Introduction to Medicinal Chemistry and Physicochemical Properties

Vocabulary flashcards covering fundamental definitions, equations, and physicochemical principles from PHAR 441.

Medicinal Chemistry

A scientific discipline at the interface of chemistry, pharmacology, and biology which involves the design, synthesis, and development of pharmaceutical drugs.

Acid

A chemical entity defined as a proton donor.

Base

A chemical entity defined as a proton acceptor.

Henderson–Hasselbalch Equation

An equation relating $pH$, $pKa$, and the ratio of conjugate base to acid: $pH = pKa + \log\left(\frac{[\text{conj. base}]}{[\text{acid}]}\right)$.

pH

A measure of the acidity or basicity of an aqueous solution, where a lower $pH$ indicates a more acidic solution.

$Ka$ (Acid Dissociation Constant)

A quantitative measure of the strength of an acid in solution, calculated as $pKa = -\log(Ka)$, where a lower $pKa$ denotes a stronger acid.

Amphoteric Substance

A substance, such as $H_2O$, that can react both as an acid and as a base.

Percent Ionization Formula for Acids

The mathematical expression used to determine the percentage of an acid in its ionized form: \% \text{ ionization} = \frac{100}{1 + 10^{(pKa - pH)}}$$.

Percent Ionization Formula for Bases

The mathematical expression used to determine the percentage of a base in its ionized form: \% \text{ ionization} = \frac{100}{1 + 10^{(pH - pKa)}}$$.

Un-ionized Drugs

Drug forms that lack a positive or negative charge, making them more lipophilic with a high $\log P$.

Partition Coefficient ($\log P$)

The ratio of concentrations of an un-ionized compound between two immiscible phases, octanol and water.

Distribution Coefficient ($\log D$)

The ratio of the sum of the concentrations of all forms of a compound (ionized plus un-ionized) in each of two phases at a specified $pH$.

Lipinski's Rule of Five

A set of guidelines evaluating small molecule drug-likeness for oral activity: molecular weight under $500\,\text{Da}$, $\log P < 5$, fewer than $5$ H-bond donors (O–H and N–H), and fewer than $10$ H-bond acceptors (N and O), with at most one violation allowed.

Structure-Activity Relationship (SAR)

The relationship between chemical structure and pharmacological activity for a series of compounds.

Physiological pH of Stomach

$3.5$, ranging from $2$ to $6$ depending on the presence of food.

Physiological pH of Intestine

$8.0$.

Physiological pH of Plasma

$7.4$.