B.Pharmacy 5th Semester Medicinal Chemistry 2 Important Question Answer
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| Medicinal Chemistry 2 Important Question Answer |
Medicinal Chemistry 2 Very Short Question Answer [2 Marks]
1. Define antihistaminic agents with suitable examples:
Antihistaminic agents are drugs that block histamine receptors to prevent allergic symptoms. They are classified as H₁ and H₂ antagonists.
Example: Diphenhydramine (H₁ antagonist) – used in allergies; Ranitidine (H₂ antagonist) – used for peptic ulcers.
2. Draw chemical structure of meprobamate:
Structure of Meprobamate:
3. Write mechanism of action of antimetabolite:
Antimetabolites mimic natural metabolites and inhibit enzymes involved in DNA/RNA synthesis. They interfere with nucleotide biosynthesis.
Example: Methotrexate inhibits dihydrofolate reductase, blocking thymidylate and purine synthesis, halting cell division.
4. Define contraceptive and its symptoms:
Contraceptives are agents that prevent pregnancy.
Symptoms/Side Effects: Nausea, weight gain, mood swings, breast tenderness, and irregular menstruation.
5. Write the synthesis and uses of methyldopa:
Synthesis (sketched briefly in exams): From α-bromo-3,4-dihydroxybenzene + methylamine → Methyldopa.
Uses: Used as antihypertensive in pregnancy-induced hypertension.
6. Classify Class I antiarrhythmic agents with example:
Class I antiarrhythmics are sodium channel blockers.
IA: Quinidine
IB: Lidocaine
IC: Flecainide
7. Enlist the name of drugs used in congestive heart failure:
Digoxin
Furosemide
Enalapril
Spironolactone
Carvedilol
8. Draw chemical structure of Sildenafil and Tadalafil:
Sildenafil:
Tadalafil:
9. Discuss the mechanism of action of Thiazolidinediones:
Thiazolidinediones activate PPAR-γ receptors, increasing insulin sensitivity in adipose tissue, muscle, and liver. This reduces blood glucose levels.
Example: Pioglitazone.
10. Write the synthesis of Benzocaine and Procaine:
Benzocaine: p-aminobenzoic acid + ethanol → Benzocaine
Procaine: p-aminobenzoic acid + diethylaminoethanol (via esterification)
11. Draw structure and write uses of diphenhydramine hydrochloride:
Structure:
Uses: Antihistaminic for allergic reactions, motion sickness.
12. Write mechanism of action of methotrexate:
Methotrexate inhibits dihydrofolate reductase, preventing the formation of tetrahydrofolate needed for DNA synthesis—causing cell cycle arrest in S-phase.
13. Draw structure and write mechanism of action of verapamil:
Structure:
MOA: Calcium channel blocker; inhibits L-type calcium channels, decreasing myocardial contractility and heart rate.
14. Draw the structure and uses of loop diuretics drugs:
Example: Furosemide
Uses: Treats edema in CHF, cirrhosis, and hypertension.
15. Discuss mechanism of action and uses of lovastatin:
Lovastatin inhibits HMG-CoA reductase, reducing cholesterol synthesis in the liver.
Uses: Hyperlipidemia, atherosclerosis prevention.
16. Write a short note on digoxin:
Digoxin is a cardiac glycoside that inhibits Na⁺/K⁺-ATPase, increasing intracellular Ca²⁺ and improving cardiac contractility.
Uses: CHF and atrial fibrillation.
17. Write mechanism of action and draw structure of sildenafil:
MOA: Inhibits phosphodiesterase-5 (PDE5), increasing cGMP → smooth muscle relaxation → vasodilation.
Structure: (Already given above in Q8)
18. Discuss the advantages of amide local anaesthetics over ester local anaesthetics:
Amides (e.g., Lidocaine) are more stable, have longer duration, and cause fewer allergic reactions than esters (e.g., Procaine).
19. Write a short note on thiazolidinediones:
Thiazolidinediones (e.g., Rosiglitazone) improve insulin sensitivity by activating PPAR-γ.
Uses: Type 2 diabetes.
Side effects: Weight gain, fluid retention.
20. Discuss about metabolic pathway of insulin:
Insulin is metabolized in the liver (via insulinase) and kidneys. It undergoes receptor-mediated endocytosis, degradation, and amino acid recycling.
21. Write the uses and mechanism of action of chlorpromazine:
MOA: D₂ receptor antagonist in CNS → antipsychotic, antiemetic.
Uses: Schizophrenia, nausea, hiccups.
22. Discuss the drugs used for the treatment of Alzheimer disease:
Donepezil (AChE inhibitor)
Rivastigmine
Galantamine
Memantine (NMDA antagonist)
23. Draw the structure of ephedrine and write its uses:
Structure:
Uses: Nasal decongestant, bronchodilator.
24. Give the synthesis of benzocaine:
p-Nitrotoluene → p-nitrobenzoic acid → p-aminobenzoic acid → Benzocaine (via esterification with ethanol)
25. Write the uses and mechanism of action of Dicyclomine:
MOA: Muscarinic receptor antagonist → relaxes GI smooth muscles.
Uses: Treats IBS and abdominal cramps.
26. Differentiate between geometrical and conformational isomers:
Geometrical isomers: Due to restricted rotation (e.g., cis-trans in alkenes)
Conformational isomers: Due to rotation around single bonds (e.g., staggered, eclipsed ethane)
27. Give the structure and uses of atropine:
Structure:
Uses: Bradycardia, pre-anesthetic, antidote for organophosphate poisoning.
28. Give the synthesis of Cimetidine:
Complex multi-step synthesis from cyanoguanidine and 2-cyano-1-methylthioimidazole. (Draw simple schematic in exam.)
Uses: H₂ receptor antagonist for ulcers.
29. State the mechanism of action and uses of Methotrexate:
(Repeated; already answered in Q12)
30. What are anti-anginal drugs? Outline the structure of Nitroglycerin:
Anti-anginal drugs reduce myocardial oxygen demand or increase oxygen supply.
Nitroglycerin structure:
31. Give the synthesis and uses of Furosemide:
Synthesis from anthranilic acid + chlorosulfonic acid.
Uses: Loop diuretic in CHF and hypertension.
32. Name any five structures of any two drugs used in Congestive Heart Failure:
Drugs:
Digoxin, Furosemide – Structures already above.
Enalapril, Carvedilol, Spironolactone.
33. State the importance of anticoagulants:
Anticoagulants prevent clot formation, used in DVT, pulmonary embolism, MI, stroke prevention.
Examples: Heparin, Warfarin.
34. Write the structure and uses of Testosterone:
Structure:
Uses: Male hypogonadism, delayed puberty.
35. Discuss mechanism of action and uses of Sildenafil:
(Repeated; see Q17)
36. Outline the synthesis of benzocaine:
(Repeated; see Q24)
37. State the mechanism of action and uses of metformin:
MOA: Activates AMPK, reduces hepatic glucose output, improves insulin sensitivity.
Uses: Type 2 diabetes mellitus.
38. Draw structure and write mechanism of action of verapamil:
(Repeated; see Q13)
39. Discuss mechanism of action and uses of lovastatin:
(Repeated; see Q15)
40. Name any five drugs used in congestive heart failure:
Digoxin
Furosemide
Enalapril
Carvedilol
Spironolactone
Medicinal Chemistry 2 Short Question Answer [5 Marks]
1. Describe the nomenclature and stereochemistry of steroids:
Steroids are named based on the cyclopentanoperhydrophenanthrene ring system, consisting of three six-membered rings (A, B, C) and one five-membered D ring.
Stereochemistry is important due to multiple chiral centers at positions like C5, C8, C9, C10, C13, C14, and C17.
Trans and cis configurations between rings influence biological activity.
Numbering starts from ring A and proceeds counterclockwise to ring D.
Example: Testosterone (17β-hydroxyandrost-4-en-3-one) indicates a 17-hydroxy group and a double bond at C4.
Steroids can have α (below plane) or β (above plane) substituents. Configuration at C5 determines if a steroid is planar or bent (5α = bent, 5β = planar).
2. Explain in detail about SAR of local anaesthetics:
The general structure: Aromatic ring – linker – amine group.
SAR:
Aromatic ring: Lipophilic part enhances membrane penetration. Electron-donating groups at ortho/para positions increase potency.
Linkage (ester/amide): Determines stability and metabolism. Amides (lidocaine) are more stable than esters (procaine).
Amino group: Usually tertiary amine, ensures water solubility and interaction with Na⁺ channels.
Increasing alkyl chain length improves potency but reduces duration.
Optimal pKa ~8–9 allows better onset time.
3. Discuss SAR and mechanism of action of alkylating agents:
MOA: Alkylating agents form covalent bonds with DNA bases, especially at N7 of guanine, causing cross-linking, mispairing, or strand breakage → apoptosis.
SAR:
Bis(β-chloroethyl) groups: Essential for cross-linking.
Electron-withdrawing groups increase activity.
Aromatic rings may improve lipophilicity and cell penetration.
Examples: Cyclophosphamide, Melphalan, Mechlorethamine.
4. Explain the synthesis and uses of acetazolamide, chlorothiazide and nitroglycerine:
Acetazolamide: Derived from sulfanilamide; used as carbonic anhydrase inhibitor in glaucoma, epilepsy, altitude sickness.
Chlorothiazide: Synthesized from benzene-1,2-disulfonamide; a thiazide diuretic used in hypertension and edema.
Nitroglycerine: Made by nitration of glycerol with nitric acid in presence of sulfuric acid. Used in angina pectoris due to vasodilation.
5. Write mechanism of action and uses of Menadione, Acetomenadione, Anisindione and clopidogrel. Also write the synthesis of warfarin:
Menadione (Vit K₃): Promotes clotting factor synthesis.
Acetomenadione: Synthetic Vit K derivative; same action.
Anisindione: Inhibits Vit K epoxide reductase → anticoagulant.
Clopidogrel: Blocks ADP receptor (P2Y12) on platelets → antiplatelet.
Warfarin synthesis: Coumarin + benzylideneacetone → condensation yields warfarin. Used as oral anticoagulant.
6. Write a note on oral contraceptives. Discuss the mechanism of action and uses of Mifepristone, Norgestrel and Levonorgestrel:
Oral contraceptives prevent ovulation by hormonal regulation.
Mifepristone: Progesterone antagonist → induces abortion.
Norgestrel/Levonorgestrel: Inhibit LH/FSH → prevent ovulation.
Used for birth control, emergency contraception.
7. Discuss in detail about insulin and its preparation. Describe the mechanism of action, uses and synthesis of Tolbutamide:
Insulin: Peptide hormone from pancreatic β-cells.
Preparation: Recombinant DNA tech in E. coli or yeast.
MOA: Binds insulin receptor → activates tyrosine kinase → glucose uptake.
Tolbutamide: 1st gen sulfonylurea; stimulates insulin release from β-cells.
Synthesis: p-toluene sulfonylurea + butylamine.
8. Give the SAR and synthesis of disopyramide phosphate:
SAR:
Aromatic ring for lipophilicity.
Tertiary amine required for Na⁺ channel blockade.
Alkyl chain spacing between nitrogen and ring.
Synthesis: 2-chloro-N,N-diisopropyl-2-phenylacetamide + 1-amino-2-methoxypropane → Disopyramide.
Used as Class IA antiarrhythmic.
9. Classify anticoagulants. Write the SAR and synthesis of warfarin:
Classification:
Oral: Warfarin, Acenocoumarol
Parenteral: Heparin, Enoxaparin
SAR of Warfarin:
Coumarin core essential.
Substituent at position 3 affects potency and duration.
Synthesis: Coumarin + benzylideneacetone condensation.
Used in DVT, stroke prevention.
10. Classify antithyroid drugs and write a detailed note on propylthiouracil:
Classification:
Thioamides: Propylthiouracil, Methimazole
Iodides: KI, Lugol's iodine
Radioactive iodine (I-131)
Propylthiouracil MOA: Inhibits thyroid peroxidase → blocks T₃, T₄ synthesis; also inhibits peripheral T₄ to T₃ conversion.
Used in hyperthyroidism.
11. Classify sulphonyl ureas and biguanides derivative. Write SAR of tolbutamide:
Sulfonylureas:
1st gen: Tolbutamide
2nd gen: Glibenclamide
Biguanides: Metformin
SAR (Tolbutamide):
Sulfonylurea moiety essential
Para-alkyl substitution improves potency
Longer alkyl chain → more activity
Tolbutamide stimulates insulin release.
12. Write the structural classification of local anaesthetics, write the mechanism of benzocaine:
Classification:
Ester type: Benzocaine, Procaine
Amide type: Lidocaine, Bupivacaine
Benzocaine MOA: Blocks voltage-gated Na⁺ channels in nerve membranes → prevents impulse conduction.
Used topically for minor pain.
13. Write the SAR and mechanism of action of mechlorethamine:
MOA: Cross-links DNA via alkylation at N7 of guanine → apoptosis.
SAR:
Bis(β-chloroethyl) group needed
Electron withdrawing group increases reactivity
Used in Hodgkin’s lymphoma.
14. Write the structural classification of oral contraceptives:
Classification:
Estrogenic: Ethinylestradiol
Progestins: Norgestrel, Levonorgestrel
Combination: Ethinylestradiol + Norgestrel
Postcoital (emergency): Mifepristone, Levonorgestrel
15. (a) Classify local anaesthetics. Discuss SAR with example:
(Already answered in Q2 and Q12)
16. (b) Describe sedative and hypnotics. SAR of barbiturates:
Sedatives calm CNS; hypnotics induce sleep.
SAR of barbiturates:
Substituents at C5 increase lipophilicity and activity
Sulfur at C2 (thiopental) increases potency
Longer chains at C5 → faster onset
Used in anxiety, epilepsy.
17. (a) Write MOA and synthesis of phenytoin and diazepam:
Phenytoin: Blocks Na⁺ channels → prevents seizure propagation.
Synthesis: Benzoin + urea
Diazepam: Enhances GABA activity via GABA-A receptor.
Synthesis: 2-amino-5-chlorobenzophenone + glycine derivative.
18. (b) Classify Parkinson drugs and write MOA:
Classification:
Dopamine precursor: Levodopa
MAO-B inhibitors: Selegiline
COMT inhibitors: Entacapone
MOA: Increase dopamine levels or mimic dopamine in CNS.
19. (a) Describe antidepressants, TCA in detail:
Classification:
TCA: Amitriptyline
SSRI: Fluoxetine
SNRI: Venlafaxine
TCA MOA: Block reuptake of serotonin and norepinephrine.
Used in depression, chronic pain.
20. (b) Forces in drug-receptor interactions:
Ionic bonds: Strong, initial attraction
Hydrogen bonding: Directional, contributes specificity
Van der Waals: Weak, close proximity
Hydrophobic interactions: Increase binding affinity
These forces determine drug efficacy and selectivity.
21. (a) Discuss cholinergic drugs and their uses:
Cholinergic drugs mimic acetylcholine and act on cholinergic receptors (muscarinic and nicotinic).
Types:
Direct-acting: Acetylcholine, Bethanechol
Indirect-acting (Anticholinesterases): Neostigmine, Physostigmine
Uses:
Bethanechol: Postoperative urinary retention
Pilocarpine: Glaucoma
Neostigmine: Myasthenia gravis
Physostigmine: Antidote for atropine poisoning
Side effects: Salivation, diarrhea, bradycardia.
22. (b) Define antitussives. Give structure, MOA, uses of dextromethorphan:
Antitussives suppress cough reflex.
Structure (Dextromethorphan): A morphinan derivative without narcotic action.
MOA: Acts on medullary cough center, non-competitive NMDA receptor antagonist.
Uses: Dry/non-productive cough.
Advantage: Lacks opioid side effects like sedation or addiction.
23. (a) Define Prodrug. Explain with examples and applications:
Prodrug is an inactive compound that gets metabolized into an active drug in the body.
Examples:
Enalapril → Enalaprilat (ACE inhibitor)
Codeine → Morphine (analgesic)
Applications:
Improve bioavailability (e.g., L-Dopa)
Reduce toxicity (e.g., Capecitabine → 5-FU)
Enhance solubility or stability
Site-specific drug delivery (e.g., Sulfasalazine in colon)
24. (b) Classify anticonvulsant agents. MOA of valproic acid and ethosuximide:
Classification:
Na⁺ channel blockers: Phenytoin
GABA enhancers: Phenobarbital
Ca²⁺ channel blockers: Ethosuximide
Mixed action: Valproic acid
Valproic acid: Enhances GABA levels, blocks Na⁺ and T-type Ca²⁺ channels.
Ethosuximide: Inhibits T-type Ca²⁺ channels in thalamic neurons.
Used in absence and generalized seizures.
25. Discuss SAR of thiazide diuretics. Outline synthesis of chlorothiazide:
SAR:
Sulfonamide group is essential for diuretic activity.
Electron-withdrawing groups at position 6 increase potency.
Saturation of 3,4 double bond → enhances activity.
Substituents at position 3 modify duration of action.
Synthesis of Chlorothiazide:
Condensation of 3,4-dihydroxybenzenesulfonamide with sulfonyl chloride, followed by cyclization gives chlorothiazide.
Uses: Hypertension, edema.
Medicinal Chemistry 2 Long Question Answer [10 Marks]
1. Classify antihistaminic agents with their chemical structure. Explain SAR of antihistamines. Discuss the synthesis and uses of Cimetidine.
Antihistamines are drugs that block histamine receptors and are classified as:
A. H₁-Antagonists (used in allergies):
First Generation: Diphenhydramine, Chlorpheniramine
Second Generation: Loratadine, Cetirizine
B. H₂-Antagonists (used in gastric ulcers):
Cimetidine, Ranitidine, Famotidine
Structure Examples:
Diphenhydramine (H₁):
Cimetidine (H₂):
SAR of H₁ Antihistamines:
Two aromatic or heteroaromatic rings provide hydrophobic interaction with receptors.
Ethylamine or ethanolamine side chain connects to the basic nitrogen.
Alkyl groups on nitrogen (e.g., dimethyl) increase lipophilicity and BBB penetration.
Electron-donating groups on rings enhance potency.
Synthesis of Cimetidine:
Starts with cyanoguanidine, which reacts with methyl mercaptoimidazole.
Introduction of side chain (methyl and cyanoguanidine groups) gives cimetidine.
Uses of Cimetidine:
Treats peptic ulcers, GERD, and Zollinger-Ellison syndrome.
Acts by selectively blocking H₂ receptors in gastric parietal cells, reducing acid secretion.
2. What is hypertension? Discuss in detail about drugs acting on Renin-Angiotensin system.
Hypertension is defined as persistently high arterial blood pressure, typically above 140/90 mmHg.
Renin-Angiotensin System (RAS):
Renin (from kidneys) converts angiotensinogen → angiotensin I.
ACE (Angiotensin-Converting Enzyme) converts I → II.
Angiotensin II causes vasoconstriction and aldosterone release, increasing BP.
Drugs acting on RAS:
1. ACE Inhibitors:
Example: Captopril, Enalapril
Inhibit ACE → reduce angiotensin II → vasodilation
Adverse effects: dry cough, hyperkalemia
2. Angiotensin Receptor Blockers (ARBs):
Example: Losartan, Valsartan
Block AT₁ receptors → reduce vasoconstriction and aldosterone effects
3. Renin Inhibitors:
Example: Aliskiren
Directly inhibits renin enzyme
4. Aldosterone Antagonists:
Example: Spironolactone, Eplerenone
Block Na⁺ and water retention, reduce preload
3. What are lipoproteins? Classify antihyperlipidemic agents with suitable examples. Discuss the SAR of fibrate acid derivatives.
Lipoproteins are lipid-protein complexes transporting cholesterol and triglycerides in blood. Types include:
Chylomicrons, VLDL, LDL, HDL
Antihyperlipidemic agents:
Statins: Simvastatin, Lovastatin (HMG-CoA reductase inhibitors)
Fibrates: Fenofibrate, Gemfibrozil (PPAR-α agonists)
Niacin: Decreases VLDL secretion
Bile acid sequestrants: Cholestyramine
Cholesterol absorption inhibitors: Ezetimibe
SAR of Fibrates:
Phenoxyisobutyric acid nucleus is essential.
Alkyl chains increase lipophilicity and activity.
Free carboxylic acid enhances binding to PPAR-α receptor.
Uses: Lower triglycerides and increase HDL.
4. Write the SAR and mechanism of action of H₂ receptor antagonists.
H₂ receptor antagonists inhibit histamine-induced gastric acid secretion by selectively blocking H₂ receptors on parietal cells.
Mechanism of Action:
H₂ antagonists (e.g., Cimetidine, Ranitidine) competitively block H₂ receptors.
Prevent activation of adenylate cyclase → ↓ cAMP → ↓ proton pump activity → ↓ HCl secretion.
Structure Activity Relationship (SAR):
Basic nucleus: Imidazole or other heterocycles (like furan in ranitidine) needed for receptor affinity.
Side chain: Flexible alkyl chain (usually 4-atom chain) links the nucleus to polar tail.
Polar tail: Usually a guanidine or cyanoguanidine group increases receptor selectivity and potency.
Substituents on nucleus affect potency, metabolism, and duration of action.
E.g., Methyl on imidazole ring increases activity (as seen in cimetidine).
Examples:
Cimetidine: First clinically used H₂ blocker
Ranitidine: More potent, fewer side effects
Famotidine: Higher potency and longer duration
Uses: Peptic ulcers, GERD, Zollinger-Ellison syndrome.
5. Write the synthesis and MOA of Acetazolamide.
Acetazolamide is a carbonic anhydrase inhibitor used as a diuretic and in glaucoma.
Synthesis of Acetazolamide:
Starts from sulfanilamide.
Sulfanilamide reacts with cyanogen bromide, forming a sulfonamide derivative.
This is then converted to the final heterocyclic ring containing acetazolamide.
Structure: Contains a 1,3,4-thiadiazole ring substituted with sulfonamide.
Mechanism of Action:
Inhibits carbonic anhydrase in proximal convoluted tubule.
Prevents conversion of CO₂ + H₂O → H⁺ + HCO₃⁻.
Leads to decreased reabsorption of Na⁺, K⁺, and bicarbonate → diuresis.
Also decreases aqueous humor formation → used in glaucoma.
Uses:
Glaucoma
Epilepsy (adjuvant)
Mountain sickness
Edema due to CHF
6. Classify antianginal drugs. Give the synthesis and SAR of isosorbide dinitrate.
Antianginal drugs relieve angina by improving oxygen supply or decreasing demand.
Classification:
Nitrates: Nitroglycerin, Isosorbide dinitrate – vasodilators
Calcium channel blockers: Verapamil, Amlodipine – reduce workload
Beta-blockers: Propranolol – decrease heart rate and contractility
Potassium channel openers: Nicorandil
Synthesis of Isosorbide Dinitrate:
Derived from isosorbide (obtained from sorbitol).
Nitration of isosorbide with nitric acid gives isosorbide dinitrate.
SAR of Organic Nitrates:
Must have nitrate ester groups (–ONO₂) which release nitric oxide (NO).
NO activates guanylate cyclase → ↑ cGMP → smooth muscle relaxation.
Lipophilicity improves membrane penetration.
Substituent position on isosorbide ring affects potency and duration.
Uses:
Angina pectoris
CHF (as adjunct)
Prevention of exercise-induced angina
7. Classify CNS stimulants. Discuss about synthesis of caffeine.
CNS stimulants enhance brain activity by increasing excitatory neurotransmitters.
Classification:
Xanthine derivatives: Caffeine, Theophylline
Amphetamine-type: Amphetamine, Methylphenidate
Analeptics: Nikethamide, Doxapram
Eugeroics: Modafinil (used in narcolepsy)
Synthesis of Caffeine:
Methylation of theobromine or xanthine derivatives.
In lab, synthesized from uric acid derivatives via methylation steps.
Caffeine is 1,3,7-trimethylxanthine.
Mechanism of Action:
Inhibits phosphodiesterase enzyme → ↑ cAMP.
Antagonizes adenosine receptors → CNS stimulation.
Increases alertness, heart rate, and reduces fatigue.
Uses:
Headache (in combination)
Drowsiness
Respiratory stimulant in neonates (caffeine citrate)
8. Define bioisosterism. Explain in detail about its applications.
Bioisosterism refers to the replacement of an atom or group in a drug molecule with another atom or group that has similar physical or chemical properties, without significantly affecting the biological activity.
Types of Bioisosteres:
Classical Bioisosteres: Similar in size and valency
Example: –OH ↔ –NH₂, –H ↔ –F
Non-Classical Bioisosteres: Dissimilar chemically, but mimic biological effect
Example: –COOH ↔ tetrazole ring
Applications of Bioisosterism:
Improved Potency: Modifying functional groups enhances target binding.
Example: Replacing COOH in angiotensin receptor blockers with tetrazole (as in Losartan).
Better Pharmacokinetics: Altering groups to resist metabolism or improve absorption.
Example: Fluorine substitution improves lipophilicity and metabolic stability.
Reduced Toxicity: Substitution of metabolically unstable groups reduces side effects.
Example: Replacing aromatic nitro groups with bioisosteres to reduce mutagenicity.
Patent Extension: Altering structure using bioisosteres can create novel entities.
Improved Selectivity: Adjusting interaction with specific receptor subtypes.
Example: Modifications in beta-blockers to enhance β1-selectivity.
Conclusion:
Bioisosterism is a vital medicinal chemistry tool used in drug design to optimize pharmacological and physicochemical properties, improve safety profiles, and generate new leads.
9. What are acetylcholinesterase inhibitors? Give the synthesis of tacrine.
Acetylcholinesterase inhibitors (AChEIs) are drugs that inhibit the enzyme acetylcholinesterase, preventing the breakdown of acetylcholine in synaptic clefts, thereby increasing its concentration.
Classification:
Reversible AChEIs: Physostigmine, Donepezil
Irreversible AChEIs: Organophosphates like echothiophate
Uses:
Alzheimer’s disease
Myasthenia gravis
Glaucoma
Antidote in anticholinergic poisoning
Mechanism of Action:
AChEIs bind to the active site of acetylcholinesterase and block hydrolysis of acetylcholine.
This enhances cholinergic transmission at synapses.
Synthesis of Tacrine (1,2,3,4-Tetrahydroacridine):
Starting from anthranilic acid, cyclized using reagents to form acridine core.
Reduction of acridine leads to tetrahydroacridine (Tacrine).
Tacrine was the first centrally acting AChEI approved for Alzheimer’s disease. However, it is now less used due to hepatotoxicity.
10. Describe skeletal muscle relaxants. Give examples along with the mechanism of action.
Skeletal muscle relaxants are drugs that reduce muscle tone and are used to treat muscle spasticity or during surgeries.
Classification:
Peripherally Acting Agents
Non-depolarizing: Tubocurarine, Pancuronium
Depolarizing: Succinylcholine
Centrally Acting Agents
Baclofen, Diazepam, Tizanidine
Mechanism of Action:
Non-depolarizing agents block nicotinic receptors at the neuromuscular junction, preventing acetylcholine binding.
Depolarizing agents (like succinylcholine) cause persistent depolarization leading to paralysis.
Central agents act on spinal cord or brain to suppress reflex arcs.
Uses:
Muscle relaxation during surgeries
Control of spasticity (in cerebral palsy, multiple sclerosis)
Relief of acute muscle spasms
11. Classify antipsychotic drugs. Discuss in detail about first generation antipsychotics.
Antipsychotic drugs are used to manage symptoms of schizophrenia, psychosis, and bipolar disorder.
Classification:
First Generation (Typical):
Phenothiazines: Chlorpromazine, Trifluoperazine
Butyrophenones: Haloperidol
Thioxanthenes: Flupenthixol
Second Generation (Atypical):
Clozapine, Risperidone, Olanzapine
First Generation Antipsychotics (FGAs):
Act mainly by blocking D₂ dopamine receptors in mesolimbic pathway.
Reduce positive symptoms (hallucinations, delusions) but have little effect on negative symptoms.
Side effects: Extrapyramidal symptoms (EPS), tardive dyskinesia, hyperprolactinemia, sedation.
Structure Example (Chlorpromazine):
Phenothiazine core with side chain at N10 linked to a basic amine.
12. Classify anti-neoplastic agents in detail. Give the synthesis of Mechlorethamine.
Anti-neoplastic agents are drugs used in the treatment of cancers.
Classification:
Alkylating agents: Cyclophosphamide, Mechlorethamine
Antimetabolites: Methotrexate, 5-FU
Plant alkaloids: Vincristine, Paclitaxel
Antibiotics: Doxorubicin
Hormonal agents: Tamoxifen
Monoclonal antibodies: Rituximab
Synthesis of Mechlorethamine:
React diethanolamine with thionyl chloride to get bis(2-chloroethyl)amine.
Methylation gives mechlorethamine.
MOA: Alkylates DNA at N7 of guanine → cross-links → apoptosis.
13. Discuss SAR of local anaesthetics.
General structure: Aromatic ring – linker (ester/amide) – amino terminus
SAR Points:
Aromatic ring: Essential for lipophilicity and nerve membrane penetration.
Electron-donating groups increase potency.
Linkage group:
Ester (Procaine): Rapid metabolism, short duration
Amide (Lidocaine): More stable and longer acting
Amine group: Tertiary amine ensures water solubility and binds to Na⁺ channel.
Alkyl chains: Increase duration of action.
Conclusion: Ideal agents must balance lipid solubility and water solubility, with proper pKa (~8–9) for effective action.
14. What are antihypertensive agents? Classify them and give mode of action and uses of methyldopa hydrochloride.
Antihypertensives lower blood pressure and reduce cardiovascular risk.
Classification:
Diuretics: Hydrochlorothiazide
Beta-blockers: Propranolol
Calcium channel blockers: Amlodipine
ACE inhibitors: Enalapril
ARBs: Losartan
Centrally acting agents: Methyldopa
Methyldopa Hydrochloride:
MOA: Converted into α-methylnorepinephrine in CNS, which stimulates central α₂ receptors, reducing sympathetic tone → lowers BP.
Uses:
Used in pregnancy-induced hypertension due to safety
Mild to moderate essential hypertension
Side Effects: Sedation, hemolytic anemia (rare), dry mouth
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B.Pharmacy 5th Semester Medicinal Chemistry 2 Important Question Answer
B.Pharmacy 5th Semester All Subject Important Question Answer
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