Murcko framework

Fig. 15.4-6 Analysis of privileged scaffold-target matrix of monoamine CPCR ligands. For each CPCR ligand assigned in the MDL Drug Data Report (MDDR) database to a specific monoamine CPCR subtype, the Bemis-Murcko frameworks were generated. The lists of frameworks were then combined and duplicates were eliminated. The comprehensive list of unique frameworks define the row vector of the matrix, and the CPCR subtypes were arranged to the column vector. The matrix...

Figure 2 Murcko structures for bioactive molecules, (a) Quinoline as Murcko framework of bioactive aminoquinolines after removing side chains and (b) different levels of structural simplification of Hsp90 inhibitor NVP-AUY922 provide different structural levels of scaffolds.

The morpholine-benzyl, phenyl isoxazole is the Murcko framework for this bioactive molecule. 

Using a chemistry-aware embedded language like Scientific Vector Language (SVL), the Molecular Operating Environment (MOE) engine is not dependent on hardware and operating system [21], More than 80 MOE nodes are included, for example, node for retrosynthetic accessibility, protonation, Murcko framework generation. Shannon entropy model creation, InChl calculation, pharmacophore... 

After the MMPs and their respective contexts and transformations had been generated and stored in the database, several descriptors were employed in order to represent the context of matched molecular pairs. The approach included the consideration of both the local environment around the attachment point and whole molecule/context representations. This division allowed for a hierarchical view of the context representation, starting from the whole molecule and focusing progressively on the well-defined local area where the transformation took place. For the whole molecule representation approach, Murcko frameworks [30] were employed. For the localized approach, atom environments [31] were used. 

Murcko frameworks allow for an abstract molecular representation, whereby the side chains of the structure are trimmed, preserving only the rings and the linkers that connect rings. An RDKit script was used in order to generate customized Murcko frameworks. Here, atom and bond types are preserved. The resulting Murcko framework descriptor was represented by a valid SMILES string. 

Bemis, G.W., Murcko, M.A. The properties of known drugs. 1. Molecular frameworks. Journal of Medicinal Chemistry 1996, 39, 2887-2893. 

Noteworthy in this perspective is the work by Bemis and Murcko, who developed a method for decomposing molecules into frameworks, sidechains, and linkers and analyzed the statistical occurrence of the frameworks within a subset of drugs listed in the CMC catalog [112]. This analysis revealed that only 32 frameworks describe the shapes of half the drugs in the CMC set (-5000 compounds) and resulted in the design of the SHAPES NMR screening library-a limited but diverse library of small molecules derived from the shapes most commonly found - which Vertex uses within the lead-finding process [113]. 

In contrast to substituents, molecular frameworks are rarely used in SAR/ QSAR/QSPR studies. In most cases, they are implicitly involved as indicator variables discriminating dilferent types of molecular motifs (see, for example, ref. 164). The distributions of different molecular frameworks and substituents (side chains) in the databases of known drug molecules has been thoroughly studied by Bemis and Murcko. ... 

Bemis GW, Murcko MA. The properties of known drags. 1. Molecular frameworks. J. Med. Chem. 1996 39 2887-2893. 

Structural Frameworks and Side Chains of Known Drugs. Databases have been mined to find structural motifs and pharmacophore features of small molecules that characterize drugs. Bemis and Murcko (44)... 

Figure 6.6. Most frequently occurring frameworks in drugs (numbers indicate percentages of occurrence in CMC database). Data are taken from Bemis and Murcko (44).

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