343°C, as described in US Patent 2,809,194.
Therapeutic Function
Diuretic; Antihypertensive
Air & Water Reactions
Insoluble in water.
Reactivity Profile
Alkaline aqueous solutions will decompose on standing or heating .
Fire Hazard
Flash point data for Chlorothiazide are not available; however, Chlorothiazide is probably combustible.
Mechanism of action
The diuretic action of chlorothiazide, like other drugs of this series, is caused by reduced
absorption of sodium and chloride ions by the kidneys during their simultaneous, intense
excretion from the organism.
Safety Profile
Moderately_toxic by
intraperitoneal and intravenous routes.
Mddly toxic by ingestion. Experimental
reproductive effects. Has been implicated in
aplastic anemia. When heated to
decomposition it emits very toxic fumes of
SOx NOx and Cl-.
Synthesis
Chlorothiazide, 1,1-dioxide 6-chloro-2H-1,2,4-benzothiadiazin-7-sulfonamide
(21.3.3) is synthesized in the exact same manner, is all thiazide diuretics. 3-
Chloroaniline (or 3-trifluoromethylaniline) undergoes sulfoylchlorination by chlorosulfonic
acid, forming 4,6-sulfonochloride-3-chloroaniline (21.3.1), the reaction of which with ammonia
gives 4,6-sulfonylamido-3-chloroaniline (21.3.2). Heating this with formamide leads to
formation of chlorothiazide (21.3.3).
Veterinary Drugs and Treatments
In veterinary medicine, furosemide has largely supplanted the use
of thiazides as a general diuretic (edema treatment). Thiazides are
still used for the treatment of systemic hypertension,
nephrogenic
diabetes insipidus, and to help prevent the recurrence of calcium
oxalate uroliths in dogs.
Chlorothiazide is approved for use in dairy cattle for the treatment
of post parturient udder edema, but the veterinary labeled
product has been discontinued in the USA.
Check Digit Verification of cas no
The CAS Registry Mumber 58-94-6 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 8 respectively; the second part has 2 digits, 9 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 58-94:
(4*5)+(3*8)+(2*9)+(1*4)=66
66 % 10 = 6
So 58-94-6 is a valid CAS Registry Number.
InChI:InChI=1/C7H6ClN3O4S2/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5/h1-3H,(H2,9,12,13)(H,10,11,14,15)
58-94-6Relevant articles and documents
Synthesis, characterization, and investigation of the antioxidant activity of some 1,2,4-benzothiadiazine-1,1-dioxides bearing sulfonylthioureas moieties
Harrouche, Kamel,Lahouel, Asma,Belghobsi, Mebrouk,Pirotte, Bernard,Khelili, Smail
, p. 824 - 832 (2019/11/28)
A series of 1,2,4-benzothiadiazine-1,1-dioxides bearing a sulfonylthiourea moiety were synthesized, characterized, and screened for their antioxidant activity, using six antioxidant analytical assays comparatively to reference compounds, ascorbic acid and quercetin. The results indicated that several compounds demonstrated strong antioxidant activity in DPPH, ABTS, H2O2, and lipid peroxidation assays where some of them were either as active as or more active than reference compounds. However, all compounds were largely less active than references compounds in the reducing power assay. The results indicated that the thiourea moiety probably played a crucial role in the antioxidant activity of the target compounds, as a thiolate ion. The most favorable R1 groups were the hydrogen atom and methyl group, followed by phenyl and benzyl groups, whereas the most favorable R2 group was iPr, followed by the phenyl and methyl groups. The combination of benzothiadiazine ring with sulfonylthiourea moieties led to valuable new antioxidants, which could be used in the treatment or the prevention of certain diseases or in the field of cosmetics, which needs further investigations in the future.
CHLOROTHIAZIDE, CHLOROTHIAZIDE SALTS AND PHARMACEUTICAL COMPOSITIONS THEREOF
-
Page/Page column 9, (2011/11/06)
The present invention relates to an improved process for the preparation of Chlorothiazide and pharmaceutically acceptable salts thereof. The present invention relates to novel polymorphs of Chlorothiazide and Chlorothiazide salts, in particular Chlorothiazide sodium. The present invention further relates to pharmaceutical compositions comprising Chlorothiazide and Chlorothiazide salts, in particular Chlorothiazide sodium and process for preparation thereof.
Synthesis and pharmacological evaluation of 1,2,4-benzothiadiazin-1,1- dioxides bearing 5- or 7-sulfonylurea moieties
Khelili, Smail,Faury, Gilles,Nicolle, Edwige,Verdetti, Jean,Leclerc, Gerard
, p. 457 - 470 (2007/10/03)
A series of substituted benzothiadiazin-1,1-dioxides bearing sulfonylurea moieties in position 5 or 7 has been synthesized. The most powerful vasodilator compound was 18a, obtained by substitution of a sulfonylurea moiety on position 7 of the diazoxide skeleton by means of a SO2 group. Interestingly, 18a and 18b were found inactive on insulin secretion at 50 μM and likely devoid of adverse effect on glycemia, suggesting a special therapeutic potential for these compounds.
