Mineralocorticoids & Estrogens/Progestins (MC)

Mineralocorticoids (aldosterone & corticosterone)

Mineralocorticoid Receptor Agonists → aldosterone

Mineralocorticoid Receptor Agonists → fludrocortisone

Mineralocorticoid Receptor Antagonists → spironolactone

Mineralocorticoid Receptor Antagonists → eplerenone

Introduction & Review: Estrogens & Progestins

Estrogenic Agonists

Estrogenic Antagonists

Introduction & Review: Estrogens & Progestins

Progestin Agonists

Progestin Antagonists

Endogenous Estrogen Receptor Agonists

Endogenous Estrogen Receptor Agonists

• Biosynthesis

Endogenous Estrogen Receptor Agonists

Required SAR

Endogenous Estrogen Receptor Agonists

Pharmacodynamic Interactions

Natural Exogenous Estrogen Receptor Agonists

Animal Sources

Natural Exogenous Estrogen Receptor Agonists

Estrogenic substances from plants (phytoestrogens)

Natural Exogenous Estrogen Receptor Agonists

Estrogenic substances from plants (phytoestrogens) continued

Estrogenic substances from plants (phytoestrogens)

Structures

Synthetic Exogenous Estrogen Receptor Agonists

Steroids: Examples

Synthetic Exogenous Estrogen Receptor Agonists

Steroids-SAR: Same as required SAR for endogenous estrogen agonists, PLUS:

Synthetic Exogenous Estrogen Receptor Agonists

Steroids SAR (cont.)

Stilbenes – No longer available in the US

Estrogen Receptors (ER)

Estrogen Receptors (ER)

• Binding & activity

SERMs (Selective Estrogen Receptor Modulators)

SERMs (Selective Estrogen Receptor Modulators)

SAR

SERMs (Selective Estrogen Receptor Modulators)

• Triphenylethylenes and related compounds as stilbene analogs

SERMs (Selective Estrogen Receptor Modulators)

• Triphenylethylenes and related compounds as stilbene analogs

Estrogen Pharmacokinetics

Metabolic transformations: Elimination & toxicity

Estrogen Pharmacokinetics SAR

Estrogen Pharmacokinetics

Enterohepatic cycling & the role of gut microbes (metabolomics)

Estrogen Pharmacokinetics synthesis

Aromatase Inhibition (CYP19)

Aromatase Inhibition (CYP19)

Therapeutic utility & relevance in cancer chemotherapy

Progestin Receptor Agonists

Endogenous progesterone receptor agonist: progesterone

Progestin Receptor Agonists

SAR

Progestin Receptor Agonists

SAR (cont.)

Progestin Receptor Agonists

SAR (cont.)

Progestin Receptor Agonists

Pharmacodyamic interactions

Exogenous Progestin Receptor Agonists

Synthetic Pregnanes

Exogenous Progestin Receptor Agonists

Synthetic Pregnanes: Note: Drospirenone

Exogenous Progestin Receptor Agonists

Synthetic Androstanes: Note: No 11B-OH

Exogenous Progestin Receptor Agonists Structures

Exogenous Progestin Receptor Antagonists

SAR & pharmacodynamics

Exogenous Progestin Receptor Antagonists

Antagonists have bulky group at pos. 11

Neurokinin Receptor Antagonists (NK1 & NK3)

KNDy* Neurons and NK Receptors

Fezolinetant & Elinzanetant

Fezolinetant & Elinzanetant SAR

Fezolinetant Metabolism

Elinzanetant Metabolism