Medicinal or pharmaceutical chemistry is a scientific discipline at the intersection of chemistry and pharmacy involved with designing and developing pharmaceutical drugs. Medicinal chemistry involves the identification, synthesis and development of new chemical entities suitable for therapeutic use by using structure. It also includes the study of existing drugs, their biological properties, and their quantitative structure-activity relationships (QSAR). Medicinal chemistry is a basically interdisciplinary science combining organic chemistry with biochemistry, computational chemistry, pharmacology, molecular biology, statistics, and physical chemistry. Compounds used as medicines are most often organic compounds, which are often divided into the broad classes of small organic molecules (e.g., atorvastatin, fluticasone, clopidogrel) and "biologics" (infliximab, erythropoietin, insulin glargine), the latter of which are most often medicinal preparations of proteins (natural and recombinant antibodies, hormones etc.). Medicines can also be inorganic and organometallic compounds, commonly referred to as metallodrugs (e.g., platinum, lithium and gallium-based agents such as cisplatin, lithium carbonate and gallium nitrate, respectively). The discipline of Medicinal Inorganic Chemistry investigates the role of metals in medicine metallotherapeutics, which involves the study and treatment of diseases and health conditions associated with inorganic metals in biological systems. There are several metallotherapeutics approved for the treatment of cancer (e.g., contain Pt, Ru, Gd, Ti, Ge, V, and Ga), antimicrobials (e.g., Ag, Cu, and Ru), diabetes (e.g., V and Cr), broad-spectrum antibiotic (e.g., Bi), bipolar disorder (e.g., Li). Other areas of study include: metallomics, genomics, proteomics, diagnostic agents (e.g., MRI: Gd, Mn; X-ray: Ba, I) and radiopharmaceuticals (e.g., 99mTc for diagnostics, 186Re for therapeutics). In particular, medicinal chemistry in its most common practice—focusing on small organic molecules—encompasses synthetic organic chemistry and aspects of natural products and computational chemistry in close combination with chemical biology, enzymology and structural biology, together aiming at the discovery and development of new therapeutic agents. Practically speaking, it involves chemical aspects of identification, and then systematic, thorough synthetic alteration of new chemical entities to make them suitable for therapeutic use. It includes synthetic and computational aspects of the study of existing drugs and agents in development in relation to their bioactivities (biological activities and properties), i.e., understanding their structure–activity relationships (SAR). Pharmaceutical chemistry is focused on quality aspects of medicines and aims to assure fitness for purpose of medicinal products. At the biological interface, medicinal chemistry combines to form a set of highly interdisciplinary sciences, setting its organic, physical, and computational emphases alongside biological areas such as biochemistry, molecular biology, pharmacognosy and pharmacology, toxicology and veterinary and human medicine; these, with project management, statistics, and pharmaceutical business practices, systematically oversee altering identified chemical agents such that after pharmaceutical formulation, they are safe and efficacious, and therefore suitable for use in treatment of disease.
In the path of drug discovery
Discovery Discovery is the identification of novel active chemical compounds, often called "hits", which are typically found by assay of compounds for a desired biological activity. Initial hits can come from repurposing existing agents toward a new pathologic processes, and from observations of biologic effects of new or existing natural products from bacteria, fungi, plants, etc. In addition, hits also routinely originate from structural observations of small molecule "fragments" bound to therapeutic targets (enzymes, receptors, etc.), where the fragments serve as starting points to develop more chemically complex forms by synthesis. Finally, hits also regularly originate from en-masse testing of chemical compounds against biological targets using biochemical or chemoproteomics assays, where the compounds may be from novel synthetic chemical libraries known to have particular properties (kinase inhibitory activity, diversity or drug-likeness, etc.), or from historic chemical compound collections or libraries created through combinatorial chemistry. While a number of approaches toward the identification and development of hits exist, the most successful techniques are based on chemical and biological intuition developed in team environments through years of rigorous practice aimed solely at discovering new therapeutic agents.
Hit to lead and lead optimization
Further chemistry and analysis is necessary, first to identify the "triage" compounds that do not provide series displaying suitable SAR and chemical characteristics associated with long-term potential for development, then to improve the remaining hit series concerning the desired primary activity, as well as secondary activities and physiochemical properties such that the agent will be useful when administered in real patients. In this regard, chemical modifications can improve the recognition and binding geometries (pharmacophores) of the candidate compounds, and so their affinities for their targets, as well as improving the physicochemical properties of the molecule that underlie necessary pharmacokinetic/pharmacodynamic (PK/PD), and toxicologic profiles (stability toward metabolic degradation, lack of geno-, hepatic, and cardiac toxicities, etc.) such that the chemical compound or biologic is suitable for introduction into animal and human studies.
… excerpt ends here. Continue reading the full article.
