Library heterocyclic/small molecule

A linker originally designed for solid-phase synthesis of peptides is the backbone amide linker (11) (BAL), this anchoring approach has now been extended to the combinatorial synthesis of diverse amide [31], hydroxamate [32], oligosaccharide [33] and heterocyclic small molecule libraries [34-36]. 

Mixture-Based Combinatorial Libraries From Peptides and Peptidomimetics to Small Molecule Acyclic and Heterocyclic Compounds... 

The first installment in this series (Volume 267, 1996) mostly covered peptide and peptidomimetic based research with just a few examples of small molecule libraries. In this volume we have compiled cutting-edge research in combinatorial chemistry, including divergent areas such as novel analytical techniques, microwave-assisted synthesis, novel linkers, and synthetic approaches in both solid-phase and polymer-assisted synthesis of peptides, small molecules, and heterocyclic systems, as well as the application of these technologies to optimize molecular properties of scientific and commercial interest. 

Small-Molecule Inhibitors of GGTase-I from the Heterocycle Library Derived from Phosphine Catalysis... 

Heterocyclic chemistry has been a major beneficiary of MW-expedited solvent-lfee chemistry utilizing mineral supported reagents. It has been exploited for parallel synthesis, a strategy that is adaptable for multicomponent reactions, such as Ugi " and Biginelli reactions " , for rapid assembly of a library of compoimds. A representative multi-component condensation reaction to create a small-molecule library of imidazo[l,2-a]pyridines, imidazo[l,2-a] pyrazines, and imidazo[l,2-a]pyrimidines is depicted in Scheme 3. 

Combinatorial chemistry uses such methods to make mixtures of many possible compounds (called libraries) that can then be screened for the desired property to select those compounds that are active.149 The methods are suitable not only for polypeptides, but also for oligonucleotides,150 oligosaccharides,151 and a variety of small molecules, including many heterocyclic compounds. The method s popularity is because our knowledge of the inter-... 

Fig. 9.1-10 Small molecule modulators of stem cell differentiation. Schultz has discovered a number of small molecules that modulate stem cell differentiation from a multiscaffold library of druglike heterocycles [39] (see Fig. 9.1-6(a)).

M. C. Desai, Strategy for the Synthesis of Heterocyclic Libraries for the Discovery of Lead Structures, conference "Small Molecule Libraries for Drug Discovery", San Diego, 19%. 

On the basis of the successful application of intramolecular tandem Pictet-Spengler cyclization of active V-acyliminium intermediates to construct small molecules library embedded with diaza-bridged heterocycles in Section 5.2.1.1, we also developed a solid-... 

The 1,3-dipolar cycloaddition reaction has been investigated on a sohd support primarily toward the construction of diverse small molecule libraries, as the reachon is capable of preparing a variety of privileged five-membered heterocycles. TypicaUy, chemoselectivity is high, and the sohd support provides only a mechanism for the rapid preparation of pure compounds in a parallel fashion however, in select cases the sohd support has been demonstrated to enhance both the chemo- and the regioselechvity of the reachon. ... 

Since the introduction of solid-phase peptide synthesis by Merrifield (1) nearly forty years ago, solid-phase techniques have been applied to the construction of a variety of biopolymers and extended into the field of small molecule synthesis. The last decade has seen the emergenee of solid-phase synthesis as the leading technique in the development and production of combinatorial libraries of diverse compounds of varying sizes and properties. Combinatorial libraries can be classified as biopolymer based (e.g., peptides, peptidomimetics, polyureas, and others [2,3]) or small moleeule based (e.g., heterocycles [4], natural product derivatives [5], and inorganie eomplexes [6,7]). Libraries synthesized by solid-phase techniques mainly use polystyrene-divinylbenzene (PS) derived solid supports. Owing to physieal and ehemical limitations of PS-derived resins, other resins have been developed (8,9). Most of these resins are prepared from PS by functionalizing the resin beads with oligomers to improve solvent compatibility and physical stability (8,9). 

At first, combinatorial chemistry focused on peptide and nucleotide libraries synthesis, but because poor pharmacokinetical properties cause poor oral availability of this kind of molecule, there is increasing interest in the development of new methods to prepare small, drug-tike molecules which obey lipinski s mle of five [303]. Heterocyclic compounds can offer a high degree of structural diversity and have proven to be useful as therapeutic agents. For these, there are recent advances in the preparation of heterocycles on solid supports [304]. The examples reported in this section are organized by their ring size. 

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