Lecture 1 -- Intro Flashcards
Medicinal chemistry is a ____ science that utilizes the knowledge of ____, ____, and ____ in the….
an APPLIED science that utilizes the knowledge of ORGANIC CHEMISTRY, BIOCHEMISTRY, and PHYSIOLOGY IN THE DISCOVERY AND DEVELOPMENT OF DRUGS
for rational drug discovery, it is important to understand what?
the basic principles behind the biochemical events that lead to drug action
as mentioned, for rational drug discovery it is important to understand the basic principles behind the biochemical events that lead to drug action.
give a specific example of this
the development of anti HIV drugs requires the knowledge of the
1. VIRAL ENZYMES (reverse transcriptase) that can be inhibited
- active site characteristics of the enzyme (reverse transcriptase), etc
what does the reverse transcriptase enzyme do?
which specific virus encodes for it?
converts RNA into DNA – HIV
what is the target of HIV
our own immune cells
is HIV an RNA or DNA virus?
RNA
give a specific example of an HIV drug class
fusion inhibitors – prevents virus envelope from fusing with host
name the 3 classes of the origins of organic medicinal chemicals
- natural products
- Synthetics based on natural products
- Pure synthesis
give 6 examples of “natural products” that are organic medicinal chemicals
-morphine
-atropine
-quinine
-cardiac glycosides
-antibiotics
-insulin
morphine is a _____ obtained from _____
an ALKALOID obtained from OPIUM
as mentioned, morphine is an ALKALOID obtained from OPIUM
where is opium obtained from?
the unripe capsules of papaver somniferum (plant)
what is an alkaloid?
an organic molecule that contains nitrogen
(obtained from a plant)
give examples of natural antibiotics
penicillin, cephalosporin
(the derivatives like amoxicillin and ampicillin are SYNTHETICS based on the NATURAL PRODUCT PENICILLIN)
give 6 examples of synthetics based on natural products
-heroin (from morphine)
-procaine (from cocaine)
-ampicillin/amoxicillin (from penicillin)
-sympathomimetics
-prostaglandins
-antispasmodics
explain how prostaglandin is considered “synthetics based on natural products”
we produce small amounts of prostaglandins in the body, but we structurally modify them to serve as drugs
a large number of drugs fall into which 1 of the 3 categories of the origins of medicinal compounds?
synthetics based on natural products
procaine and its analogues were developed as ______ using _____ as a lead compound
local anesthetics, cocaine
(synthetic based on a natural product)
why was procaine developed?
cocaine was found to have anesthetic activity, but it got into the CNS too quickly and in large amounts (addictive).
therefore, procaine was developed from cocaine to keep a similar anesthetic activity, but remove the addictive effects
_____ is the NATURAL basis of a number of antispasmatic and anticholinergic drugs
atropine
what 2 functional groups of cocaine were KEPT when developing procaine?
a tertiary aliphatic amine and an ester with an aromatic ring
“potent anesthetic derived from cocaine”
procaine
where is cocaine naturally occurring?
leaves in south america
what are the only 2 TRUE ORALLY STABLE antibiotics?
ampicillin and amoxicillin
give 7 examples of drugs whose origin is “PURE SYNTHESIS”
ethambutol, captopril, acetaminophen, aspirin, atoxyl, salvarsan, prontosil
of the 7 drugs mentioned whose origin is “pure synthesis”, which is an antihypertensive agent
captopril
how does captopril accomplish its function as an antihypertensive agent?
explain 2 specific things
captopril inhibits the conversion of angiotensin I to angiotensin II (hormone) by inhibiting ACE (angiotensin converting enzyme)
angiotensin II is a hormone that causes vasoconstriction and increased blood pressure. thus inhibiting its synthesis will decrease blood pressure
captopril also has 5 specific binding sites at the top of the molecule. – Zinc (++), 2 hydrophobic regions, an ionic region, and an H bond
give 2 examples of drugs that were used to combat syphilis in the early 20th century.
what is their origin?
atoxyl
salvarsan (neosalvarsan)
PURE SYNTHESIS = origin
what is the difference between salvarsan and neosalvarsan?
neosalvarsan has more suitable solubility and is therefore better as a drug
explain how atoxyl and salvarsan are similar, yet different.
what is their origin
origin = pure synthesis
similar because they are both changed in vivo (in the body) and bioactivated to produce arsenoxide.
They are both arsenic (As) containing organic molecules
they are different because Atoxyl accomplishes this through REDUCTION [H] and salvarsan accomplishes this through OXIDATION [H]
what is significant about the fact that Atoxyl and Salvarsan are both arsenic containing organic molecules?
arsenic is toxic.
however, the fact that they’re organic molecules lessens the toxicity of the arsenic and is supposedly safe to consume
which is better as a drug — salvarsan or neosalvarsan?
neosalvarsan.
has better solubility
what is the origin of prontosil?
explain what it is
it was created through pure synthesis as an INDUSTRIAL COLORING MATERIAL.
however, it was unintentionally discovered to have an antibiotic profile.
it is a PRODRUG for sulfanilamide - the 1st successful class of antibiotics
explain how prontosil is converted into the antibiotic, sulfanilamide
REMEMBER: prontosil’s origin is PURE SYNTHESIS
it is bioREDUCED in the body to form the active antibiotic molecule, sulfanilamide
the double N bond (N–N) is clipped in the body and a TRI-AMINO BENZENE is clipped away, while sulfanilamide remains
is protonsil an antibiotic?
NO
it is NOT bioactive.
it is a prodrug (turns into the active form once it enters the body) for the antibiotic sulfanilamide
what is tri-amino benzene?
the portion of protonsil that gets clipped away once protonsil enters the body, to produce the active antibiotic, sulfanilamide
it is a carcinogen. it is NOT an antibiotic
how can drugs be discovered through random screening?
through HTS (high throughput screening) of hundreds of thousands of new organic chemicals using cell culture assays
leads to identification of LEAD COMPOUNDS which can be modified to obtain newer drugs
____ used to be the only source of new drugs
natural products
After an HTS, what can be applied?
QSAR
-quantitative structure activity relationship
tests a smaller number of structurally similar molecules to find a scientific trend amongst similar structures
true or false
HTS is very expensive and is usually used in the industry and NOT in academia settings
true
newer drugs are CONTINUOUSLY being obtained through…..
structural modification of EXISTING DRUGS
as mentioned, newer drugs are continuously being obtained through the structural modification of existing drugs.
the goal of this is to obtain analogues with what 2 things?
increased potency
decreased toxicity
what is the purpose of HTS (high throughput screening)
to identify NEW LEAD COMPOUNDS (which can be optimized to obtain newer drugs)
drug is very active but also very toxic.
how can you decrease toxicity, but also keep the potency?
-structural modification
-prodrug approach – modify structure so pharmacologically active drug can be produced at SITE OF ACTION and not at other tissues.
makes less toxic
