CHEM 443: Principles of Medicinal Chemistry II
Spring 2006
Any
student with a documented disability needing academic adjustments or
accommodations is requested to speak with Dr. Lapinsky during the first two
weeks of class. All discussions will
remain confidential. Students with
disabilities will need to also contact Disability Support Services in the Ley Student Center.
________________________________________________________________
People:
This
course is being taught by Dr. David J. Lapinsky.
Office: 241 Dell Butcher Hall
Office phone: 713-348-3069
Fax: 713-348-4500
Email: lapinsky@rice.edu
Personal
website: http://www.geocities.com/drlapinsky/home.html
Course
website: http://www.owlnet.rice.edu/~chem443/
The secretary for this course is Naomi
Duval.
Office: 244 Dell Butcher Hall
Office phone: 713-348-3479
Email: nduval@rice.edu
________________________________________________________________
Course Description:
This course emphasizes organic chemical principles and
reactions vital to drug design and drug action.
Clinically important drugs will be used as examples. The course is aimed at undergraduates and
graduates who have a basic grounding in chemistry and are interested in
learning about drug design and the molecular mechanisms by which drugs act in
the body. Consequently, the course is of
particular interest to students who might be considering a future career in the
pharmaceutical industry or a medical field.
It attempts to convey something of the fascination of working in a field
that overlaps the disciplines of chemistry, biochemistry, cell biology, and
pharmacology.
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Prerequisites and Expectations:
1.) CHEM 211 and CHEM 212 (Organic Chemistry sequence at
Rice University)
I work under the assumption that you know all the material
covered in “Organic Chemistry: Structure
and Function”, 4th edition, Vollhardt & Schore. As a result, things like stereochemistry,
proper electron pushing, etc. will not be re-taught to you. If you find yourself having trouble with any particular
background aspect of organic chemistry, please see me as soon as possible. Otherwise, I assume you know and will be able
to apply anything from sophomore-level organic chemistry. This aspect of the class is particularly
important because some quiz / exam questions are based solely on using your
chemical intuition rather than simply regurgitating something directly from
lecture. It is perfectly fair to ask you
something based on sophomore-level organic chemistry with a medicinal chemistry
focus even though the exact details were not discussed in lecture. In other words, anything from sophomore-level
organic chemistry is fair game. You
should be able to propose a mechanism for every reaction we discuss in class
where applicable.
2.) Some background in biochemistry (though not a necessity)
It is assumed that the student has taken a course in organic
chemistry that included the bioorganic components – amino acids, proteins, and
carbohydrates (sufficiently covered by the organic sequence at Rice University
or the concluding chapters of “Organic
Chemistry: Structure and Function”, 4th edition, Vollhardt &
Schore) – and is familiar with organic
structures and basic organic reaction mechanisms. Only the chemistry and biochemistry
background information pertinent to understanding the material will be
discussed. If you find yourself having
trouble with any particular background aspect of biochemistry, please see me as
soon as possible. Otherwise, I assume
you know and will be able to apply anything from the biological aspects
discussed via a sophomore-level organic chemistry course.
Whatever the case and in any regard, it should be made clear
to you what “background information” you are responsible for. If there are any doubts as to what is
expected of you as a student, please ask immediately.
3.) CHEM 442 (“Principles of Medicinal Chemistry I”) is not
a prerequisite for CHEM 443 (“Principles of Medicinal Chemistry II”) or vice
versa. Any fundamental topics introduced
and discussed in CHEM 442 will be reviewed for the CHEM 443 student.
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Time and Location:
Lecture
will begin promptly at 9:00am and end at 9:50am, Monday, Wednesday, and Friday,
102 Baker Hall.
Office Hours:
Dr.
Lapinsky will have office hours immediately after each class for one hour for
anyone who approaches him at the end of class or who has previously scheduled a
meeting by email.
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Text Book / References:
It is not
a student requirement to purchase any of the references given below, though
they best summarize
a medicinal chemist’s reference library.
Lecture material will be derived from these references and numerous
other sources including up-to-date information on the web.
1.) Patrick, “An Introduction to Medicinal Chemistry”
2.) Williams and Lemke, “Foye’s Principles of Medicinal
Chemistry”
3.) “Wilson & Gisvold’s Textbook of Organic Medicinal
& Pharmaceutical Chemistry”
4.) Silverman, “The Organic Chemistry of Drug Design and
Drug Action”
5.) Lednicer, “Strategies for Organic Drug Synthesis and
Design”
6.) Li, Johnson, Sliskovic, and Roth, “Contemporary Drug
Synthesis”
7.) “Top Pharmaceuticals: A Look at Drugs That Changed Our
World”, Chemical and Engineering News, June 20, 2005.
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Grades:
Grading
will consist of:
13 X
20-point journal homework assignments (due Mondays) = 260 points
12 X
20-point in-class cumulative quizzes (on Fridays) = 240 points
1 X
200-point cumulative final
Total =
700 points
No grades
will be dropped. Letter grades will be assigned from numerical grades based
on a curve.
Calendar of events:
January
Wednesday
January 11th, 2006 – First day of class
Monday
January 16th, 2006 – No Class (MLK Day)
Friday
January 20th, 2006 - In-class cumulative quiz (#1)
Monday
January 23rd, 2006 – Journal homework assignment due (#1)
Friday
January 27th, 2006 - In-class cumulative quiz (#2)
Monday
January 30th, 2006 – Journal homework assignment due (#2)
February
Friday
February 3rd, 2006 - In-class cumulative quiz (#3)
Monday
February 6th, 2006 – Journal homework assignment due (#3)
Friday
February 10th, 2006 - In-class cumulative quiz (#4)
Monday
February 13th, 2006 – Journal homework assignment due (#4)
Friday
February 17th, 2006 - In-class cumulative quiz (#5)
Monday
February 20th, 2006 – Journal homework assignment due (#5)
Friday
February 24th, 2006 - In-class cumulative quiz (#6)
Monday
February 27th, 2006 – Journal homework assignment due (#6)
March
Friday
March 3rd, 2006 - In-class cumulative quiz (#7)
Monday
March 6th, 2006 – Journal homework assignment due (#7)
Friday
March 10th, 2006 - In-class cumulative quiz (#8)
Monday
March 13th, 2006 – No Class (Midterm Recess)
Wednesday
March 15th, 2006 – No Class (Midterm Recess)
Friday
March 17th, 2006 – No Class (Midterm Recess)
Monday
March 20th, 2006 – Journal homework assignment due (#8)
Friday
March 24th, 2006 - In-class cumulative quiz (#9)
Monday
March 27th, 2006 – Journal homework assignment due (#9)
Friday
March 31st, 2006 - In-class cumulative quiz (#10)
April
Monday
April 3rd, 2006 – Journal homework assignment due (#10)
Friday
April 7th, 2006 – No Class (Spring Recess)
Monday
April 10th, 2006 – Journal homework assignment due (#11)
Friday
April 14th, 2006 - In-class cumulative quiz (#11)
Monday
April 17th, 2006 – Journal homework assignment due (#12)
Friday
April 21st, 2006 - In-class cumulative quiz (#12)
Monday
April 24th, 2006 – Journal homework assignment due (#13)
Journal Homework Assignments
20 points
each X 13 = 260 points total
Collected
Mondays at the beginning of class. Late
homework will not be accepted.
Choose an
article of interest to you from any of the medicinal chemistry related journals
below. All of these journals can be
found online via the Fondren Library website.
Bioorganic
and Medicinal Chemistry
Bioorganic
and Medicinal Chemistry Letters
Current
Medicinal Chemistry
Current
Topics in Medicinal Chemistry
Journal of
Enzyme Inhibition and Medicinal Chemistry
Journal of
Medicinal Chemistry
Current
Pharmaceutical Design
Journal of
Natural Products
Letters in
Drug Design and Discovery
These
journal homework assignments cannot be more than 3 pages long (front-side only)
and may be hand-written or computer typed.
Pages 1
and 2:
Write a
brief summary of the article of interest using short descriptive bullet
statements and structures. Highlight
only the main points and conclusions of the article while avoiding
insignificant statements. From reading
your summary, I should be able to get a clear picture of what the article was
about and why / how the researchers were doing the research they were doing
without having to read the article myself.
Your summary should only feature the “take home” messages of the article
and paint a clear picture. The clearer
the picture I get about the research described in your summary, the better your
grade.
Page 3:
Write a
detailed electron pushing mechanism for any organic transformation found within
the article. In other words, you must
choose an article where some kind of organic synthesis was performed.
For a
representative example of style and format for journal homework assignments,
please see the attached example at the end of the syllabus.
In-Class Cumulative Quizzes
20 points
each X 12 = 240 points total
A ca.
15-minute in-class quiz will be given at the beginning of class on
Fridays. No make-up quizzes will be
offered. Although the quizzes are termed
“cumulative”, more than likely they will focus on material covered in lecture
over the past week. Solutions to the
quizzes will be posted on the course web site in a timely fashion. For examples of testing style, see the course
website for CHEM 442 or CHEM 443.
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Regrading Quizzes / Exams and “Nickel
and Dime” Policy:
You have
one week from the time that a quiz / exam is handed back to request a regrade
for an incorrectly graded quiz / exam.
The entire quiz / exam will be re-graded at that time.
If you
feel there has been an error in grading you should write, on a separate piece
of paper, the corrections you feel are needed, staple this to your original and
unaltered quiz / exam and submit them together to Naomi Duval (x3479; room DBH
244; email: nduval@rice.edu).
Note that if you desire a re-grade, do
not write anything new on your quiz / exam or erase anything old. Hand it back for a re-grade just as you
received it. Simply write, on a separate
piece of paper (!), the corrections you feel are needed, and staple them to the
quiz / exam. Then submit it all to Naomi
Duval within the one-week re-grade return period.
Please note that since the entire quiz
/ exam will be regraded by Dr. Lapinsky that it is possible that your quiz /
exam score will go down rather than up.
Quizzes and exams are graded in the
student’s favor, especially when it comes to questions regarding partial
credit. Students submitting their quiz /
exam for a regrade and wishing to “nickel and dime” for additional points
should note that if they choose this option, their quiz / exam will be regraded
under the utmost scrutiny with a fine-toothed comb. In other words, if you “nickel and dime” me,
I reserve the right to “nickel and dime” you.
Students choosing to “nickel and dime” should be fair warned that it is
highly possible that your quiz / exam score will go down rather than up.
Attendance:
Attendance will not be taken. However, attendance of lecture is highly
recommended especially since we are not following a formal textbook and lecture
material is presented from the most updated / recent sources. Students are responsible for all material
discussed during lecture and corresponding handouts. There is a strong correlation between
attendance of lecture and success on the quizzes / exams.
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Note
taking:
I tend to lecture using the blackboard and students are
encouraged to take notes. However,
sometimes I will use transparencies during lecture. Access to these transparencies will either be
in the form of handouts distributed before or during class, or posted on the
course website in a timely fashion.
Rather than a bound notebook, students might find it easier to purchase
a 3-ring binder in order to organize and accommodate the lecture notes and
corresponding handouts for this course.
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Potential
Topics of Discussion (Subject to Change)
- Antibiotics and Antimicrobial Agents
- DNA and Classes of Drugs That Interact with DNA (ex.
Cancer)
- Antiviral Agents and Protease Inhibitors (HIV, AIDS)
- Drugs Affecting Cholinergic, Adrenergic, and Dopaminergic
Neurotransmission (ex. Alzheimer’s Disease, Parkinson’s Disease, Depression,
etc.)
Within these topics, fundamental principles of medicinal
chemistry will be presented such as:
- Drug Design and Relationship of Functional Groups to
Pharmacological Activity
- Receptors and Drug Action
- Drug Design Through Enzyme Inhibition
- Drug Metabolism and Prodrug Design
- Peptidomimetics and Peptides as Drug Candidates
- Drug Synthesis
The course is “played by ear” with respect to time, so
material and topics are subject to change at the discretion of the instructor.
Other
Notes:
1.) Memorizing and / or regurgitation of chemical structures
It is not fair to ask you to memorize or regurgitate a
complex chemical structure (i.e. draw
Taxol), but rather to be able to recognize a molecule by its structure (i.e.
recognize the structure of Taxol), especially the key functionalities with
respect to drug action. However, it is
fair to ask you to draw the structure of a molecule if its structure is highly
correlated with drug action via structural mimicry (This will become apparent
throughout the semester). Any “other”
molecules whose structure you would be expected to memorize should be disclosed
during lecture.
2.) Class handouts, reference articles, etc.
During the course of the semester, handouts, reprints, or
references to medicinal chemistry articles will be distributed. This effort is made in an attempt to increase
student awareness towards medicinal chemistry and the potential impact it can
have on our future. Some of the articles
will be based on material covered in lecture while others are of personal
interest that I think you might find interesting as well. Whatever the case, it should be made clear to
you whether you are responsible for the material discussed in these class
handouts, reference articles, etc. as they could serve as material for quizzes
/ exams.