1024605-15-9Relevant academic research and scientific papers
Bornyl (3,4,5-trihydroxy)-cinnamate - An optimized human neutrophil elastase inhibitor designed by free energy calculations
Steinbrecher, Thomas,Hrenn, Andrea,Dormann, Korinna L.,Merfort, Irmgard,Labahn, Andreas
, p. 2385 - 2390 (2008)
Human neutrophil elastase (HNE), a serine protease, is involved in the regulation of inflammatory processes and controlled by endogenous proteinase inhibitors. Abnormally high levels of HNE can cause degradation of healthy tissues contributing to inflammatory diseases such as rheumatoid arthritis, and also psoriasis and delayed wound healing. In continuation of our research on HNE inhibitors we have used the recently developed binding mode model for a group of cinnamic acid derivative elastase inhibitors and created bornyl (3,4,5-trihydroxy)-cinnamate. This ligand exhibited improved binding affinity predicted by means of free energy calculations. An organic synthesis scheme for the ligand was developed and its inhibitory activity was tested toward the isolated enzyme. Its IC50 value was found to be three times lower than that of similar compounds, which is in line with the computational result showing the high potential of free energy calculations as a tool in drug development.
Total Synthesis of Proposed Structure of Yuremamine and All Diastereomers Using [3+2]-Cycloaddition of Platinum-Containing Azomethine Ylide
Ohyama, Tomoya,Uchida, Masako,Kusama, Hiroyuki,Iwasawa, Nobuharu
supporting information, p. 1850 - 1853 (2015/09/07)
Total synthesis of the proposed structure of yuremamine has been achieved for the first time based on the intermolecular [3+2]-cycloaddition reaction of the platinum-containing azomethine ylide. All the possible diastereomers of yuremamine were also synthesized via the common intermediate. Through these syntheses, it was confirmed that the proposed structure of yuremamine and the diastereomers differ from the natural product. The total synthesis of the proposed structure of yuremamine and its diastereomers has been achieved based on the [3+2]-cycloaddition reaction of the platinum-containing azomethine ylide. Its basic core skeleton, pyrrolo[1,2-a]indole skeleton, was efficiently constructed by this method at an early stage of the synthesis and a straightforward, short-step synthesis of the target products has been achieved.
