Chapter 1: Medicinal Organic Chemistry

What is the primary discipline devoted to the discovery and development of new agents for treating diseases?

Medicinal chemistry.

Medicinal chemistry occupies a strategic position at the interface of which two scientific fields?

Chemistry and biology.

Modern drug development has grown beyond traditional synthesis to include what exciting field?

Biotechnology, which uses the cell’s biochemistry to synthesize new compounds.

Name a technique used in biotechnology to broaden the possibilities for new disease-treating entities.

Techniques include:

• recombinant DNA

• site-directed mutagenesis

• fusion of cell lines.

Modified human insulins, which provide more convenient dosing schedules, are a product of what field of drug development?

Biotechnology.

The process of establishing a new pharmaceutical involves the talents of people from what disciplines?

• Chemistry

• biochemistry

• molecular biology

• physiology

• pharmacology

• pharmaceutics

• medicine.

The principles of medicinal chemistry are based on which three fundamental scientific fields?

• Organic chemistry

• physical chemistry

• biochemistry.

How were the earliest drug discoveries made?

Through random sampling of higher plants.

Name two crude plant drugs that have been important for centuries and were discovered through early sampling methods.

Opium and belladonna (or ephedrine).

The accidental discovery of penicillin led to the screening of what sources for new antibiotics?

Microorganisms, such as bacterial and fungal sources.

Many early antibiotics provided the _ that medicinal chemists modified to obtain drugs with better therapeutic profiles.

prototypical structure

What is the key difference in federal legislation requirements for 'nutraceuticals' compared to prescription drugs?

The efficacy requirement for 'nutraceuticals' is reduced.

What is a significant risk for patients using nontraditional medicines concurrently with physician-prescribed therapy?

The active agents in alternate medicines can potentiate or interfere with the prescribed therapy.

Term: Random Screening

A process where large numbers of new chemicals are entered into pharmacological screens to determine if they have useful biological activity.

The process of random screening, though sometimes inefficient, has resulted in the identification of new _ whose structures have been optimized to produce clinical agents.

lead compounds

The discovery that amantadine could protect against and treat early influenza A resulted from what type of process?

A general screen for antiviral agents.

How was the therapeutic use of amantadine for parkinsonian disorders discovered?

Through careful observation of its effects in long-term care facilities where it was being used for influenza.

What modern systems have greatly increased the efficiency of random screening?

Automated high-throughput screening systems.

High-throughput screening systems often utilize cell culture systems with linked __ and __ derived from gene cloning.

• enzyme assays

• receptor molecules

What chemical procedure provides enormous libraries of peptides and nucleic acids for modern screening?

Combinatorial chemistry.

What is the drug discovery approach that is considered the opposite of high-volume random screening?

Rational design.

In rational design, what methods are used to explain and optimize biological activity based on a drug's properties?

Statistical methods based on the correlation of physicochemical properties with biological potency.

Which two advanced analytical techniques make it possible to obtain detailed representations of enzymes and other drug receptors?

• X-ray crystallography

• nuclear magnetic resonance (NMR).

The techniques of _ and _ have provided novel chemical structures that led to new drugs.

• molecular graphics

• computational chemistry

The development of which two classes of inhibitors came from an understanding of their respective enzyme's active site geometry?

• Human immunodeficiency virus (HIV) protease inhibitors

• Angiotensin-converting enzyme (ACE) inhibitors.

Even if a receptor's structure is unknown, rational approaches can provide new drugs based on the _ of lead compounds.

physicochemical properties

The development of cimetidine is a classic example of rational design involving a careful study of structures based on what molecule?

Histamine.

The development of cimetidine involved studying the changes in antagonism of _ receptors by varying the physical properties of histamine-based structures.

H2-histamine