6-[(5S,9R)-9-(4-氰基苯基)-3-(3,5-二氯苯基)-1-甲基-2,4-二氧代-1,3,7-三氮杂螺[4,4] non -7-基] -3-吡啶甲酸;6-[(5S,9R)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4,4]non-7-yl]-3-pyridinecarboxylic acid
BMS-688521 (1-10 mg/kg; p.o.; BID for a three-day) is efficacious in a mouse allergic eosinophilic lung inflammation model. BMS-688521 (5 mg/kg; p.o.) treatment shows the Cmax, Tmax, AUC, F values are 0.32 μM, 1.0 μM, 1.5 μM h, and 50%, respectively. BMS-688521 (1 mg/kg; i.v.) treatment shows the T1/2, MRT, CL and Vss values are 1.6 hours, 1.7 hours, 50 mL/mim/kg, and 5.1 L/kg, respectively in BALB/c mice.
参考文献:
1. Watterson SH, et al. Small molecule antagonist of leukocyte function associated antigen-1 (LFA-1): structure-activity relationships leading to the identification of 6-((5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4