化学
生物利用度
口服活性
铅化合物
药理学
铅(地质)
生物化学
体外
医学
地貌学
地质学
作者
Conghua Xie,Hong-Xiu Xiao,Pei-Fang Song,Qingmei Liu,Haoxiang Wei,Liang Wu,Guanghao Zhu,Guang-Ming Liu,Yandong Zhang,Ping Wang,Xian‐Wen Yang
标识
DOI:10.1021/acs.jmedchem.4c00354
摘要
Food allergy (FA) poses a growing global food safety concern, yet no effective cure exists in clinics. Previously, we discovered a potent antifood allergy compound, butyrolactone I (BTL-I, 1), from the deep sea. Unfortunately, it has a very low exposure and poor pharmacokinetic (PK) profile in rats. Therefore, a series of structural optimizations toward the metabolic pathways of BTL-I were conducted to provide 18 derives (2-19). Among them, BTL-MK (19) showed superior antiallergic activity and favorable pharmacokinetics compared to BTL-I, being twice as potent with a clearance (CL) rate of only 0.5% that of BTL-I. By oral administration, Cmax and area under the concentration-time curve (AUC0-∞) were 565 and 204 times higher than those of BTL-I, respectively. These findings suggest that butyrolactone methyl ketone (BTL-BK) could serve as a drug candidate for the treatment of FAs and offer valuable insights into optimizing the druggability of lead compounds.
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