For research use only. Not for therapeutic Use.
CE-224535 is a selective P2X7 receptor antagonist.
CE-224535 is developed as a disease-modifying antirheumatic drugs (DMARD) and is a selective antagonist of the human P2X7 receptor. CE-224535 can reduce leukocyte secretion of IL-1 and IL-18, thereby providing a novel therapeutic approach for treatment of rheumatoid arthritis (RA)[1].
In rats, CE-224535 has low CLp (11 mL/min/kg) and a large Vdss of 7.6 L/kg, which results in a half-life of 2.4 h. Upon oral administration to rats at 5 mg/kg, CE-224535 provides maximal plasma exposure (Cmax) that is ~90 fold over its IC90 in human blood (Cmax=0.21 μg/mL or 0.44 μM). The oral bioavailability of CE-224535 is low in rats (F=2.6%), but this is believed to be a rat specific phenomenon since corresponding oral bioavailability in both dog (59%) and monkey (22%) is adequate[2].
| Catalog Number | I005912 |
| CAS Number | 724424-43-5 |
| Synonyms | 2-chloro-N-[(1-hydroxycycloheptyl)methyl]-5-[4-[(2R)-2-hydroxy-3-methoxypropyl]-3,5-dioxo-1,2,4-triazin-2-yl]benzamide |
| Molecular Formula | C22H29ClN4O6 |
| Purity | ≥95% |
| InChI | InChI=1S/C22H29ClN4O6/c1-33-13-16(28)12-26-19(29)11-25-27(21(26)31)15-6-7-18(23)17(10-15)20(30)24-14-22(32)8-4-2-3-5-9-22/h6-7,10-11,16,28,32H,2-5,8-9,12-14H2,1H3,(H,24,30)/t16-/m1/s1 |
| InChIKey | FUCKCIVGBCBZNP-MRXNPFEDSA-N |
| SMILES | COCC(CN1C(=O)C=NN(C1=O)C2=CC(=C(C=C2)Cl)C(=O)NCC3(CCCCCC3)O)O |
| Reference | [1]. Stock TC, et al. Efficacy and safety of CE-224,535, an antagonist of P2X7 receptor, in treatment of patients with rheumatoid arthritis inadequately controlled by methotrexate. J Rheumatol. 2012 Apr;39(4):720-7. [2]. Duplantier AJ, et al. Optimization of the physicochemical and pharmacokinetic attributes in a 6-azauracil series of P2X7 receptor antagonists leading to the discovery of the clinical candidate CE-224,535. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3708-11 |
