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Luzindole

Clinical data
Other names	N-0774, N-acetyl-2-benzyltryptamine
ATC code	None
Legal status
Legal status	In general: uncontrolled
Identifiers
IUPAC name N-acetamide
CAS Number	117946-91-5
PubChem CID	122162
ChemSpider	108959
UNII	B31Y10A9UR
ChEBI	CHEBI:131788
CompTox Dashboard (EPA)	DTXSID40151969
Chemical and physical data
Formula	C19H20N2O
Molar mass	292.382 g·mol
3D model (JSmol)	Interactive image
SMILES O=C(NCCc2c1ccccc1c2Cc3ccccc3)C
InChI InChI=1S/C19H20N2O/c1-14(22)20-12-11-17-16-9-5-6-10-18(16)21-19(17)13-15-7-3-2-4-8-15/h2-10,21H,11-13H2,1H3,(H,20,22) Key:WVVXBPKOIZGVNS-UHFFFAOYSA-N

Luzindole (N-0774; N-acetyl-2-benzyltryptamine), is a drug used in scientific research to study the role of melatonin in the body. Luzindole acts as a selective melatonin receptor antagonist, with approximately 11- to 25-fold greater affinity for the MT₂ over the MT₁ receptor. In animal studies, it has been observed to disrupt the circadian rhythm as well as produce antidepressant effects.

Synthesis

Although the "hydrogen bomb" method was reported as 54% yield by Dubococvich, Boehringer Sohn achieved 96% for this step. The difference is that B.I. conducted their hydrogenation under normal pressure at 50°C for 5 hours, whereas Dubocovich conducted theirs at 100 lbs/in2 hydrogen heated to 35°C. This proves that the hydrogenation step proceeds favorably under milder conditions.

The Pictet–Spengler reaction between tryptamine (1) and benzaldehyde gives 1-Phenyl-tetrahydrocarboline (2). Catalytic hydrogenation leads to 2-Benzyltryptamine (3). Acylation with acetic anhydride only gave 21% yield of Luzindole (4).

2-iodoaniline (1) Propargylbenzene (2) 2-(3-phenylprop-1-ynyl)aniline, PC85868179 (3) 2-benzylindole (4) 1-Dimethylamino-2-nitroethylene (5) (6)

One pot Luzindole synthesis:

References

1. Dubocovich ML (September 1988). "Luzindole (N-0774): a novel melatonin receptor antagonist". The Journal of Pharmacology and Experimental Therapeutics. 246 (3): 902–10. PMID 2843633.
2. ^ Dubocovich ML, Yun K, Al-Ghoul WM, Benloucif S, Masana MI (September 1998). "Selective MT2 melatonin receptor antagonists block melatonin-mediated phase advances of circadian rhythms". The FASEB Journal. 12 (12): 1211–20. doi:10.1096/fasebj.12.12.1211. PMID 9737724. S2CID 566199.
3. Browning C, Beresford I, Fraser N, Giles H (March 2000). "Pharmacological characterization of human recombinant melatonin mt(1) and MT(2) receptors". British Journal of Pharmacology. 129 (5): 877–86. doi:10.1038/sj.bjp.0703130. PMC 1571913. PMID 10696085.
4. Dubocovich ML, Mogilnicka E, Areso PM (July 1990). "Antidepressant-like activity of the melatonin receptor antagonist, luzindole (N-0774), in the mouse behavioral despair test". European Journal of Pharmacology. 182 (2): 313–25. doi:10.1016/0014-2999(90)90290-M. PMID 2168835.
5. Margarita L. Dubocovich, et al. WO1989001472A1 ().
6. Margarita L. Dubocovich, et al., U.S. patent 5,283,343 (1994 to Discovery Therapeutics Inc).
7. Schroeder Dr Hans-D, et al. DE1445516 (1968 to CH Boehringer Sohn AG and Co KG).
8. Tsotinis, Andrew; Afroudakis, Pandelis (2008). "Melatonin Receptor Antagonist Luzindole: A Facile New Synthesis". Letters in Organic Chemistry. 5 (6): 507–509. doi:10.2174/157017808785740561. ISSN 1570-1786.
9. Righi, Marika; Topi, Francesca; Bartolucci, Silvia; Bedini, Annalida; Piersanti, Giovanni; Spadoni, Gilberto (2012). "Synthesis of Tryptamine Derivatives via a Direct, One-Pot Reductive Alkylation of Indoles". The Journal of Organic Chemistry. 77 (14): 6351–6357. doi:10.1021/jo3010028.

• Drugs not assigned an ATC code
• Acetamides
• Tryptamines
• Melatonin receptor antagonists