Exam 3

Question 1

The first molecule with the desired pharmacological activity is the …

Answer 1

Lead compound

Question 2

Testing the purification of active compounds from plants, microbes, and animals is known as

Answer 2

Natural sources

Question 3

The scientific study of ethnic groups, physical habits, and how they use medicinal planes

Answer 3

Ethnopharmacology

Question 4

Testing a variety of compounds using a bioassay

Answer 4

Screening

Question 5

Libraries of all compounds on hand

Answer 5

Random libraries

Question 6

Synthetic libraries made up of only drug like molecules

Answer 6

Directed libraries

Question 7

Using a computer modeling program go test compounds in computer for ability to fit in a binding cavity or for 3D similarity to natural ligand

Answer 7

In Silico Library

Question 8

Identify target molecule
Design high potency enzyme inhibitors based in substrate, products, and reaction mechanism

Answer 8

Rational drug design

Question 9

Special type of drug design where 3D structure of the target is used to direct the synthesis of new compounds

Answer 9

Structure based design

Question 10

What is the goal of lead modification

Answer 10

Make lead compound fit it’s target better increasing its potency and specificity

Question 11

SAR: understand the relationship between each drugs _________ and it’s ________

Answer 11

Structure and activity

Question 12

3D arrangement of atoms that is responsible for the drugs activity

Answer 12

Pharmacophore

Question 13

3D arrangement of atoms that is responsible for the metabolic properties

Answer 13

Metabophore

Question 14

3D arrangement of atoms responsible for toxicity-eliciting interactions

Answer 14

Toxicophore

Question 15

Simplification makes the compound easier to synthesize and tells us which groups are _______ which are ______

Answer 15

Needed and not needed

Question 16

Deletion studies identify the ___________ which is the portion of a molecule containing essential functional group that directly interact with the target

Answer 16

Pharmacophore

Question 17

The pharmacophore included the _______________ of those critical functional groups

Answer 17

3D arrangement

Question 18

Inserting a methylene group between two parts of a drug molecule is called

Answer 18

Homologation

Question 19

Adding a branch point can have what kind of effects on the drugs activity

Answer 19

It can increase or decrease its activity

Question 20

In ring chain transformations atoms can rotate freely around carbon-carbon _______ bonds and this free rotation will often produce different ___________

Answer 20

Single
Conformations

Question 21

Introduction of rings restricts the shape of a molecule making it more ________ sometimes increasing the molecules potency or making it more specific

Answer 21

Rigid

Question 22

Breaking rings or removing them will slow a molecule to be more _________ this molecules might be able to alter its shape and fit more receptors but it also might produce more side effects

Answer 22

Flexible

Question 23

Converting single bonds to double bonds will after geometry and may ______ the molecule

Answer 23

Rigidify

Question 24

Bioisosteres are functional groups that possess almost equal _____________ and _____________

Answer 24

Molecular shapes and volumes
Similar distribution of electrons

Question 25

Hydrogens are the same size as what

Answer 25

Fluorine

Question 26

Methyl is the same size as what

Answer 26

Chlorine

Question 27

The more polar and charged the molecule the ______ well absorbed

Answer 27

Less

Question 28

More lipophilic to point of non-dissociation is ______ absorbed

Answer 28

Less

Question 29

Reducing the number of charged groups on a drug decreases it’s water solubility however this conversion is only _________

Answer 29

Temporary (will cleave back to normal molecule)

Question 30

A hERG pharmacophore has a lipophilic base that has a ________ _______

Answer 30

Tertiary amine (2-5 atom chain that includes rings, hetero atoms or polar groups)

Question 31

Excretion ____________ removes drug from the body. The major excretory organ is the ______

Answer 31

Physically Kidney

Question 32

What drugs are excreted often without needed major metabolism

Answer 32

Polar and ionized drugs

Question 33

Lipophilic drugs are largely _____________ back into systemic circulation during passage through renal tubules

Answer 33

Reabsorbed (require modification to make them more polar)

Question 34

The metabolism of lipophilic drugs into more _________ metabolites is essential for the elimination of these compounds from the body

Answer 34

Hydrophilic

Question 35

Phase 1 metabolism: polar functional groups are

Answer 35

Introduced into the molecule or modified by reactions

Question 36

Phase II modification (conjugation)

Answer 36

Attaching small, polar, and ionizable endogenous molecules to phase I metabolite or parent drug

Question 37

What are the 4 things that can happen in an oxidation reaction

Answer 37

Gain of oxygen Loss of hydrogen Loss of alkyl group Loss of hetero atom

Question 38

Isozymes

Answer 38

Multiple forms of same enzyme

Question 39

What CYP families cause the most of the drug metabolizing enzymes

Answer 39

CYP 1,2,3

Question 40

Unsubstituted phenyl rings are hydroxylated to ______ ________

Answer 40

Arene Oxides

Question 41

Arene Oxide spontaneously rearranges to give a ______ hydroxylated product

Answer 41

para (NIH shift)

Question 42

EWG groups ___________ rings causing a __________ in -OH

Answer 42

deactivate decrease

Question 43

EDG groups ___________ rings causing a __________ in -OH

Answer 43

activate increase

Question 44

Oxidation of alkenes

Answer 44

non aromatic carbon-carbon double bonds can be oxidized Results in epoxide Epoxide can be open to produce a diol

Question 45

Oxidation only occurs if there is a ________ atom on each alkene carbon

Answer 45

hydrogen

Question 46

Allylic carbons are aliphatic carbons directly adjacent to ________________ double bonds

Answer 46

non-aromatic

Question 47

Benzylic Carbons are aliphatic carbons ___________ attached to an aromatic ring

Answer 47

directly

Question 48

Oxidation does not usually occur if there is a __________ attached to the benzylic carbon as well

Answer 48

heteroatom

Question 49

Aliphatic chains will undergo oxidation at the terminal methyl group or at the ____________ carbon

Answer 49

penultimate

Question 50

In general, you need how many unbranched carbons in order to get oxidation

Answer 50

3-4

Question 51

Oxidation will occur at either omega or omega-1 but ___ ______ since one is usually enough to increase water solubility and facilitate excretion

Answer 51

not both

Question 52

For deamination the alpha carbon must contain at least one _________ atom. This amine attached quaternary carbons cannot undergo deamination reactions

Answer 52

Hydrogen

Question 53

N-dealkylation can occur on what three types of molecules

Answer 53

2, 3 amines and amides

Question 54

N-oxidation involves direct oxidation of the __________ instead of the adjacent carbon atom

Answer 54

Nitrogen atom

Question 55

Dealkylation of ethers usually only occur when it is a _______ ether because of steric hinderance

Answer 55

Methyl

Question 56

Oxidative dehalogenation usually occurs when

Answer 56

-Requires two halogens on carbons -Have to remove hydrogen so 3 halogens is too many

Question 57

The reduction of a functional group on a drug will result in the gain of what

Answer 57

Hydride ion

Question 58

How are aldehydes formed

Answer 58

Oxidative deamination or N, O, or S-dealkylation

Question 59

All reductions reactions require a source of electrons which is usually carried in the electron carrier

Answer 59

NADPH

Question 60

Ketones can be reduced to what

Answer 60

2’ alcohol

Question 61

Azo group (N=N) can be used in a

Answer 61

Prodrug strategy

Question 62

You usually only see nitro groups when it is attached directly to what

Answer 62

an aromatic ring

Question 63

The unmasking of polar groups does what to water solubility

Answer 63

Increases

Question 64

Functional groups that are most accessible are most _____________ to metabolism

Answer 64

Susceptible

Question 65

Conjugation reactions involve attaching small, polar, and ionizable _______ ________ to phase 1 metabolite or parent drug to further increase water solubility

Answer 65

Endogenous molecules

Question 66

Phase 2 metabolism requires what two things

Answer 66

High energy molecule Enzyme

Question 67

Most conjugates are biologically inactive and usually nontoxic because they are highly polar and unable to cross cell membranes. What are the two exceptions

Answer 67

Acetylation Methylation

Question 68

In order for glucuronic to be added to drug molecules, it first has to be converted into a high energy intermediate called what

Answer 68

UDP-Glucuronate

Question 69

In a glucuronic acid conjugation the stereo center at C1 is __________ during the nucleophilic attack by the drug

Answer 69

Inverted

Question 70

Sulfate conjugation occurs primarily with what

Answer 70

Phenolic OH

Question 71

In for for sulfate to be conjugated to drugs, it also has to be converted into a high energy intermediate is called what

Answer 71

3’-phosphoadensine 5’phosphosulfate (PAPS)

Question 72

Sometimes sulfate conjugation is unstable and this can be susceptible to nucleophilic attack by various proteins causing what

Answer 72

A toxic metabolite

Question 73

What does amino acid conjugation usually occur with

Answer 73

Aromatic COOH Aryl acetic COOH (Requires activation of amino acid before attachment to drug)

Question 74

Glutathione conjugation requirements

Answer 74

Can react with large functional groups Does not require activation before attachment to drug

Question 75

Actuation increases __________. Acetylation is usually used to terminate ________ activity and not necessarily increase excretion

Answer 75

Lipophilicy Physiological

Question 76

Methylation occurs on what

Answer 76

Catecholes Phenolic OH Amines Thiols

Question 77

Inactive material requiring conversion, usually by metabolism, to an active drug

Answer 77

Prodrug

Question 78

Typical functional groups used in the creation of prodrugs

Answer 78

Carboxylic acids and alcohols (convert to ester) Amines (convert to Azo or Amide)

Question 79

Prodrugs can improve high hydrophilicity

Answer 79

Poor oral bioavailability due to inability to cross membrane Incompatibility with lipid based formulation

Question 80

Prodrugs can improve chemical instability

Answer 80

Drug is inactivated before it reaches its site of action

Question 81

Prodrugs can improve poor aqueous solubility

Answer 81

Drug can’t be formulated in water solutions for injection Solid forms of the drug don’t dissolve well producing poor and variable oral bioavailability

Question 82

Prodrugs can improve 1st pass metabolism

Answer 82

Orally administered drug is rapidly inactivated by drug metabolizing enzymes in the intestine and liver before reaching general circulation

Question 83

The longer the alkyl chain on the ester the more lipophilic = deep intramuscular injection = ______ ______ ______

Answer 83

Longer half life

Question 84

In double esters the eaters will cleave off the _______ which will unmask the second ester, which will spontaneously decompose to ______

Answer 84

1st ester -COOH

Question 85

You can also use the acetoxymethyl method to mask a phosphate groups which does what to the drug

Answer 85

Reduce the charge and increase absorption Get the phosphate back

Question 86

Cleaving by eaters enzymes can make a diet more resistant to cleavage making the drug slower to convert from inactive prodrug to active drug what does this mean for the body

Answer 86

Active drug released at slow steady rate = extended release

Question 87

Soft drugs undergo a metabolic ________. This is because they have a soft spot and causes the drug to have a fast metabolism

Answer 87

Inactivation

Question 88

What are some benefits of soft drugs

Answer 88

Precise control over duration of action Obtain better steady state Avoid toxicity due to over medication Limit drug distribution for topicals

Question 89

__________ is hydrolysis fast which inactivated compounds making the molecule have a short half life

Answer 89

Ester

Question 90

When the ester is added to the outside of the drug it is converted to a what

Answer 90

Carboxylic acid (this is negatively charged at pH 7)