MEDICINAL CHEMISTRY Flashcards by Karrizze Basto

A chemistry-based discipline, involving the aspects of biological, medical, and pharmaceutical science.

Medicinal Chemistry

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Medicinal chemistry encompasses ____, ____, ____, and ____.

Identification, Discovery, Development, Synthesis

IDDS

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Main driving force/highlight for medicinal chemistry

Random Screening

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One of the first groups of drugs that was discovered thru medicinal chemistry

Nitrofurans

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Metronidazole (Flagyl) is indicated as an ____.

Anti-protozoal/Anti-fungal

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Chemical compound that is used to treat, mitigate, diagnose, and prevent diseases both in humans and animals.

Drugs

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Compounds that interact with a biological system to produce a biological response - beneficial or toxic.

Drugs

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Chemical compound that has a pharmacologic or biological activity whose chemical structure is used as a starting point for chemical modification in order to improve potency, selectivity, or pharmacokinetics parameters.

Lead Compound

“Prototype”

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Lead compounds thar underwent modifications.

Analogues

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Innovative or new drugs for previously unmet medical needs

Novel Drugs

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Drugs for rare medical conditions

Orphan Drugs

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Ideal drug that is free from side effects

Goal Drug

Non-existent

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Compound that undergoes biotransformation prior to exhibiting its pharmacological effects

Prodrug

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2 Broad categories of prodrugs

Carrier-linked prodrug
Bio-precursors

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Consist of the attachment of a carrier group to the active drug to alter its physicochemical properties and the subsequent enzymatic or non-enzymatic mechanisms to release the active drug moiety

Ex: Macromolecules

Carrier-linked prodrug

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Compounds that already contain the embryo of the active species within their structure.

Bio-precursors

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IDENTIFY THE PRODRUG CATEGORY.

Inactive prontosil reduction to sulphanilamide (anti-bacterial)

Bio-precursor

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IDENTIFY THE PRODRUG CATEGORY.

Inactive cyclophosphamide oxidation to phosphoramide mustard (antineoplastic)

Bio-precursor

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Mechanism of action of phosphoramide mustard

Alkylation

Cross-linking of DNA that leads to death of cancer cells

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2 Other terms for double prodrug

Pro-Prodrug or Cascade Latentiated Prodrugs

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Carried out by enzymatic conversion to prodrug is possible before the “pro-drug” release the active ingredient

Double Prodrug, Pro-Prodrug, or Cascade Latentiated Prodrugs

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Prodrugs that use macromolecules as carriers

Macromolecular Prodrugs

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Carrier acts as transporter of the active drug to a specific targeted site

Site-Specific Prodrugs

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Example of a site-specific prodrug liberated in the colon

Sulfazalazine

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Consists of two synergistic drugs chemically linked together, in order to improve the drug delivery properties of one or both drugs

Co-drug/Mutual Prodrug

# EXAMPLES OF CO-DRUG/MUTUAL PRODRUG Sulfasalazine

Sulfapyridine + 5-aminosalicylic acid | For enterocolitis

# EXAMPLES OF CO-DRUG/MUTUAL PRODRUG Benorylate

Paracetamol + Aspirin

# EXAMPLES OF CO-DRUG/MUTUAL PRODRUG Sultamicillin

Ampicillin + Sulbactam

# EXAMPLES OF PRODRUGS Metabolized into Meprobamate

Carisoprodol

# EXAMPLES OF PRODRUGS Bioactivated by esterase (hydrolysis of the ethyl ester) to the active Enalaprilat

Enalapril

# EXAMPLES OF PRODRUGS Bioactivated by esterase (valacyclovir hydrolase enzyme) to the active form Acyclovir

Valaciclovir

# EXAMPLES OF PRODRUGS Bioactivated by Peripheral DOPA decarboxylase to the active form Dopamine

Levodopa

# EXAMPLES OF PRODRUGS IV prodrug of chloramphenicol, because pure chloramphenicol is poorly soluble in water (2.5mg/mL) or palmitate ester to make a suspension (1.95mg/mL)

Chloramphenicol Succinate

# EXAMPLES OF PRODRUGS Deacetylated by esterase to the active form 6-monoacetylmorphine and morphine

Heroin | aka Diacetyl Morphine

# EXAMPLES OF PRODRUGS Designed to prolong the drug activity of its active metabolite 6-mercaptopurine

Azathioprine

# EXAMPLES OF PRODRUGS Designed to mask the toxic side effects of the active metabolite 4-hydroxy–cyclophosphamide and Phosphoramide Mustard.

Cyclophosphamide

# EXAMPLES OF PRODRUGS Designed to increase the chemical stability of the active metabolite Ampicillin.

Hetacillin | Failed prodrug

Phenomenon when a patient receives a placebo treatment will have a perceived or actual improvement of medical condition.

Placebo Effect

Region of the molecule containing the essential organic functional groups that directly interact with the receptor active site, therefore, confers the biologic activity of interest | Must remain intact upon modification

Pharmacophore

Chemical reaction that occur in the body to maintain life and supply of energy

Metabolism

This allows organisms to grow and reproduce, maintain their structures, and respond to their environments.

Metabolism

2 Categories of metabolism

1. Catabolism 2. Anabolism

Type of metabolism that breaks down organic matter

Catabolism | Hydrolysis (Addition Reaction)

Type of metabolism that uses energy to build up or contrast components of cells such as proteins and nucleic acids

Anabolism | Dehydration synthesis

The basic premise of drug metabolism is to convert ____ drugs to ____ metabolites to be excreted. | Lipophilic or Hydrophilic

Lipophilic to Hydrophilic

3 characteristics of drugs to be excreted

1. Hydrophilic/Water-soluble 2. Ionized 3. Polar

The main site for drug metabolism

Liver | High concentration of enzymes (CYP450) and it is a highly perfused organ

Metabolism converts inactive drug to active form in a process called ____.

Biotransformation/Bioactivation

Two general types of local anesthetic agents

Amides and Esters

Local anesthetic agents undergo ____ to terminate drug action.

Bio-inactivation

Disulfiram (Antabuse) is used for ____.

Alcohol Withdrawal

Termination of drug action for disulfiram

Detoxification

Termination of drug action for paracetamol metabolism

Elimination

Bioactivation: MPTP to MPP+

Toxification

Bioactivation: Imipramine to Desipramine

Active Metabolites

Reactions involved in the phase 1 of drug metabolism

1. Reduction 2. Hydrolysis 3. Oxidation

Reaction involved in the phase 2 of drug metabolism

Conjugation

Phase 1 of drug metabolism is also known as ____.

Functionalization Reaction

Aspirin is likely to transform into an ____ at room temperature. | Ester or Amide

Ester

# PHASES OF DRUG METABOLISM Main function is to provide functional groups (OH, COOD, SH, NH2)

Phase 1

# PHASES OF DRUG METABOLISM Most common Phase 1 reaction

Oxidation

# PHASES OF DRUG METABOLISM Usually results to loss of pharmacological activity

Phase 1

# PHASES OF DRUG METABOLISM Non-synthetic reaction

Phase 1

# PHASES OF DRUG METABOLISM Sometimes maybe equally or more active than parent

Phase 1

# PHASES OF DRUG METABOLISM Condensation Reaction

Phase 2

# PHASES OF DRUG METABOLISM Main goal is to attach small, polar, and ionizable endogenous substrates/compounds to the “handles”

Phase 2

# PHASE 2 REACTIONS Enzyme involved in methylation

Methyl transferase (COMT)

# PHASE 2 REACTIONS Enzymes involved in acetylation

1. S-Adenosyl Methionine 2. N-acetyltransferase (NAT)

# PHASE 2 REACTIONS Terminate or attenuate activities

Methylation and Acetylation

# PHASE 2 REACTIONS Protects the body against reactive compounds or metabolites

Glutathione (GSH)

# PHASE 2 REACTIONS Most common Phase 2 reaction

Glucuronidation

# PHASE 2 REACTIONS Enzyme for glucuronidation

Glucuronosyl Acyltransferase (GluCAT)

# PHASE 2 REACTIONS Essential in order to have sufficient supply of glucuronides

D-glucuronic acid

# PHASE 2 REACTIONS Examples of drugs that may undergo glucuronidation

* Morphine * Paracetamol * Chloramphenicol

# PHASE 2 REACTIONS Newborns are capable of this reaction but it is easily saturated

Sulfation

# PHASE 2 REACTIONS Enzyme involved in sulfation

Sulfonyl Transferase

# PHASE 2 REACTIONS Substrates for acetylation

* Hydralazine * Isoniazid * Procainamide | HIP

# PHASE 2 REACTIONS This drug undergoes phase 2 first before phase 1

Isoniazid

Grapefruit is an example of an enzyme ____. | Inhibitor or Inducer

Inhibitor | Prolongs the effect of drug

Grapefruit contains ____ that is responsible for the inhibitory effects when taken with drugs.

Furanocoumarins (Bioflavonoids)

Rifampicin acts as an enzyme ____ when taken with paracetamol and oral contraceptive pills. | Inhibitor or Inducer

Inducer | More enzymes = Faster metabolism = Less effect

# FACTORS THAT AFFECT METABOLISM Older people have ____ metabolism. | Faster or Slower

Slower

# FACTORS THAT AFFECT METABOLISM Fast acetylators are prone to experience ____ with the use of isoniazid.

Peripheral Neuropathy

# FACTORS THAT AFFECT METABOLISM Peripheral neuropathy with the use of isoniazid is managed by taking _____.

Vitamin B6 Pyridoxine

# FACTORS THAT AFFECT METABOLISM Slow acetylators are prone to experience ____ with the use of isoniazid.

Hepatotoxicity

MEDICINAL CHEMISTRY Flashcards

(85 cards)