64132-13-4Relevant academic research and scientific papers
Supramolecular luminescent lanthanide dimers for fluoride sequestering and sensing
Liu, Tao,Nonat, Aline,Beyler, Maryline,Regueiro-Figueroa, Martín,Nchiminono, Katia,Jeannin, Olivier,Camerel, Franck,Debaene, Fran?ois,Cianférani-Sanglier, Sarah,Tripier, Rapha?l,Platas-Iglesias, Carlos,Charbonnière, Lo?c J.
, p. 7259 - 7263 (2014)
Lanthanide complexes (Ln=Eu, Tb, and Yb) that are based on a C 2-symmetric cyclen scaffold were prepared and characterized. The addition of fluoride anions to aqueous solutions of the complexes resulted in the formation of dinuclear supramolecular compounds in which the anion is confined into the cavity that is formed by the two complexes. The supramolecular assembly process was monitored by UV/Vis absorption, luminescence, and NMR spectroscopy and high-resolution mass spectrometry. The X-ray crystal structure of the europium dimer revealed that the architecture of the scaffold is stabilized by synergistic effects of the Eu-F-Eu bridging motive, πstacking interactions, and a four-component hydrogen-bonding network, which control the assembly of the two [EuL] entities around the fluoride ion. The strong association in water allowed for the luminescence sensing of fluoride down to a detection limit of 24nM.
Identification of a buried pocket for potent and selective inhibition of Chk1: Prediction and verification
Foloppe, Nicolas,Fisher, Lisa M.,Francis, Geraint,Howes, Rob,Kierstan, Peter,Potter, Andrew
, p. 1792 - 1804 (2006)
Inhibition of the Chk1 kinase by small molecules binding to its active site is a strategy of great therapeutic interest for oncology. We report how computational modelling predicted the binding mode of ligands of special interest to the Chk1 ATP site, for representatives of an indazole series and debromohymenialdisine. These binding modes were subsequently confirmed by X-ray crystallography. The binding mode of a potent indazole derivative involves non-conventional C-H...O and N-H...π-aromatic interactions with the protein. These interactions are formed in a buried pocket at the periphery of the ATP-binding site, the importance of which has previously been overlooked for ligand design against Chk1. It is demonstrated that filling this pocket can confer ligands with dramatically enhanced affinity for Chk1. Structural arguments in conjunction with assay data explain why targeting this pocket is also advantageous for selective binding to Chk1. Structural overlays of known inhibitors complexed with Chk1 show that only the indazole series utilizes the pocket of interest. Therefore, the analysis presented here should prove helpful in guiding future structure-based ligand design efforts against Chk1.
Anticancer activity evaluation of indazolyl-substituted piperidin-4-yl-aminopyrimidines
Wang, Chao,Liu, Xiao-Wen,Xiao, Ting,Xu, Zhi-Qiang,Cao, Shuang,Wang, Hai-Feng,Yan, Qiong-Jiao,Gu, Shuang-Xi,Zhu, Yuan-Yuan
, p. 910 - 915 (2020)
Based on our previous work, a series of indazolyl-substituted piperidin-4-yl-aminopyrimidines, which were firstly used as anti-HIV agents, were evaluated for their anticancer potency in five cancer cell lines. Notably, they exhibited excellent activities
Biocatalytic reduction of α,β-unsaturated carboxylic acids to allylic alcohols
Aleku, Godwin A.,Leys, David,Roberts, George W.
, p. 3927 - 3939 (2020/07/09)
We have developed robust in vivo and in vitro biocatalytic systems that enable reduction of α,β-unsaturated carboxylic acids to allylic alcohols and their saturated analogues. These compounds are prevalent scaffolds in many industrial chemicals and pharmaceuticals. A substrate profiling study of a carboxylic acid reductase (CAR) investigating unexplored substrate space, such as benzo-fused (hetero)aromatic carboxylic acids and α,β-unsaturated carboxylic acids, revealed broad substrate tolerance and provided information on the reactivity patterns of these substrates. E. coli cells expressing a heterologous CAR were employed as a multi-step hydrogenation catalyst to convert a variety of α,β-unsaturated carboxylic acids to the corresponding saturated primary alcohols, affording up to >99percent conversion. This was supported by the broad substrate scope of E. coli endogenous alcohol dehydrogenase (ADH), as well as the unexpected CC bond reducing activity of E. coli cells. In addition, a broad range of benzofused (hetero)aromatic carboxylic acids were converted to the corresponding primary alcohols by the recombinant E. coli cells. An alternative one-pot in vitro two-enzyme system, consisting of CAR and glucose dehydrogenase (GDH), demonstrates promiscuous carbonyl reductase activity of GDH towards a wide range of unsaturated aldehydes. Hence, coupling CAR with a GDH-driven NADP(H) recycling system provides access to a variety of (hetero)aromatic primary alcohols and allylic alcohols from the parent carboxylates, in up to >99percent conversion. To demonstrate the applicability of these systems in preparative synthesis, we performed 100 mg scale biotransformations for the preparation of indole-3-aldehyde and 3-(naphthalen-1-yl)propan-1-ol using the whole-cell system, and cinnamyl alcohol using the in vitro system, affording up to 85percent isolated yield.
Indazolyl-substituted piperidin-4-yl-aminopyrimidines as HIV-1 NNRTIs: Design, synthesis and biological activities
Xiao, Ting,Tang, Jia-Fan,Meng, Ge,Pannecouque, Christophe,Zhu, Yuan-Yuan,Liu, Gen-Yan,Xu, Zhi-Qiang,Wu, Feng-Shou,Gu, Shuang-Xi,Chen, Fen-Er
, (2019/12/09)
A series of indazolyl-substituted piperidin-4-yl-aminopyrimidines (IPAPYs) were designed from two potent HIV-1 NNRTIs piperidin-4-yl-aminopyrimidine 3c and diaryl ether 4 as the lead compounds by molecular hybridization strategy. The target molecules 5a-q
Implementation of the CYP Index for the Design of Selective Tryptophan-2,3-dioxygenase Inhibitors
Castanedo, Georgette M.,Dement, Kevin,Dipasquale, Antonio,Gazzard, Lewis,Goon, Leanne,Gustafson, Amy,Harris, Seth F.,Jaipuri, Firoz A.,Kumar, Sanjeev,La, Hank,Li, Xiaokai,Liu, Wen,Liu, Yichin,Mautino, Mario R.,Mendonca, Rohan,Oh, Angela J.,Parr, Brendan T.,Pastor, Richard,Pavana, Roheeth K.,Pei, Zhonghua,Potturi, Hima,Sellers, Benjamin D.,Shao, Cheng,Vanderporten, Erica C.,Velvadapu, Venkata,Waldo, Jesse P.,Wu, Guosheng,Yuen, Po-Wai,Zhang, Yamin,Zhang, Zuhui
supporting information, p. 541 - 549 (2020/04/30)
A class of imidazoisoindole (III) heme-binding indoleamine-2,3-dioxygenase (IDO1) inhibitors were optimized via structure-based drug design into a series of tryptophan-2,3-dioxygenase (TDO)-selective inhibitors. Kynurenine pathway modulation was demonstrated in vivo, which enabled evaluation of TDO as a potential cancer immunotherapy target. As means of mitigating the risk of drug-drug interactions arising from cytochrome P450 inhibition, a novel property-based drug design parameter, herein referred to as the CYP Index, was implemented for the design of inhibitors with appreciable selectivity for TDO over CYP3A4. We anticipate the CYP Index will be a valuable design parameter for optimizing CYP inhibition of any small molecule inhibitor containing a Lewis basic motif capable of binding heme.
EPHA4 CYCLIC PEPTIDE ANTAGONISTS AND METHODS OF USE THEREOF
-
, (2019/11/19)
Disclosed herein are compounds and methods of use thereof for the modulation of EphA4 receptor activity. In an aspect, is provided a method of treating or preventing a disease or disorder mediated by EphA4, comprising administering to a subject in need thereof a therapeutically effective amount of a compound as described herein, including certain embodiments, or the structural Formula (I), (l-A), (II), (III), (IV), (IV-1), (V), (Vl-A), (Vl-B), (VII-1), (VII-2), (VIII-1), or (VIII-2), or an enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.
Preparation method of indazole and application of indazole in medicine synthesis
-
, (2017/04/21)
The invention belongs to the field of chemicals, and relates to a preparation method of indazole and an application of the indazole in medicine synthesis. The invention discloses a preparation method of indazole and an application of the indazole in synthesizing 1H-indazole-3-carboxylic acid, lonidamine, a compound 8, a compound 9, a compound 10, axitinib, YD-3, YC-1 and similar substances thereof.
[6,6] FUSED BICYCLIC HDAC8 INHIBITORS
-
Paragraph 00378, (2019/08/15)
The present invention is directed to compounds of Formula I: and pharmaceutically acceptable salts, prodrugs, solvates, hydrates, tautomers, or isomers or thereof, wherein R1, R2, R2', L, X, W, Y1,Y2,
Copper(I) Oxide-Mediated Cyclization of o-Haloaryl N-Tosylhydrazones: Efficient Synthesis of Indazoles
Tang, Meng,Kong, Yuanfang,Chu, Bingjie,Feng, Dan
, p. 926 - 939 (2016/04/05)
An efficient synthesis of indazoles from readily accessible E/Z mixtures of o-haloaryl N-tosylhydrazones has been developed. The thermo-induced isomerization of N-tosylhydrazones is discussed. A series of valuable indazole derivatives are prepared in good yields, and the method has been successfully applied to the synthesis of the bioactive compounds, lonidamine, AF-2785, axitinib, YC-1 and YD-3.
