Furosemide chemical structure

Need a clear understanding of furosemide’s molecular architecture? Focus on its core structure: a sulfonamide group linked to a benzene ring, further modified by a chlorosulfonyl group and a carboxyl group. This precise arrangement dictates its potent diuretic properties.

The sulfonamide moiety plays a crucial role in binding to the Na+/K+/2Cl- co-transporter in the thick ascending limb of the loop of Henle. Specifically, the electron-withdrawing chlorosulfonyl group enhances this interaction. Note the spatial configuration of these groups; subtle changes significantly alter its binding affinity and effectiveness.

Analyzing the carboxyl group reveals its contribution to the molecule’s overall polarity and its capacity to interact with renal tubule membranes. The benzene ring provides structural rigidity and influences the overall shape. Understanding this interplay offers a key to comprehending furosemide’s mechanism of action.

Remember: This detailed analysis provides a foundation for understanding furosemide’s pharmacological behavior. Further research into its conformational isomers and interactions with other biological molecules offers even more profound insights into its therapeutic efficacy.

Furosemide Chemical Structure: A Detailed Overview

Furosemide’s chemical structure comprises a sulfonamide group linked to a benzene ring, further attached to a 2-furancarboxamide moiety. This specific arrangement is responsible for its potent diuretic effects.

The benzene ring provides a stable hydrophobic core, contributing to the molecule’s interactions with its target protein, the Na+/K+/2Cl− cotransporter (NKCC2) in the kidney’s thick ascending limb of Henle. The sulfonamide group, crucial for binding, interacts with the protein’s binding site. The furancarboxamide group contributes to its overall structure and bioavailability.

Specific structural features influence its pharmacological action: The presence of chlorine atoms on the benzene ring enhances lipophilicity, facilitating membrane permeability. The carboxamide group contributes to hydrogen bonding interactions with the NKCC2 transporter, ensuring strong binding and inhibition. The precise spatial arrangement of these functional groups is critical for its activity; slight modifications can dramatically alter its potency and efficacy.

Understanding the precise three-dimensional structure is crucial for drug design and development efforts. Modifications to Furosemide’s structure are actively investigated to enhance its therapeutic properties or minimize side effects, creating new derivatives with potentially improved characteristics.

Analyzing this detailed structure allows scientists to predict its interactions and design new, improved diuretics. Studying structure-activity relationships helps refine its therapeutic application and potentially minimize unwanted effects.

Chemical Formula and Molecular Weight

Furosemide’s chemical formula is C₁₂H₁₁ClN₂O₅S. This accurately represents the atoms and their ratios within a single molecule.

Calculating Molecular Weight

To determine furosemide’s molecular weight, we sum the atomic weights of each constituent element, multiplied by their respective counts within the formula.

• Carbon (C): 12.011 x 12 = 144.132
• Hydrogen (H): 1.008 x 11 = 11.088
• Chlorine (Cl): 35.453 x 1 = 35.453
• Nitrogen (N): 14.007 x 2 = 28.014
• Oxygen (O): 15.999 x 5 = 79.995
• Sulfur (S): 32.06 x 1 = 32.06

Adding these values together yields a molecular weight of approximately 331.142 g/mol. This figure is crucial for various pharmaceutical calculations and analyses.

Variations in Reported Molecular Weight

1. Slight variations in reported molecular weight values might stem from using different isotopic abundances for the elements in the calculation.
2. Rounding errors during calculations can also contribute to minor discrepancies.

For most practical purposes, the approximate value of 331 g/mol provides sufficient accuracy.

Functional Groups and Their Significance

Furosemide’s potent diuretic action stems directly from its specific functional groups. We find a sulfonamide group (-SO₂NH₂), a crucial component interacting with the Na+/K+/2Cl- co-transporter in the kidney. This interaction blocks reabsorption of sodium, chloride, and potassium ions, leading to increased urine production.

The carbonyl group (C=O) within the furosemide structure contributes to its overall polarity and solubility, facilitating absorption and distribution within the body. This influences how readily the drug reaches its target site. Furthermore, the presence of a benzene ring enhances its lipophilicity, improving membrane permeability.

The chlorine atom’s presence subtly alters the molecule’s electronic distribution, impacting its binding affinity to the transporter protein. This fine-tuning is key to furosemide’s selectivity and efficacy. Finally, the carboxyl group (-COOH) contributes to the molecule’s acidity, affecting its absorption and excretion.

In short, the interplay of these functional groups–sulfonamide, carbonyl, benzene ring, chlorine, and carboxyl–dictates furosemide’s pharmacological profile. Their precise arrangement and properties are directly responsible for its diuretic mechanism and overall therapeutic effect.

Stereoisomers and Their Pharmacological Activity

Furosemide exists as a single stereoisomer, lacking chiral centers. This simplifies its pharmacological profile, eliminating concerns about varying activities among different isomers. The absence of stereoisomers directly contributes to its predictable diuretic effect.

However, understanding the structure-activity relationship is crucial for drug development. Modifications to furosemide’s structure, even subtle ones, could potentially introduce chiral centers and lead to stereoisomers with different potencies or side effect profiles. Researchers investigate these possibilities to improve efficacy or reduce toxicity.

For example, subtle changes near the sulfonamide group could alter receptor binding and subsequently influence diuretic power. Similarly, variations in the benzene ring might impact its bioavailability or metabolism. Careful analysis of any such modifications is needed to predict and manage their influence on the pharmacological actions.

Structural Modification	Potential Impact
Changes near the sulfonamide group	Altered receptor binding affinity, changed diuretic potency
Benzene ring substitutions	Variations in absorption, metabolism, and excretion
Introduction of chiral centers	Emergence of stereoisomers with different pharmacological properties

This lack of stereoisomerism in furosemide is a key factor in its established clinical use. Further research into related compounds focuses on structure-activity relationships to develop better diuretics with enhanced benefits and reduced adverse effects. Studies employing computational modeling and in-vitro experiments help guide these efforts.

Conformational Analysis and Binding Interactions

Furosemide’s efficacy hinges on its ability to adopt specific conformations that facilitate binding to the Na+/K+/2Cl- cotransporter (NKCC2). X-ray crystallography and molecular dynamics simulations reveal a preference for a relatively planar conformation, allowing optimal interactions with the transporter’s binding pocket. The sulfonamide group forms critical hydrogen bonds with specific amino acid residues.

The chlorobenzene ring contributes significantly to hydrophobic interactions within the binding site, enhancing binding affinity. The carbonyl group also participates in hydrogen bonding, further stabilizing the furosemide-NKCC2 complex. Subtle conformational changes, however, are observed upon binding, primarily involving rotations around the sulfonamide bond. These alterations optimize hydrogen bonding networks and van der Waals contacts within the active site.

Computational studies, such as docking and molecular dynamics simulations, are vital tools to probe these conformational changes and identify key interactions responsible for furosemide’s potency and selectivity. This data can aid in the design of furosemide analogs with improved efficacy and reduced side effects.

Specifically, modifications to the chlorobenzene ring’s substituents could influence hydrophobicity and binding interactions. Similarly, altering the sulfonamide moiety can modify hydrogen bond donor/acceptor properties, impacting binding affinity and specificity. Careful consideration of these structure-activity relationships is crucial for rational drug design.

Relationship Between Structure and Pharmacokinetic Properties

Furosemide’s potent diuretic action stems directly from its chemical structure. The sulfonamide group facilitates binding to the Na+/K+/2Cl- cotransporter in the thick ascending limb of the loop of Henle. This interaction inhibits reabsorption of sodium, potassium, and chloride ions, leading to increased urinary excretion of water and electrolytes.

Sulfonamide Moiety’s Role

The presence of the sulfonamide group is critical for the drug’s activity. Modifications to this group significantly alter binding affinity and, consequently, diuretic efficacy. For example, substitution with electron-donating or withdrawing groups can modulate the molecule’s lipophilicity, affecting its absorption and distribution.

Influence of the Furan Ring

The furan ring contributes to the molecule’s overall structure and pharmacokinetic profile. Its presence impacts the drug’s metabolism and elimination. Studies show that changes to the furan ring can significantly influence the drug’s half-life and clearance rate. Specific structural changes may alter its metabolism by liver enzymes, thereby affecting its duration of action.

Other Structural Features and Pharmacokinetics

The carboxyl group plays a role in ionization, influencing absorption and distribution. The presence of a double bond in the molecule affects its stability. Changes to these features will impact drug absorption from the gastrointestinal tract and bioavailability. Understanding the relationship between the chemical structure and resultant properties is essential for designing furosemide analogues with improved pharmacokinetic characteristics.

Structure-Activity Relationships (SAR) and Drug Design Implications

Modifying furosemide’s structure directly impacts its efficacy and side effects. Altering the sulfonamide group, for instance, affects its binding affinity to the Na+/K+/2Cl- cotransporter, the primary target. Replacing the chlorobenzene ring with other aromatic groups can alter potency and bioavailability. Studies show that electron-withdrawing groups enhance diuretic activity, while electron-donating groups generally reduce it. This understanding guides the design of more potent or less toxic analogs.

Improving Bioavailability

Furosemide’s relatively short half-life and low oral bioavailability present challenges. SAR studies reveal that modifying the carboxyl group – perhaps through esterification – can improve absorption, extending the drug’s duration of action. Investigating prodrug approaches, where the active drug is released gradually, is a promising avenue for enhancing bioavailability. This requires careful consideration of metabolic pathways and potential toxicity.

Reducing Side Effects

Ototoxicity, a serious side effect, is linked to furosemide’s structure. Research focusing on modifying the sulfamoyl moiety suggests that reducing its hydrophilicity can potentially mitigate this risk. Simultaneously, investigating alternative substituents on the benzene ring may further reduce ototoxicity without compromising diuretic efficacy. This delicate balance requires careful pharmacological evaluation during drug development.