349398-34-1Relevant articles and documents
N-Phenylbenzamide derivatives as alternative oxidase inhibitors: Synthesis, molecular properties, 1H-STD NMR, and QSAR
Barsottini, Mario R. O.,Carazzolle, Marcelo F.,Costa, Paulo C. S.,Evangelista, Joel S.,Miranda, Paulo C. M. L.,Nascimento, Andrey F. Z.,Pereira, Gon?alo A. G.,Pires, Bárbara A.,Rocco, Silvana A.,Sfor?a, Maurício L.,Silva, Jaqueline S.,Vieira, Maria L. L.,Zeri, Ana C. M.
, (2020/02/27)
In the present work, 117 N-phenylbenzamides (NPDs) were prepared and evaluated against recombinant AOX from the fungal pathogen Moniliophthora perniciosa. 1H, 13C NMR, FTIR, and mass spectra provided structural information on NPDs. The library compounds were tested as Alternative Oxidase inhibitors in two different assays using the model yeast Pichia pastoris: cell growth and oxygen consumption assays. The most active compound, 3FH, was further characterized by DRX and 1H-NMR-STD. Single crystal X-ray diffraction showed intra- and intermolecular interactions of 3FH in solid-state and elucidated its 3D structural configuration. 1H-NMR-STD allowed us to derive protein-ligand interactions in a membrane-mimetic system and evidenced an outstanding interaction of 3FH with this enzyme. Results of both biological assays were used as input to Quantitative Structure-Activity Relationship models, which highlighted the more important molecular fragments contributions for protein-ligand interaction.
Aza-acridine compound and preparation method and application thereof
-
Paragraph 0103; 0213; 0214, (2017/07/21)
The invention discloses a method for efficiently preparing an aza-acridine compound. The structural formula of the aza-acridine compound is shown as a formula I; the preparation method comprises the following steps: adding a 2-aminoquinoline-3-methanamide compound and a solvent under an air condition, and heating to reaction temperature; after the reaction is ended, separating and purifying to obtain multisubstituted acridine derivatives shown as the following formula, wherein the reaction temperature is 100 to 200DEG C, and the reaction time is 1 to 24 hours. A synthetic method of the aza-acridine compound, disclosed by the invention, has the advantages of scientificity, reasonability, simple and easily-operated synthesis process and high synthetic yield; a product is easy to purify. The invention also relates to the aza-acridine compound which can be used for inhibiting EGFR (Epidermal Growth Factor Receptor) and SrC, a preparation method of the aza-acridine compound, activity of a drug containing the aza-acridine compound and the application of the drug. The compound is shown in a formula II and can be used for preparing an EGFR and SrC activity inhibitor and a disease treatment medicine activated and mediated by the EGFR and the SrC.
Design, synthesis and evaluation of azaacridine derivatives as dual-target EGFR and Src kinase inhibitors for antitumor treatment
Cui, Zhishan,Chen, Shaopeng,Wang, Yanwei,Gao, Chunmei,Chen, Yuzong,Tan, Chunyan,Jiang, Yuyang
, p. 372 - 381 (2017/05/19)
Overexpression of EGFR is often associated with advanced stage disease and poor prognosis. In certain cancers, Src works synergistically with EGFR to promote proliferation, survival, invasion and metastasis. Development of dual-target drugs against EGFR and Src is of therapeutic advantage against these cancers. Based on molecular docking and our previous studies, we rationally designed a new series of azaacridine derivatives as potent EGFR and Src dual inhibitors. Most of the synthesized azaacridines displayed good antiproliferative activity against K562 and A549?cells. The representative compound 13b showed nM IC50 values against K562 and A549?cells, and inhibited EGFR at inhibition rate of 33.53% at 10?μM and Src at inhibition rate of 72.12% at 1?μM. Furthermore, compound 13b could inhibit the expression of EGFR, p-EGFR, Src and p-Src. Moreover, 13b efficiently inhibited the invasion of tumor cells and induced cancer cells apoptosis. Our study suggested that azaacridine scaffold can be developed as novel multi-target kinase inhibitors for cancer therapy.
Potent and selective inhibitors of the TASK-1 potassium channel through chemical optimization of a bis-amide scaffold
Flaherty, Daniel P.,Simpson, Denise S.,Miller, Melissa,Maki, Brooks E.,Zou, Beiyan,Shi, Jie,Wu, Meng,McManus, Owen B.,Aubé, Jeffrey,Li, Min,Golden, Jennifer E.
, p. 3968 - 3973 (2014/09/03)
TASK-1 is a two-pore domain potassium channel that is important to modulating cell excitability, most notably in the context of neuronal pathways. In order to leverage TASK-1 for therapeutic benefit, its physiological role needs better characterization; however, designing selective inhibitors that avoid the closely related TASK-3 channel has been challenging. In this study, a series of bis-amide derived compounds were found to demonstrate improved TASK-1 selectivity over TASK-3 compared to reported inhibitors. Optimization of a marginally selective hit led to analog 35 which displays a TASK-1 IC 50 = 16 nM with 62-fold selectivity over TASK-3 in an orthogonal electrophysiology assay.
Synthesis and SAR of novel, non-MPEP chemotype mGluR5 NAMs identified by functional HTS
Zhou, Ya,Rodriguez, Alice L.,Williams, Richard,Weaver, C. David,Conn, P. Jeffrey,Lindsley, Craig W.
scheme or table, p. 6502 - 6506 (2010/05/17)
This Letter describes the discovery and SAR of three novel series of mGluR5 non-competitive antagonists/negative allosteric modulators (NAMs) not based on manipulation of an MPEP/MTEP chemotype identified by a functional HTS approach. This work demonstrates fundamentally new mGluR5 NAM chemotypes with submicromolar potencies, and further examples of a mode of pharmacology 'switch' to provide PAMs with a non-MPEP scaffold.
EFFECT OF THE STRUCTURE OF THE REAGENTS IN THE REACTIONS OF AROYL CHLORIDES WITH N-METHYLARYLAMINES, CATALYZED BY TETRABUTYLAMMONIUM CHLORIDE IN BENZENE
Titskii, G. D.,Turovskaya, M. K.
, p. 921 - 926 (2007/10/02)
The reactions of aroyl chlorides with N-methylarylamines, catalyzed by tetrabutylammonium chloride, lead to the formation of a complex with a hydrogen bond between the arylamine and the catalyst and its subsequent slow reaction with the aroyl chloride.The influence of the inductive effects of the substituents on the rate constants for the reaction of the aroyl chlorides with the intermediate complex and on the catalytic rate constants is described by two-parameter correlation equations.The role "amide conjugation" in the investigated processes is discussed.
JOINT EFFECT OF STRUCTURE OF REAGENTS AND TEMPERATURE ON REACTIVITY OF AROYL BROMIDE-PRIMARY ARYLAMINE SYSTEMS IN BENZENE. CROSSED CORRELATION
Shpan'ko, I. V.,Goncharov, A. N.,Likhomanenko, E. E.
, p. 522 - 530 (2007/10/02)
The kinetics of the reactions of aroyl bromides with primary arylamines in benzene were studied at 10, 25, 40, and 55 deg C.The effects of factors (temperature, the structure of the aroyl bromides and primary arylamines) varied separately and in pairs and also the joint effect of the three factors on the process rate were assessed quantitatively.The joint effect of the structure of the primary arylamines and the temperature on the reactivity of the system is nonadditive, and the effect of the structure of the aroyl bromides and temperature is additive.The influence of the varied parameters on the nature of the translation states in the reactions is discussed.
TRANSITION THROUGH AN ISOPARAMETRIC POINT RELATIVE TO SUBSTITUENT IN THE REACTION OF AROYL BROMIDES WITH PRIMARY ARYLAMINES. RELATIONSHIP BETWEEN REACTIVITY AND SELECTIVITY
Shpan'ko, I. V.,Goncharev, A. N.,Chetverova, E. V.,Likhomanenko, E. E.
, p. 1290 - 1295 (2007/10/02)
Rates were measured for the reactions of aroyl bromides with primary arylamines in 1:1 chlorobenzene-cyclohexane at 25 deg C.The kinetic data were treated by the Hammett-Taft equations and cross correlation.This is the first reported transition through an isoparametric point relative to the structure of the nucleophile accompanied by inversion of the sign of the sensitivity parameter relative to the substrate structure in the aroyl bromide-primary arylamine reaction system.The results of the cross correlation analysis were interpreted on the basis of a concerted mechanism involving nucleophilic substitution at the carbonyl carbon atom.The relationship between the reactivity of the system studied and its selectivity was examined.
EFFECT OF THE STRUCTURE ON THE RATE OF THE REACTIONS OF AROYL CHLORIDES WITH PRIMARY ARYLAMINES IN MIXTURES OF tert-BUTYL ALCOHOL AND CHLOROBENZENES. THE TRANSITION THROUGH ISOPARAMETRIC POINTS WITH RESPECT TO THE STRUCTURE PARAMETERS
Shpan'ko, I. V.,Likhomanenko, E. E.
, p. 1702 - 1710 (2007/10/02)
The rate of the reactions of aroyl chlorides with primary arylamines in 3.5, 5, and 7M solutions of tert-butyl alcohol in chlorobenzene at 25 deg C was measured.The effect of the structure of the reagents on the process rate was determined quantitatively by means of the Hammett-Taft and crossed correlation equations.The isoparametric points with respect to the structure of the substrate and the nucleophile were reached experimentally, and the transition through some of these points was also realised.It was found that the specific solvation of the primary arylamines by the tert-butyl alcohol was nonuniform in that an incre ase in the concentration of the alcohol in the investigated range reduced, did not change, and increased the rates of the reactions with 3-chloroaniline, 3-nitroaniline, and 3-nitro-5-methoxycarbonylaniline respectively.The effect of specific solvation on the behavior of the correlation parameters is discussed.
MUTUAL EFFECT OF THE STRUCTURES OF THE REAGENTS ON THE RATE OF THE REACTIONS OF AROYL CHLORIDES WITH PRIMARY ARYLAMINES IN DIOXANE AND MIXTURES OF CHLOROBENZENE WITH tert-BUTYL ALCOHOL
Likhomanenko, E. E.,Shpan'ko, I. V.,Litvinenko, L. M.,Goncharov, A. N.
, p. 2341 - 2347 (2007/10/02)
The rate of the reactions of aroyl chlorides with primary arylamines in specifically solvating media (dioxane, 0.1 M and 2 M solutions of tert-butyl alcohol in chlorobenzene) was measured.The joint effect of the structures of the reagents on the rate of the process in the employed media assessed quantitatively by crossed correlation.It was shown that the mutual effect of the structural factors on the reactivity is nonadditive in a 0.1 M solution of tert-butyl alcohol in chlorobenzene and additive in dioxane and also in a 2 M solution of tert-butyl alcohol in chlorobenzene.The effect of the structure of the reagents and specific solvation on the nature of the transition states of the reactions is discussed.
