Introduction to MedOrg

Question 1

is the 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

Herbal medicine examples: important throughout human history

Answer 2

• ch’ang shang
• ma huang
• Ipecacuanha
• Cocoa
• Mushrooms
• Opium

Question 3

Crude drug preparations:

Answer 3

• Poultice
• Tinctures
• Soups
• Infusions

Question 4

The age of innovation and chemistry
* The emphasis was shifted from finding new medicaments from the vast world of plants to finding the active ingredients that accounted for their pharmacologic properties.
* Natural product chemistry

Answer 4

early 19th century

Question 5

The isolation of morphine from opium was discovered by —

Answer 5

Friedrich Serturner

Question 6

The emetine from ipacacuanha was discovered by —

Answer 6

Pelletier

Question 7

Digitalis for dropsy was invented by —

Answer 7

William Withering

Question 8

Isolation of cocaine and physostigmine from calabar bean was discovered by

Answer 8

Nieman

Question 9

• Receptor concept
• Chemotherapeutic agents posses haptophoric and
  toxophilic groups
• Chemotherapeutic agents + receptor = chemical reactions
• Labile, versatile, not firmly bound
• Methylene blue, salvarsan, trypan red
• Drug resistance

Answer 9

Paul Ehrlich

Question 10

Ancient folk medicine + natural product chemistry

• Directed to new and natural or synthetic organic compounds
• Devoted to the discovery and development of new agents for
  treating diseases.
• Concerned mainly with organic, analytical and biochemical
  aspects of drug discovery

Answer 10

Medicinal Chemistry

Question 11

Medicinal Chemistry

Answer 11

• Explores the relationship between chemical structure and observed
  biological activity
• Hallmark of Med Chem Research
  ➢ Understanding SARs at the level of physical organic properties with
  consideration of molecular conformation
• Highly interdisciplinary

Question 12

In working definition, —- chemistry uses physical organic principles to understand the interaction of small molecular displays
with the biological realm.

Answer 12

medicinal

Question 13

Two (2) Phases of Drug Design

Answer 13

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

Question 14

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

Answer 14

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 15

3 Clinical approaches of concept of drug interactions

Answer 15

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

Question 16

3 steps in drug discovery

Answer 16

• Target identification and Validation
• Lead Discovery
• Lead Optimization

Question 17

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

Answer 17

Target Identification and Validation

Question 18

In choosing a drug target,
- multitarget and it aims —

Answer 18

Specificity and selectivity

Question 19

• Determines activity of the compound at the target and other receptors
• In vitro: In an artificial environment, as in a test tube or culture media
• In vivo: In the living body, referring to tests conducted in living animals
• Ex vivo: Usually refers to doing the test on a tissue taken from a living organism.

Answer 19

Identify a Bioassay

Question 20

*Finding a lead compound
- Screening of natural products
* Plant, microorganisms, marine sources, animal sources, venoms
and toxins

• Existing drugs
• Natural ligands/ substrates/ modulator
• Combinatorial synthesis

Answer 20

Lead discovery

Question 21

In existing drugs, SOSA means

Answer 21

• SOSA – Selective Optimization of Side Activities

Question 22

In lead discovery, a method can be utilized in isolation and purification

Answer 22

Chromatography

Question 23

In lead discovery, 2 methods can be utilized in structure determination

Answer 23

• X-ray crystallography
• NMR spectroscopy

Question 24

*Involves the automated testing of large numbers of compounds versus a large number of targets
* Example: several thousand compounds can be tested at once in
30-50 biochemical tests
* Effects measured: cell growth, color change for an enzyme catalyzed reaction, or displacement of radioactive labelled
ligands from receptors

Answer 24

high-throughput screening

Question 25

NMR Spectroscopy

Answer 25

*Test of drug receptor binding * NMR spectrum of drug is taken, the protein is then added and the spectrum is re-run. * If the drug fails to bind to the protein, then the NMR spectrum will still be detected * If the drug binds to the protein, it becomes part of the protein. Nuclei will have a shorter relaxation time and no NMR spectrum will be detected

Question 26

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 26

Synthetic Banks

Question 27

Yew tree found in PACLITAXEL has scientific name:

Answer 27

Taxus brevifolia L. (Fam. Taxaceae)

Question 28

Qinghao found in ARTEMISININ has scientific name

Answer 28

Artemisia annua L. (Fam. Asteraceae)

Question 29

Poppy found in MORPHINE has scientific name

Answer 29

Papaver somniferum L. Fam- Papaveraceae

Question 30

Penicillin is made from an organism called

Answer 30

Penicillin notatum

Question 31

Epibatidine drug was formed with

Answer 31

Epipedobates tricolor

Question 32

Ziconotide

Answer 32

Marine cone snail Conus geographus

Question 33

Exenatide

Answer 33

Gila monster Heloderma suspectum

Question 34

Teprotide

Answer 34

Brazilian viper Bothrops jararaca

Question 35

Goal of Drug Design

Answer 35

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 36

* Part/group of the molecule important to biological activity * Identification of pharmacophore * Important binding groups which are required for activity

Answer 36

Structure Activity Relationships (SARS)

Question 37

Drug Optimization goals

Answer 37

Optimizing hydrophobic/ hydrophilic properties * Resistance to chemical and enzymatic degradation * Resistance to drug metabolism * Optimize targeting of drugs * Reduce toxicity * Development of Prodrugs * Drug alliances * Endogenous compounds * Peptides and peptidomimetics

Question 38

Drug optimization strategies

Answer 38

* Variation of substituents * Extension of the structure * Chain extension/ contraction * Ring expansion/ contraction * Ring variations * Ring fusions * Simplification of the structure * Rigidification * Conformational blockers Isosteres and bioisosteres

Question 39

Atoms or group of atoms which have the same valency (or number of outer shell electrons) and which have chemical or physical similarities * SH, NH2, CH3 → OH * S, NH, CH → O

Answer 39

Isosteres and bioisosteres

Question 40

Pre-clinical development includes

Answer 40

- Toxicity testing - PD/PK -pre/formulation studies

Question 41

Clinical Development does have how many phases

Answer 41

4