Substructure searches for

The next example shows how different search queries can be combined to shed more light onto a series of related reactions. A reaction substructure search for reactions that break a P-O bond provided 304 reactions as hits. Figure 10.3-27 shows one of the reactions in this hit list. 

Most corporate databases of chemical compounds (libraries) are of the 2D type. The databases are managed using software that allows fast registration of new structures, fast retrieval of previously stored compounds, and fast substructure searching. (For more information about chemical database management software, see www.mdl.com or www.daylight.com.)... 

CDD has developed and deployed a robust preliminary public antimalarial database from five sources which hosts data on approximately 16,000 public compounds. The growth of this database has fostered several key antimalarial discovery collaborations between CDD users. A substructure search for the known chemo-sensitizer substructure led to the identification of hundreds of compounds for laboratory evaluation by the laboratories of... 

In many ways, the field of chemistry is extremely fortunate in having had powerful, specialized searching tools like SciFinder Scholar, STN Express, and MDL Crossfire (for Beilstein and Gmelin) available for many years. These tools permit a high degree of flexibility in searching for example, one can find journal articles that refer to compounds containing particular substructures, search for physical properties of particular compounds, and so on. However, these are bounded tools ... 

A similarity search provides a way forward by retrieving the structures that are similar, but not identical, to a lead compound (94). Therefore, it overcomes some limitations of substructure search, for example, not requiring specific knowledge about the substructures responsible for activity, and being able to rank the output structures accordingto the overall similarity. The search query usually involves a set of descriptors that collectively specify the whole structure of the lead compound. This set of descriptors is compared with the corresponding set of descriptors for... 

The FP originate from molecular structure database software where they are used to speed up substructure searches. For this reason, routines to calculate FP are implemented in many commercial software packages and play an historically important role as a first attempt to describe diversity. Even though their applicability as descriptors is limited, the use of FP in library design is still widespread (see Section 9.7 for examples and comparison with other descriptors). In particular, similarity searches in huge databases can be performed very quickly using FPs. 

Substructure searching is probably the most basic approach to identifying compounds of interest. It is widely used for all kinds of problems. Most chemists take substructure searching for granted, testament to the decades of effort that has gone into the development of extremely powerful algorithms and database systems. 

Once the chemical identity is determined, the next step is to ascertain whether the chemical has any environmental degradation data. For this chapter, it will be assumed that literature searches will have already determined that no data on the chemical of interest are available. The approach and databases to be searched are similar to those used for substructure searching for analogs, as discussed in the next section. 

The similarity searching procedure aids creative use of the information resource by avoiding user preconceptions in searching, and by allowing the identification of unforeseen analogies.This is a powerful means of making the fullest possible use of available information. This type of searching also helps to make the system accessible to infrequent and inexpert users, and provides an alternative to conventional structure match and substructure search for all users. 

Here the user does a substructure search for a fragment of the reactant followed by a substructure search for part of the product and he then intersects the two hit lists using AND logic. 

Beside all controls, procedures and practices, the first and most important step remains to reliably identify controlled substances. Luckily this step can be reduced to the task of a simple substructure search. For each controlled substance or for a group of controlled substances, specified in the respective schedule of the legal text, a substructure can be defined that can be used to flag potential controlled... 

In addition to the familiar CRC Handbook [4], there are software-based resources for the retrieval of pK, values [5]. The advantage of these is that they are typically also substructure-searchable, such that the resource is useful even for novel compounds. Substructure searches for ionizable groups should give a reasonable idea of pfQ values for these groups present in novel species. 

In order to address the problem of performing substructure searches for chiral moieties, a method of designating both absolute and relative configuration in molecular structures was developed. Then a small chemical structure database containing 25 mono and disaccharides was created in order to test the concept. Results from tests show this method to be viable and expandable to other types of compounds. 

In order to achieve precise and accurate substructure searches for chiral moieties, at least two conditions must be met there should be a standard method of... 

Substructure search generally works intuitively, in that substructures which match must have corresponding polymer SGroup properties as well. For substructure search we recognise phase shift , and we traverse crossing bonds in all possible combinations. However, we do not currently allow for constructive substructure search for example, a query with two instances of a repeating polymer unit will not hit the structure in the database which includes just one instance. 

Figure 7. Substructure searching for formulations requires that the relative order of components match...

Table 3. Execution times in CPU seconds and speed-ups for the ranking of the outputs fi om substructure searches for three secondary structure motifs.

Fig. 101. Example for a compound found by Closed Substructure Search for piceol...

Peilarm substructure search for amides in the Pfizer fiie... 

Analysis of Research Proposals. The Army Medical Reseetrch and Development Command supports research in the directed synthesis of screening candidates. Twice yearly the Division of Eiqperi-mental Therapeutics reviews synthesis proposals. The proposed structures in each proposal are entered into the data base in the "XR" series and are also entered as identity searches to determine whether or not the compounds are already on hetnd cuid to identify duplication among the proposals. In addition, substructure searches for the major classes of compounds proposed are also run. Matches from both the identity eind sub-structure searches are then used to query the biology auid inventory files. The reviewer is presented with a report sequenced by proposal number providing him with all available information on the availability and activity of all specific compounds emd classes of compounds in each proposal. A similar procedure is used by contract monitors to review progress on synthesis contracts cind to prevent duplication of effort. 

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