Substructural fragments

Several methods have been developed for establishing correlations between IR vibrational bands and substructure fragments. Counterpropagation neural networks were used to make predictions of the full spectra from RDF codes of the molecules. 

Lipophilicity in particular, as reflected in partition coefficients between aqueous and non-aqueous media most commonly water (or aqueous buffer) and Z-octanol,has received much attention [105,141,152,153,176,199,232,233]. Logic )W for the octanol-water system has been shown to be approximately additive and constitutive, and hence, schemes for its a priori calculation from molecular structure have been devised using either substituent tt values or substructural fragment constants [289, 299]. The approximate nature of any partition coefficient has been frequently emphasized and, indeed, some of the structural features that cause unreliability have been identified and accommodated. Other complications such as steric effects, conformational effects, and substitution at the active positions of hetero-aromatic rings have been observed but cannot as yet be accounted for completely and systematically. Theoretical statistical and topological methods to approach some of these problems have been reported [116-119,175,289,300]. The observations of linear relationships among partition coefficients between water and various organic solvents have been extended and qualified to include other dose-response relationships [120-122,160,161,299-302]. 

In the technique of post hoc design, a set of descriptors are built up by examination of a set of compounds active at a particular receptor family or sub-class. Normally, the set of drugs would be from a commercial database such as MDDR or the Merck Index, etc. and the descriptors would usually be substructural fragment or key based. One example would be the GPCR-PA+ sub-class referred to above, where BCUT descriptors have been used to aid the design of a focused library of aroimd 2000 compoimds based on 8 scaffolds. Libraries have also been constructed based on peptidomimetic principles as well as on the concepts of privileged structures. ... 

A physical model usually predisposes to physicochemical descriptors, such as p/Ca, log P or molar volume for the whole molecule, or the equivalent descriptors for substituents on a common molecular framework. But different structures can have the same or similar property values, and we are interested in designing structures. So at some stage we must choose structural descriptors (atom types, substructural fragments, connections, or indices from molecular orbital calculations) or at least relate structure to property in order to design the appropriate structure. 

Varnek, A. Fourches, D. Hoonakker, F. Solov ev, V.P. Substructural fragments A universal language to encode reactions, molecular and supramolecular structures. J. Comp. -Aided Mol. Design 2005, 19 (9-10), 693-703. 

Adamson et al. studied the structural features of chemical compounds in a large computer-based file [9]. The features are based on substructural fragments of their chemical structures. Several applications with an automated extraction scheme of such a substructural descriptor has been reported in structure-property and structure-activity problems [10-13], Substructural descriptors have also been used for the comparison of structural similarity and the clustering of chemical compounds based on it [14-18], However, the analysis of structural features of the compounds is a process necessary for the recognition of similarity. 

Figure 4 illustrates the largest substructural fragment common to acesulfame and saccharin, both being artificial sweeteners, extracted on the basis of level (1)... 

Fig. 20. Fragment spectra of five psycotropic agents that were weighted by substructural fragment mass... 

Other measures of properties in 3D, such as Molecular Lipophilicity Potential (MLPot) and Molecular Hydrogen Bond Potential (MHBP), have been used to characterize 3D properties. They are defined for points on a molecular surface created around the molecule and calculated from the summation of contributions from the substructural fragments making up the molecule weighted by the distance function. The hydrogen bond potentials include an angle-dependent function. 

Later in 2001, Clark and coworkers [97] reported the isolation and structure characterization of an indolopyridoquinazoline alkaloid, 3-hydroxyrutaecarpine, (75) from Leptothyrsa sprucei. This study was particularly interesting in that the authors reported the substructural fragments 76-78, which were assembled prior to the final determination of the structure of 75. Long-range and H-... 

Free bonds (FB) the bonds may connect to other substructure fragments (a free bond type can be single, double, aromatic, etc.)... 

Identification of chemically or biologically or both functional substructural fragments... 

---