{"product_id":"case-studies-in-modern-drug-discovery-and-development-hardback-9780470601815","title":"Case Studies in Modern Drug Discovery and Development (Hardback) 9780470601815","description":"\u003cfont face=\"Georgia\"\u003e\r\n\u003cp\u003e\u003cfont size=\"6\"\u003eCase Studies in Modern Drug Discovery and Development\u003c\/font\u003e\u003cbr\u003e\r\n\r\n\r\n\r\n\r\n\r\n\u003c\/p\u003e\n\u003cp\u003e\u003cfont size=\"4\"\u003eXianhai Huang (Edited by), Robert G. Aslanian (Edited by)\u003c\/font\u003e\u003c\/p\u003e\r\n\r\n\u003cp\u003e\u003cfont size=\"3\"\u003e9780470601815, Wiley\u003c\/font\u003e\u003c\/p\u003e\r\n\r\n\u003cp\u003e\u003cfont size=\"3\"\u003eHardback, published 15 June 2012\u003c\/font\u003e\u003c\/p\u003e\r\n\r\n\u003cp\u003e\u003cfont size=\"3\"\u003e488 pages\u003cbr\u003e26.4 x 18.8 x 3.1 cm, 1.012 kg\u003c\/font\u003e\u003c\/p\u003e\r\n\r\n\r\n\r\n\u003cp align=\"justify\"\u003e\u003cem\u003e\u003cfont size=\"3\"\u003e\u003cp\u003e“This book will enrich the collection of medicinal chemists or pharmacologists involved in active drug discovery research, as well as students with a passion for pursuing a career in drug discovery.”  (\u003ci\u003eDoody’s\u003c\/i\u003e, 22 February 2013) \u003c\/p\u003e \u003cp\u003e\"A well-made glossary is available in the appendix, which defines the dozens of terms that a medicinal chemist will encounter in his\/her career. . . This book demonstrates yet again the need for new, better medicines and the reasons for the high cost of drug research. An enjoyable read!.”  (\u003ci\u003eChemMedChem\u003c\/i\u003e, 1 January 2013)\u003c\/p\u003e\u003c\/font\u003e\u003c\/em\u003e\u003c\/p\u003e\r\n\r\n\u003cp align=\"justify\"\u003e\u003cstrong\u003e\u003cfont size=\"3\"\u003e\u003cp\u003e\u003cb\u003eLearn why some drug discovery and development efforts succeed . . . and others fail \u003c\/b\u003e\u003c\/p\u003e \u003cp\u003eWritten by international experts in drug discovery and development, this book sets forth carefully researched and analyzed case studies of both successful and failed drug discovery and development efforts, enabling medicinal chemists and pharmaceutical scientists to learn from actual examples. Each case study focuses on a particular drug and therapeutic target, guiding readers through the drug discovery and development process, including drug design rationale, structure-activity relationships, pharmacology, drug metabolism, biology, and clinical studies.\u003c\/p\u003e \u003cp\u003e\u003ci\u003eCase Studies in Modern Drug Discovery and Development\u003c\/i\u003e begins with an introductory chapter that puts into perspective the underlying issues facing the pharmaceutical industry and provides insight into future research opportunities. Next, there are fourteen detailed case studies, examining:\u003c\/p\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eAll phases of drug discovery and development from initial idea to commercialization\u003c\/p\u003e \u003c\/li\u003e \u003cli\u003e \u003cp\u003eSome of today's most important and life-saving medications\u003c\/p\u003e \u003c\/li\u003e \u003cli\u003e \u003cp\u003eDrugs designed for different therapeutic areas such as cardiovascular disease, infection, inflammation, cancer, metabolic syndrome, and allergies\u003c\/p\u003e \u003c\/li\u003e \u003cli\u003e \u003cp\u003eExamples of prodrugs and inhaled drugs\u003c\/p\u003e \u003c\/li\u003e \u003cli\u003e \u003cp\u003eReasons why certain drugs failed to advance to market despite major research investments\u003c\/p\u003e \u003c\/li\u003e \u003c\/ul\u003e \u003cp\u003eEach chapter ends with a list of references leading to the primary literature. There are also plenty of tables and illustrations to help readers fully understand key concepts, processes, and technologies.\u003c\/p\u003e \u003cp\u003eImproving the success rate of the drug discovery and development process is paramount to the pharmaceutical industry. With this book as their guide, readers can learn from both successful and unsuccessful efforts in order to apply tested and proven science and technologies that increase the probability of success for new drug discovery and development projects.\u003c\/p\u003e\u003c\/font\u003e\u003c\/strong\u003e\u003c\/p\u003e\r\n\r\n\u003cp\u003e\u003cfont size=\"3\"\u003e\u003cp\u003ePreface xv\u003c\/p\u003e \u003cp\u003eContributors xvii\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 1 Introduction: Drug Discovery in Difficult Times 1\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eMalcolm MacCoss\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 2 Discovery and Development of The DPP-4 Inhibitor Januvia\u003c\/b\u003e\u003cb\u003e® (SITA-GLIPTIN) 10\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eEmma R. Parmee, Ranabir SinhaRoy, Feng Xu, Jeffrey C. Givand, and Lawrence A. Rosen\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e2.1 Introduction 10\u003c\/p\u003e \u003cp\u003e2.2 DPP-4 Inhibition as a Therapy for Type 2 Diabetes: Identification of Key Determinants for Efficacy and Safety 10\u003c\/p\u003e \u003cp\u003e2.3 Medicinal Chemistry Program 20\u003c\/p\u003e \u003cp\u003e2.4 Synthetic and Manufacturing Routes to Sitagliptin 27\u003c\/p\u003e \u003cp\u003e2.5 Drug Product Development 33\u003c\/p\u003e \u003cp\u003e2.6 Clinical Studies 36\u003c\/p\u003e \u003cp\u003e2.7 Summary 39\u003c\/p\u003e \u003cp\u003eReferences 39\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 3 Olmesartan Medoxomil: An Angiotensin II Receptor Blocker 45\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eHiroaki Yanagisawa, Hiroyuki Koike, and Shin-ichiro Miura\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e3.1 Background 45\u003c\/p\u003e \u003cp\u003e3.1.1 Introduction 45\u003c\/p\u003e \u003cp\u003e3.1.2 Prototype of Orally Active ARBs 46\u003c\/p\u003e \u003cp\u003e3.2 The Discovery of Olmesartan Medoxomil (Benicar) 47\u003c\/p\u003e \u003cp\u003e3.3 Characteristics of Olmesartan 53\u003c\/p\u003e \u003cp\u003e3.4 Binding Sites of Omlersartan to the AT1 Receptor and Its Inverse Agonoist Activity 56\u003c\/p\u003e \u003cp\u003e3.5 Practical Preparation of Olmesartan Medoxomil 58\u003c\/p\u003e \u003cp\u003e3.6 Preclinical Studies 58\u003c\/p\u003e \u003cp\u003e3.7 Clinical Studies 62\u003c\/p\u003e \u003cp\u003e3.8 Conclusion 63\u003c\/p\u003e \u003cp\u003eReferences 64\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 4 Discovery of Heterocyclic Phosphonic Acids as Novelampmimics That Are Potent and\u003c\/b\u003e \u003cb\u003eSelective Fructose-1,6-Bisphosphatase Inhibitors and Elicit Potent Glucose-Lowering Effects in\u003c\/b\u003e \u003cb\u003eDiabetic Animals and Humans 67\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eQun Dang and Mark D. Erion\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e4.1 Introduction 67\u003c\/p\u003e \u003cp\u003e4.2 The Discovery of MB06322 69\u003c\/p\u003e \u003cp\u003e4.3 Pharmacokinetic Studies of MB06322 82\u003c\/p\u003e \u003cp\u003e4.4 Synthetic Routes to MB06322 83\u003c\/p\u003e \u003cp\u003e4.5 Clinical Studies of MB06322 83\u003c\/p\u003e \u003cp\u003e4.6 Summary 84\u003c\/p\u003e \u003cp\u003eReferences 85\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 5 Setting The Paradigm of Targeted Drugs for The Treatment of Cancer: Imatinib and Nilotinib, Therapies for Chronic Myelogenous Leukemia 88\u003cbr\u003e\u003c\/b\u003e\u003ci\u003ePaul W. Manley and Jurg Zimmermann\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e5.1 Introduction 88\u003c\/p\u003e \u003cp\u003e5.2 Chronic Myelogenous Leukemia (CML) and Early Treatment of the Disease 89\u003c\/p\u003e \u003cp\u003e5.3 Imatinib: A Treatment for Chronic Myelogenous Leukemia (CML) 92\u003c\/p\u003e \u003cp\u003e5.4 The Need for New Inhibitorts of BCR-ABL1 and Development of Nilotinib 94\u003c\/p\u003e \u003cp\u003e5.5 Conclusion 99\u003c\/p\u003e \u003cp\u003eReferences 100\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 6 Amrubicin, A Completely Synthetic 9-Aminoanthracycline for Extensive-Disease Small-Cell\u003c\/b\u003e \u003cb\u003eLung Cancer 103\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eMitsuharu Hanada\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e6.1 Introduction 103\u003c\/p\u003e \u003cp\u003e6.2 The Discovery of Amrubicin: The First Completely Synthetic Anthracycline 106\u003c\/p\u003e \u003cp\u003e6.3 Toxicological Profile of Amrubicin 107\u003c\/p\u003e \u003cp\u003e6.4 DNA Topoisomerase II Inhibition and Apoptosis Induction by Amrubicin 110\u003c\/p\u003e \u003cp\u003e6.5 Amrubicin Metabolism: The Discovery of Amrubicinol 113\u003c\/p\u003e \u003cp\u003e6.6 Improved Usage of Amrubicin 116\u003c\/p\u003e \u003cp\u003e6.7 Clinical Trials 118\u003c\/p\u003e \u003cp\u003e6.8 Conclusions 122\u003c\/p\u003e \u003cp\u003eReferences 123\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 7 The Discovery of Dual IGF-1R and IR Inhibitor FQIT for the Treatment of Cancer 127\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eMeizhong Jin, Elizabeth Buck, and Mark J. Mulvihill\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e7.1 Biological Rational for Targeting the IGF-1R\/IR Pathway for Anti-Cancer Therapy 127\u003c\/p\u003e \u003cp\u003e7.2 Discovery of OSI-906 128\u003c\/p\u003e \u003cp\u003e7.3 OSI-906 Back Up Efforts 131\u003c\/p\u003e \u003cp\u003e7.4 The Discovery of FQIT 131\u003c\/p\u003e \u003cp\u003e7.5 \u003ci\u003eIn Vitro\u003c\/i\u003e Profile of FQIT 140\u003c\/p\u003e \u003cp\u003e7.6 Pharmacokinetic Properties of FQIT 144\u003c\/p\u003e \u003cp\u003e7.7 \u003ci\u003eIn Vivo\u003c\/i\u003e Profile of FQIT 146\u003c\/p\u003e \u003cp\u003e7.8 Safety Assessment and Selectivity Profile of FQIT 148\u003c\/p\u003e \u003cp\u003e7.9 Summary 150\u003c\/p\u003e \u003cp\u003eAcknowledgments 151\u003c\/p\u003e \u003cp\u003eReferences 151\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 8 Discovery and Development of Montelukast (Singulair\u003c\/b\u003e\u003cb\u003e®) 154\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eRobert N. Young\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e8.1 Introduction 154\u003c\/p\u003e \u003cp\u003e8.2 Drug Development Strategies 158\u003c\/p\u003e \u003cp\u003e8.3 LTD4 Antagonist Program 159\u003c\/p\u003e \u003cp\u003e8.4 The Discovery of Montelukast (Singulair®) 160\u003c\/p\u003e \u003cp\u003e8.5 Synthesis of Montelukast 174\u003c\/p\u003e \u003cp\u003e8.6 ADME Studies with MK-0476 (Montelukast) 179\u003c\/p\u003e \u003cp\u003e8.7 Safety Assessment of Montelukast 180\u003c\/p\u003e \u003cp\u003e8.8 Clinical Development of Montelukast 180\u003c\/p\u003e \u003cp\u003e8.9 Summary 185\u003c\/p\u003e \u003cp\u003e8.10 Personal Impact 187\u003c\/p\u003e \u003cp\u003eReferences 188\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 9 Discovery and Development of Maraviroc, A CCR5 Antagonist for the Treatment of HIV\u003c\/b\u003e \u003cb\u003eInfection 196\u003cbr\u003e\u003c\/b\u003e\u003ci\u003ePatrick Dorr, Blanda Stammen, and Elna van der Ryst\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e9.1 Background and Rationale 196\u003c\/p\u003e \u003cp\u003e9.2 The Discovery of Maraviroc 199\u003c\/p\u003e \u003cp\u003e9.3 Preclinical Studies 201\u003c\/p\u003e \u003cp\u003e9.4 The Synthesis of Maraviroc 205\u003c\/p\u003e \u003cp\u003e9.5 Nonclinical Safety and Toxicity Studies 206\u003c\/p\u003e \u003cp\u003e9.6 Clinical Development of Maraviroc 207\u003c\/p\u003e \u003cp\u003e9.7 Summary, Future Directions, and Challenges 214\u003c\/p\u003e \u003cp\u003eAcknowledgments 217\u003c\/p\u003e \u003cp\u003eReferences 217\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 10 Discovery of Antimalarial Drug Artemisinin and Beyond 227\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eWeiwei Mao, Yu Zhang, and Ao Zhang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e10.1 Introduction: Natural Products in Drug Discovery 227\u003c\/p\u003e \u003cp\u003e10.2 Natural Product Drug Discovery in China 227\u003c\/p\u003e \u003cp\u003e10.3 Discovery of Artemisinin: Background, Structural Elucidation and Pharmacological Evaluation 228\u003c\/p\u003e \u003cp\u003e10.4 The Synthesis of Artemisinin 232\u003c\/p\u003e \u003cp\u003e10.5 SAR Studies of Structural Derivatives of Artemisinin: The Discovery of Artemether 238\u003c\/p\u003e \u003cp\u003e10.6 Development of Artemether 248\u003c\/p\u003e \u003cp\u003e10.7 Conclusion and Perspective 250\u003c\/p\u003e \u003cp\u003eAcknowledgment 250\u003c\/p\u003e \u003cp\u003eReferences 251\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 11 Discovery and Process Development of MK-4965, A Potent Nonnucleoside Reverse\u003c\/b\u003e \u003cb\u003eTranscriptase Inhibitor 257\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eYong-Li Zhong, Thomas J. Tucker, and Jingjun Yin\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e11.1 Introduction 257\u003c\/p\u003e \u003cp\u003e11.2 The Discovery of MK-4965 260\u003c\/p\u003e \u003cp\u003e11.3 Preclinical and Clinical Studies of MK-4965 (19) 266\u003c\/p\u003e \u003cp\u003e11.4 Summary of Back-Up SAR Studies of MK-4965 Series 266\u003c\/p\u003e \u003cp\u003e11.5 Process Development of MK-4965 (19) 267\u003c\/p\u003e \u003cp\u003e11.6 Conclusion 290\u003c\/p\u003e \u003cp\u003eAcknowledgments 291\u003c\/p\u003e \u003cp\u003eReferences 291\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 12 Discovery of Boceprevir and Narlaprevir: The First and Second Generation of HCV NS3\u003c\/b\u003e \u003cb\u003eProtease Inhibitors 296\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eKevin X. Chen and F. George Njoroge\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e12.1 Introduction 296\u003c\/p\u003e \u003cp\u003e12.2 HCV NS3 Protease Inhibitors 298\u003c\/p\u003e \u003cp\u003e12.3 Research Operation Plan and Biological Assays 302\u003c\/p\u003e \u003cp\u003e12.4 Discovery of Boceprevir 303\u003c\/p\u003e \u003cp\u003e12.5 Profile of Boceprevir 317\u003c\/p\u003e \u003cp\u003e12.6 Clinical Development and Approval of Boceprevir 319\u003c\/p\u003e \u003cp\u003e12.7 Synthesis of Boceprevir 319\u003c\/p\u003e \u003cp\u003e12.8 Discovery of Narlaprevir 322\u003c\/p\u003e \u003cp\u003e12.9 Summary 329\u003c\/p\u003e \u003cp\u003eReferences 330\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 13 The Discoveryofsamsca\u003c\/b\u003e\u003cb\u003e® (Tolvaptan): Thefirst Oral Nonpeptide Vasopressin Receptor\u003c\/b\u003e \u003cb\u003eAntagonist 336\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eKazumi Kondo and Yoshitaka Yamamura\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e13.1 Background Information about the Disease 336\u003c\/p\u003e \u003cp\u003e13.2 Biological Rational 337\u003c\/p\u003e \u003cp\u003e13.3 Lead Generation Strategies: The Discovery of Mozavaptan 338\u003c\/p\u003e \u003cp\u003e13.4 Lead Optimization: From Mozavaptan to Tolvaptan 347\u003c\/p\u003e \u003cp\u003e13.5 Pharmacological Profiles of Tolvaptan 350\u003c\/p\u003e \u003cp\u003e13.6 Drug Development 353\u003c\/p\u003e \u003cp\u003e13.7 Summary Focusing on Lessons Learned 356\u003c\/p\u003e \u003cp\u003eAcknowledgments 357\u003c\/p\u003e \u003cp\u003eReferences 357\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 14 Silodosin (Urief\u003c\/b\u003e\u003cb\u003e®, Rapaflo\u003c\/b\u003e\u003cb\u003e®, Thrupas\u003c\/b\u003e\u003cb\u003e®, Urorec\u003c\/b\u003e\u003cb\u003e®, Silodix\u003c\/b\u003e\u003cb\u003e®): A Selective \u003c\/b\u003e\u003cb\u003eα1A Adrenoceptor\u003c\/b\u003e \u003cb\u003eAntagonist for the Treatment of Benign Prostatic Hyperplasia 360\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eMasaki Yoshida, Imao Mikoshiba, Katsuyoshi Akiyama, and Junzo Kudoh\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e14.1 Background Information 360\u003c\/p\u003e \u003cp\u003e14.2 The Discovery of Silodosin 362\u003c\/p\u003e \u003cp\u003e14.3 Pharmacology of Silodosin 369\u003c\/p\u003e \u003cp\u003e14.4 Metabolism of Silodosin 373\u003c\/p\u003e \u003cp\u003e14.5 Pharmacokinetics of Silodosin 376\u003c\/p\u003e \u003cp\u003e14.6 Toxicology of Silodosin 379\u003c\/p\u003e \u003cp\u003e14.7 Clinical Trials 382\u003c\/p\u003e \u003cp\u003e14.8 Summary: Key Lessons Learned 388\u003c\/p\u003e \u003cp\u003eReferences 389\u003c\/p\u003e \u003cp\u003e\u003cb\u003eChapter 15 Raloxifene: A Selective Estrogen Receptor Modulator (SERM) 392\u003c\/b\u003e\u003cbr\u003e\u003ci\u003eJeffrey A. Dodge and Henry U. Bryant\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e15.1 Introduction: SERMs 392\u003c\/p\u003e \u003cp\u003e15.2 The Benzothiophene Scaffold: A New Class of SERMs 394\u003c\/p\u003e \u003cp\u003e15.3 Assays for Biological Evaluation of Tissue Selectivity 394\u003c\/p\u003e \u003cp\u003e15.4 Benzothiophene Structure Activity 395\u003c\/p\u003e \u003cp\u003e15.5 The Synthesis of Raloxifene 401\u003c\/p\u003e \u003cp\u003e15.6 SERM Mechanism 402\u003c\/p\u003e \u003cp\u003e15.7 Raloxifene Pharmacology 405\u003c\/p\u003e \u003cp\u003e15.8 Summary 411\u003c\/p\u003e \u003cp\u003eReferences 411\u003c\/p\u003e \u003cp\u003eAppendix I Small Molecule Drug Discovery and Development Paradigm 417\u003c\/p\u003e \u003cp\u003eAppendix II Glossary 419\u003c\/p\u003e \u003cp\u003eAppendix III Abbreviations 432\u003c\/p\u003e \u003cp\u003eIndex 443\u003c\/p\u003e\u003c\/font\u003e\u003c\/p\u003e\r\n\r\n\u003cp\u003e\u003cfont size=\"3\"\u003eSubject Areas: Chemistry [\u003ca title=\"See our other books on Chemistry\" href=\"https:\/\/freshlyprintedbooks.co.uk\/search?q=%22Chemistry%20%5BPN%5D%22\"\u003ePN\u003c\/a\u003e]\u003c\/font\u003e\u003c\/p\u003e\r\n\r\n\r\n\u003c\/font\u003e","brand":"Wiley","offers":[{"title":"Brand New","offer_id":52507409744152,"sku":"9780470601815","price":98.19,"currency_code":"GBP","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0730\/2037\/5320\/files\/9780470601815.jpg?v=1786445973","url":"https:\/\/freshlyprintedbooks.co.uk\/products\/case-studies-in-modern-drug-discovery-and-development-hardback-9780470601815","provider":"Freshly Printed Books","version":"1.0","type":"link"}