Chem Basis ACEIs and ARBs Structures 3

The flashcards below were created by user kyleannkelsey on FreezingBlue Flashcards.

  1. Image Upload
    What is the pharamcophore of this compound (Enalapril)?
    N-carboxymethy L-alanyl-L-proline derivative
  2. Image Upload
    The phenyl ethyl group side chain has what effect on this molecules action, why?
    Enhances activity by allowing hydrophobic/Van der Waals binding to the auxiliary binding site (Enalapril)
  3. Image Upload
    The ester on the side chain carboxylic group indicates that what must happen prior to binding?
    Hydrolysis of the ester to free an OH group (Enalapril)
  4. Image Upload
    Is this an active drug?
    No, a Prodrug (Enalapril)
  5. Image Upload
    The ester also has what effect on this molecules activity?
    Increased oral absorption and bioavailability (resulting in once a day dosing)

    (Enalapril)
  6. Image Upload
    The cyclic nature of the proline provides for what benefit?
    An amide bond that is protected and not easily hydrolyzed by amidases

    (Enalapril)
  7. Image Upload
    The carbonyl oxygen may be involved with what type of interaction with the receptor?
    Hydrogen binding

    (Enalapril)
  8. Image Upload
    The methyl on the side chain may be involved with what type of interaction with the receptor
    Hydrophobic binding

    (Enalapril)
  9. Image Upload
    The NH is critical for activity because it provides what benefit?
    H-binding to ACE

    (Enalapril)
  10. Image Upload
    What is this drug?
    Enalapril
  11. Image Upload
    What is the pharamcophore of this molecule(Fosinopril)?
    Phosphinyl acetyl L-proline derivative

    (Fosinapril)
  12. Image Upload
    What must happen for this molecule to bind to the receptor?
    Hydrolysis of the phosphinyl group and ester

    (Fosinapril)
  13. Image Upload
    Can this molecule bind at the zinc binding site?
    No, needs t oundergo hydrolysis at the phosphinyl group

    (Fosinapril)
  14. Image Upload
    Is this an active drug?
    No, A prodrug

    (Fosinapril)
  15. Image Upload
    How often is this drug dosed and why?
    Once daily because it is an prodrug (see ester and phosphinyl group)

    (Fosinapril)
  16. Image Upload
    The cyclohexane on the proline is tolerated and may contribute to what?
    Hydrophobic binding to ACE

    (Fosinapril)
  17. Image Upload
    The phenyl butyl group on the side chain has what effect on activity?
    Enhances activity by binding to the auxiliary binding site via hydrophobic and Van der Waals forces

    (Fosinapril)
  18. Image Upload
    What is this drug?
    Losartan, and ARB, nonpeptide antagonist/blocker of one of the angiotensin receptors
  19. Image Upload
    What is the pharamcophore of this drug?
    1-N-benzyl 2-butyl Imidazole

    (Losartan)
  20. Image Upload
    What effect does the imidazole ring have on this drug?
    Allows for better binding to Ag-II receptor (AT1)

    (Losartan)
  21. Image Upload
    The phenyltetrazole acidic group contributes to what effects of this drug?
    Enhances binding to Ag-II receptor, metabolic stability, lipophilicity and oral bioavailability

    (Losartan)
  22. Image Upload
    What configuration should the tetrazole be in for optimal binding?
    Ortho position

    (Losartan)
  23. Image Upload
    A lack of linker between the two phenyls has what effect on this molecule?
    Good oral activity

    (Losartan)
  24. Image Upload
    The 2-butyl group has what effect on this molecule?
    Maintains activity

    (Losartan)
  25. Image Upload
    The methyl alcohol on the imidazole ring is also goodor bad for activity?
    Good

    (Losartan)
  26. Image Upload
    Is the parent structure is active?
    Yes

    (Losartan)
  27. Image Upload
    What is the half-life of the parent structure?
    Short half life (1.5-2.5 hr)

    (Losartan)
  28. Image Upload
    The parent structure is oxidized to an active 5-carboxylic acid metabolite, what activity does it have?
    10-40 times the potentency and a longer half life (6-9 hr)

    (Losartan)
  29. Image Upload
    The active 5-carboxylic acid metabolite provides for what dosing schedule?
    Increased to once or twice a day dosing

    (Losartan)
Author:
kyleannkelsey
ID:
250117
Card Set:
Chem Basis ACEIs and ARBs Structures 3
Updated:
2013-12-02 05:14:18
Tags:
Chem Basis ACEIs ARBs Structures
Folders:
Chem,Basis,ACEIs,and,ARBs,Structures,3
Description:
Chem Basis ACEIs and ARBs Structures 3
Show Answers: