The first scheme relies on [[2,2-Diphenylethylamine]] [3963-62-0], which itself is the product of the reduction of [[diphenylacetonitrile]].
The first scheme relies on [[2,2-Diphenylethylamine]] [3963-62-0], which itself is the product of the reduction of [[diphenylacetonitrile]].
However, the [[2-phenylpyrrolidine]] [1006-64-0] route is also attractive. Recently, an enantiomerically selective method of synthesis was reported using this method of synthesis.<ref>{{cite journal | vauthors=((Zhang, Y.)), ((Kong, D.)), ((Wang, R.)), ((Hou, G.)) | journal=Organic & Biomolecular Chemistry | title=Synthesis of chiral cyclic amines via Ir-catalyzed enantioselective hydrogenation of cyclic imines | volume=15 | issue=14 | pages=3006–3012 | date= 2017 | url=https://xlink.rsc.org/?DOI=C7OB00442G | doi=10.1039/C7OB00442G}}</ref>
However, the [[2-phenylpyrrolidine]] [1006-64-0] route is also attractive. Recently, an enantiomerically selective method was reported using this method of synthesis.<ref>{{cite journal | vauthors=((Zhang, Y.)), ((Kong, D.)), ((Wang, R.)), ((Hou, G.)) | journal=Organic & Biomolecular Chemistry | title=Synthesis of chiral cyclic amines via Ir-catalyzed enantioselective hydrogenation of cyclic imines | volume=15 | issue=14 | pages=3006–3012 | date= 2017 | url=https://xlink.rsc.org/?DOI=C7OB00442G | doi=10.1039/C7OB00442G}}</ref>
== References ==
== References ==
{{reflist}}
{{reflist}}
 |
This is a draft Articles for creation (AfC) submission. It is not currently pending review. While there are no deadlines, abandoned drafts may be deleted after six months. To edit the draft click on the “Edit” tab at the top of the window. To be accepted, a draft should: It is strongly discouraged to write about either yourself or your business or employer. If you do so, you must declare it. Where to get help
Improving your odds of a speedy review To improve your odds of a faster review, tag your draft with relevant WikiProject tags using the button below. This will let reviewers know a new draft has been submitted in their area of interest. For instance, if you wrote about a female astronomer, you would want to add the Biography, Astronomy, and Women scientists tags. |
 |
|
| Other names | Mcn 4612 |
|---|---|
|
|
| CAS Number | |
| PubChem CID | |
| ChemSpider | |
| Formula | C18H19N |
| Molar mass | 249.357 g·mol−1 |
| 3D model (JSmol) | |
|
|
|
|
McN-4612 is a noradrenaline preferring SNDRI (aka TRI) developed by McNeil Laboratories in the 1980’s. [1]
The Ki digits that are reported for the racemic drug are the following: NE=0.6nM, DA=11.3nM & 5-HT=23.5nM. However mostly all of the activity resides in one of the optical antipodes. The Ki values for McN 4612-z are the following: NE=0.37nM, DA=4.4nM & 5-HT=12.4nM. The opposite enantiomer is called McN-4612-Y. [2] These are the Ki digits for McN-4612-Y: NA=411nM, DA=1345nM & 5-HT=4009nM. While McN-4612-Y does not behave as a positive reinforcer, according to the reference it might possibly have utility as an antipsychotic.[2]
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 psychostimulants or to incorporate 5-HT into the pharmacophore. Some of these compounds are tremendously powerful agents.
Synthesis
A number of methods are available to synthesizing these agents in the appendant literature.
The first scheme relies on 2,2-Diphenylethylamine [3963-62-0], which itself is the product of the reduction of diphenylacetonitrile.
However, the 2-phenylpyrrolidine [1006-64-0] route is also attractive. Recently, an enantiomerically selective method was reported using this method of synthesis.[3]
References
- ^ Maryanoff BE, McComsey DF, Castanzo MJ, Setler PE, Gardocki JF, Shank RP, Schneider CR (August 1984). “Pyrroloisoquinoline antidepressants. Potent, enantioselective inhibition of tetrabenazine-induced ptosis and neuronal uptake of norepinephrine, dopamine, and serotonin”. Journal of Medicinal Chemistry. 27 (8): 943–6. doi:10.1021/jm00374a001. PMID 6747993.
- ^ a b Chrzanowski, F. A., McGrogan, B. A., Maryanoff, B. E. (March 1985). “The pKa of butaclamol and the mode of butaclamol binding to central dopamine receptors”. Journal of Medicinal Chemistry. 28 (3): 399–400. doi:10.1021/jm00381a022.
- ^ Zhang, Y., Kong, D., Wang, R., Hou, G. (2017). “Synthesis of chiral cyclic amines via Ir-catalyzed enantioselective hydrogenation of cyclic imines”. Organic & Biomolecular Chemistry. 15 (14): 3006–3012. doi:10.1039/C7OB00442G.
