Astellas Pharma Gmbh

Mitobridge, Inc.

Ryushi Seo

Hiroyuki Kaizawa

Satoshi Yamamoto

Hirofumi Yamamoto

Hidenori Azami

Kazunori Kamijo

Mari Sugita

Kazuyuki Tsuchiya

Takashi Shin

Keisuke Matsuura

Takaho Nomura

Akira Suga

Toru Watanabe

Hideki Kubota

Keizo Sugasawa

Kazuhiko Take

Kenichi Kawaguchi

Eiji Kawaminami

Kazuhiro Ikegai

Kazuyuki Sakamoto

Hiroyoshi Yamada

Shunichiro Matsumoto

Shunichiro Hachiya

Yuta Fukuda

Daisuke Kaga

Tomoaki Abe

Taisuke Takahashi

Takatoshi Kanayama

Yoh Terada

Yutaka Kondoh

Kazuyuki Kuramoto

Eisuke Nozawa

Tatsuhisa Takahashi

Makoto Oku

Tatsuya Zenkoh

Masanao Sanagi

Masayuki Tanahashi

Shinobu Akuzawa

Hidetaka Kaku

Ryotaro Ibuka

Makoto Takeuchi

Takashi Kamikubo

Noriyuki Kawano

Kenji Negoro

Akio Kamikawa

Wataru Hamaguchi

Issei Tsukamoto

Hironori Harada

Susumu Watanuki

Tomofumi Takuwa

Kousei Yoshihara

Masahiro Iwata

Ikumi Kuriwaki

Michihito Kageyama

Jeffrey Ciavarri

Junko Maeda

Yumi Yamashita

Miki Kobayashi

Kiyoshi Yahiro

Takaho Matsuzawa

Hana Mukai

Atsushi Ukai

Kai Kitamura

Kenichi Kakefuda

[Problem] A compound which is useful as a STING inhibitor is provided. [Means for Solution] The present inventors have found aryl alkynamide derivatives having an inhibitory action on STING. The aryl alkynamide derivatives of the present invention have an inhibitory action on STING and can be used as an agent for treating an autoimmune disease, a neurodegenerative disease, a type I interferonopathy and/or other STING-mediated disease.

Aryl alkynamide derivatives

Substituted imidazo[1,5-a]quinoxalin-4-one compounds of formula (I) described herein exhibit PDE9-inhibitory action and is useful as an active ingredient for an agent for treating and/or preventing storage dysfunction, voiding dysfunction, and bladder/urethral diseases, and the like.

Substituted imidazo[1,5-A]quinoxalin-4-ones are useful for preventing or treating storage dysfunction, voiding dysfunction and bladder/urethral diseases

The present inventors have investigated a compound which has a PDE9-inhibiting action and is useful as an active ingredient for an agent for treating and/or preventing storage dysfunction, voiding dysfunction, bladder/urethral diseases, and the like, and thus, have found that a pyrazoloquinoline compound has a PDE9-inhibiting action, thereby completing the present invention.

Pyrazoloquinoline compound

A substituted amide compound is useful as an active ingredient of a pharmaceutical composition, in particular a pharmaceutical composition for treating diseases caused by lysophosphatidic acid (LPA). The compound is of a formula:  In this formula, A is an optionally substituted aryl, etc.; B is an optionally substituted 5-membered aromatic hetero ring group; X is a single bond or &#x2014;(CRR)&#x2014;; n is 1, 2, 3, or 4; Rand Rare hydrogen, etc.; Yto Yare each CRor N; each Ris hydrogen, etc.; Rand Rare hydrogen, etc.; m is 1, 2, or 3; Ris hydrogen, etc.; and Ris an optically substituted lower alkyl, etc.

Substituted amide compound

Substituted imidazo[1,5-a]quinoxalin-4-ones are useful as phosphodiesterase 9 inhibitors.

Substituted imidazo[1,5-a]quinoxalin-4-ones as phosphodiesterase 9 inhibitors

A substituted amide compound is useful as an active ingredient of a pharmaceutical composition, in particular a pharmaceutical composition for treating diseases caused by lysophosphatidic acid (LPA). The compound is of a formula: In this formula, A is an optionally substituted aryl, etc.; B is an optionally substituted 5-membered aromatic hetero ring group; X is a single bond or &#x2014;(CRR)&#x2014;; n is 1, 2, 3, or 4; Rand Rare hydrogen, etc.; Yto Yare each CRor N; each Ris hydrogen, etc.; Rand Rare hydrogen, etc.; m is 1, 2, or 3; Ris hydrogen, etc.; and Ris an optionally substituted lower alkyl, etc.

[Problems] A compound, which is useful as an active ingredient of a pharmaceutical composition, for example, a pharmaceutical composition for treating chronic renal failure and/or diabetic nephropathy, is provided. [Solving Means] The present inventors have conducted extensive studies on a compound having an EP4 receptor antagonistic activity, and confirmed that the amide compound of the present invention has an EP4 receptor antagonistic activity, thereby completing the present invention. The amide compound of the present invention has an EP4 receptor antagonistic activity, and can be used as an active ingredient of a pharmaceutical composition for preventing and/or treating various EP4-related diseases, for example, chronic renal failure and/or diabetic nephropathy, and the like.

Amide compound

Substituted imidazo[1,5-a]quinoxalin-4(5H)-ones are useful as PDE9 inhibitors.

Substituted imidazo[1,5-a]quinoxalin-4(5H)-ones as PDE9 inhibitors

[Object] To provide a therapeutic and/or prophylactic agent for urinary frequency, urinary urgency, and urinary incontinence associated with various lower urinary tract diseases including overactive bladder, various lower urinary tract diseases accompanied by lower urinary tract pain, such as interstitial cystitis, chronic prostatitis, and the like, and various diseases accompanied by pain, based on an excellent trkA receptor inhibitory action. [Means for Solution] A novel azolecarboxamide compound in which a thiazole ring or an oxazole ring is bonded to a benzene ring, a pyridine ring, a pyridazine ring, a thiophene ring, a pyrazole ring or a pyrrole ring through carboxamide, or a salt thereof is confirmed to have a potent trkA receptor inhibitory activity, and found to be capable of being used as a therapeutic and/or prophylactic agent which is excellent in efficacy and safety for urinary frequency, urinary urgency, and urinary incontinence associated with various lower urinary tract diseases including overactive bladder, various lower urinary tract diseases accompanied by lower urinary tract pain, such as interstitial cystitis, chronic prostatitis, and the like, and various diseases accompanied by pain, thereby completing the present invention.

Azolecarboxamide compound or salt thereof

[Problem] To provide a compound which may be used for the prevention and/or treatment of diseases in which 5-HTreceptor and 5-HTreceptor are concerned, particularly for the treatment of irritable bowel syndrome (IBS). [Means for Resolution] It was found that a pyrrole derivative characterized by the possession of a guanidinocarbonyl group or amido group as a substituent group at the 3-position, or a pharmaceutically acceptable salt thereof, has a strong antagonism for both of the 5-HTreceptor and 5-HTreceptor. In addition, the compound of the present invention having the antagonistic activity for both of the receptors showed a good pharmacological action in comparison with the case in which an antagonist selective for either one of the receptors was used alone. Based on the above, the compound of the present invention is useful for the prevention and/or treatment of diseases in which 5-HTreceptor and 5-HTreceptor are concerned, particularly for the treatment of irritable bowel syndrome (IBS).

Pyrrole derivative or salt thereof

Provided is an agent for treating or preventing urinary frequency, urinary urgency and urinary, incontinence which are associated with overactive bladder, a lower urinary tract disease such as interstitial cystitis and chronic prostatitis accompanied by lower urinary tract pain, and various diseases accompanied by pain. A novel azolecarboxamide derivative in which an azole ring such as thioazole or oxazole is bonded to a benzene ring, pyridine ring or pyrimidine ring through carboxamide was confirmed to have a potent trkA receptor-inhibitory activity and found to be an agent for treating or preventing lower urinary tract disease and various diseases accompanied by pain, which is excellent in efficacy and safety, and thus the present invention was accomplished.

Azolecarboxamide derivative

To provide a compound which can be used for treating diseases in which a calcium sensing receptor (CaSR) participates, particularly hyperparathyroidism. It was found that a novel piperidine derivative which is characterized in that one of a 3-position and a 4-position is substituted with an aminomethyl group substituted with an arylalkyl group or the like and the other position is substituted with aryl, heteroaryl or the like, or a salt thereof, has an excellent CaSR agonistic regulatory action, and also has excellent selectivity with a CYP2D6 inhibitory action having a possibility of causing drug interaction. Based on the above, this novel piperidine derivative is useful as a therapeutic agent for diseases in which CaSR participates (hyperparathyroidism, renal osteodystrophy, hypercalcemia, and the like).

Piperidine derivative or salt thereof

Provided is a compound which is useful as a therapeutic agent for chronic renal insufficiency and a therapeutic agent for diabetic nephropathy. The present inventors have made extensive studies on an ornithine derivative having an antagonistic action against an EP4 receptor, and as a result, they have found that by introducing cycloalkanediyl at a C terminal of the ornithine part of the compound of the present invention, the physicochemical properties such as solubility, and the like can be improved, thereby giving further preferred properties as a pharmaceutical. Therefore, they have completed the present invention. The compound of the present invention exhibits a good antagonistic action against an EP4 receptor, and thus, it is useful as a therapeutic agent for chronic renal insufficiency and diabetic nephropathy.

Ornithine derivative

It was found that a compound according to the following formula: or a pharmaceutically acceptable salt thereof, has a strong antagonism for both the 5-HTand 5-HTreceptors. In addition, the compound shows good pharmacological action as compared to antagonists selective for only one of these receptors. Based on the above, the compound of the present invention is useful for the prevention and/or treatment of diseases in which 5-HTreceptor and 5-HTreceptor are concerned, particularly for the treatment of irritable bowel syndrome (IBS).

Amide derivative or salt thereof

[Problem] To provide a compound which may be used in treating diseases in which a calcium sensing receptor (CaSR) is concerned, particularly hyperparathyroidism. [Means for Resolution] It was found that novel pyrrolidine derivatives which are characterized by the possession of aminomethyl group substituted with arylalkyl group or the like, or salts thereof, have excellent CaSR agonistic regulatory activity and also have excellent selectivity with CYP2D6 inhibitory activity having a possibility of causing drug interaction. Based on the above, these novel pyrrolidine derivatives are useful as therapeutic agents for treating diseases in which CaSR is concerned (hyperparathyroidism, renal osteodystrophy, hypercalcemia and the like).

Pyrrolidine derivative or salt thereof

Growing community of inventors

Tokyo, Japan

Ryushi Seo