Pipazetate

Pipazetate (INNTooltip International Nonproprietary Name) (brand names Dipect, Lenopect, Selvigon, Theratuss, Toraxan), or pipazethate (USANTooltip 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]

Pipazetate

Clinical data
Trade names	Dipect, Lenopect, Selvignon, Selvigon, Theratuss, Toraxan
Other names	Pipazethate; D-254; LG-254; SKF-70230A; SQ-15874
AHFS/Drugs.com	International Drug Names
Routes of administration	oral
ATC code	R05DB11 (WHO)
Legal status
Legal status	?
Identifiers
IUPAC name 2-(2-piperidin-1-ylethoxy)ethyl 10H-pyrido[3,2-b][1,4]benzothiazine-10-carboxylate
CAS Number	2167-85-3 6056-11-7 (hydrochloride)
PubChem CID	22425
DrugBank	DB08796 Y
ChemSpider	21046 Y
UNII	M5EK1T5V2L
KEGG	D05484 Y
CompTox Dashboard (EPA)	DTXSID40176056
ECHA InfoCard	100.016.826
Chemical and physical data
Formula	C21H25N3O3S
Molar mass	399.51 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C(OCCOCCN1CCCCC1)N3c4c(Sc2c3nccc2)cccc4
InChI 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 Y Key:DTVJXCOMJLLMAK-UHFFFAOYSA-N Y
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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 It was withdrawn from the US market in 1972 when the manufacturer, Bristol Myers Squibb, failed to produce evidence of efficacy.^[5] Clinical studies showed that it did not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:^[7] Patent:^[8] Revised:^[9]

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).