Representing generic structures

AnnualReports in Combinatorial Chemistry andMolecularDiversity, Vol. 1, pp, 267-272 1997 ESCOMScience Publishers B. V. 

Although the representation of these queries is very similar to a combinatorial library, there are some significant differences in both design and use. Since the exact compositions of the database structures are not determined until after the query has been posed, the query typically contains query features, such as fuzzy atoms and bonds and ambiguous connectivity. There is no need for these features to represent a combinatorial library, since all the structures are known. The syntax for representing R-groups in a query can also include features such as zero occurrences to reduce the retrieval of undesired records. Such a feature is unnecessary for a combinatorial library representation, since it is a complete set of specific structures and not an open-ended query. 

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ROSDAL is used in the Beilstein-DIALOG system [17] as a data exchange format. The code can represent not only full structures and substructures but also some generic structures. 

Patent databases are therefore integrated databases because facts, text, tables, graphics, and structures are combined. In patents that include chemical aspects (mostly synthesis or processing), the chemical compounds are often represented by Markush structures (see Chapter 2, Section 2.7.1). These generic structures cover many compound families in a very compact maimer. A Markush structure has a core structure diagram with specific atoms and with variable parts (R-groups), which are defined in a text caption. The retrieval of chemical compounds from Markush structures is a complicated task that is not yet solved completely satisfactorily. 

There are bi-, tri-, and tetradentate formazan dyes7 but only the tetradentate copper complex formazan dyes have found use as commercial products. The dye Cl Reactive Blue 160, of generic structure (41), is a representative example. Because of the intensity of their colors, the metal complex formazan dyes have also found application in analysis. Thus, the dye (42) detects zinc at a concentration of 1 part in 50 million.31... 

While these stages I-IV represent generic processes applying to all food proteins, it is significant to note that even small differences in the protein primary structure can sometimes cause major changes in functionality (Wilde, 2000). For example, the genetic variants A and B of P-... 

It is important to keep in mind that the goal is to test for the identity of the molecules, and not their specific representations as drawn and entered in a database. This has implications for comparing generic structures as well. Two structures may have different roots or R-groups, as in the very simple case shown in Fig. 6, but still represent the same library. 

Another searching capability is required by the need to find a partial structure or substructure in a database that includes generic structures. The ability to do a substructure search is standard in modem chemical structure information systems. The problem is more complicated when generic structures must be searched, yet even more necessary since the generic might represent millions of specific structures. The query in Fig. 8 is compared with the generic structure to find the set of specific structures. 

The position of variable substituents on a generic structure is indicated by superatoms, such as the R designation. In a combinatorial library, R need not simply designate an alkyl radical but is conventionally used to represent any set of substituents or residues. The residues R typically define those portions of reagents or building blocks that are found in the final product of the synthesis and that vary among library members. Particular superatoms may more precisely define the composition of a library, such as Ar for a list of aromatic substituents. 

A generic substance represents more than one substance or a set of specific substances. This set of substances can be represented by a generic or Markush structure. An important use of generic structures in the literature is that they provide a compact representation of a set of specific substances. They are also commonly used to show the way the value of a particular physical or biological property varies as a particular... 

Generic structure of the polybrominated diphenyl ether (PBDE) and the structure of tetrabrominated bisphenol-A (TBBPA). Note the x and y on the PBDE structure represent the number of bromine atoms around each phenyl ring (where x = 1-5 andy = 1-5). The maximum number of 5 bromine atoms on each ring results in the fully brominated, decabrominated diphenyl ether... 

These are typically used to represent mixtures and generic structures. 

Enumeration. The systematic substitution of all the Rgroup members in a generic structure, giving each possible specific structure the generic structure represents. If some of the Rgroups are not converted in the process, it is termedpartial enumeration. 

Generic Structure. A structure convention that allows representation of, say, a combinatorial library, as a single, generalized structure. The fixed parts of the structure are represented by the "root" or "parent" structure, and variable parts are represented hy... 

Markush Structure. Essentially a generic structure, in which a root or parent structure plus Rgroups and their members can represent an entire combinatorial library. Markush structures were developed for patent purposes, and the specification of substituents are often more general than in the case of generic structures or database queries. Markush structures are also used to represent generic reactions, in which the reactants and products are represented by generic structures. 

The UvimerTM designation thus represents a generic structural type, while the diluent may be varied for the reasons explained above. For the purposes of this paper, a Uvimer may be shown with a particular reactive diluent or combination of diluents, although this composition is not currently offered commercially. We consider the Uvlmer type to be independent of the particular diluent or diluents employed. 

Not all the members of this group are, technically, quinolones, because naphthyridine, pyridopyrimidine, and cinnoline derivatives (Fig. 7-1), which each contain additional nitrogen atoms in one or the other of the two fused rings, are also represented. It may be useful to consider them all quinoline-type compounds. Thus one may view naphthyridine drugs as 8-aza-4-quinolones, the pyridopyrimidine ring compounds as 6,8-diaza-4-quinolones and the cinnoline system as a 2-aza-4-quinolone. The following compromise generic structure may depict the common denominator to all the active compounds. 

Niunerous retinoids are now known and these cannot be represented by a single generic structure. Generic stucture types I, II, and III, however, represent the structure of most retinoids synthesized to date Figure LI). Compounds represented by structure type I include isomers and closely related analogues of retinoic acid (1), acitretin (2) and its ethyl ester (etretinate), and mono-aromatic heteroarotinoids such as (6), (15)-(17), and (54)-(57). Retinoids type II include substituted naphthalene, stilbene, azobenzene, and diaromatic amides, and other hetero-substituted analogues... 

Sometimes, molecules are represented as Markush stmctures in a generic context to cover a family of molecular structures which can go beyond millions [62], Markush structures are generic structures used in patent databases such as MARPAT main-... 

Figure 11 The generic structure of terphenyl Ugands and some representative examples...

Fig. 30 Generic structure representing the simplest members of bridged cyclopentadienyl-fluorenyl zirconocenes (1)...

FIGURE 9.2 Generic structure of duplex. Symbols represent common physical parameters 0 = torsion angle D = pitch distance and d = cavity size. Both horizontal and vertical dashed lines represent interstrand interaetions that eontribute to duplex formation. (Source Copyright (2011), Wiley-VCH, Weinheim. With permission.)... 

This generic structure describes the variety of organo-modified siloxanes. R and/or R represent various organic substituents, which can be aliphatic and/or aromatic, monomers or polymers. They can be attached to a linear, comb-like, or branched siloxane backbone via an SiC Bond (z = 0) or a SiOCi bond (z = 1). In this way it is possible to control solubility and compatibility. In general, the organically substituted silicones have relatively short siloxane chain lengths (x + y = 10-200). The organic substituents play a substantial role in the properties of such products. 

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