Furosemide chemical structure

Begin your exploration of furosemide’s chemical makeup by focusing on its core structure: a sulfonamide ring fused to a benzene ring. This arrangement dictates its pharmacological properties.

Notice the presence of a chlorine atom at position 7 of the benzene ring. This seemingly minor detail significantly alters furosemide’s interaction with its target, the sodium-potassium-chloride cotransporter (NKCC2) in the kidney. The chlorine atom enhances its potency as a loop diuretic.

Further analysis reveals a carboxyl group and a sulfamoyl group. These functional groups are key to furosemide’s ability to inhibit NKCC2. Specifically, the carboxyl group contributes to its acidity, influencing its absorption and distribution within the body.

Understanding these structural components provides a foundation for grasping furosemide’s mechanism of action and its resulting diuretic effects. Remember to consult reliable chemical databases and pharmacological resources for a comprehensive analysis.

Furosemide Chemical Structure: A Detailed Analysis

Furosemide’s chemical structure is based on a benzene ring, a sulfonamide group, and a chlorobenzoic acid moiety. This unique arrangement confers its potent diuretic properties.

Understanding the Key Functional Groups

The sulfonamide group (-SO₂NH₂) plays a critical role in binding to its target, the Na+/K+/2Cl− cotransporter in the thick ascending limb of the loop of Henle. This interaction inhibits the reabsorption of sodium, potassium, and chloride ions, leading to increased excretion of water and electrolytes in urine.

• The benzene ring provides a stable, hydrophobic backbone for the molecule.
• The chlorobenzoic acid moiety contributes to the molecule’s overall lipophilicity, aiding its passage across cell membranes.
• The presence of chlorine atom influences the molecule’s activity and pharmacokinetic profile.

Analyzing the Structural Relationships to Activity

1. Modifications to the sulfonamide group significantly impact furosemide’s activity. Altering the substituents on the nitrogen atom can either enhance or diminish diuretic efficacy.
2. The position and nature of substituents on the benzene ring influence binding affinity and pharmacological properties.
3. Changing the chlorobenzoic acid moiety can affect the compound’s ability to interact with its target, altering its potency and duration of action. Specific structural alterations are explored to enhance drug delivery and stability.

Implications for Drug Development

A deep understanding of furosemide’s structure-activity relationship guides the rational design of novel diuretics. Researchers can modify specific parts of the structure to improve potency, selectivity, or pharmacokinetic characteristics. This includes strategies to minimize side effects and enhance therapeutic benefit.

Further Research Directions

• Computational modeling and molecular dynamics simulations are powerful tools to explore the interactions of furosemide analogues with the Na+/K+/2Cl− cotransporter.
• Investigating structure-activity relationships using advanced analytical techniques allows for a more refined understanding of the chemical determinants of furosemide’s action.
• Exploring novel structural modifications to improve drug delivery and reduce unwanted drug interactions can lead to improvements in treatment options.

Furosemide’s Molecular Formula and Weight

Furosemide’s molecular formula is C₁₂H₁₁ClN₂O₅S.

Its molecular weight is approximately 330.74 g/mol. This weight is calculated using the standard atomic weights of each element in the molecule.

Precise calculations may vary slightly depending on the isotopic composition of the elements used, but this value provides a highly accurate representation for most practical applications.

Identifying Key Functional Groups in Furosemide

Furosemide possesses several crucial functional groups contributing to its diuretic activity. Notice the sulfonamide group (-SO₂NH-), a key feature responsible for its interaction with the Na+/K+/2Cl- cotransporter in the nephron. This group’s electron-withdrawing properties influence the molecule’s overall reactivity.

The carboxyl group (-COOH) contributes to its acidity and water solubility, impacting absorption and distribution within the body. Observe also the presence of a chlorine atom, influencing its lipophilicity and enhancing its binding affinity to the transporter.

The furan ring system offers a distinct spatial arrangement, affecting receptor binding. Its unsaturated nature plays a role in the molecule’s overall electronic properties and pharmacological activity. Finally, the presence of a carbonyl group (C=O) in the molecule further contributes to its interaction with biological targets and overall chemical behaviour.

Spatial Arrangement of Atoms: Conformation and Isomerism

Furosemide’s effectiveness hinges on its precise three-dimensional structure. Let’s examine its conformation and isomerism.

Conformational Analysis

Furosemide possesses several rotatable bonds, leading to various conformations. These conformations, while interconvertible, differ in energy. The preferred conformation likely contributes to its binding affinity at the Na+/K+/2Cl− cotransporter.

• Specific bond rotations affect the orientation of the sulfonylurea group and the chlorobenzoic acid moiety.
• Computational methods, like molecular mechanics and dynamics, are employed to predict the most stable conformation(s).
• Experimental techniques, including X-ray crystallography and NMR spectroscopy, validate these theoretical predictions.

Isomerism

Furosemide exists as a single enantiomer, lacking chiral centers. Therefore, optical isomerism is not relevant. However, geometric isomerism (cis-trans isomerism) could theoretically be possible depending on the double bonds present in the molecule, though this is not the case with furosemide in its active form.

Implications for Activity

The precise spatial arrangement of furosemide’s atoms directly impacts its drug activity. Any alteration in conformation or the presence of different isomers would likely significantly modify its interaction with its target receptor and, consequently, its pharmacological profile. Detailed structural analysis remains crucial for understanding its mechanism of action and optimizing its design for future applications.

1. Conformational flexibility might facilitate binding and interaction with the receptor.
2. Specific interactions between functional groups and the receptor are dependent on their precise spatial orientation.
3. Altering the conformation, even subtly, could impact the drug’s bioavailability, efficacy, or toxicity.

Analysis of Bond Lengths and Angles

Furosemide’s structure reveals interesting bond characteristics. The C-O bond lengths in the carboxyl group average approximately 1.23 Å, reflecting the partial double bond character due to resonance. Expect slightly shorter C=O bond lengths (around 1.20 Å) in the carbonyl group. This difference highlights the impact of resonance on bond order.

Analyzing bond angles, the sp² hybridized carbons exhibit angles close to 120°. Deviations from this ideal value are expected and arise from steric interactions between neighboring atoms and groups. For instance, the angle around the nitrogen atom in the sulfonamide group will be less than 120° due to the presence of the bulky sulfonyl group. Precise measurements require computational analysis or X-ray crystallography data, but values between 115° and 118° are reasonable estimations.

The aromatic ring maintains angles very near 120°, demonstrating the planar geometry associated with sp² hybridized carbons in aromatic systems. Slight deviations again are possible due to the substituents attached to the ring, creating minor steric strain.

Careful examination of these bond lengths and angles provides insight into the molecule’s overall geometry and reactivity. Variations from theoretical values, particularly those related to the sulfonamide group and carboxyl group, are attributable to electronic effects and steric factors.

Note: These values are approximate and can vary slightly depending on the specific environment and measurement technique used.

Impact of Chemical Structure on Furosemide’s Pharmacological Properties

Furosemide’s potent diuretic effect stems directly from its unique chemical structure. The presence of a sulfonamide group, a crucial component, facilitates binding to the Na+/K+/2Cl− co-transporter (NKCC2) in the thick ascending limb of the loop of Henle. This interaction inhibits the reabsorption of sodium, potassium, and chloride ions, leading to increased urinary excretion of water and electrolytes. The chlorobenzene ring contributes to its lipophilicity, aiding absorption and distribution throughout the body.

Sulfonamide and its role

The sulfonamide moiety’s precise spatial arrangement and its ability to form hydrogen bonds with specific amino acid residues on NKCC2 are paramount for the drug’s activity. Slight alterations to this group significantly impact binding affinity and, consequently, diuretic potency. Studies have demonstrated that modifications to this functional group reduce efficacy.

Impact of the benzene ring

The presence of the chlorobenzene ring modulates the drug’s overall lipophilicity, influencing its absorption from the gastrointestinal tract and its distribution within various tissues. This contributes to its rapid onset of action. However, this same lipophilicity also contributes to its potential for protein binding and drug interactions. Specific modifications to the benzene ring could alter its pharmacokinetic profile, influencing factors such as absorption rate, bioavailability, and tissue distribution. For instance, increasing its hydrophilicity might reduce its protein binding. Conversely, reducing its lipophilicity might diminish its absorption.

Other structural features

The carboxyl group, in addition to its role in ionization, contributes to furosemide’s water solubility, facilitating its excretion via the kidneys. Changes to this group significantly influence its solubility. The precise spatial orientation of these different functional groups is critical for optimal binding to the NKCC2 transporter. Any deviation in the spatial arrangement can negatively influence the drug’s efficacy.

Comparison with Related Loop Diuretics

Furosemide’s chemical structure differs significantly from other loop diuretics, impacting its potency and side effect profile. Let’s examine key differences:

Diuretic	Key Structural Difference from Furosemide	Impact on Action/Side Effects
Bumetanide	Contains a butylsulfonamide group instead of furosemide’s ethylacrylic acid side chain.	More potent than furosemide; may cause more intense ototoxicity.
Torsemide	Possesses a methyl group replacing a hydrogen atom on the benzene ring.	Longer duration of action compared to furosemide; slightly lower risk of hypokalemia.
Ethacrynic acid	Entirely different chemical structure; contains a phenoxyacetic acid moiety.	Similar potency to furosemide, but carries a higher risk of gastrointestinal upset. Often preferred for patients with sulfonamide allergies.

These variations in structure lead to distinct pharmacokinetic and pharmacodynamic properties. Clinicians should consider these differences when selecting a loop diuretic, tailoring the choice to the patient’s specific needs and potential sensitivities. For instance, patients with impaired renal function might benefit from torsemide’s longer duration, reducing the frequency of administration.