1Student, Department of Pharmaceutical organic chemistry, Goel Institute of Pharmacy & Sciences, Lucknow, Uttar Pradesh
2Associate Professor, Department of pharmaceutical organic chemistry, Goel institute of pharmacy & Sciences, Lucknow, Uttar Pradesh
The ongoing challenge of antimicrobial resistance necessitates the continuous exploration of new antimicrobial agents. Among various chemical scaffolds, 2-aminopyrimidine derivatives have garnered significant attention due to their broad-spectrum antimicrobial properties. This review provides a comprehensive overview of 2-aminopyrimidine derivatives, highlighting their chemical synthesis, structural diversity, and mechanisms of action. Emphasis is placed on recent advancements in the development of these compounds, their activity against a variety of microbial pathogens, and their potential as therapeutic agents. By consolidating current knowledge and identifying future research directions, this overview aims to support the ongoing efforts in combating antimicrobial resistance through the development of novel 2-aminopyrimidine-based antimicrobials.
Any organic compound with one or more heterocyclic aromatics in its molecule is called a heteroaromatic compound. A substance other than carbon has taken the place of one or more organic molecules in a molecule's nucleus.[1].
HETEROCYCLIC COMPOUNDS:
Heteroatoms include things like oxygen, sulfur, and nitrogen. Heterocyclic compounds are the area of organic chemistry that deals with the synthesis, properties, and applications of heterocyclic molecules. Heterocyclic chemistry study revolves around unsaturated derivatives, with most studies and applications involving unstrained 5- and 6-membered rings. Among the substances are furan, pyrrole, thiophene, and pyridine. Heterocycles that are fused to benzene rings constitute a significant subclass. The easy classification of heterocyclic compounds is made possible by their molecular structure. Saturated and unsaturated heterocyclic compounds are the two primary types of heterocyclic molecules. The saturated heterocyclic compounds behave like acyclic derivatives and have changed steric properties. Tetrahydrofuran and piperidine are the most often occurring ethers and amines in this group. Unsaturated heterocyclic compounds with five and six members, however, have garnered a lot of interest due to their unrestricted nature. Among the unstrained unsaturated heterocyclic compounds include pyridine, thiophene, pyrrole, furan, and their benzo fused derivatives. Quinoline, isoquinoline, indole, benzothiophene, and benzofuran are examples of benzo-fused heterocycles. In veterinary medicine, agrochemicals, and pharmaceuticals, heterocyclic compounds are already used in this way.[2].
Importance of Heterocyclic Compounds:
Recently, pyrimidine derivatives have gained significant attention in drug design due to their effectiveness as core molecules for synthesizing various pharmacological candidates. This prominence is attributed to pyrimidine's ability to form hydrogen bonds and dipole-dipole interactions through its nitrogen atoms, enabling strong interactions with biological targets.[3]. 2-Aminopyrimidines represent a crucial class of heterocycles known for their diverse range of activities, including anticancer, antioxidant, antibacterial, antifungal, antiviral, anti-inflammatory, antimalarial, antidiabetic, antileishmanial, and antitrypanosomal properties.[4]. Interest in 2-aminopyrimidines stems from their versatility and significant value as starting materials for synthesizing various other heterocyclic compounds, including biologically active bicyclic pyrimidines. Additionally, aminopyrimidines serve as structural components in highly efficient chiral organocatalysts for asymmetric synthesis.[5]. Important components, pyrimidine and its derivatives are present in many natural products and are crucial for the production of chemicals used in pharmacological and agricultural research. Nature has a wide variety of compounds with the pyrimidine ring structure, such as thiamine (vitamin B1), alkaloids, nucleic bases, and alloxan. They can also be present in a variety of artificial substances, including barbiturates and the HIV medication zidovudine.[6].
2-aminopyrimidines: 2-Aminopyrimidine is a crucial heterocyclic compound that has gained considerable attention in various fields of chemistry and pharmacology. Characterized by a pyrimidine ring with an amino group at the second position, this molecule exhibits a diverse range of chemical and biological properties.[7].
Chemical Structure and Properties:
The basic structure of 2-aminopyrimidine consists of a six-membered ring containing two nitrogen atoms at positions 1 and 3 and an amino group (-NH2) attached at position 2. This unique arrangement allows 2-aminopyrimidine to participate in multiple types of chemical interactions, such as hydrogen bonding and dipole-dipole interactions, which enhance its reactivity and binding affinity with biological targets. [8]. Here are a few marketed medications that include a pyrimidine moiety, such as imatinib, sulfamethomidine, nilotinib, and iclaprim. Additionally, pyrimidine derivatives exhibit various biological activities, including antibacterial and antioxidant properties. Moreover, certain pyrimidine derivatives have been discovered to possess promising properties for treating metabolic imbalances and neurological disorders.[9].
Fig. 1. Some marketed drugs containing 2-aminopyrimidine moiety in their structures.
Specification of 2-aminopyrimidine:
Synthesis:
2-Aminopyrimidine can be synthesized through several methods, including:
1. Condensation reactions involving amidines and ?-dicarbonyl compounds.
2. Cyclization of appropriate precursors.
3. Multi-step organic syntheses that allow for the introduction of various functional groups.
Advances in synthetic methodologies have facilitated the efficient and high-yielding production of 2-aminopyrimidine and its derivatives.[10].
ANTIMICROBIAL ACTIVITY OF HETEROCYCLIC COMPOUNDS
Antimicrobials were discovered and developed throughout the twentieth century, revolutionizing the treatment of infectious diseases. The term "antimicrobial" derives from the Greek words anti (against), micros (small), and bios (life), and encompasses agents that target bacteria, viruses, fungi, and protozoa. Antimicrobials include antibacterials, antivirals, antifungals, and antiprotozoals, and they work by killing or inhibiting the growth of these microorganisms. Some heterocyclic chemicals and compounds lack antimicrobial activity. However, certain antimicrobial agents are both safe and effective and should be encouraged for use. Future efforts to develop effective antimicrobial agents must rigorously follow established guidelines, taking major concerns seriously.[11].
Biological Activity
Inflammation is the body's initial response to infection or injury and plays a crucial role in innate immunity. It involves a complex biological reaction of vascular tissue to harmful stimuli such as bacteria, damaged cells, and irritants. Seeking natural chemicals and phytoconstituents that can disrupt inflammatory pathways and prevent chronic inflammation may benefit human health. The anti-inflammatory properties of plant-based therapies are studied using both acute (egg albumin, croton oil, and carrageenan) and chronic (cotton pellet) in-vitro models.[12].
There are microorganisms in nearly every environment, and high-touch surfaces are a prime location for their proliferation. Adding antimicrobial substances to high-touch surfaces appears to be a practical answer for biomedical and everyday applications, given the health risks connected with acquiring infections from inanimate surfaces and the growing sanitary concerns.[13].
Classification of Antimicrobial Agents
Antimicrobial agents can be classified based on their target microorganisms and their mechanisms of action. Here are the primary categories:
Based on Target Microorganisms:
Based on Mechanism of Action:
Based on Spectrum of Activity:
Based on Origin:
CONCLUSION
The exploration of 2-aminopyrimidine derivatives as antimicrobial agents underscores their significant potential in combating a broad spectrum of microbial pathogens.
Furthermore, the structural versatility of 2-aminopyrimidines allows for extensive chemical modification, which can be utilized to enhance their antimicrobial efficacy, reduce toxicity, and overcome resistance mechanisms. This adaptability is crucial in the ongoing battle against drug-resistant strains of bacteria and fungi, which pose a growing threat to public health.
REFERENCE
Manorama, Garima Awasthi, A Overview Of The 2-Aminopyrimidine Derivatives As Antimicrobial Agents, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 8, 2420-2426. https://doi.org/10.5281/zenodo.13167948
10.5281/zenodo.13167948
