Exercise: 3 16th August 2011 ChemSketchAim: Draw the structure of any five antiviral compounds and calculate its properties. y y y y y y Draw any 5 anti-viral structures Name (IUPAC & common) 5 descriptor properties Find SMILES for each 2D & 3D optimization Calculate the bond length, bond angle & torsional angle of any 1 compound.

Solution: Introduction to ACD ChemSketch ACD/ChemSketch is an integrated software package from Advanced Chemistry Development, Inc., developed to help chemists quickly and easily draw chemical structures, reactions, and schematic diagrams, calculate chemical properties, and design professional reports and presentations. ACD/ChemSketch includes: Structure mode for drawing chemical structures and calculating their properties. Draw mode or text and graphics processing. Some Features include: Possibility to generate Standard InChI and InChI Key. Ability to generate structure(s) quickly from an InChI notation or a SMILES string contained in the Clipboard. Calculating and displaying monoisotopic mass values for ions of different types. Common Window Elements o At the very top of each window, there is a title bar that shows the name of the program, name of the current window and buttons controlling the size and position of the window. o Right below the title bar, one can find the menu bar that contains the program menus. By clicking the menus, one can access the program commands. o Below the menu bar, one can see one or two toolbars containing buttons that one use for working in that window. o Workspace is a changeable part of a window where one work (draws structures, view results of ones manipulations, sees the opened files and databases, etc.). The workspace may be divided into several sub windows each of which display a specific type of data.

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Beneath the workspace, there is usually a status bar that displays information that may be useful for ones work at the current moment, e.g., the name of the currently opened file, the position of the cursor in the workspace, etc.

1. Oseltamivir, Accession Number: DB00198 (APRD01148) IUPAC Name: ethyl (3R,4R,5S)-4-(acetylamino)-5-amino-3-(pentan-3-yloxy)cyclohex-1-ene-1carboxylate Common Name: Oseltamivir Descriptors: (Navigation Key: Structure Mode=> Tools=> Calculate)Molar Refractivity Average Mass Parachor Surface Tension Density = 84.66 0.4 cm3 = 312.4045 Da = 726.1 6.0 cm3

= 41.1 5.0 dyne/cm = 1.08 0.1 g/cm3

SMILES: O=C(OCC)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 Bond Length: (O 20, C 21)=1.479 Bond Angle: (C 13, C 16, C 17)=120 Torsion Angle: (N 7, C 3, C 8, C 1): 0

Oseltamivir, Accession Number: DB00198 (APRD01148) in DrugBank (left) & ChemSketch Structure (right) before cleaning structure (energy minimization)

Oseltamivir, Accession Number: DB00198 (APRD01148) in DrugBank (left) & ChemSketch Structure (right) after cleaning structure (energy minimization)

3D view of oseltamivir before3D Optimization

3D view of oseltamivir after3D Optimization

2. Zanamivir, Accession Number: DB00558 (APRD00378) IUPAC Name: (2R,3R,4S)-4-[(diaminomethylidene)amino]-3-acetamido-2-[(1R,2R)-1,2,3trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid Common Name: Zanamivir Descriptors:Molar Refractivity Average Mass Parachor Surface Tension Density = 71.55 0.5 cm = 332.3098 Da = 562.3 8.0 cm3 = 77.3 7.0 dyne/cm 3 = 1.75 0.1 g/cm3

SMILES: [H][C@]1(OC(=C[C@H](N=C(N)N)[C@H]1NC(C)=O)C(O)=O)[C@H](O)[C@H](O)CO

Zanamivir, Accession Number: DB00558 (APRD00378) in DrugBank (left) & ChemSketch Structure (right) before cleaning structure (energy minimization)

Zanamivir, Accession Number: DB00558 (APRD00378) in DrugBank (left) & ChemSketch Structure (right) after cleaning structure (energy minimization)

3D view of Zanamivir before3D Optimization

3D view of Zanamivir aftere3D Optimization

3. Aciclovir, Accession Number: DB00787 (APRD00567, EXPT00406) IUPAC Name: 2-amino-9-[(2-hydroxyethoxy)methyl]-6,9-dihydro-3H-purin-6-one Common Name: Aciclovir Descriptors:Molar Refractivity Average Mass Parachor Surface Tension Density = 52.43 0.5 cm = 225.2046 Da = 384.7 8.0 cm3 3

= 83.7 7.0 dyne/cm = 1.77 0.1 g/cm3

SMILES: NC1=NC(=O)C2=C(N1)N(COCCO)C=N2

Aciclovir, Accession Number: DB00787 (APRD00567, EXPT00406) in DrugBank (left) & ChemSketch Structure (right) before cleaning structure (energy minimization)

Aciclovir, Accession Number: DB00787 (APRD00567, EXPT00406) in DrugBank (left) & ChemSketch Structure (right) after cleaning structure (energy minimization)

3D view of Aciclovir before3D Optimization

3D view of Aciclovir after3D Optimization

4. Ganciclovir, Accession Number: DB01004 (APRD00263, EXPT01540) IUPAC Name: 2-amino-9-{[(1,3-dihydroxypropan-2-yl)oxy]methyl}-6,9-dihydro-3H-purin-6-one Common Name: Ganciclovir Descriptors:Molar Refractivity Average Mass Parachor Surface Tension Density = 57.90 0.5 cm = 255.2306 Da = 428.9 8.0 cm3 = 86.6 7.0 dyne/cm = 1.81 0.1 g/cm33

SMILES: NC1=NC(=O)C2=C(N1)N(COC(CO)CO)C=N2

Ganciclovir, Accession Number: DB01004 (APRD00263, EXPT01540) in DrugBank (left) & ChemSketch Structure (right) before cleaning structure (energy minimization)

Ganciclovir, Accession Number: DB01004 (APRD00263, EXPT01540) in DrugBank (left) & ChemSketch Structure (right) after cleaning structure (energy minimization)

3D view of Ganciclovir before3D Optimization

3D view of Ganciclovir after3D Optimization

5. Inosinic Acid, Accession Number: DB04566 (EXPT01874) IUPAC Name: : {[(2S,3R,4R,5R)-3,4-dihydroxy-5-(6-oxo-6,9-dihydro-1H-purin-9-yl)oxolan-2yl]methoxy}phosphonic acid Common Name: Inosinic Acid Descriptors:Molar Refractivity Average Mass Parachor Surface Tension Density = 68.84 0.5 cm = 348.206 Da 3 = 514.0 8.0 cm = 137.4 7.0 dyne/cm = 2.31 0.1 g/cm33

SMILES: O[C@H]1[C@H](COP(O)(O)=O)O[C@H]([C@@H]1O)N1C=NC2=C1N=CNC2=O

Inosinic Acid, Accession Number: DB04566 (EXPT01874) in DrugBank (left) & ChemSketch Structure (right) before cleaning structure (energy minimization)

Inosinic Acid, Accession Number: DB04566 (EXPT01874) in DrugBank (left) & ChemSketch Structure (right) after cleaning structure (energy minimization)

3D view of Inosinic Acid before3D Optimization

3D view of Inosinic Acid after3D Optimization