06520cam a2200853Ma 4500 ocn797858047 OCoLC 20170612141628.0 m o d cr cn||||||||| 110927s2012 nju ob 001 0 eng d E7B eng pn E7B OCLCF EBLCP IDEBK N$T DG1 YDXCP UIU EUX RECBK U3G OCLCQ DEBBG 792684096 795813847 860795540 898985666 1118219708 (electronic bk.) 9781118219706 (electronic bk.) 9781118219683 (electronic bk.) 1118219686 (electronic bk.) 9781118219676 (electronic bk.) 1118219678 (electronic bk.) 0470601817 9780470601815 9780470601815 9781118219706 EB00063040 Recorded Books AU@ 000049595453 DEBBG BV042794919 DKDLA 820120-katalog:000599605 NZ1 14693457 DEBBG BV043394639 (OCoLC)797858047 (OCoLC)792684096 (OCoLC)795813847 (OCoLC)860795540 (OCoLC)898985666 10.1002/9781118219683 Wiley InterScience http://www3.interscience.wiley.com RS403 .C37 2012eb MED 023000 bisacsh MED 058170 bisacsh MED 071000 bisacsh MED 072000 bisacsh 615.19 23 MAIN Case studies in modern drug discovery and development / edited by Xianhai Huang, Robert G. Aslanian. Hoboken, NJ : John Wiley & Sons, ©2012. 1 online resource (xviii, 451 pages) text txt rdacontent computer c rdamedia online resource cr rdacarrier Includes bibliographical references and index. CASE STUDIES IN MODERN DRUG DISCOVERY AND DEVELOPMENT; CONTENTS; PREFACE; CONTRIBUTORS; CHAPTER 1: INTRODUCTION: DRUG DISCOVERY IN DIFFICULT TIMES; CHAPTER 2: DISCOVERY AND DEVELOPMENT OF THE DPP-4 INHIBITOR JANUVIA; (SITA-GLIPTIN); 2.1 Introduction; 2.2 DPP-4 Inhibition as a Therapy for Type 2 Diabetes: Identification of Key Determinants for Efficacy and Safety; 2.2.1 Incretin-Based Therapy for T2DM; 2.2.2 Biological Rationale: DPP-4 is a Key Regulator of Incretin Activity; 2.2.3 Injectable GLP-1 Mimetics for the Treatment of T2DM. 2.2.11 DPP-4 Inhibitor Selectivity as a Key Parameter for Drug Development2.3 Medicinal Chemistry Program; 2.3.1 Lead Generation Approaches; 2.3.2 Cyclohexyl Glycine a-Amino Acid Series of DPP-4 Inhibitors; 2.3.3 Improving Selectivity of the a-Amino Acid Series; 2.3.4 Identification and Optimization of the ß-Amino Acid Series; 2.4 Synthetic and Manufacturing Routes to Sitagliptin; 2.4.1 Medicinal Chemistry Route to Sitagliptin and Early Modifications; 2.4.2 An Asymmetric Hydrogenation Manufacturing Route to Sitagliptin. 2.2.4 DPP-4 Inhibition as Oral Incretin-Based Therapy for T2DM2.2.5 Investigation of DPP-4 Biology: Identification of Candidate Substrates; 2.2.6 Preclinical Toxicities of In-Licensed DPP-4 Inhibitors; 2.2.7 Correlation of Preclinical Toxicity with Off-Target Inhibition of Pro-Specific Dipeptidase Activity; 2.2.8 Identification of Pro-Specific Dipeptidases Differentially Inhibited by the Probiodrug Compounds; 2.2.9 A Highly Selective DPP-4 Inhibitor is Safe and Well Tolerated in Preclinical Species; 2.2.10 A Highly Selective DPP-4 Inhibitor Does Not Inhibit T-Cell Proliferation in vitro. 2.4.3 A "Greener" Manufacturing Route to Sitagliptin Employing Biocatalytic Transamination2.5 Drug Product Development; 2.5.1 Overview; 2.5.2 Composition Development; 2.5.3 Manufacturing Process Development; 2.6 Clinical Studies; 2.6.1 Preclinical PD Studies and Early Clinical Development of Sitagliptin; 2.6.2 Summary of Phase II/III Clinical Trials; 2.7 Summary; References; CHAPTER 3: OLMESARTAN MEDOXOMIL: AN ANGIOTENSIN II RECEPTOR BLOCKER; 3.1 Background; 3.1.1 Introduction; 3.1.2 Prototype of Orally Active ARBs; 3.2 The Discovery of Olmesartan Medoxomil (Benicar); 3.2.1 Lead Generation. 3.2.2 Lead Optimization3.3 Characteristics of Olmesartan; 3.4 Binding Sites of Omlersartan to the AT1 Receptor and Its Inverse Agonoist Activity; 3.4.1 Binding Sites of Olmesartan to the AT1 Receptor; 3.4.2 Inverse Agonist Activity of Olmesartan; 3.4.3 Molecular Model of the Interaction between Olmesartan and the AT1 Receptor; 3.5 Practical Preparation of Olmesartan Medoxomil; 3.6 Preclinical Studies; 3.6.1 AT1 Receptor Blocking Action; 3.6.2 Inhibition of Ang II-Induced Vascular Contraction; 3.6.3 Inhibition of the Pressor Response to Ang II; 3.6.4 Blood Pressure Lowering Effects. Learn why some drug discovery and development efforts succeed ... and others failWritten 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. Drugs Design. Pharmaceutical chemistry. Medical. MEDICAL Drug Guides. bisacsh MEDICAL Nursing Pharmacology. bisacsh MEDICAL Pharmacology. bisacsh MEDICAL Pharmacy. bisacsh Drugs Design. fast (OCoLC)fst00898790 Pharmaceutical chemistry. fast (OCoLC)fst01060115 Electronic books. Huang, Xianhai. Aslanian, Robert G. Print version: Case studies in modern drug discovery and development 9780470601815 http://onlinelibrary.wiley.com/book/10.1002/9781118219683 Wiley Online Library EBL - Ebook Library EBLB EBL822083 ebrary EBRY ebr10560567 EBSCOhost EBSC 450383 Ingram Digital eBook Collection IDEB 362083 Recorded Books, LLC RECE rbeEB00063040 YBP Library Services YANK 7613837 YBP Library Services YANK 12671182 92 DG1 206002 206002