Binding affinity activity contrasted

For a detailed description of spectral map analysis (SMA), the reader is referred to Section 31.3.5. The method has been designed specifically for the study of drug-receptor interactions [37,44]. The interpretation of the resulting spectral map is different from that of the usual principal components biplot. The former is symmetric with respect to rows and columns, while the latter is not. In particular, the spectral map displays interactions between compounds and receptors. It shows which compounds are most specific for which receptors (or tests) and vice versa. This property will be illustrated by means of an analysis of data reporting on the binding affinities of various opioid analgesics to various opioid receptors [45,46]. In contrast with the previous approach, this application is not based on extra-thermodynamic properties, but is derived entirely from biological activity spectra. 

A dithiolane group in the I -position has been shown to be at least as effective as the l, T-dimethyl group in enhancing the binding affinity of the classical cannabinoids, as can be seen by comparing compounds (123) and (124) with compounds (83) and (85). However, the constrained dithiolane compounds (125-127) showed decreased activity compared to their l, T-dimethyl analogues (99-101). In contrast to its l, T-dimethyl and ketone analogues, (117) and (119), the phenyl dithiolane compound (128) does not exhibit any CB2 selectivity. 

In CHO cells transfected with human V], and V2 vasopressin receptors, 1 inhibits [3H]-AVP binding with K/s of 4.3 and 1.9 nM, respectively.15 Compound 1 demonstrates similar activity on rat Vla and V2 receptors, with Kj s of 0.48 nM and 3.0 nM (Table 1). As a result of significant structural homology between the vasopressin and the oxytocin receptors, 1 and AVP also demonstrate significant oxytocin receptor affinities (rat receptor Kt s of 44.4 nM and 3.4 nM, respectively).16 As seen in Table 1, the balanced binding affinities of 1 toward rat Via and V2 receptors closely parallel those of AVP in contrast, vasopressin receptor antagonists mozavaptan hydrochloride (2) and tolvaptan (3) demonstrate moderate to significant V2 receptor selectivity. 

Khurana et al. (1997) introduced tissue factor-modified TEG to study platelet glycoprotein Hb/IIIa function and to establish a quantitative assay of platelet function. With this modification, Mousa et al. (2000) found two classes of glycoprotein Ilb/IIIa antagonists, one with high binding affinity for resting and activated platelets and slow platelet dissociation rates (class I) demonstrating potent inhibition of platelet function, in contrast to those with fast platelet dissociation rates (class II). Additionally, Mousa et al. (2005) utilized the... 

Structure-based drug design approaches rely on the availability of structural information about protein-ligand complexes. In contrast, ligand-based approaches rely only on the experimental structure-activity relationships for ligands only. As discussed above, QSAR methods are typically used to find correlations between ligands binding affinities and their chemical descriptors. As an innovative use of QSAR approaches, several so-called receptor-dependent quantitative structure-activity relationship (RD-QSAR) methods have been... 

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