Medicinal Chemistry III - B. Pharma 6th Semester Notes Pdf

BP601T. MEDICINAL CHEMISTRY – III (Theory)

Scope: This subject is designed to impart fundamental knowledge on the structure, chemistry and therapeutic value of drugs. The subject emphasis on modern techniques of rational drug design like quantitative structure activity relationship (QSAR), Prodrug concept, combinatorial chemistry and Computer aided drug design (CADD). The subject also emphasizes on the chemistry, mechanism of action, metabolism, adverse effects, Structure Activity Relationships (SAR), therapeutic uses and synthesis of important drugs.

Objectives: Upon completion of the course student shall be able to

1.  Understand the importance of drug design and different techniques of drug design.

2.  Understand the chemistry of drugs with respect to their biological activity.

3.  Know the metabolism, adverse effects and therapeutic value of drugs.

4.  Know the importance of SAR of drugs.

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 by (*)

UNIT – I

Antibiotics

Historical background, Nomenclature, Stereochemistry, Structure activity relationship, Chemical degradation classification and important products of the following classes.

β-Lactam antibiotics: Penicillin, Cepholosporins, β-  Lactamase inhibitors, Monobactams

Aminoglycosides: Streptomycin, Neomycin, Kanamycin

Tetracyclines: Tetracycline, Oxytetracycline, Chlortetracycline, Minocycline, Doxycycline

UNIT – II

Antibiotics

Historical background, Nomenclature, Stereochemistry, Structure activity relationship, Chemical degradation classification and important products of the following classes.

Macrolide: Erythromycin Clarithromycin, Azithromycin.

Miscellaneous: Chloramphenicol*, Clindamycin.

Prodrugs: Basic concepts and application of prodrugs design.

Antimalarials: Etiology of malaria.

Quinolines: SAR, Quinine sulphate, Chloroquine*, Amodiaquine, Primaquine phosphate, Pamaquine*, Quinacrine hydrochloride, Mefloquine.

Biguanides and dihydro triazines: Cycloguanil pamoate, Proguanil.

Miscellaneous: Pyrimethamine, Artesunete, Artemether, Atovoquone.

UNIT – III

Anti-tubercular Agents

Synthetic anti tubercular agents: Isoniozid*, Ethionamide, Ethambutol, Pyrazinamide, Para amino salicylic acid.*

Anti tubercular antibiotics: Rifampicin, Rifabutin, Cycloserine Streptomycine, Capreomycin sulphate.

Urinary tract anti-infective agents

Quinolones: SAR of quinolones, Nalidixic Acid,Norfloxacin, Enoxacin, Ciprofloxacin*, Ofloxacin, Lomefloxacin, Sparfloxacin, Gatifloxacin, Moxifloxacin

Miscellaneous: Furazolidine, Nitrofurantoin*, Methanamine.

Antiviral agents:

Amantadine  hydrochloride,  Rimantadine  hydrochloride,  Idoxuridine trifluoride, Acyclovir*, Gancyclovir, Zidovudine, Didanosine, Zalcitabine, Lamivudine,  Loviride,  Delavirding,  Ribavirin,  Saquinavir,  Indinavir, Ritonavir.

UNIT – IV

Antifungal agents:

Antifungal antibiotics: Amphotericin-B, Nystatin, Natamycin, Griseofulvin.

Synthetic Antifungal agents: Clotrimazole, Econazole, Butoconazole, Oxiconazole Tioconozole, Miconazole*, Ketoconazole, Terconazole, Itraconazole, Fluconazole, Naftifine hydrochloride, Tolnaftate*.

Anti-protozoal Agents: Metronidazole*, Tinidazole, Ornidazole, Diloxanide, Iodoquinol, Pentamidine Isethionate, Atovaquone, Eflornithine.

Anthelmintics: Diethylcarbamazine citrate*, Thiabendazole, Mebendazole*, Albendazole, Niclosamide, Oxamniquine, Praziquantal, Ivermectin.

Sulphonamides and Sulfones

Historical development, chemistry, classification and SAR of Sulfonamides: Sulphamethizole, Sulfisoxazole, Sulphamethizine, Sulfacetamide*, Sulphapyridine, Sulfamethoxaole*, Sulphadiazine, Mefenide acetate, Sulfasalazine.

Folate reductase inhibitors: Trimethoprim*, Cotrimoxazole.

Sulfones: Dapsone*.

UNIT – V

Introduction to Drug Design

Various approaches used in drug design.

Physicochemical parameters used in quantitative structure activity relationship (QSAR) such as partition coefficient, Hammet’s electronic parameter, Tafts steric parameter and Hansch analysis.

Pharmacophore modeling and docking techniques.

Combinatorial Chemistry:  Concept and applications of combinatorial chemistry: solid phase and solution phase synthesis.

BP607P. MEDICINAL CHEMISTRY- III (Practical)

I. Preparation of drugs and intermediates

1. Sulphanilamide

2. 7-Hydroxy, 4-methyl coumarin

3. Chlorobutanol

4. Triphenyl imidazole

5. Tolbutamide

6. Hexamine

II. Assay of drugs

1. Isonicotinic acid hydrazide

2. Chloroquine

3. Metronidazole

4. Dapsone

5. Chlorpheniramine maleate

6. Benzyl penicillin

III. Preparation of medicinally important compounds or intermediates by Microwave irradiation technique

IV. Drawing structures and reactions using chem draw®

V. Determination of physicochemical properties such as logP, clogP, MR, Molecular weight, Hydrogen bond donors and acceptors for class of drugs course content using drug design software Drug likeliness screening (Lipinskies RO5)

Recommended Books (Latest Editions)

1.  Wilson and Giswold’s Organic medicinal and Pharmaceutical Chemistry.

2.  Foye’s Principles of Medicinal Chemistry.

3.  Burger’s Medicinal Chemistry, Vol I to IV.

4.   Introduction to principles of drug design- Smith and Williams.

5.  Remington’s Pharmaceutical Sciences.

6.  Martindale’s extra pharmacopoeia.

7.  Organic Chemistry by I.L. Finar, Vol. II.

8.  The Organic Chemistry of Drug Synthesis by Lednicer, Vol. 1-5.

9.   Indian Pharmacopoeia.

10. Text book of practical organic chemistry- A.I.Vogel.