Heterocyclic combinatorial library

Substituted heterocyclic compounds offer a high degree of structural diversity and have proven to be broadly and economically useful as therapeutic agents. The development of strategies for the synthesis of heterocyclic compounds on the solid phase is expanding as a greater understanding of how to carry out such reactions successfully is attained. We have reviewed the current status of heterocyclic combinatorially libraries [20]. 

A variety of heterocyclic compounds have been derived from the condensation of aldehydes with a-amino acids. Imines 1 (Fig. 3) are often used as intermediates in organic synthesis and are the starting point for chemical reactions such as cycloadditions, condensation reactions, and nucleophilic additions. The formation of imines via condensation of amines with aldehydes was first adopted for the reductive alkylation of resin-bound amino acids [29-31]. Imines have now been used as synthetic intermediates in the generation of a range of heterocyclic combinatorial libraries. 

The current status of heterocyclic combinatorial libraries A. Nefzi, J. M. Ostresh, R. A. Houghten, Chem. Rev. 1997,97, 449. 

Nefl997a Nefzi, A., Ostresh, J.M. and Houghten, R.A., The Current Status of Heterocyclic Combinatorial Libraries, Chem. Rev., 97(1997)449 72. 

Bunyapaiboonsri, T Ramstrom, H. Ramstrom, O. Haiech, J. Lehn, J.-M. Generation of bis-cationic heterocyclic inhibitors of Bacillus subtilis HPr kinase/phosphatase from a ditopic dynamic combinatorial library. J. Med. Chem. 2003,46, 5803-5811. 

Keywords Absolute configuration, Amines, Amino acids, Carbenes, Cascade reactions, 2-chloro-2-cyclopropylideneacetates. Combinatorial libraries. Cycloadditions, Cyclobutenes, Cyclopropanes, Diels-Alder reactions. Heterocycles, Michael additions. Nitrones, Nucleophilic substitutions, Peptidomimetics, Palladium catalysis. Polycycles, Solid phase synthesis, Spiro compounds. Thiols... 

To summarize this section, several research groups have effectively exploited parallels between SwAr strategies leading to [6,7]- and [6,6]-ben-zofused heterocycles and have described complementary reaction protocols suitable for generating diverse combinatorial libraries of benzothiazin-3-ones and quinoxalin-2-ones. 

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

Fig. 12. Parallel synthesis of combinatorial libraries of heterocycles via resin-bound...

A U.S. patent has been issued covering nonnatural antisense structures in a combinatorial library format that claims the combinatorial library itself in an independent claim [89], The consequences of this type of claim and/or the likelihood this type of claim will be granted for heterocyclic libraries are unknown at this time. 

Several unique heterocyclic fused-1,2,4-triazole structures have been published. Pyridine amination of 216 with O-mesitylenesulfonylhydroxylamine followed by condensation with various aryl and heterocyclic aldehydes and subsequent cyclization and oxidation gave triazolopyridines 217 <03TL1675>. Triazolopyridines 217 were utilized in the direct conversion to the triazolopyridine amides 218 with methylaluminoxane premixed with amines in a combinatorial library synthesis. A convenient synthesis of novel 4-(l,2,4-triazol-l-yl)-2-pyrazolines and their derivatives has been reported <03SC1449>. A novel triheterocyclic ring system, thieno[2,3-y][l,2,4]triazolo[l,5-a]azepines, has been published <03S1231>. 

Combinatorial libraries of chiral heterocyclic ligands for enantioselective catalysis 03CRV3071. 

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