Histamine 2 is responsible for the production of gastric acid. If the receptor is stimulated, it would produce gastric acid. Through this, they developed a compound similar to histamine 2, They modified it to antagonize or inhibit histamine 2 receptors.

Cell – stimulating factors

A single, simple, informative designation available for unrestricted public use. Specific for a given compound even though it may possess a stem common to a related group of drug

Developed by the manufacturer; selected for their ease of recall but does not give a scientific information about the drug

With enzyme linked assays or receptors from gene cloning of existing drugs lead to identification of new lead drug E.g., Amantadine

Substance of plant or animal origin that cannot be classified as pure chemical compounds

nontraditional or alternative medicinal

opium, belladona, ephedrine

The first histamine 2 antagonist developed

Compound binds to receptor and stimulates the effect or receptor to produce a pharmacologic effect

Animal models of disease states Behavioral studies Functional imaging Ex vivo studies

PHYSICOCHEMICAL PROPERTIES OF LEAD COMPOUNDS CAN PROVIDE NEW DRUGS

barbiturates, sulfonamides, ass

CNS diseases must have a drug that can pass throught the blood brain barrier and it is very difficult to develop a drug that can easily penetrate the blood brain barrier. Thus, the target is _.

field of science that manipulates living organism, cells, to create products

Once the biological target is identified, the next thing to do is to determine the lead compound. Lead compounds means has a potential to become a drug.

aliskerin

you are using living organisms you can optimize them or manipulate them to produce useful products. The two most commonly use are recombinant dna and mutagenesis

• Drug with affinity and intrinsic activity • Increases therapeutic response • Elicit pharmacologic response

In vitro – outside living organisms In vivo – conducted on living organisms

insulin and thyroid

Long process () to support that the lead compound is safe and effective before to be tested in human subjects

cell lines, cytotoxicity assays

Disorders of the human body caused by generic malfunction, environmental factors, stress, old age, etc.

CONSIDERATIONS IN UNDERSTANDING THE PRINCEIPLES OF MEDICINAL CHEMISTRY EXCEPT:

Idea on metabolic product if it may cause toxicity or easily metabolized giving an idea on duration of action Phase of metabolism and potential toxic effects and side effects of metabolites to easily optimize it e.g., easily metabolized at low pH (optimize to an enteric coating)

The biological target should be druggable

Intrinsic activity

Ability of a drug to exert a pharmacologic action

biochemical process of living organisms to design compounds that would specifically target receptors and enzymes associated with a particular specie skills and knowledge needed: 1- Chemistry 2- Biochemistry 3- Molecular Biology 4- Physiology 5- Pharmacology 6- Pharmaceutics 7- Medicine

Morphine _ to opiod receptor

HIV protease inhibitor

Allows convenient production of insulin with lesser allergic reaction Inject insulin genes on microorganism (E. coli) to produce high yield of insulin

medicinal chemistry

Pure organic compounds are the chief source of agents for the cure, mitigation, or the prevention of diseas

the higher the affinity of a compound to receptor the stronger and more stable their bonding

_ are protein that interacts with a ligand to elicit pharmacologic response _ interacts with a substrate to catalyze a chemical reaction (speeds up the biochemical reaction)

drug formulation, design appropriate formulation of drug skills and knowledge needed: 1- Chemistry 2- Biochemistry 3- Molecular Biology 4- Physiology 5- Pharmacology 6- Pharmaceutics 7- Medicine

Other things that would affect the pharmocologic activity of the drug are physicochemical properties, solubility, pH, pharmacokinetic properties. it is better to categorize drugs through indication such as inflammatory, analgesic, anti-hypertensive

Synthetically made in the laboratory using chemicals (compounds made in lab using chemicals)

Affinity

Generally, medicinal chemists can except:

receptors

KCl and lithium

If the drug has activity on a particular enzyme, the receptor or enzyme to be targeted is known which would help determine the disease to be managed as well

Took one step further by injecting Penicillium notatum on a live mice, with controlled experimentation, they found it cured mice with bacterial infections

Infectious disease and its causative agent? Pneumonia – Salmonella – Thrush –

No changes in the body normal response e.g pain, contraception, drugs that are used as anesthetic agent Alleviation of pain (analgesic), prevention of pregnancy (contraception), anesthesia

Organic medicinal chemistry

basic understanding on medical principles, develop drug for diseases occurring in the community, significance in society skills and knowledge needed: 1- Chemistry 2- Biochemistry 3- Molecular Biology 4- Physiology 5- Pharmacology 6- Pharmaceutics 7- Medicine

synthesis & Isolation Combinatorial chemistry Assay development High throughput screening

• X-ray crystallography • Nuclear magnetic resonance Evaluate the structure of the compound and design the compound in a way that it would interact with the target

Drug affinity & selectivity Cellular disease models MOA Lead candidate refinement

Athlete's foot

to optimize and modify the chemical structure of the drug to be more potent, enhance the effectiveness of the drug, and minimize the side effects skills and knowledge needed: 1- Chemistry 2- Biochemistry 3- Molecular Biology 4- Physiology 5- Pharmacology 6- Pharmaceutics 7- Medicine

Malaria

• Drug with affinity but does not have intrinsic activity • Block the activity of the receptor • Does not elicit pharmacologic response

Induce changes in the DNA sequence Induce mutation in DNA In DNA sequence, pick specific location where the mutation willhappen

Crude plant drugs as opium, belladonna, and ephedrine that have been important for centuries

Penicillium notatum (Penicillin)

Receptors a relatively small region of a macromolecule which may be an/a:

Naloxone _ opiod receptor

Logical test Has knowledge or idea (you have prior knowledge) Systematic development based on the understanding about MOA or biological target

hypertension, if you know that angiotensin enzyme is associated with an increase in bp, you can design a drug that would target the angiotensin-converting enzyme skills and knowledge needed: 1- Chemistry 2- Biochemistry 3- Molecular Biology 4- Physiology 5- Pharmacology 6- Pharmaceutics 7- Medicine

utilizing the cell culture systems with linked enzyme assays and receptor molecules derived from gene cloning

understand normal process of the body to design a drug that is more effective with lesser side effects, understand pharmacokinetic processes skills and knowledge needed: 1- Chemistry 2- Biochemistry 3- Molecular Biology 4- Physiology 5- Pharmacology 6- Pharmaceutics 7- Medicine

Ranitidine is derived from Cimetidine which is prone to side effects and various ADRs.

Buprenorphine

Inhibited in a petri dish by the mold Penicillium notatum (Penicillin)

Usually applied to compounds of known composition using the Chemical Abstract Services (CAS index)

Accidental discovery of Penicillin gave birth to a large variety of antibiotics Random sampling of higher plants based on anecdotal

In the presence of a full agonist, a compound acts as an antagonist as they compete on the same receptor. If there is a presence of a full agonist, the compound will become antagonist where if it binds to the receptor, it will block the activity and would not elicit a response In the absence of full antagonist, it will act as an agonist. It will stimulate the receptor producing a therapeutic response

The response of a compound would depend on the presence of full agonist. If full agonist is present compound will act as antagonist. If full antagonist is absent the compound will act as agonist

you are manipulating DNA or genetic material e.g insulin. The genes involved in the production of certain proteins Is inserted to a host

Racemic compound is a mixture of 3 enantiomer

Humanized monoclonal antibodies

Drug discovery

Diseases that can be transmitted from one person to another Diseases that cannot be transmitted from person to person not caused by pathological state but rather a normal aspect of life

Medicinal chemistry is devoted to the discovery and development of new agents for treating diseases Goal is to discover new therapeutic agent regardless of if it is organic or inorganic as long as it is effective

No idea on the target of the compound Expensive

ADVANCES IN RATIONAL DRUG DESIGN except:

Clinical trial would take a decade. Drug discovery usually start with target selection.

In the presence of antagonist, its effect is agonist, in the absence of an antagonist its effect is agonist The response of a compound is dependent on the presence of a full agonist

In organic medicinal chemistry, we combine expertise from chemistry and biology to:

chemical structure, nomenclature, reaction, synthesis skills and knowledge needed: 1- Chemistry 2- Biochemistry 3- Molecular Biology 4- Physiology 5- Pharmacology 6- Pharmaceutics 7- Medicine

cimetidine

identify potential biological targets, bind to specific enzyme skills and knowledge needed: 1- Chemistry 2- Biochemistry 3- Molecular Biology 4- Physiology 5- Pharmacology 6- Pharmaceutics 7- Medicine

streptomycin and erythromycin

It is important to consider the physicochemical properties of a drug in order to influence the absorption of the drug, distribution, metabolism, and even the pharmacologic response.

lead compound must have a good interaction with the biological target to prove that this compound can interact with the target.

Different enantiomers have different effects (Thalidomide R and S) one enantiomer has teratogenic effect which causes phocomelia while the other enantiomer has no teratogenic effect (remove 1 enantiomer to make it safer)

Spatial arrangement of atoms in a molecule

drugs which are used to fight pathogens, bacteria, virus, cancer cells, fungi (e.g., sulfonamides, antibiotics, anti-malarial agents, antiviral, anticancer, etc.)

Derived from plants, animals, microorganisms, fungi, bacteria

insulin and e coli

Amantadine is used Parkinsons but it was originally used in influenza. Later on, they found out that amantadine has an activity against Parkinsons disease.

Drugs that act on the various physiological functions of the body (e.g., pain reliever , anti-inflammatory agents, general anesthetic, hypnotic and sedatives, analgesic etc.)

Screen enormous libraries of peptides and nucleic acids obtained from procedures

rats, any animals

an antiviral agent protects and treats early influenza A • Treats parkinsonian disorders