I follow course DavidsonX: D001x Medicinal Chemistry on edX. Here are the notes.
Update early 2018: a new version of the course is available on edX. The essential content of the course remains largely unchanged. Instead of a 7-week course, it is now designed as self-paced course with seven modules, each of which is expected to be finished within 1-2 weeks.
7-module course plan
- Module 1: History of drug dicovery (DD hereafter)
- Module 2: Drug targets
- Module 3: Pharmacokinetics (PK)
- Module 4: Drug metabolism
- Module 5: Druggable genes
- Module 6: Lead discovery
- Module 7: Lead optimisation
Chapter 1: Pre-regulatory medicine
Ephedrine (stimulant, vasoconstrictor) from Ma Huang is an alkaloid.
Phenethylamines (neurotransmitter) can give a big class of drugs. It is considered as a pharmacophore, which is the minimal portion of a structure that is required to maintain a level of activity.
Its derivatives include Pseudoephedrine (Sudafed, decongestant), which can be converted to methamphetamine (crystal meth). Another derivative is fenfluramine.
Some related concepts on adverse effects:
- ADR (adverse drug reaction) warrants either alteration of the drug’s dosage or halting administration of the drug.
- Adverse effect: same as an adverse drug reaction but not limited to drugs
- Adverse event: a negative outcome observed during the use of a drug but not necessarility caused by the drug. If indeed caused by thde drug, the adverse event will be re-classified as an ADR.
- Side effect: non-clinical term associated with effects that are caused by a drug and yet seemingly unrelated to a drug’s intended therapeutic effect.
In the examples section, opiates, oploids, and the morphine rule is introduced.
Fluorine atoms are commonly encountered in drugs, because they can make a molecule more inert to the body’s metabolic reactions, therefore causing a lower rate of metabolism.
More on opium, opiates, and opioids
The morphine rule stipulates the structural requirements for a compound to have morphine-like activity.
Specifically, the morphine requires a compound to have (1) a benzene ring (2) attached to a quaternary carbon connected by (3) a two-carbon spacer to (4) a tertiary amine.
Typical compounds that obey the morphine rule include opiates (natural products) and opioids (synthesized products), including codeine, methadone, heroin, levorphanol, and meperidine.
An analgesic that does not follow the morphine rule is fentanyl. While fentanyl does not fit the morphine rule, it preserves the key functional groups in the correct orientation for opioid receptor binding.
Pharmacophore for sulfonamides
The pharmacophore for sulfonamides consists of a 4-aminosulfonamide core with tolerance for aryl and acyl groups on the sulfonamide nitrogen. Almost all sulfonamide antibacterials follow this simple model.
Antibiotic versus antimicrobials
Is sulfonamide an antibiotic? No, it is an antimicrobial. Antibiotic is applied to natural products.
Technically, the term antibiotic does not apply to synthetic compounds. Synthetic molecules like the sulfa drugs are antimicrobials. Antimicrobials may have antibacterial, antifungal, or antiparasitic activity. The sulfa drugs are antimicrobials with antibacterial activity.