Lecture 1 medchem

What is a diuretic

Agent that increases the rate of urine formation by decreasing the reabsorption of Na ions and their osmotic equivalent of water from kidney tubules

What are Diuretics used to treat

Mild hypertension

Edema by CHF

Pulmonary edema

What is site1 of diuretics

Proximal tubule which is what carbonic anhydrase inhibitors target

What is Site 2

Acts on thick ascending loop of henley aka loop diuretics

What is site 3 of diuretics

Thick ascending loop so thiazides act here

What is site 4

k+ sparing diuretics 

What is an example of site 1 carbonic anhydrase inhibitor

Sulfanilamide

What is the MOA of Sulfonilamide

Renal carbonic enzyme inhibitor in proximal covulated tubule but this only has mild diuresis

Which drug was based off of Sulfinilamide and created to have more potency 

meta- disulfamoylbenzene

What changes should be made to the benzene structure to be more potent on meta disulfamoylbenzene

Electron withdrawing group like Cl on the top left position

Unsubstiututed H2NO2S

Replace SO2NH2 with COOH

What is the second mechanism of meta-disulfamoulbenzene

CA inhibitory effects

What is the precursor to thiazide diuretics

Chloraminophenamide

What are DCT Site 3 diuretics

Thiazides and Thiazide like diuretics

What advantage was observed with benzothiadizines

Increased chloride excretion

What must be in position 7 of thiazides for opiimal activity 

Sulfonamide

What must be at position 6 for Thiazids

Electron withdrawing group like Halogen MUST be lipophillic like Cl, F or CF3

What structural change in thiazide diuretics make them thiazide like diuretics

Changing the SO2 to C=O

Which thiazide diuretic is more acidic

Chlorothiazide because of double bond between NH and N 

Which sulfonamides are not acidic

Tertiary

Why is Hydrochlorothiazide more potent

Saturation at 3,4 position

What lead to Quinazolinone derivatives

Replacement of SO2 with carbonyl C=O 

What is chlorothalidone derived from

Phthalimide

Which diuretic is a indoline derivative

Indapamide

What moiteys does Thiazide have 

Sulfamoyl chlorobenzamide 

2-methylindole 

What contributes to lipophiliicity in Indapamide

2 methyl indolene

What is the structure of Aminopteridines

Bicyclic ring

What is triamterene combined with 

Hydrochlorothiazide to get pronounced diuretic action 

Where does triamterene and amiloride bind

Positively charged pocket

Which potassium spring diuretic has a higher affinity for ENAC

Amiloride

What is Liddles Syndrome

Enac is Hyper active

What happens as a result of blocking ENAC chain

Increases sodium excretion

What is the site of action of Calcium Channel blockers

L type 

What is L type made up of

Pentameric units with helical structures

Which calcium channel blocker is not so basic

Nifedipine

What structure must calcium channel blockers be for activity

Dihydroperidine 

What happens if N1 of Calcium channel blockers becomes Pyridine or Piperadine

Not good

What position subsitituents must be for CCB

Ortho or Meta positon

Which CCB is non chiral 

Nefidipiene

Is 1, 4 DHP basic or acidic

Not basic

What are some important SAR of dilitiazem

Cis arrangement of phenyl ring and acetyl ester

What is the active conformation of CCB

Boat shaped 

Axial 

Perpendicular phenyl ring 

What is a key structural component of CCB

Ester groups on either side

What is the metabolite of Dilitiazem

Deacetyldilitiazem