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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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sxl8495(½ð±Ò+15,VIP+0):ÎÒÖªÓÐÕâô¶àÁË 3-11 14:48
sxl8495(½ð±Ò+15,VIP+0):ÎÒÖªÓÐÕâô¶àÁË 3-11 14:48
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mayong11
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3Â¥2009-03-10 18:47:18
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4Â¥2009-03-10 19:29:34














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