Roselyn Aperocho Naranjo, RPh, MPH
USPF, College of Pharmacy rose_may26@yahoo.com

Understanding the
Modern Drug Design
 Modern chemical techniques
 Recent knowledge on disease mechanisms & receptor properties
 Transportation of drugs in the body
 Distribution of drug through different compartments
 Metabolism of drugs in the liver and other organs
 Structural characteristics of the receptor
 Acid-base chemistry
 Availability of the computer software that determines the three-dimensional shape of the receptor in order to design new molecules that will give optimum fit to the receptor

Plant Source
Specific Plants are selected
Treatment for medical conditions
Crude extracts

Plant Source
Structure of
Natural products
Specific Plants are
Treatment for medical conditions selected
Selective changes in the molecule
Crude extracts

Selected molecules are changed due to:
 Reduction of undesirable pharmacologic response of the drug
(side-effect)
 Obtain better drug response
 Alter drug’s metabolism
 Produce more cheaper and competitive supply of the product

Selected molecules are changed due to:
Example:
Morphine
Addiction effect reduced
Analgesic effect enhanced
Cocaine
Local Anesthetic
Effect enhanced
CNS effects reduced

 Phenothiazines – first synthesized as ANTIHISTAMINES
- Careful investigation led to discover its
TRANQUILIZING PROPERTY for the mentally ill patient.
 Benzodiazepines – originated from an expected ring enlargement which resulted it to become a CNS RELAXANT

drug receptor Drug-receptor complex
Pharmacologic response

 Oral Administration

 Oral Administration
 Solubility depends on:
 Chemical Structure
 Size of particles
 Surface area
 Nature of crystal form
 Type of tablet coating
 Type of tablet matrix

 Oral Administration
 Example:
 CHLORAMPHENICOL
PRODRUG- inactive form but are easily metabolized in the liver to become active
 CHLORAMPHENICOL PALMITATE

 Can affect the drug’s effective solubility, biodistribution, half-life in the body and interaction with other drugs.
 Control access to certain body compartments
 Prolong the drug’s duration of action
 Limit the amount of drug available for biotransformation and interaction with specific receptor sites.

 Fats in the body which can be a storage for drugs
 The more Lipophilic the drug is, the more it will stay in the tissue
 Example:
 Thiopental

Statistical Prediction of
Pharmacological Activity
 Mathematical Model will explain many chemical processes
Three goals in Drug Design
• Predict biological activity in untested compounds
• define the structural requirements required to fit to a specific receptor
• design a test set of compounds

 Proposed by Crum-Brown and Fraser in 1865 to 1870
 Certain modification in the molecular structure of a poisonous compound produces an important differences in their action

 Alternate method in describing molecular structure which is based on graph theory using the bonds that connects between atoms

…to be continued
Prepare ¼ sheet of paper for the quiz