Azepines are seven‑membered nitrogen heterocycles with growing importance in medicinal chemistry and pharmacology. This concise introduction focuses on medicinal uses of azepines, azepine derivatives, structure‑activity relationships (SAR), pharmacokinetics, metabolism, toxicity and drug‑design considerations relevant to B.Pharm students. Emphasis is placed on benzazepine scaffolds, synthetic strategies (ring expansion and intramolecular cyclizations), CNS and enzyme‑targeted applications, formulation as salts, and analytical methods (NMR, MS, IR) for characterization. Keywords: azepines, benzazepine, heterocycle, medicinal chemistry, SAR, pharmacology, metabolism, adverse effects, B.Pharm, MCQs. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. What is an azepine?
- A heterocyclic compound containing a six‑membered ring with one nitrogen
- A seven‑membered heterocyclic ring containing one nitrogen atom
- A five‑membered sulfur heterocycle
- A bicyclic aromatic hydrocarbon
Correct Answer: A seven‑membered heterocyclic ring containing one nitrogen atom
Q2. How many ring atoms are present in an azepine?
- Five
- Six
- Seven
- Eight
Correct Answer: Seven
Q3. What does the prefix “benzo” in benzazepine indicate?
- Presence of an additional nitrogen in the ring
- Fusion of an azepine ring with a benzene ring
- Oxidation of the azepine nitrogen
- Reduction of the azepine double bonds
Correct Answer: Fusion of an azepine ring with a benzene ring
Q4. Which heterocycle has two nitrogen atoms in a seven‑membered ring?
- Azepine
- Diazepine
- Oxepine
- Pyridine
Correct Answer: Diazepine
Q5. In medicinal chemistry, azepine scaffolds are most commonly used as templates for which therapeutic area?
- Topical antifungals exclusively
- CNS‑active agents and receptor ligands
- Dietary supplements
- Radiocontrast agents only
Correct Answer: CNS‑active agents and receptor ligands
Q6. Which synthetic strategies are commonly used to construct azepine rings?
- Ring expansion and intramolecular cyclization
- Simple hydrogenation of benzene
- Sandmeyer reaction only
- Direct nucleophilic substitution on benzene
Correct Answer: Ring expansion and intramolecular cyclization
Q7. Protonation of azepines most commonly occurs at which site?
- Carbonyl oxygen
- Nitrogen lone pair on the azepine ring
- Allylic carbon far from the ring
- Peripheral aromatic ring only
Correct Answer: Nitrogen lone pair on the azepine ring
Q8. Which analytical technique is most informative for confirming the molecular mass of an azepine derivative?
- NMR spectroscopy
- Mass spectrometry (MS)
- Thin layer chromatography (TLC)
- Optical rotation measurement
Correct Answer: Mass spectrometry (MS)
Q9. What is a key reason medicinal chemists fuse azepine rings with aromatic rings (e.g., benzazepine)?
- To increase molecular flexibility dramatically
- To reduce planarity and lower potency
- To increase rigidity and improve target affinity
- To remove all heteroatom functionality
Correct Answer: To increase rigidity and improve target affinity
Q10. Which organ primarily metabolizes azepine‑based drugs in humans?
- Kidneys
- Liver
- Spleen
- Skin
Correct Answer: Liver
Q11. Which enzyme family is most often involved in Phase I metabolism of azepine derivatives?
- Cytochrome P450 (CYP) enzymes
- DNA polymerases
- Amylases
- Kinases
Correct Answer: Cytochrome P450 (CYP) enzymes
Q12. Formulating azepine drugs as salts is mainly done to improve which property?
- Color of the tablet
- Solubility and bioavailability
- Taste masking only
- Radioactivity
Correct Answer: Solubility and bioavailability
Q13. A common adverse effect to monitor with novel azepine candidates during preclinical testing is:
- Hepatotoxicity and CNS effects
- Immediate tooth decay
- Permanent hair growth
- Loss of fingernails
Correct Answer: Hepatotoxicity and CNS effects
Q14. Which spectroscopic method provides detailed information about the proton and carbon environment in azepine molecules?
- Infrared (IR) spectroscopy
- Nuclear Magnetic Resonance (NMR) spectroscopy
- Ultraviolet visible (UV‑Vis) only
- Polarimetry only
Correct Answer: Nuclear Magnetic Resonance (NMR) spectroscopy
Q15. Which statement about azepine ring flexibility is correct?
- Seven‑membered azepine rings are generally more conformationally flexible than six‑membered rings
- Azepine rings are always rigid and planar
- Azepine rings are less flexible than five‑membered rings
- Azepine rings cannot adopt multiple conformations
Correct Answer: Seven‑membered azepine rings are generally more conformationally flexible than six‑membered rings
Q16. In structure‑activity relationship (SAR) studies of azepines, what is a primary goal?
- To increase molecular weight without regard to activity
- To correlate structural changes with changes in biological activity and optimize potency
- To remove all heteroatoms from the scaffold
- To avoid any in vitro testing
Correct Answer: To correlate structural changes with changes in biological activity and optimize potency
Q17. Which phase II metabolic reaction commonly increases the water solubility of azepine metabolites?
- Hydrogenation
- Glucuronidation
- Alkylation with long chains
- Polymerization
Correct Answer: Glucuronidation
Q18. When designing azepine derivatives for CNS activity, which physicochemical property is most critical for blood‑brain barrier penetration?
- High molecular weight (>800 Da)
- Appropriate lipophilicity (balanced logP)
- Extremely high polar surface area (>200 Ų)
- Permanent positive charge in all conditions
Correct Answer: Appropriate lipophilicity (balanced logP)
Q19. Which modification is commonly used to reduce metabolic clearance of azepine leads?
- Introduction of metabolically labile long‑chain esters
- Introduction of electron‑withdrawing substituents at metabolically vulnerable positions
- Removal of all aromatic rings
- Conversion to highly polar zwitterions without safety testing
Correct Answer: Introduction of electron‑withdrawing substituents at metabolically vulnerable positions
Q20. What is a practical benefit of fusing an azepine to another aromatic ring in drug design?
- It always reduces potency
- It increases molecular rigidity and can improve target selectivity
- It eliminates the need for ADME studies
- It prevents any metabolism
Correct Answer: It increases molecular rigidity and can improve target selectivity
Q21. Which of the following is a general laboratory method to confirm the connectivity of atoms in an azepine scaffold?
- 2D NMR experiments (COSY, HSQC, HMBC)
- Melting point alone
- Only UV‑Vis spectroscopy
- Visual color inspection
Correct Answer: 2D NMR experiments (COSY, HSQC, HMBC)
Q22. Which property of azepine derivatives often determines oral bioavailability?
- LogP, pKa and metabolic stability
- Color and odor only
- Presence of radioactive isotopes only
- Number of chiral centers only
Correct Answer: LogP, pKa and metabolic stability
Q23. Which technique is most suitable for elucidating the solid‑state three‑dimensional arrangement of an azepine crystal?
- Gas chromatography (GC)
- X‑ray crystallography
- pH titration
- Paper chromatography
Correct Answer: X‑ray crystallography
Q24. Which change to an azepine nitrogen typically increases lipophilicity and membrane permeability?
- Oxidation to an N‑oxide
- N‑alkylation to introduce a lipophilic substituent
- Attachment of a sulfate group
- Conversion to a quaternary ammonium salt
Correct Answer: N‑alkylation to introduce a lipophilic substituent
Q25. Which statement about azepine basicity relative to aliphatic amines is generally correct?
- Azepine nitrogen is typically more basic than simple tertiary aliphatic amines
- Azepine nitrogen is non‑basic and cannot be protonated
- Azepine nitrogen is often less basic than aliphatic amines due to ring conjugation and hybridization
- Azepine nitrogen always has a pKa > 14
Correct Answer: Azepine nitrogen is often less basic than aliphatic amines due to ring conjugation and hybridization
Q26. Which modification would most likely improve aqueous solubility of an azepine drug candidate?
- Conversion to a water‑soluble salt (e.g., hydrochloride)
- Adding a long lipophilic alkyl chain
- Removing all polar groups
- Crystallizing as a free base exclusively
Correct Answer: Conversion to a water‑soluble salt (e.g., hydrochloride)
Q27. Which heterocyclic analogue contains three nitrogen atoms in a seven‑membered ring?
- Azepine
- Triazepine
- Oxepine
- Pyrrole
Correct Answer: Triazepine
Q28. Which type of in vitro study is typically used to assess receptor binding affinity of azepine derivatives?
- Receptor binding assays using radioligand or fluorescence techniques
- Basic solubility test only
- pH stability test only
- Gel electrophoresis of DNA
Correct Answer: Receptor binding assays using radioligand or fluorescence techniques
Q29. Which computational method is commonly used to predict binding modes of azepine ligands to targets?
- Molecular docking and molecular dynamics simulations
- Simple boiling point estimation
- Gravimetric analysis
- UV index forecasting
Correct Answer: Molecular docking and molecular dynamics simulations
Q30. Which structural change often reduces the rate of oxidative metabolism on an aromatic azepine substituent?
- Introduction of small electron‑donating methyl groups directly at the metabolized carbon
- Introduction of electron‑withdrawing fluorine atoms at metabolically vulnerable positions
- Adding multiple susceptible benzylic hydrogens
- Removing all heteroatoms and increasing polarity
Correct Answer: Introduction of electron‑withdrawing fluorine atoms at metabolically vulnerable positions
Q31. Which experimental assay is essential to evaluate cardiotoxic risk (e.g., QT prolongation) of new azepine molecules?
- hERG channel inhibition assay
- Starch iodine test
- Urinalysis only
- Paper chromatography
Correct Answer: hERG channel inhibition assay
Q32. Which property is directly measured by logP?
- Acid dissociation constant
- Partition coefficient between octanol and water (lipophilicity)
- Molecular weight
- UV absorbance at 280 nm
Correct Answer: Partition coefficient between octanol and water (lipophilicity)
Q33. Ring‑closing metathesis (RCM) can be applied in azepine synthesis to:
- Form seven‑membered rings from appropriate diene precursors
- Always produce five‑membered rings only
- Eliminate the need for catalysts
- Convert azepines to carbohydrates
Correct Answer: Form seven‑membered rings from appropriate diene precursors
Q34. Which IR absorption band would you most likely observe if an azepine contains an N–H group?
- A sharp band around 3200–3500 cm‑1 indicative of N–H stretching
- A band at 2200 cm‑1 only indicating triple bond
- No absorption above 1500 cm‑1
- A strong band at 6000 cm‑1
Correct Answer: A sharp band around 3200–3500 cm‑1 indicative of N–H stretching
Q35. Converting an azepine to its N‑oxide will most likely:
- Decrease polarity
- Increase polarity and alter hydrogen bonding
- Make the molecule radioactive
- Guarantee BBB penetration
Correct Answer: Increase polarity and alter hydrogen bonding
Q36. During preclinical development, which study assesses long‑term toxicity of azepine candidates in vivo?
- Acute solubility test
- Chronic toxicity studies in relevant animal species
- Thin layer chromatography only
- Single‑timepoint cell counting
Correct Answer: Chronic toxicity studies in relevant animal species
Q37. Which in vitro method helps predict metabolic stability of azepine analogs by simulating liver metabolism?
- Microsomal stability assay using liver microsomes
- Simple water miscibility test
- Paper pH strip test
- Melting point determination
Correct Answer: Microsomal stability assay using liver microsomes
Q38. What is one reason to design azepine prodrugs?
- To increase synthetic complexity only
- To improve solubility, permeability or targeted release in vivo
- To avoid regulatory requirements
- To permanently mask all activity without conversion
Correct Answer: To improve solubility, permeability or targeted release in vivo
Q39. Which descriptor is commonly used to estimate polar surface area relevant to drug absorption of azepine molecules?
- Topological polar surface area (TPSA)
- Molecular color index
- Boiling point only
- Number of aromatic rings only
Correct Answer: Topological polar surface area (TPSA)
Q40. What role does substituent pattern on an azepine ring play in target selectivity?
- Substituents have no effect on selectivity
- They modulate binding interactions, sterics and electronic properties to influence selectivity
- Only ring size matters, substituents are irrelevant
- They only affect color of the compound
Correct Answer: They modulate binding interactions, sterics and electronic properties to influence selectivity
Q41. Which in vitro assay is used to measure functional activity (agonist/antagonist) of azepine ligands at a receptor?
- Functional cell‑based assays measuring second messenger response
- Melting point test
- Simple mass balance calculations
- Paper chromatography
Correct Answer: Functional cell‑based assays measuring second messenger response
Q42. Which statement about azepine derivative patentability and novelty is important for drug development?
- Patentability requires novelty, inventive step and utility for the specific azepine scaffold
- All azepines are automatically patentable regardless of novelty
- Patents are irrelevant for medicinal chemistry
- Only natural products can be patented
Correct Answer: Patentability requires novelty, inventive step and utility for the specific azepine scaffold
Q43. Which factor most directly influences the route of administration chosen for an azepine drug?
- Solubility, stability, permeability and intended therapeutic use
- The color of the compound only
- Availability of gold packaging
- Manufacturer preference without data
Correct Answer: Solubility, stability, permeability and intended therapeutic use
Q44. In medicinal chemistry, a bioisostere is used to:
- Completely change the pharmacological target without retaining activity
- Replace a functional group with another to retain activity while improving properties
- Make the molecule larger for no reason
- Create unstable metabolites intentionally
Correct Answer: Replace a functional group with another to retain activity while improving properties
Q45. Which property is typically assessed by in silico ADMET prediction tools for azepine candidates?
- Predicted absorption, distribution, metabolism, excretion and toxicity profiles
- Only crystal habit prediction
- Exact human half‑life without experiments
- Color and taste profiles
Correct Answer: Predicted absorption, distribution, metabolism, excretion and toxicity profiles
Q46. Why is monitoring CYP‑mediated drug interactions important for azepine drugs?
- Because azepine drugs never undergo metabolism
- Because inhibition or induction of CYP enzymes can alter exposure, efficacy and toxicity
- Because CYP enzymes only affect topical creams
- Because monitoring is irrelevant after Phase I trials
Correct Answer: Because inhibition or induction of CYP enzymes can alter exposure, efficacy and toxicity
Q47. Which experimental technique helps identify metabolites formed from azepine drugs?
- LC‑MS/MS metabolite profiling
- Simple melting point analysis
- Visual inspection under a microscope
- Paper pH test only
Correct Answer: LC‑MS/MS metabolite profiling
Q48. Which structural feature often enhances target binding through hydrogen bonding in azepine ligands?
- Appropriately positioned hydrogen bond donors or acceptors such as N–H or carbonyl groups
- Large nonpolar chains only
- Absence of heteroatoms entirely
- Randomly placed heavy atoms without design
Correct Answer: Appropriately positioned hydrogen bond donors or acceptors such as N–H or carbonyl groups
Q49. What is a common goal of lead optimization for azepine drug candidates?
- To reduce potency while increasing toxicity
- To balance potency, selectivity, ADME properties and safety
- To ensure the molecule cannot be synthesized at scale
- To avoid all regulatory safety testing
Correct Answer: To balance potency, selectivity, ADME properties and safety
Q50. What is the main educational purpose of practicing MCQs on medicinal uses of azepines for B.Pharm students?
- To memorize vendor catalog numbers
- To test and reinforce understanding of structure, pharmacology, SAR, ADME and safety considerations
- To learn how to sell reagents
- To avoid reading primary literature
Correct Answer: To test and reinforce understanding of structure, pharmacology, SAR, ADME and safety considerations
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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