Chlorothiazide

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Structural formula
Structural formula of chlorothiazide
General
Non-proprietary name Chlorothiazide
other names
  • 6-chloro-2 H -1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide
  • 6-chloro-7-sulfamoyl-1,2,4-benzothiadiazine-1,1-dioxide
Molecular formula C 7 H 6 ClN 3 O 4 S 2
Brief description

white, odorless, slightly bitter solid

External identifiers / databases
CAS number
  • 58-94-6
  • 7085-44-1 (sodium salt)
ECHA InfoCard 100,000,368
PubChem 2720
DrugBank DB00880
Wikidata Q2603363
Drug information
ATC code

C03 AA04

properties
Molar mass 295.72 g mol −1
Physical state

firmly

Melting point

355 ° C

solubility
  • is very slightly soluble in water
  • slightly soluble in ethanol
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
08 - Dangerous to health

danger

H and P phrases H: 317-334
P: 261-280-342 + 311
Toxicological data
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Chlorothiazide , occasionally also chlorothiazide , is a chemical compound from the group of thiazides (benzothiadiazines) and can be regarded as the parent compound of the benzothiadiazide derivatives. Chlorothiazide is one of the first diuretics in the thiazide class. Like the carbonic anhydrase inhibitors from which they were developed, these are sulfonamide derivatives and have an SO 2 NH 2 group.

discovery

The company Merck (USA) was intensively involved in the research and development of diuretics and antihypertensive drugs and had numerous results of their research patented. The company owes numerous patents, including those for chlorothiazide , to the chemist Frederick C. Novello (1916–1986) who worked for Merck . For this invention and the development of the thiazide diuretics in general, Novello was inducted into the list of members of the National Inventors Hall of Fame in 2019 .

Extraction and manufacture

A synthesis of chlorothiazide begins with the reaction of 3-chloroaniline with chlorosulfonic acid ; subsequent treatment with ammonia leads to 4-amino-6-chloro-1,3-disulfonamide. By heating with formic acid , ring closure (cyclization) to the bicyclic thiazide is forced.

properties

Chlorothiazide is a white, odorless, slightly bitter, crystalline solid that is very slightly soluble in water. In contrast, the sodium salt of chlorothiazide, which is used for parenteral administration, is very soluble in water. Chlorothiazide is stable when exposed to light and in acids, but not in bases.

use

Chlorothiazide is used as a drug . The compound was marketed by Merck in early 1958 as a drug for the treatment of high blood pressure and heart failure under the names Diuril (USA) and Chlotride (Europe).

See also

Individual evidence

  1. a b c d e f Entry on chlorothiazide at Vetpharm, accessed on November 3, 2018.
  2. a b c d e f data sheet Chlorothiazide, thiazide diuretic from Sigma-Aldrich , accessed on November 3, 2018 ( PDF ).
  3. Jie Jack Lee: History of Drug Discovery . In: Jie Jack Li, EJ Corey (Eds.): Drug Discovery: Practices, Processes, and Perspectives . John Wiley & Sons, 2013, pp. 12 . ( limited preview in Google Book search)
  4. ^ NN: Drugs originating from the Screening of Dyes . In: Walter Sneader (Ed.): Drug Discovery: A History . John Wiley & Sons, 2005, pp. 391 . ( limited preview in Google Book search)
  5. Entry on Chlorothiazide in the Hazardous Substances Data Bank , accessed November 3, 2018.
  6. Gregory Higby, Elaine Condouris Stroud: The Inside Story of Medicines A Symposium . Amer. Inst. History of Pharmacy, 1997, ISBN 978-0-931292-32-3 , pp. 124 ff . ( limited preview in Google Book search).
  7. ^ Karl H. Beyer: THE MECHANISM OF ACTION OF CHLOROTHIAZIDE. In: Annals of the New York Academy of Sciences. 71, 1958, p. 363, doi : 10.1111 / j.1749-6632.1958.tb54609.x .