Medicinal chemistry
Medicinal or pharmaceutical chemistry is a scientific discipline at the intersection of
Medicinal chemistry is a highly interdisciplinary science combining organic chemistry with biochemistry, computational chemistry, pharmacology, molecular biology, statistics, and physical chemistry.
Compounds used as medicines are most often
In particular, medicinal chemistry in its most common practice—focusing on small organic molecules—encompasses
At the biological interface, medicinal chemistry combines to form a set of highly interdisciplinary sciences, setting its organic,
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
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 (
Process chemistry and development
The final synthetic chemistry stages involve the production of a lead compound in suitable quantity and quality to allow large scale animal testing, and then human
Synthetic analysis
The synthetic methodology employed in medicinal chemistry is subject to constraints that do not apply to traditional organic synthesis. Owing to the prospect of scaling the preparation, safety is of paramount importance. The potential toxicity of reagents affects methodology.[5][10]
Structural analysis
The structures of pharmaceuticals are assessed in many ways, in part as a means to predict efficacy, stability, and accessibility. Lipinski's rule of five focus on the number of hydrogen bond donors and acceptors, number of rotatable bonds, surface area, and lipophilicity. Other parameters by which medicinal chemists assess or classify their compounds are: synthetic complexity, chirality, flatness, and aromatic ring count.
Structural analysis of lead compounds is often performed through computational methods prior to actual synthesis of the ligand(s). This is done for a number of reasons, including but not limited to: time and financial considerations (expenditure, etc.). Once the ligand of interest has been synthesized in the laboratory, analysis is then performed by traditional methods (TLC, NMR, GC/MS, and others).[5]
Training
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Medicinal chemistry is by nature an interdisciplinary science, and practitioners have a strong background in organic chemistry, which must eventually be coupled with a broad understanding of biological concepts related to cellular drug targets. Scientists in medicinal chemistry work are principally industrial scientists (but see following), working as part of an interdisciplinary team that uses their chemistry abilities, especially, their synthetic abilities, to use chemical principles to design effective therapeutic agents. The length of training is intense, with practitioners often required to attain a 4-year bachelor's degree followed by a 4–6 year Ph.D. in organic chemistry. Most training regimens also include a postdoctoral fellowship period of 2 or more years after receiving a Ph.D. in chemistry, making the total length of training range from 10 to 12 years of college education. However, employment opportunities at the Master's level also exist in the pharmaceutical industry, and at that and the Ph.D. level there are further opportunities for employment in academia and government.
Graduate level programs in medicinal chemistry can be found in traditional medicinal chemistry or pharmaceutical sciences departments, both of which are traditionally associated with schools of pharmacy, and in some chemistry departments. However, the majority of working medicinal chemists have graduate degrees (MS, but especially Ph.D.) in organic chemistry, rather than medicinal chemistry,[11] and the preponderance of positions are in research, where the net is necessarily cast widest, and most broad synthetic activity occurs.
In research of small molecule therapeutics, an emphasis on training that provides for breadth of synthetic experience and "pace" of bench operations is clearly present (e.g., for individuals with pure synthetic organic and natural products synthesis in Ph.D. and post-doctoral positions, ibid.). In the medicinal chemistry specialty areas associated with the design and synthesis of chemical libraries or the execution of process chemistry aimed at viable commercial syntheses (areas generally with fewer opportunities), training paths are often much more varied (e.g., including focused training in physical organic chemistry, library-related syntheses, etc.).
As such, most entry-level workers in medicinal chemistry, especially in the U.S., do not have formal training in medicinal chemistry but receive the necessary medicinal chemistry and pharmacologic background after employment—at entry into their work in a pharmaceutical company, where the company provides its particular understanding or model of "medichem" training through active involvement in practical synthesis on therapeutic projects. (The same is somewhat true of computational medicinal chemistry specialties, but not to the same degree as in synthetic areas.)
See also
- Bioisostere
- Biological machines
- Chemoproteomics
- Drug design
- Pharmacognosy
- Pharmacokinetics
- Pharmacology
- Pharmacophore
- Xenobiotic metabolism
References
- ISBN 978-1-78262-419-6.
- ISBN 978-1-78548-288-5.
- PMID 32548093.
- PMID 34123239.
- ^ PMID 21504168.
- PMID 21091654.
- PMID 25516838.
- PMID 18691670.
- PMID 23428572.
- S2CID 20800243.
- .
External links
Biochemistry and Molecular Biology at