Astellas Pharma Gmbh

Kotobuki Pharmaceutical Co Ltd

Kotobuki Pharmaceuticals Co., Ltd.

Kentaro Enjo

Akira Kanai

Kenichi Kawaguchi

Yusuke Inagaki

Hajime Takamatsu

Masashi Hiramoto

Akihiro Ishihata

Kazuyuki Tsuchiya

Hiroshi Morikawa

Junichi Kazami

Hiroyuki Kaizawa

Tadaatsu Hanadate

Takashi Furutani

Akio Kamikawa

Akio Kakefuda

Masaaki Hirano

Tatsuya Niimi

Minoru Yasuda

Kazushi Watanabe

Yutaka Kondoh

Tomohiko Yamaguchi

Kenichi Suzumura

Yasushi Amano

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

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.

Bicyclic pyridine compound

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.

Pyridine derivatives

As a result of studies on compounds having a selective inhibitory activity against 17&#x3b2;HSD type 5, the present inventors have confirmed that a {1-[(indol-2-yl)carbonyl]piperidyl}alkanol derivative has a potent selective inhibitory activity against 17&#x3b2;HSD type 5. The invention has been completed based on these findings. The compound of the present invention can be used as an agent for treating and/or an agent for preventing diseases associated with 17&#x3b2;HSD type 5, such as benign prostatic hyperplasia and prostate cancer, without accompanying adverse effects due to a decrease in testosterone.

Piperidine derivative

To provide a novel and excellent method for treating and/or preventing prostatic cancer, benign prostatic hyperplasia, acne, seborrhea, hirsutism, baldness, alopecia, precocious puberty, adrenal hypertrophy, polycystic ovary syndrome, breast cancer, lung cancer, endometriosis, leiomyoma and the like based on selective inhibitory activity against 17&#x3b2;HSD type 5. It was found that an N-sulfonylindole derivative, where the indole ring is substituted by a carboxy group, a carboxy-substituted lower alkyl group or a carboxy-substituted lower alkenyl group at its carbon atom, has potent selective inhibitory activity against 17&#x3b2;HSD type 5 and may become a therapeutic agent and/or preventive agent for benign prostatic hyperplasia, prostatic cancer and the like without accompanying adverse drug reactions due to a decrease in testosterone, and the present invention has thus been completed.

17&#x3b2;HSD type 5 inhibitor

Growing community of inventors

Ibaraki, Japan

Kentaro Enjo