4-Piperidinamine, 1-[6-ethyl-8-fluoro-4-methyl-3-(3-methyl-1,2,4-oxadiazol-5-yl)-2-quinolinyl]-N-(tetrahydro-2H-pyran-4-yl)-

Product Name4-Piperidinamine, 1-[6-ethyl-8-fluoro-4-methyl-3-(3-methyl-1,2,4-oxadiazol-5-yl)-2-quinolinyl]-N-(tetrahydro-2H-pyran-4-yl)-
CAS2244614-14-8
MFC25H32FN5O2
MW453.55
EINECS
MOL File2244614-14-8.mol

Chemical Properties

Boiling point	649.8±65.0 °C(Predicted)
Density	1.26±0.1 g/cm3(Predicted)
pka	9.04±0.20(Predicted)
form	Solid
color	Off-white to light yellow
InChI	InChI=1S/C25H32FN5O2/c1-4-17-13-20-15(2)22(25-27-16(3)30-33-25)24(29-23(20)21(26)14-17)31-9-5-18(6-10-31)28-19-7-11-32-12-8-19/h13-14,18-19,28H,4-12H2,1-3H3
InChIKey	CQOJHAJWCDJEAT-UHFFFAOYSA-N
SMILES	N1(C2C(C3ON=C(C)N=3)=C(C)C3C(N=2)=C(F)C=C(CC)C=3)CCC(NC2CCOCC2)CC1

Usage And Synthesis

Uses

Navacaprant (BTRX-335140) is a selective and orally active κ opioid receptor (KOR) antagonist, has antagonist activity for κOR, μOR and δOR with IC50 values of 0.8 nM, 110 nM, and 6500 nM, respectively. Navacaprant endows with favorable in vitro ADMET and in vivo pharmacokinetic profiles and medication-like duration of action in rats. Navacaprant distributes well into the CNS and can be used for the research of neuropathy[1].

in vivo

Navacaprant (BTRX-335140) (0.01-3 mg/kg; p.o. once) reduces U69,593- stimulated plasma prolactin secretion to levels of without U69,593 treatment^[1]. Navacaprant (BTRX-335140) (1 mg/kg; i.p. once) blocks U-50488-induced antinociception from hot water^[1].

1.19Pharmacokinetic Parameters of BTRX-335140 in rodents^[1].

	Rats IV 1 mg/kg	Mice IV 3 mg/kg	Rats PO 5 mg/kg	Mice PO 10 mg/kg
CL (mL/min/kg)	105	66.5
t_1/2 (h)	1.81	1.91	6.19	2.57
AUC_0-t (hng/mL)	153	725	265	232
V_ss (L/kg)	13.8	7.72
F (%)			30.2	12

Animal Model:	Rat PRL model^[1]
Dosage:	0.01, 0.03, 0.1, 0.3, 1 and 3 mg/kg
Administration:	Oral gavage; 0.01-3 mg/kg once
Result:	Effectively decreased the high level prolactin caused by U69,593 even at a dosage of 0.1 mg/kg.

Animal Model:	Adult male ICR mice with tail dipped into 50°C hot water^[1]
Dosage:	1 mg/kg
Administration:	Intraperitoneal injection; 1 mg/kg once
Result:	Blocked the U-50488-induced antinociception at 1 h but not at 24 h pretreatment time and showed a medication-like duration of action in blocking the KOR.

IC 50

κ Opioid Receptor/KOR: 0.8 nM (IC₅₀); μ Opioid Receptor/MOR: 110 nM (IC₅₀); δ Opioid Receptor/DOR: 6500 nM (IC₅₀)

References

[1] Guerrero M, et al. Design and Synthesis of a Novel and Selective Kappa Opioid Receptor (KOR) Antagonist (BTRX-335140). J Med Chem. 2019 Feb 28;62(4):1761-1780. DOI:10.1021/acs.jmedchem.8b01679

4-Piperidinamine, 1-[6-ethyl-8-fluoro-4-methyl-3-(3-methyl-1,2,4-oxadiazol-5-yl)-2-quinolinyl]-N-(tetrahydro-2H-pyran-4-yl)- Supplier

4-Piperidinamine, 1-[6-ethyl-8-fluoro-4-methyl-3-(3-methyl-1,2,4-oxadiazol-5-yl)-2-quinolinyl]-N-(tetrahydro-2H-pyran-4-yl)- manufacturers

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