2014
DOI: 10.1021/ja508343a
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Abstract: In the search for new therapeutic agents for currently incurable diseases, attention has turned to traditionally "undruggable" targets, and collections of drug-like small molecules with high diversity and quality have become a prerequisite for new breakthroughs. To generate such collections, the diversity-oriented synthesis (DOS) strategy was developed, which aims to populate new chemical space with drug-like compounds containing a high degree of molecular diversity. The resulting DOS-derived libraries have be… Show more

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Cited by 242 publications
(162 citation statements)
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“…Thus, the design and synthesis of structurally diverse, privileged structure-based polycyclic molecules with multiple chiral centers has been intensely studied during the past 15 years [19]. Moreover, on many occasions natural product-like molecules exhibit more potent biological activities than the parent natural products [20].…”
Section: Resultsmentioning
confidence: 99%
“…Thus, the design and synthesis of structurally diverse, privileged structure-based polycyclic molecules with multiple chiral centers has been intensely studied during the past 15 years [19]. Moreover, on many occasions natural product-like molecules exhibit more potent biological activities than the parent natural products [20].…”
Section: Resultsmentioning
confidence: 99%
“…With the goal of targeting unexplored biologically relevant chemical space, we postulated that privileged structures could also serve as ‘chemical navigators' and therefore reported a privileged substructure-based DOS (pDOS) strategy, which targets the synthesis of diverse polyheterocyclic skeletons containing privileged substructures through complexity-generating reactions in order to maximize the unbiased coverage of bioactive space151617. By incorporating privileged substructures into a rigid core skeleton, we envisioned that the resulting compounds would exhibit enhanced interactions with various biomacromolecules including proteins and DNA/RNA.…”
mentioning
confidence: 99%
“…In recent years, diversity-oriented synthesis (DOS) of small chemical entities based on privileged fragments has emerged as a new strategy for exploring the interactions between chemistry and biology. 70 DOS affords spatially well-defined compounds that can be utilized not only as chemical tools for protein targets of interest but also as selective modulators of certain disease processes. Integrated high-throughput synthesis and screening of a focused library based on privileged heterocyclic or peptide fragments has been employed to seek bioactive molecules targeting epigenetic proteins such as the first cyclic tetrapeptide-derived HDAC6-selective inhibitors.…”
Section: Journal Of Medicinal Chemistrymentioning
confidence: 99%