start medchem

Common name nomenclature rule for carboxylic acids

Uses Greek letters (\alpha, \beta, \gamma, \delta, \epsilon) to indicate substituent positions relative to the -COOH group (Alpha C is next to COOH).

Origin of carboxylic acid common names

Often derived from the Latin or Greek name indicating the original source of the acid.

IUPAC nomenclature rule for carboxylic acids

Parent chain contains the -COOH group, carboxyl C is #1, and the "-e" ending is changed to "-oic acid" (e.g., Methane → Methanoic Acid).

Principal reactivity principle for carboxylic acid derivatives

Nucleophilic Substitution Reaction (NSR).

Reactants, naming, and product of Carboxylic Acid Neutralization

Reactants: Acid + Base | Naming: Cation name first, then acid name with "-ic acid" replaced by "-ate" | Product: Salt (e.g., Sodium carboxylate).

Reactants, naming, and product for Conversion to Acyl/Acid Halides

Reactants: RCOOH + Thionyl Chloride (\text{SOCl}_2) or Thionyl Bromide (\text{SOBr}_2) | Naming: Replace "-oic acid" with "-oyl chloride" or "-oyl bromide" | Product: Acyl/Acid Halide (e.g., 2-methylbutanoyl chloride).

Reactants and product for Conversion to Acid Anhydrides

Reactants: 2 molecules of RCOOH undergoing dehydration | Product: Acid Anhydride.

Reactants, naming, and product for Conversion to Esters

Reactants: RCOOH + Primary Alcohol | Naming: Alkanol portion (R') named first, then acid name with "-ic acid" replaced by "-ate" | Product: Ester (e.g., Methylhexanoate from methanol + hexanoic acid).

Two-step process for Conversion of Carboxylic Acid to Amides

Step 1: \text{RCOOH} + \text{SOCl}_2 \rightarrow \text{Acyl halide}; Step 2: \text{Acyl halide} + \text{NH}_3 \rightarrow \text{Amide}.

Naming rule and product for Conversion to Amides

Naming: Replace "-oic acid" with "amide" (e.g., 2-ethylhexanamide from 2-ethylhexanoic acid) | Product: Amide.

Reactant and product of Carboxylic Acid Reduction

Reactant: \text{RCOOH} + \text{LiAlH}_4 (Lithium Aluminum Hydride) | Product: Primary Alcohol.

Hydrolysis of Acid Halides

\text{Acyl Halide} + \text{H}_2\text{O} \rightarrow \text{RCOOH} + \text{HCl}.

Hydrolysis of Acid Anhydrides

\text{Acid Anhydride} + \text{H}_2\text{O} \rightarrow \text{RCOOH} + \text{RCOOH}.

Hydrolysis of Esters

\text{Ester} + \text{H}_2\text{O} \rightarrow \text{RCOOH} + \text{R-OH}.

Hydrolysis of Amides (Conditions and Products)

Conditions: Acidic environment + heat | Reaction: \text{Amide} + \text{H}_2\text{O} \rightarrow \text{RCOOH} + \text{NH}_3 (Ammonia gas; turns litmus Red \rightarrow Blue).

Susceptibility ranking of carboxylic acid derivatives to Hydrolysis

Acyl halide > Acid anhydride > Ester > Thioester > Amide > Carbamate > Ureides.

Definition of Organic Medicinal Chemistry

The practice of medicinal chemistry devoted to the discovery and development of new drugs.

Definition and biological purpose of Drug Metabolism

Biotransformation of drugs in the body; important for drug elimination by converting drugs into hydrophilic, inactive, and non-toxic metabolites.

Primary organ of metabolism

Liver.

The two main phases of drug metabolism

Phase I (Functionalization) and Phase II (Conjugation).

Main mechanism and functions of Phase I Metabolism

Introduces a polar group (-OH, -COOH, -NH2, -SH) via direct introduction or unmasking existing groups; converts parent drugs into polar active metabolites to create a handle for Phase II.

Three major reaction types in Phase I Metabolism

Oxidation, Reduction, Hydrolysis.

Main mechanisms and functions of Phase II Metabolism

Converts parent drugs to polar inactive metabolites by attaching small, polar, ionizable endogenous compounds; attenuates biologic activity and detoxifies chemically reactive compounds.

Major reaction types in Phase II Metabolism

Glucuronidation, Sulfation, Glutathione Conjugation, Glycine and Glutamine Conjugation, Acetylation, Methylation.

Activated coenzyme/intermediate for Glucuronic Acid Conjugation

Uridine-5-diphospho-\alpha-D-glucuronic acid (UDP-GA).

Activated coenzyme/intermediate for Sulfate Conjugation

3-phosphoadenosine-5-phosphosulfate (PAPS).

Activated coenzyme/intermediate for Methylation

S-adenosylmethionine (SAM).

Activated coenzyme/intermediate for Amide Synthesis

Coenzyme-A.

Common substrates and example of Phase I Oxidation

Substrates: Olefins, alcohols, aldehydes, aromatic moieties | Example: Phenylbutazone \xrightarrow{\text{aromatic hydroxylation}} Oxybutazone.

Conversions and examples of Phase I Reduction

Conversions: Carbonyl compounds \rightarrow OH derivatives; Nitro & Azo compounds \rightarrow Amine derivatives | Examples: Chloral Hydrate \rightarrow Trichloroethanol; Prednisone \xrightarrow{\text{ketone reduction}} Prednisolone.

Functional groups undergoing Phase I Hydrolysis and example

Lactams, esters, and amides | Example: Aspirin \rightarrow Salicylic Acid + Acetic Acid.

Coenzyme and enzyme for Glucuronidation

Coenzyme: Uridine-5-diphospho-\alpha-D-glucuronic acid (UDP-GA) | Transferase Enzyme: Glucuronyl transferase.

Reasons why Glucuronidation is the most common Phase II reaction

Readily available supply of D-glucuronic acid; numerous functional groups can combine with glucuronic acid.

Clinical exception (CE) of Glucuronidation

Not yet fully developed in infants.

Coenzyme, enzyme, and products of Sulfation

Coenzyme: PAPS | Transferase Enzyme: Sulfotransferase | Products: Yields water-soluble and inactive conjugates.

Significance and target endogenous compounds of Sulfation

Major conjugation process in neonates; conjugates steroids, heparin, chondroitin, catecholamines, and thyroxine.

Targets and functional groups involved in Glycine and Glutamine Conjugation

Conjugates carboxylic acids, particularly aromatic acids and arylalkyl acids.

Species specificity for Glycine vs Glutamine Conjugation

Glycine conjugation is common to mammals; Glutamine conjugation is specific to humans and other primates.

First mammalian metabolite discovered from glycine conjugation

Benzoic Acid \rightarrow Hippuric Acid.

Purpose and 3 amino acids of Glutathione Conjugation

Detoxifies chemically reactive electrophilic compounds; composed of Cysteine (-SH; responsible for detoxification), Glycine, and Glutamine.

Purpose, target functional group, supplier, and enzyme for Acetylation

Activity termination & detoxification; important route for primary amino acids | Supplier: Acetyl-CoA | Transferase Enzyme: N-acetyltransferase.

Drugs that undergo Acetylation (HIPS)

Hydralazine, Isoniazid (INH), Procainamide, Sulfonamides.

Acetylation Polymorphism (Slow vs Fast Acetylators)

Slow Acetylators: Europeans, Caucasians, Egyptians (require low dose); Fast Acetylators: Eskimos and Asians (require high dose).

Coenzyme, enzyme, and metabolic output of Methylation

Coenzyme: S-adenosylmethionine (SAM) | Transferase Enzyme: Methyltransferase | Output: Minor pathway leading to non-polar and inactivated compounds.

Physiological roles of Methylation

Biosynthesis of epinephrine and melatonin; Inactivation of NE, Dopamine, 5-HT, and Histamine.

Definition of First Pass / Pre-Systemic Metabolism

Occurs when orally administered drugs are extensively metabolized before reaching systemic circulation.

List of drugs with extensive first-pass metabolism

Isoproterenol, Lidocaine, Morphine, Meperidine, Nitroglycerin, Pentazocine, Propoxyphene, Propranolol, Salicylamide.

Mnemonic and list for Enzyme Inducers

Mnemonic: O-CRAP-GPTS | Drugs: Omeprazole, Carbamazepine (char-broiled foods/cruciferous vegetables), Rifampicin, Alcohol (Chronic), Phenytoin, Griseofulvin, Phenobarbital, Tolbutamide, St. John's Wort.

Mnemonic and list for Enzyme Inhibitors

Mnemonic: SICK FACES DG.DQ.COM | Drugs: Sodium valproate, Isoniazid, Cimetidine, Ketoconazole, Fluoroquinolones, Alcohol (Acute), Chloramphenicol, Erythromycin (except Azithromycin), Sulfonamides, Diltiazem, Grapefruit, Disulfiram, Quinidine/Quinine, Antivirals (Protease Inhibitors), Ciprofloxacin.

Contribution of Joseph Lister to anti-infectives

Introduced phenol (carbolic acid).

Contributions of Paul Ehrlich to anti-infectives

Discovered Salvarsan (Compound 606); introduced the concept of selective toxicity; used Atoxyl (Na Arsanilate) and Arsphenamine for sleeping sickness.

Definition of Germicides

Anti-infective agents that are used locally.

Definition of Antisepsis

Application of an agent to living tissue to prevent infection.

Definition of Decontamination

Destruction or marked reduction in the number or activity of microorganisms.

Definition of Disinfection

Chemical or physical treatment applied on inanimate surf