Synthetic drugs

Department of Chemistry

Gramin Mahavidyalaya

Vasantnagar(K.)

B. Sc. T. Y.

Introduction:

• Many diseases are caused by invading pathogenic

organisms like bacteria, protozoa, viruses, fungi etc.

• A chemical compound which is capable of controlling the infections caused by such microorganisms is called as chemotherapeutic agent or drug, provided, it is not toxic to the infected host.
• Many compounds such as phenol, formaldehyde, iodine etc

are also capable of destroying bacteria, but they tend to

destroy the tissues of the host.

• Therefore these compounds are not classified as drugs and

are called as disinfectants.

• The compound which exert various physiological effects of

therapeutic value are collectively known as drugs.

• The drugs are used in the treatment or cure of disease in man.
• They are used in the preventation and diagnosis of diseases.
• A drug may be defined as the substance with abnormal effect on

certain body functions.

• For ex:- Strychine stimulates the action of heat and aspirin stills

its action. Both effect abnormally, therefore they are called as

drugs.

• The most important requirement of a drug is that, on

administration to the host or patient, it should be localized at the

site where it is required.

Therapeutic index ( T.I.) :-

• The therapeutic properties of compounds depend upon its relative

toxicity to the parasite and the host.

• It should be highly toxic to the invading microorganisms and least toxic

to the host.

• The ratio of the amount of drug necessary to kill the patient ie

maximum tolerated dose ( M.T.D.) to that required for a

maximum curative dose ( M.C.D.).

Maximum Tolerated Dose ( M.T.D.)

Therapeutic Index ( T.I.) = -----------------------------------------------

Maximum curative dose ( M.C.D.).

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• The medicinal value of the drug is generally represented by the T.I.
• The higher the ratio, safer the drug will be.
• A therapeutic index of ten means that ten times a dose used for curative

purposes would kill the paracite as well as the patient.

Properties of good drugs:-

• The drug should be toxic and harmful to pathogenic micro-organism but

not to the host patient.

• The drug should not disturb the physiological action of the organism.
• The good drug should act on the site where it is desired to act but no

drug satisfy this condition.

• On the contrary, the drug distributes anywhere in the tissue of the host.

Drug should act on the system with efficiency and safety.

• A good drug should have negligible side effect.
• A good drug should not destroy the normal host cells and tissue.
• The micro-organisms responsible to cause the diseases should
• not become resistant to the drug after some time.
• The drug should be easily available and should have low cost.

Classification of drugs

According to the drugs therapeutic action the drugs are

classified into two broad types :-

1. Functional drugs.

2. Chemotherapeutic drugs.

1. Functional drugs :-

The drug which acts on the various functions of the body

are called as functional drugs.

a). Analgesics :-

Analgesics are the drugs that relieve the pain without the

loss of consciousness.

Analgesics are the drugs which by the virtue of their action

on the central nervous system decrease the sensation of the pain. For ex.

b). Antipyretics :-

• Antipyretics are the drugs that bring down the body

temperature, wherever it is higher than normal body temperature.

• Antipyretics drugs are responsible for lowering the temperature of a feverish organism to normal but has no effect on normal temperature states. Ex :-

c). Anesthetics :-

• Anesthetics drugs are the drugs which produce

temporary insensibility to the vital functions of all types of

cells, particularly those of the nervous system.

• Under anesthesia the operation of the patient can be

done by surgeon carefully and safely.

Anesthetics are of two types :-

1.General anesthetics bring unconsciousness and depression

in central nervous system.

Ex :- Chloroform

CH₃∙ CH₂- O – CH₂∙ CH₃

Diethyl ether

2. Local anesthetic drug bring a particular organ insensible to pain and prevent nerve action in that region only.

Antidiabetics

• Antidiabetic drugs are medicines developed to stabilise and

control blood glucose levels amongst people with diabetes.

• Antidiabetic drugs are commonly used to manage diabetes
• Ex:- Insulin, pramilintide (amylin) etc.

Hypoglycemic agents :-

The drugs which reduce blood sugar are called as hypoglycemic agents.

Ex :- Chloro-propamide, Tolbutamide.

Anti-inflammatory:

• Inflammation can be defined as series of changes that take

place in the living tissues following injury.

• This injury can be caused by variety of conditions like physical

agents the mechanical trauma, U.V. or ionzing radiations,

chemical agents like organic or inorganic compounds, the toxins

of different bacteria, intracellular replication of virus, hypersensitivity

reactions like reactions because of sensitized bacteria etc.

• Inflammation however, is a normal , essential, protective response

to any noxious stimulus that can threaten the host and can vary

from localized reaction to a complex response involving the whole

organism.

• Anti-inflammatory or antiinflammatory refers to the property

of a substance or treatment that reduces inflammation.

• Anti-inflammatory drugs make up about half of analgesics,

remedying pain by reducing inflammation as opposed

to opioids, which affect the central nervous system.

These drugs reduce inflammation in animals and men.

Ex :- 1. 6- mercapto purine.

2. 5- Fluoro uracil.

Sedatives

• A sedative or tranquilizer  a substance that induces sedation 

by reducing  irritability or excitement.

• At higher doses it may result in slurred speech, staggering gait,

poor judgment, and slow, uncertain reflexes

• Doses of sedatives such as benzodiazepines, when used as

a hypnotic to induce sleep, tend to be higher than amounts

used to relieve anxiety, whereas only low doses are needed

to provide a peaceful effect.

d). Tranquilizers :-

The drugs which improve the mood and behavior of a person

which has mental disorder are called as tranquilizers.

Ex :- Diazepam.

• Sedatives can be misused to produce an overly-calming

effect (alcohol being the classic and most common sedating drug).

• In the event of an overdose or if combined with another sedative,

many of these drugs can cause unconsciousness and even death.

2. Chemotherapeutic drugs :-

The drugs which kills the invading organisms without

harmful effects upon the host are called as chemotherapeutic

drugs.

a. Antibacterial drugs :-

• The drug which cures the infection developed due to

bacteria are called as antibacterial drugs.

• They cure tonsillitis, blood poison etc.
• These drugs may also eradicate the bacterial infection

from body.

b. Antibiotics :-

• Antibiotic is a chemical substance produced by living cells which is capable of inhibiting the life processes or even destroy the micro-organisms by the action of very small amount of antibiotics.
• More than 200 antibiotics are known at present, but very few are useful for medicinal purposes.
• The action of antibiotics is very specific.eg. a given antibiotic has been found to be effective against certain types of micro-organisms only. Ex.

c. Antimalarial drugs :

• Malaria is one of the most widespread diseases of the world.

Malaria is caused by a parasite, Plasmodium.

• It is characterized clinically by periodic fever, anemia and

enlargement of liver and spleen.

• It is the cause of higher sickness or death rate than any other

disease.

• The chemical substance which is used to prevent or treat malaria

is called as antimalarial drug.

• The important antimalarials used are quinine, plasmoquin,

mepacrine, paludrine etc.

d. Antiseptic drugs:

• Antiseptic are the antimicrobial substances that are applied

to living tissues/skin to reduce the possibility of infection,

sepsis, or putrefaction.

• Some antiseptics are true germicides, capable of

destroying microbes (bacteriocidal) while others are

bacterostatic and only prevent or inhibit their growth.

e. Antifungal drugs:

• Antifungal drugs are the drugs used for the treatment of

disease caused by fungal infections such as athlete’s, foot,

ringworm, candidiasis, serious systemic infections such as

cryptococcal meningitis.

• An antifungal medication is a pharmaceutical fungicide used

to treat and prevent mycoses such as athlete’s foot ,

ringworm, candidiasis (thrush), serious systemic infections

such as cryptococcal meningitis, and others.

• Such drugs are usually obtained by a doctor's prescription,

but a few are available over the counter.

Antituberculars,

• Any agent or group of drugs used to treat tuberculosis. 
• At least two drugs, and usually  three, are required in  various combinations in pulmonary tuberculosis therapy. 
• These include  isoniazid, ethambutol hydrochloride,  streptomycin sulfate,and rifampin.
• Supplements of pyridoxine (vitamin B₆) also may be needed 

to relieve the symptoms of peripheral neuritis thatcan occur 

as a side effect of isoniazid.

Disinfectants

• Disinfectants are antimicrobial agents that are applied to non-living objects to destroy microorganisms that are living on the objects. 
• Disinfection does not necessarily kill all microorganisms, especially resistant bacterial spores; it is less effective than sterilization, which is an extreme physical and/or chemical process that kills all types of life.

• Disinfectants are different from other antimicrobial agents such as antibiotics, which destroy microorganisms within the body, and antiseptics, which destroy microorganisms on living tissue.
• Disinfectants are also different from biocides  the latter are intended to destroy all forms of life, not just microorganisms.
• Disinfectants work by destroying the cell wall of microbes or interfering with the metabolism.

• Sanitizers are substances that simultaneously clean and disinfect.
• Bacterial endospores are most resistant to disinfectants, but some viruses and bacteria also possess some tolerance.
• Disinfectants are frequently used in hospitals, dental surgeries, kitchens, and bathrooms to kill infectious organisms.

Antivirals

Antiviral drugs are a class of medication used specifically for treating  viral  infections. 

Like antibiotics for bacteria, specific antivirals are used for specific viruses.

Unlike most antibiotics, antiviral drugs do not destroy their target pathogen; instead they inhibit their development.

Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotic (also termed antibacterial), antifungal and antiparasitic drugs,  or antiviral drugs based on monoclonal antibodies.

• Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections.
• They should be distinguished from viricides, which are not medication but deactivate or destroy virus particles, either inside or outside the body.
• Antivirals also can be found in essential oils of some herbs, such as eucalyptus oil and its constituents.

Synthesis of sulphanil amide.

1. Sulphanil amide is a crystalline white solid.

2. It’s M.P. is 437 ºK.

3. Sulphanil amide behaves as bacteriostatic.

4. It controls bacterial infections caused by pheumococci, streptococci, meningococci and gonococci.

Synthesis of sulphadiazine

The condensation of N-acetyl sulphanilyl chloride (ASC) with 2-amino pyrimidine in presence of pyridine followed by alkaline hydrolysis gives sulphadiazine.

Synthesis of aspirin

When salicylic acid is treated with acetic anhydride in presence of small quantity of conc. H₂SO₄ then aspirin is formed.

Uses :-

1. Aspirin acts as analgesic and is used for relief of pain

like headache, body ache, arthritis etc.

2. It also has antipyretic action.

3. It is also used as anti- inflammation in spondylitis

and rheumatoid arthritis.

Synthesis of p-acetamol.

1. When p- nitrophenol is reduced with conc. HCl, then p- amino phenol hydrochloride is formed which on treatment with sodium bicarbonate, gives p- amino phenol. It is then undergoes acetylation with acetic anhydride in presence of fused sodium acetate, then p- acetamole is formed.

2. p- hydroxyl acetophenone reacts with hydrazine to form hydrazone derivative which on further rearrangement gives p- acetamole.

Uses :-

1. p- acetamole possesses analgesic and antipyretic action

2. It is sold commercially under trade name crocin, metacin etc.

3. It is marked in combination with aspirin and caffeine.

Paludrine (Proguanil)

It is prepared from p- chloroaniline

It is colourless, tasteless and less toxic.

It is used in the treatment of falciparum and vivax malaria.

It is used as hydrochloride in theraphy.

Benzocaine:

Benzocaine is ethyl ester of p-aminobenzoic acid. It is prepared from p-nitrotoulene by oxidation with acidified potassium duchloromate to p-nitrobenzoic acid and subsequent esterification and reduction with tin and hydrochloric acid.

Benzocaine can also be synthesized from p-aminotoluene. p-aminotoluene on acetylation gives p-methyl acetanlide which on further oxidation with acidified potassium dichromate to yield p-acetyl aminobenzoic acid. This acid on esterificaton followed by hydrolysis gives benzocaine.

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Properties :

1. Benzocaine is a white, odourless, crystalline powder stable in air.
2. It is soluble in alcohol (1 : 5), ether ( 1 : 4), chloroform (1 : 2), fixed oils (1 : 40), glycerine, propylene glycol or mineral acids.
3. It is insoluble in water and alkaline solutions.

Uses :

1. Salt of benzocaine with p-phenol sulphonic acid is soluble in water is used for the treatment of hypodermic infection under the name subcutin.
2. It is used for local anesthetic action in powders upto 20 % in ointments, upto 20% in suppositories and for various types of surface pain and itching.
3. Generally it is used orally to prevent nausea and vomiting with compounds such as aminophylline.

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Synthesis of Isoniazide

Isoniazid may be prepared by the base hydrolysis of 4-cyanopyridine to give the amide, followed by displacement of ammonia by hydrazine

Synthesis of Tolbutamide

The addition of p-toluenesulfonamide to butyl isocyanate gives tolbutamide

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