Pharmaceutical Medicinal Chemistry: Introduction

Question 1

applied science that is focused on the design (or discovery) of new chemical entities (NCEs) and their optimization and development as useful drug molecules for the treatment of disease processes.

Answer 1

MEDICINAL CHEMISTRY

Question 2

Crude drug preparations:

Answer 2

• Poultice
• Tinctures
• Soups
• Infusions

Question 3

Isolation of morphine from opium

Answer 3

Serturner

Question 4

Emetine from ipacacuanha

Answer 4

Pelletier

Question 5

Digitalis for dropsy

Answer 5

William Withering

Question 6

Isolation of cocaine

Answer 6

Nieman

Question 7

Use of ether and chloroform as

Answer 7

anaesthetics

Question 8

Phenacetin is from

Answer 8

aniline

Question 9

physostigmine is from

Answer 9

calabar bean

Question 10

Isolation of morphine is from

Answer 10

opium

Question 11

Emetine is from

Answer 11

ipacacuanha

Question 12

Chemotherapeutic agents posses

Answer 12

haptophoric and toxophilic groups

Question 13

Chemotherapeutic agents + receptor=

Answer 13

chemical reactions

Question 14

Concerned mainly with organic, analytical and biochemical aspects of drug discovery

Answer 14

Medicinal Chemistry

Question 15

Ancient folk medicine + natural product chemistry

Answer 15

Medicinal Chemistry

Question 16

Directed to new and natural or synthetic organic compounds

Answer 16

Medicinal Chemistry

Question 17

Devoted to the discovery and development of new agents for treating diseases

Answer 17

Medicinal Chemistry

Question 18

WORKING DEFINITION:
uses physical organic principles to understand the interaction of small molecular displays with the biological realm.

Answer 18

Medicinal Chemistry

Question 19

Two (2) Phases of Drug Design

Answer 19

• Basic concepts of drugs, receptors, and drug-receptor interaction
• Clinical application of concept of drug interactions

Question 20

Basic concepts of drugs, receptors, and drug-receptor interaction
Three (3) Steps

Answer 20

1. Properties that turn a molecule into a drug
2. Properties that turn a macromolecule into a drug target
3. Designing and synthesizing a drug to fit into the target

Question 21

Clinical application of concept of drug interactions
3 Approaches

Answer 21

1. Manipulation of the body’s endogenous control systems
2. Manipulation of the body’s endogenous macromolecules
3. Inactivation of harmful exogenous substances

Question 22

Stages of drug discovery, design and development

Answer 22

Stage 1: Drug discovery
Stage 2: Drug design
Stage 3: Drug development

Question 23

Target Identification and Validation

Answer 23

Stage 1: Drug discovery

Question 24

Choosing a disease

Answer 24

Stage 1: Drug discovery

Question 25

Choosing a drug target

Answer 25

Stage 1: Drug discovery

Question 26

Identify a Bioassay

Answer 26

Stage 1: Drug discovery

Question 27

Determines activity of the compound at the target and other receptors

Answer 27

Identify a Bioassay

Question 28

• Target specificity and selectivity • Multi-target

Answer 28

Choosing a drug target

Question 29

Diseases where there is a need for new drugs • Prevalent disease • Economic factors • Orphan drug

Answer 29

Choosing a disease

Question 30

Lead Discovery

Answer 30

Stage 1: Drug discovery

Question 31

In an artificial environment, as in a test tube or culture media

Answer 31

In vitro

Question 32

In the living body, referring to tests conducted in living animals

Answer 32

In vivo

Question 33

Usually refers to doing the test on a tissue taken from a living organism

Answer 33

Ex vivo

Question 34

Salmonella typhimurium

Answer 34

Ames Test

Question 35

test for ability to inhibit potassium ion channels in the heart leading to fibrillation, heart failure

Answer 35

hERG Test

Question 36

Ames Test – Salmonella typhimurium

Answer 36

In vitro

Question 37

hERG Test – test for ability to inhibit potassium ion channels in the heart leading to fibrillation, heart failure

Answer 37

In vivo

Question 38

Acute toxicity tests on mice

Answer 38

Ex vivo

Question 39

Finding a lead compound

Answer 39

Stage 1: Drug discovery

Question 40

Screening of natural products • Plant, microorganisms, marine sources, animal sources, venoms and toxins

Answer 40

Finding a lead compound

Question 41

Isolation and Purification

Answer 41

Chromatography

Question 42

Structure determination

Answer 42

• X-ray crystallography • NMR spectroscopy

Question 43

Involves the automated testing of large numbers of compounds versus a large number of targets

Answer 43

High-throughput Screening

Question 44

Test of drug receptor binding

Answer 44

NMR Spectroscopy

Question 45

• Pharmaceutical companies have prepared thousands of compounds • These are stored (in the freezer!), catalogued and screened on new targets as these new targets are identified

Answer 45

Synthetic Banks

Question 46

A chance of occurence

Answer 46

SERENDIPITY

Question 47

Yew tree Taxus brevifolia L. (Fam. Taxaceae)

Answer 47

Paclitaxel

Question 48

Qinghao Artemisia annua L. (Fam. Asteraceae)

Answer 48

artemisinin

Question 49

Poppy Papaver somniferum L. (Fam.Papaveraceae)

Answer 49

morphine

Question 50

Penicillium notatum

Answer 50

penicillin

Question 51

Epipedobates tricolor

Answer 51

epibatidine

Question 52

Marine cone snail Conus geographus

Answer 52

ziconotide

Question 53

Gila monster Heloderma suspectum

Answer 53

exenatide

Question 54

Brazilian viper Bothrops jararaca

Answer 54

teprotide

Question 55

sulfonamide

Answer 55

tolbutamide chlorothiazide

Question 56

warfarin

Answer 56

tipranavir

Question 57

epinephrine

Answer 57

salbutamol

Question 58

histamine

Answer 58

cimetidine

Question 59

Lead Optimization

Answer 59

Stage 2: Drug design

Question 60

Goals of Drug Design

Answer 60

1. Good selectivity and level of activity for its target 2. Improve pharmacokinetic properties 3. Improve interaction with target 4. Easily synthesized 5. Chemically stable 6. Minimal side effects 7. Non-toxic

Question 61

Drug optimization goals

Answer 61

• Reduce toxicity • Development of Prodrugs • Drug alliances • Endogenous compounds • Peptides and peptidomimetics

Question 62

Drug optimization strategies

Answer 62

• Variation of substituents • Extension of the structure • Chain extension/ contraction • Ring expansion/ contraction • Ring variations • Ring fusions • Simplification of the structure • Rigidification • Conformational blockers

Question 63

Pre-clinical Development

Answer 63

Stage 3: Drug development

Question 64

Clinical Development

Answer 64

Stage 3: Drug development

Question 65

Toxicity testing

Answer 65

Pre-clinical Development

Question 66

• PD/PK • Pre/Formulation Studies

Answer 66

Pre-clinical Development

Question 67

• Phase I • Phase II • Phase III • Phase IV

Answer 67

Clinical Development