Invention Grant
- Patent Title: Pyridine derivative
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Application No.: US16544245Application Date: 2019-08-19
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Publication No.: US10975091B2Publication Date: 2021-04-13
- Inventor: Kenichi Kawaguchi , Akihiro Ishihata , Yusuke Inagaki , Kazuyuki Tsuchiya , Tadaatsu Hanadate , Akira Kanai , Hiroyuki Kaizawa , Junichi Kazami , Hiroshi Morikawa , Masashi Hiramoto , Kentaro Enjo , Hajime Takamatsu
- Applicant: Astellas Pharma Inc. , KOTOBUKI PHARMACEUTICAL CO., LTD.
- Applicant Address: JP Tokyo; JP Hanishina-gun
- Assignee: Astellas Pharma Inc.,KOTOBUKI PHARMACEUTICAL CO., LTD.
- Current Assignee: Astellas Pharma Inc.,KOTOBUKI PHARMACEUTICAL CO., LTD.
- Current Assignee Address: JP Tokyo; JP Hanishina-gun
- Agency: Oblon, McClelland, Maier & Neustadt, L.L.P.
- Priority: JP2014-110432 20140528
- Main IPC: A61K31/44
- IPC: A61K31/44 ; C07D213/70 ; C07D495/04 ; C07D491/08 ; A61K31/436 ; A61K31/4355 ; A61K31/437 ; A61K31/439 ; A61K31/443 ; A61K31/4433 ; A61K31/4436 ; A61K31/4439 ; A61K31/444 ; A61K31/4545 ; A61K31/4725 ; A61K31/497 ; A61K31/506 ; A61K31/5377 ; C07D213/74 ; C07D401/04 ; C07D401/06 ; C07D401/12 ; C07D407/06 ; C07D407/12 ; C07D409/12 ; C07D471/04 ; C07D491/048 ; C07D491/056 ; C07D213/68 ; C07D401/10 ; C07D405/06 ; C07D405/12

Abstract:
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.
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.
Public/Granted literature
- US20200055868A1 PYRIDINE DERIVATIVE Public/Granted day:2020-02-20
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