Med Chem Test #1 - intro and drug discovery

what are drugs?

chemical that can react with biological system and produce biological response

drug classification in order

1. pharmacological effect

2. chemical structure

3. target system

4. site of action

definition: pharmacological effect

biological responses.

definition: chemical structure

shared core skeleton.

definition: target system

chemical messenger targeted.

definition: site of action

exact enzyme or receptor target

example: pharmacological effect

analgesics, antibacterials

example: chemical structure

steroids, penicillins, barbiturates

example: target system

antihistamines, cholinergics

example: site of action

anticholinesterases

feature: pharmacological effects

yields wide variety of chemical structures

feature: chemical structure

similar structure often share similar activity

feature: target system

more specific than pharmacological effect

feature: site of action

highly specific

what is medicinal chemistry?

science which deals with discovery or design of new chemicals and their development into useful medicines

medicinal chemistry fields

computational chem, synthesis, itoxicology, metabolism

modern drug development type of benefits + example

societal (eradication TB, increasing HIV patient life expectancy)

modern drug development type of consequences + example

biological (antibiotic resistance) and economic (increased healthcare costs)

Stages of drug discovery and development (DDD) in order:

1. choose a disease

2. choose a drug target

3. identify a bioassay

4. find a lead compound

5. isolation, purification and structure determination of lead compound

6. SARs

7. pharmacokinetics and metabolism

8. synthesis issues

9. toxicological safety evaluation

10. clinical trials

1) choose a disease

MARKETING DECISION! common, chronic, 1st world diseases. no good competitor

2) choose drug target

understand everything about the disease

3) identify a bioassay

high throuput screening. in-vivo preferred with transgenic animals. in-vitro for quantitated results

4) finding lead compound

test multiple compounds

5) isolation, purification, structure determination of lead compound

only if active compound not known

6) SAR

identifying the pharmacophore

SAR also known as

structure activity relationships

define pharmacophore + person credited for definition.

the bare minimum structure needed to for the drug to work. Paul Ehrlich (1909)

7) pharmacokinetics and metabolism

ADME determined.

define ADME

absorption, distribution, metabolism, and excretion

8) synthesis issues

synthesis of drug while keeping low cost

9) toxicological safety evaluation

Ames test, mammalian studies, NOEAL

define NOEAL

No Adverse Event Level

10) clinical trials

4 phases. IND filed with FDA

clinical trial phase I

first exposure to humans. healthy volunteers

clinical trial phase IIa

first exposure to patients. less than 100 patients

clinical trial phase IIb

100-300 patients. double blind. ONE center

clinical trial phase III

100-3000 patients. multiple centers. 2-10 years

clinical trial phase IV

after market