Drug likeness and druggability

Drug development timeline

1. Drug discovery

2. Preclinical research

(4-7 years)

3. Clinical development (phase I, II, III) roughy 8.5 years in total

4. Market approval ( registration process and phase IV) 6 -10 months

IND

Investigating new drug

NDA

New drug application

MAA

Marketing authorisation application

CTA

Clinical Trial Application

BLA

A biologics license application

Drug discovery process - stage 1

• disease identified as unmet

• Target ID - relevance to the disease

• Specificity of the target within the body and its impact on drug selectivity

• In vitro/in vivo biology - screening technologies

• Compound screening sources - endogenous start points - me too - refers to an existing med to create new med

Describe the design, make, test process

Poison - in inhibition terms

Like a inhibitor but acts gradually and more potent

What is the structure activity relationship (SAR)

• the effect that the variation in the structure has on a biological effect

• This effect can be on the primary target, enzyme/receptor or cell.

• Can be applied to Pharmacokinetic properties

• Clearance/metabolism, absorption properties investigated

• Changing something in the structure - investigating its effect

What is Kd

Dissociation constant

How does the gibbs free energy equation link to the binding or dissociation of a drug

G desolvation

Removal of water molecules upon binding

G motion

G configuration

G interaction

Alcohol group effect on drug binding

How does a steric shield effect drug binding

Amine group effect on drug binding

Free base amines effect on drug binding

Why are tertiary amines only able to act as H bond acceptors ?

No hydrogen atoms are available to act as H bond donors

Describe how amides can behave as amine analogues ?

Aldehyde and ketone effect on drug binding

Describe how ester groups effect drug binding

Describe the real role of esters in drug design

• esters usually hydrolysed by esterases in the body

• More likely to be important for pharmacokinetic reasons - acting as pro drugs

• Esters can be used to mask polar groups, allowing the passage of polar drugs through the phospholipid membrane

Describe amide bonding in drug-receptor interaction

Describe amide analogues

Methylation of N in amides - what effect does this have ?

Carboxylic acid effect on binding

Describe carboxylate binding interaction

Describe Carboxylic acid analogues

Describe aromatic ring binding in drugs

What are some uses of aromatic rings in drug design

Describe alkyl group binding in drug design

Describe how alkyl analogues can vary

Create flashcards for each of the following functional groups (before summary)