Lead compounds biological information

Bioassays have been likened to analytical machines insofar as pharmacologists use them to assign biological properties to compounds in the same way a chemist measures the physical-chemical properties of molecules. If the fundamental role of the medicinal chemist is to optimize the pharmaceutical properties of so-called lead compounds by structural modification, then the role of the pharmacologist in the drug discovery process is to select, develop, and apply bioassays to provide relevant robust data that inform the medicinal chemist of the impact of the modifications he makes. 

Computer modelling has reduced the need to synthesize every analogue of a lead compound. It is also often used retrospectively to confirm the information derived from other sources. Combinatorial chemistry, which originated in the field of peptide chemistry, has now been expanded to cover other areas. The term covers a group of related techniques for the simultaneous production of large numbers of compounds for biological testing. Consequently, it is used for structure action studies and to discover new lead compounds. The procedures may be automated. 

The lead optimization process is highly iterative, multiparametric, and intensely interdisciplinary. Both qualitative and quantitative information is routinely obtained on analog series of compounds to correlate changes in chemical structure to biological and pharmacological data. The resulting quantitative information provides the basis for the comparison of lead compounds and the ability to establish structure activity relationships (SAR). This multistep evaluation and optimization of ADME-PK properties continues until a defined drug profile is achieved. 

In addition to providing quantitative information on the parent drug, HPLC-MS/ MS is used to analyze biological samples within drug discovery and monitor for select metabolites. This serves two functions, to help chemists identify metabolic hot spots and help identify a new lead compound or prodrug. 

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