The Vespiary

The Hive => Tryptamine Chemistry => Topic started by: Rhodium on September 06, 2002, 09:02:00 AM

Title: New LSD analogs from the Nichols Lab
Post by: Rhodium on September 06, 2002, 09:02:00 AM
Lysergamides of Isomeric 2,4-Dimethylazetidines Map the Binding Orientation of the Diethylamide Moiety in the Potent Hallucinogenic Agent N,N-Diethyllysergamide (LSD)

J. Med. Chem., 45 (19), 4344-4349 (2002)

Lysergic acid amides were prepared from (R,R)-(-)-, (S,S)-(+)-, and cis-2,4-dimethyl azetidine. The dimethylazetidine moiety is considered here to be a rigid analogue of diethylamine, and thus, the target compounds are all conformationally constrained analogues of the potent hallucinogenic agent, N,N-diethyllysergamide, LSD-25. Pharmacological evaluation showed that (S,S)-(+)-2,4-dimethylazetidine gave a lysergamide with the highest LSD-like behavioral activity in the rat two lever drug discrimination model that was slightly more potent than LSD itself. This same diastereomer also had the highest affinity and functional potency at the rat serotonin 5-HT2A receptor, the presumed target for hallucinogenic agents, and a receptor affinity profile in a panel of screens that was most similar to that of LSD itself. Both cis- and the (R,R)-trans-dimethylazetidines gave lysergamides that were less potent in all relevant assays. The finding that the S,S-dimethylazetidine gave a lysergamide with pharmacology most similar to LSD indicates that the N,N-diethyl groups of LSD optimally bind when they are oriented in a conformation distinct from that observed in the solid state by X-ray crystallography. The incorporation of isomeric dialkylazetidines into other biologically active molecules may be a useful strategy to model the active conformations of dialkylamines and dialkylamides. (

Title: Hmmmm
Post by: foxy2 on September 06, 2002, 02:54:00 PM
I smell an interesting DET analog.
Indole-ethylbromide plus 2,4-dimethylazetidine.

Only thing is those damn pyr-T experiences worry me a bit.

Those who give up essential liberties for temporary safety deserve neither liberty nor safety
Title: if rats could talk
Post by: zibarium on September 12, 2002, 05:27:00 PM
two-levered rat discrimination tests sound as if they might miss some of the more subjective aspects of a compound's attributes.

i wonder if these 'experienced rats' still prefer crack after a glimpse of the rat god-head?
Title: Nice, they use the pyBOP coupling reagent, which ...
Post by: Cyrax on September 12, 2002, 06:48:00 PM
Nice, they use the pyBOP coupling reagent, which is frequently used in peptide chemistry to couple amino acids.

pyBOP reacts with the acid to give an acyloxyphosphonium salt and the amine reacts with this intermediate to give the end product.

As a side note, pyBOP is used in place of BOP, since BOP yields the carcinogenic HMPT as a side product.

Those phosphonium coupling reagentia give better yields than DCC (dicyclohexylcarbodiimide).
Title: Ok but...
Post by: neuromodulator on September 23, 2002, 02:51:00 AM
Could you draw some structures for what ole St. Nick is up to?  Those words were German to me.  Furthermore, is LSD 025 (T26) not potent enough as it is.  I'll stick with ETH-LAD.
Title: Click the link in my post for a structuran ...
Post by: Rhodium on September 23, 2002, 06:39:00 AM
Click the link in my post for a structural formula.
Title: Dave Nichols' Essays from the Heffter Review
Post by: Rhodium on October 21, 2004, 07:23:00 AM
LSD and Its Lysergamide Cousins
David E. Nichols

The Heffter Review of Psychedelic Research, Vol. 2, pp. 80-87 (2001) (

____ ___ __ _

The Medicinal Chemistry of Phenethylamine Psychedelics
David E. Nichols

The Heffter Review of Psychedelic Research, Vol. 1, pp. 40-45 (1998) (