Structure Based Therapeutic Evaluations Flashcards
Crum-Brown and Fraser incorrectly hypothesized that muscle relaxant activity requires a __________ _________ group within the structure
Quaternary ammonium
True or false: Molecular structure does not influence biologic activity of a drug
False
True or false: Each chemical group provides one biological action
False
Ehrlich developed the concept of functional groups of drugs exerting their effect by binding with _____ ________
drug receptors
Ing hypothesized that ______ and _______ act at the same receptor
Acetylcholine and tubocurarine
What explains the blocking effect of tubocurarine?
It is a large molecule that partly occupies the receptor, preventing acetylcholine from interacting with the receptor
True or false: Different functional groups can yield similar physical physicochemical properties
True
PABA reverses the _______ action of sulfanilamide
Antibacterial
Three physicochemical properties that affect relative fit
3d spatial orientation
Functional group shape and size
Acid-base chemistry and related ionization
What is a prodrug?
Compounds that are metabolized into their active form once inside the body
What are reasons prodrugs are used?
Poor oral bioavailability due to poor GI absorption
Too hydrophobic to be dissolved in aqueous and given intravenously
Chemical instability
Unacceptable odor/taste
GI irritation
Etc.
True or false: Most common prodrugs are ethers
False: Esters
Esters are readily hydrolyzed by what?
Ubiquitous esterases
True or false: Enalapril must be converted to its active form enalaprilat to inhibit ACE
True
What is the active functional group of Enalaprilate?
Carboxylic acid. It is hydrolyzed from its ester form
What are stereoisomers?
Same # and kinds of bonds, same atoms, same arrangement, DIFFERENT 3D STRUCTURES
Enantiomers are pairs of molecules for which the 3D arrangement of atoms are ______________ mirror images
Nonsuperimposable
True or false: Diastereomers exhibit the same melting point, boiling point, solubility, and chromatographic behavior.
False
The physicochemical properties of a drug depend on what two factors?
Functional groups on the molecule
Spatial arrangement of the atoms
Approximately one in how many drugs currently on the market is some type of isomeric mixture?
1 out of 4
Differences in what between racemates lead to adverse effects and toxicity?
PK and PD
A racemate is indicated by what symbol?
±
What is the Cahn, Ingold and Prelog system?
The R & S name system that ranks atoms attached to the chiral center in order of atomic number
True or false: Enantiomers can exhibit different biologic actions
True
Easson-Stedman Hypothesis
More potent enantiomer must be involved in a minimum of three intermolecular interactions with the surface of the biologic target and the less potent enantiomer with only two sites
Diastereomers are molecules that are nonsuperimposable, _______ images
Nonmirror
What conditions can result in diastereomer formation?
More than 1 chiral center
Double bonds
Ring systems
How do conformational isomers form?
Rotation occurs around 1 bond
Explain the difference between anti/staggered conformation and Gauche/skew conformation
Anti- bond angles between groups are 180
Gauche- more stacked conformation of atoms
