Orgo II - Medicinal Chemistry

atorvastatin (Lipitor)

prozac

carboplatin

quinine

digoxin

cetirizine (Zyrtec)

artemisin

artemether

Chlorambucil

Artorvastatin

lower cholesterol; binds to enzyme (protein) - stops biochemical reaction

Prozac

anti-depressant and anti-anxiety; binds to receptor; (protein) - stops transport or signaling

Carboplatin

cancer treatment; (nucleic acid) - interferes with DNA replication

natural products

chemical produced by a living organism (50%)

semisynthetic

lab-modified version of a natural product (improved properties) (50%)

totally synthetic

completely lab-made material

Roughly half the drugs are…

natural or semisynthetic

quinine

a natural product derived from the bark of the cinchona tree, used for treating malaria

digoxin

A cardiac glycoside used to treat heart conditions, derived from the foxglove plant.

artemisinin

natural product isolated from sweet wormwood plant (Artemisia annua)';

Chinese medicine to treat fevers; potential antimalarial drug

artemether

semisynthetic drug; also antimalarial, but has different therapeutic profile and reduced side effects

cetiririzine (Zyrtec)

synthetic drug; treatment for allergies

sitagliptin (januvia)

synthetic drugs; treatment for diabetes

covalent drugs

new covalent bond forms between target and drug; drug is usually an electrophile; binding is usually irreversible

non-covalent drugs

drug binds to target through non-covalent interactions (H-bonding, ionic bonding, Van der Waals, hydrophobic); binding is usually reversible

Lipitor

• synthetic, non-covalent enzyme inhibitor

• HMG-CoA Reductase inhibitor (“statin drug”)

• Inhibits the early step in cholesterol biosynthesis

• Lowers cholesterol levels

Penicillins

• a natural product and a covalent enzyme inhibitor

• all contain B-lactam pharmacophore

• B-lactam inhibits transpeptidase enzyme involved in bacterial cell-wall crosslinking

B-lactam

• inhibits transpeptidase enzyme involved in bacterial cell-wall crosslinking

• prevents peptidoglycan cross-linking

• reacts electrophile reacts with serine nucleophile (OH) in active site

nitrogen mustards

• synthetic, covalent DNA cross-linking agent

• mustard gas was lead compound → very toxic, kill rapidly dividing cells

• lead modification → chlorambucil

• double electrophile: can crosslink DNA strands, interfering with replication and causing apoptosis