Pharmaceutical lead compound

One of the aptamers significantly reduced intradermal VEGF-induced vascular permeability in vivo. Thus, these nuclease-resistant molecules may be useful for the development of novel pharmaceutical lead compounds for epithelial hyperproliferative diseases. 

Saturated azaheterocycles such as pyrrolidines and piperidines are common structural components of drugs and pharmaceutical lead compounds. A few examples of the application of a-lithiation toward the synthesis of functionalised azaheterocycles from a variety of therapeutic areas are highlighted below. 

Fig. 9 Pharmaceutical Lead Compounds Synthesized Using Pd-Catalyzed N-Arylation as a Key Step...

Historically, drug absorption, distribution, metabolism, excretion, and toxicity ADMET) studies in animal models were performed after the identification of a lead compound. In order to avoid costs, nowadays pharmaceutical companies evaluate the ADMET profiles of potential leads at an earlier stage of the development... 

In order to parameterize a QSAR equation, a quantihed activity for a set of compounds must be known. These are called lead compounds, at least in the pharmaceutical industry. Typically, test results are available for only a small number of compounds. Because of this, it can be difficult to choose a number of descriptors that will give useful results without htting to anomalies in the test set. Three to hve lead compounds per descriptor in the QSAR equation are normally considered an adequate number. If two descriptors are nearly col-linear with one another, then one should be omitted even though it may have a large correlation coefficient. 

Pharmaceutical lead discovery and optimization have historically followed a sequential process in which relatively small sets of individual compounds are... 

Pharmaceutical discoveries are principally made by thoughtful structural variation on a lead compound which has been found, by chance or design, to have a certain amount of the desired activity. It is clear that with metalloporphyrins, there are additional structural variations to be had. In the first place, it is possible to vary the metal. It was realized at an early stage that inserting and varying the metal would modify PDT activity.61 The possibility also exists of structural changes in axial ligands in those metalloporphyrins which possess them. This structural variation occurs in the space immediately above and below the macrocycle, which is a space not readily accessible to controlled variation in metal-free compounds of this series. 

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. 

Bacterial resistance to conventional antibiotics has become a serious problem in infection control, and has led to intensive research efforts to develop an effective novel antimicrobial agent. Antimicrobial peptides have already played a crucial role in pharmaceutical research as biomedically useful agents or as lead compounds for drug development. More specifically, cyclic peptides have shown some potential as a possible new class of... 

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