Medicinal chemistry is best to be defined as an interdisciplinaryresearch area incorporating different branches of chemistry andbiology in the research for better and new drugs (Drug Discovery).

In other words, medicinal chemistry is the science, which deals withthe discovery and design of new and better therapeutic chemicalsand development of these chemicals into new medicines and drugs.

Scope of Medicinal Chemistry:1. Synthesis of new compounds2. Synthesis of known compounds3. Semi-synthesis of drugs4. Alter the structure of the compound for optimum effect and

minimum side effects through SAR (Lead Optimization)5. Study about absorption, distribution, metabolism and excretion

of drugs (ADME).6. Determine their effect on biological processes.

Drug action results from the interaction of drug molecules witheither normal or abnormal physiological processes.

The ability of a chemical compound to elicit a pharmacologiceffect is related to the influence of its various physical andchemical (physico-chemical) properties

The most pharmacologically influential physico-chemicalproperties of drugs are:

1. Solubility2. Acidity and basicity

Importance of solubility:(1) Formulation of the drug in an appropriate dosage form(2) Bio-disposition: Disposition of OMAs in the living systemafter administration (absorption, distribution, metabolism, andexcretion). The solubility expression: in terms of its affinity/ philicity or

repulsion/ phobicity for either an aqueous (hydro) or lipid(lipo) solvent.

hydrophilic....................water loving lipophobic.....................lipid hating lipophilic.......................lipid loving hydrophobic..................water hating

Majority of drugs possess balanced solubility (havesome degree of solubility in both aqueous and lipidmedia).

Because there is a need for OMAs to move throughboth aqueous (plasma, extracellular fluid, cytoplasm,etc.) and lipid media (biologic membranes) in thebiological system.

In order for a chemical compound to dissolve in aparticular solvent/ medium the compound mustestablish attractive forces between itself andmolecules of the solvent.

It is possible to estimate the solubility properties ofan OMA (hydrophilic vs. lipophilic) by examining thestructure of the molecule and noting whether itsstructural features promote affinity for aqueous orlipid media.

The most important intermolecular attractive forces(bonds) that are involved in the solubilization processare:

The relative solubility of a drug is function of thepresence of both lipophilic and hydrophilic featureswithin its structure, which serve to determine the extentof interaction of the drug with lipid and/or aqueousphases.

The relative solubility of a drug can be determined inthe laboratory.

Partition Coefficient [P]; the ratio of the solubility ofthe compound in an organic solvent to the solubility ofthe same compound in an aqueous environment i.e.,

P = Drug in lipid/ Drug in aqueousP is often expressed as a log value.

A mathematical procedures also have been developedto estimate the relative solubility of an organicmolecule based upon differential contributions ofvarious structural features to overall solubility.For example, the relative solubility of an OMA is thesum of the contributions of each group and substituentto overall solubility.

Example: Examination of the structure ofchloramphenicol (indicates the presence of bothlipophilic (nonpolar) and hydrophilic (polar) groupsand substituents.

Acidic and/or basic properties of OMAs are importantin both:

1- Pharmaceutical phase (dosage formulation, etc.) and2- Pharmacological phases (disposition, structure at target site,etc.).

Definitions: Acid: An organic compound containing a functional

group that can donate a proton (H+) and Base: An organic compound that contains a functional

group that can accept a H+