Pharmaceutical Organic Chemistry: Amines

Amines
➢ Amines are compounds in which one or more of the
hydrogens of ammonia have been replaced by alkyl
groups.
➢ Smaller amines are characterized by their fishy
odors. Fermented shark, for example, a traditional
dish in Iceland (ammonia-rich smell)
➢ The craziest fact about Icelandic fermented shark is that the
Greenland’s shark which is the prime meat used to produce it is
actually poisonous while fresh!
➢ This is due to a high content of urea and trimethylamine oxide in the
shark’s system.

Classification of Amines
➢ There are primary amines, secondary amines, and tertiary
amines. The classification depends on how many alkyl groups
are bonded to the nitrogen. Primary amines have one alkyl group
bonded to the nitrogen, secondary amines have two, and tertiary
amines have three.

Examples of Amines

pyrimidine purine

• Pyrimidine
➢ Three pyrimidine bases
➢ (PYR CUT) = Cytosine (D & R), Thymine (D), Uracil (R)

• Purine
➢ (PUR GA) = Guanine (D&R), Adenine (D&R)
Pharmaceutical Organic Chemistry: Amines

Nitrogen Compounds

Amines: Nomenclature
➢ The IUPAC system uses a suffix to denote the amine functional
group. The “e” at the end of the name of the parent hydrocarbon
is replaced by “amine”—similar to the way in which alcohols are
named.
➢ The root name is based on the longest chain with the -
NH2 attached
➢ The chain is numbered so as to give the amine unit the lowest
possible number
1. butan-1-amine
2. butan-2-amine
➢ Drop the –e then add – amine
3. Propan-1-amine ➢ The appropriate multiplier (i.e. di- for two, tri for three etc.) is
4. Ethan-1,2-diamine inserted before the -amine suffix

A number identifies the carbon to ➢ The name of any alkyl group bonded to nitrogen is preceded by
which the nitrogen is attached.
an “N” (in italics) to indicate that the group is bonded to a nitrogen
The name of any alkyl group bonded
to nitrogen is preceded by an “N” (in rather than to a carbon.
italics) to indicate that the group is
bonded to a nitrogen rather than to a
carbon.
1. N-ethylhexan-3-amine
2. N-ethyl-N-methylpropan-1-amine
➢ When other functional groups are present, the amino group is
3. 3-chloro-N-methyl-1-butanamine named as a substituent:
4. 4-bromo-N,N-dimethyl-2-
pentanamine

1. 1-aminopentan-3-one
Pharmaceutical Organic Chemistry: Amines

Physical Properties of Amines

➢ Intermolecular N-H· · ·N hydrogen bonds raise the boiling points
of primary and secondary amines but are not as strong as the
O-H· · ·O bonds of alcohols.
➢ The reason for this is that nitrogen is not as electronegative as
oxygen.

➢ All three classes of amines can form hydrogen bonds with the OH
group of water (that is, OH· · ·N). Primary and secondary amines
can also form hydrogen bonds with the oxygen atom in water:
N!H· · ·O. Thus, most simple amines with up to five or six carbon
atoms are either completely or appreciably soluble in water.
➢ So, the boiling points of the compounds in a homologous series
of ethers, alkyl halides, alcohols, and amines increase with
increasing molecular weight.
➢ Primary and secondary amines have higher boiling points than
alkanes with similar molecular weights.
➢ An amine has a lower boiling point than an alcohol with a similar
molecular weight

Common Pharmaceutical Drugs

Adrenergic drugs
➢ are medications that stimulate certain nerves in your body.
➢ They do this either by mimicking the action of the chemical
messengers epinephrine and norepinephrine or by stimulating their
Norepinephrine structure release.
➢ Adrenergic means "working on adrenaline (epinephrine) or
CATECHOL: ortho dihydroxybenzene noradrenaline (norepinephrine)" or on their receptors.
With Ethyl AMINE
➢ When not further qualified, it is usually used in the sense of enhancing
or mimicking the effects of epinephrine and norepinephrine in the
body.
➢ Classified into Catecholamine and non-catecholamines

Catecholamines
➢ refer generally to all organic compounds that contain a catechol
nucleus (ortho-dihydroxybenzene) and an ethylamine group.
➢ Epinephrine, Dopamine, Norepinephrine
Pharmaceutical Organic Chemistry: Amines

Catecholamines
➢ refer generally to all organic compounds that contain a catechol
nucleus (ortho-dihydroxybenzene) and an ethylamine group.
➢ Epinephrine, Dopamine, Norepinephrine

Epinephrine
➢ Aka adrenaline is a hormone and neurotransmitter used to treat
allergic reactions, to restore cardiac rhythm
➢ To treat allergic reactions - For severe allergic reactions which
lead to hypotension, epinephrine helps to increase blood flow
through veins by constricting blood vessels. By binding to receptors
on smooth muscles of the lungs, epinephrine helps to relax the
muscles blocking the airways and allows breathing to return to
normal.
➢ To restore cardiac rhythm - In the heart, it increases the rate and
force of contraction, thus increasing the output of blood and raising
blood pressure.

Norepinephrine
➢ is a naturally occurring chemical in the body that acts as both a
stress hormone and neurotransmitter (a substance that sends
signals between nerve cells). It's released into the blood as a stress
hormone when the brain perceives that a stressful event has
occurred.
➢ Increases alertness, arousal and attention. Constricts blood
vessels, which helps maintain blood pressure in times of stress.
Affects your sleep-wake cycle, mood.
➢ For sleep-wake cycle - it increases sleep by exciting a subset of
neurons in the VLPO (ventrolateral preoptic) nucleus in the anterior
hypothalamus is the major area of the brain that controls sleep
induction and maintenance.)
➢ For mood - Norepinephrine has been shown to play a role in a
person's mood and ability to concentrate. Low levels of
norepinephrine may lead to conditions such as attention deficit
hyperactivity disorder (ADHD), depression.

Dopamine
➢ is a neuromodulatory molecule that plays several important roles in
cells.
➢ It plays a role in many important body functions,
including movement, memory and pleasurable reward and
motivation. High or low levels of dopamine are associated with
several mental health and neurological diseases.
➢ Dopamine can provide an intense feeling of reward. Dopamine is
most notably involved in helping us feel pleasure as part of the
brain's reward systemic
Pharmaceutical Organic Chemistry: Amines

Non-catecholamines
➢ are compounds lacking catechol hydroxyl groups.
➢ Phenylephrine, Ephedrine, Amphetamine

Phenylephrine
➢ is a decongestant that is used to treat stuffy nose and sinus
congestion caused by the common cold, hay fever, or other
allergies.
➢ Phenylephrine is an agonist of α1-adrenoceptors. Nasal
decongestant action is mediated by activation of α1-
adrenoceptors in the arterioles of the nasal mucosa. This
causes vasoconstriction, which leads to decreased edema
and increased drainage of the sinus cavities.)
➢ Neozep ®, Bioflu ®
➢ Neozep® Forte contains Phenylephrine HCl,
Chlorphenamine Maleate and Paracetamol.
➢ Phenylephrine HCl a nasal decongestant clears obstructed
air passages and nasal sinuses due to congestion making
breathing easier. It also reduces postnasal drip.
➢ Chlorphenamine Maleate, an anti-allergy, relieves
symptoms such as runny nose, sneezing, and itchy, watery
eyes.
➢ Paracetamol is an effective fever reducer and pain reliever.
➢ Neozep® Non-Drowsy
➢ Neozep® Non-Drowsy contains Phenylephrine HCl and
Paracetamol.

Ephedrine
➢ is a prescription medicine used to treat the symptoms of low
blood pressure during anesthesia (Hypotension).
➢ the principal mechanism of action relies on its indirect
stimulation of the adrenergic receptor system by increasing
the activity of norepinephrine at the postsynaptic α and β
receptors.)
➢ A = ALPHA = Arteries
B = BETA = Beats (heart-b1), Breaths (lungs-b2)
1 = constrict
2 = dilate
B2 agonist = asthma
A1 agonist = constriction of blood vessels & shrinkage of
swollen nasal mucous membrane = reducing nasal
congestion
Pharmaceutical Organic Chemistry: Amines

Amphetamine
➢ Amphetamine (contracted from alpha-
methylphenethylamine) is a central nervous system (CNS)
stimulant that is used in the treatment of attention deficit
hyperactivity disorder (ADHD), narcolepsy, and obesity.
➢ is a central nervous (CNS) system stimulant that functions
by increasing the amounts of dopamine, norepinephrine, and
serotonin (to a lesser extent)
➢ Amphetamine Salts are central nervous system stimulants
that work to restore imbalance of the brain by increasing
mental alertness and improving the ability to focus. HENCE
treatment of attention deficit hyperactivity disorder (ADHD -
neurodevelopmental disorders - trouble paying attention,
controlling impulsive behaviors), narcolepsy (person to
suddenly fall asleep at inappropriate times)
➢ For obesity - They work in the brain to reduce appetite and
increase locomotion or stamina.

Diazepam
➢ medicine for anxiety, muscle spasms and seizures

Benzodiazepine Nucleus
GABA receptors ➢ work by enhancing a very important neurotransmitter called GABA
➢ occur throughout the (gamma-aminobutyric acid) at the GABA A receptor. This results in
cortex and limbic system the sedative, hypnotic (sleep-inducing), anxiolytic (anti-anxiety),
in the brain, and act to anticonvulsant, and muscle relaxant properties for which the drugs are
inhibit neuronal activity. prescribed.

Gabapentin Lorazepam
➢ approved to prevent and ➢ is a short-acting benzodiazepine commonly used to treat panic
control partial seizure disorders, severe anxiety, and seizures.
(anticonvulsant)
Verapamil
GABA analogue (substantially ➢ is indicated to treat hypertension, to treat and prevent chest pain
similar in chemical structure) (angina)
➢ is a type of medicine called a calcium channel blocker. If you have
GABA reduces the excitability high blood pressure, these medicines work by blocking calcium going
of neurons in the brain into muscles in the heart and blood vessels. Muscles need calcium to
contract, so when you block the calcium, it makes the muscles relax.
Gabapentin
➢ mirrors the effects of Febuxostat
GABA calming excited ➢ is used to lower hyperuricemia (high uric acid in the blood) in patients
neurons. with gout who have been treated with allopurinol that did not work well
or cannot be treated with allopurinol. This medicine is a xanthine
oxidase inhibitor. It works by causing less uric acid to be produced
by the body.