LESSON 1.2 (DRUG DISCOVERY AND DEVELOPMENT) Introduction to Pharmaceutical and Medicinal Organic Chemistry

Medicinal Chemistry

Drug molecules are being studied in:

Pharmaceutical Chemistry/Pharmaceutics

Dosage Forms are being studied in:

Pharmacokinetics

Dosage Regimen, Concentration VS Time in Serum, Concentration VS Time in Tissues and Other Body Fluids, and Concentration VS Time at Site of Injection are being studied in:

Pharmacodynamics

Concentration VS Time in Tissues and Other Body Fluids, Concentration VS Time at Site of Injection, Pharmacologic or Toxicologic Effect, and Antimicrobial Effect VS Time are being studied in:

Basic Pharmacology

Pharmacokinetics and Pharmacodynamics are being studied in:

Drug Discovery

Branch of Pharmaceutical Science that is related to Medicinal Chemistry and Pharmacognosy

Pharmaceutical Analysis

Branch of Pharmaceutical Science that is related to Qualitative Chemistry and Quality Control

Pharmaceutics

Branch of Pharmaceutical Science that is related to Manufacturing Pharmacy and Dosage Forms

Pharmacology

Branch of Pharmaceutical Science that is related to Pharmacokinetics and Pharmacodynamics

Mechanism of Action (MoA)

How exactly a drug works

Duration of Action (DoA)

how long a drug works

Onset of Action

the time it takes before the drug takes exhibits an effect

Indication

the approved use of a drug

Adverse Drug Reaction

these are unwanted effects of the drugs including side effects

Potency

the dose required to exhibit an effect (lower dose = higher potency)

Efficacy

actual level of a drug’s effect

Pharmacokinetics

course taken by the drug once inside the human body

Pharmacokinetics

what the body does to the drug

Absorption

FUNDAMENTAL PROCESSES OF PHARMACOKINETICS:

• Entry of the drug from site of administration to the bloodstream

Distribution

FUNDAMENTAL PROCESSES OF PHARMACOKINETICS:

• Travel of drug from bloodstream to different tissues and organs

Metabolism

FUNDAMENTAL PROCESSES OF PHARMACOKINETICS:

• Conversion of the active drug molecule to inactive products (“metabolites”), waiting excretion

• Most is done by the liver

Excretion

FUNDAMENTAL PROCESSES OF PHARMACOKINETICS:

• Permanent removal of the inactive metabolites from the body, often via the kidney

Ionization

affect absorption especially that most drugs are taken orally

Unionized

• non-polar

• uncharged

• lipophilic

Ionized

• polar

• charged

• hydrophilic

lipophilic drugs

Only __________________ are absorbed through the lipid layer between GIT and bloodstream

hydrophilic drugs

Only __________________ are distributed through the bloodstream as the blood acts as an aqueous medium.

absorption

Drug __________________ across a lipid layer between GIT and bloodstream is possible if the drug is lipophilic.

Distribution

Drug ______________________ along the bloodstream requires that the drug be somehow hydrophilic.

Pharmacodynamics

refers to the physiologic effect resulting from the drug-receptor binding

Pharmacodynamics

what the drug does to the body

target molecule

In Pharmacodynamics, absorbed drugs must find its “____________” — receptors, and bind to it effectively to elicit a response/effect.

Occupancy

no. of receptors bound is directly proportional to biologic response

Rate

The response is related to the times the drug binds to the receptor per unit time

Induced-Fit

The drug reaches inactive receptors and changes receptor conformation causing better drug binding and biologic response.

Macromolecular Perturbation

This is a combination of the rate and induced-fit theo

Activation-Aggregation

This states that receptors are always in equilibrium for active and inactive sites

and agonist/antagonist can only shift this equilibrium

Agonist

drugs that activate/increase the activity of the receptor; also known as a stimulant

Antagonist

drugs that inhibit/decrease the activity of the receptor; also known as a blocker

Drug discovery

• starts at conceptualization of new drug research (several dozens to millions of different compounds)

• Numerous stages to filter them out using computational or laboratory tests (no living creatures)

Drug Development

• gets molecules from drug discovery, tests in animals,

  then in humans, and (hopefully) approval for marketing

Hits

first filters

Leads

more filters

Drug Canditate

best one among the filters

Medicinal Chemistry

broad but essential are of chemistry required to understand the process of drug discovery and explain the mechanism of drug action

drug discovery

In _______________, medicinal chemistry refers to the technologies and laboratory experiments performed to find the best hits/leads/drug candidates.

drug action

In _____________, medicinal chemistry looks at the structure of a drug structure and analyzing its activity when admini

Structure-Activity Relationship (SAR)

• correlation between the drug structure and its effect on the body

• practical side of medicinal chemistry since analysis of the structure alone can tell us a lot of things about a drug

• similar structures exhibit similar actions.

Pharmacophore

• portion of a drug molecule that is responsible for its activity

• serves as the “face” of the molecule that interacts with a target receptor

• remain unchanged to retain the drug’s activity, but the other components of the structure can be modified to improve the drug’s PK

Biosoesteres

• functional groups or fragments which looks like and are as large as an original component of a drug structure

• usually substituted for an original component in the hopes of improving the SAR of a drug