Fine Chemicals Database

Large pharmaceutical companies often have their own libraries of compounds, collected after decades of manual synthetic chemistry, which are used as starting points for random screening. In addition to these proprietary compounds, test compounds can be obtained commercially and are derived from the Fine Chemical Database. Usually, these chemicals are organic only partially soluble in water. The amount of organic solvent required to solubilize the chemical will often determine whether or not it can be evaluated in an aqueous-based assay. Random screening of broad compound collections or mixtures of natural products is a common method of seeking new chemical leads. 

Figure 4a. An example structure extracted from the Fine Chemicals Database of MACCS and placed into a document. Note that there is some distortion to this structure.

Two key features incorporated into ChemSketch allow the creation of composite documents. The first is the MACCS interface. The user, after extracting an MDL metafile can press the M keyboard switch and quickly review or modify the structure or reaction on the screen. The second key feature is the Save for DECpage command. This command converts the currently displayed structure into a file which contains the ReGIS commands required by DECpage to produce the composite document. Figure 4a is an example of a structure that was extracted from the Fine Chemicals Database of MACCS and placed into this document. 

Figure 8.1 Profitability in the fine-chemical indnstry. Source Excelsyn / Ramakers—fine-chemical benchmarking database.)...

All major chemical companies, and most teaching establishments, now have a computerised stock-control system which enables information about on-site availability and cost of chemicals to be rapidly obtained. Many companies are now linked to a central database (e.g. Chemquest , Pergabase Inc.), which provides information (via text or graphics) on the world-wide commercial availability (from over fifty chemical catalogues) and on relative costs, etc., of fine chemicals. The hazards in use and disposal of all chemicals (see Section 2.3) may be readily checked from the catalogues of major chemical suppliers and other important sources. 

The deviation scenarios found in the previous step of the risk analysis must be assessed in terms of risk, which consists of assigning a level of severity and probability of occurrence to each scenario. This assessment is qualitative or semi-quantitative, but rarely quantitative, since a quantitative assessment requires a statistical database on failure frequency, which is difficult to obtain for the fine chemicals industry with such a huge diversity of processes. The severity is clearly linked to the consequences of the scenario or to the extent of possible damage. It may be assessed using different points of view, such as the impact on humans, the environment, property, the business continuity, or the company s reputation. Table 1.4 gives an example of such a set of criteria. In order to allow for a correct assessment, it is essential to describe the scenarios with all their consequences. This is often a demanding task for the team, which must interpret the available data in order to work out the consequences of a scenario, together with its chain of events. 

ChemCore module to three-dimensionalize 2D structures, interfaces to reformat MACCS, SMILES, or DARC-2D databases, ChemDBS-1 module to build 3D databases, and ChemDBS-3D module to search 3D databases. Database searching accounts for conformational flexibility while storing only one conformation. Chapman 8c Hall s 3D Dictionary of Drugs (12,000 medicinally interesting compounds), 3D Dictionary of Natural Products (50,000 antibiotics, alkaloids, and terpenoids), and 3D Dictionary of Fine Chemicals (105,000 organics). 

Profile The company provides scientific information products and services to the fine-chemical, pharmaceutical, agrochemical, biotechnology, and academic research communities. Synopsys operates worldwide, with offices and distributors in Europe, the United States, and Japan. It specializes in chemical reaction databases that deliver added-value information and refined data. 

This brief description should serve to demonstrate that 3-D substructure searching is very similar in concept to 2-D substructure searching, and this has meant that it has been possible for systems to be developed very rapidly over the last few years. Systems have been developed in-house by fine-chemicals companies (77,78,91), by commercial software vendors (82,83,92,93), and by academic research groups (60,75) a review of the systems that were available as of mid-1992 is presented by Willett (94) and it is likely that other systems will be introduced over the next few years. The availability of such software has provided molecular modelers with new tools for the identification of novel active compounds. The results of combining modeling and database searching are discussed further in the next section. 

For chemical reaction literature, chemists use the SYNLIB database from Distributed Chemical Graphics. SYNLIB is a well-documented, user-friendly system, designed for end user browsing. Figure 6 shows sample SYNLIB printed output, two records to the page. For chemical supplier information, the Fine Chemicals Directory from Fraser Williams (Scientific Systems) Ltd. is available through MACCS, as is an internally developed database of chemicals available in our Chemical Stockroom. 

Figure 14 shows usage patterns for various t3q>es of data in the Cousin database for all users. Although chemical structures are clearly the most desired piece of information, other components of the database are frequently retrieved as well. An inventory of fine chemicals ordered by each laboratory was created and linked to the FCD by supplier catalogue number to provide a method of locating chemicals available in-house. This capability was recently introduced but has already more than doubled use of the FCD. 

Fine Chemicals Directory - Database of commercially available chemicals, available from Fraser Williams (Scientific Systems) Ltd., London House, London Rd. Sth., Poynton, Cheshire SK12 lYP, U.K. and Molecular Design Limited, 2132 Farallon Drive, San Leandro, CA 94577, U.S.A. 

At this point, which we hope to reach by the end of 1987 or soon after, our major objectives will be met. However, we still have manyplans for ABACUS if the effort can be spared. We are making the Fine Chemicals Directory available on OSAC and expect to be adding several other substantial databases over the next year. We hope to integrate our analytical sample request system with ABACUS to provide substructure access to analytical and physico-chemical data. We are adding procedures to summarise data and, if needed, to interface with RS/1. And we plan to extend the scope of ABACUS to include data other than routine screening data on compounds. 

Most chemical research groups using MACCS created one or more databases of proprietary chemical structures and associated property data. They also utilised the FCD database that was available from MDL in MACCS database format. That database was derived from the Fine Chemicals Directory published by Fraser Williams (Scientific Systems) Limited. 

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