Astellas Pharma Gmbh

Kotobuki Pharmaceutical Co Ltd

Nkk Corporation

Sony/tektronix Corporation

Kotobuki Pharmaceuticals Co., Ltd.

Hajime Takamatsu

Yusuke Inagaki

Akira Kanai

Kenichi Kawaguchi

Masashi Hiramoto

Hiroaki Tanaka

Kentaro Enjo

Akihiro Ishihata

Kenji Negoro

Kazuyuki Tsuchiya

Taisuke Takahashi

Hiroshi Morikawa

Junichi Kazami

Jun Maeda

Hiroyuki Kaizawa

Takanori Koike

Kazuhiro Yokoyama

Tadaatsu Hanadate

Issei Tsukamoto

Michinori Akaiwa

Hisashi Mihara

Hideyoshi Fuji

[Problem] To provide a compound which is useful as an active ingredient for a pharmaceutical composition for preventing or treating urine storage dysfunction, voiding dysfunction, lower urinary tract dysfunction, and the like. [Means for Solution] The present inventors have found that a thiazole derivative substituted with pyrazinylcarbonylamino at the 2-position is an excellent muscarinic Mreceptor-positive allosteric modulator and is expected as an agent for preventing or treating bladder/urinary tract diseases associated with bladder contractions via a muscarinic Mreceptor, thereby completing the present invention. 2-Acylaminothiazole derivative or a salt thereof of the present invention is expected as an agent for preventing or treating bladder/urinary tract diseases associated with bladder contractions via a muscarinic Mreceptor, for example voiding dysfunction such as underactive bladder.

2-acylaminothiazole derivative or salt thereof

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

A compound which is useful as an active ingredient for a pharmaceutical composition for treating urine storage dysfunction, voiding dysfunction, lower urinary tract dysfunction, and the like. The present inventors have found that a 2-aminothiazole derivative has an excellent muscarinic Mreceptor-positive allosteric modulator activity and is expected as an agent for preventing or treating bladder/urinary tract diseases associated with bladder contractions via a muscarinic Mreceptor, thereby completing the present invention. 2-aminothiazole derivative or a salt thereof of the present invention is expected as an agent for preventing or treating bladder/urinary tract diseases associated with bladder contractions via a muscarinic Mreceptor, for example voiding dysfunction such as underactive bladder.

2-aminothiazole derivative or salt thereof

Thiazole derivatives having pyrazine-2-carbonylamino substituted at the 2-position of the following formula (I): are excellent muscarinic Mreceptor positive allosteric modulators, and are useful for treating bladder or urinary tract diseases, related to bladder contraction by a muscarinic Mreceptor. The 2-acylaminothiazole derivatives and salts thereof can be used for treating bladder or urinary tract diseases, related to bladder contraction by a muscarinic Mreceptor, for example, voiding dysfunctions such as underactive bladder.

Multiprocessor system having a plurality of gateway units and wherein

A variable gain amplifier including common emitter input transistor, a plurality of common base switching transistor to form a cascode amplifier with said input transistor and a resistive network including a plurality of series resistors is disclosed. A plurality of predetermined gains are obtained by programming the resistors. The resistive network may be shared by two or more variable gain amplifiers to provide a selection amplifier.

Variable gain amplifier

Growing community of inventors

Tokyo, Japan

Hajime Takamatsu