Privileged scaffold

There continues to be interest in small-molecular scaffolds as good starting points for drug discovery [50]. Indoles [51], 2-oxindoles [52], 2-arylben-zothiazoles [53], rhodanines [54], quinolones [55], (3-D-glucose [56], and y-pyrones [57] have all recently been reviewed as privileged scaffolds. 

A method to identify common scaffolds in databases by scaffold detection, alignment, and assignment has been reported [58]. This method could be used to create meaningful SAR analyses of large medicinal chemistry databases. 

---

Ponnuswamy MN, Gromiha MM, Sony SMM, Saraboji K (2006) Conformational Aspects and Interaction Studies of Heterocyclic Drugs. 3 81-147 Prabhakar YS, Solomon VR, Gupta MK, Katti SB (2006) QSAR Studies on Thiazolidines A Biologically Privileged Scaffold. 4 161-248... 

Privileged" scaffolds are often incorporated in the design of DOSs. An unprecedented asymmetric catalytic 1,3-dipolar cycloaddition... 

Aryl indole as a G-protein-coupled receptor (GPCR) privileged scaffold. The indole ring is a premier example of a privileged scaffold. The heterocycle is present in a profusion of medicinally important natural products and pharmaceutical substances, and it is associated with an extraordinary manifold of biological... 

In addition to physical properties, the chemical structure of fragments can play a role in their success as screening hits. Hajduk and coworkers showed that certain privileged scaffolds tend to show up repeatedly in successful fragment screening campaigns... 

Fast binary filtering methods can also be used for scaffold ranking, i.e., the prioritization of combinatorial scaffolds based on predicted properties. Privileged scaffolds were selected to demonstrate this idea [82], Piperazines SI, benzodiazepines S2, and spiroindolines S3 have been described as GPCR-privileged scaffolds [83], Scaffold S4 represents a SPIKET motif for tubulin binding which is effective for inhibiting cellular proliferation [84], Dysidiolide-derived compounds... 

A list of privileged scaffolds - several of which are natural-product derived - for target-family-biased combinatorial libraries was recently presented by Muller [94], These scaffolds were proven to produce biologically active compounds for more than one member of a given target family. A rough-and-ready in-silico evaluation... 

Figure 13.13 SOM showing the distribution of known serine protease inhibitors (left), and a virtual combinatorial library that was constructed around a serine protease-privileged scaffold [94], Red areas indicate high compound density. Note that each map forms a torus.

Privileged Scaffolds - Look Where the Light is Brightest... 

Figure 13 Four examples of biologically active compounds discovered from libraries based on the tetrahydro-P-carboline natural product privileged scaffold...

QSAR Studies on Thiazolidines A Biologically Privileged Scaffold 163... 

---