Drug Rings Database with Web Interface. A Tool for Identifying Alternative Chemical Rings in Lead Discovery Programs

Lewell, Xiao Qing; Jones, Andrew C.; Bruce, Craig L.; Harper, Gavin; Jones, Matthew M.; McLay, Iain M.; Bradshaw, John Thomas

doi:10.1021/jm0300429

Cited by 72 publications

(117 citation statements)

References 22 publications

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“…[22] Further dissection of the complex Murcko scaffold II by cleaving linker bonds between the rings provides different levels of scaffold simplification ( Figure 1a). [23] Ad ifferent terminology is used in the cyclic skeleton (CSK) [24] concept. Here,aside from the removal of appendages,a ll non-hydrogen atoms are converted into sp 3 carbon atoms (VI;F igure 1a).…”

Section: Scaffolds and Scaffold Diversitymentioning

confidence: 99%

“…Thec ollection also contained molecules that are highly selective against Mycobacterium smegmatis. [23] In avery innovative and interesting approach that leads to structurally rich and diverse NP scaffolds,W aldvogel and coworkers employed an electrochemical transformation to build an intermediate (176)t hat was utilized to generate various complex molecular scaffolds (Scheme 15). [64] Anodic oxidation of 2,4-dimethylphenol (175)onplatinum electrodes with Ba(OH) 2 ·8 H 2 Oi nm ethanol as the electrolyte afforded oxygen-rich compound 176.F urther simple transformations (one to two steps) of 176 led to fourteen compounds based on four distinct scaffolds with almost exclusive selectivity and in reasonable yields.…”

Section: Angewandte Chemiementioning

confidence: 99%

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Scaffold Diversity Synthesis and Its Application in Probe and Drug Discovery

et al. 2016

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Scaffold diversity is a crucial feature of compound collections that has a huge impact on their success in biological screenings. The synthesis of highly complex and diverse scaffolds, which could be based on natural products, for example, is an arduous task that requires expertise in various aspects of organic synthesis and structural analysis. This challenge has been addressed by a number of synthesis designs, which employ natural products as a source of scaffold diversity, transform suitably designed common intermediates into various molecular frameworks, or entail highly concise synthetic routes to a number of distinct and complex scaffolds. In this Minireview, we highlight recent synthetic developments towards the construction of diverse and complex scaffolds and the application of the resulting compound collections in drug and probe discovery.

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Section: Scaffolds and Scaffold Diversitymentioning

confidence: 99%

Section: Angewandte Chemiementioning

confidence: 99%

Scaffold Diversity Synthesis and Its Application in Probe and Drug Discovery

et al. 2016

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“…A number of studies have analyzed diversity based on the ring systems in structures. [5][6][7][8][9][10][11] 10.1021/jo8001276 CCC: $40.75  2008 American Chemical Society is that structures having such features in common often belong to the same chemical family.…”

Section: Introductionmentioning

confidence: 99%

Structural Diversity of Organic Chemistry. A Scaffold Analysis of the CAS Registry

Lipkus¹,

Yuan²,

Lucas³

et al. 2008

J. Org. Chem.

280

261

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By analyzing the scaffold content of the CAS Registry, we attempt to characterize in a comprehensive way the structural diversity of organic chemistry. The scaffold of a molecule is taken to be its framework, defined as all its ring systems and all the linkers that connect them. Framework data from more than 24 million organic compounds is analyzed. The distribution of frameworks among compounds is found to be top-heavy, i.e., a small percentage of frameworks occur in a large percentage of compounds. When frameworks are analyzed at the graph level, an even more top-heavy distribution is found: half of the compounds can be described by only 143 framework shapes. The most significant finding is that the framework distribution conforms almost exactly to a power law. This suggests that the more often a framework has been used as the basis for a compound, the more likely it is to be used in another compound. This may be explained by the cost of synthesis: making a new derivative of a framework is probably less costly if many other derivatives are known. We believe this power law is evidence that the minimization of synthetic cost has been a key factor in shaping the known universe of organic chemistry.

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“…For instance, removing the side chains of the medicinally important aminoquinolines, as presented in Figure 2a, provides the quinoline as a Murcko scaffold. A complex Murcko scaffold can be further dissected into more than one ring system by cleaving linker bonds between the rings [37]. Each molecule has n + 1 levels, which are numbered sequentially from level 0 (the single remaining ring) up to level n (the whole molecule).…”

Section: Box 272 Defining a Scaffoldmentioning

confidence: 99%

Scaffold Diversity Synthesis with Branching Cascades Strategy

Kumar

2014

Concepts and Case Studies in Chemical Biology

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Drug Rings Database with Web Interface. A Tool for Identifying Alternative Chemical Rings in Lead Discovery Programs

Cited by 72 publications

References 22 publications

Scaffold Diversity Synthesis and Its Application in Probe and Drug Discovery

Scaffold Diversity Synthesis and Its Application in Probe and Drug Discovery

Structural Diversity of Organic Chemistry. A Scaffold Analysis of the CAS Registry

Scaffold Diversity Synthesis with Branching Cascades Strategy

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