MedOrg L1: HISTORY AND EVOLUTION OF MEDICINAL CHEMISTRY & DEVELOPMENTS LEADING TO VARIOUS MEDICINAL CLASSES OF DRUGS

_____ is the chemistry discipline concerned with the design, development, and synthesis of pharmaceutical drugs.

Medicinal chemistry

The discipline combines expertise from chemistry and pharmacology to identify, develop, and synthesize chemical agents that have a therapeutic use and to evaluate the properties of existing drugs.

Medicinal chemistry

When a parent molecule is too toxic thus it needs modification to make it into a lesser toxic new drug molecule

Chemical Modification

Two ways to alter drugs?

○ Create a novel/discover new drugs
○ Alter existing drugs for other purposes

The oldest records of the use of therapeutic plants and minerals were derived from the ancient civilizations of the ______(4) peoples of antiquity

Chinese,
Hindus,
Mayans,
Mediterranean

DRUGS OF ANTIQUITY: This consists of ______(3) as antiquity refers to old drugs.

crude herbs, plants, minerals

Father of Chinese Agriculture and Chinese Medicine

EMPEROR SHEN NUNG

Tested hundred of medicinal herbs to test medicinal value

EMPEROR SHEN NUNG

EMPEROR SHEN NUNG authored?

Pen Tsao

Earliest extent chinese pharmacopeia

Pen Tsao

Ephedrine was isolated here

MA HUANG

What can be isolated from Ma huang?

Ephedrine

Ephedrine is ____ and used as a ____

non-selective;bronchodilator

Tx of skin conditions such as psoriasis and eczema

CHAULMOOGRA FRUIT

What part of chaulmoogra fruit is used?

seeds

Roots have Emetine which is used for the tx of dysentery and amoebiasis

IPECACUANHA

What can be isolated from ipecacuanhua?

emetine

Cocaine is isolated from here which is used as a local anesthetic

Coca leaves

What can be isolated from coca leaves?

cocaine

Contains tryptamine which is used as hallucinogen

Mushrooms

What can be isolated from mushrooms?

tryptamine

In what era does Herbs such as opium, squill, and Hyoscyamus, viper toxin, and metallic drugs such as copper and zinc ores, iron sulfate, and cadmium oxide could be found.

Greek Era

On what period does focuses on the use of chemicals, shifting from the use of plants, to treat certain diseases.

MIDDLE AGES

He glorified antimony and its salts in elixirs in the belief that chemicals could cure disease

Paracelsus

This period focuses on finding active ingredients that accounted for their pharmacologic properties

19TH CENTURY: AGE OF INNOVATION AND CHEMISTRY

This period focuses on identifying the chemicals in crude plants or extracts that are responsible for pharmacological activity.

19TH CENTURY: AGE OF INNOVATION AND CHEMISTRY

Synthesis of acetic acid in 1845

ADOLPH KOBE

What did ADOLPH KOBE synthesize?

acetic acid

Synthesis of methane in 1856

PIERRE BERTHELOT

What did PIERRE BERTHELOT sythesized?

methane

Isolation of morphine in 1803

FRIEDRICH SERTURNER

What did FRIEDRICH SERTURNER isolated?

morphine

Isolation of emetine from ipecacuanha in 1816

PIERRE-JOSEPH PELLETIER

What did PIERRE-JOSEPH PELLETIER isolated?

emetine

PIERRE-JOSEPH PELLETIER also identified(4)?

○ Caffeine as stimulant
○ Quinine as antimalarial
○ Colchicine as antigout
○ Emetine

He used digitalis (foxglove) for the treatment of edema

WILLIAM WITHERING

WILLIAM WITHERING used what to treat edema?

digitalis (foxglove)

Isolated cocaine from Erythroxylon coca

ALBERT NIEMANN

ALBERT NIEMANN isolated what form erythroxylon coca?

cocaine

This period focuses on chemotherapeutic agents

20TH CENTURY AND THE PHARMACEUTICAL INDUSTRY

In this period, Disease of protozoal and spirochetal origin responded to synthetic chemotherapeutic agents

20TH CENTURY AND THE PHARMACEUTICAL INDUSTRY

Reported that red dyestuff 2,4-diaminoazobenzene-4’-sulfonamide (Prontosil) cured dangerous systemic gram positive bacterial infections in man and animals.

GERHARD DOMAGK

this drug is also known as 2,4-diaminoazobenzene-4’-sulfonamide

Prontosil

Prontosil is also known as

2,4-diaminoazobenzene-4’-sulfonamide

What did GERHARD DOMAGK reported?

(Prontosil) cures dangerous systemic gram positive bacterial infections in man and animals.

What can prontosil cure?

Gram positive bacterial infections

Discovered penicillin in 1929 by serendipity: through P. Notatum

ALEXANDER FLEMING

ALEXANDER FLEMING discovered what drug through what fungi?

penicillin,penicillium notatum

Discovered benzylpenicillin (PEnG) in 1941 (2)

HOWARD FLOREY AND ERNST CHAIN

Led to water-soluble powder of much higher antibacterial potency and lower toxicity

benzylpenicillin (PEnG)

What did HOWARD FLOREY AND ERNST CHAIN discovered?

benzylpenicillin (PEnG)

Discovery of what drugs were based on observations of effects on the behavior of animal bioassay?

CNS DRUGS

Drug that acts on the brain?

CNS drugs

_____(for depression) and ______(for hyperactivity) were used to modify the mood and mental states of psychiatric patients

Stimulants,depressants

_____(3) were used to stimulate or depress the mental states of patients.

Amphetamine, sedatives, and hypnotics

CNS drugs 7 categories (XPMConDeAnesAb)

Anxiolytics and Hypnotics

Antipsychotics

Antimanic agents

Anticonvulsants

Antidepressants

Anesthetic Agents

Drugs of Abuse

Anxiolytics and Hypnotics(2)

Benzodiazepines (-pam)

Barbiturates (-barbital_

Antipsychotics(2)

Typical and atypical antipsychotics

Antidepressants(3)

Tricyclic antidepressants (TCAs) Selective Serotonin Reuptake Inhibitors (SSRIs) Monoamine Oxidase Inhibitors (MAOIs)

Anesthetic Agents(3)

Inhaled, intravenous, local agents

Crystal

Methamphetamine

Pot,Weed,Skunk

Marijuana

Black Tar, Smack

Heroin

Crack

Cocaine

Lack of Norepinephrine, 5-HT (serotonin), and dopamine

Depression

What enzyme metabolizes metabolizes NE, 5-HT & dopamine. And what drug is used to inhibit this enzyme?

MAO, MAO inhibitor

First line drug of depression

SSRI

Excess neuron goes back unless you’re depressed

Reuptake

Increased catecholamines

Anxiety

Unpleasant emotional state consisting of apprehension, tension, and feelings of danger, without real or logical cause

Anxiety

MAO-A inhibitors (2)

○ Phenelzine

○ Tranylcypromine

MAO-B inhibitors (2)

Selegiline

Isopropyl congener of isoniazid (for Tuberculosis)

Iproniazid

___exhibits MAO inhibiting activity

Isopropyl

________refers to a compound or substance that has a structural similarity or chemical relationship to isopropyl alcohol

Isopropyl congener

Iproniazid led to a series of compounds including ___ (Nardil) and ________ (Parnate)

phenelzine,tranylcypromine

Iproniazid led to a series compounds like phenelzine & tranylcypromine. What are their brand names?

Nardil,Parnate

These are not antipsychotic, but instead elevate mood by blocking the transport inactivation of monoamine neurotransmitters including norepinephrine and serotonin

TRICYCLIC ANTIDEPRESSANTS (TCA)

Inhibit the reuptake of serotonin and norepinephrine

TRICYCLIC ANTIDEPRESSANTS (TCA)

Other examples of TCAs: (3)

Nortriptyline, Desipramine, Trimipramine

1st commercially successful SSRI

Fluoxetine (Prozac®)

______the rise in catecholamines, an unpleasant emotional state consisting of apprehension, tension, and feelings of danger, without real or logical cause.

ANXIETY

Anxiolytics such as _____ and _______are serendipitous discovery of new drugs

benzodiazepines, carbamate meprobamate

Anxiolytics examples

Benzodiazepines (e.g. chlordiazepoxide (Librium®), diazepam (Valium®)) Carbamate (e.g. meprobamate (Miltown®)

1st benzodiazepine

chlordiazepoxide (Librium)

There was a need for drugs of greater selectivity in the treatment of anxiety because of the side effects often encountered with ______

phenothiazines

Synthesized 40 compounds, all which were disappointing in pharmacologic tests

LEO STERNBACK

During clean up, one had crystallized (___???) and submitted to L.O. Randall and was later reported to have hypnotic, sedative and had antistrychnice effects (similar to meprobamate).

i.e. chlordiazepoxide (Librium)

First pure hormone to be isolated from the endocrine gland was______

epinephrine

Norepinephrine was identified from ______nerves

sympathetic

DIFFERENCE: Epinephrine is ______ while Norepinephrine has no____group.

methylated; methyl

ENDOCRINE THERAPY AND STEROIDS affects what agents?

hormonal agents

Who isolated thyroxine from the thyroid gland and discovered the activity of cortisone

EDWARD KENDALL

■ Precursor of cortisol

■ No biologic activity

Cortisone

Used in market to mimic action of cortisol

Cortisone

■ Glucocorticoid

■ Regulates metabolism, inflammatory response, and immune function

■ Natural hormone

Cortisol

Two thyroid hormones,______ and have similar effects in the body, regulating metabolism

thyroxine (T4); triiodothyronine (T3)

synthetic form of triiodothyronine (T3)

liothyronine

What thyroid hormone is T3?

triiodothyronine

What thyroid hormone is T4?

thyroxine