PMOC Pharm Chem Topic 1

Pharmaceutical Chemistry

Focused on quality aspects of medicines and aims to assure fitness for the purpose of medicinal products.

Quantitative Structure-Activity Relationships

QSAR means

Structure-Activity Relationship

Relationship of how structural features of the molecule contribute to, or take away from, the desired biologic activity.

1.Drug discovery

2.Understanding mechanisms

3.Predictive Modeling

Importance of SAR

tertiary amine groups

Many compounds containing ______ exhibited activity as

muscle relaxants when converted to quaternary ammonium compounds.

morphine

Methylation of _______ can alter its pharmacokinetic and pharmacodynamic properties, potentially leading to muscle relaxant effects similar to those of tubocurarine.

nicotine

Methylation can enhance the lipophilicity and receptor affinity, potentially converting _____ into a quaternary ammonium compound that exhibits muscle relaxant properties akin to

atropine

Methylating ________ can alter its pharmacological profile, possibly leading to muscle relaxant effects. However, it may also amplify its anticholinergic effects, which can complicate its use.

N-methylmorphine

morphine

Tubocurarine

Nicotine ——> N-methylnicotine

Atropine → methylatropine

Acetylcholine

Natural neurotransmitter and activator of muscle contraction

Loewri and Navrati

Acetylcholine discovered by:

magic bullet

Selectivity of drug action via the concept of a _____ by Ehrlich

selective toxicity

Modified by Albert into ______

d-Tubocurarine

non-depolarizing competitive antagonist at nicotinic acetylcholine receptors, causing the relaxation of skeletal muscle.

Acetylcholine

binding of two molecules to receptors on the α-β and δ-α subunits causes opening of the channel, subsequent movement of potassium through the channel is associated with a graded depolarization causing muscle contraction

Acid-Base Properties

Have a direct effect on absorption, excretion, and compatibility with other drugs in solution.

Acid

any substance capable of donating a proton

Base

any substance capable of accepting a proton

pKa 2

strong acid; conjugate base has no meaningful basic properties in water

pKa 4 to 6

weak acid; weak conjugate base

very weak acid; conjugate base getting stronger

pKa 8 to 10

essentially no acidic properties in water; strong conjugate base

pKa 12

solubility

The ______of a drug molecule in water greatly affects the routes of administration that are available, as well as its absorption, distribution, and elimination.

Hydrogen bond formation
Ionization of one or more functional groups

Factors that affect water/fat solubility

F, O, N, S, Se

strongly electronegative atoms

ortho-hydroxybenzaldehyde

Sodium Phenobarbital

Atropine Sulfate

Isomers

These are compounds with the same molecular

formula and same molecular weight but different

structural formula, this differ in physical and

chemical properties

Stereoisomers

are molecules that contain the same number and kinds of atoms, the same arrangement of bonds, but different three-dimensional structures

Chirality

the ability of a drug to exist as optically active stereoisomers or enantiomers

Individual enantiomers

_______ may not have the same pharmacokinetic and pharmacodynamic activity.

Enantiomers

______ are mirror images of each other and non-superimposable

Diastereomers

______ are not mirror images of each other and non-superimposable

Isosteres

compounds or groups of atoms having the same number and arrangement of electrons

Xanthine

Alloxanthine

Alexander Crum Brown

Thomas Richard Fraser.

Which two scientists established the foundation for the relationship between molecular structure and biologic activity?

Methylation

What chemical process can convert Morphine from an analgesic into a muscle relaxant?