Medicinal Chemistry Cheat Sheet

The core ideas of Medicinal Chemistry distilled into a single, scannable reference — perfect for review or quick lookup.

PiqCue — piqcue.com/medicinal-chemistry/cheatsheet

Quick Reference

Structure-Activity Relationship (SAR)

The systematic study of how modifications to a molecule's chemical structure affect its biological activity, potency, and selectivity. SAR analysis guides iterative optimization of lead compounds toward drug candidates.

Pharmacophore

The ensemble of steric and electronic features in a molecule that are necessary for optimal interaction with a specific biological target and for triggering or blocking its biological response.

Lipinski's Rule of Five

A set of guidelines predicting that poor oral absorption or permeation is more likely when a compound has a molecular weight over 500 Da, logP over 5, more than 5 hydrogen bond donors, or more than 10 hydrogen bond acceptors.

ADMET Properties

The pharmacokinetic and safety profile of a drug candidate encompassing Absorption, Distribution, Metabolism, Excretion, and Toxicity — collectively determining whether a compound can reach its target at therapeutic concentrations safely.

Lead Optimization

The iterative process of chemically modifying a lead compound to improve its drug-like properties — including potency, selectivity, metabolic stability, solubility, and safety — before it enters preclinical development.

Bioisostere

A chemical substituent or group that possesses similar physical, chemical, or biological properties to another group, used to replace moieties in a molecule to improve its pharmacological profile without losing activity.

High-Throughput Screening (HTS)

An automated method that rapidly tests large libraries of chemical compounds (often hundreds of thousands to millions) against a biological target to identify initial hits that show activity.

Prodrug Strategy

The design of pharmacologically inactive compounds that are converted into active drugs in vivo through enzymatic or chemical transformation, used to overcome limitations in absorption, distribution, or tolerability.

Fragment-Based Drug Design (FBDD)

A strategy that identifies small, low-molecular-weight chemical fragments that bind weakly to a target, then grows, links, or merges these fragments into larger, more potent lead compounds with optimized binding.

Drug-Target Interaction

The specific molecular recognition event between a drug molecule and its biological target (typically a protein), mediated by non-covalent forces such as hydrogen bonds, hydrophobic interactions, van der Waals forces, and electrostatic interactions.

Key Terms at a Glance

ADMET:Absorption, Distribution, Metabolism, Excretion, and Toxicity — the key pharmacokinetic and safety parameters evaluated during drug development.

Bioavailability:The fraction of an administered drug dose that reaches systemic circulation in its active form.

Bioisostere:A chemical substituent or group with similar physical, chemical, or biological properties that can replace another in a drug molecule.

Chirality:A property of molecules that are non-superimposable on their mirror images, resulting in enantiomers with potentially different biological activities.

Combinatorial Chemistry:The rapid synthesis of large numbers of structurally related compounds for screening against biological targets.

Cytochrome P450:A superfamily of heme-containing enzymes in the liver responsible for the oxidative metabolism of the majority of therapeutic drugs.

Drug-Drug Interaction:A change in a drug's effect caused by the co-administration of another drug, often through competition for metabolic enzymes or transporters.

EC50:The concentration of a drug that produces 50% of the maximum possible effect, used as a measure of potency for agonists.

Enantiomer:One of a pair of molecules that are mirror images of each other but cannot be superimposed, often having different biological activities.

First-Pass Metabolism:The initial metabolism of an orally administered drug by the liver and intestinal wall before it reaches systemic circulation.

Half-Life:The time required for the plasma concentration of a drug to decrease by 50%, determining dosing frequency.

High-Throughput Screening:An automated method for rapidly testing large numbers of compounds for activity against a biological target.

IC50:The concentration of an inhibitor that reduces the activity of its target by 50%, a standard measure of inhibitory potency.

Lead Compound:A chemical compound with demonstrated activity against a target that serves as the starting point for optimization into a drug candidate.

Lipophilicity:A compound's affinity for lipid environments relative to aqueous environments, quantified by logP or logD.

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