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Search for "lead optimization" in Full Text gives 10 result(s) in Beilstein Journal of Organic Chemistry.
Finding the most potent compounds using active learning on molecular pairs
Beilstein J. Org. Chem. 2024, 20, 2152–2162, doi:10.3762/bjoc.20.185
- during medicinal chemistry projects. We believe that ActiveDelta and other pairwise approaches show particular promise for adaptive machine learning when training data hungry neural networks on limited data and can serve as accurate platforms to guide lead optimization and prioritization during drug
2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space
Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163
- importance in medicinal chemistry, as it can be employed as a rational to expand bioactive chemical space to tackle lead optimization issues like lack of potency, efficacy, and selectivity or pharmacokinetic/dynamic issues. One of the most important building blocks (in the sense of participating in a vast
Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers
Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241
- the clinic, continuous discovery and development efforts are required. Especially the lead optimization stage is strongly dependent on integrated medicinal chemistry and biological profiling teams. In addition to potency considerations, drug-like properties aiming at favorable pharmacokinetics move
New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized
Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104
- of Ugi-4CR together with the ability to incorporate a variety of functionalities and modifications extend its application for the generation of organic compound libraries, following hit-to-lead optimization, choosing the hit structure and final marketed drug production [54][55][56][57][58]. Moreover
Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa
Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277
- modelling and chemical lead optimization. Examples of successful inhibitors are represented by the scaffolds of various 2-benzamidobenzoic acids [11][25][26], 2-nitrophenyl derivatives [27][28][29], ureidothiophene-2-carboxylic acids [24][30], and catechol-based compounds [31]. Many promising in vitro
Computational methods in drug discovery
Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267
- methods are discussed. Advances in virtual high-throughput screening, protein structure prediction methods, protein–ligand docking, pharmacophore modeling and QSAR techniques are reviewed. Keywords: ADME; computer-aided drug design; docking; free energy; high-throughput screening; LBDD; lead optimization
- structure prediction tools that are routinely used in structure-based drug discovery, widely used docking algorithms, scoring functions, virtual high-throughput screening, lead optimization and methods of assessment of ADME properties of drugs. Review Structure-based drug discovery (SBDD) If the three
Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation
Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144
- binding affinity and not the activity. Nevertheless, we focused on the most active compounds and determined the main interactions with the target protein that will be required for lead optimization. We first analysed compounds with the smallest substituent on the triazole nucleobase (derivatives 1n–q). As
Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods
Beilstein J. Org. Chem. 2016, 12, 415–428, doi:10.3762/bjoc.12.45
- /candidate energy surface. Overall Strategy Because the quest for new and effective oxazolidinone binders is a typical lead optimization problem, our strategy in order to predict new linezolid analogs is therefore settled just in middle between these two extremes: a combination of computational power and
Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway
Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103
- industry, all probes discussed provide qualified starting points for advanced lead-optimization programs. The probes were evaluated using known in vitro ADME/T assays to understand their overall pharmacological properties (Table 2). Probe 4 exhibited good solubility especially as the pH decreased from 6.2
- efforts are ongoing to improve molecular potency and properties to make each chemical scaffold family suitable for advanced in vivo studies. Each probe represents a low-molecular-weight, “rule of 5” compliant starting point for target identification or lead optimization efforts. In screening the MLSMR
Asymmetric synthesis of host-directed inhibitors of myxoviruses
Beilstein J. Org. Chem. 2013, 9, 197–203, doi:10.3762/bjoc.9.23
- compound from this series for development, we sought to increase both the potency and the aqueous solubility of 1. Lead optimization has achieved compounds with potent antiviral activity against a panel of myxovirus family members (EC50 values in the low nanomolar range) and much improved aqueous
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