Dr. Lattman's Lectures

Question 1

Give examples of drugs which are derived from natural sources.

Answer 1

All antibiotic lead structures
Anti cancer drugs
CNS illicit use
Statin lead structure
Pain opiates
Aspirin

Question 2

Give examples of synthetic drugs.

Answer 2

Antibacterial: Ciprofluxacin, F, gyrase inhibitor, sulfonamides
Anti cancer: Anti-metabolites, alkylating agents
CNS: Amphetamines
Metabolism: Rosuvastatin
Pain: Fentanyl
Inflammation: NSAIDs
CV: beta-blocker, sartanes
CNS: benzodiazepines

Question 3

Describe the acute toxicology phase of drug development.

Answer 3

4 weeks, 90 days, rodents, dogs, 4 weeks, costs up, early failure

Question 4

What is a contract research organisation?

Answer 4

A contract research organization (CRO) is a company that provides support to the pharmaceutical, biotechnology, and medical device industries in the form of research services outsourced on a contract basis.

Question 5

Describe phase 1 clinical trials in drug development.

Answer 5

Phase 1, PK, Cmax, AUC, healthy volunteers

Question 6

Describe phase 1 clinical trials in cancer studies.

Answer 6

Cancer: Phase 1, patients, surrogate endpoint instead of clinical endpoints e.f. biomafrkers.

Question 7

Describe phase 2 clinical trials in drug development.

Answer 7

Phase 2, efficacy, patients

Question 8

How much do phase 1 clinical trials cost?

Answer 8

2-3 million.

Question 9

How can drugs be fast-tracked to phase 3 clinical trials?

Answer 9

By proving that there is an unmet medical need.

Question 10

Which organisation sets the trends for clinical trials, the trends which the rest of the world tends to follow?

Answer 10

The FDA.

Question 11

What percentage of drugs in trial fail do to poor pharmacokinetics?

Answer 11

~39%.

Question 12

What percentage of drugs in trial fail do to adverse effects in man?

Answer 12

~10%.

Question 13

Can adverse effects of drugs in man be predicted?

Answer 13

No.

Question 14

What percentage of drugs in trial fail due to unacceptable animal toxicology?

Answer 14

~11%.

Question 15

What percentage of drugs in trial fail due to lack of efficacy?

Answer 15

~30%.

Question 16

What percentage of drugs in trial fail due to commercial reasons?

Answer 16

~5%.

Question 17

What percentage of drugs in trial fail due to other reasons?

Answer 17

~5%.

Question 18

For what commercial reasons may a drug in trial fail?

Answer 18

The product won’t give a return on investment. The earlier the drug is withdrawn from trials, the less money it costs.

Question 19

What are generic drugs?

Answer 19

A generic drug is a pharmaceutical drug that has the same chemical substance as the drug that was originally developed, patented and innovated. Generic drugs are allowed for sale after the expiry of the patent of the original drugs.

Question 20

What techniques are used to determine the structure of pharmaceutical compounds?

Answer 20

FT-IR spectroscopy, mass spectroscopy, 1H-NMR, 13C-NMR. Comparison to data bases.

Question 21

What is the gold standard for determining structure?

Answer 21

x-ray crystallography.

Question 22

Describe the semi-synthetic approach for synthesis of drugs.

Answer 22

Starting molecule from nature, isolated.
Cheap and available on large scale
Example: progesterone from ergosterol
Limited small number of chemical steps
Not all modifications can be made for full SAR optimisation

Question 23

Describe the total synthesis of drugs.

Answer 23

Full SAR may be required, Me group only by semi-synthesis
All homologues can be prepared by total synthesis
Starting material from industrial, technical synthesis
Usually, high number of steps
May not be commercially viable

Limited use for natural products, standard for synthetic drugs

Question 24

Through what kinds of interactions can drugs interact with receptors?

Answer 24

Aromatic interactions (charge transfer complex), hydrogen bonding, induced dipole/Van der Waals, ionic bonding.

Question 25

Describe aromatic interactions (charge transfer complex).

Answer 25

Non-covalent interactions between aromatic rings, since they contain pi bonds. Also known as pi stacking. There is no unified description of the factors that contribute to this.

Question 26

What key functional group contributes to aromatic interactions?

Answer 26

Benzene rings.

Question 27

Give examples of functional groups which are hydrogen bond acceptors.

Answer 27

Any lone electron pairs present on the oxygen or nitrogen in the carbonyl, ether, the hydroxyl, the amino, the imino, and the nitrile groups are hydrogen-bond accepting

Question 28

Give examples of hydrogen bond donors.

Answer 28

The hydrogens on hydroxyl, amino, and imino groups.

Question 29

What functional group can be involved in ionic bonding?

Answer 29

Carboxylic acids.

Question 30

Give examples of groups which can interact through Van der Waals interactions.

Answer 30

Example Alanine of receptor and isopropyl group or ligand , drug molecule.

Question 31

What molecule is displaced during Van der Waals interactions.

Answer 31

Water.

Question 32

Give examples of groups which can interact through ionic bonding.

Answer 32

Example Lysine , amino group and carboxylic acid (of Aspirin or Diclophenac).

Question 33

What is a homologue/homologous group of drugs?

Answer 33

A group where the base structure remains the same but slight changes are made which impacts the activity and efficacy of the drug.

Question 34

In drug design what is a spacer?

Answer 34

A spacer is a chain connecting two sites of binding which can be changed to alter the activity of the drug.

Question 35

Define bioisostere.

Answer 35

In medicinal chemistry, bioisosteres are chemical substituents or groups with similar physical or chemical properties which produce broadly similar biological properties to another chemical compound. In drug design,[1] the purpose of exchanging one bioisostere for another is to enhance the desired biological or physical properties of a compound without making significant changes in chemical structure.