Molindone: Difference between revisions
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==Synthesis== |
==Synthesis== |
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[[File:Molindone synthesis.svg|thumb|center|555px|Molindone synthesis: SCHOEN KARL, J PACHTER IRWIN; {{Cite patent|BE|670798}} (1965 to Endo Lab).]] |
[[File:Molindone synthesis.svg|thumb|center|555px|Molindone synthesis: SCHOEN KARL, J PACHTER IRWIN; {{Cite patent|BE|670798}} (1965 to Endo Lab).]] |
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Condensation of oximinoketone '''2''' (from [[nitrosation]] of 3-pentanone), with [[1,3-Cyclohexanedione]] ('''1''') in the presenec of zinc and acetic acid leads directly to the partly reduced indole derivative '''6'''. The transformation may be rationalized by assuming as the first step, reduction of '''2''' to the corresponding α-aminoketone. [[Conjugate addition]] of the amine to '''1''' followed by elimination of hydroxide (as water) would give ene-aminoketone '''3'''. This enamine may be assumed to be in [[Tautomer|tautomeric equilibrium]] with imine '''4'''. [[Aldol condensation]] of the side chain carbonyl group with the doubly activated ring [[methylene]]{{dn}} would then result in cyclization to pyrrole '''5'''; simple tautomeric transformation would then give the observed product. [[Mannich reaction]] of '''6''' with formaldehyde and morpholine gives the tranquilizer molindone ('''7'''). |
Condensation of oximinoketone '''2''' (from [[nitrosation]] of 3-pentanone), with [[1,3-Cyclohexanedione]] ('''1''') in the presenec of zinc and acetic acid leads directly to the partly reduced indole derivative '''6'''. The transformation may be rationalized by assuming as the first step, reduction of '''2''' to the corresponding α-aminoketone. [[Conjugate addition]] of the amine to '''1''' followed by elimination of hydroxide (as water) would give ene-aminoketone '''3'''. This enamine may be assumed to be in [[Tautomer|tautomeric equilibrium]] with imine '''4'''. [[Aldol condensation]] of the side chain carbonyl group with the doubly activated ring [[methylene]]{{dn|date=August 2015}} would then result in cyclization to pyrrole '''5'''; simple tautomeric transformation would then give the observed product. [[Mannich reaction]] of '''6''' with formaldehyde and morpholine gives the tranquilizer molindone ('''7'''). |
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== See also == |
== See also == |
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Revision as of 14:26, 20 August 2015
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| Clinical data | |
|---|---|
| Trade names | Moban |
| AHFS/Drugs.com | Consumer Drug Information |
| MedlinePlus | a682238 |
| Pregnancy category |
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| Routes of administration | Oral |
| ATC code | |
| Legal status | |
| Legal status |
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| Pharmacokinetic data | |
| Metabolism | Hepatic |
| Elimination half-life | 1.5 hours |
| Excretion | Minor, renal and fecal |
| Identifiers | |
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| CAS Number | |
| PubChem CID | |
| IUPHAR/BPS | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.254.109 |
| Chemical and physical data | |
| Formula | C16H24N2O2 |
| Molar mass | 276.374 g/mol g·mol−1 |
| 3D model (JSmol) | |
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Molindone (Moban) is a therapeutic antipsychotic, used in the treatment of schizophrenia.[1] It works by blocking the effects of dopamine in the brain, leading to diminished psychoses. It is rapidly absorbed when taken orally.
It is sometimes described as a typical antipsychotic,[2] and sometimes described as an atypical antipsychotic.[3]
Molindone was discontinued by its sole supplier, Endo Pharmaceuticals, on January 13, 2010. [4]
Adverse effects
The side effect profile of molindone is similar to that of other typical antipsychotics. Unlike most antipsychotics, however, molindone use is associated with weight loss.[3][5]
Synthesis
Condensation of oximinoketone 2 (from nitrosation of 3-pentanone), with 1,3-Cyclohexanedione (1) in the presenec of zinc and acetic acid leads directly to the partly reduced indole derivative 6. The transformation may be rationalized by assuming as the first step, reduction of 2 to the corresponding α-aminoketone. Conjugate addition of the amine to 1 followed by elimination of hydroxide (as water) would give ene-aminoketone 3. This enamine may be assumed to be in tautomeric equilibrium with imine 4. Aldol condensation of the side chain carbonyl group with the doubly activated ring methylene[disambiguation needed] would then result in cyclization to pyrrole 5; simple tautomeric transformation would then give the observed product. Mannich reaction of 6 with formaldehyde and morpholine gives the tranquilizer molindone (7).
See also
References
- ^ "molindone". F.A. Davis Company.
- ^ Aparasu RR, Jano E, Johnson ML, Chen H (October 2008). "Hospitalization risk associated with typical and atypical antipsychotic use in community-dwelling elderly patients". Am J Geriatr Pharmacother. 6 (4): 198–204. doi:10.1016/j.amjopharm.2008.10.003. PMID 19028375.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b Bagnall A, Fenton M, Kleijnen J, Lewis R (2007). Bagnall, Anne-Marie (ed.). "Molindone for schizophrenia and severe mental illness". Cochrane Database Syst Rev (1): CD002083. doi:10.1002/14651858.CD002083.pub2. PMID 17253473.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm050794.htm
- ^ Allison DB; Mentore JL; Heo M; et al. (1999). "Antipsychotic-induced weight gain: a comprehensive research synthesis". Am J Psychiatry. 156 (11): 1686–96. PMID 10553730.
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