Lead compounds chemistry control

Aqueous solubility, potency and permeability are three factors under medicinal chemistry control that must be optimized to achieve a compound with acceptable oral absorption. Typically, a lead (chemistry starting point) is deficient in all three parameters. The inter-relationships of these three parameters has been described in a series of publications from Pfizer researchers [7, 8]. Figure 9.1 depicts graphically the minimum acceptable solubility as a function of projected clinical potency and intestinal permeability. A minimum thermodynamic aqueous solubility of 52... 

Heterostructures based on III-V compounds (InP, GaAs, GalnAlAs, GalnAsP) are very important in the field of high frequency optoelectronic devices. Interface chemistry control is a key point for device quality and reliability. III-V compounds have highly reactive surfaces leading to an easy formation of vacancies for instance which are detrimental to the electronical characteristics. To solve these problems passivation treatments are needed. Classical treatments are based on vapor phase reactions or other wet procedures like chemical oxidation or ammonium sulfide treatments. 

In vitro potency has always been under excellent chemistry control, the hallmark of good control being tight chemistry SAR. With respect to combinatorial chemistry several exceptions should be noted. Compounds are often encountered as leads in HTS screening and can be characterized as... 

By focussing on the synthetic benefits of MBFTs, one should recognize the opportunity for great diversification from easily accessible starting materials, which is an enormous benefit in medicinal chemistry. The concomitant economic benefits are evident through the savings on purification steps, use of solvents, batch reactors, and operational control. Finally, MBFT-based scaffold exploitation might considerably simplify lead compound optimization. 

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