Synthesis of (aryloxyacetylamino)-isonicotinic/nicotinic acid analogues as potent hypoxia-inducible factor (HIF)-1α inhibitors

  • Boovanahalli, Shanthaveerappa K.
  • Jin, Xuejun
  • Jin, Yinglan
  • Kim, Jin Hwan
  • Dat, Nguyen Tien
  • ... Lee, Jeong Hyung
  • 외 4명
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초록

We report a new series of HIF-1 alpha inhibitors which were obtained through structural modifications of previously reported lead 1. The in vitro inhibitory potencies of newly synthesized compounds were evaluated against hypoxia-induced HIF-1 activation using cell-based reporter assay in three human cancer cell lines including SK-Hep-1, Hep3B, and AGS cells. Several compounds displayed significant inhibitory activity in all the three tested cell lines. In particular, analogue 17 displayed potent inhibition of hypoxia-induced accumulation of HIF-1 alpha protein in Hep3B cell line, in addition to the dose-dependent inhibition of HIF-1 target genes VEGF and EPO. (C) 2007 Elsevier Ltd. All rights reserved.

키워드

hypoxiahypoxia-inducible factorHIF-inhibitorHIF-1isonicotinic/nicotinic acid analoguesFACTOR-IFACTOR 1-ALPHAHIFIDENTIFICATIONANGIOGENESISGROWTHOVEREXPRESSIONEXPRESSIONTARGET
제목
Synthesis of (aryloxyacetylamino)-isonicotinic/nicotinic acid analogues as potent hypoxia-inducible factor (HIF)-1α inhibitors
저자
Boovanahalli, Shanthaveerappa K.Jin, XuejunJin, YinglanKim, Jin HwanDat, Nguyen TienHong, Young-SooLee, Jeong HyungJung, Sang-HunLee, KyeongLee, Jung Joon
DOI
10.1016/j.bmcl.2007.09.005
발행일
2007-11
유형
Article
저널명
Bioorganic & Medicinal Chemistry Letters
17
22
페이지
6305 ~ 6310