2017
DOI: 10.1002/minf.201700080
|View full text |Cite
|
Sign up to set email alerts
|

Multi‐objective Optimization of Benzamide Derivatives as Rho Kinase Inhibitors

Abstract: Despite recent advances in Computer Aided Drug Discovery and High Throughput Screening, the attrition rates of drug candidates continue to be high, underscoring the inherent complexity of the drug discovery paradigm. Indeed, a compromise between several objectives is often required to obtain successful clinical drugs. The present manuscript details a multi-objective workflow that integrates the 4D-QSAR and molecular docking methods in the simultaneous modeling of the Rho Kinase inhibitory activity and acute to… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
2

Citation Types

0
4
0

Year Published

2019
2019
2023
2023

Publication Types

Select...
5
1

Relationship

1
5

Authors

Journals

citations
Cited by 8 publications
(4 citation statements)
references
References 40 publications
0
4
0
Order By: Relevance
“…It would be therefore of huge interest to investigate these properties in the preliminary stages to in silico design of safer and more efficient drugs. Hence, the ADMET evaluations involve sequential and iterative assessments of the efficacy, PK, PD, metabolic and toxicological properties in the model of potential drug candidates 54 . From the ADMET results, the theoretical parameters of toxicity (LD 50 ) were obtained for each compound: N-4-Q (2.53 mol kg −1 ), N-4-QO (2.56 mol kg −1 ), CQ (2.95 mol kg −1 ), CQO (2.68 mol kg −1 ), HCQ (2.66 mol kg −1 ), HCQO (2.69 mol kg −1 ).…”
Section: Resultsmentioning
confidence: 99%
“…It would be therefore of huge interest to investigate these properties in the preliminary stages to in silico design of safer and more efficient drugs. Hence, the ADMET evaluations involve sequential and iterative assessments of the efficacy, PK, PD, metabolic and toxicological properties in the model of potential drug candidates 54 . From the ADMET results, the theoretical parameters of toxicity (LD 50 ) were obtained for each compound: N-4-Q (2.53 mol kg −1 ), N-4-QO (2.56 mol kg −1 ), CQ (2.95 mol kg −1 ), CQO (2.68 mol kg −1 ), HCQ (2.66 mol kg −1 ), HCQO (2.69 mol kg −1 ).…”
Section: Resultsmentioning
confidence: 99%
“…Along this line, the absorptiondistribution-metabolism-excretion-toxicity (ADMET) evaluations involve sequential and iterative assessments of the e cacy, pharmacokinetics, pharmacodynamics, metabolic and toxicological properties in the model of therapeutic agents, and hence contributing to design safer and more e cient drugs. [42] The ADMET analysis was carried out in order to evaluate the toxicity of our compounds, singleand co-crystals, under investigation. According to our results in Table 3, the LD 50 value found for ER, 2.23 mol.kg -1 , indicates more toxicity in relation to other single-and co-crystal compounds.…”
Section: Resultsmentioning
confidence: 99%
“…Previous literature on the construction of QSAR models shows that the most used feature selection methods are the following: chi-square (CS), , gain ratio (GR), , information gain (IG), , unbalanced correlation score (UCS), mutual information (MI), , standard correlation score (Fisher score, FS), , F-score (FS) base ranking, Shannon entropy (SE), , recursive feature elimination (RFE), and the fast clustering-based feature selection algorithm (FAST) …”
Section: Introductionmentioning
confidence: 99%