Lead-likeness quality

Lead-likeness and drug-likeness were introduced to describe high-quality medicinally relevant compounds and a great deal of effort was devoted over the last 10... 

Partly due to the limited throughput of Caco-2 permeability measurements, the structure-activity evaluation of compounds tested in the hit-to-lead phase is done with minimal permeability information, at best. Given the importance of membrane permeability in drug absorption, early consideration of the permeability characteristics of hit compounds would enhance the drug-like quality, and ultimately the probability of success, of selected lead candidates. To incorporate permeability information into the hit-to-lead phase of the drug discovery process it is necessary that permeability measurements be made quickly and with small amounts of material. Thus, efforts have been made to automate and miniaturize the Caco-2 permeability assay. 

Q-score Compound quality score based on molecular weight, biological promiscuity, and other data commonly accepted to measure lead-like properties of a compound. 

What kind of chemistry and reagents will then be capable of delivering arrays of compounds suitable for the identification of high-quality leads as outlined above As discussed in the introduction, for the preparation of highly diverse, lead-like libraries the incorporation of pharmacophore-rich reagents into the final products is required. The majority of important... 

In practice, an HTS collection of microclusters around diverse scaffolds provides a certain redundancy in noisy primary HTS data and facilitates the data analysis methods described above to identify active series. Recent library design efforts have shifted away from the optimal diversity approach and focus more on scaffold representation, high quality lead-like (Hann and Oprea, 2004) compounds, synthetic feasibility, and smart focused libraries to provide the best starting points for medicinal chemistry (Davies, Glick, and Jenkins 2006 Schnur, 2008). 

The selection and quality of a screening library with drug-like and lead-like structures is a critical endeavour. The features of drug-like and lead-like structures continue to be better defined, at the same time as the diversity of drug-like and lead-like molecular space continues to be explored and categorised. Other areas of development focus on the discovery of small molecules suitable for modulating protein-protein interactions, with a greater focus on natural product-like compounds. 

Capacity measurements by discharge are most reliable and one would anticipate repeatable readings, but this is not always the case, especially with lead-acid batteries. Independent lab tests, including those at Cadex, have revealed differences in capacity readings of more than 10% under identical test conditions. The reason for this discrepancy is not fully understood other than to realize that batteries are electrochemical devices that exhibit human-like qualities. (Our IQ [intelligence quotient] level also diverges depending on time of day and other conditions.) These tolerances... 

The mechanical performance of equipment is likely to deteriorate with use due to wear, corrosion, erosion, vibration, contamination and fracture, which may lead to failure. Since this would threaten a typical production objective of meeting quality and quantity specifications, maintenance engineering provide a service which helps to safely achieve the production objective. 

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