Propizepine

Propizepine (brand names Depressin, Vagran) is a tricyclic antidepressant (TCA) used in France for the treatment of depression which was introduced in the 1970s.[1][2][3][4]

Propizepine

Clinical data
Trade names	Depressin, Vagran
Routes of administration	Oral
ATC code	none
Legal status
Legal status	In general: ℞ (Prescription only)
Identifiers
IUPAC name 6-(2-dimethylaminopropyl)-11H-pyrido[3,2-c][1,5]benzodiazepin-5-one
CAS Number	10321-12-7 14559-79-6 (hydrochloride)
PubChem CID	112029
ChemSpider	100443
UNII	09B57945V9
ChEMBL	ChEMBL2104749
ECHA InfoCard	100.030.629
Chemical and physical data
Formula	C17H20N4O
Molar mass	296.374 g·mol^−1

Synthesis

Propizepine synthesis:[5][6]

Condensation of 2-chloronicotinic acid (2) with o-phenylenediamine (1) leads directly to the tricyclic lactam (3) Although the reaction involves amide formation and nucleophilic aromatic displacement of chlorine, the order of these steps is not known. Alkylation of the anion obtained by treatment if 3 with the 1-chloro-2-dimethylaminopropane (4) affords the antidepressant compound propizepine (5).

The last step in this sequence there is considerable evidence that such alkylations often proceed via the aziridinium ion. Attack of the anion at the secondary or tertiary carbon of the aziridinium ring will lead to different products. Extensive investigation of this problem (e.g. Promethazine, ethopropazine, etc.) has established that the product from attack at secondary carbon usually predominates.

What this intends to say is that even if the chloroamine used is actually 1-dimethylamino-2-chloro-propane, although could still be a mixture of products one still gets predominantly the same reaction product as above and not the "iso" product.

References

1. Swiss Pharmaceutical Society (2000). Index Nominum 2000: International Drug Directory (Book with CD-ROM). Boca Raton: Medpharm Scientific Publishers. p. 888. ISBN 3-88763-075-0.
2. Triggle DJ (1996). Dictionary of Pharmacological Agents. Boca Raton: Chapman & Hall/CRC. p. 1680. ISBN 0-412-46630-9.
3. Muller NF, Dessing RP (1997). European Drug Index. European Society of Clinical Pharmacy. 33. CRC Press. p. 1339. ISBN 3-7692-2114-1.
4. Dereux JF (1976). "[Vagran 50: a situational antidepressant]". Semaine des Hopitaux. Therapeutique (in French). 52 (7–8): 385–8. PMID 996559.
5. Hoffman C, Faure A (1966). "Réactions de l'acide chloro-2-nicotinique". Bull. Soc. Chim. Fr. 7: 2316.
6. NL 6600065, issued 1966, assigned to Labs. U.P.S.A.