1565-17-9Relevant articles and documents
Simple and efficient synthesis of 3,4-dihydro-2-pyridones via novel solid-supported aza-annulation
Wagman,Wang,Nuss
, p. 9103 - 9113 (2000)
A diverse array of 3,4-dihydro-2-pyridones 13 were produced utilizing the unique properties of solid-supported reactions to both drive the reactions to completion and isolate the desired products. The pyridones were synthesized in high purity by a simple sequence of novel steps commencing from an acetophenone-functionalized resin. The para-substituted acetophenone 9 could be anchored to the resin through either a sulfonamide or a carboxamide linkage. The sulfonamide resin 9a, which gave the best results, was treated with several aryl aldehydes and ethoxide to give a variety of chalcones 10a-k in excellent yield (82-99%) upon TFA cleavage. Addition of either methyl or allyl malonate and DBU to 10a-k afforded smoothly the Michael adducts 11a-j (70-99%) which were subsequently cyclized in one step employing acetic acid as a catalyst and several diverse amines to give pure 3,4-dihydro-2-pyridones 13a-p in moderate to excellent yields (30-98%).
Palladium-Catalyzed ortho-Benzoylation of Sulfonamides through C?H Activation: Expedient Synthesis of Cyclic N-Sulfonyl Ketimines
Ojha, Subhadra,Panda, Niranjan
, p. 561 - 571 (2019/12/24)
The ortho-carbonylation of sulfonylarenes by non-hazardous aryl aldehydes as a carbonyl precursor was reported. In this method, the sulfonamide group serves as a directing group for C?H activation in the presence of a Pd catalyst under ligand-free conditions. The scope of this strategy has been extended to the one-pot two-step synthesis of cyclic N-sulfonyl ketimines under mild reaction conditions. Our approach could be considered as an alternative by circumventing the use of highly reactive organolithium or Grignard reagents to access a wide range of biologically potent cyclic N-sulfonyl ketimines. (Figure presented.).
Design, Synthesis, and Biological Evaluation of Novel Allosteric Protein Disulfide Isomerase Inhibitors
Yang, Suhui,Shergalis, Andrea,Lu, Dan,Kyani, Anahita,Liu, Ziwei,Ljungman, Mats,Neamati, Nouri
, p. 3447 - 3474 (2019/04/16)
Protein disulfide isomerase (PDI) is responsible for nascent protein folding in the endoplasmic reticulum (ER) and is critical for glioblastoma survival. To improve the potency of lead PDI inhibitor BAP2 ((E)-3-(3-(4-hydroxyphenyl)-3-oxoprop-1-en-1-yl)benzonitrile), we designed and synthesized 67 analogues. We determined that PDI inhibition relied on the A ring hydroxyl group of the chalcone scaffold and cLogP increase in the sulfonamide chain improved potency. Docking studies revealed that BAP2 and analogues bind to His256 in the b′ domain of PDI, and mutation of His256 to Ala abolishes BAP2 analogue activity. BAP2 and optimized analogue 59 have modest thiol reactivity; however, we propose that PDI inhibition by BAP2 analogues depends on the b′ domain. Importantly, analogues inhibit glioblastoma cell growth, induce ER stress, increase expression of G2M checkpoint proteins, and reduce expression of DNA repair proteins. Cumulatively, our results support inhibition of PDI as a novel strategy to treat glioblastoma.
