Retrometabolic drug design and targeting / Nicholas Bodor, Peter Buchwald.

Format:

Book

Author/Creator:

Bodor, Nicholas.

Contributor:

Buchwald, Peter.

Language:

English

Subjects (All):

Drug targeting.

Drug development.

Physical Description:

1 online resource (440 p.)

Edition:

1st ed.

Place of Publication:

Hoboken, N.J. : John Wiley & Sons, c2012.

Summary:

Innovative approach to drug design that's more likely to result in an approvable drug product Retrometabolic drug design incorporates two distinct drug design approaches to obtain soft drugs and chemical delivery systems, respectively. Combining fundamentals with practical step-by-step examples, Retrometabolic Drug Design and Targeting gives readers the tools they need to take full advantage of retrometabolic approaches in order to develop safe and effective targeted drug therapies. The authors, both pioneers in the fields of soft drugs and retrometabolic drug design, of

Contents:

RETROMETABOLIC DRUG DESIGN AND TARGETING; Contents; Preface; 1 Introduction; 1.1 New Drugs and Medical Progress; 1.2 The Challenge of New Drug Discovery; References; 2 Mechanism of Drug Action: Basic Concepts; 2.1 Pharmacodynamic Phase: Drug-Receptor Interactions; 2.1.1 The Receptor Concept and Receptor Types; 2.1.2 Ligand-Receptor Binding; 2.1.3 Receptor Occupancy and Activation; 2.2 Pharmacokinetic Phase: ADME; 2.2.1 Drug Absorption and Distribution; 2.2.2 Drug Metabolism and Excretion; 2.2.3 Basic Pharmacokinetic Concepts; 2.3 Structural Requirements: Keeping It "Drug-Like"

2.3.1 The Drug-Like Chemical Space2.3.2 Oral Drugs: The Challenge of Bioavailability; References; 3 The Drug Discovery and Development Process; 3.1 Discovery Research; 3.1.1 Prediscovery; 3.1.2 Target Identification; 3.1.3 Target Validation; 3.1.4 Target-to-Hit and Hit-to-Lead Development; 3.1.5 Early Distribution and Safety Tests; 3.1.6 Lead Optimization; 3.2 Preclinical Development; 3.2.1 Preclinical Testing; 3.2.2 Investigational New Drug Application and Safety; 3.3 Clinical Development; 3.3.1 Phase I Clinical Trials; 3.3.2 Phase II Clinical Trials; 3.3.3 Phase III Clinical Trials

3.4 Regulatory Approval and PostMarketing Development3.4.1 New Drug Application and Regulatory Approval; 3.4.2 Manufacturing; 3.4.3 Postapproval Studies and Phase IV Trials; 3.4.4 Patent Expiration and Generic Approval; 3.5 Problems with the Current Paradigm; 3.5.1 Decreasing R&D Efficiency; 3.5.2 The Drug Discovery Process: Improvements Needed; References; 4 Retrometabolic Drug Design; 4.1 Design Principles; 4.2 Terminology; 4.2.1 Soft Drug vs. Hard Drug; 4.2.2 Soft Drug vs. Prodrug; 4.2.3 Chemical Delivery System vs. Prodrug; References; 5 Soft Drugs; 5.1 Enzymatic Hydrolysis

5.1.1 Esterases5.1.2 Interspecies Variability; 5.1.3 Interorgan and Interindividual Variability; 5.1.4 Mechanism: Catalytic Triad and Oxyanion Hole; 5.1.5 Kinetics; 5.1.6 Stereoselectivity; 5.1.7 Activation Energy and Temperature Dependence; 5.1.8 Structure-Metabolism Relationships; 5.1.9 Rate-Influencing Role of the Alcohol or Acyl Side; 5.2 Soft Drug Approaches; 5.3 Inactive Metabolite-Based Soft Drugs; 5.3.1 Soft Beta-Blockers; 5.3.2 Soft Opioid Analgetics: Remifentanil; 5.3.3 Soft Corticosteroids; 5.3.4 Soft Calcitriol (1α,25-Dihydroxyvitamin D3) Analogs; 5.3.5 Soft Estrogens

5.3.6 Soft β2-Agonists5.3.7 Soft Psychostimulants; 5.3.8 Soft Insecticides and Pesticides; 5.3.9 Soft Anticholinergics: Inactive Metabolite-Based Approach; 5.4 Soft Analogs; 5.4.1 Soft Anticholinergics: Soft Quaternary Analogs; 5.4.2 Soft Antimicrobials; 5.4.3 Soft Antiarrhythmic Agents; 5.4.4 Soft Serotonin Receptor Agonists: Naronapride; 5.4.5 Soft Anticoagulants (Vitamin K Antagonists):Tecarfarin; 5.4.6 Soft Angiotensin Converting Enzyme Inhibitors; 5.4.7 Soft Dihydrofolate Reductase Inhibitors; 5.4.8 Soft Calcineurin Inhibitors (Soft Immunosuppressants); 5.4.9 Soft Cytokine Modulators

5.4.10 Soft Phosphodiesterase 4 Inhibitors

Notes:

Description based upon print version of record.

Includes bibliographical references and index.

ISBN:

1-118-40778-4

1-283-59326-2

9786613905710

1-118-40771-7

OCLC:

794228038