Unit 1. Intro to Pharmaceutical and Medicinal Organic Chemistry

organic compound

Almost all the drug in the market is an _

Organic chemistry

is vital in further pharmacy studies

Open-chain

not cyclic or linear structures

Cyclic - ring

Can be classified based on # of rings: monocyclic, bicyclic…

Cyclic - ring

Can be classified based on ring atoms: homocyclic and heterocyclic

Conjugated

contains 2 or more C-C double bonds separated by single bonds (alternating)

Saturated

contains C-C bonds which are purely single bonds

Unsaturated

contains at least 1 C-C double or triple bond

Alpha Carbon

carbon atom directly attached to a functional group

Vinylic/Olefinic Carbon

carbon atom directly holding a double bond

Allylic Carbon

carbon atom positioned next to a vinylic carbon

Benzylic Carbon

carbon atom positioned next to a benzene

Ortho/Meta/Para

1,2 / 1,3 / 1,4 respective patterns around a benzene ring

Polarity and Solubility

play a role in the formulation and pharmacokinetics of drugs

Polarity and Solubility

It is determined not only by the presence of electronegative

Polar

is water-soluble

Non-polar

is lipid-soluble

Acidic and Basic

property are always related to ionization of compounds which has a vital role in the pharmacokinetic of drugs.

RCOOH

organic acids

RNH2

organic bases

Amphoteric

has both carboxyl and amino groups

Stereoisomerism

plays a role in the drug’s effect on the human body, particularly in enzyme binding.

Configurational isomers

• Geometric (cis/trans; E/Z)

• Optical (R/S)

Isomers

can demonstrate different effect to the body.

Conformational isomerism

isomers can be interconverted just by rotations about formally single bonds

S-ibuprofen

more potent ibuprofen

R-ibuprofen

less potent ibuprofen

Quinine

used for antimalarial

Quinidine

used as anti-arrhtymic

Transplatin

is inactive

Cisplatin

is active

R-Thelidomide

Used as antiemetic

S-Thelidomide

causes birth defects

Drug Discovery

Medicinal Chemistry and Pharmacognosy

Pharmaceutical Analysis

Qualitative Chemistry and Quality Control

Pharmaceutics

Manufacturing Pharmacy, Dosage Forms

Pharmacology

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 (ADR)

These are unwanted effects of the drugs including side effects

Potency

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

Efficacy

This is the actual level of a drug’s effect

Pharmacokinetics

refers to the course taken by the drug once inside the human body.

Pharmacokinetics

PK

Pharmacokinetics

what the body does to the drug

Pharmacokinetics

LADME

Absorption

Entry of the drug from site of administration to the bloodstream

Distribution

Travel of drug from bloodstream to different tissues and organs

Metabolism

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

Metabolism

Most drug metabolism is done by the liver

Excretion

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

Liberation

describes the way that a drug is released from its administered form

Ionization

of drugs can affect absorption especially that most drugs are taken orally.

Unionized

non-polar, uncharged, lipophilic

Ionized

polar, charged, hydrophilic

lipophilic

Only _ drugs are absorbed through the lipid layer between GIT and bloodstream

hydrophilic

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

lipophilic

Drug ABSORPTION across a lipid layer between GIT and bloodstream is possible if the drug is _.

hydrophilic

Drug DISTRIBUTION along the bloodstream requires that the drug be somehow _.

Balance

_ is between hydrophilicity and lipophilicity

Pharmacodynamics

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

Pharmacodynamics

what the drug does to the body

target molecule

Absorbed drugs must find its “_” — receptors, and bind to it effectively to elicit a response/effect

Occupancy

The 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 theory

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

Antagonist

drugs that inhibit/decrease the activity of the receptor

DRUG DISCOVERY

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

DRUG DISCOVERY

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 in drug development

HITS

Hits confirmation; potency & cytotoxicity; prelim animal efficacy; intial SAR

Target ID and Validation

Link disease and target; Biomarkers; High-throughput screening; Rational Design; Insilcon screening

Lead Gen and Optimization

Potency studies; selectivity studies; PK/ADME - Tox properties; SAR pharmacophore modeling

LEADS

more filters

Drug candidate

best ones among the filters

Medicinal Chemistry

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

medicinal chemistry

In drug discovery, _ refers to the technologies and laboratory experiments performed to find the best hits/leads/drug candidates.

Structure-Activity Relationship

In drug action, medicinal chemistry looks at the structure of a drug structure and analyzing its activity when administer to humans or other organisms — _.

Structure-Activity Relationship

this is the correlation between the drug structure and its effect on the body.

Structure-Activity Relationship

is the practical side of medicinal chemistry since analysis of the structure alone can tell us a lot of things about a drug. In _, similar structures exhibit similar actions.

Pharmacophore

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

Pharmacophore

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

Pharmacophore

Ex. Penicillins and their beta-lactam ring

Pharmacophore

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

Bioisosteres

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

Bioisosteres

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