Part II. Development of novel colchicine-derived immunosuppressants with improved pharmacokinetic properties
Dong-Jo Chang1, Sujin Lee, Jaebong Jang
1College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
Abstract:
We have developed a new series of immunosuppressant with improved pharmacokinetic properties as the second-generation of colchicine analogs, which were designed based on the privileged structure derived from our previous work. In particular, we identified an analog (14), which exhibited a potent in vitro activity (IC(50): 5 nM) in MLR and excellent in vivo efficacy in the Zymosan A-induced arthritis model, in the Carrageenan-induced edema model and in the local lymph node assay (LLNA). Analog 14 also revealed a good oral bioavailability (F: 67.3%) in BALB/c mice.
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