Propizepine

Propizepine

Clinical data
Routes of administration	Oral
ATC code	none
Legal status
Legal status	℞ (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	296.37 g/mol

Propizepine (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]

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 (eg 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. David J. Triggle (1996). Dictionary of Pharmacological Agents. Boca Raton: Chapman & Hall/CRC. p. 1680. ISBN 0-412-46630-9.
3. Niels F. Muller, Rudolf P. Dessing, European Society of Clinical Pharmacy (1997). European Drug Index, Volume 33. CRC Press. p. 1339. ISBN 3-7692-2114-1.
4. Dereux JF (1976). "[Vagran 50: a situational antidepressant]". Semaine des Hôpitaux. Thérapeutique (in French). 52 (7-8): 385–8. PMID 996559.
5. Hoffmann, C.; Faure, A.; Bull. Soc. Chim. Fr. 1966, 2316.
6. NL 6600065  (1966 to Labs. U.P.S.A.)