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med chem
umb med chem 1
188
Chemistry
Professional
05/14/2011

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Term
what are some protein protein interaction examples
Definition

cellular structure
immune response
signal transduction
apoptosis (cell death)

Term
even though protein protein interactions don't contain covalent bonds why are they able to have such strong  bonds
Definition
because of the large surface areas that interacy
Term
what is the hotspot in protein protein interactions
Definition
patches of area on the amino acid that have hydrogen bond doner/acceptor
Term
can your inhibitor work if it does not have the same or more favorable bindining affinity as the substrate
Definition
yes if you have a higher concentration
Term
do you need to know the entire protein structure to block binding of proteins
Definition
no you can target enzyme active sites
Term
explain how target based drug design narrows down the library of molecules
Definition
Experimental screening (competitive binding, enzyme assay, fluorometry) and computational screening 
Term
what is peptidomimetics
Definition
Inhibitors based on primary or secondary structure of the part of the partner protein that participate in PPIs  (this means you will conserve the key parts)
Term
when do you use partial atomic charges
Definition
when dealing with H bonds (accounts for the dipole moment)
Term
why use peptidomimetics
Definition
this is because you will have the save binding points to compete with your protein
Term
what are some challenges for developing PPI
Definition

1.Natural small molecules known to bind at protein – protein interfaces are rare --> no template available for designing antagonists
2.Difficult to locate small, deep cavities that could make good small-molecule binding sites from  X-ray structures
3.Assaying inhibition is difficult in contrast to enzyme inhibition (recall Michaelis-Menten: competitive vs. allosteric antagonists of enzyme activity)
4.Therapeutic antibodies although effective (e.g. Herceptin), are not cell-permeable and so cannot be given orally
5.“Hot spots” appear to have conformational flexibility, and can adapt from a near-flat surface to a cavity capable of binding a small molecule.

Term
why is ERK a great target for drug design
Definition

nActive in cell proliferation in many types of cancers
nCrystal structures of the active and inactive form are available
nMutagenesis studies have discovered residues important for binding to its substrates (blue and green)

Term
how does signal transduction relate to drug design
Definition
 this is typically a good target for PPI inhibitors
Term
what is HCK
Definition
a non receptor tyrosine kinase that is part of a signal transduction pathway for cell proliferation
Term
what are the targets for PPI
Definition

transcription factors (BCl6 in cancer)

signal transduction pathways ( Erk of the mitogen pathway,

and HCK of the SRC family

Term
why target DNA transcription factors for PPI
Definition
cancer has a misregulation of these
Term
what are two important methods of developing inhibitors of protein protien interactions
Definition

target based

peptidomimetics

Term
what is the first protein based drug
Definition
insulin
Term
in 1977 we cloned somatostatin what is this called
Definition
genetic engineering
Term
what is erythropoietin
Definition

i ) Kidney glycoprotein that stimulates growth of red blood cells in bone marrow
ii) Approximately equal mass of protein (34
kD) and carbohydrate
iii) Used in anemia
iv) Abused by athletes

Term
what are some examples of biotech drugs
Definition

erythropoeitin

blood factors

growth factors

human growth hormone

cytokines

enzymes (adenosine deaminase

MABS

Term
describe what human growth hormone is
Definition

i) From pituitary gland, used for growth deficiencies in children (nanism, dwarfism)
ii) Hormone originally isolated from human cadaver pituitary (Creutzfeldt-Jakob syndrome)

Term
what is somatotropin
Definition
this will cause the release of human growth hormone
Term
explain what cytokines are produced as a drug
Definition

i) Interleukins (ILs)
    a) Immune system hormones
    b) Interleukin-11 (rhIL-11,
oprelvekin, Neumega, Genetics Institue) for treatment of Chemotherapy induced Thrombocytopenia

     ii) Interferons

          a) Generally antiviral, antiproliferative and immunomodulatory effects.
    b) Interferon Beta-1A and 1B: used in treatment of relapsing multiple sclerosis

Term
what are the issues with protein based drugs
Definition

1) Antigenicity (non self vs self)

2) Stability

3) Drug Delivery

the protein needs to have the appropriate 3D structure

Term
how do we get around antigeneicity in MABs
Definition

i) chimeric antibodies
    ii) antibodies produced in transgenic mice, rats or yeast

        iii) phage display antibodies

Term
what contributes o instability in protein drugs
Definition

   deamidation: Asn, Gln

   oxidation: Met

   proteolysis: Arg, Lys

   racemization and acid labile: Asp

   disulfide exchange: Cys, disulfide

   aminolysis: Lys

   beta-elimination: Cys, Ser, Thr, Lys

b) Proteolysis during storage due to enzymes associated with bacterial contamination

Term
how can you help preserve protein drugs
Definition

c) Protein often more stable in dry form (lyophilized)

d) Additives to enhance stability

e) Detection of instability

Term
what methods do you use to measure the stability of a recombinant protein
Definition

  1. SDS page-detecs frafmentation, crosslinking, oligomerization
  2. RP-HPLC- deamidation, crosslinking, methionin oxidation, disulfide scrambling
  3. IEF- deamidiation
  4. potency determination- disulfide scrambline (most important)

Term
what are some issues with drug delivery of protein drugs
Definition

hard to give without denaturation (chemical alteration)

rapid liver clearance

Term
what are some solutions to drug delivery pproblems with protein based drugs
Definition
give drugs parenterally, nasal, implants, use microspheres for sustained release, inhalers
Term
what kind of changes would you see in a 2nd generation protein based drug
Definition
      i) Modification or removal of selected amino
      ii) Production via an alternate source (see below)
      iii) Deletion of unessential portion of the protein (e.g.
Sermorelin)
      iv) Introduction of disulfide bonds
      v) Proper phosphorylation required for biological activity
Term
what will maintain a proteins 3d structure when it is dried out
Definition
glycosylation (sugars)
Term
what receptor recognizes the carbs on the surface of a protein
Definition
asialoglycoprotein receptor (basically there to replace damaged proteins)
Term
why would you pegylate your protein
Definition
this should decrease clearance and thus increase efficacy
Term
what are some sources of protein products
Definition

E.coli

yeast

mammalian cells

transgenic animal/ plant sources

 

Term
what are some charecterisitcs of using E.coli to produce your proteins
Definition

i) Cheapest
ii) No glycosylation or
disulphide formation
iii) Fusion proteins

      iv) Met at N terminus of the
v) Toxins (gram positive bacteria) in
E.Coli

Term
what are some charecteristics of using yeast to make your proteins
Definition

i) Relatively inexpensive
ii) Hyper or incorrectly glycosylates

      iii) Correct disulfides 
iv) No toxins
v) Proteins excreted into medium

Term
what are some charecteristics of using mammalian cells to produces your proteins
Definition

i) Most expensive of cell-based methods
ii) Produces the most active protein due to proper modifications
iii) Proper post-translational modifications

          glycosylation
    phosphorylation
    disulfides
   
propeptide processing

Term
what is the deal with using transgenic animals as a source for proteins
Definition
insert a gene so that the animal will express the protein of interest and maybe secrete it in it's milk or egg
Term
in a protein based durg is it easier to prove bioequivelance
Definition
no since you have very subtle changes in production that alter bioequivelance
Term
what does an antisense oligodeoxynucleotide do
Definition
it binds to the DNA strand to block expression of the protein
Term
what is the difference betweent antisense and sens agents
Definition
antisense you only need to develop a 1 dimensional drug (know the sequence of the DNA) where as in sens you need a particular 3-d structure
Term
if you increase the length of an antisens agent what increases and what decrease
Definition

affinity increases (and your able to miss a pair)

you decrease specificity

Term
what is the magic number to max affinity before you lose specificty
Definition
15 base pairs
Term
in a antisense agent what type of base pairs will increase affinity
Definition
G/C 
Term
what are some antisense targets
Definition

Target genes at DNA or RNA level that code for

     i) proteins in microorganisms to kill invading organism

     ii) proteins specific to cancer

     iii) any undesired protein

Term
in leukemia how can use antisense agents
Definition

remove the bad bone marrow and replace it with good bone marrow

kill the leukemia cells in the bone marrow

Term
how does an antisense agent work at the DNA level
Definition

blocks transcription by forming a triplex (three strands)

 works at single strand to form a bubble

Term
how is the antisense agent going to work on the mRNA level
Definition

during synthesis

at the intron exon junction

inhibits protein initiation factors

Term
how does an antisense agetn work to block ribosome interactions
Definition

at the start codon

and overall interactions

Term
what are some issues with antisens development
Definition

absorption (limited ability to cross membaranes

stability

affinity to binding

Term
how can you enhance antisense products uptake
Definition

co-admin with cationic lipids

encapsulation in carbs

chimeric molecules

alternate backbones (with methylphosphonate)

Term
how can you increase stability of antisense products
Definition

block 3 prime exonuclease activity

sub the phosphodiesterase bond with a peptide bond

 

Term
what kind of sugar modifications can you make to antisense molecules
Definition

i) Enhance stability and affinity: alpha-anomer at 1' position of 2'deoxyribose

     ii) Resistance to nucleases: 2-OH modifications of ribose including 2'methyl,  2'-allyl, or 2'-fluoro (also enhance affinity)

Term
what kind of base modifications can you make to your antisense molecules
Definition

Hydrophobic modifications of 5' position of pyrimidines that enhance affinity for target RNA or DNA

Term
what is interference RNA
Definition
a molecule that forms a duplex of with mRNA then it degrades it (this ultimately causes gene silencing)
Term
how do they deliver interference RNA
Definition
give it a short hairpin then once it gets into cell the dicer will cut it up
Term
what is a ribozyme
Definition
RNA molecules that assume tertiary structures and have the ability to catalyze chemical reactions, making them catalysts
Term
what are some applications of ribozymes
Definition

target HIV

and lower expression  of MDR (transporters that eject drug from cell)

Term
what are goals of target based drug design
Definition

1) Understand atomic details of drug binding strength and specificity

 
2) Identify or create novel molecules to bind to a selected target and elicit a biological response via de novo drug design or database searching techniques


3) Optimize the therapeutic index of an already available drug or lead compound

Term
what stabilizes a beta sheet 
Definition
the bond between the carbonyl and the NH group
Term
where can you find a prosthetic group
Definition
in vitamins (tertiary structure)
Term
what kind or receptor is rhodpsin
Definition
G-protein coupled receptor
Term
what is molecular modeling
Definition

3D representation of molecules based on graphic or mathematical representations of chemical structures

Term
what is quantum mechanics
Definition

treat electrons explicitly

limited to 100 atoms

Term
what is molecular mechanics
Definition

deals with atom as smallest particle

every atom interacts with ever other atom

allos you to study a system with millions of atoms

Term
what is the empiracal energy finction
Definition

V total=Vinternal+Vexternal

where Vinternal=Vbonds+Vangles+Vdihedrals

Vexternal=Vvanderwaals+Velectrostatic

Term
what is dihedral angle talking about
Definition
rotation about the central bond
Term
when looking at the COS function for a dihedral bond how can you tell the difference between a single bond and double bond
Definition

double bond has 2 peaks (a peakseperated by 180 degrees)

in a single bond you have 4 peaks (each peak seperated by 60 degrees)

Term
when looking at the van der waals energy diagram what happens to attractive forces and repulsive foces
Definition

the closer you get the less your attractive forces are

the closer you are the greater your repulsive forces

Term
for a double bond how many maxima and minima are there
Definition
2
Term
if a molecules graph (dihedral angle vs potential energy goes to 0 at 0 degreess and 360 how many global minima are there
Definition
1
Term
what is energy minimization
Definition
figuring out how to alter your structure to get to the lowest energy level (must go from energy to force)
Term
what happens to force the further away from the minima you are
Definition
the more posative or negative it becomes
Term
how do you figure out how many degrees of freedom you have
Definition
the amoung of conformations raised to the power of the amount of atoms are in the molecule
Term
how long can you predict movement in an atom of a molecule
Definition
fentos second (10to the -15S)
Term
MD simulations can give you what values
Definition
entropy but ultimately free energy
Term
what info is required for calculations of energy for minimization and for molecular dynamics
Definition

energy (atom positions)

energy minimizations (atoms positions, forces)

molecular dynamic simulation (atom simulation, forces, atomic velocities)

Term
what id docking (database searching)
Definition
screening through a list of none compounds to see if they will bind to your site
Term
what is de novo design
Definition
design novel compounds by putting diffrent pieces together to fit your recteptor
Term
what is pharmacophore
Definition

geometric arrangment of functional groups

can be determined by 3d structure, knowledge of ligand

Term
what is grid in relation to pharmacophore
Definition

this is a way to develop a pharmacophore by

a) Prepare a 3D lattice of grid points encompassing the binding site


b) Determine interaction energy of different types of functional groups with binding site at each grid point.

 

c) Select favorable interaction sites

 

d) Determine relative spatial orientations of the selected interaction sites

Term
in a grid what yields a pharmacophore
Definition
types of functional groups and their positions
Term
what counter acts a dipole
Definition
solvation energy this may facot for example a carbonyle
Term
explain what docking is
Definition
Computationally identify compounds with a high probability of binding to a site on a protein or RNA
Term
what are the steps in docking
Definition

  1. determine solvent accessible surface of binding pocket (spheres)
  2. generate a negative image of receptor based on spheres
  3. determin sphere distances of the negative image
  4. convert sphere distances to atom distances
  5. compare atom distances with actual atom distances
  6. select ligands with greatest overlap
  7. calculate ligand receptor interaction energies

Term
what is groupbuild
Definition
this is a de novo computer program that builds a molecule up from scratch to the receptor
Term
how do you perform a group build
Definition

  1. develop a grid for binding site (include electrostatic, VDW)
  2. generate a structures (first is the core, then you build up on it then randomly select one of the top 25%
  3. synethesise compounds

Term
how do analyse yo'u groupbuilt structure
Definition
A)Visual examination of structures for chemical feasibility

B) Identify specific positions of certain functional groups etc. that my be related to a known pharmacophore

C) Database screening for similar compounds in chemical databases (avoid synthesis!).

Term
what are the limitations of database screening and de novo design
Definition

 

Rigid geometry of receptor and ligand

  Ligands often treated as flexible

  Multiple conformations of receptor can partially overcome rigid representation

Inherent assumptions and simplifications in molecular mechanics

 

Term
how do you perform lead compound optimization
Definition
use free energy perturbation 
Term
what are the steps involved in drug receptor interactions
Definition

1) diffusion controlled encounter

2) initial Michaelis complex

3) desolvation of both inhibitor and binding site

4) conformational changes of both inhibitor and binding site upon binding

5) correct orientation between drug and receptor binding site

Term
what is Thermodynamic cycle applied to relative binding of two inhibitors
Definition

a method to compare 1 drug receptor complex to another

Keq2/Keq1=Kreceptor/Ksolution

Term
how is alchemical perturbation performed
Definition

  1. in a computer you change molcule 1 that is bound to the receptor to molecule 2 in the receptor
  2. this is done by change the equilibrium and force constants in small steps

Term
why perform alchemical perturbation since in reality you can't do it
Definition
since you can just develop the final product (the final state is the only thing that matters)
Term
how does free enery component analysis work
Definition
you will essentially add up all the portions that contribute to the whole
Term
Dihydrofolate Reductase is a target for drugs why
Definition
it is involved in synthesis of DNA and can be a target to stop cancer
Term
what diseases are Dihydrofolate Reductase targets involved in
Definition

1) Anticancer agents

2) Antibacterials

3) Non-surgical abortions

Term

Dihydrofolate Reductase uses what as an electron source

Definition
NADPH
Term
what makes up Dihydrofolate Reductase, and which are good targets for drugs
Definition

glutamic acid

benzoic acid

bridge

pteridyl

the drug target is the pteridyl

Term
what are the three different types of Dihydrofolate Reductase inhibitors
Definition

  1. amino pteridine (competative inhibitor)
  2. methotrexate (just adds a cabonyl to the amino group of the pteridyl )
  3. trimethoprim

Term
why use natural products
Definition

  • we evolved with them
  • chemistry is similiar
  • diverse plants and diverse chmistry as a result
  • tend to be nourshing and supportive

Term
what is the doctrine of signature
Definition

using a plant that mimics human anatomy or disease

ex 

 

Walnut for brain health •

Red juice of bloodwort for blood disorders •

Kidney-shape leaves of Hepatica to treat  •

kidney disease

Term
why eat organs
Definition
some cultures believe that eating an organ will give you a healthy organ kidney for enhanced kidney
Term
what were some other uses of natural producte
Definition

  1. arrow poison
  2. religous rituals (phyostigma
  3. belladonna oracle of apollo, and cosmetics
  4. as corecers drug

 

Term
traditional chinese med started by shen nung used what
Definition

wormwood against malaria, fever

toad skin for heart conditions (digitalis glycosides)

used ephedra sinica as stimulant

Term
what is pen tsao kang mu
Definition
this is a book of chinese traditional meds compiled in the ming dunasty
Term
what is the ebers papyrus
Definition

16th century book on its meds

 

Term
what are some herbals that were dated back to egypt
Definition
aloe and poppy seeds
Term
where was snake root used first
Definition
india
Term
what laid the foundation of western medicine
Definition
ancient greeks (hippocrates esp)
Term
what is de materia medica
Definition
this was a compliation by roman dioscorides that had over 600 species of plants with medical values
Term
whats the deal with mandrake
Definition
it was used as a pain killer anesthatic
Term
how did islam contribute to medicine
Definition
pharmacy had the highest reputation in arab world, and was the first time it was independent
Term
where was the fist pharmacy
Definition
baghdad in 8th centurary
Term
what is hindiba
Definition
a plant to treat cancer
Term
what is black seed
Definition

regarded as the greatest form of healing med in islam

now it is none to have many of the nutrients reccomended by the FDA

Term
the start of the renasissance rang in
Definition
the age of herbals
Term
how many americans use CAM
Definition

40% of american population

73% of cancer patients

Term
what is the largest part of CAM
Definition

herbal medicine

ingested

aroma

ointments

Term
what is the problem with herbals branded as supplements
Definition

labeling issues

no quality control

misinformation in literature

Term
are herbal meds standarized (guranteed to have certain amount of active ingredient)
Definition
some are some are not
Term
what are the top three challenegs with herbal products
Definition

supply issue

quality issue

safety issue (herbal drug food interactions)

Term
thermogenics are herbs to control weight loss what is the most common
Definition

caffeine

followed by ephedra

Term
what is nother name for ephedra
Definition
brigham tea
Term
what is fo-ti root
Definition

long life elixer

reverses gray hair, ED, vaginal discharge

Term
research on fo-ti root revealed what
Definition

it may lower cholesterol

mild laxative

Term
what is bay chi root supposed to do
Definition
be an antioxident lower blood pressure
Term
what is konjac used for
Definition
reduce appetite, regulate insulin, help with weight, regulate LDL cholesterol
Term
what can apple cider vinegar do for you
Definition

weight loss

lower blood pressure

reduce cholesterol

fight arthritis pain

relief sore throat

Term
glucosamine is safe for regular use for how long
Definition
4 years
Term
what is SAMe used for
Definition
depression arthritis liver disease heart disease
Term
what are the top ten herbals
Definition

Ginko

echinacea

garlic

ginseng

soy bean

saw palmetto

st john's wort

valerian

bilberry

black cohosh

Term
what is active ingredient in ginko and is effective for what
Definition

increase blood flow

possibly effective in dementias

only safe for a year use

Term
when should you not use ginko
Definition
with caffeine and stimulants, with antiplatelets
Term
what does echinacea do for you
Definition

produces nonspecefic immune activation

use with flu

Term
how long can you use echinacea for
Definition

12 weeks

8 weeks in autoimmune disease

Term
why not use long term
Definition
can be immunosupprsive and in autoimmune disease will exacerbate symptos
Term
what is garlic used for
Definition

active ingredient allicin will lower lipids and cholesterol

 

Term
how should you take garlic
Definition
enteric coated since it will be destroyed by gastric acid
Term
what is ginsing used for
Definition
possibly effective for improved cognitive function, type 2 DM, bronchitis
Term
how should you use ginsing (how long)
Definition
3 months on and a period off
Term
what are some interactions of ginsing and precautions
Definition

interacts with lasix, inhibit barbitutes

may increase BP and overuse can give insomnia headaches etc..

Term
what is soybean used for
Definition
estrogen replacement
Term
what is saw palmetto used for
Definition
helps relieve stage 1 and 2 BPH due to anti-teterterone action
Term
what can you use st. johns wort for
Definition
may work on mild to moderate depression
Term
what are some contraindications to st johns wort
Definition

sever depression, suicidal tendencies, sever agitation, prego, may induce seratonin syndrome with triptans, mat interfere with cyclosporin, inhibits CYP450

may cause photosensitvity

Term
what do you use valerian for
Definition
sleep sedation
Term
what is black cohosh used for
Definition
relieved premenstrual symptoms
Term
what is milk thistle used for
Definition
used to help chronic liver disorders
Term
what is ginger used for
Definition
anti emetic antimotion sickeness
Term
what percentage of drugs are derived from natural products
Definition

about 25%

74% of anticancers

78% of anti-bacterial

Term
why has natural products for drugs been on the decline
Definition
 incompatablity with HTS
Term
what are natural products as drug sources
Definition

natural products produced in cells

primary metabolites

secondary metoblites

Term
what are lipinski's rule of 5 for oral drugs
Definition

 

 

  1. Not more than  ƒ5 H bond doners (OH and NH groups) 
  2. hydrogen bond acceptors  10 (5X2) Not more than (notably N and O) 
  3. A molecular weight under 500 (5x100)  ƒ
  4.   A partition coefficient logP 5 under
  5. < then 10 rotatable bonds

 

 

Term
what are the three most common toxic substances within herbals
Definition

pyrrolizidine alkaloids

phorbal esters

aristolochic acids

Term
what is wrong with BOrage
Definition

it can be teratogenic, carcinogenic, hepatoxic

contains pyrrolizodine alkaloids

Term
what is wrong with sweet flag
Definition
contains cis-isoasarone that is a carcinogen
Term
what is wrong with chaparral
Definition

is nephrotoxic and hepatotoxic

contains NDGA

Term
what is wrong with coltsfoot
Definition
hepatotoxic pyrrolizidine alkaloids
Term
what is wrong with comfrey
Definition
this is hepatotoxic due to pyrrolizadine alkaloids
Term
what is wrong with germander
Definition
 hepatotoxic due to diterpenoids
Term
what is wrong with licorice
Definition

it is a pseudoaldosteronism (retains Na, water and depletes K)

this is dose dependent

Term
what is wrong with poke root
Definition
this is highly toxic to organs due to triterpenoid saponins
Term
what is wronge with sassafras
Definition
contains safrole which is a carcinogen
Term
rule of thumb for herbals
Definition

 Avoid using herbs in 

infants, children, pregnant women, 

nursing mothers, patients w/ daisy 

allergies, patients on multiple 

medications

Term
herbals can effect drugs how
Definition

they can alter transporters

they can alter CYPS

alter absorption

compete with drug targets

Term
what drug interacted with saquinavir
Definition
Garlic
Term
how does St.Johns wort affect CYPD3A4
Definition
it will induce it
Term
what are the applications of QSAR
Definition

classification

diagnosis of mechanisms of drug action

prediction of activity (in congeneric series)

lead compound optimization

Term
how did we make sulmazole stop giving us halucinations
Definition
used QSAR to do a bio-isoteric replacement lowreing coefficient to 1.2 so it dind't cross BBB
Term
what is the hammemett electronic parameter (σ)
Definition
this will tell you the electron donatin or withdrawing properties
Term
what does a positive σ tell you
Definition
that you have an electron withdrawing group and increase Ka
Term
what does a negative σ
Definition
it is electron donating  and it will decrease Ka
Term
when you substitute at the para position how will this effect the ring, how about ortho and meta
Definition

  1. the ortho position will have minimal transferability
  2. the meta position will have an inductive effect (may favor unionized thus smaller Ka) a -σ
  3. if you have a para substituant then you will have resonance effects(increasing Ka) a +σ

Term
what is the general utility of σ values
Definition
it allows you to predict it's value and contribution for similiar compounds
Term
when graphing σ what is a posative slope and a negative slope
Definition

the posative slope is an electron withdrawing group

the negative group is electron donating

Term
what is tafts seric parameter
Definition

Es

this says that the impact of the substiuant is dependent on size( the term is always negative and the more so it is the more steric hinderance)

Term
what does molar refractivity tell you
Definition
the molar refractivity goes down as the molecule becomes more dense and this is better
Term
how can we apply QSAR to the biologic system (biological hammet relationship)
Definition

Consideration of need to cross membranes

Blood brain barrier

Lipophilicity (hydrophobicity)-this will dictate how fast it can cross the barrier

Term
what is the hydrophobicity
Definition

if it is + then it will be more hydrophobic

if it is- it will be more hydrophillic

Term
say you have a functional group that adds a ∏ of.5 and the same thing next to it how would you calculate the overall effect
Definition
.5+.5+interaction factor
Term
when you use the linear equation you will have a final K what is this
Definition
this the activity of the unsubstituted compound
Term
if you want to increase activity what do you want ∏ to be and σ
Definition

  1. ∏ you will want this to be negative, but not so much to where it wont go into the lipid bilayer (more hydrophillic)
  2. σ you will want this to be posative (electron withdrawing)

Term
what is the disadvantage of hansch equation
Definition

hard to extrapolate byond your list

predictions are limited to rings

you will need 5 compounds for every term you use

Term
what is the spanned substituion space
Definition
range of physical properties covered by the compounds in the training set (QSAR)
Term
the free wilson model tells you what
Definition

it's like an on off switch

I is substituant and J is location

Term
what is the topliss decision tree
Definition

  • basically trying to find your drug without using a training set
  • measure then add what you think is needed measure then keep doing this till you are close to what you want

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