Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

531 Med Chem > Exam 3 > Flashcards

Exam 3 Flashcards

You may prefer our related Brainscape-certified flashcards:
AP® Chemistry flashcards Periodic Table flashcards Chemistry 101 flashcards Organic Chemistry 101 flashcards
1
Q

True or False: most drugs on the market are large biologics.

A

False. Most drugs are small organic molecules(>80%), but biologics are on the rise.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Major sources of drugs

A

-natural extracts
-natural products-pure molecules isolated from nature
-synthetic drugs
-new drugs from existing drugs
-Synthetic chemical libraries
-natural product libraries
-rational drug design

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Nature as the first source of drugs

A

-almost exclusivly from plants
-many drugs isolated: morphine, quinine, colchine but they were unoptimized for human use(toxic)
-often very large and complex molecules, more rings

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

synthetic drugs

A

-carbon source is petroleum
-often much simpler than natural products
-ex) aspirin, chloral hydrate, chloroform, ether

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

True or false: natural products tend to be larger and more polar molecules than synthetic molecules.

A

True. Synthetic libraries are often too conservative in their structural properties(Lipinski’s rule of 5)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

New drugs from existing drugs

A

-one drug is structurally modified to make another with a different effect
-ex)antimalaria drug->antihistamin –> Antipsychotic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Screening Corporate Chemical Libraries

A

-Bayer begins program screening dyes for antimicrobial activity based on Gram’s dye and the discovery of salvarsan
-discovered red dye, Protosil, protects mice from strptococcus
-Protosil is converted into its active metabolite sulfaliamide(antibiotic)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Screening Natural Product COllections

A

-Paclitaxel discoved as anti cancer drug when screening plant extracts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

High Troughput screening(HTS) of chemical libraries

A

-trial and error approach by using huge libraries to test each molecule againist a validated drug target or organism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

WHat is required for a good high throuput screen(HTS)?

A

-robust assay that asses validated drug target
-assay must be statistically sound
-rapid and inexpensive to assess many molecules
-variety of potentially active substances
-molecule should be slightly water soluble and not prone to aggregation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Rational drug design

A

-using knowledge of drug target structure or enzyme mechanism to discover molecules that bind to the target
-ex) HIV protease inhibitors
-ex) carbidopa to treat parkinson’ss desease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How does carbidopa work?

A

Inhibits AADC which converts L-DOPA into dopamine. This allows for more L-DOPA to cross the BBB and be converted into dopanine which can be used for signaling.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Cisplatin

A

-anti cancer drug
-inhibits cell division
-hydrolysis from Pt electrode
-elongation of mititic spindles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How much does it cost to develop a new drug?

A

-$2 billion
->10 years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Lead optimization

A

-optimizes drug to give important attributes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Characteristics of a good drug

A

-oral bioavailability: water soluble but also small and lipophillic
-chemically stable
-chemically unreactive: avoid immune response
-metabolically stable
-pharmacologically specific
-potent but not too potent
-good toxicity profile
-inexpensive to manufacture

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

reasons for failuers of drug candidates

A

-problems with efficacy and toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

ionic(charge-charge) interaction

A

-ions are solvated by water which competes the interaction
-energy is proportional to 1/Dr
Interaction between two charges species

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

dipole and induced dipole Interactions

A

-Can be permant or temporary
Induced by random fluctuation in electron density in a non polar group

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

London Dispersion/ Van der Waal interactions

A

-optimal distance between two atoms that is energetically favorable
-significant amount of binding energy if atoms are close
-explains importance of “fit” between drug and it’s protein target binding site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Hydrogen bonding interactions

A

-between H atom(attached to N, O) and another oxygen
-strongest when linear
-water can solvate polar groups via H-Bonds
-protiens use H bonds to fold into secondary and tertiary structures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How does vancomycin work?

A

-antibiotic
-clamps down on terminus end of peptodogylcan
-H-bond is key to binding(amide is needed. when replaced with ester, binding is weakened 1000x)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

cation pi-interactions

A

-share pi cloud
-aromatic rings are stacked
non-covalent interaction between electron rich pi system and nearby hard metal cation or ammonium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How does acetylcholinesterase bind?

A

-through cation pi interactions
-aromatic rings of Try-84 and ammonium in achetylcholine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

entropy

A

-measure of uncertantity/probability
-number of microstates available
-ex) more translational and rotational freedom

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Hydrophobic effect

A

-placing nonpolar molecules in water is energetically unfavorable
-oil reduces motion of the water because of noncalvealent interations
-restriction of motion reduces entropy of the system(entropic cost)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

True or False: binding if the drug with the drug target is often favorable and the release of water is unfavorable.

A

False. binding is unfavorable but the release of the water is what makes the reation energetically favorable.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Log P values

A

-measure used to determine hydrophobicity
-higher value=more lipophillic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

what is a pi value?

A

pi values=log P

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

log D

A

-for molecules that are ionizable
-pH dependent
-at pH where molecule is neutral, log D=log P

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

The main target of drugs

A

-75% proteins
-21% pathogen protein targets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

True or false: most small molecule drugs target protein receptors such as G coupled receptors, ion channels, and nucleur receptors

A

true

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Agonist

A

induce the proper conformational change in their target receptor that triggers downstream signaling events

34
Q

Antagonist

A

inhibit conformational change due to steric clash

35
Q

partial agonist

A

mimics the acivity but plateaus at a lower level

36
Q

Inverse agonist

A

has the opposite activity of the agonist

37
Q

competitive antagonists

A

-shift activity curve to the right
-takes more agonist to get full effect

38
Q

Noncompetitive antagonist

A

-affect binding and activity and prevent agonist from achiving full effect by binding at different site on protein

39
Q

therapeutic index

A

-want to limit human toxicity while achiving therapeutic effect
-goal is to achieve a wide therapeutic index

40
Q

true or false: full receptor occupancy is required for maximum activity

A

False. there are enzymes that amplify the signal

41
Q

Racemic mix

A

1:1 ration of each enatiomer

42
Q

How are single enatiomers formed?

A

-use enatiomerically pure starting materials(inefficient, old tech)
-diasteromeric salts
-enzymes
-synthetic chiral catalysts
-chiral chromatography

43
Q

Diasteriomeric salts

A

-add a single enatiomer of a chiral acid to resolve a mixture of amine bases, vice versa
-only works with amine bases and carboxylic acids
-salts are then seperated by solubility

44
Q

Enzyme catalysts

A

-esterases, reductase, asnd other enzymes are often able to distinguish between enatiomers and creat single enatiomers
-often involving aqueous phase and organic phase

45
Q

Synthetic chiral catalysts

A

-act like enzymes in that they bind the starting molecule and modify it to produce mostly one enatiomer
-must use single enatiomer of either D or L-tartrate
-forms a metal schafolding and chiral catalytic binding pocket

46
Q

Monsanto

A

-anti parkinson’s drug
-uses chiral phodium catalyst to hydrogentat the alkene
-makes enatiospecific route to give L-DOPA
-example of a synthetic catalyst

47
Q

Chiral chromatography

A

-single enatiomer is attached to polymer or silica beads
-one enatiomer interacts more tightly via non covalent interations
-expensive and not practical large scale

48
Q

synthetic biology

A

-use of recombinand DNA tech to create GMOs for the synthesis of novel products
-sysnthesis of bioactive molecules or their precursors

49
Q

Chiral center unstability

A

-some chiral centers are not stable in vivo
-racemization is catalyzed by base(phosphate, amino acids) and protiens(human serum albumin

50
Q

bioactive conformation

A

drug molecules that have flexibility due to rotatable bonds can have different bound conformations
-the drug structure when it binds to the target complex is the bioactive conformation

51
Q

conformational restriction

A

-uses cross linkers to restrict conformation
-“pre-pays” entropic cost before binding step

52
Q

Why do natural products contain many rings?

A

-constrain atoms and limit the number of possible conformations
-improve binding affinity (by reducing entropy loss upon binging)and specificity to the target(rigid molecule)

53
Q

induced fit

A

ligand induces a conformational change in the protein
-ligand concentration independent

54
Q

global minimun conformation

A

-lowest energy conformation
-usually free of steric hinderence

55
Q

risks of conformational restriction

A

-might restrick the molecule in a non binding conformation but this has been perfected by nature

56
Q

ADME(T)

A

-absorption
-distribution
-metabolism
-excretion
-toxicity

57
Q

Lipinski’s rule of 5

A

-no more than 5 H-bond donars
-less than 10 H bond acceptors
-less that 10 rotatable bonds
-MW<500 daltons
-Log P less than 5

58
Q

True or false: approved oral drugs always follow Lipinski’s rule of 5.

A

False. getting a little larger and more complex.
-MW and #rotatable bonds has increased
-LOG P and #HBDs has stayed constant

59
Q

Does cyclosporine follow Lipinski’s rule of 5?

A

-NO, because of intramolecular interactions
-3 intramolecular H bonds which sheils polar groups

60
Q

Do CNS drugs generally follow Lipinski’s rule?

A

yes, because molecules need to be smaller(<350_ and less polar

61
Q

active transport

A

-trans membrane protein pumps/channels
-complete saturation=rate limiting

62
Q

passive diffusion

A

-high conc to low conc
-no rate limiting step

63
Q

Enterocyte

A

transporter between blood and GI

64
Q

Hepatocyte

A

transporter between blood and the bile

65
Q

Relationship between Log P and permeability

A

-positive correlation between lipophilicity and passive diffusion

66
Q

Relationship between log P and BBB passage

A

-CNS bioavailability requires neutral species for passive diffusion
-above the trend line: active transport
-below trend: efflux pumps

67
Q

isosteric substitution

A

-the process of replacing groups of molecules so that it still has similiar properties
-can be done with small groups of atoms, whole rings, an bioactive functional groups

68
Q

molecular mimicry

A

-replacements that have very similiar steric properties and involve single atom substitutions
-this sometimes significantly changes drug properties

69
Q

Non classical biosteric replacments

A

-replacement has widly different steric properties but it retain properties such as polarity, pKa that are important to retain bioactivity

70
Q

Cyclic bioisosteres

A

-mimic carbonyl containing groups as well as pKa and other properties
-But rigity of the ring can induce risk because it is conformationally restricted

71
Q

Positive aspects for Me-too drugs

A

-claim to improve ADMET or specific issues
-sometimes have new activities
-can compete with first drug to drive down prices

72
Q

Negative aspects of Me-Too drugs

A

-use up resources that could be spent on drug for mor pressing diseases
-minimal additional benefit
-marketing may be exaggerated
-drive up price by delaying entry of generics

73
Q

Deuterium substitution

A

-form of isotopic substitution
-prediction was that binding would be identical but this may not be true
-Deuterium has slightly shronger and shorter bond that is kinetically slower to break

74
Q

kinetic isotope effect

A

the slower rate of C-D bond breaking vs C-H
-useful if we want to slow down metabolism

75
Q

antimetabolite

A

-substrates that block vital metabolic pathways

76
Q

Multisubstrate analog inhibitors

A

-reversible inhibitor
-derive binding energy by thethering multiple substrates in one molecule-pre pay entropic cost by freesing the translation of the substrates

77
Q

transition state analogs

A

-reversible inhibitor
-derive binding energy by mimicking high energy reaction intermediates and/or transition states

78
Q

Affinity labels

A

-irriversible labels
-substrate analogs specific for enzyme active site and contain highly reactive electrophillic group

79
Q

Mechanism based inhibitors(suicide substrate)

A

-irreversible
-substrate is converted to a reactve species by the action of the target enzyme

80
Q

Sulfanilamide

A

-example of an antimetabolite
-alternative substreate in folic acid biosynthesis
-competes with PABA

81
Q

6-mercaptopurine(6-MP)

A

-antimetabolite
-substrate of purine salvage pathway
-end in pathway toxicity and cell death

531 Med Chem (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions