Antianginal Drugs Classification in Medicinal Chemistry
From a medicinal chemistry perspective, antianginal drugs can be classified based on their chemical structures, pharmacophores, and structure-activity relationships (SARs). This classification provides insights into the molecular basis of their therapeutic effects and guides the development of new, more effective antianginal agents. Here's an overview of the major classes of antianginal drugs from a medicinal chemistry standpoint:
Nitrates and Nitrate-like Compounds:
Nitrates are characterized by the presence of a nitrate ester (-ONO2) functional group. The key pharmacophore is the ability to release nitric oxide (NO) in vivo. Examples include:
a) Glyceryl trinitrate (nitroglycerin): Contains three nitrate ester groups.
b) Isosorbide dinitrate and mononitrate: Bicyclic compounds with nitrate ester groups.
c) Molsidomine: A sydnonimine that acts as an NO donor without the nitrate ester group.
Structure-Activity Relationship (SAR): The number and position of nitrate groups affect the potency and duration of action. Compounds with more nitrate groups generally have faster onset but shorter duration.
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Beta-Blockers:
These compounds share a common aryloxypropanolamine structure. The key pharmacophore includes:
a) An aromatic ring
b) An alkyl spacer (usually propyl)
c) A secondary amine
d) A beta-hydroxy group
Examples include propranolol, metoprolol, and atenolol.
SAR: Modifications to the aromatic ring and amine substituents affect selectivity for 尾1 vs. 尾2 receptors and lipophilicity, influencing tissue distribution and pharmacokinetics.
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Calcium Channel Blockers:
This class is diverse in structure but can be broadly categorized into:
a) Dihydropyridines (e.g., nifedipine, amlodipine): Contain a 1,4-dihydropyridine ring with ester substituents.
b) Phenylalkylamines (e.g., verapamil): Feature a phenylalkylamine core with multiple aromatic rings.
c) Benzothiazepines (e.g., diltiazem): Contain a benzothiazepine ring system.
SAR: The nature and position of substituents on these core structures affect potency, selectivity for vascular vs. cardiac tissue, and pharmacokinetic properties.
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Potassium Channel Openers:
Exemplified by nicorandil, which combines features of nitrates and potassium channel openers. It contains:
a) A pyridine ring
b) A nitrate ester group
c) A nicotinamide-like structure
SAR: The presence of both the nitrate and nicotinamide-like moieties contributes to its dual mechanism of action.
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Metabolic Modulators:
Represented by ranolazine, which has a complex structure featuring:
a) A piperazine core
b) Multiple aromatic rings
c) An acetamide group
SAR: The unique structure of ranolazine contributes to its specific action on the late sodium current in cardiac cells.
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If Channel Inhibitors:
Ivabradine, the primary example, has a unique structure containing:
a) A benzocyclobutane core
b) A seven-membered heterocyclic ring
c) Multiple chiral centers
SAR: The complex structure of ivabradine is crucial for its selective inhibition of the If current in the sinoatrial node.
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Miscellaneous Agents:
This category includes drugs with diverse structures that don't fit neatly into the above classes, such as:
a) Trimetazidine: A piperazine derivative with a trimethoxybenzyl group.
b) Fasudil: A isoquinoline sulfonamide derivative.
In medicinal chemistry research, these structural classifications serve as starting points for developing new antianginal drugs. Strategies include:
Modifying existing structures to improve potency, selectivity, or pharmacokinetic properties.
Designing hybrid molecules that combine pharmacophores from different classes.
