LEADER 07555nam 22013693u 450 001 9910133588303321 005 20210114065954.0 010 $a1-280-59122-6 010 $a9786613621054 010 $a0-470-91509-9 010 $a0-470-91511-0 035 $a(CKB)3400000000000281 035 $a(EBL)698845 035 $a(OCoLC)695561347 035 $a(SSID)ssj0000550563 035 $a(PQKBManifestationID)11341225 035 $a(PQKBTitleCode)TC0000550563 035 $a(PQKBWorkID)10509126 035 $a(PQKB)10906858 035 $a(MiAaPQ)EBC698845 035 $a(PPN)237853906 035 $a(EXLCZ)993400000000000281 100 $a20131014d2012|||| u|| | 101 0 $aeng 135 $aur|n|---||||| 181 $ctxt 182 $cc 183 $acr 200 10$aADMET for Medicinal Chemists$b[electronic resource] $eA Practical Guide 210 $aHoboken $cWiley$d2012 215 $a1 online resource (524 p.) 300 $aDescription based upon print version of record. 311 $a0-470-48407-1 327 $aADMET for Medicinal Chemists: A Practical Guide; CONTENTS; Preface; Contributors; 1 Introduction; 1.1 Introduction; 1.2 Voyage Through The Digestive System; 1.2.1 The Mouth; 1.2.2 The Stomach; 1.2.3 The Small Intestine: Duodenum; 1.2.4 The Small and Large Intestine: Jejunum, Ileum, Colon; 1.2.5 Hepatic-Portal Vein; 1.3 The Liver Metabolism; 1.3.1 CYP450 (CYPs); 1.4 The Kidneys; 1.4.1 Active Tubular Secretion; 1.4.2 Passive Tubular Reabsorption; 1.5 Conclusions; References; 2 In Silico ADME/Tox Predictions; 2.1 Introduction; 2.2 Key Computer Methods for ADME/Tox Predictions 327 $a2.2.1 Drug Discovery2.2.2 Applying or Not ADME/Tox Predictions, Divided Opinions; 2.2.3 In Silico ADME/Tox Methods and Modeling Approaches; 2.2.4 Physicochemistry, Pharmacokinetics, Drug-Like and Lead-Like Concepts; 2.2.5 Lipophilicity; 2.2.6 pKa; 2.2.7 Transport Proteins; 2.2.8 Plasma Protein Binding; 2.2.9 Metabolism; 2.2.10 Elimination; 2.2.11 Toxicity; 2.3 Preparation of Compound Collections and Computer Programs, Challenging ADME/Tox Predictions and Statistical Methods; 2.3.1 Preparation of Compound Collections and Computer Programs 327 $a2.3.2 Preparing a Compound Collection: Materials and Methods2.3.3 Cleaning and Designing the Compound Collection; 2.3.4 Searching for Similarity; 2.3.5 Generating 3D Structures; 2.4 ADME/Tox Predictions within Pharmaceutics Companies; 2.4.1 Actelion Pharmaceuticals Ltd.; 2.4.2 Bayer; 2.4.3 Bristol-Myers Squibb; 2.4.4 Hoffmann-La Roche Ltd.; 2.4.5 Neurogen Corporation; 2.4.6 Novartis; 2.4.7 Schering AG; 2.4.8 Vertex Pharmaceuticals; 2.5 Challenging ADME/Tox Predictions; 2.5.1 Tolcapone; 2.5.2 Factor V Inhibitors; 2.5.3 CRF-1 Receptor Antagonists; 2.6 Statistical Methods 327 $a2.6.1 Principal Component Analysis2.6.2 Partial Least Square; 2.6.3 Support Vector Machine; 2.6.4 Decision Trees; 2.6.5 Neural Networks; 2.7 Conclusions; References; 3 Absorption and Physicochemical Properties of the NCE; 3.1. Introduction; 3.2. Physicochemical Properties; 3.3. Stability; 3.4. Dissolution and Solubility; 3.4.1. Dissolution Rate, Particle Size, and Solubility; 3.4.2. pH and Salts; 3.4.3. In Vivo Solubilization; 3.5. Solid State; References; 4 ADME; 4.1 Introduction; 4.2 Absorption; 4.2.1 Route of Administration; 4.2.2 Factors Determining Oral Bioavailability; 4.3 Distribution 327 $a4.3.1 Drug Distribution4.3.2 Volume of Distribution; 4.3.3 Free Drug Concentration; 4.3.4 CNS Penetration; 4.4 Elimination; 4.4.1 Elimination Versus Clearance; 4.4.2 Metabolism Versus Excretion; 4.4.3 Drug-Free Fraction and Clearance; 4.4.4 Lipophilicity and Clearance; 4.4.5 Transporters and Clearance; 4.4.6 Metabolism; 4.4.7 Excretion; 4.5 Drug Interactions; 4.5.1 Absorption-Driven DDI; 4.5.2 Distribution-Driven DDI; 4.5.3 Excretion-Driven DDI; 4.5.4 Metabolism-Driven DDI; 4.5.5 Tools for Studying Drug Metabolism; 4.5.6 Applications of Drug Metabolism Tools 327 $a4.5.7 Tools for Studying Drug Excretion 330 $aThis book guides medicinal chemists in how to implement early ADMET testing in their workflow in order to improve both the speed and efficiency of their efforts. Although many pharmaceutical companies have dedicated groups directly interfacing with drug discovery, the scientific principles and strategies are practiced in a variety of different ways. This book answers the need to regularize the drug discovery interface; it defines and reviews the field of ADME for medicinal chemists. In addition, the scientific principles and the tools utilized by ADME scientists in a discovery setting, as appl 606 $aDrug Design 606 $aDrug Toxicity 606 $aDrugs - Testing 606 $aDrugs --Testing --Juvenile literature 606 $aPharmaceutical Preparations - chemistry 606 $aPharmacokinetics 606 $aDrugs$xTesting$vJuvenile literature 606 $aMetabolic Phenomena 606 $aDrug Discovery 606 $aPharmacological Phenomena 606 $aNatural Science Disciplines 606 $aKinetics 606 $aChemicals and Drugs 606 $aPoisoning 606 $aBiochemical Phenomena 606 $aChemistry, Pharmaceutical 606 $aSubstance-Related Disorders 606 $aDisciplines and Occupations 606 $aInvestigative Techniques 606 $aPhysiological Phenomena 606 $aPhenomena and Processes 606 $aChemical Phenomena 606 $aDiseases 606 $aPharmacology 606 $aAnalytical, Diagnostic and Therapeutic Techniques and Equipment 606 $aBiological Science Disciplines 606 $aDrug Design 606 $aPharmacokinetics 606 $aChemistry 606 $aDrug Toxicity 606 $aPharmaceutical Preparations 606 $aHealth & Biological Sciences$2HILCC 606 $aPharmacy, Therapeutics, & Pharmacology$2HILCC 615 4$aDrug Design. 615 4$aDrug Toxicity. 615 4$aDrugs - Testing. 615 4$aDrugs --Testing --Juvenile literature. 615 4$aPharmaceutical Preparations - chemistry. 615 4$aPharmacokinetics. 615 0$aDrugs$xTesting 615 2$aMetabolic Phenomena 615 2$aDrug Discovery 615 2$aPharmacological Phenomena 615 2$aNatural Science Disciplines 615 2$aKinetics 615 2$aChemicals and Drugs 615 2$aPoisoning 615 2$aBiochemical Phenomena 615 2$aChemistry, Pharmaceutical 615 2$aSubstance-Related Disorders 615 2$aDisciplines and Occupations 615 2$aInvestigative Techniques 615 2$aPhysiological Phenomena 615 2$aPhenomena and Processes 615 2$aChemical Phenomena 615 2$aDiseases 615 2$aPharmacology 615 2$aAnalytical, Diagnostic and Therapeutic Techniques and Equipment 615 2$aBiological Science Disciplines 615 2$aDrug Design 615 2$aPharmacokinetics 615 2$aChemistry 615 2$aDrug Toxicity 615 2$aPharmaceutical Preparations 615 7$aHealth & Biological Sciences 615 7$aPharmacy, Therapeutics, & Pharmacology 676 $a615.19 676 $a615/.19 700 $aTsaioun$b Katya$0875551 701 $aKates$b Steven A$0240767 801 0$bAU-PeEL 801 1$bAU-PeEL 801 2$bAU-PeEL 906 $aBOOK 912 $a9910133588303321 996 $aADMET for Medicinal Chemists$91954875 997 $aUNINA