96400-72-5Relevant academic research and scientific papers
Discovery of a series of selective and cell permeable beta-secretase (BACE1) inhibitors by fragment linking with the assistance of STD-NMR
Fang, Wei-Shuo,Sun, De-yang,Yang, Shuang,Cheng, Chen,Moschke, Katrin,Li, Tianqi,Sun, Shanshan,Lichtenthaler, Stefan F.,Huang, Jian,Wang, Yinghong
, (2019/09/30)
Two β-secreatase (BACE1) inhibitors from natural products (cinnamic acid and flavone) were linked to furnish potent, cell permeable BACE1 inhibitors with noncompetitive mode of inhibition, with the assistance of saturated transfer difference (STD)-NMR technique. Some of these conjugates also exhibited selective BACE1 inhibition over other aspartyl proteases such as BACE-2 and renin, as well as poor cytotoxicity. Taken together, conjugates 4 represent a new series of BACE inhibitors warrants further investigation for their potential in Alzheimier's disease therapy.
Synthesis and inhibitory activity of mechanism-based 4-coumaroyl-CoA ligase inhibitors
Watanabe, Bunta,Kirikae, Hiroaki,Koeduka, Takao,Takeuchi, Yoshinori,Asai, Tomoki,Naito, Yoshiyuki,Tokuoka, Hideya,Horoiwa, Shinri,Nakagawa, Yoshiaki,Shimizu, Bun-ichi,Mizutani, Masaharu,Hiratake, Jun
, p. 2466 - 2474 (2018/04/30)
4-Coumaroyl-CoA ligase (4CL) is ubiquitous in the plant kingdom, and plays a central role in the biosynthesis of phenylpropanoids such as lignins, flavonoids, and coumarins. 4CL catalyzes the formation of the coenzyme A thioester of cinnamates such as 4-coumaric, caffeic, and ferulic acids, and the regulatory position of 4CL in the phenylpropanoid pathway renders the enzyme an attractive target that controls the composition of phenylpropanoids in plants. In this study, we designed and synthesized mechanism-based inhibitors for 4CL in order to develop useful tools for the investigation of physiological functions of 4CL and chemical agents that modulate plant growth with the ultimate goal to produce plant biomass that exhibits features that are beneficial to humans. The acylsulfamide backbone of the inhibitors in this study was adopted as a mimic of the acyladenylate intermediates in the catalytic reaction of 4CL. These acylsulfamide inhibitors and the important synthetic intermediates were fully characterized using two-dimensional NMR spectroscopy. Five 4CL proteins with distinct substrate specificity from four plant species, i.e., Arabidopsis thaliana, Glycine max (soybean), Populus trichocarpa (poplar), and Petunia hybrida (petunia), were used to evaluate the inhibitory activity, and the half-maximum inhibitory concentration (IC50) of each acylsulfamide in the presence of 4-coumaric acid (100 μM) was determined as an index of inhibitory activity. The synthetic acylsulfamides used in this study inhibited the 4CLs with IC50 values ranging from 0.10 to 722 μM, and the IC50 values of the most potent inhibitors for each 4CL were 0.10–2.4 μM. The structure–activity relationship observed in this study revealed that both the presence and the structure of the acyl group of the synthetic inhibitors strongly affect the inhibitory activity, and indicates that 4CL recognizes the acylsulfamide inhibitors as acyladenylate mimics.
Convergent Total Synthesis of (+/-)-Tenellin
Rigby, James H.,Qabar, Maher
, p. 5852 - 5853 (2007/10/02)
A convergent total synthesis of the fungal biochrome tenellin is reported.The synthesis features an efficient cyclocondensation of a cinnamate derived isocyanate with a fully elaborated diene β-keto ester enolate reaction partner.
