KAWAGUCHI, KENICHI,川口贤一,川口賢一,ISHIHATA, AKIHIRO,石畠明裕,INAGAKI, YUSUKE,稲垣勇典,TSUCHIYA, KAZUYUKI,土屋和之,HANADATE, TADAATSU,花舘忠笃,花舘忠篤,KANAI, AKIRA,金井章,KAIZAWA, HIROYUKI,贝沢弘行,貝沢弘行,KAZAMI, JU
申请号：
TW104117175
公开号：
TW201609654A
申请日:
2015.05.28
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-{[4-(substituted pyridine)-2-yl]methyl}-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，特別為適用於夜間頻尿的治療上之化合物。藉由將AVP之代謝酵素的胎盤性亮胺酸胺基肽酶(Placental leucine aminopeptidase：P-LAP)在夜間被阻礙，介著內生性AVP濃度之維持．增加所引起的抗利尿作用，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-〔(4-取代吡啶-2-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老鼠的抗利尿作用試驗，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。因此，本發明為提供一種可期待作為將P-LAP阻礙為機制的夜間頻尿治療劑使用的化合物。
