Summary

Heterocyclic compounds with aromatic characteristics are called aromatic heterocyclic compounds, which can be classified into monoaromatic heterocycles and fused heterocycles. The common monoaromatic heterocycles are five-membered Furan, Pyrrole, Thiophene, Pyrazole, Imidazole, Oxazole, etc., and six-membered Pyridine, Pyranone, Pyridazine, Pyrimidine, Triazine, etc. (Figure 1).

Aromatic heterocyclic molecules, as one of the cyclic molecules with special properties in organic chemistry, have abundant modification sites, which can be modified or rearranged through alkylation, hydro bromination, and other methods to engender new physical and chemical properties. Aromatic heterocycles can be used to change the original molecular structure and function, which is helpful for novel Drug research and design.

Aromatic heterocycles have broad application prospects in many fields such as chemistry, pharmacy, biology, and material science. 

*Thiazole

Thiazole is an important aromatic five-membered heterocycle, and its structure that contains both nitrogen and sulfur heteroatoms determines its abundant electrons and physicochemical properties, such as easy hydrogen bonding, coordination with nonmetallic ions, π-π stacking, electrostatic and hydrophobic interactions, and other non-covalent bond interactions.

In medicinal research, thiazoles and their derivatives have a variety of biological and pharmacological activities, such as antibacterial, anti-malaria, anti-cancer, anti-schizophrenia, anti-hypertension, anti-inflammatory, and anti-HIV. Thiazole compounds as drugs show significant potential as many thiazole drugs have been used in the clinical treatment of a variety of diseases to protect human health.

For instance, the thrombopoietin receptor agonist (TPO-RAs) Avatrombopag Maleate (Figure 2), developed by Astellas Pharma, Inc. and approved by the US FDA in 2018, is currently the conventional drug for thrombocytopenia in European and American countries, which plays the most important regulatory role in megakaryocyte proliferation, differentiation, maturation, and mediating platelet generation.

Another example is Takeda Pharmaceutical’s broad-spectrum cephalosporin Ceftaroline Fosamil (Figure 2), which has an affinity for penicillin-binding protein 2A (PBP2A) and is used to treat infections caused by certain sensitive bacteria.

*Imidazole

Imidazole is a five-membered heterocyclic compound containing two nitrogen atoms. It is not only a component of histidine in living organisms, but also of RNA and DNA purines. Imidazole molecules are characterized by high electron transfer and easy functionalization. Many compounds containing imidazole rings play a crucial role in medicine due to their excellent biological activity.

*Pyrimidine

Pyrimidine cyclic compounds have a variety of physiological activities and are the dominant structures in drug design. There are numerous active compounds with pyrimidine ring structure units that are contained in many commercially available and clinical drug molecules. These compounds have a wide range of pharmacological activities and are extensively used in the treatment of tumors, inflammation, cardiovascular, asthma, neurodegenerative, and other diseases in clinical practice. Its pharmacological effects involve a variety of targets.

*Pyridine

Pyridine is a six-membered heterocyclic compound containing one nitrogen heteroatom. Its molecular structure has significant biological activity. The pyridine-based ring system is one of the most common heterocycles in drug design and is widely used in drug synthesis.

What does BOC Sciences offer: synthesis of drug molecules containing monoaromatic heterocycles

A variety of Monoaromatic Heterocycle Blocks offer more inspiration and wider applications for drug design. BOC Sciences supplies monoaromatic heterocycle blocks in large packages, with stable production and affordable prices.

*Synthetic Cefdinir

Cefdinil, an antibiotic of cephalosporin, is used for anti-infection treatment. It kills bacteria by inhibiting bacterial cell walls (Figure 3). Developed by Astellas Pharma, Inc., it was first marketed in Japan in 1991 and approved by the U.S. FDA in 1997.

*Synthetic Vericiguat

Acting as a stimulator of soluble guanylate cyclase (sGC) (Figure 4), Vericiguat catalyzes the synthesis of intracellular cyclic guanosine monophosphate (cGMP) and increasing intracellular cGMP levels, thereby relaxing smooth muscle and vasodilating for heart failure. The drug, developed by Bayer AG and approved by the FDA in 2021, is the first to be marketed as a treatment for patients with worsening chronic heart failure.

*Other products

Other products, such as 3-Amino-2-methoxypyridine-5-boronic acid pinacol ester (893440-50-1), can be used to synthesize the first highly selective PI3Kδ inhibitor Linperlisib in China (Figure 5a) while 1-Isopropyl-1H-pyrazole-5-boronic acid pinacol ester (1282518-60-8) is employed to synthesize the sickle cell disease (SCD) drug Voxelotor (Figure 5b).

Figure 5. Synthesis of Linperlisib and Voxelotor