Structural Properties 4 Lecture

Question 1

Define bioisosteres

Answer 1

Substituents or functional groups that have similar chemical and/or physical properties and which produce broadly similar biological properties
- Lead compound optimization approach

Question 2

Biososterism is used for what?

Answer 2

Reduce toxicity
Increase metabolic stability
Improve solubility and or ADME properties
Provide greater target selectivity
Simplify synthesis
Allow compounds based on fragment hopping to be patented

Question 3

What parameters where effected?

Answer 3

Size (radius)
Conformation (cis vs trans)
EDG EWG and resonance effects
Polarization
H bond forming capacity
pKa
Solubility
Hydrophobicity
Reactivity
Stability

Question 4

What are two major forms of biososteres?

Answer 4

Classical and Non-classical

Question 5

What are classical biososteres?

Answer 5

Monovalent
Divalent (take an ether in the middle of the drug molecule and replace it with an NH- proton donor)
Trivalent (no H on it but has 3 bonds)
Tetravalent (get rid of C, put N in there, potential to ionize and ability to HBA)

Question 6

Define antibacterials?

Answer 6

Aromatic group may be replaced by heterocyclic aromatics to produce active and resistance free compounds

Question 7

What are non-classical bioisosteres?

Answer 7

Exchangeable groups
Cyclic vs non-cyclic
Do not rigidly comply with the steric and electronic properties

Question 8

What is CF3?

Answer 8

Non-classical bioisostere for a methyl group due to size but has widely different electronic properties

Question 9

Define Stereochemistry

Answer 9

the specific spatial arrangement of a compounds functional groups and carbon backbone in 3D space

Question 10

How does stereochemistry play into pharmacological properties of drugs

Answer 10

Any changes will alter the interactions of functional groups
Isomers can have different properties and can differ in pKa, logP
- Both alter pharmacological properties of the drugs

Question 11

What are the three main stereochemical factors influencing the pharmacological profile?

Answer 11

Conformational isomers
Geometrical isomers
Optical isomers

Question 12

Define conformational isomers

Answer 12

Non-identical spatial arrangement of atoms and groups in a molecule that result from rotating around a single bond
- Almost all drugs have more than one conformation and can bind to different receptors

Question 13

Define geometric isomers

Answer 13

Occurs as a result of restricted rotation about a chemical bond owing to double bonds or a rigid ring system in the molecule
Not mirror images; different physicochemical properties and pharamacological activity bc different distance between functional groups
General do not fit in the same receptor

Question 14

When do axial and equitorial positions appear?

Answer 14

6 membered rings do not exist as hexagons

• Adopt chair conformation to minimize angles and torsional strain
• -> substituents occupy orientations

Question 15

Define optical isomers

Answer 15

Compounds that contain at least one chiral carbon atoms

Question 16

Define dextrorotatory

Answer 16

(+)

Isomer rotates light to the right (clockwise)

Question 17

Define levorotatory

Answer 17

(-)

isomer rotates light to the left (counterclockwise)

Question 18

Dextrorotary and levorortatory tell you what?

Answer 18

light rotations

NOTHING about chemical structure

Question 19

Define enantiomers

Answer 19

One of two steroisomers that are non-superimposable mirror images of each other
- Can have large differences in potency, receptor fit, activity, etc
Change in one position (1 is R, 1 is S)

Question 20

Define eutomer

Answer 20

Most active isomer delivering the desired activity

Question 21

Define diastereomers

Answer 21

Molecules that are non-superimposable AND non-mirror images due to containing more than one chiral carbon
- Different physicochemical properties –> different biological activities

Question 22

Define racemates

Answer 22

A mixture of the two left and right handed optical isomers in equal amounts (R and S)
- Chemical synthesis or in vitro

Question 23

What is ibuprofen

Answer 23

NSAID
Sold as a racemate of R and S forms
S acts within 15 minutes and has 50% reduced side effects than the R isomer

Question 24

What is the International Union of Pure & Applied Chemistry (IUPAC) name?

Answer 24

The chemical name of the active pharmaceutical ingredient compound

• Leaves no room for ambiguity
• Often too long to mess with

Question 25

What is the International Nonproprietary Name (INN) or generic name?

Answer 25

US Adopted Name used to ID the same active pharmaceutical ingredient over a number of products

Question 26

What is the brand name?

Answer 26

Owned by the producing company