25 terms

IS3 Exam 3 Med Chem

Metabolism of Nilutamide occurs on the _____ and ____ groups.
nitro and methyl
What is the result of Nilutamide metabolism on the nitro group? on the methyl group?
1. nitro group=formation of reactive NO and oxygen species that facilitate toxic effects
2. methyl group= D-isomers are formed are active metabolites
Which group on Nilutamide are less susceptible to metabolism?
What is the result when methyl is substituted at position 7 on 7-oxo-DHEA derivatives?
inactive molecule
Exemestane is a _____ generation _______ inhibitor used to treat excess amounts of estrogens.
third generation, aromatase
Exemestane is a ________ inactivator that ______ binds to the substrate binding site. This drug causes levels of aromatase to ______.
steroidal, irreversibly, decrease
This androgen receptor inhibitor is used as a racemic mix, but the active androgen inhibitor is the R-isomer.
Raloxifene is a SERM that is derived from _______ and can be used to decrease osteoporosis in post-menopausal women and as a breast cancer treatment.
5-alpha-reductase inhibitors can be used in the treatment of excess _____________. What type of 5-alpha reductase do they inhibit?
androgens, type 2
On 5-alpha-reductase inhibitors, a substitution with a 16-methyl or a 7-beta substitution are both?
well tolerated
On 5-alpha reductase inhibitors, there is usually a 3-keto group. What substitutions are not well tolerated at this position?
On 5-alpha reductase inhibitors, there is a 4-aza group. A hydrogen or small hydrophobic group is preferred. What other group (R1) can increase androgen receptor affinity?
On 5-alpha reductase inhibitors, a 7-membered A-ring is tolerated. What size ring is less potent?
5-membered A-ring
On 5-alpha reductase inhibitors, unsaturation at the 1,2 position is tolerated. On what position does unsaturation decrease potency?
On 5-alpha reductase inhibitors, what R2 group is preferred at position 17?
lipophilic amides or ketones
What first generation aromatase inhibitor has a lactone ring in place of the 5-membered D-ring?
Nandrolone drugs are used as esters. How does the length of the ester chain affect onset and half-life?
longer the ester=slower onset and longer half-life
The SAR of aromatase requires a ______ in order to form a H-bond with His480.
3-keto group
Other than the 3-keto group, the SAR of aromatase requires what?
19-beta-methyl group
Long term use of 17-alpha-methyltestosterone can result in increased ____________.
What prevents 17-beta-hydroxyl metabolism on 17-alpha-methyltestosterone?
The 17-alkyl group, which is methyl (any groups larger than methyl will decrease activity)
Steroidal hormones such as testosterone undeconate and testosterone enanthate have a 17-beta-hydroxyl group that has been esterified. What is the result of this esterification?
increased lipophilicity and increased duration of action of testosterone
Delestrogen is an estradiol derivative with a _______ that allows for slow absorption and prolonged duration of action.
17-ester (the 17-ester group is valerate, which is an alkyl ester group)
Oxymetholone is an anabolic derivative of testosterone. What substitution on this molecule increases anabolic activity?
What are the active metabolites formed when Norgestimate undergoes extensive GI and hepatic metabolism?
17-deacetyl-norgestime (levonorgestrel-3-oxime) and levonorgestrel