5-Amino-4-imidazolecarboxamide
[CAS# 360-97-4]

Identification

• Classification: Analytical chemistry >> Standard >> Pharmacopoeia standards and magazine standards
• Name: 5-Amino-4-imidazolecarboxamide
• Synonyms: 4-Aminoimidazole-5-carboxamide
• Molecular Formula: C₄H₆N₄O
• Molecular Weight: 126.12
• CAS Registry Number: 360-97-4
• EC Number: 206-641-4
• SMILES: C1=NC(=C(N1)C(=O)N)N

Properties

• Density: 1.5±0.1 g/cm³ Calc.^*
• Melting point: 164 - 170 ºC (Expl.)
• Boiling point: 522.1±30.0 ºC 760 mmHg (Calc.)^*
• Flash point: 269.6±24.6 ºC (Calc.)^*
• Index of refraction: 1.708 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovory and Applicatios

5-Amino-4-imidazolecarboxamide is a heterocyclic organic compound featuring an imidazole ring substituted at the 4-position with a carboxamide group and at the 5-position with an amino group. This structure combines the aromaticity and nitrogen-rich character of imidazole with functional groups that confer significant chemical reactivity and biological relevance. The molecular formula for this compound is C₄H₆N₄O, reflecting its composition of carbon, hydrogen, nitrogen, and oxygen atoms.

The imidazole ring system is a five-membered aromatic heterocycle containing two nitrogen atoms positioned at non-adjacent locations. This arrangement allows the molecule to participate in various hydrogen bonding interactions and coordinate with metal ions, characteristics that are essential in biological systems and catalysis. The presence of an amino group at the 5-position enhances the molecule’s nucleophilicity and potential to form additional hydrogen bonds, while the carboxamide at the 4-position introduces both hydrogen bond donor and acceptor functionalities.

5-Amino-4-imidazolecarboxamide has garnered interest due to its structural similarity to naturally occurring biomolecules and its role as an intermediate in biochemical pathways. Derivatives of imidazolecarboxamide are found in nucleotides and cofactors, serving as essential components in processes such as DNA synthesis and enzymatic catalysis. For example, the compound shares features with intermediates in purine biosynthesis, where imidazole-containing molecules are central.

The chemical synthesis of 5-amino-4-imidazolecarboxamide can be achieved through cyclization reactions involving amidines and α-haloketones or related precursors. Alternatively, it may be accessed by functional group transformations on imidazole derivatives, including selective amination and carboxamidation steps. The versatility of synthetic routes allows for structural modifications, enabling the development of analogs with tailored properties for research or therapeutic applications.

In medicinal chemistry, compounds related to 5-amino-4-imidazolecarboxamide have been explored for their biological activities, including antiviral, anticancer, and enzyme inhibitory effects. The imidazole core is known to interact with biological targets through hydrogen bonding, electrostatic interactions, and coordination with metal centers in metalloproteins. The amino and carboxamide substituents enhance binding specificity and solubility, which are valuable for drug design.

Physicochemically, 5-amino-4-imidazolecarboxamide is typically a crystalline solid with moderate solubility in water and polar organic solvents such as dimethyl sulfoxide and methanol. Spectroscopic analysis reveals characteristic features: the imidazole ring exhibits distinct signals in nuclear magnetic resonance (NMR) spectroscopy, while the carboxamide carbonyl group absorbs strongly in the infrared region around 1650 cm⁻¹. Mass spectrometry confirms the molecular weight and fragmentation pattern consistent with the substituted imidazole.

The compound’s stability under various conditions allows its use as a building block in synthetic chemistry. It can participate in condensation reactions, nucleophilic substitutions, and metal coordination. These properties facilitate its incorporation into more complex molecules, including heterocyclic libraries for drug discovery.

From a biochemical perspective, 5-amino-4-imidazolecarboxamide derivatives play roles in cellular metabolism and signaling. For instance, imidazolecarboxamide ribonucleotides are intermediates in the biosynthesis of purines, essential components of nucleic acids. This connection underscores the importance of imidazolecarboxamide compounds as structural and functional motifs in life sciences.

Research has also investigated the potential of imidazolecarboxamide derivatives as enzyme inhibitors targeting kinases, hydrolases, and other proteins implicated in disease. Their ability to chelate metal ions in enzyme active sites or mimic natural substrates provides a basis for therapeutic development.

In summary, 5-amino-4-imidazolecarboxamide is a nitrogen-rich heterocyclic compound combining an imidazole ring with amino and carboxamide substituents. Its chemical versatility, biological relevance, and structural features make it a significant molecule in synthetic chemistry, medicinal research, and biochemistry. The compound serves as both a synthetic intermediate and a scaffold for the development of bioactive agents, reflecting its importance across multiple scientific disciplines.

References

2007. Associations of common polymorphisms in the thymidylate synthase, reduced folate carrier and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase genes with folate and homocysteine levels and venous thrombosis risk. Clinical chemistry and laboratory medicine.
DOI: 10.1515/cclm.2007.091

1964. Induction of Inosine 5�-Phosphate Dehydrogenase and Xanthosine 5�-Phosphate Aminase by Ribosyl-4-amino-5-imidazolecarboxamide in Purine-requiring Mutants of Escherichia coli B. The Journal of biological chemistry.
DOI: 10.1016/s0021-9258(18)97740-9

2003. 5-Amino-Imidazole Carboxamide Riboside Increases Glucose Transport and Cell-Surface GLUT4 Content in Skeletal Muscle From Subjects With Type 2 Diabetes. Diabetes, 52(5).
DOI: 10.2337/diabetes.52.5.1066