McN-4612
McN-4612 is a noradrenaline preferring SNDRI developed by McNeil Laboratories in the 1980’s.
Pharmacology
The Ki digits are reported to be the following :| Compound | NE | DA | 5-HT |
| racemic | 0.6 | 11.3 | 23.5 |
| McN 4612-z | 0.37 | 4.4 | 12.4 |
| McN-4612-Y | 411 | 1345 | 4009 |
As can be seen nearly all of the Ki activity resides in a single optical antipode. Hence, there is a good eudysmic ratio
While McN-4612-Y does not function as a positive reinforcer, according to the reference it might possibly have utility as an antipsychotic. It appears alongside a compound called McN-4171, which is an analog of butaclamol.
Self-administration studies
Although McN-4612 was never publically taken by humans, the self-administration by rats is reported in the literature.Analogs
McN-4612 is the lead compound in a series of agents and the antecedent to such agents as McN5652, McN 5707, JNJ-7925476, Mcn-5292, McN-5558, McN-5908 or McN-5847 for example. The SAR can be manipulated to place particular emphasis on catecholaminergic neurotransmission or to incorporate 5-HT into the pharmacophore. Some of these compounds are tremendously powerful agents. At the time of discovery, McN-5908 was the most powerful psychostimulant ever discovered, although it was claimed that it was also quite toxic. Only a few of the phenyltropanes are believed to have potencies that can rival this agent.Synthesis
A number of methods are available to synthesizing these agents in the appendant literature.The first scheme relies on 2,2-Diphenylethylamine, which itself is the product of the reduction of diphenylacetonitrile.
However, the 2-phenylpyrrolidine route is also attractive. Recently, an enantiomerically selective method was reported using this method of synthesis. It is worth noting that this compound is itself made from 4-Chlorobutyronitrile.