Computer-aided discovery of phenylpyrazole based amides as potent S6K1 inhibitors
Literature Information
Publication Date
2020-04-30
DOI
10.1039/C9MD00537D
Impact Factor
0
Authors
Yan Yin, Yuxing Sun, Lianhua Zhao, Jinpeng Pan
View Original
Abstract
Ribosomal protein S6 kinase beta-1 (S6K1) is an attractive therapeutic target. In this study, computational analysis of five thiophene urea-based S6K1 inhibitors was performed. Molecular docking showed that the five compounds formed hydrogen bonds with residues Glu173 and Leu175 of S6K1 and hydrophobic interactions with residues Val105, Leu97 and Met225, and these interactions were key elements for the inhibitory potency of the compounds. Binding free energy (ΔGbind) decomposition analysis showed that Leu97, Glu173, Val 105, Leu175, Leu97 and Met225 contribute the most to ΔGbind. Based on the computer results, phenylpyrazole based amides (D1–D3) were designed and synthesized. Biological evaluation revealed that D2 exhibited 15.9 nM S6K1 inhibition, medium microsomal stability and desirable bioavailability.
Related Literature
Enhancing spectral shifts of plasmon-coupled noble metal nanoparticles for sensing applications
Kristian L. Göeken, Ron Gill
2014-11-05
Paper
DOI: 10.1039/C4CP03739A
Investigation of molecular partitioning between non polar oil droplets and aqueous solution using double potential step chronoamperometry
Jonathan C. Newland, Patrick R. Unwin, Julie V. Macpherson
2014-03-06
Paper
DOI: 10.1039/C4CP00231H
Density of state determination of two types of intra-gap traps in dye-sensitized solar cells and its influence on device performance
Yi Wang, Dapeng Wu, Li-Min Fu, Xi-Cheng Ai, Dongsheng Xu, Jian-Ping Zhang
2014-04-24
Paper
DOI: 10.1039/C4CP00779D
Electronic structure and spectra of (Cu2O)n–H2O complexes
Jerry Whitten
2014-11-07
Paper
DOI: 10.1039/C4CP04303K
Generalized approximate spin projection calculations of effective exchange integrals of the CaMn4O5 cluster in the S1 and S3 states of the oxygen evolving complex of photosystem II
H. Isobe, M. Shoji, S. Yamanaka, H. Mino, Y. Umena, K. Kawakami, N. Kamiya, J.-R. Shen
2014-02-21
Paper
DOI: 10.1039/C4CP00282B
Superbasicity of silylene derivatives achieved via non-covalent intramolecular cation⋯π interactions and exploited as molecular containers for CO2
Rabindranath Lo, Mrinal Kanti Si
2014-05-07
Paper
DOI: 10.1039/C4CP01394H
Reactive molecular simulations of protonation of water clusters and depletion of acidity in H-ZSM-5 zeolite
Kaushik L. Joshi, George Psofogiannakis, Adri C. T. van Duin, Sumathy Raman
2014-07-16
Paper
DOI: 10.1039/C4CP02612H
IrO2 as a promoter of Pt–Ru for methanol electro-oxidation
V. Baglio, R. S. Amin, K. M. El-Khatib, S. Siracusano, C. D'Urso, A. S. Aricò
2014-04-08
Communication
DOI: 10.1039/C4CP00466C
The effect of nitrogen doping on mercury oxidation/chemical adsorption on the CuCo2O4(110) surface: a molecular-level description
Zhijian Mei, Ruiqing Zhang, Zhemin Shen, Wenhua Wang
2014-05-23
Paper
DOI: 10.1039/C4CP01362J
You might also like
Compound Q&A
What are the main uses of 1-(3-Aminophenyl)-3-[(3R)-1-(3,3-dimethyl-2-oxobutyl)-2-oxo-5-(2-pyridinyl)-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]urea (CAS: 155412-88-7)?
This compound is mainly used as an intermediate in the synthesis of antipsychoti...
155412-88-71-(3-Aminophenyl)-3-...
Compound Q&A
How should waste containing 1-(D-Ribofuranosyl)-1,4-dihydro-3-pyridinecarboxamide (CAS: 19132-12-8) be handled?
Waste containing 1-(D-Ribofuranosyl)-1,4-dihydro-3-pyridinecarboxamide (CAS: 191...
19132-12-81-(D-Ribofuranosyl)-...
Compound Q&A
What regulatory guidelines apply to 2-Methyl-2-propanyl 3-bromo-3-(hydroxymethyl)-1-azetidinecarboxylate (CAS: 2007919-81-3)?
2-Methyl-2-propanyl 3-bromo-3-(hydroxymethyl)-1-azetidinecarboxylate (CAS: 20079...
2007919-81-32-Methyl-2-propanyl ...
Compound Q&A
What is N-(4-Chloro-2-pyridinyl)acetamide (CAS: 245056-66-0)?
N-(4-Chloro-2-pyridinyl)acetamide (CAS: 245056-66-0) is a chemical compound with...
245056-66-0N-(4-Chloro-2-pyridi...
Compound Q&A
What is 5-Chloro-2-hydroxybenzoic acid (CAS: 321-14-2)?
5-Chloro-2-hydroxybenzoic acid, also known as 5-chlorosalicylic acid, is an arom...
321-14-25-Chloro-2-hydroxybe...
Compound Q&A
What precautions should be taken when handling 1,1-Dichloro-1-fluoroethane (CAS: 1717-00-6)?
When handling 1,1-Dichloro-1-fluoroethane (CAS: 1717-00-6), it is important to u...
1717-00-61,1-Dichloro-1-fluor...
Compound Q&A
What are the physical and chemical properties of Fmoc-(2S,3R)-3-phenylpyrrolidine-2-carboxylic acid (CAS: 281655-32-1)?
Fmoc-(2S,3R)-3-phenylpyrrolidine-2-carboxylic acid is a white crystalline solid ...
281655-32-1Fmoc-(2S,3R)-3-pheny...
Compound Q&A
What are the main uses of 4-Amino-5-bromo-2-pyridinecarboxylic acid (CAS: 1363381-01-4)?
4-Amino-5-bromo-2-pyridinecarboxylic acid is primarily used as a precursor in th...
1363381-01-44-Amino-5-bromo-2-py...
Compound Q&A
What precautions should be taken when handling (S)-tert-butyl 2-((2-(4-bromophenyl)-2-oxoethyl)carbamoyl)pyrrolidine-1-carboxylate (CAS: 1007881-98-2)?
Handling this compound should be done with personal protective equipment (PPE) i...
1007881-98-2(S)-tert-butyl 2-((2...
Compound Q&A
What precautions should be taken when handling 8-bromo-2,2-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-3-one (CAS: 688363-73-7)?
When handling 8-bromo-2,2-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-3-one, use prop...
688363-73-78-bromo-2,2-dimethyl...
Source Journal
Recommended Compounds
![tert-Butyl N-[(2-chloropyridin-4-yl)methyl]carbamate structure](https://static.chemtradehub.com/structs/916/916210-27-0-9f95.webp "tert-Butyl N-[(2-chloropyridin-4-yl)methyl]carbamate structure")
tert-Butyl N-[(2-chloropyridin-4-yl)methyl]carbamate
CAS Number:
916210-27-0
Molecular Formula:
C11H15ClN2O2
Recommended Suppliers
Disclaimer
This page provides academic journal information for reference and research purposes only. We are not affiliated with any journal publishers and do not handle publication submissions. For publication-related inquiries, please contact the respective journal publishers directly.
If you notice any inaccuracies in the information displayed, please contact us at support@chemtradehub.com. We will promptly review and address your concerns.