Introduction to Structure-Activity Relationships

Question 1

Physicochemical properties influence what properties?

Answer 1

Pharmacokinetic

Question 2

What is SAR?

Answer 2

Systematic modifications of molecules by altering the functional groups and determine how these modifications affect the biological activity.

Question 3

In 1869, Brown and Fraser conducted what structure-activity relationship study?

Answer 3

Turning tertiary amines into quaternary ammonium(charge independent of pH) compounds to (1) see if they had a muscle relaxant effect and (2) see if molecular structure influenced the biological effect.

Question 4

What was the conclusion of the Early SAR studies?

Answer 4

Acetacholine act as agonist while N-Methylmorphine, N-methylnicotine, N-methylatropine, and Tubocurarine all act as an antagonist. So not all quaternary ammonium compounds are muscle relaxants. However, it is true that molecular structure influences the biological activity.

Question 5

What does Acetylcholine (a muscle relaxant) look like?

Answer 5

Smaller size, lower molecular weight, ester group, quaternary amine.

Question 6

What is an agonist?

Answer 6

Interacts with the receptor, has affinity.

Produces a biological response, efficacy or intrinsic activity.

Question 7

What is an antagonist?

Answer 7

Interacts with the receptor, has affinity.

Does not produce a response are classified as antagonists.

Question 8

Molecules that block the effects of natural neurotransmitter?

Answer 8

They are generally larger in size than the native compound

Question 9

What is a example of a physical chemical property?

Answer 9

stereochemistry
Acid-base properties
Water solubility
Partition coefficient

Question 10

What do physicochemical properties influence?

Answer 10

Pharmacokinetic properties: Absorption, distribution, metabolism, excretion, and toxicity

Question 11

Each functional group contributes to overall physicochemical properties. T/F

Answer 11

True

Question 12

What is a Bronsted-Lower Acid and Base?

Answer 12

Bronsted-Lowry Acid - Proton donor

Bronsted-Lowry Base - Proton acceptor

Question 13

How is pKa related to the strength of the acid?

Answer 13

the lower the pKa the stronger the acid.

Question 14

How does an electron withdrawing group and electron donating group affect acidity?

Answer 14

Electron withdrawing groups increase acidity

Electron donating groups decrease acidity

Question 15

Resonance increases or decreases acidity?

Answer 15

Increases acidity

Question 16

Rank N-Arylsulfonamide, Alkylthiol, Sulfonamide, Imide, and Thiophenol in order of increasing acidity.

Answer 16

Sulfonamide, Imide, Alkylthiol, Thiophenol, and N-Arylsulfonamide.

Question 17

What is the term that describes a molecule that can act as an acid or base.

Answer 17

amphoteric

Question 18

Rank R3N, RNH2, R2NH in order of increasing acidity.

Answer 18

R2NH, RNH2, R3NW

Question 19

Alkyls are electron donating or accepting groups?

Answer 19

Electron-donating

Question 20

Are tertiary amines less or more basic then secondary amines and why?

Answer 20

less basic because of steric effect.

Question 21

Aryl Amines are less or more basic than aliphatic amines?

Answer 21

Less basic