A greener pharmaceutical industry 

The pathway to putting a medicine on the market begins by targeting an illness. The biological mechanisms that inhibit symptoms or treat the underlying cause of the disease are identified, and then chemicals are designed to have the desired biological activity. There are two generally types of active pharmaceutical ingredient (API), aptly called small molecules and big molecules. The small molecules are indeed small, chemical entities that are designed to be agonists or antagonists. The former bind to a receptor in the body and cause a response that is desirable as a medical treatment; the latter also bind to receptors in the body but do not cause a response, instead the antagonist regulates/prevents the action of agonists that are responsible for the illness (Burg and Clarke, 2018). Small molecule pharmaceuticals are a triumph of 20th century science, including penicillin and ibuprofen. The 21st century has seen advances in large molecule API. These large molecules are peptides, consisting of amino acids. As with small molecule APIs, these can be naturally occurring and extracted or cultivated from organisms, or artificially synthesised by scientists. The most well known peptide medicine is insulin. Artificial peptides are created step by step, one amino acid at a time (Rasmussen, 2018).

Medicinal chemistry: from R&D to process plant

The development of a new medicine will often involve making and testing thousands of chemicals. There is usually a 'lead compound' identified, a molecule that exhibits some biological activity but is far from optimum. This may be because of low efficacy (performance), or other properties that make it ineffective in the body (for example it may be unstable or rapidly excreted). Research and Development (R&D) medicinal chemists focus on laboratory-scale synthesis of a variety of analogues of the lead compound(s) for preliminary testing in cellular assays, aiming to prove or improve efficacy and safety while ensuring the drug's suitability for patient administration (Patrick, 2023). In contrast, process chemists are concerned with designing practical, safe, and cost-effective methods for synthesising compounds on a larger scale, typically working on a single target molecule identified by the medicinal chemists and determining the most efficient route to that specific target. 

A medicinal chemist evaluates various factors including physicochemical properties, such as those analysed through Quantitative Structure-Activity Relationships (QSAR), which are used to predict the biological activities of new chemical compounds based on statistical models (Verma et al., 2010). Additionally, the chemist examines pharmacodynamics, the study of how drugs bind to their target sites and produce pharmacological effects, and pharmacokinetics, which involves the absorption, distribution, metabolism, and excretion (ADME) of drugs. They also consider potential toxicological effects and freedom to operate (which can be restricted by pre-existing intellectual property). 

Note that vaccines work differently to medicines by mimicking a microorganism responsible for a specific disease, and prompting the immune system of the patient to develop a resistance. Vaccines are out of the scope of this learning hub.

Modern discovery chemistry

Medicinal chemistry operates on a small scale for the rapid generation of novel compounds. Meeting this objective relies on robust, well understood (often antiquated) chemistry that requires the use of very hazardous chemicals and wasteful procedures. To address this, various tools (see the sections on solvent guides and reagent guides) have been developed to refine and optimise the drug discovery process, streamlining experiments and minimising waste. Green chemistry practice has begun to enhance the environmental and economic profile of medicinal chemistry, ultimately contributing to more sustainable pharmaceutical industry. Due to the larger scales involved, process chemistry is governed by slightly different parameters:  

• Price of starting materials.

• Safety (risks are exaggerated when the quantities of hazardous substances are greater).

• Environmental impact (preempting regulatory control on later manufacturing processes).

• Throughput time (minimising space and time requirements).

• Active pharmaceutical ingredient (API) formulation and characterisation, including impurities, polymorphism, and particle size.