EXAM 2 - Functional Groups in Drug Molecules (part 2) Flashcards
Describe amines and their properties.
Key interactions:
Role for solubility:
Metabolism:
Significant acid-base:
Chemical reactivity:
-
Characterized by what the nitrogen is bound to.
(primary amine - N bound to one carbon)
Key interactions: H-bond acceptor or donor
(donor - as long as there is a hydrogen bound to it)
Role for solubility: increase water solubility (H-bonding)
Metabolism: complex; mainly oxidation (replace amine with oxygen)
Significant acid-base: weak base (significantly ionized at ph 7)
Chemical reactivity: reacts as nucleophiles
Why are anilines less basic than ordinary amines?
Anilines are less basic because of resonance
- the lone pair of electrons on the nitrogen is not available to interact with the acids (ring structure) because they are delocalized
A. Secondary; Hydrogen bond donating AND accepting
Ethers and Acetals Overview
Key interactions:
Role for solubility:
Metabolism:
Significant acid-base:
Chemical reactivity:
Key interactions: H-bond acceptors at oxygen lone pair, dipole interactions
Role for solubility: slightly increase water solubility
Metabolism: very little if stable
Significant acid-base: none
Chemical reactivity:
* hemiacetal - very unstable; reversible (can convert to aldehyde or alcohol)
* acetal - stable; reversible (can convert to aldehyde or alcohol)
* ethers - very stable; not prone to nucleophilic attack
What are epoxides?
A special type of ether
* highly strained
* very prone to ring opening
* very electrophilic
What makes a hemiacetal? hemiketal?
Hemiacetal - aldehyde attached to an alcohol
Hemiketal - ketone attached to an alcohol
* Only stable in cyclic systems
D. 1= hemiacetal, 2 = ketal, 3 = acetal
Draw an acetal group.
Draw a ketal group.
Draw a hemiacetal.
Draw a hemiketal.
Carbonyl derivatives overview
Key interactions:
Role for solubility:
Metabolism:
Significant acid-base:
Chemical reactivity:
Key interactions: H-bond acceptor at carbonyl oxygen, donor only with amide N-H, dipole-dipole interactions
Role for solubility: increases water solubility
Metabolism: reduction or hydrolysis
Significant acid-base: slightly basic
Chemical reactivity: fairly reactive toward nucleophillic attack bc of electrophilic carbonyl carbon
How does the electrophilicity of carbonyl carbon change depending on funcitonal groups?
O is nucleophilic and C is electrophilic
Withdrawing groups on C -
* increase electrophilicity of carbonyl carbon
* decrease nucleophilicity of O
Donor groups on C -
* decrease electrophilicity on C
* increase nucleophilicity of O
Are aldehydes usually found in drugs?
No. They are rare in drugs
* very sensitive to oxidation
Are ketones rare?
Are they stable?
Ketones are very common in drugs and are very stable.
Draw an ester.
What are prodrugs?
Inactive until they are converted to active drugs in the body.
* must make sure prodrugs must be efficiently converted in the body
* liberated groups must be non-toxic
What problems can prodrugs be used to target?
- solubility
- absorption and distribution
- instability
- prolonged release
- toxicity
- patient accessibility
What is a very common prodrug?
Esters
* can undergo hydrolysis
* releases alcohol or carboxylic acid
* result: dramatically change key physicochemical properties
Esters are acylating agents for…
Salicyclic acid
* prodrug for salicyclic acid (very toxic in the body)
C. Prone to hydrolysis
