Organic Medicinal Chemistry

Question 1

• The biotransformation of drugs in the body
• Important in the elimination of drugs from the body
• Converts drugs to hydrophilic, inactive and nontoxic
• Has 2 Phases: Functionalization & Conjugation

Answer 1

Metabolism

Question 2

• Introduce a polar functional group (OH, COOH, NH2, SH) by:
- Direct introduction
- Modifying/Unmasking existing functionalities
• Produce a handle on the molecule for Phase II
• Reactions: Oxidation, Reduction, Hydrolysis

Answer 2

Phase 1 (Functionalization)

Question 3

What are the 3 Reactions in Phase 1 Functionalization in Metabolism

Answer 3

1. Oxidation
2. Reduction
3. Hydrolysis

Question 4

What Reactions in Phase I stated below?

• Most common Phase 1 reaction
• Undergone by Olefins, Alcohols, Aldehydes & Aromatic moieties

Answer 4

Oxidation

Question 5

What Reactions in Phase I stated below?

• Carbonyl compounds → Alcohol derivatives
• Nitro and Azo compounds → Amine derivatives

Answer 5

Reduction

Question 6

What Reactions in Phase I stated below?

• Commonly undergone by lactams, esters and amides
• ex. Aspirin → Salicylic acid + Acetic acid

Answer 6

Hydrolysis

Question 7

• Attach small, Ionizable, endogenous compounds to the functional handles
• Reactions: Glucuronidation, Sulfation, Glycine & Glutamine conjugation, Glutathione, Acetylation, Methylation

Answer 7

Phase II (Conjugation)

Question 8

What Reactions in Phase II stated below?

Coenzyme: Uridine-5’-diphospho-α-D-glucuronic acid (UDPGA)
• Transferase enzyme (TE): Glucuronyltransferase
• Most common
• Readily available supply of D-glucuronic acid
• Not yet developed in neonates

Answer 8

Glucoronidation

Question 9

What Reactions in Phase II stated below?

Coenzyme: 3-phosphoadenosine-5-phosphosulfate(PAPS)
• TE: Sulfotransferase
• Conjugate endogenouscompounds such as steroids, heparin, chondroitin, catecholamines,thyroxine
• In neonates, it is the major process.

Answer 9

Sulfation

Question 10

What Reactions in Phase II stated below?

• Conjugate Carboxylic acid, particularly aromatic acids & arylalkyl acid
• Glycine – common to mammals
• Glutamine – humans & other primates
• Minor pathway

Answer 10

Glazine and Glutamine Conjugation

Question 11

What Reactions in Phase II stated below?

The first mammalian metabolite discovered from glycine conjugation

Answer 11

Benzoic acid → Hippuric acid

Question 12

What Reactions in Phase II stated below?

• For detoxifying chemically reactive Electrophilic compounds

Answer 12

Glutathione

Question 13

Glutathione is composed of 3 amino acids: [CGG]

Answer 13

1. Cysteine - (-SH) is responsible for detoxification
2. Glycine
3. Glutamine

Question 14

What Reactions in Phase II stated below?

• For termination of activity & detoxification
• Important route of primary amino groups
• Acetyl group supplier: Acetyl-CoA
• TE: N-acetyltransferase

Answer 14

Acetylation

Question 15

Slow acetylators (Low dose)

[EEC]

Answer 15

Europeans
Egyptians
Caucasians

Question 16

Fast acetylators (High dose)

[EA]

Answer 16

Eskimos
Asians

Question 17

What Reactions in Phase II stated below?

• Coenzyme: S-Adenosylmethionine (SAM)
• TE: Methyl transferase
• Minor pathway that leads to non-polar & inactivated compounds
• Biosynthesis of epinephrine, melatonin
• Inactivation of norepinephrine, dopamine, serotonin, histamine

Answer 17

Methylation

Question 18

When orally administered drugs are extensively metabolized before reaching the systemic circulation

Answer 18

First-Pass Metabolism / Pre-systemic metabolism