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Molecular Conceptor - Table of Contents: A - Drug Discovery
Molecular Conceptor - Table of Contents: A - Drug Discovery
A - DRUG DISCOVERY 1. Case Studies in SAR Analyses 2. Success Stories in Drug Discovery B - ANALOG DESIGN AND MOLECULAR MIMICRY 1. Case Studies in Advanced Analog Design 2. Case Studies in 3D Mimic Design 3. Case Studies in Peptidomimetics C - SYNTHESIS AND LIBRARY DESIGN 1. Case Studies in Library Design D - ADME PROPERTIES AND PREDICTIONS 1. Case Studies in ADME/Tox Predictions E - STRUCTURE-BASED DESIGN 1. Case Studies in Structure-Based Design 2. Case Studies of Docking in Drug Discovery F - CHEMINFORMATICS 1. Case Studies in 3D Database Searching G - LIGAND-BASED DESIGN 1. Case Studies in Ligand-Based Design H - QSAR AND CHEMOMETRICS 1. Case Studies in QSAR and 3D-QSAR
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A. DRUG DISCOVERY
A1. CASE STUDIES IN SAR ANALYSES
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A2.1.20 Finding a Lead Compound A2.1.21 The Discovery of Captopril A2.1.22 The Captopril Project Timeline A2.1.23 What Made the Success of the Project Possible? A2.1.24 Structure-Based Component A2.1.25 Ligand-Based Component A2.1.26 Following the Discovery A2.1.27 Recent Structure of Captopril-ACE Complex A2.1.28 Other Drugs in This Class
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A2.2.36 X-rays of Complex with CGP38560 A2.2.37 X-ray Determination of Lead Inhibitors A2.2.38 The Indole X-ray A2.2.39 The S3sp sub-Pocket A2.2.40 Other Work on Drugs in this Class
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B1.3.6 Database Searching B1.3.7 3D Electrostatic Potential B1.3.8 Synthesis of the Exact Anthranilamide Mimetic B1.3.9 Biological Tests B1.3.10 3D Overlay of Mimic Structures B1.3.11 Determinants for Anilinophtalazine KDR/Flt-1 Activities B1.3.12 Summary
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B1.8.1 Salicylamide Mimics B1.8.2 SAR of Salicylamide 1 B1.8.3 Removing the Hydroxyl or the Carbonyl B1.8.4 Analyzing if Ortho Electron Lone-Pair is Sufficient B1.8.5 Potent Inhibition at Ki at Different pH B1.8.6 Pseudo-Ring of 1 Binds as a Whole Unit B1.8.7 Design of Quinazoline Mimic B1.8.8 3D Alignment of Salicylamide 1 and Quinazoiline 2 B1.8.9 Conclusion B1.8.10 Summary
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B2.1.2 Cimetidine has a Folded Conformation B2.1.3 3D Mimicry between Cimetidine and Triazole
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B3.1.2 Somatostatin Receptors B3.1.3 Subtypes of Somatostatin Receptors B3.1.4 The Drug Discovery Strategy B3.1.5 The Somatostatin Pharmacophore B3.1.6 Successful Reduction of the Somatostatin B3.1.7 Mimics of L-363,377 with Database Searching B3.1.8 Results of the Database Searching B3.1.9 A Good Mimic of the Reference Cyclic Peptide B3.1.10 Development of a Combinatorial Chemistry Approach B3.1.11 Combinatorial Chemistry Results B3.1.12 An Integrated Approach to Drug Discovery
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B3.3.13 Geometry of Trans Isomer: Substituents Equatorial B3.3.14 Cis Isomer Equatorial Aligned with Peptidic Agonist B3.3.15 Cis Isomer Axial Aligned with Peptidic Agonist B3.3.16 Trans Isomer Aligned with Peptidic Agonist B3.3.17 Discovery of a Nanomolar Non-Peptidic Agonist B3.3.18 A Good Starting Point for Further Developments
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C1.3.8 Fragment-Based Enumeration C1.3.9 Properties Profiling of the Virtual Library C1.3.10 Simple Property Profiling C1.3.11 Profiling of Knowledge-Based Properties C1.3.12 Analysis of the Diversity of the Virtual Library C1.3.13 Optimal Subset of the Virtual Library for Synthesis C1.3.14 Frequency Analysis Method C1.3.15 Advanced Frequency Analysis C1.3.16 Example of Advanced Frequency Analysis C1.3.17 Multicriteria Optimization C1.3.18 The Weighted Sum Approach C1.3.19 Limitation of the Weighted Sum Approach C1.3.20 Multiple Objective Genetic Algorithms (MOGA) C1.3.21 MOGA Plot and Pareto Ranking C1.3.22 Example of Multi-Dimensional Optimization C1.3.23 MOGA Results C1.3.24 Expanding one MOGA Solution
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D1.3.23 Mibefradil D1.3.24 Lessons from Withdrawals Due to Secondary Pharmacology D1.3.25 Impact on Discovery Screening Programs D1.3.26 Type B and C Toxicity Drug Withdrawals (1/4) D1.3.27 Type B and C Toxicity Drug Withdrawals (2/4) D1.3.28 Type B and C Toxicity Drug Withdrawals (3/4) D1.3.29 Type B and C Toxicity Drug Withdrawals (4/4) D1.3.30 Lessons Learned from Type B/C Toxicity D1.3.31 Importance of Dose in B and C Toxicity D1.3.32 Type D Toxicity Drug Withdrawals D1.3.33 Thalidomide D1.3.34 Balancing Benefit / Risk D1.3.35 Benefit Analyses for Antidepressants D1.3.36 Monitoring
E. STRUCTURE-BASED DESIGN
E1. CASE STUDIES IN STRUCTURE-BASED DESIGN
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E1.4.15 Additional SAR Analyses made by Parke-Davis E1.4.16 Parke-Davis Model of the Quinazoline Analogs E1.4.17 Specificity Observed in EGF-R Kinase Inhibition E1.4.18 Anilino Towards the Sugar Pocket not Reasonable E1.4.19 Parke-Davis Model Consistent with Observed SAR E1.4.20 Binding Mode of the Pyrrolo-Pyrimidine Series E1.4.21 Binding Mode of the Quinazoline Series E1.4.22 What is the Correct Solution? E1.4.23 Ligand Observed with a Novartis Binding Mode E1.4.24 Alignment with the Novartis Model E1.4.25 Ligand Observed with a Parke-Davis Binding Mode E1.4.26 Alignment with the Parke-Davis Model E1.4.27 X-Ray Resolution of Tarceva Bound to EGF-R Kinase E1.4.28 Conclusion
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E2.3.1 Two Methods of Virtual Screening E2.3.2 Combining Structure-Based and Ligand-Based VS E2.3.3 Screening Protocol E2.3.4 Steps of the Docking Treatment E2.3.5 Specificity Pockets in Thrombin E2.3.6 Development of the Hybrid Approach E2.3.7 Inhibition Assays of Top-Scoring Compounds E2.3.8 Analysis of the Binding Mode of Compound 1 E2.3.9 Binding Mode Compared with Known Inhibitors E2.3.10 What was Learned in this Test Study ? E2.3.11 Analyzing Top Ranked Compounds E2.3.12 Limitations of Scoring Functions
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F. CHEMINFORMATICS
F1. CASE STUDIES IN 3D DATABASE SEARCHING
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F1.4.5 Analysis of the Content of the Hit F1.4.6 Replacing Cyclohexanone by a 7-Membered Ring F1.4.7 Problem of the 6-membered Ring F1.4.8 Optimal Framework: 7-membered Cyclic Urea F1.4.9 Design of Cyclic Urea Scaffold F1.4.10 XK-263 is a Non-Peptidic Mimic of A-77003 F1.4.11 Summary
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F1.6.26 Browser Associated to the Third Pharmacophore F1.6.27 Fourth Pharmacophore F1.6.28 Aligning Low Energy Conformers F1.6.29 Characteristics of the Fourth Pharmacophore F1.6.30 3D Searching with the Fourth Pharmacophore F1.6.31 Optimization of the Substituted Pyridine Hit F1.6.32 Browser Associated to the Fourth Pharmacophore F1.6.33 Summary
G. LIGAND-BASED DESIGN
G1. CASE STUDIES IN LIGAND-BASED DESIGN
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G1.3.5 Browser for Antidepressant Agents G1.3.6 The Design of RU-22249 G1.3.7 Browser for Antidepressant Agents
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H1.2.2 The Biological Data H1.2.3 Molecular Alignment H1.2.4 CoMFA Field Calculations H1.2.5 CoMFA and PLS Results vs. Classical QSAR H1.2.6 Steric CoMFA Map for Binding to TBG H1.2.7 Electrostatic CoMFA Map for Binding to TBG H1.2.8 CBG Affinities of New Steroids H1.2.9 Predicting the CBG Affinities of New Steroids
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