LY-78335
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| Other names | DCMB |
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| Formula | C8H9Cl2N |
| Molar mass | 190.07 g·mol−1 |
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LY-78335 (also known as 2,3-dichloro-α-methylbenzylamine, DCMB) is a high-affinity inhibitor of phenylethanolamine N-methyltransferase (PNMT). It has been shown to strongly suppress growth hormone release in vivo, making it a useful compound for laboratory research on neurotransmitter regulation and endocrinology.[1]
LY-78335 has also been investigated for its potential to reduce the intoxicating effects of alcohol. In animal studies, it produced several notable effects: (1) increased spontaneous motor activity in rats, (2) elevated extracellular concentrations of the norepinephrine metabolite MHPG in the hypothalamus as measured by microdialysis, and (3) blocked the stimulation of growth hormone secretion normally induced by clonidine. These findings suggest that LY-78335 inhibits α2-adrenoceptor function in vivo.[2][3]
In addition to its PNMT-inhibiting properties, LY-78335 has been reported to act as a reversible inhibitor of monoamine oxidase (RIMA).[4]
Synthesis
The synthesis of LY-78335 begins with a Kolbe nitrile synthesis performed on 1-bromo-2,3-dichlorobenzene (1), affording 2,3-dichlorobenzonitrile (2). Treatment of compound (2) with methylmagnesium halide converts the nitrile functional group into a ketone, yielding 2′,3′-dichloroacetophenone (3). Finally, a Leuckart reaction using a mixture of formamide and formic acid furnishes LY-78335 (4).[5]
See also
References
- ^ Fuller RW, Roush BW, Snoddy HD, Molloy BB (February 1973). "Inhibition of phenylethanolamine N-methyltransferase by benzylamines. 2. In vitro and in vivo studies with 2,3-dichloro-α-methylbenzylamine". Journal of Medicinal Chemistry. 16 (2): 106–109. doi:10.1021/jm00260a004. PMID 4683104.
- ^ Durcan MJ, Lister RG, Linnoila M (June 1990). "Behavioral effects of the inhibitors of phenylethanolamine-N-methyltransferase, LY 78335 and LY 134046, and their interactions with ethanol". Psychopharmacology. 101 (2): 196–202. doi:10.1007/BF02244126. PMID 2349361.
- ^ Kuboia M, Atobe M, Nakagawara M, Kariya T (1996). "Effect of a phenylethanolamine N-methyltransferase inhibitor, 2,3-dichloro-α-methylbenzylamine, on the alpha-2-adrenoceptor function in the hypothalamus in rats". Neuropsychobiology. 33 (3): 132–137. doi:10.1159/000119263. PMID 8776741.
- ^ Fuller RW, Hemrick SK (April 1978). "Steric influence on inhibition of monoamine oxidase forms by 2,3-dichloro-α-methylbenzylamine". Research Communications in Chemical Pathology and Pharmacology. 20 (1): 199–202. PMID 663404.
- ^ Fuller RW, Molloy BB, Day WA, Roush BW, Marsh MM (February 1973). "Inhibition of phenylethanolamine N-methyltransferase by benzylamines. 1. Structure–activity relationships". Journal of Medicinal Chemistry. 16 (2): 101–106. doi:10.1021/jm00260a003. PMID 4734201.