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McN-5558
Identifiers
  • (6S,10bR)-6-[3-(trifluoromethyl)phenyl]-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinoline
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
FormulaC19H18F3N
Molar mass317.355 g·mol−1
3D model (JSmol)
  • C1C[C@@H]2C3=CC=CC=C3[C@@H](CN2C1)C4=CC(=CC=C4)C(F)(F)F
  • InChI=1S/C19H18F3N/c20-19(21,22)14-6-3-5-13(11-14)17-12-23-10-4-9-18(23)16-8-2-1-7-15(16)17/h1-3,5-8,11,17-18H,4,9-10,12H2/t17-,18+/m0/s1
  • Key:LWXKKDYZAXBAPH-ZWKOTPCHSA-N

McN-5558 is a drug which acts as a selective noradrenaline reuptake inhibitor. It was investigated for potential application as an antidepressant, but was never developed for clinical use.[1][2]

Pharmacology

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McN-5558 is described as a serotonin–norepinephrine reuptake inhibitor (SNRI) with equilibrium constants (Kis) for various neurotransmitter transporters:[2]

Compound 37b norepinephrine transporter
(NE) 		dopamine transporter
(DAT) 		serotonin transporter
(SERT)
racemic 1.0 54.3 23.0
(+) 1.5 25.7 9.1
(-) 2570 7690 2920

These data show that virtually all of the binding affinities resides in a single enantiomer. Consequently, the compound displays a very high eudysmic ratio.

SAR

[edit]

In terms of the SAR, the meta-trifluorophenyl group was seen for fenfluramine, Benfluorex, and Ethyltrifluoromethylaminoindane.[3][4][5] These are anorexigenic agents for the treatment of obesity and eating disorders.

See also

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References

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  1. ^ Maryanoff BE, McComsey DF, Gardocki JF, Shank RP, Costanzo MJ, Nortey SO, et al. (August 1987). "Pyrroloisoquinoline antidepressants. 2. In-depth exploration of structure-activity relationships". Journal of Medicinal Chemistry. 30 (8): 1433–1454. doi:10.1021/jm00391a028. PMID 3039136.
  2. ^ a b Frazee WJ, Ohnmacht CJ, Malick JB (1985). Chapter 4. Antidepressants. Annual Reports in Medicinal Chemistry. Vol. 20. Elsevier. pp. 31–40. doi:10.1016/S0065-7743(08)61030-1. ISBN 978-0-12-040520-6.
  3. ^ Cozzi NV, Frescas S, Marona-Lewicka D, Huang X, Nichols DE (March 1998). "Indan analogs of fenfluramine and norfenfluramine have reduced neurotoxic potential". Pharmacology, Biochemistry, and Behavior. 59 (3): 709–715. doi:10.1016/s0091-3057(97)00557-1. PMID 9512076.
  4. ^ "2-[1-Methyl-4-[3-(trifluoromethyl)phenyl]piperidin-4-yl]propan-2-ol". PubChem. U.S. National Library of Medicine. CID 13363402.
  5. ^ US 4485109, Ciganek E, "4-Aryl-4-piperidinecarbinols", issued 27 November 1984, assigned to Bristol Myers Squibb Pharma Co. 
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