Diclofensine

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Diclofensine
Diclofensine.svg
Clinical data
ATC code
  • None
Legal status
Legal status
  • In general: legal
Identifiers
  • 4-(3,4-dichlorophenyl)-7-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
Formula C17H17Cl2NO
Molar mass 322.23 g·mol−1
3D model (JSmol)
  • CN1CC(C2=C(C1)C=C(C=C2)OC)C3=CC(=C(C=C3)Cl)Cl
  • InChI=1S/C17H17Cl2NO/c1-20-9-12-7-13(21-2)4-5-14(12)15(10-20)11-3-6-16(18)17(19)8-11/h3-8,15H,9-10H2,1-2H3 X mark.svgN
  • Key:ZJDCGVDEEHWEIG-UHFFFAOYSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Diclofensine (Ro 8-4650) was developed by Hoffmann-La Roche in the 1970s [1] in the search for a new antidepressant. It was found that the (S)-isomer was responsible for activity. [2] Diclofensine is a stimulant drug which acts as a triple monoamine reuptake inhibitor, [3] [4] primarily inhibiting the reuptake of dopamine [5] and norepinephrine, [6] with affinities (Ki) of 16.8 nM, 15.7 nM, and 51 nM for DAT, NET, and SERT (dopamine, norepinephrine and serotonin transporters), respectively. [7] It was found to be an effective antidepressant in human trials, [8] [9] [10] with relatively few side effects, [11] but was ultimately dropped from clinical development, possibly due to concerns about its abuse potential. [12] [13]

Contents

Diclofensine is chemically a tetrahydroisoquinoline (THIQ) derivative, as is nomifensine.

Synthesis

Patents: Also: Diclofensine synthesis.svg
Patents: Also:

The condensation of m-anisaldehyde [591-31-1] (1) with methylamine gives N-methyl-3-methoxybenzenemethanimine [16928-30-6]. Reduction of this Schiff-base intermediate with sodium borohydride gives (3-methoxybenzyl)methylamine [41789-95-1] (2). Alkylation of this with 3,4-dichlorophenacylbromide [2632-10-2] (3) would give CID:59580342 (4). Reduction of the benzoyl ketone with sodium borohydride gives the alcohol [802051-24-7] (5). Acid catalyzed intramolecular cyclization then completes the synthesis of the 4-aryl-THIQ derivative, diclofensine (6).

See also

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References

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