Lu AF27139

• CAT Number: I045322
• CAS Number: 2097117-06-9
• Molecular Formula: C21H19ClF3N5O2S
• Molecular Weight: 497.92
• Purity: ≥95%
• Synonyms: N-[(2S)-2-(4-chlorophenyl)-2-morpholin-4-ylethyl]-2-pyrimidin-2-yl-4-(trifluoromethyl)-1,3-thiazole-5-carboxamide
• InChI: InChI=1S/C21H19ClF3N5O2S/c22-14-4-2-13(3-5-14)15(30-8-10-32-11-9-30)12-28-19(31)16-17(21(23,24)25)29-20(33-16)18-26-6-1-7-27-18/h1-7,15H,8-12H2,(H,28,31)/t15-/m1/s1
• InChIKey: FGPQIEDRTXLBES-OAHLLOKOSA-N
• SMILES: C1COCCN1C(CNC(=O)C2=C(N=C(S2)C3=NC=CC=N3)C(F)(F)F)C4=CC=C(C=C4)Cl

Lu AF27139 (Cat No.: I045322) is Lundbeck’s potent, selective, orally bioavailable P2X7 receptor antagonist optimized for central-nervous-system penetration. It exhibits nanomolar potency across rat, mouse, and human P2X7, high brain/plasma ratios, and suitable pharmacokinetics with ~0.8 L h-1 kg-1 clearance and good oral bioavailability. In rodents, oral doses (3–100 mg kg-1) markedly suppress LPS-primed, BzATP-evoked IL-1β release in frontal cortex, confirming functional CNS target engagement. Lacking significant off-target or toxicity signals, Lu AF27139 serves as a valuable preclinical tool for elucidating neuroinflammatory roles of P2X7 and advancing CNS-focused therapeutics research.

Reference

[1]. Hopper AT, et al. Synthesis and Characterization of the Novel Rodent-Active and CNS-Penetrant P2X7 Receptor Antagonist Lu AF27139. J Med Chem. 2021 Apr 22;64(8):4891-4902.
[Content Brief]

[2]. Hopper AT, et al. Synthesis and Characterization of the Novel Rodent-Active and CNS-Penetrant P2X7 Receptor Antagonist Lu AF27139. J Med Chem. 2021;64(8):4891-4902.