Introduction:

            The process of designing a new drug and bringing it to market is very complex. According to a 1997 government report, it takes 12 years and 350 million dollars for the average new drug to go from the research laboratory to patient use. Pieces of this process are often repeated to create successively better drugs for the same condition. In the case of antibiotics, drugs loose effectiveness as an immunity is built up, thus leading to a continuing "arms race".

Main Idea:

            Medicinal Chemistry is a problem-solving discipline concerned with the discovery, design, and use of drugs. Scientists find new targets for drug development, research how drugs work at a molecular level and the harmful effects of drugs, and determine how drugs' properties, dosages, and delivery systems affect their performance.

The major steps in the drug design process are as follows:

• Find what is known
• Develop an assay
• Consider financial issues
• Find lead compounds
• Isolate the molecular basis for the disease
• Refine drug activity
• Drug testing
• Formulation
• Production
• Marketing
• Non-prescription sales
• Generic production

Soft drug design: general principles and recent applications      

         Soft drug design represents a new approach aimed to design safer drugs with an increased therapeutic index by integrating metabolism considerations into the drug design process. Soft drugs are new therapeutic agents that undergo predictable metabolism to inactive metabolites after exerting their therapeutic effect. Hence, they are obtained by building into the molecule, in addition to the activity, the most desired way in which the molecule is to be deactivated and detoxified. In an attempt to systematize and summarize the related work done in a number of laboratories, including ours, the present review presents an overview of the general soft drug design principles and provides a variety of specific examples to illustrate the concepts. A number of already marketed drugs, such as esmolol, remifentanil, or loteprednol etabonate, resulted from the successful application of such design principles. Many other promising drug candidates are currently under investigation in a variety of fields including possible soft antimicrobials, anticholinergics, corticosteroids, beta-blockers, analgetics, ACE inhibitors, antiarrhythmics, and others. Whenever possible, pharmacokinetic and pharmacodynamic properties are briefly summarized and compared to those of other compounds used in the same field.

Computer-Aided Drug Design:

          As a result, the last few years have seen a technological switch in the methodology used by your drug discovery team; the serendipitous, individual approach that you once used has been largely replaced by rational drug design using a multidisciplinary, team approach which uses new computer-aided drug design methods that speed up the drug discovery process and generate more accurate, viable lead compounds. In turn, your job description and skill requirements have changed dramatically. No longer do you mainly concern yourself with synthetic problems, but the increased use of computer-aided drug design has created greater opportunities for you to work with experts from a range of specialities and for you to understand and predict the impact of your daily work on the drug design process as a whole.

Rational drug design:  

       Rational drug design is the approach of finding drugs by design, based on their biological targets. Typically a drug target is a key molecule involved in a particular metabolic or signalling pathway that is specific to a disease condition or pathology, or to the infectivity or survival of a microbial pathogen.

        Some approaches attempt to stop the functioning of the pathway in the diseased state by causing a key molecule to stop functioning. Drugs may be designed that bind to the active region and inhibit this key molecule. However these drugs would also have to be designed in such a way as not to affect any other important molecules that may be similar in appearance to the key molecules. Sequence homologies are often used to identify such risks.

         Other approaches may be to enhance the normal pathway by promoting specific molecules in the normal pathways that may have been affected in the diseased state.

         Newer approaches have also suggested the use of drug molecules that are large and proteinaceous in nature rather than as small molecules. There have also been suggestions to make these using mRNA. Gene silencing may also have therapeutical applications.