Pharmaceutical Chemistry II Joseph o. oweta | PHc 3201

Course Description A core course intended for third year Bachelor of Pharmacy students. Chemical Classification, Synthesis, SARs, Pharmacopoeial Standards at least one representative drug for the following classes Diuretics CVS agents General and Local Anaesthetics Histamine and Antihistamine agents Analgesics Steroids Prostaglandins, Leukotrienes and other Eicosanoids Hormones Peptides Vitamins L1, L2, Pharm. Chem Lab Lectures: Two periods a week Labs: Once a week Prerequisites: Pharm Chem 1, Basic Organic Chemistry. Credits: 4 45 Teaching Hours 30 Practical Hours Total: 60 Contact Hours

Course Objectives Identify the chemical classes to which different drugs belong Draw structures of drugs Describe physical and chemical properties of a drug or group of drugs where appropriate Write the chemical equations and mechanisms, where appropriate, to describe the synthetic routes for different drugs Relate the chemical structure to biological availability, activity, routes of delivery/metabolism for some pharmacological classes of drugs Describe the identification methods, purity assessment and assay procedures for the drugs

Required Materials Books Articles Web Other Reading ACD labs software (Optional) Technology/Tools

Instructional Methods – Lectures – Class discussion – Labs

Assessment Criteria Continuous Assessments 30 % Final Examination 70%

Instructor Contact Information

Diurectics Are chemicals that increase the rate of urine formation. Primarily act by direct inhibition of Na + transport along the nephron. 2 o / indirect actions may occur as a result of 1 o diuretic actions. Are X-teristic of each class and determined by locus of diuretic action and downstream nephron response Both 1 o and 2 o X-tics determine the electrolyte secretion pattern E.g. some combination of natriuretic, chloruretic, saluretic, kaliuretic, bicabonuretic or calciruretic properties

Therapeutic classes of diuretics

Carbonic Anhydrase Inhibitors Discovered shortly after the introduction of sulphanilamide as an antibacterial. It was observed that sulphanilamide also produced systemic acidosis and an alkaline urine (HCO3− excretion). It was shown that this activity was a result of renal carbonic anhydrase (CA) inhibition.

Mechanism of Action of CAI’s

Acetazolamide N-(5-Sulfamoyl-1,3,4-thiadiazol-2-yl)acetamide

Methazolamide N

Structure Activity Relationships 1.The sulphamoyl/carbamoyl (—SO 2 NH 2 ) group is responsible for in vitro CA inhibition and in vivo diuresis. 2.The carbonic anhydrase inhibitors must have a substituted sulphamoyl (—SO 2 NH 2 ) group. – i.e. substitution of the sulphamoyl Nitrogen lead to loss of diuretic activity (i.e. all antibacterial except sulphanilamide.) – In contrast, substitution of a methyl group on the aromatic nitrogen atoms leads to methazolamide

Structure Activity Relationships 3.The moiety to which the sulfomyl group is attached must possess aromatic character. – However, within a series of heterocyclic sulphonamides, Lipid/ Water partition and P ka gives CA inhibition and diuresis.