RTIOX-276

{{Short description|Orexin antagonist}}

{{Drugbox

| verifiedrevid =

| 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

| image = RTIOX-276 Structure.svg

| width =

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| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 1451412-34-2

| PubChem = 73294135

| ChEMBL = 2418834

| ChemSpiderID = 30820110

| C=29 | H=32 | F=3 | N=3 | O=5

| StdInChI=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)

| StdInChIKey = KFNSZWWIIUHELF-UHFFFAOYSA-N

| 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

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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.{{cite journal | vauthors = Perrey DA, German NA, Gilmour BP, Li JX, Harris DL, Thomas BF, Zhang Y | title = Substituted tetrahydroisoquinolines as selective antagonists for the orexin 1 receptor | journal = Journal of Medicinal Chemistry | volume = 56 | issue = 17 | pages = 6901–16 | date = September 2013 | pmid = 23941044 | doi = 10.1021/jm400720h | pmc = 3849818 }}{{cite journal | vauthors = Perrey DA, Decker AM, Li JX, Gilmour BP, Thomas BF, Harris DL, Runyon SP, Zhang Y | display-authors = 6 | title = The importance of the 6- and 7-positions of tetrahydroisoquinolines as selective antagonists for the orexin 1 receptor | journal = Bioorganic & Medicinal Chemistry | volume = 23 | issue = 17 | pages = 5709–24 | date = September 2015 | pmid = 26216017 | doi = 10.1016/j.bmc.2015.07.013 | pmc = 4554834 }}{{cite journal | vauthors = Perrey DA, German NA, Decker AM, Thorn D, Li JX, Gilmour BP, Thomas BF, Harris DL, Runyon SP, Zhang Y | display-authors = 6 | title = Effect of 1-substitution on tetrahydroisoquinolines as selective antagonists for the orexin-1 receptor | journal = ACS Chemical Neuroscience | volume = 6 | issue = 4 | pages = 599–614 | date = April 2015 | pmid = 25643283 | doi = 10.1021/cn500330v | pmc = 4400266 }}