Drug-like scaffolds

Drug-like scaffolds Small molecular probes... 

Fig. 18.2 Elaboration-based strategies. Left In SHAPES screening [3], simple drug-like scaffolds are screened using ligand-detected experiments. In the follow-up step, information about binding scaffolds is used to design a follow-up library comprised of analogous compounds. Successive rounds of screening lead to increasingly complex...

Linked drug-like scaffolds Combi-chem scaffolds Truncated lead compound... 

Fig. 18.3 Variation-based strategies. Left The SHAPES Linking Library [11] consists of drug-like scaffolds connected by linkers that are amenable to combinatorial chemistry (dashed line). Hits are followed up by synthesizing a combinatorial library in which the scaffolds are systematically varied. Center Directed Combinatorial Librari es [12] are comprised of scaffolds containing multiple sites for substituents. Hits are followed up by...

The SHAPES Linking Library was designed to facilitate the use of combinatorial chemistry to follow up screening hits [11]. This library consists primarily of commercially available compounds containing two drug-like scaffolds connected by a linkage that is synthetically accessible. To construct this library, a database of commercially available compounds was filtered to select for drug-likeness and the presence of the desired molecular... 

Combinatorial synthesis and screening of heterocyclic, drug-like scaffold libraries... 

Fig. 4. Bioactive molecules from the synthesis and screening of drug-like scaffold, small-molecule libraries.

Silicon allows for chemical reactions, which are not accessible to standard carbon chemistry, prompting the synthesis of novel drug-like scaffolds. 

The utility of the privileged structure concept is illustrated by compound library synthesis based on the indole scaffold and the biologically active compounds resulting from that. The indole scaffold is found in natural products, like for example, the neurotransmitter serotonin (5-hydoxytriptamine, 5-HT) and in well-know drugs, like for example, the... 

The piperazine scaffolds based on MCR chemistry and some of their physicochemical properties are summarized in Fig. 4. Such scaffolds are suitable for lead generation in terms of drug-like properties (molecular weight, H-bond acceptors and donors, and sp character). In the following, the different piperazine scaffolds, their 3D structures, and the synthetic approaches are discussed. 

Bemis and Murcko (10) analyzed known drugs in an effort to identify common features and scaffolds, which could be used to bias fragment libraries toward drug-like structures. An optimal molecular complexity was also discussed by Hann and coworkers... 

Derivatization Reactions of Heterocyclic Scaffolds on Solid Phase Tools for the Synthesis of Drug-Like Molecule Libraries... 

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