Small structural modifications can significantly affect the pharmacokinetic properties of drug candidates. This book, written by a medicinal chemist for medicinal chemists, is a comprehensive guide to the pharmacokinetic impact of functional groups, the pharmacokinetic optimization of drug leads, and an exhaustive collection of pharmacokinetic data, arranged according to the structure of the drug, not its target or indication. The historical origins of most drug classes and general aspects of modern drug discovery and development are also discussed. The index contains all the drug names and synonyms to facilitate the location of any drug or functional group in the book.
This compact working guide provides a wealth of information on the ways small structural modifications affect the pharmacokinetic properties of organic compounds, and offers plentiful, fact-based inspiration for the development of new drugs. This book is mainly aimed at medicinal chemists, but may also be of interest to graduate students in chemical or pharmaceutical sciences, preparing themselves for a job in the pharmaceutical industry, and to healthcare professionals in need of pharmacokinetic data.
Table of contents
PART I: Introduction
THE DRUG DISCOVERY PROCESS
The Future of Small-Molecule Drugs
What Limits/Reduces Oral Bioavailability?
What Limits/Reduces Plasma Half-Life?
How to Improve bbb-Penetration?
How to Avoid CYP Inhibition/Induction?
How to Avoid Interaction with the HumanEther-'a-go-go-Related Gene (hERG)?
How to Prevent Toxicity?
Examples of PK-Optimization in Animals
PART II: The Pharmacokinetic Properties of Compound Classes
ALKENES AND ALKYNES
NITRATES AND NITRITES
Rates of N-Dealkylation
QUATERNARY AMMONIUM SALTS
GUANIDINES, ACYLGUANIDINES, AND BIGUANIDES
HYDRAZINES, ACYLHYDRAZINES, AND HYDRAZONES
Bioisosteres of Carboxylic Acids
Amino Carboxylic Acids, N-Acyl Amino Acids, and Related Compounds
LACTAMS AND IMIDES
Five-Membered Lactams as Nootropics
Carbamates as Hypnotics
SULFATES AND SULFAMIC ACIDS
PHOSPHORIC ACID DERIVATIVES
N-(AMINOALKYL)BENZAMIDES, -BENZOATES, AND RELATED COMPOUNDS
Biological Activity of Phenethylamines
Tetrahydroisochinolines and Related Compounds
AMINOALKYLINDOLES AND INDOLE ALKALOIDS
DIBENZAZEPINES AND RELATED TRICYCLIC COMPOUNDS
3-ARYLOXY-2-HYDROXYPROPYLAMINES (B-ADRENERGIC ANTAGONISTS; 'B-BLOCKERS')
N-(CARBOXYALKYL)-a-AMINO ACID AMIDES (PRILS)
ANILIDES AND AMIDES OF GLYCINE
PEPTIDES, PEPTIDOMIMETICS, AND RELATED OLIGOAMIDES
Thrombin Inhibitors and Related Compounds
OLIGOARYLAMINES, OLIGOARYLAMIDES, OLIGOARYLCARBAMATES, AND OLIGOARYLUREAS
PYRIDINES, PYRIMIDINES, AND RELATED COMPOUNDS
Proton Pump Inhibitors
ARYLACETIC, BENZOIC, AND RELATED CARBOXYLIC ACIDS (NSAIDS)
QUINOLONECARBOXYLIC ACIDS (GYRASE INHIBITORS)
FOLIC ACID ANALOGS (ANTIFOLATES)