Quiz2 timmerman AntiEstrogens, Progestins, Androgens Flashcards
Antiestrogens
Important in the modification of?
What are the two major groups? Of drug types
Triphenylethylene Analogs
What structure is retained? But features what type of moeity that is critical for antiestrogenic activity?
Clomiphene
What bulky group does it have that gives it antagonist activity?
What isomer is the ant antagonist and what one is the agonist?
Clomphene
Employed to promote?
Form?
What SEs?
Tamoxifen
What isomer is used? What type of compound is it?
Used to treat?
form?
Selective estrogen Receptor Modulators
SERM
What are these trying to circumvent
What was developed?
SERMs
All approved drugs in this category exhibit?
Why have they been given the name SERM?
Raloxifene
What type of activity? And what two things does this help?
What effect on breast tissue?
No ___ effect on the uterus?
form?
Toremifene
Related to?
What reduces its anti-estrogenic potency?
Other SERMs in trials?
Fulvestrant Analog of what?
and Acolbifene has to be converted?
Triazole ___ inhibitors
2 of them
Prevent what?
What type of inhibitors?
Role of aromatase?
Role of Aromatase in Cancer?
Block conversion of?
Control?
Aid in?
What binds heme in Anastrozole and Letrozole
Anastrozole
Specific?
Tx of?
Letrozole
What does it do?
Tx of? Second line to?
Exemestane?
What is it?
Reversible or irreversible?
Tx of?
Phytoestrogens?
Phytoestrogens
Soy isoflavone B-glycosides are?
Phytoestrogens
What activity do they have?
The two hydroxyl groups?
Tx of Phytoestrogens?
Where is the focus of progesterone drug in the pathway?
Nat sources of Progestin
4
What is an important note about synthesized progestterone?
Semi and Bio synthetic sources of progestins?
Indications for progestins?
Pregnane nucleus what are the important features? For derivates
Key progesterone functional groups
What do they do?
What are the two main progestin products?
Progestin Products: Progesterone and Derivatives
Starting at Nat Progestins then from there
What are synthetic products made from?
Progesterone
Prometrium
Duration? Due to?
Where from?
What places are susceptible for metabolism?
Progesterone: Metabolism to?
What is added and different?
What does it get metabolized by?
Addition at 6 you should know whay its metabolized to
Progesterone metabolism due to reduction
what is the product and where are the changes
Progesterone
Progestasert
Despite?
17a-Hydroxyprogesterone what is it?
Where is it produced?
Where is 17a-Hydroxyprogesterone in the Steroid Hormone Syn pathway
17a-Hydroxyprogesterone
Metabolism
what is teh same and what is different in comparison to progesterone metabolism
What does this limit?
Blocking the Metabolism of 17a-Hydroxyprogesterone
Progestin Products: Progesterone Derivatives
3
Blocking 3-keto-4-ene metabolism and 6ahydroxyation
What aspects are improved?
Medroxyprogesterone Acetate
What SC is introduced? What does this cause?
Slow reduction of the keto and double bond 4-5
Medroxyprogesterone Acetate
at teh C6 position ___ is added and this decreases?
This blocks?
Medroxyprogesterone Acetate (Provera)
What does the liver do? Similar to ___ except for?
What is active?
What decreases reduction of 20-keto
Medroxyprogesterone Acetate
How is it active? Like what form?
What types are active how is this different?
What form provide contraception for 3 months?
Medroxyprogesterone Acetate
In Prempro
Used in combination with?
Megesterol Acetate
(Megace)
What on the B ring increases activtiy?
How much of oral dose is metabolized?
How does it differ from Medroxyprogesterone?
How does it block metabolism
Megesterol Acetate
Active in what form?
Acitivty similar to?
What decreases reduction of 20-keto?
Ethisterone and Analogues
_ derivative of what?
SAR summary of Progesterone and Derivatives
Progestational effects depend on wha 4 things
What mays it fit better to the receptor?
Alkene
SAR Summary of Progesterone and Derivatives Synthetic Mods
2 main mods and talk about their effects
Progestin Products
19-Norandrostane Derivatives
The rapid metabolism of progesterone triggered?
Key 19-Andro SAR
Androstane Nucleus without?
19-Norandrostane Derivative products
19-Norandrostane
SAR
What contribute to the androgenic/anabolic effects?
Readily metabolized to?
what is in the A ring?
19-Norandrostane
SAR at c17 what is added and what does it block?
Analogues with what are inactive?
19-Norandrostane
SAR at C17 Improving Progestational over Androgenic acitivty
What group here changes to more progestational?
Ethynyl
What does the 17 ethynyl 19-Norandrostane do ofr activity across the board?
17 ethylyl 19-Norandrostane products
7
Norethindrone
What blocks what?
Typically given?
Norethindrone Acetate Combipatch
Ester __? Metabolized where to form?
Prolonged action in what form?
Androstane Nuc
what are the parts?
C13 Ethyl Derivatives
All have what at C13? What does this mean for activity?
All haev what at C17
Norgestrel and Levonorgestrel
Norgestimate
Desogestrel
Gestodene
SAR for 19-Norandrostane Derivatives
4
SAR for 19-Norandrostane Derivatives
Modifications
4 and what do they do
Other progestins to look at
Antiprogestin: Progesterone Receptor Antagonists
Mifepristine also known as?
What does it do?
How does it do it?
Key structural features of RU-486
Antagonism is mediated by?
Pathway from testosterone to androsterone
Intermediates and enzymes needed
Androgens actions and indications
Has two types of activity
and then
SAR and the Androstane Nucleus
What is the minimal requirement for activity?
What are the important positions?
What are the key portions for androgenic activity?
What would make it not have androgenic activit?
What portion also exhibits progestin effects?
Testosterone 4-ene metabolism
what enzyme does it?
What is the product of this? where is this enzyme located?
3-keto 4 ene testosterone metabolism via?
What is the product?
SAR
What causes anabolic activity in androgens?
How can a drug be resistant to aromatase?
A 3-keto like system can mimic the anabolic activity of an androgen drug what modification increases anabolic acitivty over andorgenic activity? What does it look like?
17a-Methyltestosterone
What are the key features?
What is blocked?
What does this mean for the drug?
What two modifications at the 17a position do not provide anabolic/androgenic activity?
But one does provide what type of activity?
What is another strategy to prevent the oxidation of the 17b-OH group?
Androgen
SAR 17bhydroxyl esterification
Example: testosterone heptanoate
What type of molecule does this end up being?
What is the forM?
SAR
19-nortestosterone
What does the NOR mean?
What type of effect does this give?
SAR
19-Nortestosterone derivatives
What effect predominate and why?
A combination of what two things provides and overall ____ effect?
Androgen preparations 3 classes
Androgenic + anabolic agents
flow chart
Does Testosterone have more anabolic or androgenic acitivty?
Short or fast acting?
Metabolism?
Bitransformation of testosterone?
What is the primary route for inactivation?
testosterone biotransformation another route
What is the most potent androgen?
how is it formed?
Synthetic Derivatives of Testosterone
What has led to the development of synthetic testosterones?
What are the 2 strats:?
Testosterone esters
longer the chain longer the?
What type of drugs are they?
what is inhibited?
testosterone esters are subject to?
What is there physiological concentration like?
admin?
Testosterone esters
In general?
Testosterone undecanoate
oral?
Methyltestosterone
What are its featureS?
Activity compared to testosterone? An improvement is?
androgenic or anabolic?
what metabolism?
Fluoxymesterone
Bloicks what?
what makes it 5-10x more potent than testosterone?
Fluoxymesterone
Androgen or anabolic acitivy?
more resistant to?
Anabolic Agents
flow chart
THG article
Nandrolone esters
Decanoate and Phenprionate
in general if some thing doesnt have ___ it is more anabolic
What are some features about these esters?
Nandrolone Decanoate
Absence of? gives it what activity?
what form?
Phenpropionate
what activity? why?
DOA compared to Decanoate?
Promotes?
Oxandrolone
WHat blocks 17 keto? what else does this do form wise?
What is going on wiht the A ring?
what form?
Oxymetholone
Of the anabolic steroids?
What blocks 17 keto?
Stimulates production of what?
form?
Stanozolol
What does it contain?
blocks oxidatio?
forms? What type of activity?
Danazol
Contains what type of ring?
Inhibitor of waht?
Suppresses?
form?
what blocks 17 keto
AntiAndrogen Chart
5a-Reductase where does it act?
what is its product formation with testosterone?
Finasteride
what does it do?
what does it treat?
Dutasteride
What does it do?
and how
forms?
Androgen Antagonists
Toluidides
What are they ?
what doe they do?
what are they used with?
Flutamide
All compounds in this group have what?
Flutamide
Where is it absobed ?
What type of metabolism and what does it produce?
what is more potent than this?
Nilutamide
Absorbed where?
Hydantoin analof that blocks?
Biclutamide
Administered as a?
what enantiomer is inactive?
What does it bind to?
Saw palmetto
Saw palmetto
Saw palmetto
Saw palmetto
