104499-27-6Relevant academic research and scientific papers
SAR-mediated similarity assessment of the property profile for new, silicon-based AChE/BChE inhibitors
Bak, Andrzej,Pizova, Hana,Kozik, Violetta,Vorcakova, Katarina,Kos, Jiri,Treml, Jakub,Odehnalova, Klara,Oravec, Michal,Imramovsky, Ales,Bobal, Pavel,Smolinski, Adam,Trávní?ek, Zdeněk,Jampilek, Josef
, (2019)
A set of 25 novel, silicon-based carbamate derivatives as potential acetyl-and butyrylcholinesterase (AChE/BChE) inhibitors was synthesized and characterized by their in vitro inhibition profiles and the selectivity indexes (SIs). The prepared compounds w
Site-Selective Esterifications of Polyol β-Hydroxyamides and Applications to Serine-Selective Glycopeptide Modifications
Takemoto, Kohei,Nishikawa, Yasuhiro,Moriguchi, Shohei,Hori, Yuna,Kamezawa, Yuki,Matsui, Takami,Hara, Osamu
, p. 7534 - 7538 (2019)
The site-selective acylations of β-hydroxyamides in the presence of other hydroxyl groups are described. Central to the success of this modification is the metal-template-driven acylation using pyridine ketoxime esters as acylating reagents in combination
Synthesis and use of N-Fmoc-l-fluoroalanine
Carpentier, Claudia,Godbout, Rapha?l,Otis, Fran?ois,Voyer, Normand
, p. 1244 - 1246 (2015)
We report a practical synthesis of N-Fmoc protected l-fluoroalanine 6 from l-serine. The key step involves a deoxofluorination reaction which was best achieved using XtalFluor-E in the presence of triethylamine trihydrofluoride. We also report the use of 6 in solid-phase peptide synthesis for the preparation of a model tripeptide demonstrating the possibility of incorporating a fluorinated probe in a peptide without elimination. Furthermore, cleavage of the dipeptide permitted to verify that 6 has a high enantiopurity.
Design, Synthesis, and Conformation-Activity Study of Unnatural Bridged Bicyclic Depsipeptides as Highly Potent Hypoxia Inducible Factor-1 Inhibitors and Antitumor Agents
Koike, Kota,Nagano, Masanobu,Ebihara, Masahiro,Hirayama, Tasuku,Tsuji, Mieko,Suga, Hiroaki,Nagasawa, Hideko
, p. 4022 - 4046 (2020)
By carrying out structural modifications based on the bicyclic peptide structure of echinomycin, we successfully synthesized various powerful antitumor derivatives. The ring conformation in the obtained compounds was restricted by cross-linking with an unnatural bond. The prepared derivatives were demonstrated to strongly suppress the hypoxia inducible factor (HIF)-1 transcriptional activation and hypoxia induction of HIF-1 protein expression. Particularly, alkene-bridged derivative 12 exhibited remarkably potent cytotoxicity (IC50 = 0.22 nM on the MCF-7 cell line) and HIF-1 inhibition (IC50 = 0.09 nM), which considerably exceeded those of echinomycin. Conformational analyses and molecular modeling studies revealed that the biological activities were enhanced following restriction of the conformation by cross-linking through a metabolically stable and rigid bridge bond. In addition, we proposed a new globular conformation stabilized by intramolecular πstacking that can contribute to the biological effects of bicyclic depsipeptides. The developments presented in the current study serve as a useful guide to expand the chemical space of peptides in drug discovery.
Amino acid derivatives of ligustrazine-oleanolic acid as new cytotoxic agents
Chu, Fuhao,Xu, Xin,Li, Guoliang,Gu, Shun,Xu, Kuo,Gong, Yan,Xu, Bing,Wang, Mina,Zhang, Huazheng,Zhang, Yuzhong,Wang, Penglong,Lei, Haimin
, p. 18215 - 18231 (2014)
A series of novel ligustrazine-oleanolic acid (TOA) derivatives were designed, and synthesized by conjugating amino acids to the 3-hydroxy group of TOA by ester bonds. Their cytotoxicity was evaluated on four cancer cell lines (HepG2, HT-29, Hela and BGC-823) by standard MTT assays. The ClogP values were calculated by means of computer simulation, and logP values of both 3β-glycine ester olean-12-en-28-oic acid-3,5,6-trimethylpyrazin-2-methyl ester (6a) and TOA were determined using a shake flask-ultraviolet spectrophotometry method. It was found that 6a and the 3β-L-lysine ester-6g not only displayed good cytotoxicity (IC50 50 = 4.884 μM) had lower nephrotoxicity than both 6g (IC50 = 2.310 μM) and cisplatin (CDDP, IC50 = 3.691 μM) on MDCK cells. Combining Giemsa and DAPI staining, it was further verified that 6a could induce HepG2 apoptosis via nuclei fragmentation and had lower nephrotoxicity. In addition, the structure-activity relationships of these derivatives are briefly discussed.
Rational Design and Synthesis of Selective PRMT4 Inhibitors: A New Chemotype for Development of Cancer Therapeutics**
Sutherland, Mathew,Li, Alice,Kaghad, Anissa,Panagopoulos, Dimitrios,Li, Fengling,Szewczyk, Magdalena,Smil, David,Scholten, Cora,Bouché, Léa,Stellfeld, Timo,Arrowsmith, Cheryl H.,Barsyte, Dalia,Vedadi, Masoud,Hartung, Ingo V.,Steuber, Holger,Britton, Robert,Santhakumar, Vijayaratnam
, p. 1116 - 1125 (2021/03/08)
Protein arginine N-methyl transferase 4 (PRMT4) asymmetrically dimethylates the arginine residues of histone H3 and nonhistone proteins. The overexpression of PRMT4 in several cancers has stimulated interest in the discovery of inhibitors as biological tools and, potentially, therapeutics. Although several PRMT4 inhibitors have been reported, most display poor selectivity against other members of the PRMT family of methyl transferases. Herein, we report the structure-based design of a new class of alanine-containing 3-arylindoles as potent and selective PRMT4 inhibitors, and describe key structure–activity relationships for this class of compounds.
SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF
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, (2019/08/26)
Disclosed are compounds having potency in the modulation of NMDA receptor activity. Such compounds can be used in the treatment of conditions such as depression and related disorders as well as other disorders.
MACROCYCLIC BROAD SPECTRUM ANTIBIOTICS
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Paragraph 00776, (2017/08/01)
Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of bacterial type 1 signal peptidase (SpsB), an essential protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.
Preparation method and application of antitumor drug X-TOA
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Paragraph 0108; 0109, (2016/10/17)
The invention provides a preparation method of compounds with the structure represented by general formula 1, and an application of the compounds in the preparation of antitumor drugs. The compounds are prepared through ester bond condensation of a 3th hy
Enantioselective aldol reaction between isatins and cyclohexanone catalyzed by amino acid sulphonamides
Wang, Jun,Liu, Qi,Hao, Qing,Sun, Yanhua,Luo, Yiming,Yang, Hua
, p. 314 - 319 (2015/03/30)
Sulphonamides derived from primary α-amino acid were successfully applied to catalyze the aldol reaction between isatin and cyclohexanone under neat conditions. More interestingly, molecular sieves, as privileged additives, were found to play a vital role in achieving high enantioselectivity. Consequently, high yields (up to 99%) along with good enantioselectivities (up to 92% ee) and diastereoselectivities (up to 95:5 dr) were obtained. In addition, this reaction was also conveniently scaled up, demonstrating the applicability of this protocol.
