Clotiapine

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Clotiapine
Systematic (IUPAC) name
8-chloro-6-(4-methylpiperazin-1-yl)benzo[b][1,5]benzothiazepine
Clinical data
Trade names Etumina, Etumine, Entumin, Etomine, Entumine
AHFS/Drugs.com International Drug Names
Legal status Prescription only
Routes Oral, Intravenous and Intramuscular
Identifiers
CAS number 2058-52-8 N
ATC code N05AH06
PubChem CID 16351
ChemSpider 15510 YesY
UNII Z05HCY0X1T YesY
KEGG D01597 YesY
ChEMBL CHEMBL304902 YesY
Chemical data
Formula C18H18ClN3S 
Mol. mass 343.87 g/mol
 N (what is this?)  (verify)

Clotiapine (Entumine) is an atypical antipsychotic[1] of the dibenzothiazepine chemical class.[2] It was first introduced in a few European countries (namely, Belgium, Italy, Spain and Switzerland), Argentina, Taiwan and Israel in 1970.[3]

Some sources regard clotiapine as a typical antipsychotic rather than atypical due to its high incidence of extrapyramidal side effects compared to the atypicals like clozapine and quetiapine, to which it is structurally related.[4] Despite its profile of a relatively high incidence of extrapyramidal side effects it has demonstrated efficacy in treatment-resistant schizophrenic patients according to a number of psychiatrists with clinical experience with it, some weak clinical evidence supports this view too.[4][5][3]


Synthesis[edit]

Ullmann condensation of the substituted thiosalyciclic acid () with ortho-chloronitrobenzene results in the displacement of chlorine by thiophenoxide and the formation of the thioether (). The nitro group in this last intermediate is then reduced to an aniline (); the resulting amino acid is then cyclized thermally to the lactam (). Treatment of that with phosphorus oxychloride gives the imino chloride (). Reaction with N-methylpiperazine leads to the replacement of chlorine by nitrogen and the formation of clothiapine ().[2]

Clothiapine production.png

References[edit]

  1. ^ Seminara, G.; Trassari, V.; Prestifilippo, N.; Chiavetta, R.; Calandra, C. (1993). "Atypical tricyclic neuroleptics for treatment of schizophrenia. Clothiapine and clozapine". Minerva psichiatrica 34 (2): 95–99. PMID 8105359.  edit
  2. ^ a b Schmutz, J.; Künzle, F.; Hunziker, F.; Gauch, R. (1967). "Über in 11-Stellung amino-substituierte Dibenzo[b,f]-1, 4-thiazepine und -oxazepine. 9. Mitteilung über siebengliedrige Heterocyclen". Helvetica Chimica Acta 50: 245. doi:10.1002/hlca.19670500131.  edit
  3. ^ a b Lokshin, P; Kotler, M; Belmaker, RH (September 1997). "Clotiapine: Another forgotten treasure in psychiatry?". European Neuropsychopharmacology 7 (Suppl 2): S217. doi:10.1016/S0924-977X(97)88712-3. 
  4. ^ a b Geller, V; Gorzaltsan, I; Shleifer, T; Belmaker, RH; Bersudsky, Y (December 2005). "Clotiapine compared with chlorpromazine in chronic schizophrenia". Schizophrenia Research 80 (2-3): 343–347. doi:10.1016/j.schres.2005.07.007. PMID 16126373. 
  5. ^ Van Wyk, AJ; Marais, GF (August 1971). "chlorpromazine, clotiapine and thioridazine--a comparative clinical trial on Bantu psychotic patients" (PDF). South African Medical Journal 45 (34): 945–947. PMID 4939661.