Diclofensine (Ro 8-4650) was developed by Hoffmann-La Roche in the 1970s in the search for a new antidepressant. It was found that the (''S'')-isomer was responsible for activity. Is a stimulant drug which acts as a triple monoamine reuptake inhibitor, primarily inhibiting the reuptake of dopamine and norepinephrine, with affinities ( K_i) of 16.8 nM, 15.7 nM, and 51 nM for DAT,

NET Net or net may refer to: Mathematics and physics * Net (mathematics), a filter-like topological generalization of a sequence * Net, a linear system of divisors of dimension 2 * Net (polyhedron), an arrangement of polygons that can be folded up ...

, and SERT (dopamine, norepinephrine and serotonin transporters), respectively. It was found to be an effective antidepressant in human trials, with relatively few side effects, but was ultimately dropped from clinical development, possibly due to concerns about its

abuse potential Substance abuse, also known as drug abuse, is the use of a drug in amounts or by methods which are harmful to the individual or others. It is a form of substance-related disorder. Differing definitions of drug abuse are used in public health, ...

. Diclofensine is chemically a

tetrahydroisoquinoline Tetrahydroisoquinoline (TIQ or THIQ) is an organic compound with the chemical formula C9H11N. Classified as a secondary amine, it is derived from isoquinoline by hydrogenation. It is a colorless viscous liquid that is miscible with most organic s ...

(THIQ) derivative, as is

nomifensine Nomifensine (Merital, Alival) is a norepinephrine-dopamine reuptake inhibitor, i.e. a drug that increases the amount of synaptic norepinephrine and dopamine available to receptors by blocking the dopamine and norepinephrine reuptake transporters ...

Synthesis

The condensation of m-anisaldehyde 91-31-1(1) with methylamine gives N-methyl-3-methoxybenzenemethanimine

6928-30-6 69 may refer to: * 69 (number) * A year, primarily 69 BC, AD 69, 1969, or 2069 * 69 (sex position) Arts and media Music * ''69'', a 1988 album by A.R. Kane * "'69", a song by Deep Purple from ''Abandon'' * Major 6 add 9, a jazz chord * "Summ ...

Reduction of this Schiff-base intermediate with sodium borohydride gives (3-methoxybenzyl)methylamine 1789-95-1(2). Alkylation of this with 3,4-dichlorophenacylbromide

632-10-2 63 may refer to: * 63 (number) * one of the years 63 BC, AD 63, 1963, 2063 * +63, telephone country code in the Philippines * Flight 63 (disambiguation) * ''63'' (album), by Tree63 * ''63'' (mixtape), by Kool A.D. * "Sixty Three", a song by Karm ...

(3) would giv
CID:59580342
(4). Reduction of the benzoyl ketone with

sodium borohydride Sodium borohydride, also known as sodium tetrahydridoborate and sodium tetrahydroborate, is an inorganic compound with the formula Na BH4. This white solid, usually encountered as an aqueous basic solution, is a reducing agent that finds applica ...

gives the alcohol 02051-24-7(5). Acid catalyzed intramolecular cyclization then completes the synthesis of the 4-aryl-THIQ derivative, diclofensine (6).

References

{{Monoamine reuptake inhibitors Chlorobenzenes Phenol ethers Tetrahydroisoquinolines Serotonin–norepinephrine–dopamine reuptake inhibitors Stimulants

Synthesis

See also

References