Highly Stereoselective Synthesis of a Compound Collection Based on the Bicyclic Scaffolds of Natural Products
| Autor: | Kamal Kumar, Raquel Ortega, Martyna Bielska, Murali Annamalai, Stanimira Hristeva |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Computer science
natural products Pharmaceutical Science Nanotechnology Aza-heterocycles 010402 general chemistry 01 natural sciences Article Natural (archaeology) Analytical Chemistry drug discovery Small Molecule Libraries lcsh:QD241-441 chemistry.chemical_compound Lead (geology) Drug likeness lcsh:Organic chemistry European Lead Factory Physical and Theoretical Chemistry Pharmaceutical industry scaffolds Biological Products Natural product Cycloaddition Reaction Molecular Structure Bicyclic molecule 010405 organic chemistry business.industry Drug discovery Organic Chemistry Stereoisomerism Bridged Bicyclo Compounds Heterocyclic 0104 chemical sciences chemistry Chemistry (miscellaneous) Drug Design Molecular Medicine Biochemical engineering business |
| Zdroj: | Molecules; Volume 22; Issue 5; Pages: 827 Molecules, Vol 22, Iss 5, p 827 (2017) Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules22050827 |
| Popis: | Despite the great contribution of natural products in the history of successful drug discovery, there are significant limitations that persuade the pharmaceutical industry to evade natural products in drug discovery research. The extreme scarcity as well as structural complexity of natural products renders their practical synthetic access and further modifications extremely challenging. Although other alternative technologies, particularly combinatorial chemistry, were embraced by the pharmaceutical industry to get quick access to a large number of small molecules with simple frameworks that often lack three-dimensional complexity, hardly any success was achieved in the discovery of lead molecules. To acquire chemotypes beholding structural features of natural products, for instance high sp3 character, the synthesis of compound collections based on core-scaffolds of natural products presents a promising strategy. Here, we report a natural product inspired synthesis of six different chemotypes and their derivatives for drug discovery research. These bicyclic hetero- and carbocyclic scaffolds are highly novel, rich in sp3 features and with ideal physicochemical properties to display drug likeness. The functional groups on the scaffolds were exploited further to generate corresponding compound collections. Synthesis of two of these collections exemplified with ca. 350 compounds are each also presented. The whole compound library is being exposed to various biological screenings within the European Lead Factory consortium. |
| Databáze: | OpenAIRE |
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