Astellas Pharma Gmbh

Kotobuki Pharmaceutical Co Ltd

Kotobuki Pharmaceuticals Co., Ltd.

Tadaatsu Hanadate

Hiroyuki Kaizawa

Akira Kanai

Yusuke Inagaki

Kenichi Kawaguchi

Hajime Takamatsu

Kazuyuki Tsuchiya

Kentaro Enjo

Hiroshi Morikawa

Akihiro Ishihata

Masashi Hiramoto

Junichi Kazami

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.

Pyridine derivative

Growing community of inventors

Tokyo, Japan

Tadaatsu Hanadate