Biosteric Transformation

This graphical field depicts the bioanalogous compound pairs with their respective bio steric fragments highlighted. As a rule, members of an analogue pair are arranged 

SUL disulfide, sulfamate, sulfonamide, sulfbne, sulfonylurea, sulfoxide, sultam 378 

THI isolhiourea, sulfide, thiazole, thioethei thiol, ihiocarbamate, thiophene, thiophenol, thiourea 574 

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Figure 4.2 Notation of a biosteric transformation for two analogous molecules (top) with their replaceable fragment highlighted by thick bonds (bottom).

A unique index number is assigned to each biosteric transformation record. The first three letters of the ID code specify the chemical type of the starting lead fragment while the subsequent three to four numbers are sequence indicators. The first part of the ID code can be used for a quick search for replacements for a common coded functionality, such as QUI, which stands for quinazoline in the example shown in Figure 4.3. The ID codes in the current version of the database are cataloged in Table 4.1. 

The hydantoin moiety has been utilized as a biostere for the peptide linkage, transforming a peptide lead into an orally available drug candidate. Therefore, an Arg-Gly-Asp-Ser tetrapeptide (18) lead structure was modified to a non-peptide RGD mimetic as an orally active fibrinogen receptor antagonist 19. ° ... 

Useful reviews on redox transformations of thiophen derivatives (179 references), on the stereochemistry of carbonyl derivatives of five-membered heterocycles (257 references), on synthetic approaches to dihydrothiophens (135 references), and on biosteric thiophens" have been published. Aspects of thiophen chemistry have been treated in reviews on the synthesis of heterocycles by thermal [2 + 2] cycloaddition reactions of acetylenes and on aspects and perspectives of organic heterocyclic chemistry. A review comparing the chemistry of thieno[2,3-h]- and thieno [3,2-i ]-thiophen with that of benzo[ft] thiophen and quinoline has been published. In Advances in Heterocyclic Chemistry, the development of benzo[6] thiophen from 1968 to 1980 and of selenophen from 1970 to 1980 was presented. Other aspects of thiophen chemistry are treated in chapters on Dewar Heterocycles," on Cyclizations under Vilsmeier Conditions, on Polyfluoroheteroaromatic Compounds, and on Reactions of Benzyne with Heterocyclic Compounds. " Several dissertations treating various aspects of thiophen chemistry have appeared. " ... 

In data records of Bioster, two analogous molecule pairs are formally comiected by an arrow like in a chemical transformation (Figure 4.2, bottom). This depiction is not only famUiar to medicinal chemists but is readily adaptable to existing chemical reaction database programs. Obviously, this hypothetical transformation does not correspond to a chemical reaction but cormects two molecules with little atom-atom correspondence. 

Figure 4.3 A typical database record. Analogous compound pairs are depicted as a hypothetical transformation with the biosteric fragments highlighted (thick bonds).

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