Luzindole
{{Short description|Chemical compound}}
{{Drugbox
| IUPAC_name = N-[2-(2-benzyl-1H-indol-3-yl)ethyl]acetamide
| image = Luzindole.svg
| CAS_number = 117946-91-5
| CAS_number_Ref = {{cascite|correct|CAS}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = B31Y10A9UR
| ATC_prefix = None
| ATC_suffix =
| PubChem = 122162
| ChemSpiderID = 108959
| ChEBI_Ref = {{ebicite|correct|EBI}}
| synonyms = N-0774, N-acetyl-2-benzyltryptamine
| ChEBI = 131788
| C = 19
| H = 20
| N = 2
| O = 1
| smiles = O=C(NCCc2c1ccccc1[nH]c2Cc3ccccc3)C
| StdInChI = 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)
| StdInChIKey = WVVXBPKOIZGVNS-UHFFFAOYSA-N
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life =
| excretion =
| pregnancy_category =
| legal_status = Uncontrolled
| routes_of_administration =
}}
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,{{cite journal | author = Dubocovich ML | title = Luzindole (N-0774): a novel melatonin receptor antagonist | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 246 | issue = 3 | pages = 902–10 |date=September 1988 | pmid = 2843633 | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=2843633}} with approximately 11- to 25-fold greater affinity for the MT2 over the MT1 receptor.{{cite journal |vauthors=Dubocovich ML, Yun K, Al-Ghoul WM, Benloucif S, Masana MI | title = Selective MT2 melatonin receptor antagonists block melatonin-mediated phase advances of circadian rhythms | journal = The FASEB Journal | volume = 12 | issue = 12 | pages = 1211–20 |date=September 1998 | pmid = 9737724 | doi = 10.1096/fasebj.12.12.1211 | doi-access = free | s2cid = 566199 | url = http://www.fasebj.org/cgi/pmidlookup?view=long&pmid=9737724}}{{cite journal |vauthors=Browning C, Beresford I, Fraser N, Giles H | title = Pharmacological characterization of human recombinant melatonin mt(1) and MT(2) receptors | journal = British Journal of Pharmacology | volume = 129 | issue = 5 | pages = 877–86 |date=March 2000 | pmid = 10696085 | pmc = 1571913 | doi = 10.1038/sj.bjp.0703130 }} In animal studies, it has been observed to disrupt the circadian rhythm as well as produce antidepressant effects.{{cite journal |vauthors=Dubocovich ML, Mogilnicka E, Areso PM | title = Antidepressant-like activity of the melatonin receptor antagonist, luzindole (N-0774), in the mouse behavioral despair test | journal = European Journal of Pharmacology | volume = 182 | issue = 2 | pages = 313–25 |date=July 1990 | pmid = 2168835 | doi = 10.1016/0014-2999(90)90290-M}}
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 [61-54-1] (1) and benzaldehyde gives 1-Phenyl-tetrahydrocarboline [3790-45-2] (2). Catalytic hydrogenation leads to 2-Benzyltryptamine [22294-23-1] (3). Acylation with acetic anhydride only gave 21% yield of Luzindole (4).
File:Luzindole synthesis 2.svg
2-iodoaniline [615-43-0] (1)
Propargylbenzene [10147-11-2] (2)
2-(3-phenylprop-1-ynyl)aniline, PC85868179 (3)
2-benzylindole [3377-72-8] (4)
1-Dimethylamino-2-nitroethylene [1190-92-7] (5)
(6)
One pot Luzindole synthesis: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.
References
{{Reflist|2}}
{{Melatonergics}}
{{Tryptamines}}