LEADER 05426nam 2200673Ia 450 001 9910827925703321 005 20200520144314.0 010 $a1-281-76371-3 010 $a9786611763718 010 $a0-08-095162-7 010 $a0-08-055761-9 035 $a(CKB)1000000000547622 035 $a(EBL)365589 035 $a(OCoLC)476198605 035 $a(SSID)ssj0000141613 035 $a(PQKBManifestationID)11134533 035 $a(PQKBTitleCode)TC0000141613 035 $a(PQKBWorkID)10090176 035 $a(PQKB)10706378 035 $a(MiAaPQ)EBC365589 035 $a(Au-PeEL)EBL365589 035 $a(CaPaEBR)ebr10251256 035 $a(EXLCZ)991000000000547622 100 $a20070828d2008 uy 0 101 0 $aeng 135 $aur|n|---||||| 181 $ctxt$2rdacontent 182 $cc$2rdamedia 183 $acr$2rdacarrier 200 10$aDrug-like properties $econcepts, structure design and methods : from ADME to toxicity optimization /$fEdward H. Kerns and Li Di 205 $a1st ed. 210 $aAmsterdam ;$aBoston $cAcademic Press$dc2008 215 $a1 online resource (xix, 526 pages, 2 unnumbered pages of plates) $cillustrations (some color) 311 0 $a0-12-369520-1 320 $aIncludes bibliographical references (p. 492) and index. 327 $aFront Cover; Drug-like Properties: Concepts, Structure Design and Methods: from ADME to Toxicity Optimization; Copyright Page; Table of Contents; Preface; Dedication; Part 1 Introductory Concepts; Chapter 1 Introduction; Problems; References; Chapter 2 Advantages of Good Drug-like Properties; 2.1 Drug-like Properties Are an Integral Part of Drug Discovery; 2.1.1 Many Properties Are of Interest in Discovery; 2.1.2 Introduction to the Drug Discovery and Development Process; 2.1.3 Development Attrition is Reduced by Improving Drug Properties 327 $a2.1.4 Poor Drug Properties Also Cause Discovery Inefficiencies; 2.1.5 Marginal Drug Properties Cause Inefficiencies During Development; 2.1.6 Poor Properties Can Cause Poor Discovery Research; 2.2 Changing Emphasis on Properties in Discovery; 2.3 Property Profiling in Discovery; 2.4 Drug-like Property Optimization in Discovery; Problems; References; Chapter 3 Barriers to Drug Exposure in Living Systems; 3.1 Introduction to Barriers; 3.2 Drug Dosing; 3.3 Barriers in the Mouth and Stomach; 3.4 Gastrointestinal Tract Barriers; 3.4.1 Permeation of the Gastrointestinal Cellular Membrane 327 $a3.4.2 Passive Diffusion at the Molecular Level; 3.4.3 Metabolism in the Intestine; 3.4.4 Enzymatic Hydrolysis in the Intestine; 3.4.5 Absorption Enhancement in the Intestine; 3.5 Barriers in the Bloodstream; 3.5.1 Plasma Enzyme Hydrolysis; 3.5.2 Plasma Protein Binding; 3.5.3 Red Blood Cell Binding; 3.6 Barriers in the Liver; 3.6.1 Metabolism; 3.6.2 Biliary Excretion; 3.7 Barriers in the Kidney; 3.8 Blood-Tissue Barriers; 3.9 Tissue Distribution; 3.10 Consequences of Chirality on Barriers and Properties; 3.11 Overview of In Vivo Barriers; Problems; References; Part 2 Physicochemical Properties 327 $aChapter 4 Rules for Rapid Property Profiling from Structure; 4.1 Lipinski Rules; 4.2 Veber Rules; 4.3 Other Rules; 4.4 Application of Rules for Compound Assessment; Problems; References; Chapter 5 Lipophilicity; 5.1 Lipophilicity Fundamentals; 5.2 Lipophilicity Effects; 5.3 Lipophilicity Case Studies and Structure Modification; Problems; References; Chapter 6 pKa; 6.1 pKa Fundamentals; 6.2 pKa Effects; 6.3 pKa Case Studies; 6.4 Structure Modification Strategies for pKa; Problems; References; Chapter 7 Solubility; 7.1 Solubility Fundamentals 327 $a7.1.1 Solubility Varies with Structure and Physical Conditions; 7.1.2 Dissolution Rate; 7.1.3 Structural Properties Affect Solubility; 7.1.4 Kinetic and Thermodynamic Solubility; 7.2 Effects of Solubility; 7.2.1 Low Solubility Limits Absorption and Causes Low Oral Bioavailability; 7.2.2 Good Solubility is Essential for IV Formulation; 7.2.3 Acceptance Criteria and Classifications for Solubility; 7.2.4 Molecular Properties for Solubility and Permeability Often are Opposed; 7.3 Effects of Physiology on Solubility and Absorption; 7.3.1 Physiology of the Gastrointestinal Tract; 7.3.2 Species Differences in Gastrointestinal Tract 330 $aOf the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, typically only a fraction of these have sufficient ADME/Tox properties to become a drug product. Understanding ADME/Tox is critical for all drug researchers, owing to its increasing importance in advancing high quality candidates to clinical studies and the processes of drug discovery. If the properties are weak, the candidate will have a high risk of failure or be less desirable as a drug product. 606 $aPharmaceutical chemistry 606 $aDrugs$xStructure-activity relationships 606 $aDrug development 606 $aDrugs$xDesign 615 0$aPharmaceutical chemistry. 615 0$aDrugs$xStructure-activity relationships. 615 0$aDrug development. 615 0$aDrugs$xDesign. 676 $a615/.19 700 $aKerns$b Edward Harvel$01701614 701 $aDi$b Li$01701615 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910827925703321 996 $aDrug-like properties$94085506 997 $aUNINA