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Medicinal Chemistry

Terms in this set (67)

Phenol acid or base and strength?
Acid, weak, has to be reacted with a base like water which allows for a strong phenolate iom conjugate base more water soluble
Phenol metabolism in vitra
02 air forms o
Phenols bonding
Aromatic ring van der waals and OH hydrogen bond dipole interaction
Water solubility portions of phenols
Aromatic ring is lipophillic and phenol is hydrophillic, dipole dipole is within the phenol itself
Solubility of phenol when added to water
Ion- dipole more water soluble
What determines the acidity of a phenol group?
The ability to stabalize the phenolate ion, more e- withdrawing more stable
Order these compounds in increasing basicitiy
-NH2 -NO2 -COH -OH -NH3+ -Br -CH3
-NO2 -NH3+ -COH -Br -CH3 --OH -NH2
Order in increasing acidity
-alkylNH2 -H2O -arylOH -NaOH -HCl -COOH
-NaOH -alkyl NH2 -H2O -arylOH -COOH -HCl
Where does an electron donating group direct? Electron withdrawing? How does this effect the phenolate ion?
An electron withdrawing group direct meta and stabilizes the Phenolate
ED directs ortho para, pushes lone pair of electrons onto oxygen decreasing stability
Metabolism of thioethers
Dealkylation --->thiol---->disulfide bond
oxidation to form sulfoxide ---> sulfone
Metabolism of ethers
Dealkylation to form primary alcohols and aldehydes by CYP enzymes
What undergoes oxidation with 02 to form a peroxide intermediate in vitro?
Liquid Ethers to form primary alcohols and aldehyde
Is an ether water soluble? If not why? If so, when?
An ether is not water soluble unless it has 2 solubizing carbons, more carbon substituents more van der walls more lipophillic
Determine activity of the following on an aromatic ring, most to least activating....
Amide, 1 amine, carboxylic acid, ether, ester, alcohol
Amine, OH, ether, amide, ester, carboxylic acid
Does this reaction favor K1 or K-1? Which value is larger?
Phenol + KOH -> phenolate + H2O + K+
K1 is greater than K-1 favoring products, strong base, weak acid
Does this reaction favor K1 or K-1? Which value is larger?
H2SO4 + NaOH -> H2O + HSO4- + Na+
What would happen if this was reacted with bicarbonate?
K-1 is larger due to the high strength of acid and base
Bicarb is a weak base, K1 would be larger
When a phenol is substituted with a nitro group, which position on the ring would it be most acidic? Give 3 groups each in order of activation which would place nitro in that orientation besides phenol?
Para more acidic, than meta
3. -ether -amide -ester
3. -1 amine - NR2 -OH
3. -R -aromatic ring -double bond
What functional group undergoes phase 2 metabolism with amino acid conjugation? How so?
Carboxylic acids, add acyl group to make OH a good leaving group, end product NH2 amino acid
What is the phase 1 metabolism of carboxylic acids?
Beta oxidation only if theres a beta hydrogen available!!!
Split into CA and acyl
If you react a tertiary amine where one R group is a Br- with H30+ how does it effect the Ka and Kb of the reaction?
Reaction will favor the strongest acid (weakest base) so it will favor the reactants with the tertiary amine bound to the halogen versus the strong base secondar amine
Starting with aniline how would the following affect bascitity and the relative pKa?
-pNO2 -mBr -pCH3 -mNH3+
-pNO2 decreases pKa
-mNH3+
-mBr
-pCH3 will increase pKa in relative to aniline
When reacting a NH3with hydrochloride, what intermolecular bonds will be present in aqueous solution?
What if the ammounium salt formed was reacted with H2PO4? What effects does it have on pH and the media it would be found?
Due to the salt formation (NH4+ with Cl-) in water will make
Ion-dipole between the ammonium and the water

Dissolvable salt formation, due to the strong acid which would therefore decrease the pH and be found in blood, cytoplasm, and water.
Determine the increasing acidity of the following groups
-H2O -CONHCO -SO2NH2 -ArOH -H30+ - KOH -RCO2H
KOH, H2O, CONHCO, SO2NH2, ArOH, RCO2H, H3O+
What happens when an ammonium salt reacts with a weak acid? Example of a weak acid?
A neutral pH results if it's a weak salt. Tartarate
Do aldehydes undergo oxidation or reduction more commonly in vivo?
Oxidation to form a carboxylic acid with dehydrogenase or oxidase
What's an important reaction for aldehydes for chemical reactivity?
Reversible Polymerization, intermediate with O groups as a cyclic ring, reversible, not a chemical instability
What is an irreversible reaction of a functional group that forms a carboxylic acid?
Oxidation of aldehydes
Which is true of chemical reactivity of aldehydes and ketones?
1. Must react 2 mol of OH to form a hemiacetal with an aldehyde
2. A ketal can be noted as an irreversible chemical instability
3. A ketal can be reversed to a hemiketal by removing water and reacting with a strong acid
4. Ketones undergo polymerization to an irreversible product
1 would be true if using 2 moles to form acetal
2 it's a reversible rxn and is stable
4 aldehydes, is reversible
3 is true
Explain the difference between alpha and beta configuration of a hemiacetal?
-OH group beta would be Equatorial
-OH group alpha would be axial
Explain 3 important chemical properties of a thioether
1. Strong Nucleophiles
2. Large molecules
3. Lipophilic
Explain phase 2 reaction would make an amine less soluble?
1. Methylation of primary or secondary amines
When a ketone is reacted with water, what change in conformation occurs and are products or reactants be favored?
Favors reactants, tautomerization occurs favors the keto not the enol
What is the only metabolic process a tertiary amine can undergo in the body? What phase of metabolism would this be?
Dealkylation- Phase One
Determine the ability to dissolve in water of the following compounds..
-HNO3 -AlkylNH2 -Ph-OH -ArylCOOH -COOH -ArylNH2
HNO3, -ArylCOOH -COOH -Ph-OH -ArylNH2 -AlkylNH2
Starting with TOLUENE Order these substituents on an aromatic ring from most to least acidic

-NH2 -NR3+ -OR -OOR -COOH - SOO(OH) -I -F -CHO
-NR3+ -SOO(OH) -COOH -CHO -F -I -OOR -OR -NH2
Name the intermolecular forces from weakest to strongest
Van der walls, dipole-dipole, H-bonds, ion-dipole, ionic, covalent
Which intermolecular bond is most dependent on temp and distance?
Van deer waals
Give 3 examples of a dipole dipole bond
H20 + CH3Cl
S-H
C=0
N-H
O-H
T/F ion ion bonding is not affected by T and Distance
True
Give 2 examples of ion ion bonding, what does this do to solubility?
NH4+ Cl-
NH4 + OH- Increases solubility
Give an example of a lipid media, all.
Plasma membrane, GI tract, blood brain barrier, blood vessels, water immiscible solvents
When would you use a insoluble salt? What does this due to solubility? What types of bonds are formed as a result?
Hydroxy naphthalene or pamoate, make amines more in soluble in the mouth, can not use strong acid because this would result in acidic taste in the patients mouth. Van der waals
What is ibuprofen an example of, and what metabolism will it undergo in the body?

Bonus Points- which psychological disorder ibuprofen would cause
Carboxylic acid, it can undergo beta oxidation only after acylation or phase 2 gluconation
Delerium
Order compounds in increasing dipole moment
-CHCl3 -(CH3)Cl -(CH3)OH -(CH3)3Br -CH3NH2 -(CH3)2C=O
-CHCl3 -CH3BR -CH3NH2 -CH3OH -CH3
What results from an unequal sharing of electrons in a covalent bond?
Dipole moment
What account for lipid solubility in organic compounds?
What accounts for water solubility in organic compounds?
Van der Waals, dipole dipole
What is the bond for an electrostatic attraction between a cation and anion?
Ion-ion bonding
What can play a major role in increasing the dissolving properties of organic compounds in water?
Ion dipole bonding
Electrostatic attraction that occurs between a formally charged ion and a dipole?
Ion dipole
What type of bonding is present in a lipid media? Examples of a lipid media?
Van Der Waals, all aliphatic and aromatic have this property.
Lipid media include blood vessels, GI, blood brain barrier, plasma membrane, immiscible solvents
What type of bonding occurs in water soluble media? Examples?
Dipole Dipole interactions for solubility and solubility with water ion dipole
What does the addition of a halogen do to the properties of an aliphatic compound? What type of bond is present?
VERY Lipophilic, increases lipophillicity. A small dipole exists but van der waals overcomes the dipole so there is only van der waals present
How do halogen substituents effect flammability?
Increase in flammability with decrease amount of halogens
What is the exception to chemical reactivity of halogenated hydrocarbons?
Poly halogenated ethyl and methyl derivatives with 02 and heat to form phosgene
What is the reactivity of a halogenated benzene ring?
NO REACTION!!!!
Which functional group develops a reactive intermediate in which in nephro and hepatotoxic? What conditions does this reaction occur?
Halogenated hydrocarbons only if there is an alpha hydrogen available. Forms halo hybrid intermediate than release of HCl to form XC=O
What functional group does alcohol dehydrogenase work on? What are the products formed? What Phase reaction is this?
Phase 1 reaction of alcohols.
1 alcohol forms aldehyde than CA
2 alcohol forms Ketone
What reaction increases the water solubility of alcohols?
UDP conjugation
6 types of Phase 2 metabolism
1. UDP conjugation
2. Amino acid conjugation
3. Sulfonation
4. Methylation
5. Acetylation
6. Glutathione conjugation
What is the goal of a phase 1 metabolism? 3 examples?
Exposing a functional group within a molecule to make it more water soluble by increasing the polarity of the compound.
Oxidation, reduction,hydrolysis
Addition of S-H -COOH -OH -NH2
At a physiological pH what is the water solubility of a sulfate group? What significance does this have in metabolism?
Sulfate a are ionized at a physiological pH so they are very water soluble. They play a role in Phase 2 metabolism.
How are you able to reverse the formation of a ketal or acetal?
Addition of a strong acid
When are acetals considered unstable?
In an acid media
Give an example of 3 oxidizing enzymes and their effect on a particular functional group
Aldehyde dehydrogenase
Xanthinine oxidase
Aldehyde oxidase
Make aldehydes into carboxylic acids
What happens when you react r-NH3 and COOH
A weak base and a weak acid form a weak dis soluble salt, does not readily dissociate because weak acid and weak base, does not increase water solubility
Are amines more or less soluble than ethers?
More soluble
What reduces aqueous solubility when added to a carboxylic acid?
Heavy salts become insoluble in water, Ca, Mg, Al, Zn
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