Pipazetate

Last updated
Pipazetate
Pipazethate.png
Clinical data
Trade names Dipect, Lenopect, Selvignon, Selvigon, Theratuss, Toraxan
Other namesPipazethate; D-254; LG-254; SKF-70230A; SQ-15874
AHFS/Drugs.com International Drug Names
Routes of
administration
oral
ATC code
Legal status
Legal status
  •  ?
Identifiers
  • 2-(2-piperidin-1-ylethoxy)ethyl 10H-pyrido[3,2-b][1,4]benzothiazine-10-carboxylate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard 100.016.826 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C21H25N3O3S
Molar mass 399.51 g·mol−1
3D model (JSmol)
  • O=C(OCCOCCN1CCCCC1)N3c4c(Sc2c3nccc2)cccc4
  • InChI=1S/C21H25N3O3S/c25-21(27-16-15-26-14-13-23-11-4-1-5-12-23)24-17-7-2-3-8-18(17)28-19-9-6-10-22-20(19)24/h2-3,6-10H,1,4-5,11-16H2 Yes check.svgY
  • Key:DTVJXCOMJLLMAK-UHFFFAOYSA-N Yes check.svgY
   (verify)

Pipazetate (INN Tooltip International Nonproprietary Name) (brand names Dipect, Lenopect, Selvigon, Theratuss, Toraxan), or pipazethate (USAN Tooltip United States Adopted Name), is a 1-azaphenothiazine drug that was briefly marketed as a cough suppressant. [1] [2] It binds to the sigma-1 receptor with an IC50 value of 190 nM. [3] It also has local anesthetic action, and in large doses can produce seizures. [4]

As the brand name Theratuss, it was approved by the FDA in 1962, on evidence of safety only. It was withdrawn from the US market in 1972 when the manufacturer, Bristol Myers Squibb, failed to produce evidence of efficacy. [5] Clinical studies showed that it did not decrease cough frequency at recommended dosages. [6]

Infrequent side effects include nausea, vomiting, drowsiness, fatigue, rash, tachycardia and seizures. [6]

Synthesis

Note: 1-azaphenothiazine is also used for making Prothipendyl & Isothipendyl.

Thieme Synthesis: Patent: Revised: Pipazethate synthesis.svg
Thieme Synthesis: Patent: Revised:

The reaction of 1-azaphenothiazine [261-96-1] (1) with phosgene gives 1-azaphenothiazine-10-carbonyl chloride [94231-78-4] (2). The reaction of this reactive intermediate with 2-[2-(piperidyl)ethoxy]ethanol [3603-43-8] (3) gives the ester, thus completing the synthesis of Pipazethate (4).

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References

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  4. Martín, Alfonso Velasco (2004). "Tratamiento sintomático de la tos y del resfriado común". Farmacología clínica y terapéutica médica. p. 259. ISBN   9788448604271.
  5. Certain Preparations Containing Dihyprylone or Pipazethate Hydrochloride; Notice of Withdrawal of Approval of New-Drug Applications (PDF). Federal Register (Report). Vol. 37. August 5, 1972. p. 15887. FDC–D–458.
  6. 1 2 Council on Drugs (1971). AMA Drug Evaluations (Report). Chicago: American Medical Association. p. 360–3. LCCN   75147249 . Retrieved April 5, 2021.
  7. Schuler, Wilhelm A.; Klebe, Hans; Schlichtegroll, Ansgar V. (1964). "Synthesen von 4-Aza-phenothiazinen, II. Derivate der 4-Aza-phenothiazin-10-carbonsäure". Justus Liebigs Annalen der Chemie. 673 (1): 102–112. doi:10.1002/jlac.19646730114.
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