499237-99-9Relevant academic research and scientific papers
New methodology for the preparation of 3-hydroxy-2-pyridinone (3,2-HOPO) chelators - Reaction of amines with a novel electrophilic 3,2-HOPO precursor
Lambert, Timothy N,Chittamuru, Sumathi,Jacobs, Hollie K,Gopalan, Aravamudan S
, p. 7379 - 7383 (2002)
The preparation of the new electrophilic iminium ester mesylate salt 5 and its reaction with primary and secondary amines have been investigated. Aniline, t-butylamine, and secondary amines react with 5 via ring opening to give the corresponding HOPO derivatives in high yields. The usefulness of this methodology has been demonstrated by the preparation of two new di-HOPO derivatives 19 and 21. This method allows the introduction of the HOPO ligand onto a variety of amine platforms without the concomitant formation of an amide bond and provides access to HOPO chelators of increased water solubility.
Synthesis and structure-activity relationship of 3-hydroxypyridine-2- thione-based histone deacetylase inhibitors
Sodji, Quaovi H.,Patil, Vishal,Kornacki, James R.,Mrksich, Milan,Oyelere, Adegboyega K.
, p. 9969 - 9981 (2014/01/17)
We previously identified 3-hydroxypyridine-2-thione (3HPT) as a novel zinc binding group for histone deacetylase (HDAC) inhibition. Early structure-activity relationship (SAR) studies led to various small molecules possessing selective inhibitory activity against HDAC6 or HDAC8 but devoid of HDAC1 inhibition. To delineate further the depth of the SAR of 3HPT-derived HDAC inhibitors (HDACi), we have extended the SAR studies to include the linker region and the surface recognition group to optimize the HDAC inhibition. The current efforts resulted in the identification of two lead compounds, 10d and 14e, with potent HDAC6 and HDAC8 activities that are inactive against HDAC1. These new HDACi possess anticancer activities against various cancer cell lines including Jurkat J.γ1 for which SAHA and the previously disclosed 3HPT-derived HDACi were inactive.
