Foundations of Medicinal Chemistry

Vocabulary flashcards covering key terms and concepts from medicinal chemistry foundations, drug discovery, receptor interaction, pharmacokinetics, biopharmaceutics, and notable historical figures and drugs.

Medicinal chemistry

Incorporation of chemistry and biology in research for discovery and design of new therapeutic chemicals and their development into medicines; aims to create/develop new medicines and optimize effectiveness.

SAR (Structure-Activity Relationship)

Study of how changes in chemical structure affect the pharmacologic activity and pharmacokinetic profile of a compound.

ADME

Absorption, Distribution, Metabolism, and Excretion; the body's handling of a drug.

Ligand

A chemical agent that binds to a receptor.

Affinity

The ability of a ligand to bind to a receptor.

Intrinsic activity

The ability of a bound ligand to elicit a pharmacologic response.

Receptor

The biological site to which a drug or ligand binds to produce an effect.

Pharmacophore

The key features of a ligand that interact with a receptor to produce a biological response.

Analogs

Synthetic compounds developed from a lead compound to improve activity or properties.

Lead compound

An initial compound with desired activity used to develop a drug; leads to High Throughput Screening (HTS) and further optimization.

High Throughput Screening (HTS)

Rapid testing of large compound libraries to identify potential lead candidates.

Preclinical trials

In vitro, in vivo, and in silico studies conducted before human testing.

Clinical trials

Phased testing (I–IV) in humans to assess safety, efficacy, and pharmacovigilance.

Nucleus (drug structure context)

Section of a drug’s structure responsible for its pharmacological activity.

Natural origin

Drugs derived from plants or animals.

Synthetic origin

Drugs produced entirely by chemical synthesis.

Semi-synthetic origin

Drugs derived from a natural product that is chemically modified.

Chemotherapeutic agent

A drug used to treat malignant cells or infectious microorganisms.

Pharmacodynamic agent

A drug that acts on various functions of the body to produce a therapeutic effect.

Infectious disease

Diseases caused by microorganisms that can be contagious or externally transmitted.

Non-infectious disease

Disorders caused by genetic, environmental, or other non-microbial factors.

Non-disease (alleviation of disease)

Interventions aimed at pain relief, prevention, or anesthesia rather than curing a disease.

Paracelsus

Father of Toxicology; asserted that dose determines poison vs. drug.

The dose makes the poison

Benign quote by Paracelsus highlighting dose-dependency of toxicity.

Dioscorides

Author of De Materia Medica, an influential ancient medical text.

Ebers Papyrus

Ancient Egyptian medical document documenting remedies and substances.

Cocaine (isolation)

Isolated from the coca plant; notable in historical pharmacology development.

Penicillin

Antibiotic discovered by Alexander Fleming; isolation and purification advanced by Florey and Chain.

Alexander Fleming

Scientist who discovered penicillin accidentally in 1928.

Howard Florey and Ernst Chain

Researchers who purified and developed penicillin for clinical use.

Chlorpromazine (Thorazine)

First antipsychotic; developed from antihistamines with Charpentier and Laborit involved in early trials.

Promethazine

Antihistamine from which chlorpromazine was developed; used as a lead in early psychopharmacology studies.

Diazepam (Valium)

Benzodiazepine; 5–10 times more potent than chlordiazepoxide with a shorter half-life; developed via structural modification.

Chlordiazepoxide (Librium)

First benzodiazepine introduced for anxiety disorders.

Meprobamate

First mass-marketed psychiatric drug (tranquilizer) developed from mephenesin.

Insulin

Hormone used to treat diabetes; isolated from pancreas by Banting and Best; purified from cattle by Collip and MacLeod.

Banting and Best

Researchers who isolated insulin for diabetes management.

Collip and MacLeod

Researchers who purified insulin for clinical use.

Cisplatin

First-generation platinum chemotherapy; MOA includes binding to DNA to disrupt replication; considered a gold standard in platinum therapy.

Prontosil

First broad-spectrum antibacterial; dye activated by metabolism to sulfanilamide-like compounds; developed by Gerard Domagk.

Gerard Domagk

Pioneer of the red dye Prontosil and broad-spectrum antibacterial research.

Cocaine (pharmacology history)

Early isolations contributed to understanding cocaine’s properties in medicine.

Promethazine

Antihistamine that served as a precursor in the development of chlorpromazine.

Promethazine–chlorpromazine connection

Early pharmacology link showing how modifications yielded antipsychotics.

Insulin (historical context)

Classic example of translating a natural product into a therapeutic protein.

6-Mercaptopurine

First effective drug for leukemia (antimetabolite chemotherapy).

George Hitchings and Gertrude Elion

Pioneers of rational drug design in the development of targeted therapies.

Cisplatin MOA

Binds DNA at purine bases, causing cross-links and inhibition of cell replication.

Prodrugs

Bioreversible derivatives designed to release the active drug in vivo to improve ADME or oral bioavailability.

Hard prodrug

A prodrug that is biochemically active with increased water or lipid solubility.

Self prodrug

Biotransforms rapidly into non-toxic moieties in the body.

Carrier-linked prodrug

Active drug linked to a carrier group that is removed enzymatically.

Mutual prodrug

Two drugs chemically linked to exploit synergistic effects.

Bioprecursors

Inert molecules activated in vivo to yield the active drug.

Chloramphenicol palmitate

A prodrug example where chloramphenicol is esterified to alter pharmacokinetics.

Olsalazine – Mesalamine

Prodrug pair where olsalazine is converted to the active mesalamine.

Enalapril – Enalaprilat

Prodrug (enalapril) converted to active enalaprilat in the body.

Levodopa – Dopamine

Prodrug approach where levodopa is converted to active dopamine.

Heroin – Morphine

Prodrug relationship where heroin is converted to morphine in vivo.

Biopharmaceutical Classification System (BCS) Class 1

High solubility and high permeability drugs (examples: metoprolol, acetaminophen, verapamil, etc.).

BCS Class 2

Low solubility and high permeability drugs (examples: griseofulvin, diazepam, ketoconazole, etc.).

BCS Class 3

High solubility and low permeability drugs (examples: acyclovir, chloramphenicol).

BCS Class 4

Low solubility and low permeability drugs (examples: furosemide, paclitaxel).

LogP

Partition coefficient representing drug lipophilicity; ratio of concentration in octanol to water; higher logP = more lipophilic.

Salt formation

Neutralization reaction between acid and base forming water and a salt; salt form often increases solubility; most salts are strong electrolytes.

pKa (acid–base ionization constant)

Negative log of Ka; indicates relative acidity/basicity; lower pKa means higher acidity.

Ionization/polarity

Acidic/basic functional groups are polar and ionized in solution; neutral groups are nonpolar and non-ionized.

Dissolution

Process by which a substance forms a solution in a solvent; rate is influenced by surface area, particle size, and the boundary layer.

Noyes–Whitney equation

Describes drug dissolution rate: rate ∝ D×A×(Cs−C)/h; factors include diffusion coefficient, surface area, concentration gradient, and boundary layer thickness.

Solubility

Maximum amount of solute that can dissolve in a solvent at equilibrium.

Disintegration

Rate-limiting step for solid dosage forms before dissolution.

Stability

Maintaining physicochemical, therapeutic, and microbial properties during storage and use.

Gastrointestinal physiology terms

Stomach and small intestine regions; villi and microvilli increase surface area for absorption; gastric emptying time (GET) affects absorption.

Absorption (physiologic vs pharmacologic)

Physiologic: rate/extent of drug disappearance at administration site; Pharmacologic: rate/extent of drug entering systemic circulation.

Gastric emptying time (GET) and GER

GET influences absorption; slower GET can reduce or delay absorption; GER relates to reflux impacting absorption.

GIT anatomy terms

Stomach, duodenum, jejunum, ileum with villi/microvilli increasing surface area for nutrient/drug absorption.