Opium Analgesics

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					Opium Analgesics
    Chapter 21
Opiates

   Analgesic properties
   Problem?
   Why opiates?
   What are opiates?
Opium Poppy

   Papaver somniferum
   “Sleep-bringing poppy”
   Many varieties, colors
   Poppy seed
   Latex from pod
   Tincture
   Smoked
Opium

   Oldest drug
   History
   Mixture of alkaloids
       Morphine
Morphine
                                   HO




   Timeline:
                                      O
       1803 isolated
       1833 purified                                            N

       1853 medicine                                   H                 CH3

       1881 functional groups     HO

        identified
       1925 structure proposed
       1953 synthesis
        1968 structure confirmed
                                   (CH3)2NOC        N
                                              Ph
                                                            OH




   Properties
                                                                     Cl
                      HO


Morphine
                       O
   Structure
   Stereochemistry            N

                           H       CH3

                      HO
Structure-activity
relationships

   Phenolic OH      HO




                      O


                              N

                          H       CH3

                     HO
Structure-activity
relationships

   Phenolic OH      HO


   Other alcohol

                      O


                              N

                          H       CH3

                     HO
Structure-activity
relationships

   Phenolic OH      HO


   Other alcohol
   Double bond
                      O


                              N

                          H       CH3

                     HO
Structure-activity
relationships

   Phenolic OH      HO


   Other alcohol
   Double bond
   N-methyl group    O


                              N

                          H       CH3

                     HO
Structure-activity
relationships

   Phenolic OH      HO


   Other alcohol
   Double bond
   N-methyl group    O


   Aromatic ring             N

                          H       CH3

                     HO
Structure-activity
relationships

   Phenolic OH      HO


   Other alcohol
   Double bond
   N-methyl group    O


   Aromatic ring             N


    Ether bridge          H       CH3

                     HO
Pharmacophore?

   Based on SARs…
                     HO




                      O


                              N

                          H       CH3

                     HO
Development of
morphine analogues
   Remember this pharmacophore example?
 Development of
 morphine analogues                            HO




    Extension of drug                          O


    Vary substituents                                        N

                                                         H         CH3

                                               HO


HO                           HO                     HO




 O                            O                      O


                   N                     N                         N

             OH        CH3          H                         OH
HO                           HO                     O

     oxymorphine                  nalorphine             naltrexone
Development of
morphine analogues                               HO




    Extension of drug                               O


    Vary substituents                                                 N

                                                                 H           CH3
    Simplification                              HO




HO



                                                                                       CH3



                      HO
     Et                                                        EtOC                N
                  N            EtO2C             N                     Ph
                                                                            H3C
                                                                                        CH3
          CH3                                            CH3

                bremazocaine           Demerol                        methadone
Development of
morphine analogues      HO




   Extension of drug    O


   Vary substituents            N

                             H       CH3
   Simplification      HO


   Rigidification




        buprenorphine
Receptor theory

   m receptor
   k receptor
   d receptor

   s receptor
                        N




                 phencyclidine
Scientific fact
or urban legend?

				
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posted:12/9/2011
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