SKF-64139

Last updated
SKF-64139
SKF 64139.svg
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
Formula C9H9Cl2N
Molar mass 202.08 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 tetrahydroisoquinoline (THIQ). It has pharmacology that is described as an inhibitor of phenylethanolamine N-methyltransferase (PNMT). [1] [2] Effects on serotonin (5-HT) and catecholamines is thought to stem from MAOI. [3]

Contents

Additionally, SKF-64139 is an alpha-2 blocker [4] that lowers the blood pressure in hypertensive rats. [5] SKF-64139 causes inhibition of guinea pig lordosis behavior. [6]

According to the patent, [7] the tablet strength is formulated to contain 150mg of the API.

Synthesis

SKF-64139 synthesis.svg

Synthesis (Compound #13 See Method A): [1] Patent: [7]

Pomeranz–Fritsch reaction between 2,3-dichlorobenzaldehyde [6334-18-5] (1) and aminoacetaldehyde dimethyl acetal [22483-09-6] (2) gives [57987-75-4] (3). Treatment with acid leads to 7,8-dichloroisoquinoline [61563-36-8] (4). Catalytic hydrogenation completes the synthesis of SKF-64139 (5).

See also

References

  1. 1 2 Bondinell, W. E., Chapin, F. W., Girard, G. R., Kaiser, C., Krog, A. J., Pavloff, A. M., Schwartz, M. S., Silvestri, J. S., Vaidya, P. D. (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.
  2. ↑ Park, D. H., Ruggiero, D. A., Anwar, M., Joh, T. H. (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.
  3. ↑ Mefford, I. N., Roth, K. A., Gilberg, M., Barchas, J. D. (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.
  4. ↑ Drew, G. M. (1 September 1981). "α2-Adrenoceptor-blocking action of the phenylethanolamine- N -methyltransferase inhibitor SKF 64139". Journal of Pharmacy and Pharmacology. 33 (1): 187–188. doi:10.1111/j.2042-7158.1981.tb13750.x. PMID   6116766.
  5. ↑ Goldstein, M., Kinguasa, K., Hieble, J. P., Pendleton, R. G. (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.
  6. ↑ Feder, H. H., Crowley, W. R., Nock, B. (March 1989). "Inhibition of guinea pig lordosis behavior by the phenylethanolamine N-methyltransferase (PNMT) inhibitor SKF-64139: Mediation by α noradrenergic receptors". Hormones and Behavior. 23 (1): 106–117. doi:10.1016/0018-506X(89)90078-0. PMID   2538388.
  7. 1 2 Carl Kaiser & Robert G. Pendleton, U.S. patent 3,988,339 (1976 to SmithKline Beecham Corp).
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