Progestins Overall Organization of the Topic Structure and

Progestins Overall Organization of the Topic Ö Structure and function of natural progestin - Progesterone Ö Ö Ö Nomenclature of progestational steroids Biosynthesis and metabolism of progesterone Progesterone Agonists Generalizations on Structure-Activity Relationships Progesterone antagonist - RU-486 1/20/2022 MEDC 603 Steroids 1

Progestins Progesterone Progest-4 -ene-3, 20 -dione 1/20/2022 MEDC 603 Steroids 2

Functions of Progesterone • Maintains pregnancy • Inhibits follicular maturation and ovulation • prevents spontaneous uterine contraction 1/20/2022 MEDC 603 Steroids 3

Progesterone Metabolism Reduction C-20 Reduction C-4, C-3 Reduction C-20 1/20/2022 MEDC 603 Steroids 4

Progesterone Agonists 1. Derivatization of the 17 - position 17 a-hydroxyprogesterone caproate Click here to view the 3 D structure of 17 -substitution 1/20/2022 MEDC 603 Steroids 5

Progesterone Agonists 2. Derivatization of A/B rings Megestrol acetate Medroxyprogesterone acetate (Oral Activity = 12 -25) Chlomadinone acetate 1/20/2022 MEDC 603 Steroids 6

Progesterone Agonists 3. Testosterone Derivatives Ethisterone Relative Oral Activity = 1 1/20/2022 Dimethisterone Relative Oral Activity = 12 MEDC 603 Steroids 7

Progesterone Agonists 4. 19 -Nortestosterone Derivatives Norethindrone Norgestrel Relative Oral Activity = 5 -10 1/20/2022 MEDC 603 Steroids 8

Generalizations on Structure-Activity Relationships for Oral Progestational Activity • Steroid skeleton • Unsaturated A ring • Either a progesterone or a testosterone skeleton • If testosterone derivative, 17 -ethinyl substitution • 19 -nor substitution is useful 1/20/2022 MEDC 603 Steroids 9

Progesterone Antagonist RU-486: Mifepristone 1/20/2022 MEDC 603 Steroids 10