85515-44-2Relevant articles and documents
Metal-Free Direct Amidation of Naphthoquinones Using Hydroxamic Acids as an Amide Source: Application in the Synthesis of an HDAC6 Inhibitor
Zhang, Cheng,Chou, C. James
, p. 5512 - 5515 (2016/11/17)
A novel synthetic approach to amidoquinones by the reaction of naphthoquinones with hydroxamic acids under basic conditions was developed. The reaction is mild and operationally simple, and it affords high yields of amidoquinones. With this new method, a novel, very strong HDAC6 inhibitor, which showed high toxicity to AML cells, was successfully synthesized.
Novel 5α-reductase inhibitors: Synthesis, structure-activity studies, and pharmacokinetic profile of phenoxybenzoylphenyl acetic acids
Salem, Ola I. A.,Frotscher, Martin,Scherer, Christiane,Neugebauer, Alexander,Biemel, Klaus,Streiber, Martina,Maas, Ruth,Hartmann, Rolf W.
, p. 748 - 759 (2007/10/03)
Novel substituted benzoyl benzoic acids and phenylacetic acids 1-14 have been synthesized and evaluated for inhibition of rat and human steroid 5α-reductase isozymes 1 and 2, The compounds turned out to be potent and selective human type 2 enzyme inhibitors, exhibiting IC50 values in the nanomolar range. The phenylacetic acid derivatives were more potent than the analogous benzoic acids. Bromination in the 4-position of the phenoxy moiety led to the strongest inhibitor in this class (12; IC50 = 5 nM), which was equipotent to finasteride. Since oral absorption is essential for a potential drug, 12 was further examined. In the parallel artificial membrane permeation assay (PAMPA) it turned out to be a good permeator, whereas it was a medium permeator in Caco2 cells. After oral administration (40 mg/kg) to rats a high bioavailability and a biological half-life of 5.5 h were observed, making it a promising candidate for clinical evaluation.
