532 - Med Chem Ii - Exam Ii - Cardiovascular Agents

Front 1

Four major classes of drugs for anti-hypertensive therapy?

Back 1

1) B-blockers, 2). ACE-I, 3) ARBs, & 4) CCBs

Front 2

Four common structural features of Losartan and analogs?

Back 2

1) CO2H, CH2OH, akyl, or aryl group, 2) imidazole ring, 3) hydrocarbon side chain, & 4) ionized carboxylate or tetrazole entity

Front 3

What AA does the imidazole ring on losartan mimic?

Back 3

His in Ang II

Front 4

What AA does the hydrophobic side chain on losartan mimic?

Back 4

Ile in Ang II

Front 5

What AA does the acidic group mimic on losartan?

Back 5

Asp in Ang II

Front 6

What AA does the CO2H, CH2OH, akyl, or aryl group on losartan mimic?

Back 6

Phe on c-terminal of Ang II

Front 7

Why does the tetrazole in Losartan have better bioavailability than COOH?

Back 7

Charge delocalization and more metabolically stable- often excreted unchanged

Front 8

Is -OH more or less lipophilic than -COOH?

Back 8

more lipophilic (e.g. losartan development)

Front 9

Is the metabolite of losartan more or less active than losartan itself?

Back 9

MORE active- but still not a prodrug, because losartan does have some activity

Front 10

How is losartan metabolized?

Back 10

14% to active carboxylic acid (more potent), 80% excreted unchanged, the rest is metabolized to inactive metabolites

Front 11

What CYP enzymes are used to metabolize Losartan?

Back 11

2C9 and 3A4

Front 12

Ester prodrugs of ARBs (2)

Back 12

Candesartan cilexetil and olmesartan medoxomil

Front 13

Losartan (class)

Back 13

ARB

Front 14

Key interactions of Losartan with AT1 receptor (2)

Back 14

Arg and Lys with Tetrazole ring

Front 15

How does Ca cause muscle contraction?

Back 15

Binding of Ca2+ to troponin caused a conformational change in tropomyosin that uncovers myosin binding sites on the actin filiment, thus facilitating the cross-bridge cycling process.

Front 16

Nifedipine (class and subclass)

Back 16

CCB - 1,4-dihydropyridine

Front 17

SAR of dihydropyridines

Back 17

1) 1, 4- dihydropyridine ring, 2) R2 and R3 are esters, 3) X-substituted phenyl ring, 4) substituted X blocks rotation (perpendicular conformation is locked) (ORTHO OR META)

Front 18

Conformational restriction of Dihydropyridines

Back 18

Ortho or meta substitution in phenyl ring locks perpendicular conformation (no rotation allowed)

Front 19

What is the Hantzsch reaction?

Back 19

Synthesis of Dihydropyridines

Front 20

What are dihydropyridines?

Back 20

CCBs

Front 21

Building blocks for the Hanzsch reaction

Back 21

NH3, aldehyde, 2 (ketone ester combos) --> three molecules of water are lost in the condensation reaction

Front 22

What is the conformation of the o-NO2 group of nifedipine for activity?

Back 22

Perpendicular

Front 23

Metabolism of 1,4-dihydropyridines

Back 23

1) CYP3A4 oxidation to more stable pyridine, 2) esterase hydrolysis, 3) glucuronic acid conjugates

Front 24

How to synthesize unsymmetric dihydropyridines?

Back 24

Stepwise Hantzsch reaction (add NH3 and aldehyde to each of the ketone/ester combos first, then combine the two)