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BPS 4125/CHM 4123

Medicinal Chemistry
Midterm 1 (October 5, 2018)

T


IAnswer key
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Cellular phones, unauthorized electronic devices or course notes (unless an open-book exam) are
not allowed during this exam. Phones and devices must be turned off and put away in your bag.
Do not keep them in your possession, such as in your pockets. If caught with such a device or
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your obtaining a 0 (zero) for the exam.

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BPS 4125/CHM 4123
Medicinal Chemistry 2018
Midterm 1 (October 5, 2018)
Name:
ID #:

1) Salicylic acid is an anti-inflammatory agent that also reduces fever and pain.
a) Which drug company was the first to market salicylic acid? (1 Point)

Bayer

b) Salicyclic acid is not found in nature. What is the name and structure of the precursor to
salicylic acid? Show how this precursor is converted into salicylic acid (7 Points).

f a.es bdrss EIEotit9 II.q x


hydrolysis
c) Name two natural sources of salicylic acid precursor. (2 Point) forgot
Willo bark birdobark Toko
solicylifid
2) In the early 1600’s there was no science for drug design and folk remedies and other irrational
methods were employed. However, Jakob Bohme (1575-1624) proposed a “method” to identify
natural substances with desirable medicinal properties. What was the name of this method? As part
of your answer explain the rationale behind the method and provide a relevant example from class.
(3 Points)

Doctrine
ofsignatures how to
God left us clues to tell us use things
walnut brains
e.g
Eyesight Eagles tfish
Efate ascended often c'm't
2
III ment
Mandrake root etc
Rhino horn etc
3) What is the only difference between a drug and a poison? List three natural products that were
known since the early 15th Century that clearly illustrate this concept. As part of your answer, please
identify the beneficial effect and the undersirable/toxic effect. (6 Points)

Dose
Poison e
Drug
Morphine Narcotic painkiller sedative 0

Cocaine Topical painkiller stimulant


Ergotamine smoothymouggldebfonythraction Hallucinogen

4) a) Despite a dramatic improvement in the understanding of science in the late 1800’s and early
1900’s, problems with drugs increased significantly. This has been attributed to four factors. List
these four factors. (4 points)

No regulation
Increased industrialization
Aggressive marketing
Lotsofopportunities forfraud
b) In the 1800’s individuals tended to utilize “patented medicine” under the misconception
that because they were patented they were proven safe and effective. Of course many
patented medicines were not safe and contained very toxic “medicinal” ingredients. List six
ingredients that were common to patented medicines. (6 Points)

Ethanol Copper Salts

Opium Mercury Salts


Arsenic Cyanide

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5) What is the Nuremberg Code? List the five criteria that must be observed. (6 points)

Guidelines for researchonHuinsubjects


Informed consent
Prior Animal studies
Benefits outweigh risks
Qualified scientists

toeing
6) Companies that produce generic drugs must adhere to specific guidelines for their products. What
are the two essential requirements in order to market a generic drug. (4 points)

substance is identical
Drug
Same dose
Generic must be biologically equivalent
Drug
same PK profile
Imax C max A afeta

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7) Aspirin is traditionally made using a Kolbe-Schmidt reaction. Using phenol (isolated from Coal
Tar) as your starting material, show how you would synthesize Aspirin using any other reagents
you require. You do not need to include a detailed mechanism but must show all intermediates as
part of your answer. (7 points)

Es I
Cdistilledfran
Coaltar A
0 AGO 2 04 Heat oH
Los
YEH pyridine Kody Excozo
Aspirin DMAP
ASA

8) Drugs can be classified as acids, bases and neutral compounds. What is the percentage of each?
(3 points)

Bases 75
Acids 20 0
Neutral 5 0
Took
5
9) The preclinical phase of drug development is essential. What does this phase assess/examine?
Clearly describe what is accomplished in each aspect of preclinical development. (8 marks)

Assesses SafI
Safetytesting I In vitro methods loads
ofRuns
Safety testing II Animal tests
At least one primatemodel
Rats Dogs

10) What is the metric routinely used to assess enzyme/receptor binding? As part of your answer
please show the relevant equation. What are the typical units for this metric? (4 points)

kd Di tant mm

Drug Bmidificate Biologicalmolecule


I Drug t

Kd EDragIBrologicalmdeate
Biological Molecule
11) Intermolecular forces are important for Drug
the binding of a drug to its target.
Which intermolecular
forces are directional in nature? Using a specific example explain what the term “directional”
means What is the relative strength of this interaction? (4 points)

Hydrogen Bonds CH bonds 4 8kc m of


strongest interaetic when pointingtowardseach other
Donor Accepted
bandi
Y strongest

weeder H band
Q 6
12) What are the four principles of modern structure-activity relationship (SAR) studies? (4 points)

Changeonly 1 structural element a time at


Putat least 3 points on a curve Goldilocksprinciple
Make propose compounds to answer questions
Focus on solvable problems
13) The Mitsunobu reaction is commonly used in the synthesis of many drugs. Using the reagents
provided below please provide a detailed mechanism (just like in your notes). (10 points)

PPh 3, DEAD
Ph Ph O
CH 3CO2H
OH O CH 3

Ito Qs on
real Et
Php
t
Ftoe o_O
IN N 4
Php
bet
45024
Gtsco
4990
Eto
f CEEt CH
ph p of o
F
Hoo
L Ph
Pha
Ctb
f P'T

O t I
PPhzetotty
H cozet
H
Ph THz
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