TCS-OX2-29 is an orexin antagonist. It was the first non-peptide antagonist developed that is selective for the orexin receptor subtype OX2, with an IC50 of 40nM and selectivity of around 250x for OX2 over OX1 receptors.[1] Orexin antagonists are expected to be useful for the treatment of insomnia, with subtype-selective antagonists such as TCS-OX2-29 potentially offering more specificity of action compared to non-selective orexin antagonists like almorexant.[2]

  • (2S)-1-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-3,3-dimethyl-2-(pyridin-4-ylmethylamino)butan-1-one
CAS Number
PubChem CID
Chemical and physical data
Molar mass397.519 g·mol−1
3D model (JSmol)
  • c3cnccc3CNC(C(C)(C)C)C(=O)N(Cc2cc1OC)CCc2cc1OC


  1. ^ Hirose M, Egashira S, Goto Y, Hashihayata T, Ohtake N, Iwaasa H, et al. (December 2003). "N-acyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline: the first orexin-2 receptor selective non-peptidic antagonist". Bioorganic & Medicinal Chemistry Letters. 13 (24): 4497–9. doi:10.1016/j.bmcl.2003.08.038. PMID 14643355.
  2. ^ Roecker AJ, Coleman PJ (2008). "Orexin receptor antagonists: medicinal chemistry and therapeutic potential". Current Topics in Medicinal Chemistry. 8 (11): 977–87. doi:10.2174/156802608784936746. PMID 18673167.