Database LHASA

Although the philosophy of CHAOS is the classical one and very similar to that of other programs which work with a "database" (LHASA, SECS, MARSEIL, etc.), the difference lies in the fact that the "substructures" and the corresponding "disconnection tables" are not in a separate "database", but are an integral part of the program itself. This allows fast access to the necessary information. However, the major novelty of CHAOS is, perhaps, the way in which the "substructures" have been organised for access to them. 

A number of approaches are available or under development to predict metabolism, including expert systems such as MetabolExpert (Compudrug), Meteor (Lhasa), MetaFore [42] and the databases Metabolite (MDL) and Metabolism (Synopsys) [43]. Ultimately such programs may be linked to computer-aided toxicity prediction based on quantitative structure-toxicity relationships and expert systems for toxicity evaluation such as DEREK (Lhasa) (see also Chapter 8) [44]. 

The chemical transforms are the heart and soul (11) of LHASA which has a database of over 600 common chemical reactions. This feature, ironically, shows its limitations. The empirical information about known chemical reactions limits the generation of synthetic pathways. The value of LHASA, however, is in its ability to investigate all possible known synthetic routes, a task which a chemist would find exceedingly tedious. 

In silico tools make a significant contribution to the SAR-based early identification of potential toxicity. An increasing volume of published preclinical and clinical toxicity data are collected and used to build structure-related searchable databases. These expert knowledge databases can analyze chemical structures and match them with potential mechanisms of toxicity. DEREK for Windows (Lhasa Ltd.)39 is one of such broadly used knowledge-based expert systems to provide toxicology alerts for new compounds. Although certainly not comprehensive, numerous efforts have been made to predict hepatotoxicity. Recently,... 

This account of the LHASA and CAMEO programs has been necessarily very limited readers interested in further details should contact the suppliers of the software as listed in the Software appendix. Another approach to the problem of synthesis planning is to provide literature references to model reactions, thus allowing the chemist user to make his or her own assessment of feasibility, using his or her own expert system A number of reaction database systems are in common use (e.g., REACCS,... 

In this paper we describe how the ORAC reaction database system has been integrated with the LHASA synthesis planning program. This interface allows literature precedents for synthetic steps proposed by LHASA to be retrieved from ORAC and displayed to the user. The problem of sequence searching in reaction database systems is also explored and approaches to this problem are described. Finally, the potential use of synthesis planning systems to identify and classify links between reactions in ORAC for use during sequence searching is considered. 

The primary purpose of a reaction database system is to provide quick and easy access to the reaction literature. Users of synthesis planning programs have a need for such access to the literature in elaborating routes suggested by an analysis. An interface between LHASA and ORAC has recently been developed to provide such a link. The interface allows literature precedents for synthetic steps proposed by LHASA to be retrieved automatically from ORAC s database of over 120,000 reactions and to be displayed to the user on an ORAC Display Form. Company databases can also be accessed to search and display in-house preparative methods and processes in conjunction with databases supplied by ORAC Ltd. 

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