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Since the first isolation of melatonin in 1959. interest in this hormone has grown steadily. Of particular interest are the reports that melatonin has the ability to inhibit LH secretion. A major difficulty in assessing the physiological properties of melatonin is its very rapid metabolism. This rate of metabolism combined with the polyphasic nature of  the process complicates estimation of  a  biological  half-life  for melatonin.  Kopin et al, estimate  that  exogenously administered melatonin disappears from whole mice with a half-life of  about 2 min through the first 10 min following injection but that after 40 min the half-life has grown to about 35 min. In this same report,  data are presented indicating a plasma half-life in rats through the first 30 min of about 15 min. Maickel et al. have estimated the plasma half-life in rats to be about 12 min through the first 2 h following administration.
     We  undertook  the synthesis of  a variety of  melatonin analogues with the intention of  producing compounds with similar physiological  properties but greater resistance  to metabolism.  A more general goal was  to establish which features of  the melatonin molecule are essential for activity and which  sites will  tolerate  structural modification.  In view of the evidence  that the major route  in  the metabolism of melatonin  is hydroxylation at the 6 position,' we were  particularly  interested  in  synthesizing  analogues bearing  substituents  in  that position.
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