Pharmaceutical industry structure

DiMasi, J. New Drug Innovation and Pharmaceutical Industry Structure Trends in the Output of Pharmaceutical Firms. Drug Information Journal 34 (2000) 1169-94. 

Foremost we hope - and believe - that chemoinformatics will become of increasing importance in the teaching of chemistry. The instruments and methods that are used in chemistry will continue to swamp us with data and we have to manage these data to increase our chemical knowledge. We have to understand more deeply, and exploit, the results of our experiments. Concomitantly, demands on the properties of the compounds that are produced by the chemical and pharmaceutical industries will continue to rise. We will need materials that are better we need them to be more selective, have fewer undesirable properties, able to be broken down easily in the environment without producing toxic by-products, and so on. This asks for more insight into the relationships between chemical structures and their properties. Furthermore, we have to plan and perform fewer and more efficient experiments. 

The commercial exploitation of our increased understanding of protein stmcture will not, of course, be restricted to the pharmaceutical industry. The industrial use of enzymes in the chemical industry, the development of new and more specific pesticides and herbicides, the modification of enzymes in order to change the composition of plant oils and plant carbohydrates are all examples of other commercial developments that depend, in part, on understanding the structure of particular proteins at high resolution. 

Examples of Synthesis Routes Inherently Safer Than Others As summarized by Bodor (1995), the ethyl ester of DDT is highly effective as a pesticide and is not as toxic. The ester is hydrolytically sensitive and metabolizes to nontoxic products. The deliberate introduction of a structure into the molecule which facilitates hydrolytic deactivation of the molecule to a safer form can be a key to creating a chemical product with the desired pesticide effects but without the undesired environmental effects. This technique is being used extensively in the pharmaceutical industry. It is applicable to other chemical industries as well. 

The Jacobsen-Katsuki epoxidation reaction has been widely used for the preparation of a variety of structurally diverse complex molecules by both academia and the pharmaceutical industry. Summarized below are a few examples. 

Method development remains the most challenging aspect of chiral chromatographic analysis, and the need for rapid method development is particularly acute in the pharmaceutical industry. To complicate matters, even structurally similar compounds may not be resolved under the same chromatographic conditions, or even on the same CSP. Rapid column equilibration in SFC speeds the column screening process, and automated systems accommodating multiple CSPs and modifiers now permit unattended method optimization in SFC [36]. Because more compounds are likely to be resolved with a single set of parameters in SFC than in LC, the analyst stands a greater chance of success on the first try in SFC [37]. The increased resolution obtained in SFC may also reduce the number of columns that must be evaluated to achieve the desired separation. 

Traditionally, organic compounds have been synthesized one at a time. This works well for prepar- ing large amounts of a few substances, but it 1 doesn t work so well for preparing small amounts of 1 a great many substances. This latter goal is particu- larlv important in the pharmaceutical industry, w here vast numbers of structurally similar com-< pounds must be screened to find the optimum drug J candidate. 

Pectin belongs to a family of plant polysaccharides in which the polymer backbone consists of (1— 4)-linked a-D-galacturonic acid repeating-units. Often, (1— 2)-linked a-L-rhamnose residues interrupt the regular polygalacturonate sequence. The high viscosity and gelling properties of pectins are exploited by the food and pharmaceutical industries. X-Ray studies on sodium pectate, calcium pectate, pectic acid, and pectinic acid (methyl ester of pectic acid) have disclosed their structural details. 

Influencing the efficacy or potency of chemicals is a strategy used by the pharmaceutical industry as part of the drug discovery process that can be incorporated into designing safer industrial chemicals. Efficacy is the maximal effect, either therapeutic or toxic, that a chemical can achieve. Potency is a measure of the amount of a substance that is needed to attain a given response level. Opioid analgesics are examples of where structural modifications have been used to establish a relationship between structure and activity. ... 

The objective for Medicinal Chemistry is the identification of the chemical structures for potential new medicines. Eventually, these new medicines will be launched into the market to address unmet medical needs and to improve the quality of life for all human beings. The marketing of new medicines is the lifeblood of the pharmaceutical industry. Due to the broad impact Medicinal Chemistry has in the drug discovery process, it is recognized as a top job for synthetic organic chemists. 

Chirality at surfaces can be manifested in a number of forms including the intrinsic chirality of the surface structure and even the induction of chirality via the adsorption of achiral molecules onto achiral surfaces. The ability of STM to probe surfaces on a local scale with atomic/molecular resolution has revolutionized the understanding of these phenomena. Surfaces that are globally chiral either due to their intrinsic structure or due to the adsorption of chiral molecules have been shown by STM to establish control over the adsorption behavior of prochiral species. This could have profound consequences for the understanding of the origin of homochirality in life on Earth and in the development of new generations of heterogeneous chiral catalysts that may, finally, make a substantial impact on the pharmaceutical industry. 

Whole-cell biotransformation processes have been successfully applied for commercial production of pharmaceuticals, either as the drug substance itself or as an intermediate for the synthesis of the final drug substance. Some examples of the whole-cell biotransformation processes used by pharmaceutical industry are shown in Table 10.1. The structures of the biotransformation products are shown in Figure 10.1. 

One advantage of whole-cell biotransformation that has not been addressed adequately in this chapter is the ability to modify compounds with complex structure, such as natural products. Natural products are ideal substrates for biotransformation reactions since they are synthesized in a series of enzymatic reactions by the whole cells. The modification of natural products by biotransformation has been reviewed recently by Azerad [ 13] and a majority of the modifications were carried out by whole-cell biotransformations. Additional examples of modification of natural products by whole-cell biotransformations can also be found in the review article by Patel [2]. Natural products are an important source of new drugs and new drug leads [53]. The use of biotransformation, especially whole-cell biotransformation, in modification of natural products for lead optimization and generating libraries of derivatives for S AR and screening studies is important for the pharmaceutical industry. 

The pharmaceutical industry has taken great interest of late in the study of polymorphism and solvatomorphism in its materials, since a strong interest in the phenomena has developed now that regulatory authorities understand that the nature of the structure adopted by a given compound upon crystallization can exert a profound effect on its solid-state properties. For a given material, the heat capacity, conductivity, volume, density, viscosity, surface tension, diffusivity, crystal... 

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