Chemistry experimental screening

Combinatorial chemistry, developed in the mid-90s [227-229], allows the efficient synthesis of large sets of compounds with diverse features. It is therefore a widely used technology for creating screening libraries. For experimental screening, the most... 

Tlie ultimate test of new, theoretically motivated protocols for materials discovery is, of course, experimental. To motivate such experimentation, the effectiveness of these protocols is demonstrated by combinatorial chemistry experiments where the experimental screening step is replaced by hgures of merit returned by the random-phase volume model. The random phase volume model is not fundamental to the protocols it is introduced as a simple way to test, parameterize, and validate the various searching methods,... 

Effectiveness of ADME (absorption, distribution, metabolism, excretion) design implementation depends on whether chemistry protocol development or chemistry production is rate determining. If chemistry production is rate determining there will be excess validated protocols relative to library production. This means that protocols can be prioritized as to their ADME attractiveness and the least attractive protocols from an ADME perspective may never be translated into actual library production. However, protocol development and not library production is often the rate-detemiining step. This eventuality is unfortunate because there is an understandable reluctance to discontinue chemistry synthetic efforts because of a poor ADME experimental profile if considerable chemistry effort has already been expended. Consider the following situation. The effort towards library production is 70% complete. The experimental ADME profile is poor. Would you discontinue completion of library synthesis because of poor ADME if 70% of the chemistry effort had already been completed Thus a key issue becomes how much chemistry experimental effort takes place before exemplars are experimentally profiled in ADME screens ... 

High-throughput screening (HTS) is a method of scientific experimentation widely used in drug discovery and relevant to the fields of biology and chemistry. A screen... 

Key words analog design, combinatorial chemistry, experimental design, high throughput screening, QS AR, series design, similarity... 

The development of combinatorial chemistry and high throughput screening programmes has stimulated efforts to find experimental and computational models to estimate and predict drug absorption, distribution, metabolism and elimination based on drug physicochemical properties. 

The products of photochemical rearrangements are occasionally quite different from what one may intuitively expect and this creates difficulty in their identification. In such cases, computational chemistry is perhaps our only resort. Several possible structures can be screened computationally with rather little cost in terms of time, effort, and money. Unfortunately, computational chemistry cannot predict a priori the structure of the unknown. However, if a good match between theoretically derived and experimental IR spectrum is found, then this constitutes a strong case and often is taken as proof of identification. 

---