Synthesis and Biological Evaluation of 1,2-dithiol-3-thiones and pyrrolo[1,2-a]pyrazines as Novel Hypoxia Inducible factor-1 (HIF-1) Inhibitor

Young Hun Lee, Jung Min Lee, Sang Geon Kim, Yong Sup Lee

Bioorg Med Chem. 2016 Jun 15;24(12):2843-51.

PMID: 27157007

Abstract:

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor which is strongly associated with tumor survival, progression, and therapeutic resistance. Accordingly, it has been suggested that the inhibition of the HIF-1 pathway can suppress tumor, and it has become an important therapeutic target. In present study, oltipraz, its metabolite M2, and their derivatives were synthesized and evaluated as HIF-1α inhibitors. Among the synthesized, benzyl-substituted pyrrolo[1,2-a]pyrazine 2g most potently inhibited HIF-1α protein accumulation (81% at 10μM) and VEGF, GLUT-1 transcription (77% and 92% at 10μM, respectively).

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP84201401	Oltipraz metabolite M2		84201-40-1	Price