[MEDICINAL CHEMISTRY] Hormonal Therapy & Cardiac Drugs

a. Responsive

Palliative hormonal therapy

a. Responsive

b. Dependent

c. Ablative

d. Suppressive

b. Responsive

Palliative hormonal therapy where the tumor regresses after treatment with the hormone.

a. Dependent
b. Responsive
c. Ablative
d. Suppressive

b. Dependent

Removal of the hormone source causes tumor regression

• Example: Surgery ,

a. Responsive

b. Dependent

c. Palliative

d. Adjuvant

c. Dependent

Hormonal therapy where removal of the hormone source causes tumor regression ((e.g., surgery, breast cancer treated with Tamoxifen).

a. Responsive

b. Ablative

c. Dependent

d. Adjuvant

a. Tamoxifen

Breast cancer is treated with _______

a. Tamoxifen
b. Flutamide
c. Goserelin
d. Megestrol

• Fluoxymesterone

• Testosterone

Androgens used in hormonal therapy include:

a. Fluoxymesterone and Testosterone
b. Flutamide and Nilutamide
c. Tamoxifen and Toremifene
d. Goserelin and Leuprolide

• Flutamide

• Nilutamide

Antiandrogens used in prostate cancer with Goserelin or Leuprolide include:

a. Flutamide and Nilutamide
b. Tamoxifen and Toremifene
c. Fluoxymesterone and Testosterone
d. Megestrol and Aminoglutethimide

• Goserelin

• Leuprolide

Antiandrogens (Flutamide and Nilutamide) are used in prostate cancer with ______ drugs?

a. Tamoxifen and Toremifene

b. Goserelin or Leuprolide

c. Fluoxymesterone and Testosterone

d. Megestrol and Aminoglutethimide

d. Both a and b

• Toremifene

• Tamoxifen

Antiestrogens used for ER-positive breast cancer include:

a. Toremifene

b. Tamoxifen

c. Nilutamide

d. Both a and b

c. Aminoglutethimide

Aromatase inhibitor used as second-line therapy for metastatic breast cancer.

a. Tamoxifen

b. Toremifene

c. Aminoglutethimide

d. Flutamide

c. Both a and b

• Dexamethasone

• Prednisone

Corticosteroids used for lymphoma and Acute Lymphocytic Leukemia (ALL) include:

a. Dexamethasone

b. Prednisone

c. Both a and b

d. Both a and b

• Diethylstilbestrol

• Ethinyl estradiol

Estrogen / Nitrogen mustard combination used for prostate cancer includes:

a. Diethylstilbestrol

b. Ethinyl estradiol

c. Tamoxifen
d. Both a and b

c. Both a and b

• Goserelin

• Leuprolide

GnRH or LHRH agonists used for prostate cancer include:

a. Goserelin

b. Leuprolide

c. Both a and b

• Medroxyprogesterone

• Megestrol

Progestins used in hormonal therapy include:

a. Medroxyprogesterone and Megestrol

b. Flutamide and Nilutamide

c. Tamoxifen and Toremifene

d. Goserelin and Leuprolide

c. Monoclonal antibodies

Monoclonal antibodies target growth factor receptors and inhibit cell growth.

a. Alkylating agents

b. Antimetabolites

c. Monoclonal antibodies

d. Hormonal agents

b. Trastuzumab

Monoclonal antibody that inhibits HER-2/Neu.

a. Bevacizumab

b. Trastuzumab

c. Rituximab

d. Cetuximab

b. Bevacizumab

Monoclonal antibody that inhibits human vascular endothelial growth factor (VEGF), preventing angiogenesis.

a. Trastuzumab
b. Bevacizumab
c. Rituximab
d. Cetuximab

b. Tyrosine kinase inhibitors

Inhibits tyrosine kinase

a. Monoclonal antibodies

b. Tyrosine kinase inhibitors

c. Hormonal agents

d. Antimetabolites

b. Tyrosine kinase inhibitors

Inhibits tyrosine kinase and prevents phosphorylation of kinase substrate by ATP.

a. Monoclonal antibodies

b. Tyrosine kinase inhibitors

c. Hormonal agents

d. Antimetabolites

b. -tinib

Tyrosine kinase inhibitors are identified by the suffix:

a. -mab

b. -tinib

c. -zumab

d. -ximab

b. Erlotinib

Tyrosine kinase inhibitor that is an EGFR inhibitor.

a. Imatinib

b. Erlotinib

c. Bevacizumab

d. Trastuzumab

c. EGFR

Erlotinib is a tyrosine kinase inhibitor that inhibits:

a. BCR-ABL kinase

b. HER-2/Neu

c. EGFR

d. VEGF

c. Imatinib

Tyrosine kinase inhibitor that is a BCR-ABL kinase inhibitor.

a. Erlotinib

b. Gefitinib

c. Imatinib

d. Sorafenib

c. Chronic Myelogenous Leukemia (CML)

Imatinib is a tyrosine kinase inhibitor used for:

a. Breast cancer

b. Colorectal cancer

c. Chronic Myelogenous Leukemia (CML)

d. Lung cancer

c. Nifedipine

DHP derivative that bears no structural resemblance to other calcium channel antagonists.

a. Verapamil

b. Diltiazem

c. Nifedipine

d. Amlodipine

b. Pyridine ring

[Structure Activity Relationship of Nifedipine]

Nucleus of Nifedipine is a partially saturated:

a. Pyrimidine ring

b. Pyridine ring

c. Benzene ring

d. Pyrrole ring

c. Nitro group

[Structure Activity Relationship of Nifedipine]

Essential for the antianginal effect of Nifedipine but is not a nitrate.

a. Methyl group

b. Carboxyl group

c. Nitro group

d. Hydroxyl group

b. 2 and 6

[Structure Activity Relationship of Nifedipine]

At positions _______ of Nifedipine, substitution with an alkyl group plays a role in the agent's duration of action (DOA).

a. 1 and 3
b. 2 and 6
c. 3 and 5
d. 4 and 7

b. Duration of action (DOA)

[Structure Activity Relationship of Nifedipine]

At positions 2 and 6 of Nifedipine, substitution with an alkyl group plays a role in the agent's:

a. Potency

b. Duration of action (DOA)

c. Solubility

d. Absorption

c. 3 and 5

[Structure Activity Relationship of Nifedipine]

At positions _______ of Nifedipine, carboxylic groups must be protected with ester functional groups

a. 1 and 3

b. 2 and 6

c. 3 and 5

d. 4 and 7

c. Ester functional groups

[Structure Activity Relationship of Nifedipine]

At positions 3 and 5 of Nifedipine, carboxylic groups must be protected with:

a. Methyl groups

b. Amide groups

c. Ester functional groups

d. Hydroxyl groups

c. Position 4

[Structure Activity Relationship of Nifedipine]

At ________ of Nifedipine, aromatic substitution with an electron-withdrawing group (EWG) such as Cl or NO₂ in the ortho and/or meta position results in increased antianginal activity.

a. Position 2
b. Position 3
c. Position 4
d. Position 5

b. Ortho and/or meta position

[Structure Activity Relationship of Nifedipine]

At Position 4 of Nifedipine, aromatic substitution with an electron-withdrawing group (EWG) such as Cl or NO₂ in the ________ results in increased antianginal activity.

a. Para position only
b. Ortho and/or meta position
c. Only ortho position
d. Only meta position

b. Increased antianginal activity

[Structure Activity Relationship of Nifedipine]

At position 4 of Nifedipine, aromatic substitution with an electron-withdrawing group (EWG) such as Cl or NO₂ in the ortho and/or meta position results in:

a. Decreased antianginal activity
b. Increased antianginal activity
c. No change in activity
d. Increased duration of action

• Phenolic hydroxyl group

• 6 hydroxyl group

• Double bond between 7 and 8 C

• N-methyl group

• Ether (E) bridge

• Aromatic ring

Biological action of opioids depends on [6]

b. Phenolic OH

[Structure Activity Relationship of Opoids]

_______ group is needed for binding of mu and kappa receptors.

a. Hydroxymethyl
b. Phenolic OH
c. Carboxyl
d. Amino

b. Mu and kappa

[Structure Activity Relationship of Opoids]

Phenolic OH group is needed for binding of _________ receptors?

a. Mu and delta

b. Mu and kappa

c. Kappa and delta

d. Mu only

b. Phenolic OH group

[Structure Activity Relationship of Opoids]

Seen in all mu agonists.

a. Hydroxymethyl group
b. Phenolic OH group
c. Carboxyl group
d. Amino group

b. Lowered activity

[Structure Activity Relationship of Opoids]

Changing the phenolic -OH to -H or -OCH₃ results in:

a. Increased activity

b. Lowered activity

c. No change in activity

d. Complete loss of activity

b. Decrease

[Structure Activity Relationship of Opoids]

When the R=C₃ substituent is changed from -OH to -H, the activity effect is:

a. Increase
b. Decrease
c. No change
d. Complete loss

b. Morphine

[Structure Activity Relationship of Opoids]

_______ has an -OH group at R=C₃.

a. Codeine

b. Morphine

c. Heroin

d. Hydromorphone

a. Codeine

[Structure Activity Relationship of Opoids]

Morphine has an -OH group at R=C₃. Codeine has which substituent at the -OCH₃

a. Codeine

b. Morphine

c. Heroin

d. Hydromorphone

b. -OCH₃

[Structure Activity Relationship of Opoids]

Morphine has an -OH group at R=C₃. Codeine has which substituent at the _______

a. -H
b. -OCH₃
c. -NH₂
d. -CH₃

c. 1/3

[Structure Activity Relationship of Opoids]

Codeine has approximately what fraction of the activity of morphine?

a. 1/2
b. 1/4
c. 1/3
d. 1/5

c. Decrease by 1/3

[Structure Activity Relationship of Opoids]

The activity effect when the R=C₃ substituent is changed from -OH to -OCH₃ (morphine to codeine) is:

a. Increase

b. No change

c. Decrease by 1/3

d. Complete loss

b. N-methyl group

[Structure Activity Relationship of Opoids]

Interacts hydrophobically with the mu receptor.

a. N-ethyl group

b. N-methyl group

c. N-propyl group

d. N-benzyl group

b. Potency and agonist/antagonist activity

[Structure Activity Relationship of Opoids]

The size of the substituent on the nitrogen of opioids dictates the ______

a. Duration of action only

b. Potency and agonist/antagonist activity

c. Oral bioavailability only

d. Protein binding only

b. Size of the substituent

[Structure Activity Relationship of Opoids]

The _______ on the nitrogen of opioids dictates the potency and agonist/antagonist activity.

a. Charge
b. Size of the substituent
c. Polarity
d. Number of hydrogens

[Structure Activity Relationship of Opoids]

R=N substituent with 3-5 carbons containing a double bond or small cyclic/aromatic rings results in:

a. Mu agonist

b. Mu antagonist

c. Delta agonist

d. Kappa agonist

b. Mu antagonist

[Structure Activity Relationship of Opoids]

R=N substituent example CH₂CH=CH₂ (allyl group) results in:

a. Mu agonist

b. Mu antagonist

c. Delta agonist

d. Kappa antagonist

c. Mu agonist

[Structure Activity Relationship of Opoids]

R=N substituent with greater than 5 carbons results in:

a. Mu antagonist

b. Delta agonist

c. Mu agonist

d. Kappa antagonist

d. Mu agonist (10x morphine)

[Structure Activity Relationship of Opoids]

R=N substituent that is aralkyl (e.g., CH₂CH₂Ph) results in:

a. Mu antagonist

b. Delta agonist

c. Kappa agonist

d. Mu agonist (10x morphine)

c. 10x morphine

[Structure Activity Relationship of Opoids]

The aralkyl substituent CH₂CH₂Ph has approximately how many times the potency of morphine?

a. 2x morphine
b. 5x morphine
c. 10x morphine
d. 20x morphine

c. Mu agonist

[Structure Activity Relationship of Opoids]

R=N substituent with a total of 8 carbons results in:

a. Mu antagonist

b. Delta agonist

c. Mu agonist

d. Kappa antagonist

b. 2-3x

[Structure Activity Relationship of Opoids]

Addition of OH at 14β in opioids increases activity by how many times?

a. 1-2x

b. 2-3x

c. 3-4x

d. 5-6x

b. Blood-brain barrier (BBB)

[Structure Activity Relationship of Opoids]

Addition of OH at 14β in opioids increases penetration of which barrier?

a. Placental barrier

b. Blood-brain barrier (BBB)

c. Intestinal barrier

d. Renal barrier

b. Respiratory depression

[Structure Activity Relationship of Opoids]

Addition of OH at 14β in opioids results in a decrease in:

a. Analgesic action

b. Respiratory depression

c. Antitussive action

d. Sedative action

b. 14 β H/OH Moiety (Addition of OH at 14 β)

[Structure Activity Relationship of Opoids]

The addition of ______ in opioid:

• Increases opioid activity 2-3x

• Increases penetration in BBB

• Decreases antitussive action.

a. Methyl group at N

b. 14 β H/OH Moiety

c. Phenolic OH

d. Double bond at 7-8

b. Increased activity

[Structure Activity Relationship of Opoids]

Reduction of the 7,8 double bond in opioids results in:

a. Decreased activity

b. Increased activity

c. No change in activity

d. Complete loss of activity

b. Lipophilicity

[Structure Activity Relationship of Opoids]

Removal of the OH at position 6 in opioids increases:

a. Water solubility

b. Lipophilicity

c. Protein binding

d. Renal excretion

c. Hydrocodone

[Structure Activity Relationship of Opoids]

Oxidation of OH to a keto group at position 6 plus reduction of the 7,8 double bond results in which drug?

a. Morphine

b. Codeine

c. Hydrocodone

d. Heroin

d. Heroin

[Structure Activity Relationship of Opoids]

Acetylation of the hydroxyl group at position 6 in opioids produces which drug?

a. Morphine

b. Codeine

c. Hydrocodone

d. Heroin

c. Removal of OH

[Structure Activity Relationship of Opoids]

Which modification of the 6 OH in opioids increases activity by increasing lipophilicity?

a. Acetylation

b. Methylation

c. Removal of OH

d. Oxidation to keto group

b. Oxidation of OH to keto at 6

[Structure Activity Relationship of Opoids]

Hydrocodone is formed by which modification of morphine?

a. Removal of OH at 6

b. Oxidation of OH to keto at 6

c. Acetylation of hydroxyl at 6

d. Reduction of 7,8 double bond only

b. Oxidation of OH to keto at 6

[Structure Activity Relationship of Opoids]

Heroin is formed by which modification of morphine?

a. Removal of OH at 6

b. Oxidation of OH to keto at 6

c. Acetylation of hydroxyl at 6

d. Reduction of 7,8 double bond

a. H

[R=C₆ substituent]

Increases activity by 10x

a. H

b. O (Keto)

c. O (Keto w/ 7,8 reduction)

d. H3CC=O (Acetyl)

b. O (Keto)

[R=C₆ substituent]

Decreases activity by 1/3

a. H

b. O (Keto)

c. O (Keto w/ 7,8 reduction)

d. H3CC=O (Acetyl)

c. O (Keto w/ 7,8 reduction)

[R=C₆ substituent]

Increases activity by 6x

a. H

b. O (Keto)

c. O (Keto w/ 7,8 reduction)

d. H3CC=O (Acetyl)

a. Increases activity

[R=C₆ substituent]

H₃CC=O (acetyl) → _______ activity

a. Increases activity

b. Decreases activity

b. Morphinans

Removal of the ether linkage in opioids produces_______

a. Morphine

b. Morphinans

c. Codeine

d. Benzomorphans

b. Increased activity

Removal of the ether linkage in opioids produces Morphinans which has ______

b. Increased activity

c. No change in activity

d. Complete loss of activity

c. Removal of ether linkage

Morphinans are produced by which structural modification of morphine?

a. Removal of phenolic OH

b. Removal of N-methyl group

c. Removal of ether linkage

d. Reduction of 7,8 double bond