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二環式吡啶化合物
专利权人:
ASTELLAS PHARMA INC.;KOTOBUKI PHARMACEUTICAL CO., LTD.
发明人:
KAWAGUCHI, KENICHI,川口贤一,川口賢一,ISHIHATA, AKIHIRO,石畠明裕,KANAI, AKIRA,金井章,INAGAKI, YUSUKE,稲垣勇典,HIRAMOTO, MASASHI,平本昌志,ENJO, KENTARO,远城健太郎,遠城健太郎,TAKAMATSU, HAJIME,髙松肇
申请号:
TW104139686
公开号:
TW201636352A
申请日:
2015.11.27
申请国别(地区):
TW
年份:
2016
代理人:
摘要:
The problem to be solved by the present invention is to provide a compound suitable for a pharmaceutical composition, specifically a pharmaceutically composition for treating nocturia. The inventors have assumed that inhibition of nocturnal activity of placental leucine aminopeptidase (P-LAP), i.e. aminopeptidase that cleaves AVP, would maintain and/or increase an endogenous AVP level to enhance the antidiuretic effect, which would contribute to a decreased number of nocturnal voids, and have extensively studied compounds which inhibit P-LAP. As a result, the inventors have found that (2R)-3-amino-2-(bi-cyclic pyridylmethyl)-2-hydroxy-propanoic acid derivatives have excellent P-LAP inhibitory activity. The inventors have evaluated antidiuretic effects in water-loaded rats and have found that the compounds increase endogenous AVP levels by inhibiting P-LAP and consequently reduce urine production. The present invention therefore provides compounds expected to be used as an agent for treating nocturia based on P-LAP inhibition.本發明之課題為提供一種醫藥組成物,特別適用於夜間頻尿之治療的化合物。藉由將AVP的代謝酵素之胎盤性亮胺酸胺基肽酶(Placental leucine aminopeptidase:P-LAP)在夜間經阻礙,介著內生性AVP濃度的維持‧增加之抗利尿作用,期待可減少夜間排尿次數,對於阻礙P-LAP之化合物進行詳細檢討。其結果,發現(2R)-3-胺基-2-(二環式吡啶基甲基)-2-羥基丙烷酸衍生物具有良好P-LAP阻礙作用,且對於使用飲水負荷鼠之抗利尿作用試驗,該化合物具有依據P-LAP阻礙的內生性AVP濃度上昇所引起的尿生成抑制作用作為見解。藉此,本發明為提供可期待作為將P-LAP阻礙作為機制之夜間頻尿治療劑使用的化合物。
来源网站:
中国工程科技知识中心
来源网址:
http://www.ckcest.cn/home/

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