Phosphodiesterases and their inhibitors / edited by Spiros Liras and Andrew S. Bell.

Includes bibliographical references at the end of each chapters and index.

Print version record.

Phosphodiesterases and Their Inhibitors; Contents; List of Contributors; Preface; A Personal Foreword; 1 Introduction; 2 Toward a New Generation of PDE5 Inhibitors through Advances in Medicinal Chemistry; 2.1 Introduction; 2.2 The First-Generation Agents; 2.3 PDE5 as a Mechanism and Alternative Indications Beyond MED; 2.4 A Summary of PDE5 Chemotypes Reported Post-2010; 2.5 Second-Generation PDE5 Inhibitors from Pfizer: Pyrazolopyrimidines; 2.6 Second-Generation PDE5 Inhibitors from Pfizer: Pyridopyrazinones; 2.7 Conclusions; References.

3 PDE4: New Structural Insights into the Regulatory Mechanism and Implications for the Design of Selective Inhibitors3.1 Introduction; 3.2 Isoforms, Domain Organization, and Splice Variants; 3.3 Structural Features of the Catalytic Site; 3.4 Regulation of PDE4 Activity; 3.5 Crystal Structure of Regulatory Domains of PDE4; 3.6 UCR2 Interaction and Selectivity; 3.7 Conclusions; References; 4 PDE4: Recent Medicinal Chemistry Strategies to Mitigate Adverse Effects; 4.1 Introduction; 4.2 Brief Summary of pan-PDE4 Inhibitors; 4.2.1 Rolipram; 4.2.2 Roflumilast; 4.2.3 Cilomilast; 4.2.4 Apremilast.

4.3 PDE4 Strategies to Avoid Gastrointestinal Events4.3.1 Allosteric Modulation; 4.3.2 PDE4D Selectivity; 4.3.3 Pfizer; 4.3.4 Novartis; 4.3.5 Merck-Frosst; 4.3.6 GEBR-7b; 4.3.7 PDE4B Selectivity; 4.3.8 Asahi Kasei; 4.3.9 GlaxoSmithKline; 4.3.10 Pfizer; 4.3.11 Tissue Targeting; 4.3.12 Polypharmacology; 4.3.13 Olanzapine Derivatives; 4.4 Conclusions; References; 5 The Function, Enzyme Kinetics, Structural Biology, and Medicinal Chemistry of PDE10A; 5.1 Enzymology and Protein Structure; 5.2 Papaverine-Related PDE10A Inhibitors; 5.3 MP-10/PF-2545920 Class of Inhibitors.

5.4 PF-2545920/MP-Inspired Inhibitors5.5 PF-2545920/Papaverine/Quinazoline Hybrid Series of Inhibitors; 5.6 PET Ligand Development; 5.7 Summary and Future; References; 6 The State of the Art in Selective PDE2A Inhibitor Design; 6.1 Introduction; 6.2 Selective PDE2A Inhibitors; 6.2.1 Bayer; 6.2.2 Altana AG; 6.2.3 Biotie Therapies; 6.2.4 Boehringer Ingelheim; 6.2.5 Janssen; 6.2.6 Lundbeck; 6.2.7 Merck; 6.2.8 Neuro3d; 6.2.9 Pfizer; 6.3 Methods; 6.4 Conclusions; References; 7 Crystal Structures of Phosphodiesterase 9A and Insight into Inhibitor Discovery; 7.1 Introduction.

7.2 Subtle Asymmetry of the PDE9 Dimer in the Crystals7.3 The Structure of the PDE9 Catalytic Domain; 7.4 Interaction of Inhibitors with PDE9; 7.5 Implication on Inhibitor Selectivity; References; 8 PDEs as CNS Targets: PDE9 Inhibitors for Cognitive Deficit Diseases; 8.1 PDE9A Enzymology and Pharmacology; 8.2 Crystal Structures of PDE9A Inhibitors; 8.3 Medicinal Chemistry Efforts toward Identifying PDE9A Inhibitors for Treating Cognitive Disorders; 8.3.1 Bayer; 8.3.2 Pfizer; 8.3.3 Boehringer Ingelheim; 8.3.4 Sun Yat-Sen University, China; 8.3.5 Envivo Pharmaceuticals.