Lecture 6

Drug molecules that mimic peptides.

Peptidomimetic class where R groups are bound to N.

Drug interaction w/ target.

Absorption, distribution, metabolism, excretion (ADME).

• 1) Low water solubility
• 2) Easily metabolized
• 3) Bind excessively to plasma protein
• 4) Can build up in tissue

Poor membrane solubility.

• [compound]oct/[compound]aq(1-a)
• a = ________ of compound in ________

• <0   = injection
• 0-3  = oral administration
• 4-5  = transdermal application
• <5  = toxic issue due to build up in tissue

• 1. Put compound in flask with octanol and water.
• 2. Shake
• 3. Measure solubility using UV-vis, GC/MC, HPLC

Came from sabermetrics

• 1. Not more than 5 HBD
• 2. Not more than 10 HBA
• 3. MW < 500
• 4. LogP < 5

• LogP of ionizable compound at pH n.
• D stands for distribution.

if pH = pKA, 50% base and 50% acid form of compound. if pH > pKa, more in acid form, if pH < pKa, more in basic form.

Drug must be polar enough to be aqueous soluble and lipophilic enough to pass membrane.

Adding electron withdrawing or donating species to compound.