| Identification | Back Directory | [Name]
2-Propenamide, N-[4-[2-[[4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]phenyl]- | [CAS]
2412734-00-8 | [Synonyms]
JAK3-IN-11
N-[4-(2-{[4-(morpholin-4-yl)phenyl]amino}pyrimidin-4-yl)phenyl]prop-2-enamide
2-Propenamide, N-[4-[2-[[4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]phenyl]- | [Molecular Formula]
C23H23N5O2 | [MOL File]
2412734-00-8.mol | [Molecular Weight]
401.46 |
| Hazard Information | Back Directory | [Uses]
JAK3-IN-11 (Compound 12), a potent, noncytotoxic, irreversible, orally active JAK3 inhibitor with IC50 value of 1.7 nM, has excellent selectivity (>588-fold compared to other JAK isoforms), covalently bind to the ATP-binding pocket in JAK3. JAK3-IN-11 strongly inhibits JAK3-dependent signaling and T cell proliferation, is a promising tool for study autoimmune diseases[1]. | [in vivo]
JAK3-IN-11 (Compound 12) (Oxazolone (OXZ)-induced DTH Balb/c mice; 0-30 mg/kg; PO, prior to and during the challenge phase, 6 days) inhibits oxazolone (OXZ)-induced delayed type hypersensitivity (DTH) responses in a dose-dependent manner[1]. | Animal Model: | Oxazolone (OXZ)-induced DTH Balb/c mice model[1].
| | Dosage: | 30, 10, and 3 mg/kg.
| | Administration: | PO, prior to and during the challenge phase, 6 days. | | Result: | Inhibited oxazolone (OXZ)-induced delayed type hypersensitivity (DTH) responses in a dose-dependent manner. |
| Animal Model: | Male ICR mice[1].
| | Dosage: | 30 mg/kg for oral gavage, 10 mg/kg for intravenous administration.
| | Administration: | Pharmacokinetic Analysis | | Result: | Preliminary pharmacokinetic data of JAK3-IN-11 (Compound 12) in male ICR Mice[1]
Male ICR mice, 30 mg/kg for oral gavage, 10 mg/kg for intravenous administration[1].
| Compound 12 | iv (10 mg/kg) | po (30 mg/kg) | | AUC(0-t) (mg/L*h)a | 1244.41 ± 77.83 | 889.42 ± 48.32 | | AUC(0-∞) (mg/L*h) | 1274.41 ± 57.18 | 897.12 ± 56.72 | | MRT (0-∞) (h)b | 0.73 ± 0.08 | 1.42 ± 0.38 | | Vz (L/kg)c | 8.36 ± 1.83 | 220.42 ± 24.71 | | CLz (L/h/kg)d | 8.15 ± 1.21 | 97.14 ± 20.87 | | t1/2 (h)e | 0.47 ± 0.06 | 1.52 ± 0.34 | | Cmax (mg/L)f | 8763.23 ± 324.65 | 2008.21 ± 189.44 | | Bioavailability(%)g | | 23.82% |
a Area under the concentration time curve.
b Mean residence time.
c Volume in steady state.
d Plasma clearance.
e Terminal half-life.
f Peak plasma concentrations.
g Bioavailability = AUC0-t(po)/AUC0-t × 100%.
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| [IC 50]
JAK3: 1.7 nM (IC50); JAK2: 1 μM (IC50); JAK1: 1.32 μM (IC50) | [References]
[1] Lei Shu, et al. Design, synthesis, and pharmacological evaluation of 4- or 6-phenyl-pyrimidine derivatives as novel and selective Janus kinase 3 inhibitors. Eur J Med Chem. 2020 Apr 1;191:112148. DOI:10.1016/j.ejmech.2020.112148 |
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