56904-63-3Relevant academic research and scientific papers
Mechanism of Acylative Oxidation-Reduction-Condensation Reactions Using Benzoisothiazolones as Oxidant and Triethylphosphite as Stoichiometric Reductant
Gangireddy, Pavankumar,Patro, Vidyavathi,Lam, Leighann,Morimoto, Mariko,Liebeskind, Lanny S.
, p. 3513 - 3529 (2017/04/11)
We previously described a new organocatalytic oxidation-reduction-condensation for amide/peptide construction. The reaction system relies on triethylphosphite as the stoichiometric reductant and organocatalytic benzoisothiazolone/O2 in air as the oxidant. The reaction was assumed to generate catalytic quantities of S-acylthiosalicylamides as electrophiles, which are rapidly intercepted by amine reactants to generate amides/peptides and o-mercaptobenzamides. The latter are then gently reoxidized to the benzoisothiazolones under Cu-catalyzed aerobic conditions to complete the catalytic cycle. To gain a mechanistic understanding, we describe herein our studies of the stoichiometric generation of S-acylthiosalicylamides under oxidation-reduction-condensation conditions from a variety of benzoisothiazolones and carboxylic acids using triethylphosphite as the terminal reductant. These studies have revealed the presence of more than one reaction pathway when benzoisothiazolones react with triethylphosphite (including a rapid, direct deoxygenation of certain classes of benzoisothiazolones by triethylphosphite) and allow the identification of optimal reaction characteristics (benzoisothiazolone structure and solvent) for the generation of thioesters. These explorations will inform our efforts to develop highly effective and robust organocatalytic oxidation-reduction-condensation reactions that are based on the benzoisothiazolone and related motifs.
Fragment-based design, synthesis, and biological evaluation of N-substituted-5-(4-isopropylthiophenol)-2-hydroxynicotinamide derivatives as novel Mcl-1 inhibitors
Zhang, Zhichao,Liu, Chengwu,Li, Xiangqian,Song, Ting,Wu, Zhiyong,Liang, Xiaomeng,Zhao, Yan,Shen, Xiaoyun,Chen, Hongbo
, p. 410 - 420 (2013/04/10)
We have previously reported a nanomolar inhibitor of antiapoptotic Mcl-1 protein, 3-thiomorpholin-8-oxo-8H-acenaphtho [1,2-b] pyrrole-9-carbonitrile (S1). S1 plays its function by binding to the BH3 groove of Mcl-1. Basing on this spacial structural characteristic, we developed a novel class of Mcl-1 inhibitor using fragment-based drug discovery approach. By dissecting S1, we identified the compound 4 with a 2-hydroxypyridine core as the starting fragment. In the following molecular growth, we used the ligand efficiency evaluation and fit quality score to assess the fragments. A novel potent compound, N-benzyl-5-(4-isopropylthiophenol)-2-hydroxyl nicotinamide (12c), which binds Mcl-1 with an IC50 value of 54 nM was obtained. Compound 12c demonstrated a better aqueous solubility than S1.
Nicotinamide Ethers: Novel Inhibitors of Calcium-Independent Phosphodiesterase and Rolipram Binding
Vinick, Fredric J.,Saccomano, Nicholas A.,Koe, B. Kenneth,Nielsen, Jann A.,Williams, Ian H.,et al.
, p. 86 - 89 (2007/10/02)
The synthesis and biological properties of a series of nicotinamide ethers are described.These compounds, structurally novel calcium-independent phosphodiesterase inhibitors, also inhibit the binding of rolipram to rat brain membranes and reverse rese
