INTRODUCTION TOMEDICINAL CHEMISTRY

What is medicinal chemistry?Graham Patrick: The science that deals with the design and synthesis of novel drugs, based on an understanding of how they work at the molecular level. A useful drug must interact with a molecular target in the body (Pharmacodynamics) and also be capable of reaching that target (Pharmacokinetics)

What is medicinal chemistry?IUPAC: Medicinal chemistry concerns the discovery, development, identification, and the interpretation of the mode of action of biologically active compounds at the molecular levelAlfred Burger: Medicinal chemistry involves the isolation, characterization, and synthesis of compounds that can be used in medicine for the prevention, treatment, and cure of disease

What is medicinal chemistry?Based on the hope of finding biochemical rationales for drug discoveryFinding the biochemical pathway through which drugs exert their beneficial effects has become a dominating activity of medicinal chemist

What is medicinal chemistry?Also called therapeutic chemistry, pharmaceutical chemistry or pharmaco-chemistryConcerned primarily with modifications of structures having known physiological or pharmacological effect and with drug analysis

Medicinal chemistSkilled in the field of organic synthesis, molecular modeling and drug designCanMake new compoundsDetermine their effect on biological processes.Alter the structure of the compound for optimum effect and minimum side effects.Study uptake, distribution, metabolism and excretion of drugs

MedicineDrugs, pharmaceuticsNormally low molecular weight molecules that interact with macromolecular targets in the body to produce a pharmacological effects. That effect may be beneficial or harmful depending on the drug used and the dose administered

Medicine sourcesPlant sourcesAnimal sourcesMineral/ Earth sourcesMicrobiological sourcesSemi synthetic sources/ Synthetic sourcesRecombinant DNA technology

A lead compoundA chemical compound that has pharmacological or biological activity and whose chemical structure is used as a starting point for chemical modifications in order to improve potency, selectivity, or pharmacokinetic parameters

Good and Bad medicinesNo medicine has only benefits or drawbacksDepends on:Dosage: Almost anything in excess will be toxicChronic exposure

Good and Bad medicinesMorphineExcellent analgesicAddictive, toleranceRespiratory depressionBarbituratesDepressants, sedatives, anaestheticsUsed in surgeryOverdose fatal

Therapeutic indexMeasure of safety of medicineMeasure of a drugs harmful effects at high dose vs. beneficial effects at low dose (or the ratio of undesirable to desirable medicine effects)Comparison of dose levels which lead to toxic effects to dose levels which lead to maximum therapeutic effects

Therapeutic indexFor in vivo systems thee therapeutics index could be the ratio of the LD50 (the lethal dose for 50 % of the test animals) to the ED50 (the effective dose that produces the maximum therapeutic effect in 50 % of the test animals

High therapeutic index = large margin of safety

Classification of medicinesBased on their originNatural compounds: vitamins, hormones, amino acids, antibiotics, alkaloidsSynthesis compounds: either pure synthesis or synthesis naturally occurring compounds (e.g. morphine, atropine, steroids and cocaine) to reduce their cost

Classification of medicinesBased on their originSemi-synthesis compounds: Some compounds either can not be purely synthesised or can not be isolated from natural sources in low cost the natural intermediate of such drugs could be used for the synthesis of a desired product (e.g. semi synthetic penicillins)

Classification of medicinesBased on their pharmacological actionsAnalgesics, antipyretics, antidepressant, antibiotics, tranquilliserLarge and varied assortment of medicinesMany mechanisms of action

Classification of medicinesBased on chemical structuresPenicillins, steroids, sulfonamidesCommon skeletonFunctions may be similar or different

Classification of medicinesBased on target systemContraceptions, for digestive system, for endocrine systemsAffect a target systemVariety of structures due to large number of stages in system

Classification of medicinesBased on molecular targetsTargets are the biomolecules with which drugs interact (carbohydrates, lipids, proteins and nucleic acids)Very specific classificationStructural similarity and common mechanism

*IUPAC: International Union of Pure and Applied ChemistryBurger: founder the Journal of Medicinal Chemistry (1958)

*****************