Unit 1

Dr. Kratika DanielAssociate ProfessorDept of Pharmacy

Content

INTRODUCTION TO MEDICINAL CHEMISTRY• History and development of medicinal chemistryPhysicochemical properties in relation to biologicalaction• Ionization, Solubility, Partition Coefficient, Hydrogen

bonding, Protein binding, Chelation,• Bioisosterism, Optical and Geometrical isomerism.Drug metabolism• Drug metabolism principles- Phase I and Phase II.• Factors affecting drug metabolism including stereo

chemical aspects.

CHEMISTRYWhat is Chemistry? • Chemistry is known as the central of science.

• It is a branch of physical science that studiesthe composition, structure, properties andchanges of matter.

• MATTER = Solid / Liquid/ Gas.

BRANCHES OF CHEMISTRYPHYSICAL CHEMISTRY• the branch of chemistry concerned with the application of the

techniques and theories of physics to the study of chemical systems. • Branches : chemical Kinetics, Electrochemistry, spectroscopy,

photochemistry.

INORGANIC CHEMISTRY• deals with the synthesis and behaviour of inorganic and

organometallic compounds• Branches :Bioinorganic, Cluster, Material & Nuclear Chemistry

ORGANIC CHEMISTRY• study of the structure, properties, and reactions of organic

compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.

• Branches : Biochemistry, biophysical, Biorganic, P’ceutical, Medicinal

WHAT IS MEDICINAL CHEMISTRY

• It is a discipline or intersection of chemistry especially synthetic organic chemistry & pharmacology.

OR• Medicinal chemistry involves discovery,

development, identification & interpretation of Mode of action of biologically active compounds at molecular level.

Medicinal chemistry covers three critical steps:

1. Discovery step

2. An optimization step

3. Development stage

•Involving choice of therapeutic target (receptor, enzyme & target group,cellular or in vivo model).•& identification or discovery and production of new active substancesinteracting with selected targets. Such compounds called LEAD COMPOUND.

•Which deals with improvement of lead compound.•The optimization process takes primarily into account the increase in potency, selectivity and toxicity

•Whose purpose is continuation of improvement of pharmacokinetic properties

Primary objective of medicinal chemistry

Generally, we can identify the following stages in drug discovery, design and development Drug discovery-finding a lead • Choose a disease.• Choose a drug target. • Identify a bioassay. • Find a lead compound. • Isolate and purify the lead

compound if necessary.• Determine the structure of the

lead compound if necessary. Drug design • Identify structure-activity

relationships (SARs) • Identify the pharmacophore.

• Improve target interactions (pharmacodynamics).

• Improve pharmacokinetic properties,

Drug development • Patent the drug. • Carry out preclinical trials (drug

metabolism, toxicology, formulation and stability test, pharmacology studies, etc).

• Design a manufacturing process (chemical and process development).

• Carry out clinical trials. • Register and market the drug. • Make money.

Finally medicinal chemistry ….

• Medicinal chemistry includes synthetic &computational aspects of the study ofexisting drugs and agents in development inrelation to their bioactivities i.e.,understandings a SARs (Structure ActivityRelationships).

OR• It is a tailoringof drug

How drugs can be discovered

Techniques involved in • Random screening.

• Molecular manipulation.

• Molecular designing.

• Metabolites of drugs.

• Serendipity.

e.g., hydrogenation of the parent thiazide diuretic chlorothiazide has increased the sodium losing, and decreased the potassium losing potential of the resultant compounds, thereby raising their potency and lessening side effects

In its simplest form, this may involve the synthesis of a naturally occurring substance, a hormone, a vitamin, or a precursor of a neurotransmitter, e.g.,levodopa for Parkinsonism

Sometimes active metabolites of drugs are found to possess therapeutic advantages over the parent compound, e.g., paracetamol is a metabolite of phenacetin and is effective as an analgesic, but does not cause renal damage.

HAPPY OBSERVATION BY CHANCE e.g., penicillin as an antibacterial agent.

Origins of Medicinal Chemistry