Lead-like

Lead, like tin, forms only one hydride, plumbane. This hydride is very unstable, dissociating into lead and hydrogen with great rapidity. It has not been possible to analyse it rigorously or determine any of its physical properties, but it is probably PbH4. Although this hydride is unstable, some of its derivatives are stable thus, for example, tetraethyllead, Pb(C2Hj)4, is one of the most stable compounds with lead in a formal oxidation state of + 4. It is used as an antiknock in petrol. 

Prediction of various physicochemical properties such as solubihty, lipophhicity log P, pfQ, number of H-donor and acceptor atoms, number of rotatable bonds, polar surface area), drug-likeness, lead-likeness, and pharmacokinetic properties (ADMET profile). These properties can be applied as a filter in the prescreening step in virtual screening. 

Lead tetramethyl and lead tetraethyl are covalent lipophilic liquids of low water solubility. Certain inorganic forms of lead, for example, lead tetrachloride, have similar properties, but other forms such as lead nitrate and lead dichloride are ionic and water soluble. Covalent and lipophilic forms of lead, like lipophilic forms of organomercury and organotin, can readily cross membranous barriers such as the... 

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... 

Combining molecular properties with potency provides a simple yet powerful overview of a screening dataset and can be used to quickly identify ligand-efficient lead-like compounds. In Fig. 17.5, a set of 429 compounds active against 5-hydroxytryptamine lA receptor are displayed in a PSA-ClogP plot with the size of the circle related to ligand efficiency. One can easily spot the efficient binders in area of favorable properties. 

Fig. 17.5 Plot of ClogP versus PSA for a set of ligand efficiency. Such visualization is useful 429 compounds active against 5- to identify ligand-efficient lead-like...

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