Muutke küpsiste eelistusi

E-raamat: Phosphodiesterases and Their Inhibitors [Wiley Online]

Edited by (Pfizer, Groton, USA), Edited by (Imperial College, London, UK), Series edited by (Swiss Institute of Technology (ETH), Zürich, Switze), Series edited by (University of Heidelberg, Germany), Series edited by (University of Düsseldorf, Ge)
Teised raamatud teemal:
  • Wiley Online
  • Hind: 185,03 €*
  • * hind, mis tagab piiramatu üheaegsete kasutajate arvuga ligipääsu piiramatuks ajaks
Phosphodiesterases and Their InhibitorsSuurem pilt
Teised raamatud teemal:
Wiley Online e-raamatudRohkem infot Wiley Online kohta
Raamatu kodulehekülg: https://onlinelibrary.wiley.com/doi/book/10.1002/9783527682348
Written by the pioneers of Viagra, the first blockbuster PDE inhibitor drug.
Beginning with a review of the first wave of phosphodiesterase (PDE) inhibitors, this book focuses on new and emerging PDE targets and their inhibitors. Drug development options for all major human PDE families are discussed and cover diverse therapeutic fields, such as neurological/psychiatric, cardiovascular/metabolic, pain, and allergy/respiratory diseases. Finally, emerging chemotherapeutic applications of PDE inhibitors against malaria and other tropical diseases are discussed.
List of Contributors
xi
Preface xv
A Personal Foreword xvii
1 Introduction
1(8)
Andrew S. Bell
Spiros Liras
2 Toward a New Generation of PDE5 Inhibitors through Advances in Medicinal Chemistry
9(20)
Dafydd R. Owen
2.1 Introduction
9(1)
2.2 The First-Generation Agents
10(1)
2.3 PDE5 as a Mechanism and Alternative Indications Beyond MED
11(1)
2.4 A Summary of PDE5 Chemotypes Reported Post-2010
11(1)
2.5 Second-Generation PDE5 Inhibitors from Pfizer: Pyrazolopyrimidines
12(6)
2.6 Second-Generation PDE5 Inhibitors from Pfizer: Pyridopyrazinones
18(7)
2.7 Conclusions
25(4)
References
25(4)
3 PDE4: New Structural Insights into the Regulatory Mechanism and Implications for the Design of Selective Inhibitors
29(16)
Jayvardhan Pandit
3.1 Introduction
29(1)
3.2 Isoforms, Domain Organization, and Splice Variants
30(1)
3.3 Structural Features of the Catalytic Site
31(1)
3.4 Regulation of PDE4 Activity
32(1)
3.5 Crystal Structure of Regulatory Domains of PDE4
33(5)
3.6 UCR2 Interaction and Selectivity
38(1)
3.7 Conclusions
39(6)
References
40(5)
4 PDE4: Recent Medicinal Chemistry Strategies to Mitigate Adverse Effects
45(20)
Etzer Darout
Elnaz Menhaji-Klotz
Thomas A. Chappie
4.1 Introduction
45(1)
4.2 Brief Summary of pan-PDE4 Inhibitors
46(3)
4.2.1 Rolipram
47(1)
4.2.2 Roflumilast
48(1)
4.2.3 Cilomilast
48(1)
4.2.4 Apremilast
49(1)
4.3 PDE4 Strategies to Avoid Gastrointestinal Events
49(10)
4.3.1 Allosteric Modulation
49(4)
4.3.2 PDE4D Selectivity
53(1)
4.3.3 Pfizer
53(1)
4.3.4 Novartis
54(1)
4.3.5 Merck-Frosst
54(1)
4.3.6 GEBR-7b
55(1)
4.3.7 PDE4B Selectivity
55(1)
4.3.8 Asahi Kasei
56(1)
4.3.9 GlaxoSmithKline
56(1)
4.3.10 Pfizer
57(1)
4.3.11 Tissue Targeting
57(1)
4.3.12 Polypharmacology
58(1)
4.3.13 Olanzapine Derivatives
58(1)
4.4 Conclusions
59(6)
References
60(5)
5 The Function, Enzyme Kinetics, Structural Biology, and Medicinal Chemistry of PDE10A
65(18)
Thomas A. Chappie
Patrick Verhoest
5.1 Enzymology and Protein Structure
66(3)
5.2 Papaverine-Related PDE10A Inhibitors
69(3)
5.3 MP-10/PF-2545920 Class of Inhibitors
72(2)
5.4 PF-2545920/MP-Inspired Inhibitors
74(1)
5.5 PF-2545920/Papaverine/Quinazoline Hybrid Series of Inhibitors
75(2)
5.6 PET Ligand Development
77(2)
5.7 Summary and Future
79(4)
References
79(4)
6 The State of the Art in Selective PDE2A Inhibitor Design
83(22)
Christopher W. am Ende
Bethany L Kormos
John M. Humphrey
6.1 Introduction
83(1)
6.2 Selective PDE2A Inhibitors
84(16)
6.2.1 Bayer
84(1)
6.2.2 Altana AG
85(2)
6.2.3 Biotie Therapies
87(1)
6.2.4 Boehringer Ingelheim
88(1)
6.2.5 Janssen
89(3)
6.2.6 Lundbeck
92(1)
6.2.7 Merck
93(2)
6.2.8 Neuro3d
95(1)
6.2.9 Pfizer
95(5)
6.3 Methods
100(1)
6.4 Conclusions
100(5)
References
101(4)
7 Crystal Structures of Phosphodiesterase 9A and Insight into Inhibitor Discovery
105(12)
Hengming Ke
Yousheng Wang
Yiqian Wan
Hai-Bin Luo
7.1 Introduction
105(1)
7.2 Subtle Asymmetry of the PDE9 Dimer in the Crystals
105(2)
7.3 The Structure of the PDE9 Catalytic Domain
107(1)
7.4 Interaction of Inhibitors with PDE9
108(2)
7.5 Implication on Inhibitor Selectivity
110(7)
References
114(3)
8 PDEs as CNS Targets: PDE9 Inhibitors for Cognitive Deficit Diseases
117(24)
Michelle M. Claffey
Christopher J. Helal
Xinjun Hou
8.1 PDE9A Enzymology and Pharmacology
117(2)
8.2 Crystal Structures of PDE9A Inhibitors
119(1)
8.3 Medicinal Chemistry Efforts toward Identifying PDE9A Inhibitors for Treating Cognitive Disorders
120(15)
8.3.1 Bayer
120(5)
8.3.2 Pfizer
125(4)
8.3.3 Boehringer Ingelheim
129(3)
8.3.4 Sun Yat-Sen University, China
132(1)
8.3.5 Envivo Pharmaceuticals
133(2)
8.4 Analysis of CNS Desirability of PDE9A Inhibitors
135(1)
8.5 Conclusions
135(6)
References
137(4)
9 Phosphodiesterase 8B
141(14)
Stephen W. Wright
9.1 Introduction
141(1)
9.2 Identification
141(1)
9.3 Properties
142(1)
9.4 Expression and Tissue Distribution
143(1)
9.5 Functions of PDE8B
143(2)
9.5.1 Thyroid
144(1)
9.5.2 Adrenal Gland
144(1)
9.5.3 Pancreatic Islets
144(1)
9.6 Inhibitors and Potential Therapeutic Uses
145(10)
References
150(5)
10 Selective New Small-Molecule Inhibitors of Phosphodiesterase 1
155(10)
John M. Humphrey
10.1 Introduction
155(1)
10.2 PDE1 Enzymology
155(1)
10.3 PDE1 Inhibitors
156(5)
10.3.1 Non-Selective PDE1 Inhibitors
156(2)
10.3.2 Selective PDE1 inhibitors
158(3)
10.4 Conclusion
161(4)
References
163(2)
11 Recent Advances in the Development of PDE7 Inhibitors
165(19)
Nigel A. Swain
Rainer Cewald
11.1 Introduction
165(1)
11.1.1 PDE7: Subtypes and Distribution
165(1)
11.1.2 Rationale for PDE7 as a Therapeutic Target
166(1)
11.2 Historical Development of PDE7 Inhibitors
166(3)
11.2.1 Early Examples of Nonselective and Selective Lead Matter
166(1)
11.2.2 Developing Selective Lead Matter from Nonselective Hits
167(1)
11.2.3 Targeting PDE4/7 Dual Inhibitors
168(1)
11.3 Recent Advances in the Discovery of PDE7 Inhibitors for Peripheral Therapeutic Benefit
169(4)
11.3.1 PDE7 Inhibitors for the Treatment of T Cell-Related Disorders
169(1)
11.3.1.1 Developments in PDE7 Inhibitors for the Treatment of Airway-Related Disorders
170(1)
11.3.1.2 Developments in PDE7 Inhibitors for the Treatment of Nonairway-Related Disorders
171(1)
11.3.1.3 Summary of T-Cell-Related Research
171(1)
11.3.2 PDE7 Inhibitors for the Treatment of Neuropathic Pain
172(1)
11.4 Recent Advances in the Discovery of PDE7 Inhibitors for CNS-Related Disorders
173(5)
11.4.1 Creating PDE7 Inhibitors by Ligand-Based Virtual Screening Methods
173(3)
11.4.2 Repositioning PDE7 Inhibitors Designed for the Treatment of Peripheral Diseases
176(2)
11.5 Recent Advances in the Discovery of Dual PDE7 Inhibitors
178(3)
11.5.1 Dual PDE4/7 Inhibitors
178(2)
11.5.2 Dual PDE7/8 Inhibitors
180(1)
11.6 Identifying Next-Generation PDE7 Inhibitors
181(3)
11.6.1 Emerging Chemotypes as Novel PDE7 Inhibitors
181(1)
11.6.2 Novel Methods to Identify PDE7 Inhibitors
182(1)
11.6.2.1 Computational Methods to Identify New PDE7 Inhibitors
182(1)
11.6.2.2 Fission Yeast-Based HTS to Identify New PDE7 Inhibitors
183(1)
117 Summary
184(7)
References
185(6)
12 Inhibitors of Protozoan Phosphodiesterases as Potential Therapeutic Approaches for Tropical Diseases
191(20)
Jennifer L. Woodring
Michael P. Pollastri
12.1 Introduction
191(1)
12.2 Malaria
192(3)
12.2.1 PfPDE Inhibition Studies
193(2)
12.3 Chagas Disease
195(2)
12.4 Leishmaniasis
197(3)
12.5 Human African Trypanosomiasis
200(5)
12.6 Conclusion
205(6)
References
206(5)
Index 211
Spiros Liras is the head of the cardiovascular metabolic and endocrine diseases (CVMED) medicinal chemistry department at Pfizer R&D in Cambridge, MA (USA). Previously, he was Senior Director of medicinal chemistry in Neuroscience at Pfizer, working on treatments for addiction, depression, schizophrenia, cognition and Alzheimer's disease. In Neuroscience he worked on multiple PDE targets for the treatment of neuropsychiatric diseases including PDE10, PDE9, PDE2 and PDE1. Dr. Liras obtained his PhD in organic chemistry in 1989 from Iowa State University. He joined Pfizer in 1994 after postdoctoral studies at the University of Texas at Austin. He is a coauthor in more than 70 publications and patents.

Andrew Bell was with Pfizer for over 30 years, following studies at York University (UK). He spent his early career working on PDE inhibitors leading to the inotrope/ vasodilator (PDE3) candidate, nanterinone, and the PDE5 inhibitor, sildenafil (Viagra, Revatio). Soon after the launch of sildenafil in 1998, he was given responsibility for File Enrichment, as part of Pfizer's collaborations with ArQule and Tripos. He has subsequently applied the results of the File Enrichment investment to generate new lead series for multiple projects, including novel series of selective PDE- 4,5,8 and 9 inhibitors. He is currently involved in research into parasitic diseases at Imperial College, London.
Püsilink: https://www.kriso.ee/db/9783527682348_pe.html
Märksõnad: