Medicinal Chemistry Properties

Medicinal Chemistry Properties of Aspirin 

Quantitative Estimate of Drug-likeness (QED)

• Definition: A measure integrating eight molecular properties (MW, logP, HBA, HBD, PSA, rotatable bonds, aromatic rings, and structural alerts) to quantify drug-likeness 12.

• Importance: Provides a comprehensive assessment of a compound's potential as an oral drug. Higher values indicate better drug-like properties.

• Expected Range: QED > 0.67 is considered excellent, 0.49-0.67 is moderate, and <0.34 is poor. Aspirin has a QED of approximately 0.55.

Synthetic Accessibility Score (SAscore)

• Definition: Estimation of how easy or complex a molecule is to synthesize (1 = easy, 10 = difficult).

• Importance: Helps assess the practical feasibility of compound synthesis during drug development.

• Expected Range: Scores ≤ 6 indicate compounds that are relatively easy to synthesize. Aspirin has a SAscore of approximately "easy", indicating very high synthetic accessibility.

Natural Product-likeness Score (NPscore)

• Definition: Measures similarity to known natural products based on molecular fragmentation patterns.

• Importance: Natural product-like compounds often have better bioactivity and target selectivity.

• Expected Range: Typically between -5 to 5 (Figure 1), with higher scores indicating greater natural product similarity. Aspirin has a 0.122 NPscore, as it is a synthetic derivative of salicylic acid (though inspired by natural compounds).

Lipinski's Rule of Five

Importance: A classic rule of thumb for evaluating if a compound has properties that would make it a likely orally active drug. A molecule is likely to have poor absorption if it violates two or more of these rules: MW ≤ 500, LogP ≤ 5, nHBD ≤ 5,  nHBA ≤ 10

Aspirin Example: 0 Violations. Aspirin passes all criteria, indicating good drug-like properties.

Pfizer, GSK, Golden Triangle Rules

Importance: These are additional rules developed by pharmaceutical companies to refine drug-likeness criteria, often focusing on optimizing properties to avoid late-stage failures. For example, the Golden Triangle rule balances LogD and MW to predict good membrane permeability and metabolic clearance.

Expected Range: Passing these rules (output is "Yes" or "No").

Aspirin generally passes Pfizer and GSK.

PAINS (Pan Assay Interference Compounds)

Importance: PAINS are chemical structures that are known to interfere with many different biological assays, often by reacting non-specifically with proteins or producing false positive signals. Identifying and removing these compounds early is crucial.

Expected Range: 0 alerts. The output is "Yes" if an alert is found.

Aspirin : 0 alerts. Aspirin is not a PAINS compound.