Chemistry:SKF-64139
SKF-64139 is a synthetic tetrahydroisoquinoline (THIQ) derivative that functions as a potent and selective inhibitor of phenylethanolamine N-methyltransferase (PNMT), the enzyme that catalyzes the conversion of norepinephrine to epinephrine in both the adrenal medulla and the central nervous system. By lowering epinephrine levels through PNMT inhibition, SKF-64139 has been widely used as a research tool to study the physiological functions of epinephrine, particularly its roles in cardiovascular regulation and metabolic processes.[1]
This compound also exhibits additional actions, such as weak monoamine oxidase (MAO) inhibition at higher doses, which may contribute to broader neurochemical and hemodynamic effects.[2] Additionally, SKF-64139 is an alpha-2 blocker[3] that lowers the blood pressure in hypertensive rats.[4]
Synthesis
The isoquinoline core of SKF-64139 is prepared by a stepwise Pomeranz–Fritsch reaction, in which the benzaldehyde (1) and 2,2-dimethoxyethylamine (2) undergo condensation followed by cyclization:[5]
See also
- LY-134046
References
- ↑ "Possible mechanism of action of SKF 64139 in vivo on rat adrenal and brain phenylethanolamine N-methyltransferase activity". Biochemical Pharmacology 37 (2): 313–318. January 1988. doi:10.1016/0006-2952(88)90734-4. PMID 3342087.
- ↑ "In vivo intraneuronal MAO inhibition in rat brain SKF 64139, comparison to other potent PNMT inhibitors". European Journal of Pharmacology 70 (3): 345–353. March 1981. doi:10.1016/0014-2999(81)90168-0. PMID 7227455.
- ↑ "α2-adrenoceptor-blocking action of the phenylethanolamine-N-methyltransferase inhibitor SKF 64139". The Journal of Pharmacy and Pharmacology 33 (3): 187–188. March 1981. doi:10.1111/j.2042-7158.1981.tb13750.x. PMID 6116766.
- ↑ "Lowering of blood pressure in hypertensive rats by SKF 64139 and SKF 72223". Life Sciences 30 (23): 1951–1957. June 1982. doi:10.1016/0024-3205(82)90433-7. PMID 6125862.
- ↑ "Inhibitors of phenylethanolamine N-methyltransferase and epinephrine biosynthesis. 1. Chloro-substituted 1,2,3,4-tetrahydroisoquinolines". Journal of Medicinal Chemistry 23 (5): 506–511. May 1980. doi:10.1021/jm00179a007. PMID 7381849. "Compound #13 Method A".
 |  |
