L4 - Medicinal chem of corticosteroids

Question 1

SAR?

Answer 1

Structure activity relationship

Question 2

Pharmacophore define

Answer 2

Pharmacophore only has relevant groups that interact with receptor and are responsible for the activity

Question 3

How SAR determine pharmacophores

Answer 3

Lead > possible binding groups > analogue series removing one of these binding groups at a time > test analogues bio activity > identify pharmacophore

Question 4

Fluorine Isosteres

What effect does substituting H with F have?

Answer 4

Similar size, change electro properties - alter pKa of amine/h bond acceptor

Question 5

What can changes in chemical structure result in

Answer 5

Inc/dec affinity for target, solubility, logP = different biophysiological effect

Question 6

Give potencies, and changes in structure within corticosteroid potency Class’s A, B, C D

Answer 6

A - low, no change in D ring

B - mix, diol/ketol in D ring

C - high, ch3 group at c16 in D ring

D - very active, esters/halogenated compound on ring D