公开(公告)号：US20180327418A1

公开(公告)日：2018-11-15

申请号：US16041117

申请日：2018-07-20

Applicant: Astellas Pharma Inc. ,  KOTOBUKI PHARMACEUTICAL CO., LTD.

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

IPC: C07D495/04 ,  C07D491/08 ,  C07D405/06 ,  C07D405/12 ,  C07D213/70 ,  C07D213/68 ,  C07D491/056 ,  C07D491/048 ,  C07D471/04 ,  C07D409/12 ,  C07D407/12 ,  C07D407/06 ,  C07D401/12 ,  C07D401/06 ,  C07D401/04 ,  C07D213/74 ,  A61K31/5377 ,  A61K31/506 ,  A61K31/497 ,  A61K31/4725 ,  A61K31/4545 ,  A61K31/444 ,  A61K31/4439 ,  A61K31/4436 ,  A61K31/4433 ,  A61K31/443 ,  A61K31/44 ,  A61K31/439 ,  A61K31/437 ,  A61K31/4355 ,  A61K31/436 ,  C07D401/10

CPC classification number: C07D495/04 ,  A61K31/4355 ,  A61K31/436 ,  A61K31/437 ,  A61K31/439 ,  A61K31/44 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/4436 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/4725 ,  A61K31/497 ,  A61K31/506 ,  A61K31/5377 ,  C07D213/68 ,  C07D213/70 ,  C07D213/74 ,  C07D401/04 ,  C07D401/06 ,  C07D401/10 ,  C07D401/12 ,  C07D405/06 ,  C07D405/12 ,  C07D407/06 ,  C07D407/12 ,  C07D409/12 ,  C07D471/04 ,  C07D491/048 ,  C07D491/056 ,  C07D491/08

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.

公开(公告)号：US20170362209A1

公开(公告)日：2017-12-21

申请号：US15532772

申请日：2015-12-04

Applicant: Astellas Pharma Inc. ,  KOTOBUKI PHARMACEUTICAL CO., LTD.

Inventor： Kenichi KAWAGUCHI ,  Akihiro ISHIHATA ,  Akira KANAI ,  Kazuyuki TSUCHIYA ,  Yusuke INAGAKI ,  Junichi KAZAMI ,  Hiroshi MORIKAWA ,  Masashi HIRAMOTO ,  Kentaro ENJO ,  Hajime TAKAMATSU

IPC: C07D405/04 ,  C07D221/20 ,  C07D221/04 ,  C07D217/24 ,  C07D217/16 ,  C07D401/04 ,  C07D213/55

CPC classification number: C07D405/04 ,  A61K31/435 ,  A61K31/438 ,  A61K31/44 ,  A61K31/4418 ,  A61K31/4433 ,  A61K31/444 ,  A61K31/472 ,  A61K31/4747 ,  A61P7/12 ,  C07D213/55 ,  C07D213/63 ,  C07D217/16 ,  C07D217/24 ,  C07D221/02 ,  C07D221/04 ,  C07D221/20 ,  C07D401/04

Abstract: The problem to be solved by the present invention is to provide a compound suitable for a pharmaceutical composition, specifically an agent 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-(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.

公开(公告)号：US20200055868A1

公开(公告)日：2020-02-20

申请号：US16544245

申请日：2019-08-19

Applicant: Astellas Pharma Inc. ,  KOTOBUKI PHARMACEUTICAL CO., LTD.

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

IPC: C07D495/04 ,  C07D405/12 ,  C07D405/06 ,  C07D401/10 ,  C07D213/70 ,  C07D213/68 ,  C07D491/056 ,  C07D491/048 ,  C07D471/04 ,  C07D409/12 ,  C07D407/12 ,  C07D407/06 ,  C07D401/12 ,  C07D401/06 ,  C07D401/04 ,  C07D213/74 ,  A61K31/5377 ,  A61K31/506 ,  A61K31/497 ,  A61K31/4725 ,  A61K31/4545 ,  A61K31/444 ,  A61K31/4439 ,  A61K31/4436 ,  A61K31/4433 ,  A61K31/443 ,  A61K31/44 ,  A61K31/439 ,  A61K31/437 ,  A61K31/4355 ,  A61K31/436 ,  C07D491/08

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.

公开(公告)号：US20180022755A1

公开(公告)日：2018-01-25

申请号：US15551222

申请日：2015-11-27

Applicant: Astellas Pharma Inc. ,  KOTOBUKI PHARMACEUTICAL CO., LTD.

Inventor： Kenichi KAWAGUCHI ,  Akihiro ISHIHATA ,  Akira KANAI ,  Yusuke INAGAKI ,  Masashi HIRAMOTO ,  Kentaro ENJO ,  Hajime TAKAMATSU

IPC: C07D491/048 ,  C07D495/04

CPC classification number: C07D491/048 ,  A61K31/4355 ,  A61K31/4365 ,  C07D495/04

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-(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.

公开(公告)号：US20170190715A1

公开(公告)日：2017-07-06

申请号：US15313712

申请日：2015-05-28

Applicant: ASTELLAS PHARMA INC. ,  KOTOBUKI PHARMACEUTICAL CO., LTD.

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

IPC: C07D495/04 ,  C07D405/06 ,  C07D491/056 ,  C07D401/12 ,  C07D409/12 ,  C07D471/04 ,  C07D401/10 ,  C07D405/12 ,  C07D401/04 ,  C07D213/68 ,  C07D491/048

CPC classification number: C07D495/04 ,  A61K31/4355 ,  A61K31/436 ,  A61K31/437 ,  A61K31/439 ,  A61K31/44 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/4436 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/4725 ,  A61K31/497 ,  A61K31/506 ,  A61K31/5377 ,  C07D213/68 ,  C07D213/70 ,  C07D213/74 ,  C07D401/04 ,  C07D401/06 ,  C07D401/10 ,  C07D401/12 ,  C07D405/06 ,  C07D405/12 ,  C07D407/06 ,  C07D407/12 ,  C07D409/12 ,  C07D471/04 ,  C07D491/048 ,  C07D491/056 ,  C07D491/08

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.