Med-Chem Sedatives & Hypnotics

Count and Label the general structure of the Benzodiazepine Ring

clockwise, skip the occupied carbon

What functional group is the seven-membered ring?

iminolactam

What class of BZDs is this?

Class B (triazolo)

Properties of Class B Benzodiazepines

Short half life <6h; Inactive metabolites; Imidazole or triazolo ring

What class of BZDs is this?

Class A

What are the properties of Class A BZDs?

Long-Intermediate action; azepam; active metabolites

generic (Brand); duration

Estazolam (ProSom); Short (Class B)

generic (Brand); duration

Chlordiazepoxide (Librium); Long

generic (Brand); duration

Diazepam (Valium); Long

generic (Brand); duration

Clorazepate (Tranxene); Long

generic (Brand); duration

Flurazepam (Dalmane); Long

generic (Brand); duration

Quazepam (Doral); Long

generic (Brand); duration

Lorazepam (Ativan); Intermediate (Class A)

generic (Brand); duration

Oxazepam (Serax); Intermediate (Class A)

generic (Brand); duration

Alprazolam (Xanax); Short (Class B)

What is this metabolite, its half life, and metabolism?

N-desalkylflurazepam (major active metabolite of quazepam and flurazepam) (t = 50h) before oxidation followed by Phase II glucouronide conjugation and excretion

What is this metabolite, its half life, and metabolism?

Nordazepam (major active metabolite of diazepam, clorazepate, and chlordiazepoxide); (t = 50h) before oxidation followed by Phase II glucouronide conjugation and excretion

Identify drug and functional groups

Zolpidem (Ambien); imidazopyridine (imidazole + pyridine)

Identify drug and functional groups

Eszoplicone - the active S isomer (pyrrolopyrazine = pyrrole + pyrazine)

Identify drug and functional groups

Zaleplon (pyrazolopyrimidine = pyrazole + pyrimidine); cyano group

Identify drug and functional groups

Melatonin (indole)

Identify drug and functional groups

ramelteon (indane)

Identify drug, duration, and potency

Secobarbital; Short duration, high potency. Only allylic 5a

Identify drug, duration, and potency

Pentobarbital; Short duration, high potency.

Identify drug, duration, and potency

Amnobarbital; Medium duration (6-8h), Medium potency

Identify drug, duration, and potency

Butabarbital; Medium duration (6-8h), Medium potency

Identify drug, duration, and potency

Phenobarbital: Long duration (12h>), low potency

How do 5b subsitutions affect pharmacology of barbituric acid

Longer chain, more carbons, more branches = more lipophilic = more potency and increased metabolism.