Heterocyclic compounds in Lead Optimisation

Heterocyclic compounds are a diverse class of molecules that play an important role in drug discovery. Heterocycles are defined as molecules that contain one or more atoms other than carbon in their ring structure. The most common heteroatoms found in heterocycles are nitrogen, oxygen, and sulfur.

Heterocyclic compounds have a number of properties that make them attractive for drug discovery. First, heterocyclic compounds are often more potent and selective than their aliphatic counterparts. This is because heterocyclic atoms can interact with the target protein in a variety of ways, including through hydrogen bonding, pi-stacking, and electrostatic interactions. Second, heterocyclic compounds often have improved physicochemical properties, such as solubility and permeability. This makes them more likely to be absorbed and distributed throughout the body. Third, heterocyclic compounds often have reduced toxicity. This is because heterocyclic atoms can help to reduce the interaction of the drug with off-target proteins.

As a result of these properties, heterocyclic compounds are commonly used in lead optimization. Lead optimization is the process of identifying compounds that have the potential to be developed into safe and effective drugs. Heterocyclic compounds are often used in lead optimization because they can provide a number of benefits, including increased potency, selectivity, improved physicochemical properties, and reduced toxicity.

There are a variety of different heterocyclic groups that can be used in lead optimization. Some of the most common include:

• Aromatic heterocycles, such as pyridine, pyrimidine, and thiophene
• Aliphatic heterocycles, such as piperidine, morpholine, and imidazole
• Heterocyclic rings with multiple heteroatoms, such as quinoline and isoquinoline

The choice of the heterocyclic group will depend on the target protein and the desired properties of the drug. For example, aromatic heterocycles are often used for their increased potency and selectivity, while aliphatic heterocycles are often used for their improved physicochemical properties.

Heterocyclic compounds are an important tool in lead optimization. They can provide a number of benefits that can help to improve the chances of developing a safe and effective drug.

Here are some examples of drugs that contain heterocyclic groups:

Nitrogen-containing heterocyclic compounds are not only present as the backbone in several biologically active natural products used as traditional medications or approved prescribed drugs, but some of their synthetic derivatives in different sizes, nowadays are prescribed and market purchasable drugs. The most famous are diazepam, isoniazid, chlorpromazine, metronidazole, barbituric acid, captopril, chloroquinine, azidothymidine and anti-pyrine. Furthermore, most of the vitamins, nucleic acid, enzymes, co-enzymes, hormones, and alkaloids contain N-based heterocycles as scaffolds

These are just a few examples of the many drugs that contain heterocyclic groups. Heterocyclic compounds are an important tool in drug discovery and play a vital role in the development of safe and effective medications.

References

• Heravi MM, Zadsirjan V. Prescribed drugs containing nitrogen heterocycles: an overview. RSC Adv. 2020 Dec 15;10(72):44247-44311. doi: 10.1039/d0ra09198g
• Jampilek J. Heterocycles in Medicinal Chemistry. Molecules. 2019 Oct 25;24(21):3839. doi: 10.3390/molecules24213839. 
• Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry" Molecules | Special Issue : Heterocycles in Medicinal Chemistry (mdpi.com)

These articles provide a comprehensive overview of the importance of heterocyclic compounds in drug discovery. They discuss the different types of heterocyclic compounds, their biological activities, and their potential as drug candidates. The articles also highlight some of the challenges associated with the development of heterocyclic drugs.