Structure Activity Relationships, Pharmacophore, Potency, Therapeutic Activity Flashcards
What is a pharmacophore?
The smallest part of the drug that exhibits its desired biological activity
True or false: Methadone and morphine have the same pharmacophore
True
What do other parts attached to the pharmacophore help determine?
Intensity and secondary properties Pharmacokinetic properties (ADMET)
True or false: Desired pharmacological activity of a drug molecule means there is no degree of toxicity
False. Always some degree of toxicity
What is a toxicophore?
The part of the molecule responsible for its toxic effect
Sometimes toxicophores emerge via metabolism of a molecule. Which enzyme is often responsible?
Cytochrome P450 (oxidative metabolism)
What functional group often acts as a toxicophore? How is its toxic effect exhibited?
Nitro (NO2). It is reduced to nitroso then hydroxylamine, which can attach to DNA and cell proteins, altering them
Which enantiomer of thalidomide exhibits toxicity and how?
S-enantiomer. The glutarimide portion is the toxicophore
________-_________ relationships explore relationship between a molecule’s biological activity and the 3d structure
Structure-activity
What are 4 structural modifications that can change a compound’s pharmacodynamic properties?
Alkyl substituent modifications
Structural simplifications
Rigidification
Conformational blocker
Thiazide diuretics are weakly (acidic/basic)
Weakly acidic
trifluoromethyl-substituted diuretics are more lipid soluble and have a (shorter/longer) duration of action than their chloro-substituted analogs
Longer
True or false: Acidic protons help form a water-soluble sodium salt that can be used for intravenous administration of the diuretics
True
True or false: “Rule of five” by Ing states that there should be more than five atoms between the cationic nitrogen and the terminal hydrogen atom for optimal mACh binding and stimulation
False
True or false: Lengthening the chain of mACh analogues increases activity
False
