SB269652

SB269652
Clinical data
Other names	SB-269652; SB-269,652
Drug class	Dopamine D2 and D3 receptor negative allosteric modulator
Identifiers
	IUPAC name N-[4-[2-(7-cyano-3,4-dihydro-1H-isoquinolin-2-yl)ethyl]cyclohexyl]-1H-indole-2-carboxamide;
CAS Number	215802-15-6;
PubChem CID	9910352;
ChemSpider	26000574;
ChEMBL	ChEMBL2219578;
Chemical and physical data
Formula	C27H30N4O
Molar mass	426.564 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1CC(CCC1CCN2CCC3=C(C2)C=C(C=C3)C#N)NC(=O)C4=CC5=CC=CC=C5N4;
	InChI InChI=1S/C27H30N4O/c28-17-20-5-8-21-12-14-31(18-23(21)15-20)13-11-19-6-9-24(10-7-19)29-27(32)26-16-22-3-1-2-4-25(22)30-26/h1-5,8,15-16,19,24,30H,6-7,9-14,18H2,(H,29,32); Key:JGLGOAQPUQITLD-UHFFFAOYSA-N;

SB269652 is an experimental dopamine D₂ and D₃ receptor negative allosteric modulator.^[1]^[2] It is of interest in the potential development of novel antipsychotics for treatment of schizophrenia with reduced side effects, such as extrapyramidal symptoms.^[1]^[2] The drug is described as a dual orthosteric and allosteric (i.e., bitopic) modulator of the dopamine D₂ and D₃ receptors, as an atypical allosteric modulator of these receptors, and as specifically targeting D₂–D₃ receptor dimers.^[1]^[2] SB269652 was first described in the scientific literature by 1999.^[3]^[4] It was originally thought to act purely as an antagonist of the dopamine D₂ and D₃ receptors, but was serendipitously found to be a negative allosteric modulator of these receptors in 2010.^[1]^[2] It was the first dopamine D₂ and D₃ receptor negative allosteric modulator to be discovered.^[1] More potent analogues of SB269652 have been developed.^[2]^[5]

References

^ ^a ^b ^c ^d ^e Rossi M, Fasciani I, Marampon F, Maggio R, Scarselli M (June 2017). "The First Negative Allosteric Modulator for Dopamine D2 and D3 Receptors, SB269652 May Lead to a New Generation of Antipsychotic Drugs". Mol Pharmacol. 91 (6): 586–594. doi:10.1124/mol.116.107607. PMC 5438131. PMID 28265019.
^ ^a ^b ^c ^d ^e Fasciani I, Petragnano F, Aloisi G, Marampon F, Carli M, Scarselli M, Maggio R, Rossi M (November 2020). "Allosteric Modulators of G Protein-Coupled Dopamine and Serotonin Receptors: A New Class of Atypical Antipsychotics". Pharmaceuticals (Basel). 13 (11): 388. doi:10.3390/ph13110388. PMC 7696972. PMID 33202534.
^ Taylor, S. G., Riley, G., Hunter, A. J., Stemp, G., Routledge, C., Hagan, J. J., & Reavill, C. (1999). SB-269652 is a selective D3 receptor antagonist in vitro and in vivo. European Neuropsychopharmacology, (9), 266. https://scholar.google.com/scholar?cluster=9009628132294457655
^ Taylor, S. G., Riley, G., Hunter, A. J., Stemp, G., & Routledge, C. (1999). A selective dopamine D 3 receptor antagonist, SB-269652, shows functional selectivity for D 3 receptors in vivo. Monitoring molecules in neuroscience. SUNY at Stony Brook, New York, 254-255. https://scholar.google.com/scholar?cluster=7754123302347796269
^ Kopinathan A, Draper-Joyce C, Szabo M, Christopoulos A, Scammells PJ, Lane JR, Capuano B (January 2019). "Subtle Modifications to the Indole-2-carboxamide Motif of the Negative Allosteric Modulator N-(( trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1 H)-yl)ethyl)cyclohexyl)-1 H-indole-2-carboxamide (SB269652) Yield Dramatic Changes in Pharmacological Activity at the Dopamine D2 Receptor". J Med Chem. 62 (1): 371–377. doi:10.1021/acs.jmedchem.8b00192. PMID 29890071.

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[RossiFascianiMarampon2017-1] Rossi M, Fasciani I, Marampon F, Maggio R, Scarselli M (June 2017). "The First Negative Allosteric Modulator for Dopamine D2 and D3 Receptors, SB269652 May Lead to a New Generation of Antipsychotic Drugs". Mol Pharmacol. 91 (6): 586–594. doi:10.1124/mol.116.107607. PMC 5438131. PMID 28265019.

[FascianiPetragnanoAloisi2020-2] Fasciani I, Petragnano F, Aloisi G, Marampon F, Carli M, Scarselli M, Maggio R, Rossi M (November 2020). "Allosteric Modulators of G Protein-Coupled Dopamine and Serotonin Receptors: A New Class of Atypical Antipsychotics". Pharmaceuticals (Basel). 13 (11): 388. doi:10.3390/ph13110388. PMC 7696972. PMID 33202534.

[TaylorRileyHunter1999a-3] Taylor, S. G., Riley, G., Hunter, A. J., Stemp, G., Routledge, C., Hagan, J. J., & Reavill, C. (1999). SB-269652 is a selective D3 receptor antagonist in vitro and in vivo. European Neuropsychopharmacology, (9), 266. https://scholar.google.com/scholar?cluster=9009628132294457655

[TaylorRileyHunter1999b-4] Taylor, S. G., Riley, G., Hunter, A. J., Stemp, G., & Routledge, C. (1999). A selective dopamine D 3 receptor antagonist, SB-269652, shows functional selectivity for D 3 receptors in vivo. Monitoring molecules in neuroscience. SUNY at Stony Brook, New York, 254-255. https://scholar.google.com/scholar?cluster=7754123302347796269

[KopinathanDraper-JoyceSzabo2019-5] Kopinathan A, Draper-Joyce C, Szabo M, Christopoulos A, Scammells PJ, Lane JR, Capuano B (January 2019). "Subtle Modifications to the Indole-2-carboxamide Motif of the Negative Allosteric Modulator N-(( trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1 H)-yl)ethyl)cyclohexyl)-1 H-indole-2-carboxamide (SB269652) Yield Dramatic Changes in Pharmacological Activity at the Dopamine D2 Receptor". J Med Chem. 62 (1): 371–377. doi:10.1021/acs.jmedchem.8b00192. PMID 29890071.

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