SKF-64139

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SKF-64139
Clinical data
Other namesSK&F 64139, DCTQ.
Identifiers
  • 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
Chemical and physical data
FormulaC9H9Cl2N
Molar mass202.08 g·mol−1
3D model (JSmol)
  • C1CNCC2=C1C=CC(=C2Cl)Cl
  • InChI=1S/C9H9Cl2N/c10-8-2-1-6-3-4-12-5-7(6)9(8)11/h1-2,12H,3-5H2
  • Key:WFPUBEDBBOGGIQ-UHFFFAOYSA-N

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

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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

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References

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  1. ^ Park DH, Ruggiero DA, Anwar M, Joh TH (January 1988). "Possible mechanism of action of SKF 64139 in vivo on rat adrenal and brain phenylethanolamine N-methyltransferase activity". Biochemical Pharmacology. 37 (2): 313–318. doi:10.1016/0006-2952(88)90734-4. PMID 3342087.
  2. ^ Mefford IN, Roth KA, Gilberg M, Barchas JD (March 1981). "In vivo intraneuronal MAO inhibition in rat brain SKF 64139, comparison to other potent PNMT inhibitors". European Journal of Pharmacology. 70 (3): 345–353. doi:10.1016/0014-2999(81)90168-0. PMID 7227455.
  3. ^ Drew GM (March 1981). "α2-adrenoceptor-blocking action of the phenylethanolamine-N-methyltransferase inhibitor SKF 64139". The Journal of Pharmacy and Pharmacology. 33 (3): 187–188. doi:10.1111/j.2042-7158.1981.tb13750.x. PMID 6116766.
  4. ^ Goldstein M, Kinguasa K, Hieble JP, Pendleton RG (June 1982). "Lowering of blood pressure in hypertensive rats by SKF 64139 and SKF 72223". Life Sciences. 30 (23): 1951–1957. doi:10.1016/0024-3205(82)90433-7. PMID 6125862.
  5. ^ Bondinell WE, Chapin FW, Girard GR, Kaiser C, Krog AJ, Pavloff AM, et al. (May 1980). "Inhibitors of phenylethanolamine N-methyltransferase and epinephrine biosynthesis. 1. Chloro-substituted 1,2,3,4-tetrahydroisoquinolines". Journal of Medicinal Chemistry. 23 (5): 506–511. doi:10.1021/jm00179a007. PMID 7381849. Compound #13 Method A