RTIOX-276

RTIOX-276

Identifiers
IUPAC name 2-(1-(3,4-dimethoxybenzyl)-6-methoxy-7-(2,2,2-trifluoroethoxy)-3,4-dihydroisoquinolin-2(1H)-yl)-N-(pyridin-3-ylmethyl)acetamide
CAS Number	1451412-34-2  Y
PubChem CID	73294135
ChemSpider	30820110
ChEMBL	ChEMBL2418834
CompTox Dashboard (EPA)	DTXSID201336763
Chemical and physical data
Formula	C29H32F3N3O5
Molar mass	559.586 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C(NCC1=CC=CN=C1)CN2C(CC3=CC(OC)=C(OC)C=C3)C4=CC(OCC(F)(F)F)=C(OC)C=C4CC2
InChI InChI=1S/C29H32F3N3O5/c1-37-24-7-6-19(12-25(24)38-2)11-23-22-14-27(40-18-29(30,31)32)26(39-3)13-21(22)8-10-35(23)17-28(36)34-16-20-5-4-9-33-15-20/h4-7,9,12-15,23H,8,10-11,16-18H2,1-3H3,(H,34,36) Key:KFNSZWWIIUHELF-UHFFFAOYSA-N

RTIOX-276 is an orexin antagonist. RTIOX-276 binds selectively to the orexin 1 receptor (K_E = 8.5nM) and lacks significant affinity for the orexin 2 receptor (K_E = > 10,000nM). RTIOX-276 may have therapeutic utility for the treatment of cocaine addiction. In conditioned place preference studies, RTIOX-276 attenuated the development of place preference in mice exposed to cocaine. ^{[1] [2] [3]}

References

1. Perrey DA, German NA, Gilmour BP, Li JX, Harris DL, Thomas BF, Zhang Y (September 2013). "Substituted tetrahydroisoquinolines as selective antagonists for the orexin 1 receptor". Journal of Medicinal Chemistry. 56 (17): 6901–16. doi:10.1021/jm400720h. PMC   3849818 . PMID   23941044.
2. Perrey DA, Decker AM, Li JX, Gilmour BP, Thomas BF, Harris DL, et al. (September 2015). "The importance of the 6- and 7-positions of tetrahydroisoquinolines as selective antagonists for the orexin 1 receptor". Bioorganic & Medicinal Chemistry. 23 (17): 5709–24. doi:10.1016/j.bmc.2015.07.013. PMC   4554834 . PMID   26216017.
3. Perrey DA, German NA, Decker AM, Thorn D, Li JX, Gilmour BP, et al. (April 2015). "Effect of 1-substitution on tetrahydroisoquinolines as selective antagonists for the orexin-1 receptor". ACS Chemical Neuroscience. 6 (4): 599–614. doi:10.1021/cn500330v. PMC   4400266 . PMID   25643283.