Facinicline

Facinicline
Names
	IUPAC name N-[(3S)-1-Azabicyclo[2.2.2]octan-3-yl]-1H-indazole-3-carboxamide
	Other names RG3487
Identifiers
CAS Number	677306-35-3; HCl: 677305-02-1;
3D model (JSmol)	Interactive image;
ChEMBL	ChEMBL2151439; HCl: ChEMBL5095032;
ChemSpider	8145949; HCl: 8555915;
PubChem CID	9970357; HCl: 10380472;
UNII	6A6FX0J03K; HCl: O6J463N18M;
	InChI InChI=1S/C15H18N4O/c20-15(14-11-3-1-2-4-12(11)17-18-14)16-13-9-19-7-5-10(13)6-8-19/h1-4,10,13H,5-9H2,(H,16,20)(H,17,18)/t13-/m1/s1 Key: TXCYUSKWBHUVEP-CYBMUJFWSA-N;
	SMILES C1CN2CCC1[C@@H](C2)NC(=O)C3=NNC4=CC=CC=C43;
Properties
Chemical formula	C15H18N4O
Molar mass	270.336 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

Facinicline (development code RG3487) is a α7 nicotinic acetylcholine receptor partial agonist and antagonist to serotonin-3 receptors (5-HT₃). It demonstrated initial efficacy for treating cognitive impairment in Alzheimer's disease in a phase 2a trial, but development was discontinued following the conclusion of a later phase 2 trial.^[1]

A later study evaluating the effects of facinicline on cognitive deficits in schizophrenia failed to demonstrate an effect on its primary endpoints, although post-hoc analysis showed improvements in patients with high negative PANSS scores.^[1]^[2]

Pharmacology

Facinicline is an a7 nicotinic partial agonist and 5-HT₃ antagonist.^[3]^[4] Facinicline shares much of its structure with tropesitron, another α7 and 5HT3 agonist/antagonist.

References

1 2 "RG3487". www.alzforum.org. Retrieved 2023-12-23.
↑ Umbricht, Daniel; Keefe, Richard S. E.; Murray, Stephen; Lowe, David A.; Porter, Richard; Garibaldi, George; Santarelli, Luca (June 2014). "A randomized, placebo-controlled study investigating the nicotinic α7 agonist, RG3487, for cognitive deficits in schizophrenia". Neuropsychopharmacology. 39 (7): 1568–1577. doi:10.1038/npp.2014.17. ISSN 1740-634X. PMC 4023143. PMID 24549101.
↑ Terry Jr., Alvin V.; Callahan, Patrick M.; Hernandez, Caterina M. (2015-10-15). "Nicotinic ligands as multifunctional agents for the treatment of neuropsychiatric disorders". Biochemical Pharmacology. Nicotinic Acetylcholine Receptors as Therapeutic Targets: Emerging Frontiers in Basic Research and Clinical Science (Satellite to the 2015 Meeting of the Society for Neuroscience) Oct 14-15, Chicago, IL USA. 97 (4): 388–398. doi:10.1016/j.bcp.2015.07.027. ISSN 0006-2952. PMC 4752163. PMID 26231940.
↑ Wallace, Tanya L.; Callahan, Patrick M.; Tehim, Ashok; Bertrand, Daniel; Tombaugh, Geoffrey; Wang, Shaojie; Xie, Walter; Rowe, Wayne B.; Ong, Voon; Graham, Elizabeth; Terry, Alvin V.; Rodefer, Joshua S.; Herbert, Brian; Murray, Michael; Porter, Richard (January 2011). "RG3487, a novel nicotinic α7 receptor partial agonist, improves cognition and sensorimotor gating in rodents". The Journal of Pharmacology and Experimental Therapeutics. 336 (1): 242–253. doi:10.1124/jpet.110.171892. ISSN 1521-0103. PMID 20959364.

[:0-1] 1 2 "RG3487". www.alzforum.org. Retrieved 2023-12-23.

[2] Umbricht, Daniel; Keefe, Richard S. E.; Murray, Stephen; Lowe, David A.; Porter, Richard; Garibaldi, George; Santarelli, Luca (June 2014). "A randomized, placebo-controlled study investigating the nicotinic α7 agonist, RG3487, for cognitive deficits in schizophrenia". Neuropsychopharmacology. 39 (7): 1568–1577. doi:10.1038/npp.2014.17. ISSN 1740-634X. PMC 4023143. PMID 24549101.

[3] Terry Jr., Alvin V.; Callahan, Patrick M.; Hernandez, Caterina M. (2015-10-15). "Nicotinic ligands as multifunctional agents for the treatment of neuropsychiatric disorders". Biochemical Pharmacology. Nicotinic Acetylcholine Receptors as Therapeutic Targets: Emerging Frontiers in Basic Research and Clinical Science (Satellite to the 2015 Meeting of the Society for Neuroscience) Oct 14-15, Chicago, IL USA. 97 (4): 388–398. doi:10.1016/j.bcp.2015.07.027. ISSN 0006-2952. PMC 4752163. PMID 26231940.

[4] Wallace, Tanya L.; Callahan, Patrick M.; Tehim, Ashok; Bertrand, Daniel; Tombaugh, Geoffrey; Wang, Shaojie; Xie, Walter; Rowe, Wayne B.; Ong, Voon; Graham, Elizabeth; Terry, Alvin V.; Rodefer, Joshua S.; Herbert, Brian; Murray, Michael; Porter, Richard (January 2011). "RG3487, a novel nicotinic α7 receptor partial agonist, improves cognition and sensorimotor gating in rodents". The Journal of Pharmacology and Experimental Therapeutics. 336 (1): 242–253. doi:10.1124/jpet.110.171892. ISSN 1521-0103. PMID 20959364.

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