Orvepitant

Orvepitant (GW823296) is a drug developed by GlaxoSmithKline which acts as a selective antagonist for the NK₁ receptor.[1] It was under development as a potential antidepressant drug, and early stage human clinical trials showed it to have some antidepressant effects, though not with sufficient efficacy to justify further development for this application. It was however considered a successful proof of concept for NK₁ antagonists as potential antidepressants, and efforts are continuing to find more potent compounds which might be more effective.[2]

Orvepitant

Clinical data
ATC code	none
Identifiers
IUPAC name (2R,4S)-4-[(8aS)-6-oxo-1,3,4,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-2-yl]-N-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]-2-(4-fluoro-2-methylphenyl)-N-methylpiperidine-1-carboxamide
CAS Number	579475-18-6
PubChem CID	9852175
ChemSpider	8027888
UNII	IIU6V0W3JD
CompTox Dashboard (EPA)	DTXSID40973522
Chemical and physical data
Formula	C31H35F7N4O2
Molar mass	628.636 g·mol^−1
3D model (JSmol)	Interactive image
SMILES CC1=C(C=CC(=C1)F)[C@H]2C[C@H](CCN2C(=O)N(C)[C@H](C)C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)N4CCN5[C@H](C4)CCC5=O
InChI InChI=1S/C31H35F7N4O2/c1-18-12-23(32)4-6-26(18)27-16-24(40-10-11-41-25(17-40)5-7-28(41)43)8-9-42(27)29(44)39(3)19(2)20-13-21(30(33,34)35)15-22(14-20)31(36,37)38/h4,6,12-15,19,24-25,27H,5,7-11,16-17H2,1-3H3/t19-,24+,25+,27-/m1/s1 Key:XWNBGDJPEXZSQM-VZOBGQTKSA-N

References

1. Di Fabio R, Alvaro G, Braggio S, Carletti R, Gerrard PA, Griffante C, et al. (November 2013). "Identification, biological characterization and pharmacophoric analysis of a new potent and selective NK1 receptor antagonist clinical candidate". Bioorganic & Medicinal Chemistry. 21 (21): 6264–73. doi:10.1016/j.bmc.2013.09.001. PMID 24075145.
2. Ratti E, Bettica P, Alexander R, Archer G, Carpenter D, Evoniuk G, et al. (May 2013). "Full central neurokinin-1 receptor blockade is required for efficacy in depression: evidence from orvepitant clinical studies". Journal of Psychopharmacology. 27 (5): 424–34. doi:10.1177/0269881113480990. PMID 23539641.