Antianginal Drugs_ A Medicinal Chemistry Perspective

Antianginal Drugs: A Medicinal Chemistry Perspective

Introduction to Antianginal Drugs

Definition and therapeutic goals

Pathophysiology of angina pectoris

Major classes of antianginal drugs

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Nitrates

Chemical structure: Organic nitrates (R-ONO2)

SAR: Importance of nitrate group for activity

Mechanism: NO release 鈫?cGMP activation 鈫?vasodilation

Examples: Nitroglycerin, Isosorbide dinitrate, Isosorbide mononitrate

Metabolism: Enzymatic reduction to nitric oxide

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Beta-Blockers

General structure: Aryloxypropanolamine

SAR: Importance of 尾-phenethylamine moiety

Selectivity: 尾1 vs. 尾2 receptor binding

Examples: Propranolol (non-selective), Metoprolol (尾1-selective)

Metabolism: Hepatic, often via CYP2D6

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Calcium Channel Blockers

Subclasses: Dihydropyridines, Benzothiazepines, Phenylalkylamines

SAR: Importance of heterocyclic ring systems

Mechanism: L-type calcium channel blockade

Examples: Amlodipine (DHP), Diltiazem (BZT), Verapamil (PAA)

Metabolism: Hepatic, often via CYP3A4

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Ranolazine

Chemical structure: Piperazine derivative

SAR: Importance of aromatic rings and piperazine core

Mechanism: Late sodium current inhibition

Metabolism: Hepatic, primarily via CYP3A4

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Ivabradine

Chemical structure: Benzocyclobutane derivative

SAR: Importance of lactam ring for If channel binding

Mechanism: Selective If current inhibition in SA node

Metabolism: Hepatic, primarily via CYP3A4

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Trimetazidine

Chemical structure: Piperazine derivative

SAR: Importance of methoxy groups for activity

Mechanism: Inhibition of long-chain 3-ketoacyl-CoA thiolase

Metabolism: Renal excretion, minimal hepatic metabolism

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Structure-Activity Relationships (SAR)

Key pharmacophores for each drug class

Modifications affecting potency and selectivity

Importance of stereochemistry in antianginal drugs

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Drug-Receptor Interactions

Binding sites for nitrates, beta-blockers, and CCBs

Molecular basis for drug selectivity

Role of allosteric modulation in antianginal drug action

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Pharmacokinetics and Drug Metabolism

Absorption and distribution characteristics