Mosapramine

Mosapramine (Cremin) is an atypical antipsychotic used in Japan for the treatment of schizophrenia.[1][2] It is a potent dopamine antagonist with high affinity to the D2, D3, and D4 receptors,[3] and with moderate affinity for the 5-HT2 receptors.[4]

Mosapramine
Clinical data
Trade namesCremin (クレミン, JP)
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral (tablets, oral solution)
ATC code
Legal status
Legal status
  • Rx-only (JP)
Identifiers
IUPAC name
  • 1'-[3-(2-chloro-5,6-dihydrobenzo[b][1]benzazepin-11-yl)propyl]spiro[1,5,6,7,8,8a-hexahydroimidazo[1,2-a]pyridine-3,4'-piperidine]-2-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC28H35ClN4O
Molar mass479.07 g·mol−1
3D model (JSmol)
SMILES
  • C1CCN2C(C1)NC(=O)C23CCN(CC3)CCCN4C5=CC=CC=C5CCC6=C4C=C(C=C6)Cl
InChI
  • InChI=1S/C28H35ClN4O/c29-23-12-11-22-10-9-21-6-1-2-7-24(21)32(25(22)20-23)16-5-15-31-18-13-28(14-19-31)27(34)30-26-8-3-4-17-33(26)28/h1-2,6-7,11-12,20,26H,3-5,8-10,13-19H2,(H,30,34)
  • Key:PXUIZULXJVRBPC-UHFFFAOYSA-N
  (verify)

Synthesis

Note that if the ring cylization step was missed you instead get Clocapramine.

Patents:[5][6]

The Strecker like condensation between 1-Benzyl-4-piperidone [3612-20-2] (1), piperidine, and potasssium cyanide gives 1-benzyl-4-piperidin-1-ylpiperidine-4-carbonitrile [84254-97-7] (2). Partial hydrolysis of the nitrile to the amide gives 1-benzyl-4-piperidin-1-ylpiperidine-4-carboxamide [1762-50-1] (3). Catalytic hydrogenation then removes the benzyl protecting group to give 4-piperidin-1-ylpiperidine-4-carboxamide [39633-82-4] (4). Treatment with a palladium on carbon catalyt apparently forms spiro[1,5,6,7,8,8a-hexahydroimidazo[1,2-a]pyridine-3,4'-piperidine]-2-one, CID:13002712 (5).

Convergent synthesis with 3-(2-chloro-5,6-dihydrobenzo[b][1]benzazepin-11-yl)propyl methanesulfonate, CID:20533966 (6) completed the synthesis of Mosapramine (7).

See also

References
  1. Takahashi N, Terao T, Oga T, Okada M (1999). "Comparison of risperidone and mosapramine addition to neuroleptic treatment in chronic schizophrenia". Neuropsychobiology. 39 (2): 81–5. doi:10.1159/000026565. PMID 10072664. S2CID 6554048.
  2. Miyamoto S (2010). "Mosapramine". In Stolerman IP (ed.). Encyclopedia of Psychopharmacology. Berlin, Heidelberg: Springer. p. 76. doi:10.1007/978-3-540-68706-1_1839. ISBN 978-3-540-68706-1. Retrieved 21 March 2022.
  3. Futamura T, Ohashi Y, Yano K, Takahashi Y, Haga K, Fukuda T (May 1996). "[The affinities of mosapramine for the dopamine receptor subtypes in human cell lines expressing D2, D3 and D4 receptors]". Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica. 107 (5): 247–53. doi:10.1254/fpj.107.247. PMID 8690306.
  4. Sumiyoshi T, Suzuki K, Sakamoto H, Yamaguchi N, Mori H, Shiba K, Yokogawa K (February 1995). "Atypicality of several antipsychotics on the basis of in vivo dopamine-D2 and serotonin-5HT2 receptor occupancy". Neuropsychopharmacology. 12 (1): 57–64. doi:10.1016/0893-133X(94)00064-7. PMID 7766287.
  5. Chiaki Tashiro & Ichiro Horii, EP 0073845 (1985 to Welfide Corp).
  6. Chiaki Tashiro & Ichiro Horii, U.S. Patent 4,337,260 (1982 to Mitsubishi Pharma Corp).
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