Sleep Disorders Med Chem Flashcards
What is the name of the functional group outlined in red in Zolpidem (Ambien)?
A. Imidazotetrazole
B. Imidazoline
C. Imidazopyridine
D. Imidazopyrazine
C. Imidazopyradine
If you look at the structures provided in the picture below the:
Imidazole on the left is a 5-member ring with 2 nitrogens.
The group on the right is a Pyradine (Pyr=double bond, Dine=One nitrogen)
When they are both combinded it becomes ImidazoPyradine.
Which of these statments comparing Benzodiazepines and Non-Benzodiazepine GABAA Agonists is true? (Select All)
A. Both bind at the same allosteric sites and increase GABA A interaction with the receptor.
B. Both classes yield multiple active metabolites that lead to cumulative effects.
C. Most Non-BZD medications yield inactive metabolites while BZDs typically yield active metabolites
D. BZDs and Non-BZDs are structurally similar to each other and act at different allosteric sites on GABAA receptors.
E. BZDs and Non-BZDs are structurally different to each other and act at different allosteric sites on GABAA receptors.
C. Most Non-BZD medications yield inactive metabolites while BZDs typically yield active metabolites
E. BZDs and Non-BZDs are structurally different to each other and act at different allosteric sites on GABAA receptors.
The bioavailability of Zolpidem (Ambien) is ___ due to its ___ lipophilicity.
A. High, Low
B. Low, High
C. High. High
D. Low, Low
C. High, High
What is the name of the core structure in the medication Zaleplon (Sonata)?
A. Imidazopyradine
B. Zoleperidine
C. Pyrazolopyrimidine
D. Pyrazolamine
C. Pyrazolopyrimidine
The structure consists of a Pyrazole (smaller ring containing two nitrogens) and a Pyrimidine (larger ring containing two nitrogens. They both share one nitrogen but in the picture provided you can see the structures of pyrimidine (left) and Pyrazole (Right)
T/F
Zaleplon (Sonata) is a Non-BZD GABAA Agonist that has a rapid onset of action
T
What is the name of the enzyme that Zaleplon (Sonata) uses to convert the active drug to the 5-Oxozaleplon metabolite?
A. Aldehyde Dehydrogenase
B. Aldehyde Oxidase
C. Aldehyde Reductase
D. Aldehyde Hydroxylase
B. Aldehyde Oxidase
What is true regarding the metabolites of Zaleplon? (Sonata)
A. They are completely inactive
B. They are completely active
C. They are more active than the parent drug Zaleplon
D. They are weakly-active-to-inactive
D. They are weakly-active-to-inactive
Eszopiclone (Lunesta) is the ___ Isomer of the racemic mixture Zopiclone.
A. R
B. S
B. S-Isomer
Since it is the prefered isomer it is called the eutomer. Also known as S-Zopiclone
What is the name of the core structure in Eszopiclone?
A. Imidazopyridine
B. Cyclopyrrolone
C. Pyrazolopyrimidine
D. Pyrazolamine
B. Cyclopyrrolone
The only way I can think of memorizing this functional group is that cyclopyrrolone sounds similar to piclone
What would you expect to see in a patient that smokes while taking Eszopiclone (lunesta)?
A. There would be more of 1A2 metabolite (left) produced
B. There would be more of 3A4 metabolite (right) produced
C. There would be less of 1A2 metabolite (left) produced
D. There would be less of the 3A4 metabolite (right) produced
A. There would be more of 1A2 metabolite (left) produced
Which of the following statements is true regarding the metabolites Eszopiclone (Lunesta)?
A. The CYP1A2 metabolite is inactive and the CYP3A4 metabolite is weakly-active
B. The CYP1A2 metabolite is weakly-active and the CYP3A4 metabolite is inactive
C. The CYP1A2 and CYP3A4 metabolites are both inactive
D. The CYP1A2 and CYP3A4 metabolites are both weakly-active.
A. The CYP1A2 metabolite is inactive and the CYP3A4 metabolite is weakly-active
Why are barbituates not used as commonly as other agents?
A. They are more expensive agents with larger therapeutic index
B. They are associated with increased hepatotoxicity in comparison to newer agents on the market
C. They are associated with a more narrow therapeutic index and higher rates of abuse and CNS depression.
D. None of the above
C. They are associated with a more narrow therapeutic index and higher rates of abuse and CNS depression.
What is the name of the core structure in all barbituate mdications?
A. Barbinaric Acid
B. Barorteric Acid
C. Butryoteric Acid
D. Barbituric acid
D. Barbituric acid
What is true regarding the Barbituric acid core structure in Barbiturates medications?
A. Only exhibits activity when it undergoes structural modification
B. Exhibits activity even when unmodified
C. Enables the medication to act as a base
D. None of the above
A. Only exhibits activity when it undergoes structural modification
What is the MOA of barbituates?
A. Allosterically bind to GABA receptors and increase receptor affinity for GABA
B. Block cholinesterases and prevent the breakdown of ACh
C. Facilitate Cl- conduction even in the absence of GABA
D. Opens calcium channels and allows a higher outflow of secretory vesicles and neurotransmitter.
C. Facilitate Cl- conduction even in the absence of GABA
This statement basically means that barbituates will open Cl- channels without the need of GABA.
Regarding the SAR or Barbituates, adding R groups on the 5th carbon or the Nitrogen will ___ lipophilicity of the molecule.
A. Decrease
B. Increase
B. Increase
The NH group on Barbiturates allows it to act as a weak ___.
A. Acid
B. Base
A. Acid
Look at slide 9 in sleep med chem to see pH facts
Phenobarbital (Luminal) was obtained from the anticonvulsant Mephobarbital through the process of___.
A. O-Demethylation
B. N-Methylation
C. N-Acetylation
D. N-Demethylation
D. N-Demethylation
What type of metabolism does phenobarbital (Luminal) undergo in order to be deactivated?
A. Sulfation
B. OH-Oxidation
C. O-Glucuronidation
D. O-Methylation
C. O-Glucuronidation
The medications Amobarbital and Butabarbital contain large alkyl side chains. Deactivation of these medications involves these side chains in a process called___.
A. Reduction
B. Omega Reduction (w)
C. Oxidation
D. Omega Oxidation (w)
D. Omega Oxidation
Omega meaning an area near the last carbon (omega,w) that is oxidized.
Amobarbital undergoes ___ oxidation and Butabarbital undergoes ___ oxdiation. The areas of oxidation are depicted by where the red arrows are.
A. w, w-1
B. w-1, w-2
C. w-2, w-3
D. w-4, w-5
B. w-1, w-2
Judging by the red arrow on Secobarbital, what type of metabolism do you expect it to undergo?
A. W-1 reduction
B. W-1 oxidation
C. W-2 reduction
D. W-2 oxidation
B. W-1 Oxidation
Secobarbital can undergo a unique type of metabolism known as ___ that yields a ___ metabolite.
A. Olefinic Reduction, Gem Diol
B. Olefinic Oxidation, Gem Diol
C. Olefinic Oxidation, Vicinal Diol
D. Olefinic Reduction, Vicinal Diol
C. Olefinic Oxidation, Vicinal Diol
When a double bond is oxidized and two carbons adjacent to one another are hydroxylated it is called a Vicinal Diol. However when one carbon has two hydroxyl groups on it at one time it is called a Gem Diol
Regarding the SAR of Barbiturates, adding a(n)___group to the R1 position on the nitrogen will ___ lipophilicity.
A. Sulfur, Increase
B. Chlorine, Decrease
C. Alkyl, Increase
D. Nitrogen, Decrease
C. Alkyl, Increase
What happens to the onset and DOA?
quick onset and shorter DOA
Regarding the SAR of the Barbiturates, replacing the O group on the ring with a ___ will ___ lipophilicity.
A. Sulfur, Increase
B. Nitrogen, Decrease
C. Chlorine, Increase
D. Fluorine, Decrease
A. Sulfur, Increase
For some reason adding the sulfur and increasing lipophilicity only gives it a faster onset
Also know that the 5,5 disubstitutions will impact the activity and DOA of the drug molecule as well
One of the main modifications done to melatonin in the production of Ramelteon was changing the ___ in melatonin to an ___.
A. Indole, Indane
B. Pyrazole, Pyrazine
C. Pyridine, Piperidine
D. Imidazole, Imidazane
A. Indole, Indane
In the structural modifcation from Melatonin to Ramelteon, the methoxy group of melatonin became a ___ group in Ramelteon.
A. Furan
B. Constrained
C. Constrained ester
D. Free ester
B. Constrained
The group is considered constrained now because it loses its ability to rotate freely like it could in its methoxy form.
When looking at the two isomers of Ramelteon, which isomer is the more-active S isomer?
A. Blue
B. Red
A. Blue
Just remember the oxygen that is pointing down is the one that is the more potent S-Isomer
Regarding the metabolites of Ramelteon, which of the following statements is true? (Select All)
A. The metabolite that is produced from CYP3A4 contains a new cyclized-ester group.
B. The metabolite that is generated by enzyme CYP1A2 is an active metabolite.
C. Both enzymes CYP1A2 and CYP3A4 produce active metabolites of Ramelteon
D. The Alkyl-OH metabolite produced by 1A2 is the major and only active metabolite of Ramelteon.
A. The metabolite that is produced from CYP3A4 contains a new cyclized-ester group.
B. The metabolite that is generated by enzyme CYP1A2 is an active metabolite.
D. The Alkyl-OH metabolite produced by 1A2 is the major and only active metabolite of Ramelteon.
