Foye's Principles Of Medicinal Chemistry (lemke, Foye's Principles Of Medicinal Chemistry)

1 of 9 http://thepointeedition.lww.com/pt/re/9780781768795/bookContentPane_... Color Section Fig. 3.1. Visualization of a drug molecule N-(4-hydroxyphenyl)-acetamide (Tylenol or acetaminophen) computerized with different levels of graphic representations. (A) Molecular structure of the drug Tylenol. (B) Ball-stick model showing atomic positions and types. (C) Ball-stick model with van der Waals dot surfaces. (D) Space-filled model showing van der Walls radii of the oxygen, nitrogen, and carbon atoms. (E) Solvent accessible surface model (solid) (solvent radius, 1.4Å). (See black and white image.) Fig. 3.3. Graphic visualization of molecular orbital surface 11/5/2008 3:01 AM 2 of 9 http://thepointeedition.lww.com/pt/re/9780781768795/bookContentPane_... HOMO/LUMO calculation for the drug molecule acetaminophen. (See black and white image.) Fig. 3.7. Nuclear magnetic resonance NOE-constrained molecular dynamics/molecular mechanics structure calculation of (A) the polypeptides CB 2 I298-K319; (B) the amino acid backbone superimposition of 10 low-energy conformers; (C) the cylinder representation with a turn at the fifth residue, arginine; (d) and the ribbon display of the two helical segments, showing a curve side chain of Arg302 forming a salt bridge (green line) with Glu305. (See black and white image.) 11/5/2008 3:01 AM 3 of 9 http://thepointeedition.lww.com/pt/re/9780781768795/bookContentPane_... Fig. 3.8. A workflow of in silico virtual screening process: receptor-based and ligand-based approaches. (See black and white image.) Fig. 3.9. Three-dimensional G protein–coupled CB 2 receptor structure (right) constructed by homology and multiple sequence alignment 11/5/2008 3:01 AM 4 of 9 http://thepointeedition.lww.com/pt/re/9780781768795/bookContentPane_... method (left), including the seven transmembrane helices (cylinders, I–VII) and loop regions (ribbons). (From Xie XQ, Chen JZ, Billings EM. 3D structural model of the G protein–coupled cannabinoid CB2 receptor. Proteins: Structure, Function, and Genetics 2003;53:307–319; with permission.) (See black and white image.) Fig. 3.10. MOLCAD-predicted CB 2 -binding pocket surrounded by active amino acid residues, showing an amphipathic contour, hydrophilic center (blue), and hydrophobic cleft (brown). The site-directed mutagenesis– 11/5/2008 3:01 AM 5 of 9 http://thepointeedition.lww.com/pt/re/9780781768795/bookContentPane_... detected binding residues are color-coded in terms of their distance to the pocket (magenta > yellow > green > blue) as the interaction weakens. (See black and white image.) Fig. 3.11. CoMFA contour maps for arylpyrazole antagonists of cannabinoid receptor subtypes CB 1 (A) and CB 2 (B). Sterically favored areas (contribution level, 80%) are shown in green. Sterically unfavored areas (contribution level, 20%) are shown in yellow, and positivepotential favored areas (contribution level, 80%) are shown in blue. Positive-potential unfavored areas (contribution level, 20%) are shown in red. Plots of the corresponding CoMFA-calculated and experimental values of binding affinity (given as pK i ) of arylpyrazole compounds at CB 1 (AA) and CB2 (BB) receptor, respectively are shown as well. (Adapted with permission from Chen J, Han X, Lan R, et al. 3D-QSAR studies of arylpyrazole antagonists of cannabinoid receptor subtypes CB1 and CB2. A combined NMR and CoMFA approach. J Med Chem 2006;49:625–636; with permission.) (See black and white image.) 11/5/2008 3:01 AM 6 of 9 http://thepointeedition.lww.com/pt/re/9780781768795/bookContentPane_... Fig. 17.4. Ribbon diagram of monomeric PDE4D2 (PDB 1PTW). 5′-AMP is shown as balls-and-sticks, whereas two dival