121189-89-7Relevant academic research and scientific papers
CA amide analogs and its preparation method and application
-
Paragraph 0084-0086, (2016/10/09)
The invention relates to the technical field of medicines. Piplartine is alkaloid extracted from perennial herbaceous vine piper longum of piperaceae. The invention provides a Piplartine analogue, which comprises a cis-trans-isomer, and any arbitrary mixture in those forms or medicinal salt thereof, and the structural formula of the Piplartine analogue is shown in a general formula (I). The invention also provides a preparation method of substituted Piplartine compounds, and an application thereof in preparation of an antitumor medicament.
Phenyl Esters Are Potent Inhibitors of Caseinolytic Protease P and Reveal a Stereogenic Switch for Deoligomerization
Hackl, Mathias W.,Lakemeyer, Markus,Dahmen, Maria,Glaser, Manuel,Pahl, Axel,Lorenz-Baath, Katrin,Menzel, Thomas,Sievers, Sonja,B?ttcher, Thomas,Antes, Iris,Waldmann, Herbert,Sieber, Stephan A.
supporting information, p. 8475 - 8483 (2015/07/15)
Caseinolytic protease P (ClpP) represents a central bacterial degradation machinery that is involved in cell homeostasis and pathogenicity. The functional role of ClpP has been studied by genetic knockouts and through the use of beta-lactones, which remain the only specific inhibitors of ClpP discovered to date. Beta-lactones have served as chemical tools to manipulate ClpP in several organisms; however, their potency, selectivity and stability is limited. Despite detailed structural insights into the composition and conformational flexibility of the ClpP active site, no rational efforts to design specific non-beta-lactone inhibitors have been reported to date. In this work, an unbiased screen of more than 137000 compounds was used to identify five phenyl ester compounds as highly potent ClpP inhibitors that were selective for bacterial, but not human ClpP. The potency of phenyl esters largely exceeded that of beta-lactones in ClpP peptidase and protease inhibition assays and displayed unique target selectivity in living S. aureus cells. Analytical studies revealed that while phenyl esters are cleaved like native peptide substrates, they remain covalently trapped as acyl-enzyme intermediates in the active site. The synthesis of 36 derivatives and subsequent structure-activity relationship (SAR) studies provided insights into conserved structural elements that are important for inhibition potency and acylation reactivity. Moreover, the stereochemistry of a methyl-substituent at the alpha position to the ester, resembling amino acid side chains in peptide substrates, impacted ClpP complex stability, causing either dissociation into heptamers or retention of the tetradecameric state. Mechanistic insights into this intriguing stereo switch and the phenyl ester binding mode were obtained by molecular docking experiments.
Design, synthesis and biological activity of piperlongumine derivatives as selective anticancer agents
Wu, Yuelin,Min, Xiao,Zhuang, Chunlin,Li, Jin,Yu, Zhiliang,Dong, Guoqiang,Yao, Jiangzhong,Wang, Shengzheng,Liu, Yang,Wu, Shanchao,Zhu, Shiping,Sheng, Chunquan,Wei, Yunyang,Zhang, Huojun,Zhang, Wannian,Miao, Zhenyuan
, p. 545 - 551 (2014/07/07)
In an effort to expand the structure-activity relationship of the natural anticancer compound piperlongumine, we have prepared sixteen novel piperlongumine derivatives with halogen or morpholine substituents at C2 and alkyl substituents at C7. Most of 2-halogenated piperlongumines showed potent in vitro activity against four cancer cells and modest selectivity for lung normal cells. The highly active anticancer compound 11h exhibited obvious ROS elevation and excellent in vivo antitumor potency with suppressed tumor growth by 48.58% at the dose of 2 mg/kg. The results indicated that halogen substituents as electrophilic group at C2 played an important role in increasing cytotoxicity.
A facile one-pot stereoselective synthesis of trisubstituted (E)-2-methylalk-2-enoic acids from unactivated Baylis-Hillman adducts and a simple access to some important insect pheromones
Das, Biswanath,Chowdhury, Nikhil,Banerjee, Joydeep,Majhi, Anjoy
, p. 6615 - 6618 (2007/10/03)
An efficient one-pot stereoselective synthesis of trisubstituted (E)-2-methylalk-2-enoic acids has been accomplished by treatment of unactivated Baylis-Hillman adducts, 3-hydroxy-2-methylenealkanoates, with Al-NiCl2·6H2O in methanol at room temperature followed by hydrolysis. The method has been applied to the synthesis of three important insect pheromones, (4S,2E)-2,4-dimethyl-2-hexenoic acid, (+)-(S)-manicone and (+)-(S)-normanicone.
Intramolecular Oxidative Coupling of Aromatic Compounds. II. The Synthesis of (2RS,3SR)- and (2RS,3RS)-2,3-Dimethyl-1,4-bis(3,4,5-trimethoxyphenyl)butan-1-one and the Determination of Stereochemistry
Krauss, Adrian S.,Taylor, Walter C.
, p. 1335 - 1340 (2007/10/02)
The C-methylation of 3-methyl-1,4-bis(3,4,5-trimethoxyphenyl)butan-1-one (9) gave in a ratio of 4:1 the diastereoisomers, (2RS,3SR)- and (2RS,3RS)-2,3-dimethyl-1,4-bis(3,4,5-trimethoxyphenyl)butan-1-one, (7) and (8) respectively.The stereochemistry of eac
