[(4-Hydroxyl-benzo[4,5]thieno[3,2-c]pyridine-3-carbonyl)-amino]-acetic acid derivatives; HIF prolyl 4-hydroxylase inhibitors as oral erythropoietin secretagogues

  • Bioorg Med Chem Lett. 2013 Nov 1;23(21):5953-7. doi: 10.1016/j.bmcl.2013.08.067.
Yong Rae Hong  1 ,  Hyun Tae Kim ,  Seung-Chul Lee ,  Seonggu Ro ,  Joong Myung Cho ,  In Su Kim ,  Young Hoon Jung
Affiliations
  • 1. 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.
PMID: 24042008 DOI: 10.1016/j.bmcl.2013.08.067
Abstract

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.

Keywords
Erythropoiesis; HIF-PH (PHD); Inhibitor; Stabilizer.
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