Chemistry:Pirlindole

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Short description: Chemical compound
Pirlindole
Clinical data
Trade namesPirazidol
Routes of
administration
Oral
ATC code
  • none
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability20–30%
Protein binding95%
Metabolismhepatic
Onset of action2 to 8 hours
Elimination half-lifeup to 8 days [1]
Excretionurine (50–70%), feces (25–45%)
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC15H18N2
Molar mass226.323 g·mol−1
3D model (JSmol)

Pirlindole (Lifril, Pyrazidol) is mainly a reversible inhibitor of monoamine oxidase A (RIMA) and secondly a SNRI which was developed and is used in Russia as an antidepressant.[2] It is structurally and pharmacologically related to metralindole.

Synthesis

Synthesis:[3][4][5] Patents:[6][7][8][9][10] Sino:[11] Enantiomers:[12]

The Fischer indole synthesis between p-Tolylhydrazine Hydrochloride [637-60-5] (1) and 1,2-Cyclohexanedione [765-87-7] (2) gives 6-methyl-2,3,4,9-tetrahydrocarbazol-1-one [3449-48-7] (3). Imine formation with ethanolamine [141-43-5] (4) gives CID:2838578 (5). Halogenation with phosphorus oxychloride gives (6).[13] Intramolcular alkylation with the indole nitrogen resulted in Dehydropirlindole [75804-32-9] (7). Reduction of the imine with sodium borohydride completes the synthesis of pirlindole (8).

See also

References

  1. ↑ "Pirlindole: results of an open clinical study in out-patients and of a double-blind study against maprotiline.". Psychiatry the State of the Art. Boston, MA.: Springer. 1985. pp. 283–289. doi:10.1007/978-1-4613-2363-1_44. ISBN 978-1-4613-2363-1. 
  2. ↑ "Pirlindole: a selective reversible inhibitor of monoamine oxidase A. A review of its preclinical properties". Pharmacological Research 36 (1): 23–33. July 1997. doi:10.1006/phrs.1997.0196. PMID 9368911. 
  3. ↑ "Tetrahydrocarbazole derivatives and their antitubercular activity in vitro. I. N-Substituted hexahydro-1H-pyrazino[3,2,1-j,k]carbazoles" (in Russian). Khimiko-Farmatsevticheskii Zhurnal 20 (3): 300–303. 1986. 
  4. ↑ "New approach to the synthesis of pyrazidol". Pharmaceutical Chemistry Journal 21 (1): 62–65. January 1987. doi:10.1007/BF00764890. .
  5. ↑ "First Preparative Enantiomer Resolution of Pirlindole, a Potent Antidepressant Drug". Helvetica Chimica Acta 81 (3–4): 539–547. 1998. doi:10.1002/hlca.19980810307. ISSN 0018-019X. .
  6. ↑ , FR patent 2132514 (1972 to Inst Im Sergo); CA, 78, 124628r
  7. ↑ Massimo Ferrari, et al. EP patent 1044976 (2002 to Erregierre SpA).
  8. ↑ Massimo Ferrari, et al. CZ20001348 (2000).
  9. ↑ DE patent 2114230
  10. ↑ GB patent 1340529
  11. ↑ Chen Weidong, et al. CN patent 110950873 (2020 to Henan University).
  12. ↑ Carla Patricia Da Costa Pereira Rosa, et al. WO patent 2018193415 (to Tecnimede Sociedade Tecnico Medicinal SA).
  13. ↑ "N-(2-chloroethyl)-6-methyl-2,3,4,9-tetrahydrocarbazol-1-imine". PubMed. U.S. National Library of Medicine. https://pubchem.ncbi.nlm.nih.gov/compound/135418359.