Pirlindole, sold under the brand names Lifril and Pyrazidol, is mainly a reversible inhibitor of monoamine oxidase A (RIMA) and secondly a serotonin–norepinephrine reuptake inhibitor (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. ↑ Pöldinger W (1985). "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. pp. 283–289. doi:10.1007/978-1-4613-2363-1_44. ISBN 978-1-4613-2363-1.
  2. ↑ Bruhwyler J, Liégeois JF, Géczy J (July 1997). "Pirlindole: a selective reversible inhibitor of monoamine oxidase A. A review of its preclinical properties". Pharmacological Research. 36 (1): 23–33. doi:10.1006/phrs.1997.0196. hdl:11380/708913. PMID 9368911.
  3. ↑ Filitis LN, Fedotova OA, Akalaeva TV, Bokanov AI, Ivanov PY, Neustroeva VD, Nyrkova VG, Pershin GN, Shvedov VI (1986). "Tetrahydrocarbazole derivatives and their antitubercular activity in vitro. I. N-Substituted hexahydro-1H-pyrazino[3,2,1-j,k]carbazoles". Khimiko-Farmatsevticheskii Zhurnal (in Russian). 20 (3): 300–303.
  4. ↑ Ivanov PY, Alekseeva LM, Bokanov AI, Shvedov VI, Sheinker YN (January 1987). "New approach to the synthesis of pyrazidol". Pharmaceutical Chemistry Journal. 21 (1): 62–65. doi:10.1007/BF00764890. S2CID 22179419..
  5. ↑ De Tullio P, Felikidis A, Pirotte B, Liégeois JF, Stachow M, Delarge J, Ceccato A, Hubert P, Crommen J, Géczy J (1998). "First Preparative Enantiomer Resolution of Pirlindole, a Potent Antidepressant Drug". Helvetica Chimica Acta. 81 (3–4): 539–547. Bibcode:1998HChAc..81..539D. doi:10.1002/hlca.19980810307. ISSN 0018-019X..
  6. ↑ , FR 2132514 (1972 to Inst Im Sergo); CA, 78, 124628r
  7. ↑ Massimo Ferrari, et al. EP 1044976 (2002 to Erregierre SpA).
  8. ↑ Massimo Ferrari, et al. CZ20001348 (2000).
  9. ↑ DE 2114230
  10. ↑ GB 1340529
  11. ↑ Chen Weidong, et al. CN 110950873 (2020 to Henan University).
  12. ↑ Carla Patricia Da Costa Pereira Rosa, et al. WO 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.
source: https://en.wikipedia.org/wiki/Pirlindole