Drugs and Chirality Flashcards
Week 1
What is the composition of a pharmaceutical and its %?
AP(8-10), fillers (80%), disintegration (, disaggregation and dissolution (10%)
what are pharmaceuticals?
Solids, liquids and gas formulations that treat, cure and prevent disease
What is the basis of many drugs and why?
carbon, has 4 valence electrons so can have covalent bonding.
What are the properties of API?
Carbon/Hydrogen backbone with functional groups that create a biologically active substance.
What is the role of functional groups?
Determines the role of action of the pharmaceutical through binding and the given properties.
What properties do functiocal groups determine?
Chemical (acid/base, solubility, reactivity) , physical (something that is measured) and chemical stability.
What is drug likeliness?
Predictor of drug’s biological activeness.
what is needed for water solubility?
H bonding and ion-dipole interaction. AThe drug must have polar functional groups (hydrophobic and philic molecules)
what does drug likeliness depend on?
water solubility and binding
What is Lipinski’s rule?
HBD less than 5, HBA less than 10, MM less than 500 and coefficient Log P less than 5.
What is needed in a H bond?
a polarised H-X bond where the H is sharing the electron and hetero atom with lone pair of electrons (negative)
What is a dipole-dipole bond?
attraction between positive and negative poles as electrons are shared and tried to be pulled to each other.
what creates a greater polarity?
Greater difference in electronegativity
when is EN considered a Non-Polar Covalent
EN between 0.2 and 0.4
when is EN considered a Polar Covalent
En between 0.6 and 2.0
when is EN considered Ionic?
2.2-3.2
What makes something more polar in water?
Polar bonds
What are the stages of drug action?
absorption, distribution to target, binding at target, metabolism and excretion.
What are the properties that are crucial to drug binding ability?
3D Shape and Polarisation of functional groups
what are the crucial properties of drug absorption?
Hydrophobicity (across cell membrane) and hydrophilicity (through blood)
What are the two types of enzyme inhibitors?
reversible and irreversible
What is the geometry of a molecule with single, double and triple bond?
tetrahedral, trigonal planar and linear
what are the three types of constitutional isomers?
skeletal, functional group and positional isomers
What is a chiral centre
Carbon atom with four different functional groups that is not superimposable on its mirror image.
How do you determine chilarity?
- find centre
- prioritise according to atomic number
- oriented so lowest priority number is going away from you
- determine of r or s
what does r and s mean respectively?
r= clockwise
s= anticlockwise
What are enantiomers?
Non superimpsobale mirror images
What is chiral recognition?
enzymes that are drug targets are chiral and so usually only occur as a single enantiomer. drugs should only recognise one.
diastereoisomers
stereoisomers that are not mirror images (differ three-dimensionally)
How do you deterine the diastereoisomers of a molecule?
reverse the chilarity of any chiral centre (not all of them though)
What does the wedge represent?
Towards me (out of the page)
What does the dotted wedge mean?
Going away from me (into the page)
What is the acronym for identifying HBA and HBD
A(acceptors)N(not)D(donors)Y(yes)
Why in lipinski’s rule can there be 10 HBA but only 5 HBA?
Because all donors are also acceptors, except for amides
What are incompatbilities?
antacids
what do antacids do?
Alter the pH of the stomach via neutralisation, ionise drugs based on the relationship of pH and pKA and affect absorption and distribution.
what is pKA?
Acid dissociation constant to the negative base log 10. Determines acids strentth
The smaller the pKa, the. … the acid
stronger
what are some antacid drugs?
Maalox, Tums and Rennie
