Ocaperidone

Ocaperidone
Names
	Preferred IUPAC name 3-{2-[4-(6-Fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl}-2,9-dimethyl-4H-pyrido[1,2-a]pyrimidin-4-one
Identifiers
CAS Number	129029-23-8 ;
3D model (JSmol)	Interactive image;
ChemSpider	64451;
IUPHAR/BPS	46;
KEGG	D02675;
MeSH	C072259
PubChem CID	71351;
UNII	26HUS7139V ;
CompTox Dashboard (EPA)	DTXSID10156042 ;
	InChI InChI=1S/C24H25FN4O2/c1-15-4-3-10-29-23(15)26-16(2)19(24(29)30)9-13-28-11-7-17(8-12-28)22-20-6-5-18(25)14-21(20)31-27-22/h3-6,10,14,17H,7-9,11-13H2,1-2H3 Key: ZZQNEJILGNNOEP-UHFFFAOYSA-N; InChI=1/C24H25FN4O2/c1-15-4-3-10-29-23(15)26-16(2)19(24(29)30)9-13-28-11-7-17(8-12-28)22-20-6-5-18(25)14-21(20)31-27-22/h3-6,10,14,17H,7-9,11-13H2,1-2H3 Key: ZZQNEJILGNNOEP-UHFFFAOYAT;
	SMILES CC1=CC=CN2C1=NC(=C(C2=O)CCN3CCC(CC3)C4=NOC5=C4C=CC(=C5)F)C;
Properties
Chemical formula	C24H25FN4O2
Molar mass	420.488 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Ocaperidone (R 79598) is a benzisoxazole antipsychotic.^[1] It was initially developed by Janssen, later licensed to French laboratory Neuro3D and then acquired in 2007 by German company Evotec. It was found to be more potent than risperidone in animal studies,^[2] but its testing was abandoned in 2010 after unfavorable results in human Phase II trials,^[3] as while it was effective at controlling symptoms of schizophrenia, ocaperidone produced an unacceptable amount of extrapyramidal side effects.^[4]

Synthesis

The last step requires attachment of the sidechain between 3-(2-bromoethyl)-2,9-dimethyl 4H-pyrido[1,2-a]pyrimidin-4-one (1) and 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2) completing the convergent synthesis of ocaperidone (3).

Patented method for the synthesis of ocaperidone^[5]

References

^ Leysen, JE; Janssen, PM; Gommeren, W; Wynants, J; Pauwels, PJ; Janssen, PA (1992). "In vitro and in vivo receptor binding and effects on monoamine turnover in rat brain regions of the novel antipsychotics risperidone and ocaperidone". Molecular Pharmacology. 41 (3): 494–508. PMID 1372084.
^ Megens AA, Awouters FH, Meert TF, Schellekens KH, Niemegeers CJ, Janssen PA. Pharmacological profile of the new potent neuroleptic ocaperidone (R 79,598). J Pharmacol Exp Ther. 1992 Jan;260(1):146-59. PMID 1370538
^ "Ocaperidone — AdisInsight". Adis Insight. Adis International Ltd, part of Springer Science+Business Media. Retrieved 10 December 2015.
^ Geerts, Hugo; Spiros, Athan; Roberts, Patrick; Twyman, Roy; Alphs, Larry; Grace, Anthony A. (2012). "Blinded Prospective Evaluation of Computer-Based Mechanistic Schizophrenia Disease Model for Predicting Drug Response". PLOS ONE. 7 (12): e49732. Bibcode:2012PLoSO...749732G. doi:10.1371/journal.pone.0049732. PMC 3522663. PMID 23251349.
^ Ludo E. J. Kennis, Jan Vandenberk, & Albertus H. M. T. Van Heertum, U.S. patent 5,482,943 (1996 to Janssen Pharmaceutica NV).

[1] Leysen, JE; Janssen, PM; Gommeren, W; Wynants, J; Pauwels, PJ; Janssen, PA (1992). "In vitro and in vivo receptor binding and effects on monoamine turnover in rat brain regions of the novel antipsychotics risperidone and ocaperidone". Molecular Pharmacology. 41 (3): 494–508. PMID 1372084.

[2] Megens AA, Awouters FH, Meert TF, Schellekens KH, Niemegeers CJ, Janssen PA. Pharmacological profile of the new potent neuroleptic ocaperidone (R 79,598). J Pharmacol Exp Ther. 1992 Jan;260(1):146-59. PMID 1370538

[3] "Ocaperidone — AdisInsight". Adis Insight. Adis International Ltd, part of Springer Science+Business Media. Retrieved 10 December 2015.

[4] Geerts, Hugo; Spiros, Athan; Roberts, Patrick; Twyman, Roy; Alphs, Larry; Grace, Anthony A. (2012). "Blinded Prospective Evaluation of Computer-Based Mechanistic Schizophrenia Disease Model for Predicting Drug Response". PLOS ONE. 7 (12): e49732. Bibcode:2012PLoSO...749732G. doi:10.1371/journal.pone.0049732. PMC 3522663. PMID 23251349.

[5] Ludo E. J. Kennis, Jan Vandenberk, & Albertus H. M. T. Van Heertum, U.S. patent 5,482,943 (1996 to Janssen Pharmaceutica NV).

[1]

[2]

[3]

[4]

[5]

Ocaperidone

Synthesis

See also

References