Structure series

The effect of substituents in the ring on the mobility of a methyne proton can be followed from the series of 5-substituted l-methyl-4-ethynylpyrazoles and 1,3-dimethyl-4-ethynylpyrazoles. In both structural series, the acidity of compounds increases with a change in the character of substituents in the following order CH3 < H < CH2NH2 < Cl. 

Figure 2. Comparison of the various structure types belonging to two homologous structure series based on the CeCojBj, CaCuj and MgZn2 structure types.

With increasing B content, the covalent component of the bonding in boride lattices increases owing to the appearance of direct B—B bonds and a decrease in the metallic bond character, e.g., in the structural series of the CUAI2 family ... 

With decreasing My B ratio, two or three B zigzag chains are connected at bonding distances, thus forming double or triple chains (Fig. 1). This tendency toward two-dimensional boron net formation (i.e., AlBj type) is recognized from the structural series within the V-B system VnB +, = (n - 1) VB -I- VBj (n = 1,2,3,5 not known for n = 4). ... 

Figure 1. Structural series of vanadium borides and mode of formation VnB + i (n - 1) VB + VB2 n = 1,2,3,5. The structures are projeeted along [100] large eireles are metal atoms small eircles are B atoms filled circles are atoms in x — 1/2, open eireles are atoms in x = 0.

Figure 2. Structural series of Cr-AI borides and mode of formation Crn. AlB2 = CrAI + nCrB2, n = 1,2. The structures are projected along [001] the B net and Al atoms in z = 1 /2 Cr atoms are in z = 0.

Because the goal of hit triage is to identify chemical series that hold promise for further optimization, an approach to characterize the ADME properties of a series, not just individual compounds is often useful. Where possible, characterizing the structure-ADME property relationship, in much the same way that a structure-potency relationship is defined, can be valuable for assessing the probability that a given structural series can be successfully optimized. The goals of this ADME property characterization are twofold (1) to identify specific structural features that may be liabilities (benefits), and (2) to identify general structure-ADME property correlations. 

By experiments performed as discussed here, the reversible inhibition modality of each lead compound, representing a distinct pharmacophore or chemical structural class, can be defined and the dissociation constant (A) or aK<) can be determined from the data fitting to Equations (3.1) through (3.6). As lead analogues are produced within a structural series, one can generally assume that the inhibiton modality will be the same as that of the founder molecule (i.e., the lead) of that structural series. This assumption simplifies the determination of dissociation constants for other series molecules, as described below. However, this assumption must be... 

In an ideal situation a structural series of compounds will have unlimited cell permeability, and one can therefore expect a strict correlation between rank-order enzyme affinity (as measured by K, values) and the EC50 for cellular effects (the EC50 is the cellular or organismal equivalent of the in vitro IC50 i.e., the EC50 is the con-... 

Figure 5. An illustration of the first three members of the structural series BisWnOan+a, viewed along [100]. The structures consist of Bi20t sheets separated by one, two, three, etc. (n = 1, 2, 3, etc., respectively), corner-sharing sheets of...

Eckert H, Moran K, Franke D, Hudalla C (1993) In Tosell JA (ed) Nuclear magnetic shieldings and molecular structure (Series C Mathematical and Physical Sciences), vol 386. Kluwer, Dordrecht, p 49... 

Strictly related to this kind of description are the concepts of Recombination Structures and of Intergrowth Structure Series, to be discussed in the following see 3.9.4. 

With the advent of modern LC/MS instrumentation and sophisticated software, metabolic profiling has gradually become a significant tool to support drug discovery. Early identification of active or toxic metabolites and characterization of metabolic liability of a particular structural series will significantly reduce the cycle time of the lead opti-... 

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