Firazorexton

Firazorexton
Clinical data
Other names	TAK-994
Identifiers
	IUPAC name N-[(2S,3S)-2-[[3-(3,5-difluorophenyl)-2-fluorophenyl]methyl]-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]methanesulfonamide;
CAS Number	2274802-95-6 ;
PubChem CID	137460733;
ChemSpider	115009503;
UNII	U9MOX60GHD;
Chemical and physical data
Formula	C22H25F3N2O4S
Molar mass	470.51 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC(C)(C(=O)N1CC[C@@H]([C@@H]1CC2=C(C(=CC=C2)C3=CC(=CC(=C3)F)F)F)NS(=O)(=O)C)O;
	InChI InChI=1S/C22H25F3N2O4S/c1-22(2,29)21(28)27-8-7-18(26-32(3,30)31)19(27)11-13-5-4-6-17(20(13)25)14-9-15(23)12-16(24)10-14/h4-6,9-10,12,18-19,26,29H,7-8,11H2,1-3H3/t18-,19-/m0/s1; Key:VOSAWOSMGPKQEQ-OALUTQOASA-N;

Firazorexton (INNTooltip International Nonproprietary Name; development code TAK-994) is an experimental orexin 2 (OX₂) receptor agonist first described in a 2019 patent filed by Takeda Pharmaceutical Company.^[1]^[2]

Quick Facts Clinical data, Other names ...

Firazorexton was studied by Takeda for the treatment of narcolepsy.^[3]^[4]^[5] It is a small-molecule and orally active compound and acts as a highly selective agonist of the orexin receptor 2 (OX₂) with >700-fold selectivity over the orexin receptor 1 (OX₁).^[3]^[4]^[6]^[7] Firazorexton is related to danavorexton (TAK-925).^[8]

The compound reached phase 2 clinical trials for narcolepsy.^[9] However, clinical development was discontinued in October 2021 for safety reasons.^[8]^[10]^[11]^[12]^[13] More specifically, it produced severe drug-induced liver injury in phase 2 trials.^[14] This hepatotoxicity is unlikely to be related to firazorexton's orexin receptor agonism.^[14]

See also