Progress in medicinal chemistry / edited by G. Lawton, David R. Witty.

Format:

Book

Contributor:

Lawton, G., editor.

Witty, David R., editor.

Series:

Progress in Medicinal Chemistry, 0079-6468 ; Volume 54

Language:

English

Subjects (All):

Pharmaceutical chemistry.

Physical Description:

1 online resource (314 p.)

Edition:

First edition.

Place of Publication:

Amsterdam, Netherlands ; Oxford, England : Elsevier, 2015.

Language Note:

English

Summary:

Progress in Medicinal Chemistry provides a review of eclectic developments in medicinal chemistry. This volume continues in the serial's tradition of providing an insight into the skills required of the modern medicinal chemist; in particular, the use of an appropriate selection of the wide range of tools now available to solve key scientific problems, including g-secretase modulators, P2X7 antagonists as therapeutic agents for CNS disorders, N-type calcium channel modulators for the treatment of pain, and more.Extended timely reviews of topics in medicinal chemistryTargets and technologies re

Contents:

Front Cover; Progress in Medicinal Chemistry; Copyright; Contents; Contributors; Preface; Chapter 1: Recent Advances in Cancer Therapeutics; 1. Introduction; 2. Chaperone Inhibitors; 3. Kinase Inhibitors; 3.1. Introduction; 3.2. Vemurafenib-An Inhibitor Targeting a Mutated Kinase; 3.3. Ibrutinib-A Covalent, Irreversible Inhibitor; 3.4. Tumour Resistance to Kinase Inhibitors; 4. HDAC Inhibitors; 4.1. Introduction to Histone Deacetylases; 4.2. Histone Deacetylase Inhibitors; 4.2.1. Biological Activity; 4.2.2. Hydroxamic Acids; 4.2.3. Cyclic Tetrapeptides; 4.2.4. Benzamides

4.2.5. Aliphatic Acids4.2.6. HDAC Class-Selective Inhibitors; 4.2.7. Histone Deacetylase Inhibitors as Part of Single Agent Therapies; 4.2.8. Histone Deacetylase Inhibitors as Part of Combinatorial Therapies; 5. Inhibitors of Protein-Protein Interactions (PPIs); 5.1. Background; 5.2. BCL-2/BH3-Domain Small-Molecule Inhibitors; 5.3. Inhibiting P53/MDM2 Interaction; 5.4. Rapalogs as Allosteric PPI Inhibitors; References; Chapter 2: Fluorine in Medicinal Chemistry; 1. Introduction; 2. Survey of Fluorine Chemotypes in Marketed Drugs; 3. Impact of Fluorine on Lipophilicity; 3.1. Aromatic Systems

3.2. Aliphatic Systems4. Impact of Fluorine on pKa; 4.1. pKa Modulation and Brain Penetration; 4.2. pKa Modulation and Cell Potency; 4.3. pKa Modulation and Reducing hERG Activity; 5. Impact of Fluorine on Metabolism; 5.1. Aromatic Ring Oxidation; 5.2. Aliphatic Oxidation; 6. Metabolism to Toxic Metabolites; 7. Fluorine Interactions in Proteins; 8. Conformational Influences of Fluorine; 8.1. Influence on Geometry at Carbon; 8.2. Charge-Dipole Interactions; 8.3. Hyperconjugation; 8.4. Dipole-Dipole Interactions; 9. Marketed Drug Case Studies; 9.1. Ezetimibe (Zetia TM)

9.2. Celecoxib (Celebrex TM)9.3. Sitagliptin (Januvia TM); 9.3.1. Impact of Fluorine on Pharmacology Profile; 9.3.2. Contribution of Fluorine to Pharmacokinetic Profile; 9.3.3. Structural Aspects; 9.3.4. Contribution of Fluorine to Safety Profile; 9.4. Fluconazole (Diflucan TM) and Voriconazole (Vfend TM); 9.5. Fluoroquinolones; 9.6. Fluticasone Propionate (Flovent TM, Flixotide TM); 9.6.1. Structural Aspects; 9.7. Aprepitant (Emend TM); 10. Summary and Future Outlook; References

Chapter 3: A Perspective on the Next Generation of Antibacterial Agents Derived by Manipulation of Natural Products1. Introduction; 2. Glycopeptides; 3. Tetracyclines; 4. Aminoglycosides; 5. Ketolides; 6. Thiazolyl Peptides; 7. Pleuromutilins; 8. Polymyxins; 9. Conclusion; References; Chapter 4: A New Era for Chagas Disease Drug Discovery?; 1. Introduction; 2. Benznidazole as Historic Anti-Chagasic Chemotherapy; 3. CYP51 as a Drug Target for T. cruzi Growth Inhibition; 4. Clinical Trials; 5. Evolution of Screening Cascades; 6. Compound Landscape for Chagas Disease Chemotherapies

6.1. T. cruzi CYP51 Inhibitors

Notes:

Description based upon print version of record.

Includes bibliographical references and indexes.

Description based on online resource; title from PDF title page (ebrary, viewed February 21, 2015).

ISBN:

9780444634856

0444634851