CrystalGenomics, Inc., 5F, Tower A, Korea Bio Park 694-1, Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, Republic of Korea; School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Bioorg Med Chem Lett. 2013 Nov 1;23(21):5953-7. doi: 10.1016/j.bmcl.2013.08.067. Epub 2013 Aug 23.
A new series of PHD (HIF prolyl 4-hydroxylase) inhibitors was designed based on the X-ray co-crystal structure of FG-2216. Using a lead generation process, a series of [(4-Hydroxyl-benzo[4,5]thieno[3,2-c]pyridine-3-carbonyl)-amino]-acetic acid derivatives was developed as potent PHD2 inhibitors. This class of compounds also showed the ability to stabilize HIF-α, to stimulate EPO secretion in in vitro studies, and to increase hematocrit, red blood cell count, and hemoglobin levels in an animal efficacy study.
基于 FG-2216 的 X 射线共晶结构，设计了一系列新型 PHD（HIF 脯氨酰 4-羟化酶）抑制剂。通过一个先导化合物生成过程，开发了一系列[(4-羟基苯并[4,5]噻吩并[3,2-c]吡啶-3-羰基)-氨基]-乙酸衍生物作为有效的 PHD2 抑制剂。该类化合物还具有稳定 HIF-α、在体外研究中刺激 EPO 分泌以及在动物疗效研究中增加红细胞压积、红细胞计数和血红蛋白水平的能力。
