ChemicalBook Product Catalog Organic Chemistry Organic fluorine compound 8-Quinolinecarbonitrile, 5-[(3R,5S)-3-amino-5-(trifluoromethyl)-1-piperidinyl]-

8-Quinolinecarbonitrile, 5-[(3R,5S)-3-amino-5-(trifluoromethyl)-1-piperidinyl]-

Product Name8-Quinolinecarbonitrile, 5-[(3R,5S)-3-amino-5-(trifluoromethyl)-1-piperidinyl]-
CAS2101938-42-3
MFC16H15F3N4
MW320.31
EINECS
MOL File2101938-42-3.mol

Chemical Properties

Boiling point	477.8±45.0 °C(Predicted)
Density	1.37±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
solubility	DMSO : 24.44 mg/mL (76.30 mM; Need ultrasonic)
pka	9.50±0.40(Predicted)
form	Solid
color	Light yellow to yellow

Usage And Synthesis

Uses

Enpatoran (M5049) is a potent, orally active and dual TLR7/8 inhibitor with IC50s of 11.1 nM and 24.1 nM in HEK293 cells, respectively. Enpatoran is inactive against TLR3, TLR4 and TLR9. Enpatoran can block molecule synthetic ligands and natural endogenous RNA ligands. Enpatoran exhibits excellent pharmacokinetic properties in vivo. Enpatoran can be used for both innate and adaptive autoimmunity blocking research [1].

in vivo

Pre-treatment with Enpatoran (M5049; oral gavage; 1 mg/kg) before R848 (intraperitoneal injection of 25 μg) dose-dependently inhibits the production of IL-6 and IFN-α in mice^[1].
Enpatoran (M5049) exhibits high oral bioavailability (mouse 100%, rat 87%, dog 84%) following oral administration (mouse, rat and dog 1.0 mg/kg)^[1].
Enpatoran exhibits moderate half-lives (mouse 1.4, rat 5.0 and dog 13 h) due to high plasma clearance (1.4, 1.2 and 0.59 L/h/kg, respectively) combined with large volumes of distribution (2.7, 8.7 and 5.7 L/kg, respectively) following intravenous administration (mouse, rat and dog 1.0 mg/kg)^[1].

Animal Model:	Female C57BL/6 mice^[1]
Dosage:	0.1 mg/kg and 1 mg/kg
Administration:	Oral gavage; administered 1 hour prior to R848 challenge
Result:	The TLR7/8 agonist R848 stimulated both IFN-α and IL-6 production in mice. Enpatoran decreased IFN-α and IL-6 production stimulated by R848.

Animal Model:	Female CD1 mice, Female Wistar rats, Female beagle dogs^[1]
Dosage:	1 mg/kg (Pharmacokinetic Analysis)
Administration:	Intravenous (i.v.) or oral gavage
Result:	T_1/2s of 1.4, 5.0 and 13 h for mice, rats and dogs, respectively.

IC 50

TLR7: 11.1 nM (IC₅₀, in HEK293 cells); TLR8: 24.1 nM (IC₅₀, in HEK293 cells); TLR7: 68.3 nM (IC₅₀, in peripheral blood mononuclear cells (PBMCs)); TLR8: 620 nM (IC₅₀, in peripheral blood mononuclear cells (PBMCs)); TLR7: 2.2 nM (IC₅₀, in whole blood (WB) cells); TLR8: 120 nM (IC₅₀, in whole blood (WB) cells)

References

[1] Jaromir Vlach, et al. Discovery of M5049: A Novel Selective TLR7/8 Inhibitor for Treatment of Autoimmunity. J Pharmacol Exp Ther. 2020 Dec 16;JPET-AR-2020-000275. DOI:10.1124/jpet.120.000275

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