06305cam a2200913Mi 4500 ocn878141373 OCoLC 20171030134440.0 m o d cr cn||||||||| 140325t20142014gw a ob 001 0 eng d 9783527682355 (electronic bk.) 352768235X (electronic bk.) 9783527682348 (electronic bk.) 3527682341 (electronic bk.) 3527332197 9783527332199 9781306531955 1306531950 3527682376 (Mobi) 9783527682379 (Mobi) 3527682368 (ePub) 9783527682362 (ePub) 9783527332199 9783527682379 (Mobi) 9783527682362 (ePub) CHBIS 010259738 CHVBK 325940886 DEBBG BV042795782 DEBBG BV042989481 DEBSZ 431651620 DEBSZ 449419991 GBVCP 814301746 DEBSZ 475023528 DEBBG BV043396710 (OCoLC)878141373 (OCoLC)874321908 (OCoLC)881423826 (OCoLC)961577287 (OCoLC)962694307 584446 MIL E7B eng rda pn E7B N$T YDXCP DG1 CDX EBLCP IDEBK SFB DEBSZ COO DEBBG OCLCQ CASUM MAIN QP609.C92 .P467 2014eb QU 136 MED 075000 bisacsh SCI 036000 bisacsh 612.01519 23 Phosphodiesterases and their inhibitors / edited by Spiros Liras and Andrew S. Bell. [electronic resource] Weinheim an der Bergstrasse, Germany : Wiley-VCH, 2014. ©2014 1 online resource (238 pages) : illustrations. text txt rdacontent computer c rdamedia online resource cr rdacarrier Methods and Principles in Medicinal Chemistry ; Volume 61 Includes bibliographical references at the end of each chapters and index. 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. Print version record. Cyclic nucleotide phosphodiesterases. Phosphodiesterases Inhibitors. Phosphodiesterases Inhibitors Therapeutic use. Cyclic nucleotide phosphodiesterases. Nucleotides, Cyclic physiology. Phosphodiesterase Inhibitors therapeutic use. Phosphoric Diester Hydrolases physiology. Phosphoric Diester Hydrolases. MEDICAL Physiology. bisacsh SCIENCE Life Sciences Human Anatomy & Physiology. bisacsh Phosphodiesterase Inhibitors chemistry. Phosphodiesterase Inhibitors therapeutic use. Electronic books. Liras, Spiros, editor. Bell, Andrew S., editor. Print version: Phosphodiesterases and their inhibitors. Weinheim an der Bergstrasse, Germany : Wiley-VCH, ©2014 xviii, 218 pages Methods and principles in medicinal chemistry ; Volume 61 9783527332199 Methods and principles in medicinal chemistry ; Volume 61. http://onlinelibrary.wiley.com/book/10.1002/9783527682348 Wiley Online Library ddc BK 207392 207392