Diclofensine (Ro 8-4650) was developed by

Hoffmann-La Roche F. Hoffmann-La Roche AG, commonly known as Roche (), is a Swiss multinational holding healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on ...

in the 1970s in the search for a new antidepressant. It was found that the (''S'')-isomer was responsible for activity. Diclofensine is a

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

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 may refer to: Broadcast media United States * National Educational Television, the predecessor of the Public Broadcasting Service (PBS) in the United States * National Empowerment Television, a politically conservative cable TV network ...

, and SERT (dopamine, norepinephrine and serotonin transporters), respectively. It was found to be an effective

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

in human trials, with relatively few side effects, but was ultimately dropped from clinical development, possibly due to concerns about its

abuse potential Substance misuse, also known as drug misuse or, in older vernacular, substance abuse, is the use of a drug in amounts or by methods that are harmful to the individual or others. It is a form of substance-related disorder, differing definitions ...

. Diclofensine is chemically a

tetrahydroisoquinoline Tetrahydroisoquinoline (TIQ or THIQ), also known as AMPH-CR, 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 mis ...

(THIQ) derivative, as is

nomifensine Nomifensine, formerly sold under the brand names Merital and Alival, is a norepinephrine–dopamine reuptake inhibitor (NDRI) drug that was developed in the 1960s by Hoechst AG (now Sanofi-Aventis), who then test marketed it in the United States ...

Synthesis

The condensation of m-anisaldehyde 91-31-1(1) with methylamine gives N-methyl-3-methoxybenzenemethanimine 6928-30-6 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 (Las Vegas), a shopping mall * ''63'' (album), by Tree63 * ''63'' (mixtape), by Kool A. ...

(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 (sometimes written as ). It is a white crystalline solid, usually encountered as an aqueous basic solution. Sodi ...

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 Chlorobenzene derivatives Phenol ethers Tetrahydroisoquinolines Serotonin–norepinephrine–dopamine reuptake inhibitors Stimulants

Synthesis

See also

References