Estrogens/Progestins Med Chem

What is the general structure of estrogens?

aromatic ring, 3-OH, 17-OH, lacks 19-methyl

What is needed for action of estrogens?

3-OH, 17-OH

What is the potency from high to low for estrogens?

estradiol > estrone > estriol

What is the general structure of estradiol?

3-OH, 17-OH

What is the general structure of estrone?

3-OH, 17-ketone

What is the general structure of estriol?

3-OH, 17-OH, 16-OH

What is the irreversible metabolism of estradiol?

sodium sulfate ester of estrone

What is the general structure of sodium sulfate ester of estrone?

estrone + sodium sulfate on C3

What is the reversible metabolism of estradiol?

sodium glucuronide of estriol

What is the general structure of sodium glucuronide of estriol?

estriol + glucuronide on C16

What is the ADME of estrogen?

undergoes enterohepatic cycling and reabsorbed in GI

What is the activating enzyme of estrogen?

bacterial glucuronidase

What are endogenous estrogens?

estradiol, estrone, estriol

What are conjugated/esterified estrogens?

sodium sulfate on C3, estrone structure, prodrug

What is the difference between esterified and conjugated estrogens?

esterified has more sodium estrone than sodium equilin ratio compared to conjugated

What is the difference in structure for estropipate?

negative charge due to piperazine

What is the difference for estrogen esters?

esters on C3 or C17 = prodrug

What is the difference for semisynthetic estrogens?

alkene on C17

What is the purpose of the alkene on C17 in semisynthetic estrogens?

prevent becoming less potent estrogen = improve metabolic stability

What is the difference of mestranol (semisynthetic estrogen)?

prodrug due to methoxy on C3

What is the general structure of pregnanes?

21 carbons, 19-methyl, 17-ethyl

What is the general structure of androstanes?

19 carbons, 19-methyl, 17-H

What is the general structure of estranes?

18 carbons, 19-H, 17-H

What is the general structure of progestins?

3-ketone, 17-ketone, C4=C5

What is the pharm class of pregnane derivatives?

agonist

What agents are pregnane derivatives?

medroxyprogesterone acetate

What is the general structure of medroxyprogesterone acetate?

17-acetyl = long duration, 6-methyl = metabolic stability

What agents are 19-norandrostanes?

nor-, ethynodiol acetate, levonorgestrel, desogestrel, dienogest

What is the general structure of 19-norandrostanes?

3-ketone, 19-H, 17-OH, C4=C5, 18-ethyl, 17-ethylene

What is the purpose of 19-methyl in 19-norandrostanes?

more androgenic ADR

What is the purpose of 19-H in 19-norandrostanes?

increase progesterone activity, decrease androgenic activity

What is the purpose of 3/19-acetyl group or 3-H in 19-norandrostanes?

prodrug

What is the purpose of 18-ethyl in 19-norandrostanes?

decrease ADR

What is the purpose of the C5-C10 double bond in 19-norandrostanes?

decrease ADR

What is the purpose of 3-oxime in 19-norandrostanes?

retains activity

What is the pharm class of spironolactone based progestins?

progesterone agonist, mineralocorticoid/androgen antagonist

What agent is a spironolactone based progestin?

drospirenone

What are the benefits of drospirenone?

less weight gain/bloating, less androgenic ADR

What is the chemical class of progesterone receptor antagonist?

19-norandrostane

What agents are progesterone receptor antagonist?

mifepristone, ulipristal

What is the general structure of mifepristone?

3-ketone, 17-OH, 17-ethylene, bulky group

What is the general structure of ulipristal?

3-ketone, 17-ketone, 17-acetyl group = prodrug, bulky group

What DF do progestin only products come in?

pills, depot/IJ, implant, IUD

What DF do combo products come in?

oral, patch, vaginal ring

What DF do non-hormonal contraceptives come in?

copper IUD

What is the general structure of pregnanes for progestins?

3-ketone, C4=C5, 17-ketone

What is the general structure of 19-androstanes for progestins?

3-ketone, C4=C5, 19-H, 17-OH

What is the general structure of androstanes for progestins?

3-ketone, C4=C5, 19-methyl, 17-OH