Physicochemical Properties of Drugs in relation to Drug Action


Physicochemical Properties of

Drugs in relation to Drug Action

Roselyn Aperocho Naranjo, RPh, MPH

USPF, College of Pharmacy

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

History: General

Plant Source

Specific Plants are selected

Treatment for medical conditions

Crude extracts

History: General

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


 Obtain better drug response

 Alter drug’s metabolism

 Produce more cheaper and competitive supply of the product

Selected molecules are changed due to:



Addiction effect reduced

Analgesic effect enhanced


Local Anesthetic

Effect enhanced

CNS effects reduced

Medicinal Chemistry in 1900’s

 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


Drug Distribution

 Oral Administration

Drug Distribution

 Oral Administration

 Solubility depends on:

 Chemical Structure

 Size of particles

 Surface area

 Nature of crystal form

 Type of tablet coating

 Type of tablet matrix

Drug Distribution

 Oral Administration

 Example:


PRODRUG- inactive form but are easily metabolized in the liver to become active


Protein Binding

Protein Binding

 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.

Tissue Depot

 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

Drug Metabolism & Excretion

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


Topological Descriptors

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

Combinatorial Chemistry

…to be continued

Prepare ¼ sheet of paper for the quiz

Study collections