BP402T - Medicinal Chemistry-1

Scope: This subject is designed to impart fundamental knowledge on the structure, chemistry and therapeutic 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

UNIT-1

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.

Unit-2

Drugs acting on Autonomic Nervous System
Adrenergic Neurotransmitters:
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, Dobutamine, Isoproterenol, Terbutaline, Salbutamol*, Bitolterol, Naphazoline, Oxymetazoline and Xylometazoline.

Indirect acting agents: Hydroxyamphetamine, Pseudoephedrine, Propylhexedrine.

Agents with mixed mechanism: Ephedrine, Metaraminol.
Adrenergic Antagonists:
Alpha adrenergic blockers: Tolazoline*, Phentolamine, Phenoxybenzamine, Prazosin, Dihydroergotamine, Methysergide.
Beta adrenergic blockers: SAR of beta blockers, Propranolol*, Metibranolol, Atenolol, Betazolol, Bisoprolol, Esmolol, Metoprolol, Labetolol, Carvedilol.

UNIT-3

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 hydrobromide, Homatropine hydrobromide, Ipratropium bromide*.
Synthetic cholinergic blocking agents: Tropicamide, Cyclopentolate
hydrochloride, Clidinium bromide, Dicyclomine hydrochloride*, Glycopyrrolate, Methantheline bromide, Propantheline bromide, Benztropine mesylate, Orphenadrine citrate, Biperidine hydrochloride, Procyclidine hydrochloride*, Tridihexethyl chloride, Isopropamide iodide, Ethopropazine hydrochloride.

UNIT-4

Drugs acting on Central Nervous System
A. Sedatives and Hypnotics:
Benzodiazepines: SAR of Benzodiazepines, Chlordiazepoxide, Diazepam*, Oxazepam, Chlorazepate, Lorazepam, Alprazolam, Zolpidem
Barbiturtes: SAR of barbiturates, Barbital*, Phenobarbital, Mephobarbital, Amobarbital, Butabarbital, 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 hydrochloride*, Triflupromazine, Thioridazine
hydrochloride, Piperacetazine hydrochloride, Prochlorperazine 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: Phenacemide, Carbamazepine*
Benzodiazepines: Clonazepam
Miscellaneous: Primidone, Valproic acid , Gabapentin, Felbamate

UNIT-5

Drugs acting on Central Nervous System
General anesthetics:
Inhalation anesthetics: Halothane*, Methoxyflurane, Enflurane, Sevoflurane, Isoflurane, Desflurane.

Ultra short acting barbiturates: 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 hydrochloride, Anilerdine hydrochloride, Diphenoxylate hydrochloride, Loperamide hydrochloride, Fentanyl 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.