Course Content

Study of the development of the following classes of drugs, Classification, mechanism of action, uses of drugs mentioned in the course, Structure activity relationship of selective class of drugs as specified in the course and synthesis of drugs superscripted (*)

Unit I

Introduction to Medicinal Chemistry

History and development of medicinal chemistry

Physicochemical properties in relation to biological action

Ionization, Solubility, Partition Coefficient, Hydrogen bonding, Protein binding, Chelation, Bioisosterism,
Optical and Geometrical isomerism.

Drug metabolism

Drug metabolism principles- Phase I and Phase II.
Factors affecting drug metabolism including stereo chemical aspects.

(10 Hours)

Unit II

Adrenergic Neurotransmitters:

Introduction to Medicinal Chemistry

Biosynthesis and catabolism of catecholamine.
Adrenergic receptors (Alpha & Beta) and their distribution.

Sympathomimetic agents: SAR of Sympathomimetic agents

Direct acting: Nor-epinephrine, Epinephrine, Phenylephrine*, Dopamine, Methyldopa, Clonidine, Dobu- tamine, Isoproterenol, Terbutaline, Salbutamol*, Bitolterol, Naphazoline, Oxymetazoline and Xylometazo- line.

• Indirect acting agents: Hydroxyamphetamine, Pseudoephedrine, Propylhexedrine.
• Agents with mixed mechanism: Ephedrine, Metaraminol.

Adrenergic Antagonists:

Alpha adrenergic blockers: Tolazoline*, Phentolamine, Phenoxybenzamine, Prazosin, Dihydroergota- mine, Methysergide.

Beta adrenergic blockers: SAR of beta blockers, Propranolol*, Metibranolol, Atenolol, Betazolol, Bisopro- lol, Esmolol, Metoprolol, Labetolol, Carvedilol.

(10 Hours)

Unit III

Cholinergic neurotransmitters:

Biosynthesis and catabolism of acetylcholine.
Cholinergic receptors (Muscarinic & Nicotinic) and their distribution.

Parasympathomimetic agents: SAR of Parasympathomimetic agents

Direct acting agents: Acetylcholine, Carbachol*, Bethanechol, Methacholine, Pilocarpine.

Indirect acting/ Cholinesterase inhibitors (Reversible & Irreversible): Physostigmine, Neostigmine*, Pyridostigmine, Edrophonium chloride, Tacrine hydrochloride, Ambenonium chloride, Isofluorphate,
Echothiophate iodide, Parathione, Malathion.

Cholinesterase reactivator:

Pralidoxime chloride.

Cholinergic Blocking agents:

SAR of cholinolytic agents

Solanaceous alkaloids and analogues:

Atropine sulphate, Hyoscyamine sulphate, Scopolamine hydrobro- mide, Homatropine hydrobromide, Ipratropium bromide*.

Synthetic cholinergic blocking agents: Tropicamide, Cyclopentolate hydrochloride, Clidinium bromide, Dicyclomine hydrochloride*, Glycopyrrolate, Methantheline bromide, Propantheline bromide, Benz- tropine mesylate, Orphenadrine citrate, Biperidine hydrochloride, Procyclidine hydrochloride*, Tridihex- ethyl chloride, Isopropamide iodide, Ethopropazine hydrochloride.

(10 Hours)

Unit IV

Drugs acting on Central Nervous System

A. Sedatives and Hypnotics:

Benzodiazepines: SAR of Benzodiazepines, Chlordiazepoxide, Diazepam*, Oxazepam, Chloraze- pate, Lorazepam, Alprazolam, Zolpidem
Barbiturtes: SAR of barbiturates, Barbital*, Phenobarbital, Mephobarbital, Amobarbital, Butabarbi- tal, Pentobarbital, Secobarbital
Miscelleneous: Amides & imides: Glutethmide.
Alcohol & their carbamate derivatives: Meprobomate, Ethchlorvynol.
Aldehyde & their derivatives: Triclofos sodium, Paraldehyde.

B. Antipsychotics

Phenothiazeines: SAR of Phenothiazeines – Promazine hydrochloride, Chlorpromazine hydrochlo- ride*, Triflupromazine, Thioridazine hydrochloride, Piperacetazine hydrochloride, Prochlorpera- zine maleate, Trifluoperazine hydrochloride.
Ring Analogues of Phenothiazeines: Chlorprothixene, Thiothixene, Loxapine succinate, Clozapine.
Fluro buterophenones: Haloperidol, Droperidol, Risperidone.
Beta amino ketones: Molindone hydrochloride.
Benzamides: Sulpieride.

C. Anticonvulsants: SAR of Anticonvulsants, mechanism of anticonvulsant action

Barbiturates: Phenobarbitone, Methabarbital.
Hydantoins: Phenytoin*, Mephenytoin, Ethotoin .
Oxazolidine diones: Trimethadione, Paramethadione
Succinimides: Phensuximide, Methsuximide, Ethosuximide* Urea and monoacylureas: Phenace- mide, Carbamazepine*
Benzodiazepines: Clonazepam
Miscellaneous: Primidone, Valproic acid , Gabapentin, Felbamate

(08 Hours)

Unit V

Drugs acting on Central Nervous System

General anesthetics:

Inhalation anesthetics: Halothane*, Methoxyflurane, Enflurane, Sevoflurane, Isoflurane, Desflurane.
Ultra short acting barbitutrates: Methohexital sodium*, Thiamylal sodium, Thiopental sodium.
Dissociative anesthetics: Ketamine hydrochloride.*

Narcotic and non-narcotic analgesics

Morphine and related drugs: SAR of Morphine analogues, Morphine sulphate, Codeine, Meperidine hy- drochloride, Anilerdine hydrochloride, Diphenoxylate hydrochloride, Loperamide hydrochloride, Fentan- yl citrate*, Methadone hydrochloride*, Propoxyphene hydrochloride, Pentazocine, Levorphanol tartarate.

Narcotic antagonists: Nalorphine hydrochloride, Levallorphan tartarate, Naloxone hydrochloride.

Anti-inflammatory agents: Sodium salicylate, Aspirin, Mefenamic acid*, Meclofenamate, Indomethacin, Sulindac, Tolmetin, Zomepriac, Diclofenac, Ketorolac, Ibuprofen*, Naproxen, Piroxicam, Phenacetin, Acetaminophen, Antipyrine, Phenylbutazone.

(07 Hours)

‘Medicinal Chemistry – I (Theory)’ is a course offered in the fourth semester of B. Pharm program at School of Pharmacy, Health Sciences campus, Amrita Vishwa Vidyapeetham.

Course Duration: 45 Hours

Scope:

This subject is designed to impart fundamental knowledge on the structure, chemistry and thera- peutic value of drugs. The subject emphasizes on structure activity relationships of drugs, importance of physicochemical properties and metabolism of drugs. The syllabus also emphasizes on chemical synthesis of important drugs under each class.

Objectives:

Upon completion of the course, the student shall be able to

1. Understand the chemistry of drugs with respect to their pharmacological activity
2. Understand the drug metabolic pathways, adverse effect and therapeutic value of drugs
3. Know the Structural Activity Relationship (SAR) of different class of drugs
4. Write the chemical synthesis of some drugs