Flashcards in Lecture 1 (Intro to MedChem) Deck (101):
What is a lead compound?
A lead compound is like the first draft of a drug. It has the correct pharmacological effect but it is not perfect. It most likely needs to be tweaked to obtain the most optimal and effective drug function.
How are drugs improved?
By using a SAR (structure activity relationship) we can turn lead compounds into safe and effective drugs.
Two types of SARs?
-this is the only one we are concerned with
How is a QSAR used?
Uses a mathematical relationship between PHYSICOCHEMICAL PROPERTIES to their pharmacological activity to predict the most potent structure.
Why won't we be studying QSAR?
Because it cannot easily be extrapolated to new drugs. It requires extensive research for each drug.
How is a SAR used?
-uses the relationship of the STRUCTURE (arrangement of the functional groups) and the pharmacological activity of the drug
What are the chemical properties of drugs we need to consider?
-placement of covalent bonds
-electron effects of functional groups
-ED (electron donating)
-EW (electron withdrawing)
What drug properties are going to be affected by different things?
Describe sigma bonds
-formed by hybrid orbitals
-free rotation around this bond
Describe pi bonds
-formed by overlapping P orbitals
-no free rotation around this double bond
ability to attract electron density
How does EN increase on the periodic table?
to the right and up it increases
What 2 ways can electron density move through a molecule?
movement of electron density through pi bonds (conjugated system)
Every 1st bond is ____?
Every 2nd or 3rd bond is ___?
What are sigma bonds made from?
hybridized orbitals (sp)
What are pi bonds made from?
leftover p orbitals
movement of electron density through sigma bonds (saturated carbons)
How do you determine whether a functional group with be ED or EW?
-presence of lone pair electrons
-multiple bonds (geometry of the molecule)
Electronegative atoms with a lone pair (excluding halogens) are __ through _________.
Alkyl groups - the more branched, the more _____.
Attached group with a double bond O or N or triple bond N are __ through __________.
pKa _____ for acids
low (inverse of Ka)
Ka ____ for acids
high (if they dissociate there is more of the ions than the acid - so a bigger number/ smaller number = high number)
pKa ____ for bases
high (inverse of Ka)
Ka ______ for bases
low (bases don't like to dissociate so there would be less of the ions than the base - small number/big number = low number)
Ratio of ionization of a weak acid is what ratio?
[HA] / [A-]
Ratio of ionization of a weak base is what ratio?
[HB+] / [B]
To maximize ionization of HA to A-
pH > pKa
To minimize ionization of HA to A-
pKa > pH
To maximize ionization of B to HB+
pKa > pH
To minimize ionization of B to HB+
pH > pKa
We use pKa to measure ___ ________.
We always assume the solvent is _____?
When we talk about the pKa of a base we will most likely be talking about ??
primary, secondary, or tertiary amines
What is the difference between primary, secondary, and tertiary amines?
The N is attached to 1 R group and 2 H's
The N is attached to 2 R groups and 1 H
The N is attached to 3 R groups
How does the scale of basicity go for amines?
Secondary > Primary > Tertiary
What is a substituent?
-an atom or group of atoms substituted in place of a HYDROGEN on the parent organic compound
-bond angle 109.5
C-C bond length 1.5A
-bond angle 120
C=C bond length 1.3A
-non-polar (but depends what R groups are)
-usually ED but can be EW depending on substituents
-bond angle 180
-C=-C (triple bond) bond length 1.2A
-non polar (hydrophobic)
Are alkanes and alkenes water soluble?
No way jose
What happens when an alkane or alkene gets larger or more branched?
Becomes less hydrophilic or more lipophilic
Halogenated hydrocarbons are generally less _____ than the alkyl form.
Halogenated hydrocarbons are ______.
Halogens on saturated hydrocarbons are ___ by _______.
Why are alcohols more water soluble?
They have an OH group (hydroxyl) which increases polarity and therefore makes it more water soluble because water is also a polar molecule.
Describe the hybridization and geometry of alcohols
Alcohols from bonds with water through what type of bond?
How is an OH ED?
How is an OH EW?
T or F: an alcohol only accepts hydrogen bonds
alcohols are H bond donors and acceptors
Why do alcohols have a permanent dipole?
*those two bad boys result in a permanent freaking dipole
With increasing length of hydrocarbon chain on an alcohol - how does that affect solubility?
Are alcohols very acidic?
NO WAY JOSE
Does alcohol solubility depend on location of OH?
Describe a phenol
-special type of alcohol
Are phenols generally more acidic (more acidic means LOWER pKa) than aliphatic alcohols?
you bet your ass they are :D
aromatic hydrocarbons are ________
SH (sulfhydryl) groups are ALWAYS __?
ED (sulfur is not very EN so it's not going to withdraw - it will donate)
SH group is _____ polar
RSH is more _____ than ROH
R-O-R is a ??
R-S-R is a ???
ethers and thioethers are weakly _____
SR (thioalkoxy) is ____
OR (alkoxy) is ____
sulfoxide is always ___
sulfone is always __
Describe the hybridization and geometry of aldehydes and ketones
aldehydes and ketones are always __
EW (they have an oxygen which is highly EN) - so therefore it will withdraw electrons
aldehydes and ketones are in rapid equilibrium with ____ to form hemiketals and hemiacetals
_____ have an sp3 tetrahedral N centre
Are amines basic or acidic?
Are amines polar?
The N of amines are basic due to what?
free lone pair of electrons
describe the hybridization and geometry of carboxylic acids (RCOOH)
Are carboxylic acids polar?
neutral form of carboxylic acids are ____
anionic form of carboxylic acids are ____
Are esters (RCOOR) polar?
Are esters (RCOOR) ED or EW?
esters are susceptible to _____
What are esters frequently incorporated for?
To facilitate absorption of carboxylic acid drugs (they act as a pro drug)
Describe hybridization and geometry of amides
are amides polar?
heck yes (napoleon dynamite voice)
Is the N of an amide (RCONHR) basic?
NO (because lone pair of electrons forms resonance structure and therefore is not available to accept a proton)
* N of amine = basic
* N of amide = not basic
The H of RCONHR (amide) is usually ___?
only very weakly acidic
Are amidines and guanidine's polar?
In neutral form amidines are ___
In neutral form guanidine's are ___?
weakly EW and weakly ED due to electronegative nature of the N
*see slide 48 for details of structure
In ionized form, both amidines and guanidine's are ___
Are amidines and guanidine's less basic than amines?
No, they are more basic.
Are Nitro (RNO2) highly EW or ED?
EW all the way
Is the negative charge on the O in a nitro (RNO2) able to accept a proton?
no way man
Describe hybridization and geometry of sulfonic acids and sulfonamides
T or F: sulfonic acids and sulfonamides are highly polar and EW
true true true
Heterocycles usually contain what 3 elements?
S, O, and N
Drugs with a 3 or 4 membered ring (heterocycle) are usually ???
strained and unstable (like me after a night of drinking)