Uses
5-(4-Phenoxybutoxy)psoralen (CAS# 870653-45-5) is a selective small molecule blocker of the lymphocyte K+ channel Kv1.3 and is used for the suppression of effector memory T cells in autoimmune diseases.
Biochem/physiol Actions
Selective inhibitor of Kv1.3, voltage-gated K+ channel. PAP-1 (EC50=2 nM) potently inhibits human T effector memory cell proliferation and delayed hypersensitivity. Effective orally or intraperitoneally. 5-(4-Phenoxybutoxy)psoralen has 23-fold selectivity for Kv1.3 over Kv1.5, and 33-125-fold selectivity over other Kv1 family channels.
Synthesis
The reaction was carried out in 30 mL of 2-butanone at reflux for 24 h in the presence of excess anhydrous potassium carbonate (2 g) and catalytic amount of potassium iodide, using 4-hydroxy-7H-furo[3,2-g]benzopyran-7-one (5-hydroxypsoralen, 700 mg, 3.462 mmol) and 4-phenoxybutyl bromide (600 mg, 3.462 mmol) as raw materials. The reaction process was monitored by thin layer chromatography (TLC). After completion of the reaction, the reaction mixture was concentrated under reduced pressure and cooled to give an oily residue, which was diluted with water. The aqueous solution was acidified to pH 1 with concentrated hydrochloric acid, stirred for 15-20 min, and then extracted with dichloromethane (3 x 100 mL). The dichloromethane layer was extracted with 25 mL of 1% sodium hydroxide solution to separate unreacted 5-hydroxypsoralen, followed by washing with 30 mL of 2% hydrochloric acid, drying with anhydrous sodium sulfate and concentration. The solid residue was dissolved in a methanol-acetone mixture, treated with activated charcoal and recrystallized from the methanol-acetone (80:20) mixture to afford the target product 4-(4-phenoxybutoxy)-7H-furo[3,2-g][1]benzopyran-7-one in a yield of 733.6 mg (60.48% yield) with a melting point of 104 °C. The structure of the product was confirmed by 1H-NMR, 13C-NMR and mass spectrometry (MS).
in vivo
PAP-1 (0.3-3 mg/kg; i.p.; three times daily for 48 hours) prevents delayed type hypersensitivity (DTH) in lewis rats[1].
| Animal Model: | 9- to 11- week-old female Lewis rats[1] |
| Dosage: | Intraperitoneal injection; three times daily for 48 hours |
| Administration: | 0.3, 1, 3 mg/kg |
| Result: | Dose-dependently suppressed the DTH reaction. |
References
[1] Molecular Pharmacology, 2005, vol. 68, # 5, p. 1254 - 1270
[2] Patent: US2006/79535, 2006, A1. Location in patent: Page/Page column 4-5
