Med Chem Exam 2

Front 1

Common structural features of Losartan

Back 1

Ionized carboxylic acid at end of chain
Imidazole ring (5 membered 2=, 2N)
Hydrocarbon Side Chain
Additional Tetrazole (5 membered, 4N, 1=)

Front 2

Purpose of Tetrazole in Sartans?
Purpose of butyl side chain? Imidazole ring?

Back 2

Mimics terminal Asp of AngII.
Butyl side chain mimics Isoleucine of AngII
Imidazole ring mimics of His of AngII

Front 3

How is Losartan metabolized?

Back 3

14% metabolized OH > Carboxylic Acid making an active metabolite.
Most of the rest excreted unchanged, a bit metabolized to inactive.

Front 4

How do Losartan prodrugs work? Names?

Back 4

Esters are hydrolyzed to carboxylic acids by esterases.
Named Candesartan Cilexetil and Olmesartan medoxomil.

Front 5

Common Structural Features of 1-4 Dihydropyridines and active conformer?

Back 5

H's on 1,4 (1 being top) positions.
R2 (C5) and R3 (C3) are esters.
X Substituted phenyl ring on 4, never para
ALWAYS Perpindicular conformation

Front 6

Hantzsch reaction?

Back 6

For synthesis of 1-4 Dihydropyridines.
2 Ketones and an Ammonium and 3 H2O's lost.

Eileen help?

Front 7

Metabolism of -Dipines?

Back 7

3A4 removes H's from ring and gives aromatic.
Esterases can give R2 and R3 as carboxylic acids.

Front 8

Types of Lipids?

Back 8

Triacylglycerols have glycerol head group with 3 FA's.
Glycerophospholipids have glycerol head group with 2 FA's and a PO4-X (where X is polar).
Sphingolipids have Sphingosine head group with 1 FA and 1 PO4-Choline or PO4-Saccharide.

Front 9

Cholesterol Esters?

Back 9

3OH of cholesterol is turned into ester (by Lecithin Cholesterol Acyltransferase (LCAT)) which takes ester from phosphatidylcholine. Cholesterol Esters are less polar and are the preferred form for transport in plasma and storage.

Front 10

R-Mevalonic Biosynthesis?

Back 10

Acyl-CoA + Acetyl-CoA + Acetoacetyl-CoA > Beta-Hydroxyl-Beta-Methylglutaryl-CoA.
BHBM-CoA is acted on by HMG CoA Reductase to reduce the COSCoA to OH.

Front 11

Lipoproteins?

Back 11

LDL has 1 Molecule of B-100 per LDL particle. Non-Exchangable apoprotein. Does lipid recognition and binding to LDL. Mostly cholesterol.

HDL has A-I and promotes cholesterol efflux from tissue to liver. Mostly protein.

Chylomicrons are least dense. Are used to transport triacylglycerols from intestine to tissues. Exogenous pathway. Mostly made up of triacylglycerols.

VLDL binds triacylglycerols and carries them to fat tissue. Endogenous pathway. Part cholesterol, mostly TAG.

Front 12

MoA and Effects of Fibrates?

Back 12

Agonist of PPARArpha. Decreases serum triglycerides and VLDL.

Some are prodrugs that require esterases to give COOH.

Front 13

MoA and Effects of Bile Acid Sequestrants?

Back 13

Cations that have positively charged N atoms that bind anionic bile acid to prevent their resorption.
This lowers cholesterol (LDL) levels.

Front 14

MoA and Effects of Ezetimibe?

Back 14

Inhibits NPC1L1 protein to reduce cholesterol absorption from diet. Reduces LDL and increases HDL.

Front 15

MoA and rationale for design of Statins?

Back 15

Mimic substrate and product (mevalonate) HMG-CoA. Inhibits HMG-CoA reductase.

Front 16

Which statins are fungal metabolites and which are synthetic?

Back 16

Fungal: Lova, Prava, Simva
Synthetic: Fluva, Ceriva, Atorva, Rosuva

Front 17

Adrenal vs Sex Hormones?

Back 17

Adrenal corticoids: Gluco + Mineral. Secreted by adrenal cortex. Mineral controls cellular electrolyte and water balance. Gluco regulate carb, fat, protein metabolism and regulates inflammatory, allergic and stress response.

Sex hormones: Estrogens, Progestins, Androgens. Estrogens are made in ovary and placenta used for reproduction and female sex organs and bone density. Treated for birth control. Progestins made in ovary and placenta. Maintain pregnancy, inhibit follicular maturation and ovulation, prevents uterine contractions. Used for birth control. Androgens made in testes and adrenal cortex. Cause sex organ development and secondary sexual characteristics and anabolic activity.

Front 18

Nomenclature of steroid hormones

Back 18

27=Cholestanes
24=Cholanes
21=Pregnanes
19=Androstanes
18=Estranes

Beta = Out of page.

Front 19

Function of enzymes in steroid hormone biosynthesis?

Back 19

Hydroxylase adds OH's at named positions.
Lyase cuts between named C's, giving Ketone.
Hydroxysteroid Dehydrogynase changes OH to Ketone
Oxosteroid Isomerase moves double bond to name position.
Hydroxylase on C not in a ring makes ALDEHYDE.
Aromatase changes Ketone to OH and makes it Aromatic and removes 19CH3.
Estradiol Dehydrogenase can turn Ketone to Alcohol

Front 20

Most active anti-inflammatory steroid with no mineralcorticoid activity?

Back 20

Dexamethasone which has an F.

Front 21

Estrogen metabolism?

Back 21

2/4 Hydroxylase adds OH at either 2 or 4. COMT adds Methyl to OH at new OH.

Front 22

Main chemical modification for synthetic estrogens?

Back 22

Block C17 to prevent Oxidation, which makes it much more orally active.

Front 23

Non-Steroidal Estrogens?

Back 23

Must have rigid structure and fixed distance for two OH's or OMe's.

Front 24

Main structural requirements for anabolic and androgenic activity?

Back 24

Steroid skeleton.
Ketone at C17 is androgenic. Alkyl group at 17Arpha is anabolic.

Front 25

19-Norandrogens?

Back 25

Remove 19CH3 group to reduce androgenic properties while maintaining anabolic ones.

Front 26

Eicosanids classes?

Back 26

Control inflammatory response.

Front 27

Aspirin?
Main metabolite?

Back 27

Acetylates Ser530 on COX1 and Ser516 on COX2.
Irreversibly inhibits COX1.
Salicyluric Acid. Replaces Carboxylic acid of salicylic acid with CONHCH2CO2H thingy.

Front 28

Non-Selective COX inhibitors RAS?

Back 28

Acidic group mimics CO2H of arachidonic acid.
Acidic group is 1C from flat surface (Ph ring) that mimics the 5 and 8 ='s of arachidonic acid.
Second lipophilic group mimics 11 double bond.

Front 29

AE of nonselective COX inhibitors?
Of selective COX-2 inhibitors?

Back 29

Gastric irritation.
Higher risk of CV events.

Front 30

Acetaminophen toxicity?

Back 30

N-Hydroxyamide which is converted to N-Acetylimidoquinone.

N-Acetyl.. is detoxified by hepatic glutathione (GSH) which can be depleted. If so, the quinone will react with cysteines on hepatic proteins, causing damage.