Title of article
Novel vitamin D3 antipsoriatic antedrugs: 16-En-22-oxa-1α,25-(OH)2D3 analogs Original Research Article
Author/Authors
Kazuki Shimizu، نويسنده , , Akira Kawase، نويسنده , , Tsuyoshi Haneishi، نويسنده , , Yasuharu Kato، نويسنده , , Takamitsu Kobayashi، نويسنده , , Nobuo Sekiguchi، نويسنده , , Tessai Yamamoto، نويسنده , , Masaki Ishigai، نويسنده , , Kazuo Tokuda، نويسنده , , Tomochika Matsushita، نويسنده , , Shin Shimaoka، نويسنده , , Kazumi Morikawa، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2006
Pages
13
From page
1838
To page
1850
Abstract
A series of 16-en-22-oxa-derivatives of vitamin D3 based on the structure of maxacalcitol (2) were prepared. Maxacalcitol is currently used topically for the treatment of psoriasis and is recognized as the most successful antedrug of natural vitamin D3 because it retains the original antiproliferative activity of calcitriol without increased calcemic activity. We introduced 16-olefinic functionality to accelerate the oxidative metabolism of the drug in liver, presumed to be essential for the reduction of calcemic activity, and modified the side-chain moiety by placing the 22-oxygen on the more labile allylic carbon center. Novel 22-oxa analogs (7a–i), carrying either the 24-alkynyl bond or 24-hydroxy functionality in addition to the 16-double bond were synthesized and their pharmacokinetics were evaluated.
Keywords
Psoriasis , 16-En-22-oxa-1? , 25-dihydroxyvitamin D3 analogs , Antedrug , Low calcemic activity
Journal title
Bioorganic and Medicinal Chemistry
Serial Year
2006
Journal title
Bioorganic and Medicinal Chemistry
Record number
1305563
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