| Identification | Back Directory | [Name]
3-(3,4-Difluorobenzoyl)-1,2,3,6-tetrahydro-1,1-dimethylazepino[4,5-b]indole-5-carboxylic acid 1-methylethyl ester | [CAS]
629664-81-9 | [Synonyms]
XL335
CS-899
Fxr 450
Way 362450
Unii-S6kdm312I5
WAY-362450 (XL335
Turofexorate isopropyl
WAY-362450 >=98% (HPLC)
WAY362450 - FXR450 - XL335
XL335;TUROFEXORATE ISOPROPYL
Turofexorate isopropyl [usan]
Turofexorate Isopropyl (XL335)
XL335; WAY 362450; TUROFEXORATE ISOPROPYL; WAY-362450
isopropyl 3-(3,4-difluorobenzoyl)-1,1-diMethyl-1,2,3,6-tetrahydr
propan-2-yl 3-(3,4-difluorobenzoyl)-1,1-dimethyl-2,6-dihydroazepino[4,5-b]indole-5-carboxylate
Isopropyl 3-(3,4-difluorobenzoyl)-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carbox
Isopropyl 3-(3,4-difluorobenzoyl)-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxyla
isopropyl 3-(3,4-difluorobenzoyl)-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate
(E)-isopropyl 3-(3,4-difluorobenzoyl)-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate
isopropyl 3-(3,4-difluorobenzoyl)-1,1-dimethyl-1,2,3,4,5,5a,6,10b-octahydroazepino[4,5-b]indole-5-carboxylate
3-(3,4-Difluorobenzoyl)-1,2,3,6-tetrahydro-1,1-dimethylazepino[4,5-b]indole-5-carboxylic acid 1-methylethyl ester
Azepino[4,5-b]indole-5-carboxylic acid, 3-(3,4-difluorobenzoyl)-1,2,3,6-tetrahydro-1,1-dimethyl-, 1-methylethyl ester | [Molecular Formula]
C25H24F2N2O3 | [MDL Number]
MFCD13181507 | [MOL File]
629664-81-9.mol | [Molecular Weight]
438.47 |
| Chemical Properties | Back Directory | [Boiling point ]
617.3±55.0 °C(Predicted) | [density ]
1.275 | [storage temp. ]
room temp | [solubility ]
DMSO : 25 mg/mL (57.02 mM; Need ultrasonic) | [form ]
powder | [pka]
16.49±0.60(Predicted) | [color ]
white to beige | [InChI]
InChI=1S/C25H24F2N2O3/c1-14(2)32-24(31)17-12-29(23(30)15-9-10-18(26)19(27)11-15)13-25(3,4)21-16-7-5-6-8-20(16)28-22(17)21/h5-12,14,28H,13H2,1-4H3 | [InChIKey]
INASOKQDNHHMRE-UHFFFAOYSA-N | [SMILES]
N1C2=C(C=CC=C2)C2C(C)(C)CN(C(=O)C3=CC=C(F)C(F)=C3)C=C(C(OC(C)C)=O)C1=2 |
| Hazard Information | Back Directory | [Uses]
Turofexorate isopropyl (FXR-450) is a potent, selective, and orally bioavailable FXR agonist with EC50 of 4 nM[1]. | [Definition]
ChEBI: Turofexorate isopropyl is a member of indoles. | [Biochem/physiol Actions]
WAY-362450 is a potent and selective Farnesoid X receptor (FXR) agonist that lowers total plasma cholesterol (all lipoprotein species). WAY-362450 reduced the levels of high-density lipoprotein cholesterol (HDLc) in Cynomolgus monkeys, mice and hamsters. Apparently HDL lowering is achieved through increased transhepatic cholesterol efflux. | [in vivo]
Turofexorate isopropyl (WAY-362450) also shows potent effects on cholesterol and triglyceride lowering in LDLR-/- mice and antiatherogenic activity with respect to reduction of aortic arch lesions. Oral administration of Turofexorate isopropyl (WAY-362450) to LDLR-/- mice results in lowering of cholesterol and triglycerides. Chronic administration in an atherosclerosis model results in significant reduction in aortic arch lesions. Turofexorate isopropyl (WAY-362450) is dosed in rat at 3 mg/kg (po and iv) and shows good oral bioavailability (38%). There is a protracted half-life of 25 h, modest volume of distribution, and low clearance (3.3 L/kg, ~10% of hepatic blood flow). Additional pharmacokinetic studies in mice and higher species have been completed, and the data will be reported elsewhere[1]. In rats, Turofexorate isopropyl (WAY-362450) results in an elevation in HDLc levels, whereas in hamsters it causes a reduction similar to that observed in mice[2] Treatment of wild-type mice with 30 mg/kg Turofexorate isopropyl (WAY-362450) results in induction of SHP expression in wild-type mice but not in FXR-/- mice. Consistent with the known effects of SHP induction on bile acid synthetic gene expression, Turofexorate isopropyl (WAY-362450) strongly represses expression of the CYP8B1 bile acid synthetic gene in wild-type mice but had no effect on CYP8B1 gene expression in FXR-/- mice[3]. | [storage]
Store at -20°C | [References]
[1] Flatt B, et al. Discovery of XL335 (WAY-362450), a highly potent, selective, and orally active agonist of the farnesoid X receptor (FXR). J Med Chem. 2009 Feb 26;52(4):904-7. DOI:10.1021/jm8014124
[2] Evans MJ, et al. A synthetic farnesoid X receptor (FXR) agonist promotes cholesterol lowering in models of dyslipidemia. Am J Physiol Gastrointest Liver Physiol. 2009 Mar;296(3):G543-52. DOI:10.1152/ajpgi.90585.2008
[3] Hartman HB, et al. Activation of farnesoid X receptor prevents atherosclerotic lesion formation in LDLR-/- and apoE-/- mice. J Lipid Res. 2009 Jun;50(6):1090-100. DOI:10.1194/jlr.M800619-JLR200 |
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