Medicinal Organic Chemistry: Key Concepts and Drug Classifications

What is medicinal chemistry?

The science that incorporates different branches of chemistry and biology for the research, discovery, and design of new therapeutic chemicals and their development into medicines.

Define a drug.

Any substance intended for the prevention, diagnosis, cure, mitigation, or treatment of symptoms of a disease or to alter the structure or function of the body.

What are the three origins of drugs?

Natural compounds, synthetic compounds, and semi-synthetic compounds.

What are chemotherapeutic agents?

Drugs that fight malignant cells or tissues.

What types of diseases are treated with antibacterials?

Infectious diseases transmitted via person-to-person or outside agents.

What is the role of a receptor in drug action?

A protein molecule that binds various chemical compounds to produce a pharmacological response.

What is the Lock and Key Theory?

The theory that a substrate is completely complementary in shape to the active site of the receptor, fitting perfectly.

What does the Induced Fit Theory propose?

The substrate and active site are not completely complementary, but the enzyme conforms to the shape of the substrate.

What is the Hypothesis of Clark?

The pharmacologic effect of a drug depends on the percentage of receptors occupied.

What is the significance of the Partition Coefficient (P)?

It describes the lipophilicity of a drug, indicating its ability to dissolve in a lipid phase when an aqueous phase is present.

What does a higher dissociation constant (Ka) indicate for acids?

A stronger acid, as it has a higher tendency to give out protons.

What is metabolism in the context of drugs?

The process where the body chemically modifies a drug, typically breaking it down into smaller, more water-soluble compounds called metabolites.

What are the four possible effects of drug metabolism on its action?

Decreased pharmacologic activity, increased pharmacologic activity, increased toxicity, and altered pharmacologic activity.

What is the purpose of Natural Product Screening in drug discovery?

To assay natural sources from folklore medicine for their pharmacologic actions.

What is Rational Drug Design?

A focused approach on structural knowledge of receptors or ligands to design, identify, or create a lead compound.

What does the term 'bioavailability' refer to?

The extent and rate at which the active ingredient or active moiety is absorbed and becomes available at the site of action.

What are the two types of drug interactions?

Pharmacokinetic interactions and pharmacodynamic interactions.

What is the role of pharmacodynamics?

To study the effects of drugs and their mechanisms of action in the body.

What is the purpose of drug metabolism studies?

To assess the biological activity of metabolites and clinical candidates.

What is the difference between infectious and non-infectious diseases?

Infectious diseases are caused by pathogens, while non-infectious diseases are caused by genetic malfunction, environmental factors, or stress.

What is the significance of weak chemical bonds in drug-receptor interactions?

Most drug-receptor interactions are reversible and occur via weak chemical bonds.

What does the term 'selective toxicity' refer to?

The ability of a drug to target specific pathogens without harming the host.

What is the Hypothesis of Baker?

It involves active-site-directed irreversible inhibition through covalent bond formation between receptor and ligand.

What is the Eason-Steadman Hypothesis?

It states that the more potent enantiomer should be involved in a three-point fit to the receptor.

What is the importance of solubility in drug action?

It determines the concentration of dissolved solute in equilibrium with the solid solute, affecting drug absorption.

What is the significance of ionization in drug properties?

Ionization affects the solubility and absorption of drugs in the body.

What is the most important site for drug metabolism?

The liver

What is the first-pass effect?

The process where orally administered drugs are absorbed into the bloodstream through the GI tract and must pass through the liver before distribution.

Name a drug that undergoes first-pass metabolism.

Morphine

What is a prodrug?

A chemically modified inert precursor of the drug that, upon biotransformation, liberates the pharmacologically active parent compound.

What are the ideal properties of a prodrug?

1. The drug and carrier linkage must be cleared in vivo. 2. It should not have intrinsic pharmacologic activity. 3. It should rapidly transform into the active form. 4. The metabolic fragments should be nontoxic.

List one advantage of prodrugs.

Enhanced drug bioavailability.

What is Phase I metabolism?

Functionalization reactions that introduce or modify functional groups to increase polarity and promote excretion.

What is Phase II metabolism?

Conjugation reactions that convert Phase I metabolites into more polar and water-soluble products.

Which enzyme system is commonly involved in Phase I metabolism?

CYP450 system

What is bioisosterism?

The concept of groups that have nearly equal molecular shape and volume, and similar physicochemical properties.

What are classical bioisosteres?

Groups that replace certain atoms while maintaining biological properties.

What is an example of a glycine conjugation pathway?

Benzoic acid to hippuric acid.

How does stereoisomerism affect pharmacokinetics?

Stereoisomers can differ in absorption, distribution, metabolism, and excretion.

What is the significance of L-methotrexate compared to D-methotrexate?

L-methotrexate is better absorbed than D-methotrexate.

What is the effect of (S)-ibuprofen compared to (R)-ibuprofen?

(S)-ibuprofen has desired pharmacologic effects while (R)-ibuprofen is inactive.

What therapeutic use does quinine have?

Antimalarial activity.

What is the Hantzsch-Widman nomenclature used for?

Naming heterocyclic compounds.

What is a heterocyclic compound?

A ring system made up of carbon atoms and at least one other element (e.g., sulfur, nitrogen, oxygen).

What is the goal of structure-activity relationship (SAR) studies?

To find relationships between chemical structure and biological activity of compounds.

Which metabolic reaction converts phenacetin to paracetamol?

O-demethylation.

What is the role of drug metabolizing enzymes?

To facilitate the biotransformation of drugs into metabolites.

What is the main purpose of Phase I metabolic reactions?

To increase the polarity of drug molecules to promote excretion.

What are non-classical bioisosteres?

Groups that are structurally similar but do not meet steric and electric requirements.

What is the relationship between stereoisomerism and therapeutic uses?

Isomerism can lead to different therapeutic uses and adverse drug reactions.

What is the significance of (S,R) and (R,R) isomers in labetalol?

(S,R) is a potent alpha-blocker, while (R,R) is a potent beta-blocker.

What is the effect of D-ethambutol compared to L-ethambutol?

D-ethambutol is anti-TB while L-ethambutol can cause blindness.

What are common heterocycles found in drugs?

Sulfoxide, sulfonyl, carbamate, urea, guanidine, hydroquinone, phenol, catechol, resorcinol, salicylic acid, benzoic acid, toluene, aniline, anthranilic acid, benzaldehyde, anisole, cresol, phenanthrene, naphthalene, anthracene, thiophene, pyran, pyrrolidine, pyrrole, furan, imidazole, thiazole, piperazine, pyrimidine, pyridine, piperidine, pyrazine, isoquinoline, purine, quinoline, indoline, indole.

What is a privileged scaffold in medicinal chemistry?

Core molecular frameworks that can bind to multiple biological targets, serving as versatile starting points for drug discovery.

Define antiseptic.

Compounds that kill (-cidal) or inhibit the growth (-static) of microbes when applied to living tissue.

What are the ideal characteristics of an antiseptic?

1. Low toxicity, 2. Rapid and sustained lethal action, 3. Low surface tension, 4. Non-irritating to tissues, 5. Retains activity in the presence of body fluids.

What is a disinfectant?

Destruction of pathogens on inanimate objects.

What is the mechanism of action (MOA) of alcohol and its derivatives?

Protein denaturation.

How does chain length affect the antibacterial potency of primary alcohols?

The antibacterial potencies increase with molecular weight until the 8-carbon atom.

What is denatured alcohol?

Alcohol rendered unfit for drinking.

What is formaldehyde used for?

As embalming fluid and disinfectant.

What is the phenol coefficient?

The ratio of dilution of a given test disinfectant to the dilution of phenol required to kill a strain of Salmonella typhi.

What is the MOA of phenol at low concentrations?

Protein denaturation.

What is the MOA of phenol at high concentrations?

Lysis of bacterial membranes.

What is cresol also known as?

Methylphenol.

What is the use of thymol?

As a mild fungicide for Tinea infections.

What is carbamide peroxide composed of?

Urea and hydrogen peroxide.

What are iodine-containing compounds used for?

As germicides, with a MOA of protein inactivation by iodination or oxidation.

What is the composition of iodine tincture?

2% iodine in 50% alcohol with NaI.

What is the role of chlorine in disinfection?

Releases hypochlorous acid (HClO) when dissolved in water, used as a municipal water disinfectant.

What are cationic surfactants?

Quaternary ammonium compounds with antimicrobial properties.

What is the MOA of cationic surfactants?

Dissolution into microbial cell membranes, adsorption, destabilization, and subsequent lysis.

What is the use of benzalkonium?

As a disinfectant, detergent, emulsifying agent, and wetting agent.

What are mercurials used for?

Topically to treat localized infections and syphilis.

What is the MOA of mercurials?

Reaction with sulfhydryl groups and formation of covalent bonds.

What is the significance of glutaraldehyde?

Used to sterilize heat-sensitive equipment and pharmaceuticals that cannot be autoclaved.

What is the primary use of hydrous benzoyl peroxide?

As a topical OTC agent for acne.

What is the use of chlorhexidine gluconate?

As a biguanide antiseptic used for irrigation and mouthwash.

What is the main application of iodine solution?

Used for disinfection, typically as a 2% iodine in water with NaI.

What type of bacteria are cationic dyes effective against?

Gram-positive (G+) bacteria and fungi, but generally not effective against Gram-negative (G-) bacteria.

What is Gentian Violet used for?

It is used as vaginal suppositories for yeast infections and as an oral anthelmintic for strongyloidiasis and oxyuriasis.

What is the primary use of Methylene Blue?

It is used in the treatment of cystitis, urethritis, and cyanide poisoning.

What is the role of preservatives in medicinal formulations?

Preservatives are added to prevent microbial contamination and must be effective at low concentrations, nontoxic, stable, and compatible with other constituents.

What is Methylparaben used against?

Mold growth.

What is the function of Benzyl Alcohol in injectable drugs?

It is used in vials of injectable drugs in water or saline solution (1-4%) but can cause gasping syndrome in neonates.

What is the mechanism of action (MOA) of antifungals that are polyenes?

They bind with ergosterol, creating false membranes and forming pores that lead to the loss of cell constituents.

What is the size of the macrolide ring in Nystatin?

38-membered macrolide ring.

What is the mechanism of action of azole antifungals?

They inhibit 14-a-demethylase, blocking the demethylation of lanosterol to ergosterol, which inhibits ergosterol synthesis.

Name a drug that is a triazole antifungal.

Voriconazole or Itraconazole.

What is the source of quinine?

Cinchona bark.

What is the primary use of Primaquine?

It is used for the prevention of relapse in malaria and is gametocidal against P. vivax, P. ovale, and P. malariae.

What is the drug of choice for the treatment of scabies?

Permethrin (Kwell®).

What is Methicillin used for?

It is the drug of choice for penicillin-resistant Staphylococcus aureus (PRSA).

What are beta-lactamase inhibitors?

They are 'suicide substrates' that are partnered with lactamase-susceptible penicillins.

What is the mechanism of action of Vancomycin?

It inhibits cell wall synthesis by binding to the D-Ala-D-Ala terminus.

What adverse effect is associated with Vancomycin?

Flushing (Red Man syndrome) and nephrotoxicity.

What is the primary action of antifungals that are allylamines?

They inhibit squalene biosynthesis via inhibiting squalene epoxidase.

What is the mechanism of action of 4-aminoquinolines?

They inhibit the conversion of hematin to hemozoin.

What is the prototype of artemisinins?

Dihydroartemisinin.

What is the significance of the 26-membered macrolide ring in Natamycin?

It is fungicidal and fungistatic within the same concentration range.