Medicinal Chemistry Exam #3

What is the principle site of drug metabolism? What other sites can participate? In pregnant women?

The liver.

Intestine, lung, kidney, plasma, and skin

Placenta and Mammary glands

When a drug (nonpolar) is ingested and carried to liver aka Phase I, what reactions take place? (What three letter acronym are these considered)

Oxidation, Reduction, and Hydrolysis (The CYP’s)

A slightly polar metabolite (active/inactive/toxic) continues traveling to Phase II (can be in liver, lung, kidney, brain, etc.) what reactions can take place there? (What 3 letter acronym are these reactions classified under)

Glucuronidation, Sulfation, Acetylation, Methylation (UGT’s)

What substances affect drug metabolism?

Grapefruit Juice, St John’s Wort, Isosafrole, Safrole

What does grapefruit juice elevate?

Plasma Peak Drug Concentration (Makes it too-effective and last unhealthily longer)

Phase I Enzymes: what they attack

Oxidation: aromatic and side chain hydroxylation

Reduction: Nitroreduction, alcohol dehydrogenase

Hydrolysis: Ester and Amide hydrolysis

Demethylation: remove lone methyl

Phase II Enzymes: What they attack

Glucuronide Conjugation: ether, ester, amide

Peptide Conjugation

Methylation: N- and O- methylation

Acetylation: Making an acetyl

Sulfate Conjugation

Majority of time what carries out oxidation reactions?

Cytochromes (P450) (18 different kinds identified in humans)

What type of substituents slow down hydroxylation?

EWGs (Cl, COOH, SO2NHR, -N+R3

What type of substituents accelerate oxidation?

EDG

To be classified aromatic, how many pi-electrons must there be?

2, 6, 10, 14, 18, 22, 26, 30, etc.

When enzymatic oxidation takes place at a terminal carbon, what oxidation is that known as?

ω (Omega) oxidation

When enzymatic oxidation takes place at the carbon atom next to a terminal carbon, what type of oxidation is that?

ω-1 Oxidation