DRUG SYNTHESIS:

ANALOGUES AND PRODRUGS

Prodrugs are frequently used to improve pharmacological or biological properties. Analogues are primarily employed to increase potency and to achieve specificity of action.

In the course of drug design the two major types of chemical modifications are achieved through the formation of analogues and prodrugs.

An analogue is normally accepted as being that modification which brings about a carbon-skeletal transformation or substituent synthesis. Examples : oxytetracycline, demclocycline, chlortetracycline, trans-diethylstilbesterol with regard to oestradiol.

The term prodrug is applied to either an appropriate derivative of a drug that undergoes in vivo hydrolysis to the parent drug, e.g., testosterone propionate, chloramphenicol palmitate and the like; or an analogue which is metabolically transformed to a biologically active drug, for instance : phenylbutazone undergoes in vivo hydroxylation to oxyphenbutazone.

DRUG DESIGN: Seeks to explain

(a) Effects of biological compounds on the basis of molecular interaction in terms of molecular structures or precisely the physico-chemical properties of the molecules involved. (b) Various processes by which the drugs usually produce their pharmacological effects. (c) How the drugs specifically react with the protoplasm to elicit a particular pharmacological response. (d) How the drugs usually get modified or detoxicated, metabolized or eliminated by the organism. (e) Probable relationship between biological activity with chemical structure. In short, drug design may be considered as an integrated whole approach which essentially involves various steps, namely : chemical synthesis, evaluation for activity-spectrum, toxicological studies, metabolism of the drug, i.e., biotransformation and the study of the various metabolites formed, assay procedures, and lastly galenical formulation and biopharmaceutics.

The ‘drug design’ in a broader sense implies random evaluation of synthetic as well as natural products in bioassay systems, creation of newer drug molecules based on biologically-active-prototypes derived from either plant or animal kingdom, synthesis of congeners displaying

interesting biological actions, the basic concept of isosterism and bioisosterism, and finally precise design of a drug to enable it to interact with a receptor site efficaciously

DIAZEPAM:

Diazepam is a benzodiazepine. It affects chemicals in the brain that may become unbalanced and cause anxiety.

7-chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one

Diazepam is used to treat anxiety disorders, alcohol withdrawal symptoms, or muscle spasms. Diazepam is sometimes used with other medications to treat seizures. It may also be used to cause memory loss during certain medical procedures. It can be taken by mouth, inserted into the rectum, injected into muscle, orinjected into a vein.

USES:

1. Treatment of anxiety, panic attacks, and states of agitation. 2. Treatment of neurovegetative symptoms associated with vertigo. 3. Treatment of the symptoms of alcohol, opiate, and benzodiazepine withdrawal. 4. Short-term treatment of insomnia. 5. Treatment of tetanus, together with other measures of intensive treatment. 6. Adjunctive treatment of spastic muscular paresis (paraplegia/tetraplegia) or spinal cord

injury. 7. Palliative treatment of stiff person syndrome. 8. Pre- or postoperative sedation, anxiolysis and/or amnesia (e.g., before endoscopic or

surgical procedures). 9. Treatment of complications with a hallucinogen crisis and stimulant overdoses and

psychosis, such as LSD, cocaine, ormethamphetamine. 10. Preventative treatment of oxygen toxicity during hyperbaric oxygen therapy.

SIDE EFFECTS:

1. Sleepiness and trouble with coordination. 2. Suicide, 3. Decreased breathing, 4. And an increased risk of seizures

SYNTHESIS OF DIAZEPAM: Diazepam was first synthesized by Leo Sternbach, and was first manufactured by Hoffmann-La Roche.

1. One of the more straightforward approaches to this compound involves first the acetylation of aminobenzophenone with chloroacetyl chloride to give the chloromethyl amide . Heating this compound with ammonia or its latent equivalent, hexamethylene tetramine (HMTA), can be envisaged to involve the initial displacement of chlorine to give a glycineamide. Cyclization by imine formation then affords diazepam.

2. The second way consists of the direct cyclocondensation of 2-amino-5-chlorobenzophenone with glycine ethyl ester hydrochloride. The amide nitrogen atom of the obtained 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one, is methylated by dimethylsulfate, which leads to the formation of diazepam.

OMEPRAZOLE:

Omeprazole is a proton pump inhibitor used in the treatment ofdyspepsia, peptic ulcer disease,gastroesophageal reflux disease,laryngopharyngeal reflux, and Zollinger–Ellison syndrome.

6-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methanesulfinyl]-1H-1,3-benzodiazole

USES:

Omeprazole can be used in the treatment of

1. Gastroesophageal reflux disease (GERD),

2. Peptic ulcers,

3. Erosive esophagitis,

4. And Zollinger-Ellison syndrome.

SIDE EFFECTS:

The most frequent significant adverse effects occurring in at least 1% of patients include:[10]

1. Central nervous system: headache (7%), dizziness (2%) 2. Respiratory: upper respiratory tract infection (2%), cough (1%) 3. Gastrointestinal: abdominal pain (5%), diarrhea (4%), nausea (4%), vomiting (3%),

flatulence (3%), acid regurgitation (2%), constipation (2%) 4. Neuromuscular and skeletal: back pain (1%), weakness (1%) 5. Dermatologic: rash (2%)

SYNTHESIS:

CHLORPROMAZINE:

Chlorpromazine (CPZ) marketed as Thorazine among others is a dopamine antagonist of the typical anti-psychotic class of medications possessing additional antiadrenergic, anti-serotonergic, anticholinergic and antihistaminergic properties used to treatschizophrenia.

3-(2-chloro-10H-phenothiazin-10-yl)-N,N-dimethyl-propan-1-amine

USES:

1. In the treatment of both acute and chronic psychoses 2. Schizophrenia and the manic phase of bipolar disorder 3. Amphetamine-induced psychoses

SIDE EFFECTS:

1. Weight gain 2. Sedation 3. Acute movement disorder 4. Parkinsonism 5. Decreased blood pressure with dizziness

SYNTHESIS:

ANTICANCER DRUGS

Anticancer, or antineoplastic, drugs are used to treat malignancies, or cancerous growths. Drug therapy may be used alone, or incombination with other treatments such as surgery or radiation therapy.

5-FLUOROURACIL:

Fluorouracil is also known as FU or 5FU and is one of the most commonly used drugs to treat cancer.

5-Fluoro-1H,3H-pyrimidine-2,4-dione

USES:

1. Breast cancer 2. Head and neck cancers 3. Anal cancer 4. Stomach cancer 5. Colon cancer 6. Some skin cancers

SIDE EFFECTS

1. Hair thinning

2. Brittle, chipped and ridged nails – you may have a blue tinge or darkening or the nails, flaking of the nails, or pain and thickening of the area where the nail starts growing (the nail bed)

3. Sensitivity of the skin to sunlight – you should not use sunbeds or sit in the sun if having fluorouracil. Cover up or use a sun block

4. Rashes, which may be itchy 5. Watery eyes from increased production of tears 6. Gritty, red, sore eyes and blurred vision – if you have this do not operate machinery or

drive 7. Loss of appetite 8. Brown marking on the skin following the line of the vein where fluorouracil has been

injected 9. Loss of fertility – you may not be able to become pregnant or father a child after

treatment with this drug. Talk to your doctor before starting treatment if you think you may want to have a baby in the future. Men may be able to store sperm before starting treatment

SYNTHESIS:

Cis-PLATIN:

Cis-platin is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. Cis-platin is classified as an "alkylating agent."

(SP-4-2)-diamminedichloroplatinum(II)

USES:

Used to treat

1. Testicular, ovarian, bladder, head and neck, esophageal, small and non-small cell lung, breast, cervical, stomach and prostate cancers.

2. Also to treat Hodgkin's and non-Hodgkin's lymphomas, neuroblastoma, sarcomas, multiple myeloma, melanoma, and mesothelioma.

SIDE EFFECTS:

1. Most people do not experience all of the Cisplatin side effects listed. 2. Cisplatin side effects are often predictable in terms of their onset and duration. 3. Cisplatin side effects are almost always reversible and will go away after treatment is

complete. 4. There are many options to help minimize or prevent Cisplatin side effects. 5. There is no relationship between the presence or severity of Cisplatin side effects and the

effectiveness of Cisplatin. 6. The Cisplatin side effects and their severity depend on how much Cisplatin is given. In

other words, high doses may produce more severe side effects.

SYNTHESIS:

The synthesis of cisplatin starts from potassium tetrachloroplatinate. The tetraiodide is formed by reaction with an excess of potassium iodide. Reaction with ammoniaforms K2[PtI2(NH3)2] which is isolated as a yellow compound. When silver nitrate in water is added insoluble silver iodide precipitates and K2[Pt(OH2)2(NH3)2] remains in solution. Addition of potassium chloride will form the final product which precipitates. In the triiodo intermediate the addition of the second ammonia ligand is governed by the trans effect.

ANALGESIC:

An analgesic or painkiller is any member of the group of drugs used to achieve analgesia, relief from pain

ANTIPYRETICS:

Antipyretics from the Greek anti, against, and pyreticus, pertaining to fever, are substances that reducefever. Antipyretics cause the hypothalamus to override an interleukin-induced increase in temperature. The body then works to lower the temperature, resulting in a reduction in fever.

ASPIRIN:

2-(acetoxy)benzoic acid

USE OF ASPIRIN:

Aspirin is used in the treatment of a number of conditions, including

1. Fever, 2. Pain, 3. Rheumatic fever, 4. Inflammatory diseases, such asrheumatoid arthritis, pericarditis, and Kawasaki

disease. 5. Lower doses of aspirin have also shown to reduce the risk of death from a heart

attack, or the risk of stroke in some circumstances. 6. There is some evidence that aspirin is effective at preventingcolorectal cancer,

though the mechanisms of this effect are unclear.

SIDE EFFECT OF ASPIRIN:

1. Contraindications 2. Gastrointestinal 3. Central effects 4. Reye's syndrome 5. Hives and swelling

SYNTHESIS: The synthesis of aspirin is classified as an esterification reaction. Salicylic acid is treated with acetic anhydride, an acid derivative, causing a chemical reaction that turns salicylic acid's hydroxyl group into an ester group (R-OH → R -OCOCH3). This process yields aspirin and acetic acid, which is considered a byproduct of this reaction. Small amounts of sulfuric acid (and occasionally phosphoric acid) are almost always used as a catalyst.

IBUPROFEN:

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID). It works by reducing hormones that cause inflammation and pain in the body.

(RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid

USES:

1. Fever (including postimmunisation fever), 2. Fild-to-moderate pain (including pain relief after surgery), 3. Painful menstruation, osteoarthritis, 4. Dental pain, 5. Headaches and pain from kidney stones.

6. It is used for inflammatory diseases such as juvenile idiopathic arthritis and rheumatoid arthritis. It is also used for pericarditis and patent ductus arteriosus.

SIDE EFFECTS:

1. Nausea 2. Dyspepsia 3. Gastrointestinal ulceration/bleeding, raised liver enzymes 4. Diarrhea 5. Constipation, 6. Nosebleed 7. Headache 8. Dizziness 9. Rash, salt and fluid retention 10. And hypertension

SYNTHESIS:

PARACETAMOL:

Paracetamol (acetaminophen) is a pain reliever and a fever reducer. The exact mechanism of action of is not known. Paracetamol is used to treat many conditions such as headache, muscle aches, arthritis, backache, toothaches, colds, and fevers.

N-(4-hydroxyphenyl)acetamide

USES:

1. Fever 2. Pain 3. Osteoarthritis 4. Low back pain 5. Headaches 6. Postoperative pain

SIDE EFFECTS:

1. Liver damage 2. Skin reactions 3. Asthma

SYNTHESIS:

ANTIMICROBIAL AGENTS:

"Antimicrobial" is a general term that refers to a group of drugs that includes antibiotics, antifungals, antiprotozoals, and antivirals. These are drugs used to treat a microbial infection.

ANTIFUNGAL DRUGS:

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.

FLUCONAZOLE:

Fluconazole is an antifungal medication

2-(2,4-Difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol

USES:

Fluconazole is used for treating

1. Vaginal, oral, and esophageal fungal infections caused by Candida. 2. It may also be effective in treating urinary tract infections, 3. Peritonitis, 4. Pneumonia 5. And disseminated infections caused by Candida

SIDE EFFCTS:

1. Common (≥1% of patients): rash, headache, dizziness, nausea, vomiting, abdominal pain, diarrhea, and/or elevated liver enzymes

2. Infrequent (0.1–1% of patients): anorexia, fatigue, constipation 3. Rare (<0.1% of patients): oliguria, hypokalaemia, paraesthesia,

seizures, alopecia, Stevens–Johnson syndrome, thrombocytopenia, other blood dyscrasias, serioushepatotoxicity including liver failure, anaphylactic/anaphylactoid reactions

4. Very rare: prolonged QT interval, torsades de pointes 5. FDA is now saying treatment with chronic, high doses (400–800 mg/day) of fluconazole

during the first trimester of pregnancy may be associated with a rare and distinct set of birth defects in infants

SYNTHESIS:

ANTIBACTERIAL DRUGS:

An antibacterial drugs are agents that inhibit bacterial growth or kills bacteria.

ISONIAZID:

Isoniazid (marketed under numerous brand names, including Hydra, Isovit, Laniazid, Nydrazid), also known asisonicotinylhydrazide (or INH), is an organic compound that is the first-line medication in prevention and treatment of tuberculosis. Isoniazid is an antibiotic and works by stopping the growth of bacteria.

Isonicotinohydrazide

USES:

Isoniazid is used with other medications to treat active tuberculosis (TB) infections. It is also used alone to prevent active TB infections in people who may be infected with the bacteria (people with positive TB skin test).

SIDE EFFECTS:

1. An allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives)

2. Unusual weakness or fatigue 3. Nausea, vomiting, or loss of appetite 4. Abdominal pain 5. Yellow skin or eyes 6. Dark urine 7. Numbness or tingling in your hands or feet; 8. Seizures 9. Blurred vision 10. Confusion or abnormal behavior

SYNTHESIS:

SULPHAGUANIDINE:

4-Amino-N-[amino(imino)methyl]benzenesulfonamide

USES:

It Is Used For Enteric Infections.

SIDE EFFECTS:

1. Gastrointestinal effects 2. Hypersensitivity reactions 3. Kidney damage 4. Liver impairment 5. Heart disease

6. Low blood sugar, under active thyroid 7. Neurological reactions 8. Intestinal inflammation 9. Jaundice

SYNTHESIS:

ANTIVIRAL DRUGS:

Antiviral drugs are medicines that decrease the ability of flu viruses to reproduce.

CARBOVIR:

Carbovir is a nucleoside reverse transcriptase inhibitor analog of guanosine.

2-amino-9-[(1R,4S)-4-(hydroxymethyl)cyclopent-2-en-1-yl]-3H-purin-6-one

USES:

Carbovir decreases HIV viral loads, retards or prevents the damage to the immune system, and reduces the risk of developing AIDS.

SIDE EFFECTS:

1. Nausea 2. Stomach pain 3. Diarrhoea, headache 4. Insomnia, rash 5. Fever 6. And dizziness as well as fatal hypersensitivity reactions

SYNTHESIS:

ZIDOVUDINE:

Zidovudine (ZDV), also known as azidothymidine (AZT), is an antiretroviral medication used to prevent and treat HIV/AIDS.

1-[(2R,4S,5S)-4-Azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione

USES:

1. HIV treatment 2. HIV prevention

SIDE EFFECTS:

1. Constipation 2. Headache 3. Loss of appetite 4. Nausea 5. Tiredness 6. Vomiting 7. Weakness

SYNTHESIS:

ANTIPROTOZOAL AGENTS:

Antiprotozoal agents are a class of pharmaceuticals used in treatment of protozoan infection.

METRONIDAZOLE:

Metronidazole is an antibiotic. It fights bacteria in body.

2-(2-methyl-5-nitro-1H-imidazol-1-yl) ethanol

USES:

Metronidazole is used to treat bacterial infections of the vagina, stomach, skin, joints, and respiratory tract. This medication will not treat a vaginal yeast infection.

SIDE EFFECTS:

1. Numbness or tingling in your hands or feet 2. White patches or sores inside your mouth or on your lips 3. Pain or burning when you urinate 4. Diarrhea that is watery or bloody 5. Vision problems, pain behind your eyes 6. Trouble concentrating, slurred speech, mood or behavior changes, tremors, muscle

twitching, seizure (convulsions) 7. Fever, chills, muscle pain, confusion, headache, sore throat, neck stiffness, increased

sensitivity to light, drowsiness, nausea and vomiting 8. Severe skin reaction fever, sore throat, swelling in your face or tongue, burning in your

eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Less serious metronidazole side effects may include:

1. Stomach pain, diarrhea; 2. Dizziness, loss of balance; 3. Vaginal itching or discharge; 4. Dry mouth or unpleasant metallic taste; 5. Cough, sneezing, runny or stuffy nose; or 6. Swollen or sore tongue.

SYNTHESIS: