Thiazole: A versatile pharmacophore moiety
Introduction
Figure 0
Thiazole has been introduced since early century.1 Thiazole moiety is versatile moiety in way that it serves in several marketed medicines. Thiazole moiety has been used in synthesis and as active constituent in addition to the several functional groups and moieties in many medicines. Some examples where thiazole has been employed in as functional groups include antibacterial,1 antifungal, 2 antitubercular, 3 anticancer,4 antiparasitic, 5 diabetes, 6 anti-gout.7 anti-inflammatory8 and antioxidant9 properties.
Figure 0
Thiazole: Thiazole is a five-membered, unsaturated, planar, π-excessive heteroaromatic containing one sulfur atom and one pyridine-type nitrogen atom at position 3 of the cyclic ring system.
IUPAC: 1,3 Thiazole
The properties of thiazole moiety has been shown in the following table.
Table 1
Prefers iupac name properties
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Chemical formula
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C3H3NS
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Molar mass
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85.124g/mol
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Melting point
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117C
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Acidity (pKa)
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2.5 (for the conjugate acid)
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Review
Owing to the versatility of thiazole moiety the marketed medicines containing thiazole ring has been exemplified in this review paper. For the purpose of their utility they have classified into the categories of their clinical uses.
Drugs containing thiazole ring /derivatives
Cefotaxime10
Figure 0
It is a third-generation broad-spectrum antibiotic to treat patients with Gram-positive and negative bacteria. As a β-lactam antibiotic, Cefotaxime effectively blocks bacterial cell wall synthesis by interacting with penicillin-binding proteins (PBPs). The use of Cefotaxime results in the inhibition of peptidoglycan synthesis in the final transpeptidation step.
Marketed preparation
Figure 0
Anti-fungal
Isavuconazole 11
Figure 0
Isavuconazole, a triazole prodrug, was approved by the FDA in 2015 and sold under the brand name Cresemba (Isavuconazonium) to treat invasive mucormycosis and aspergillosis. Isavuconazole disrupts the structure and function of fungal membrane by inhibiting the biosynthesis of ergosterol. As a moderate inhibitor of CYP3A4, it inhibits lanosterol 14-alpha-demethylase that stimulates the generation of ergosterol from lanosterol. Cresemba engages the heme moiety at the base of the binding.
Marketed preparation
Figure 0
In market Isavuconazole injection & capsule are available.
Anti-parasitic
Nitazoxanide12
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It was approved by FDA and helps to treat diarrhoea and Giardial infections.Nitazoxanide displays broad-spectrum activity against various protozoa, helminths, and intestinal bacteria that induce animal and human infections. Nitazoxanide exhibits inhibitory activity against Giardia lamblia trophozoite proliferation.
Marketed preparation
Figure 1
Nitazoxanide is available in Tablet & syrup formulation.
Anti-inflammatory
Meloxicam13
Figure 0
Meloxicam is NSAID with anti-inflammatory, antiplatelet aggregatory and antipyretic activity. Fentiazac can be used to research inflammatory diseases such as rheumatoid arthritis, osteoarthritis and tendinitis.
Marketed preparations
Figure 0
Anti-ulcer
Nizatidine 14
Figure 0
Nizatidine is a histamine H₂ receptor antagonist that inhibits stomach acid production, and is commonly used in the treatment of peptic ulcer disease and gastroesophageal reflux disease.
Marketed Preparations
Figure 2
Nizatidine are available in capsule and oral solution form
Anti-HIV
Ritonavir15
Ritonavir is approved by FDA and old under the brand name Norvir used in HIV / AIDS. It is used in combination of Lopinavir and may also find its use in COVID inferctions. This combination treatment is known as highly active antiretroviral therapy. Ritonavir is a protease inhibitor and is used with other protease inhibitors.
Marketed preparation
Figure 3
Ritonavir is available in tablet & oral solution formulation
.
Anti-diabetics
Thiazolidinediones 16
These are mainly used to treat hyperglycaemia and diabetes. Although saturated Thiazole ring is involved in the structure of these agents however they have been classified Thiazolidinediones. Mainly used as PPAR-ϒ stimulators.
Pioglitazone 17
Figure 0
Sold under the brand name of Actos. Pioglitazone is PPAR-ϒ stimulator. It is also used in conjunction with metformin, sulfonylureas and insulin to show significant hypoglycemic effect in diabetes.
Rosiglitazone 18
Figure 0
Some examples of Thiazolidinediones have been exemplified here. Thiazolidinediones serve as insulin sensitizers and examples include Pioglitazone and Rosiglitrazone.
Marketed Preparations
Figure 0
Conclusion
Thiazole moiety plays a vital role in allopathic medicine and its role as pharmacophore has been exemplified here. Some marketed medicines containing thiazole pharmacophores have been acknowledged for their use for the betterment and discoveries in human and veterinary medicine.
Conflict of Interest
None.
Acknowledgment
The Author AGN thanks Shri R.S. Yadav, President, CAYMET for their moral support and several research facilities. The Author SG thanks author AGN for his supervision throughout the research project.
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