1308677-02-2

Upstream product

• 1967-93-7 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluorooctanedioyl dichloride 
• 678-45-5 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluorooctanedioic acid 
• 1355356-58-9 benzyl 7-chlorocarbonyl-2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoroheptanoate 

Relevant academic research and scientific papers

Perfluorinated hydroxamic acids are potent and selective inhibitors of HDAC-like enzymes from Pseudomonas aeruginosa

A series of perfluorinated SAHA (PFSAHA) was prepared and profiled against a panel of human and bacterial members of the Histone deacetylase (HDAC) family. Some of the active substances show nanomolar inhibitory activity and several hundred fold selectivity for the HDAC like enzyme PA3774 from P. aeruginosa. The extraordinary selectivity against human HDACs results from the distinct oligomeric state of PA3774 which consists of two head-to-head dimers. The binding pocket is defined by the surface of both opposite monomers confining the access of ligands to the active site. In addition, the aromatic cap group of PFSAHA undergoes an edge-to-face aromatic interaction with phenylalanine from the opposite monomer.

Synthesis and biochemical analysis of 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoro- N-hydroxy-octanediamides as inhibitors of human histone deacetylases

Inhibition of human histone deacetylases (HDACs) has emerged as a novel concept in the chemotherapeutic treatment of cancer. Two chemical entities, SAHA (ZOLINZA, Merck) and romidepsin (Istodax, Celgene) have been recently approved by the FDA as first-in-class drugs against cutaneous T-cell lymphoma. Clinical use of these drugs revealed several side effects including gastro-intestinal symptoms, fatigue, thrombocytopenia, thrombosis. Romidepsin is associated with an yet unresolved cardiotoxicity issue. A general hypothesis for the diminishment of unwanted adverse effects and an improved therapeutical window suggests the development of more isotype selective inhibitors. In this study the first time HDAC inhibitors with perfluorinated spacers between the zinc chelating moiety and the aromatic capping group were synthesized and tested against representatives of HDAC classes I, IIa and IIb. Competitive binding assays and a combined approach by using blind docking and molecular dynamics support binding of the perfluorinated analogs of SAHA to the active site of the HDAC-like amidohydrolase from Bordetella/Alcaligenes and presumably also to human HDACs. In contrast to the alkyl spacer of SAHA and derivatives, the perfluorinated alkyl spacer seems to contribute to or facilitate the induction of selectivity for class II, particularly class IIa, HDACs even though the overall potency of the perfluorinated SAHA analogs in this study against human HDACs remained still rather moderate in the micromolar range.

HISTONE DEACETYLASE (HDAC) INHIBITING COMPOUNDS AND METHOD OF MAKING SAME

The invention relates to novel HDAC inhibitors and a method of making such HDAC inhibitors. The present invention provides novel HDAC inhibitors having a perfluorinated linker between the metal-binding group and the cap group.

Histone deacetylase (HDAC) inhibiting compounds and method of making same

The invention relates to novel HDAC inhibitors and a method of making such HDAC inhibitors. The present invention provides novel HDAC inhibitors having a perfluorinated linker between the metal-binding group and the cap group.