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2667681-71-0

2667681-71-0 Structure

2667681-71-0 Structure
IdentificationBack Directory
[Name]

Pyrido[3,2-d]pyrimidin-2-amine, 7-fluoro-4-[(1-methylcyclopropyl)oxy]-N-[1-(1-methyl-4-piperidinyl)-1H-pyrazol-4-yl]-6-(2-methyl-5-pyrimidinyl)-
[CAS]

2667681-71-0
[Synonyms]

IRAK4-IN-14
Pyrido[3,2-d]pyrimidin-2-amine, 7-fluoro-4-[(1-methylcyclopropyl)oxy]-N-[1-(1-methyl-4-piperidinyl)-1H-pyrazol-4-yl]-6-(2-methyl-5-pyrimidinyl)-
[Molecular Formula]

C25H28FN9O
[MOL File]

2667681-71-0.mol
[Molecular Weight]

489.55
Chemical PropertiesBack Directory
[Boiling point ]

686.4±65.0 °C(Predicted)
[density ]

1.48±0.1 g/cm3(Predicted)
[form ]

Solid
[pka]

8.52±0.10(Predicted)
[color ]

Light yellow to yellow
Hazard InformationBack Directory
[Uses]

IRAK4-IN-14 (compound 28) is a potent, selective and orally active IRAK4 inhibitor with an IC50 of 0.003 μM. IRAK4-IN-14 shows good PK parameters in rats and mouse. IRAK4-IN-14 shows synergistic in vitro activity against MyD88/CD79 double mutant ABC-DLBCL in combination with Acalabrutinib[1].
[in vivo]

IRAK4-IN-14 (i.v. or p.o.) shows good PK parameters with oral bioavailability of 66% for mouse[1].
Pharmacokinetic Parameters of IRAK4-IN-14 in Male Han Wistar rats, male CD1 mice, male Cynomolgus monkeys[1].

parameterValue
A2B Papp31
Efflux ratio1.4
Solubility (μM)800
Rat/mouse/monkey/human %free21/16/33/21
Rat LM/H CLint16/5.6
Mouse LM/H CLint13/11
Minipig LM/H CLint18/8.2
Dog LM/H CLint21/4.5
Monkey LM/H CLint35/4.7
Rat CL15
Vdss4.3
t1/25.2
F%55%
Mouse CL17
Vdss4.1
t1/24.2
F%66%
Monkey CL68
Vdss8.6
t1/21.4
Male Han Wistar rats; 1 mg/kg i.v.; 2 mg/kg p.o.; Male CD1 mice; 0.5 mg/kg i.v.; 1 mg/kg p.o.; Male Cynomolgus monkeys; 1 mg/kg i.v.[1].
[IC 50]

IRAK4: 0.003 μM (IC50)
[References]

[1] Degorce SL, et al. Improving metabolic stability and removing aldehyde oxidase liability in a 5-azaquinazoline series of IRAK4 inhibitors. Bioorg Med Chem. 2020 Dec 1;28(23):115815. DOI:10.1016/j.bmc.2020.115815
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