Hydrophobic features

Figure 5.5. Examples of a ceUular automata modeUng of miceUe formation. The dark faces of each cell model the hydrophihc part of the amphiphile, while the light faces model the hydrophobic features of the amphiphile molecule...

Figure 20.2 Pharmacophore models for P-gp inhibition. A. P-gp inhibition pharmacophore aligned with the potent inhibitor LY335979. B. P-gp substrate pharmacophore aligned with verapamil. C. P-gp inhibition pharmacophore 2 aligned with LY335979. Green indicates H-bond acceptor feature, and cyan indicates hydrophobic feature. See color plate.

Fig. 1.16 The interaction of hymenialdisine with the backbone of a kinase. Arrows mark the location and direction of hydrogen-bonding groups, the filled circles represent the hydrophobic features.

The relevance of size-related properties of hERG-blocking molecules was also detected in a 2D QSAR model developed by Coi et al. [22] after the analysis of 82 compounds through the CODESSA method. These authors developed two multiparameter models with strong predictive properties, from which, besides the involvement of hydrophobic features, the importance of linearity as opposed to globularity of the hERG blockers emerged. 

Figure 16.3 P-gp-verapamil binding inhibition pharmacophore (orange, ring aromatic feature green, hydrogen bond acceptor cyan, hydrophobic features). Reprinted with permission from ref. [45], Copyright 2002 American Society for Pharmacology and Experimental Therapeutics.

A correlation exists for a surfactant s spermicidal activity and partition coefficient, such that the MEC is in the order of nonionic > cationic > anionic for given stmctural variables [47]. Such design parameters need to be factored when designing polymer vehicles and formulations with ionic and hydrophobic features. 

The —CF3 substituent matches the hydrophobic feature next to the central 5-membered ring hypothesized by both ComPharm and HipHop - both approaches agreeing that the trifluoromethyl group actually is a hydrophobe. The interaction map, however, shows a more subtle picture while the —CF3 group is partly surrounded by hydrophobes, it also forms a close contact to Arg 120, a cation and hydrogen bond donor. 

D pharmacophore models for competitive inhibitors of CYP2C9 were built using Catalyst (173). Three different metabolic reactions, diclofenac 4 -hydroxylation, (S)-warfarin 7-hydroxylation, and tolbutamide 4-hydroxylation, were considered. The general characteristics of the three models were similar with distances between a hydrogen bond acceptor and a second hydrogen bond acceptor/donor being 3.4—5.7 A and the hydrophobic feature was positioned... 

Four hydrophobic features and at least one hydrogen bonding [55]. 

Fig. 7.5 11 L8 GBPM preliminary model. Grey meshes represent hydrophobic features, hydrogen bond donors are reported in blue and hydrogen bond acceptors in red.

The coordination interaction, one aromatic ring, two hydrophobic features and two excluded volume spheres make up the final model (shown in Figure... 

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