Chapter
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
3 PDE4: New Structural Insights into the Regulatory Mechanism and Implications for the Design of Selective Inhibitors
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
4 PDE4: Recent Medicinal Chemistry Strategies to Mitigate Adverse Effects
4.2 Brief Summary of pan-PDE4 Inhibitors
4.3 PDE4 Strategies to Avoid Gastrointestinal Events
4.3.1 Allosteric Modulation
4.3.13 Olanzapine Derivatives
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 Inhibitors
5.5 PF-2545920/Papaverine/Quinazoline Hybrid Series of Inhibitors
5.6 PET Ligand Development
6 The State of the Art in Selective PDE2A Inhibitor Design
6.2 Selective PDE2A Inhibitors
6.2.4 Boehringer Ingelheim
7 Crystal Structures of Phosphodiesterase 9A and Insight into Inhibitor Discovery
7.2 Subtle Asymmetry of the PDE9 Dimer in the Crystals
7.3 The Structure of the PDE9 Catalytic Domain
7.4 Interaction of Inhibitors with PDE9
7.5 Implication on Inhibitor Selectivity
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
8.3.3 Boehringer Ingelheim
8.3.4 Sun Yat-Sen University, China
8.3.5 Envivo Pharmaceuticals
8.4 Analysis of CNS Desirability of PDE9A Inhibitors
9.4 Expression and Tissue Distribution
9.6 Inhibitors and Potential Therapeutic Uses
10 Selective New Small-Molecule Inhibitors of Phosphodiesterase 1
10.3.1 Non-Selective PDE1 Inhibitors
10.3.2 Selective PDE1 inhibitors
11 Recent Advances in the Development of PDE7 Inhibitors
11.1.1 PDE7: Subtypes and Distribution
11.1.2 Rationale for PDE7 as a Therapeutic Target
11.2 Historical Development of PDE7 Inhibitors
11.2.1 Early Examples of Nonselective and Selective Lead Matter
11.2.2 Developing Selective Lead Matter from Nonselective Hits
11.2.3 Targeting PDE4/7 Dual Inhibitors
11.3 Recent Advances in the Discovery of PDE7 Inhibitors for Peripheral Therapeutic Benefit
11.3.1 PDE7 Inhibitors for the Treatment of T Cell-Related Disorders
11.3.1.1 Developments in PDE7 Inhibitors for the Treatment of Airway-Related Disorders
11.3.1.2 Developments in PDE7 Inhibitors for the Treatment of Nonairway- Related Disorders
11.3.1.3 Summary of T-Cell-Related Research
11.3.2 PDE7 Inhibitors for the Treatment of Neuropathic Pain
11.4 Recent Advances in the Discovery of PDE7 Inhibitors for CNS-Related Disorders
11.4.1 Creating PDE7 Inhibitors by Ligand-Based Virtual Screening Methods
11.4.2 Repositioning PDE7 Inhibitors Designed for the Treatment of Peripheral Diseases
11.5 Recent Advances in the Discovery of Dual PDE7 Inhibitors
11.5.1 Dual PDE4/7 Inhibitors
11.5.2 Dual PDE7/8 Inhibitors
11.6 Identifying Next-Generation PDE7 Inhibitors
11.6.1 Emerging Chemotypes as Novel PDE7 Inhibitors
11.6.2 Novel Methods to Identify PDE7 Inhibitors
11.6.2.1 Computational Methods to Identify New PDE7 Inhibitors
11.6.2.2 Fission Yeast-Based HTS to Identify New PDE7 Inhibitors
12 Inhibitors of Protozoan Phosphodiesterases as Potential Therapeutic Approaches for Tropical Diseases
12.2.1 PfPDE Inhibition Studies
12.5 Human African Trypanosomiasis
Phosphodiesterases and Their Inhibitors, Volume 61
( Methods and Principles in Medicinal Chemistry )
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