Medicinal Chemistry: SAR and Drug Classes

Definition: Relationship between chemical structure of compounds and their biological activity.
Key Concepts:
- Changes in structure can alter potency and specificity.
- Functional groups influence interaction with biological targets.
- 3D conformation affects binding affinity.
- Analog synthesis can be used to refine drug properties.

Function: Promote the excretion of water and electrolytes.
Types:
- Thiazides: Inhibit Na+/Cl- symporter; reduce hypertension.
- Loop Diuretics: Act on the Loop of Henle; potent, used in heart failure.
- Potassium-Sparing: Inhibit aldosterone; retain potassium.
Common Drugs: Hydrochlorothiazide, Furosemide, Spironolactone.

Function: Prevent blood coagulation, reducing thrombus formation.
Mechanisms:
- Vitamin K Antagonists: Inhibit synthesis of clotting factors (e.g., Warfarin).
- Direct Oral Anticoagulants (DOACs): Target specific factors (e.g., Dabigatran - thrombin, Rivaroxaban - factor Xa).
Clinical Uses: Manage atrial fibrillation, deep vein thrombosis.

Function: Lower lipid levels in the blood to prevent cardiovascular disease.
Classes:
- Statins: Inhibit HMG-CoA reductase; reduce cholesterol synthesis (e.g., Atorvastatin).
- Fibrates: Increase lipoprotein lipase; lower triglycerides (e.g., Fenofibrate).
- PCSK9 Inhibitors: Enhance LDL receptor recycling; lower LDL cholesterol.
Mechanism: Different pathways for cholesterol and triglyceride reduction.

Function: Block nerve conduction to produce temporary loss of sensation.
Mechanism:
- Block voltage-gated sodium channels; prevent action potential generation.
Common Agents: Lidocaine, Bupivacaine, Procaine.
Uses: Surgical procedures, dental work, pain management.

Function: Manage blood glucose levels in diabetes mellitus.
Classes:
- Insulin: Hormonal therapy for Type 1 diabetes and some Type 2.
- Biguanides: Improve insulin sensitivity (e.g., Metformin).
- Sulfonylureas: Stimulate insulin secretion from the pancreas.
- DPP-4 Inhibitors: Enhance incretin levels, improving insulin action.
Key Concepts: Importance of monitoring glycemic control and side effects.

The relationship between the chemical structure of compounds and their biological activity.
Changes in molecular structure can significantly impact a compound's potency and specificity.
Specific functional groups can influence the interaction with biological targets.
The 3D conformation of a molecule affects its binding affinity to its target
Analog synthesis, the systematic modification of a compound's structure, is a valuable tool for refining drug properties.

Promote the excretion of water and electrolytes from the body.
Thiazides inhibit the Na+/Cl- symporter, decreasing sodium reabsorption and reducing hypertension.
Loop diuretics act on the Loop of Henle, powerfully promoting fluid excretion, commonly used for heart failure.
Potassium-sparing diuretics inhibit aldosterone, promoting potassium retention and sodium excretion.
Examples include hydrochlorothiazide, furosemide, and spironolactone.

Prevent blood coagulation, reducing thrombus (blood clot) formation.
Vitamin K antagonists, like warfarin, inhibit the synthesis of clotting factors, ultimately slowing coagulation.
Direct oral anticoagulants (DOACs) target specific factors in the clotting cascade, like Dabigatran (thrombin) and Rivaroxaban (factor Xa) offering more targeted and predictable anticoagulation.
Clinical uses include management of atrial fibrillation and deep vein thrombosis.

Lower lipid levels in the blood to prevent cardiovascular disease.
Statins, such as atorvastatin, inhibit HMG-CoA reductase, an enzyme essential for cholesterol synthesis.
Fibrates like fenofibrate increase lipoprotein lipase activity, lowering triglyceride levels.
PCSK9 inhibitors, a newer class, enhance LDL receptor recycling, leading to reduced LDL cholesterol.
Each class targets different pathways within lipid metabolism for effective lipid reduction.

Block nerve conduction to produce temporary loss of sensation.
Blockage of voltage-gated sodium channels in cell membranes prevents action potential generation, thus halting nerve impulse transmission.
Common agents include lidocaine, bupivacaine, and procaine.
Used in various settings: surgical procedures, dental work, pain management.

Manage blood glucose levels in individuals with diabetes mellitus.
Insulin, a hormonal therapy, is the primary treatment for type 1 diabetes and certain cases of type 2 diabetes.
Biguanides, like metformin, enhance insulin sensitivity, improving glucose utilization.
Sulfonylureas stimulate insulin secretion from the pancreas.
DPP-4 inhibitors enhance incretin levels, hormones that promote insulin action and reduce glucagon secretion.
Continuous monitoring of glycemic control and awareness of side effects are crucial for effective diabetes management.