Page 38 - Medicinal Chemistry Self Assessment
P. 38

Section 2  Whole Molecule Drug Evaluation







                                                                                          1.8 Aliskiren







            Aliskiren is an orally active agent used in the treatment of hypertension. This non-peptide drug acts as an inhibitor
            of renin, the enzyme that converts angiotensinogen (its endogenous substrate) to angiotensin I. Biologically inactive,
            angiotensin I is rapidly converted to angiotensin II by angiotensin converting enzyme. Angiotensin II is a potent
            agonist when bound to its receptor and produces significant vasoconstriction, as well as an increase in blood pressure.
            In the presence of aliskiren, angiotensinogen is not converted to angiotensin I so less angiotensin II is produced to
            activate the angiotensin II receptor. Consequently, less vasoconstriction occurs, and a drop in blood pressure results.
                                                      Medicinal Chemistry Self-Assessment Book: Batch Two
                                                                      Chapters 1.8 and 2.8

            1.  Conduct a structural evaluation of aliskiren, focusing on the boxed functional groups, and use the infor-
                                  Chapter 1.8/2.8 (remove bold from drug name x2)
                mation in the grid to inform your answers to the questions that follow.


                                                             E
                                                        D                              F
                                            A
                                                 B






                                                                      Aliskiren
                                                         C




                                                                                           Function
                                               Character                  Function         Amino Acids That
                                               Acidic, Basic,             Interaction(s)   Can Interact with the
                               Character       or Neutral   Function      Possible with    Functional Group via
                  Name of      Hydrophilic     Provide      ↑ Solubility  Biological Target   Ion–Dipole Interactions
                  Functional   and/or          pK  When     and/or        at Physiological   at pH=7.4
                                                  a
                  Group        Hydrophobic     Relevant     ↑ Absorption  pH=7.4           None Is Acceptable
             A                                                      Aliskiren

             B

             C
             D
             E

             F



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