| Identification | Back Directory | [Name]
Benzamide, N-(cyanomethyl)-4-[2-[[1-(cyanomethyl)-1H-pyrazol-4-yl]amino]-5-methyl-4-pyrimidinyl]- | [CAS]
2445499-20-5 | [Synonyms]
JAK-IN-21
JAK-IN-21 LNK01003
Benzamide, N-(cyanomethyl)-4-[2-[[1-(cyanomethyl)-1H-pyrazol-4-yl]amino]-5-methyl-4-pyrimidinyl]- | [Molecular Formula]
C19H16N8O | [MOL File]
2445499-20-5.mol | [Molecular Weight]
372.38 |
| Hazard Information | Back Directory | [Uses]
JAK-IN-21 (Example 4) is a selective and potent JAK inhibitor with IC50s of 1.73, 2.04, 109 and 62.9 nM against JAK1, JAK2, J2V617F and TYK2, respectively[1]. | [in vivo]
JAK-IN-21 (Example 4) shows low bioavailability (F=1.9%)[1]. | Animal Model: | SD rats[1] | | Dosage: | 10 mg/kg | | Administration: | Oral gavage (Pharmacokinetic Study) | | Result: | Rat Colon Pharmacokinetic Study[1]
| Compound | Plasma Cmax
(ng/mL) | Plasma AUC
(h*ng/mL) | t1/2 (h) | Colon AUC
(h*ng/g) | Colon + Feces AUC
(h*ng/g) | | JAK-IN-21 | 68.8 | 96 | 1.6 | 6,623 | 545,501 |
|
| Animal Model: | SD rats[1] | | Dosage: | 1 mg/kg or 2 mg/kg | | Administration: | Intravenous injection (1 mg/kg) or oral gavage (2 mg/kg) (Pharmacokinetic Study) | | Result: | Pharmacokinetic Parameters in Sprague-Dawley Rats by Intravenous Administration and Oral Administration[1]
| Compound | Dose
(mg/kg) | AUC
(h*ng/mL) | T1/2 (h) | Cl
(mL/min/kg) | Vd
(L/kg) | Cmax
(ng/mL) | F (%) | | JAK-IN-21 (iv) | 1 | 854.8 | 0.22 | 19.4 | 0.37 | | | | JAK-IN-21 (ig) | 2 | 29.8 | 0.38 | | | 40.4 | 1.9 |
|
| [IC 50]
JAK1: 1.73 nM (IC50); JAK2: 2.04 nM (IC50); Tyk2: 62.9 nM (IC50); JAK2-V617F: 109 nM (IC50) | [References]
[1] Zhaokui WAN, et al. Benzamides of pyrazolyl-amino-pyrimidinyl derivatives, and compositions and methods thereof. Patent WO2020119819. |
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