公开(公告)号：US08076348B2

公开(公告)日：2011-12-13

申请号：US11997956

申请日：2006-08-07

申请人： Hiroyoshi Yamada ,  Hirotsune Itahana ,  Ayako Moritomo ,  Takaho Matsuzawa ,  Eisuke Nozawa ,  Shinobu Akuzawa ,  Koichiro Harada

发明人： Hiroyoshi Yamada ,  Hirotsune Itahana ,  Ayako Moritomo ,  Takaho Matsuzawa ,  Eisuke Nozawa ,  Shinobu Akuzawa ,  Koichiro Harada

IPC分类号： A61K31/435

CPC分类号： C07D209/88 ,  C07D221/16 ,  C07D265/38 ,  C07D333/78 ,  C07D401/04 ,  C07D403/04 ,  C07D405/04 ,  C07D405/06 ,  C07D413/04 ,  C07D413/06 ,  C07D471/04 ,  C07D491/10 ,  C07D495/10

摘要： [Problem] To provide a compound which can be used in the prevention and/or treatment of diseases in which 5-HT2B receptor and 5-HT7 receptor are concerned, particularly in the treatment of irritable bowel syndrome (IBS) and/or prevention of migraine.[Means for Resolution] It was found that an acylguanidine derivative having a tricyclic structure or a pharmaceutically acceptable salt thereof has a strong antagonism to 5-HT2B receptor and 5-HT7 receptor. In addition, the compound of the present invention having antagonism to both of the receptors showed superior pharmacological action in comparison with the case of the single use of an antagonist selective for either one of the receptors. Based on the above, the compound of the present invention is useful in preventing and/or treating diseases in which 5-HT2B receptor and 5-HT7 receptor are concerned, particularly in treating irritable bowel syndrome (IBS) and/or preventing migraine.

摘要翻译： [问题]提供可用于预防和/或治疗5-HT 2B受体和5-HT7受体的疾病的化合物，特别是用于治疗肠易激综合征（IBS）和/或预防 偏头痛 [解决方法]发现具有三环结构的酰基胍衍生物或其药学上可接受的盐具有对5-HT 2B受体和5-HT7受体的强拮抗作用。 此外，与单次使用对任一受体选择性拮抗剂的情况相比，本发明对两种受体具有拮抗作用的化合物显示出优异的药理作用。 基于上述，本发明的化合物可用于预防和/或治疗涉及5-HT 2B受体和5-HT7受体的疾病，特别是用于治疗肠易激综合征（IBS）和/或预防偏头痛。

公开(公告)号：US20100168096A1

公开(公告)日：2010-07-01

申请号：US11997956

申请日：2006-08-07

申请人： Hiroyoshi Yamada ,  Hirotsune Itahana ,  Ayako Moritomo ,  Takaho Matsuzawa ,  Eisuke Nozawa ,  Shinobu Akuzawa ,  Koichiro Harada

发明人： Hiroyoshi Yamada ,  Hirotsune Itahana ,  Ayako Moritomo ,  Takaho Matsuzawa ,  Eisuke Nozawa ,  Shinobu Akuzawa ,  Koichiro Harada

IPC分类号： A61K31/5377 ,  C07C69/76 ,  C07D209/56 ,  C07D401/02 ,  C07D413/02 ,  C07D221/16 ,  C07D211/00 ,  A61K31/24 ,  A61K31/403 ,  A61K31/4439 ,  A61K31/4355 ,  A61P1/06 ,  A61P1/12

CPC分类号： C07D209/88 ,  C07D221/16 ,  C07D265/38 ,  C07D333/78 ,  C07D401/04 ,  C07D403/04 ,  C07D405/04 ,  C07D405/06 ,  C07D413/04 ,  C07D413/06 ,  C07D471/04 ,  C07D491/10 ,  C07D495/10

摘要： [Problem] To provide a compound which can be used in the prevention and/or treatment of diseases in which 5-HT2B receptor and 5-HT7 receptor are concerned, particularly in the treatment of irritable bowel syndrome (IBS) and/or prevention of migraine.[Means for Resolution] It was found that an acylguanidine derivative having a tricyclic structure or a pharmaceutically acceptable salt thereof has a strong antagonism to 5-HT2B receptor and 5-HT7 receptor. In addition, the compound of the present invention having antagonism to both of the receptors showed superior pharmacological action in comparison with the case of the single use of an antagonist selective for either one of the receptors. Based on the above, the compound of the present invention is useful in preventing and/or treating diseases in which 5-HT2B receptor and 5-HT7 receptor are concerned, particularly in treating irritable bowel syndrome (IBS) and/or preventing migraine.

摘要翻译： [问题]提供可用于预防和/或治疗5-HT 2B受体和5-HT7受体的疾病的化合物，特别是用于治疗肠易激综合征（IBS）和/或预防 偏头痛 [解决方法]发现具有三环结构的酰基胍衍生物或其药学上可接受的盐具有对5-HT 2B受体和5-HT7受体的强拮抗作用。 此外，与单次使用对任一受体选择性拮抗剂的情况相比，本发明对两种受体具有拮抗作用的化合物显示出优异的药理作用。 基于上述，本发明的化合物可用于预防和/或治疗涉及5-HT 2B受体和5-HT7受体的疾病，特别是用于治疗肠易激综合征（IBS）和/或预防偏头痛。

公开(公告)号：US20080200551A1

公开(公告)日：2008-08-21

申请号：US10568684

申请日：2005-02-17

申请人： Hiroyoshi Yamada ,  Hirotsune Itahana ,  Ayako Moritomo ,  Takaho Matsuzawa ,  Koichiro Harada ,  Jiro Fujiyasu ,  Yuji Koga ,  Makoto Oku ,  Toshio Okazaki ,  Shinobu Akuzawa ,  Toshihiro Watanabe

发明人： Hiroyoshi Yamada ,  Hirotsune Itahana ,  Ayako Moritomo ,  Takaho Matsuzawa ,  Koichiro Harada ,  Jiro Fujiyasu ,  Yuji Koga ,  Makoto Oku ,  Toshio Okazaki ,  Shinobu Akuzawa ,  Toshihiro Watanabe

IPC分类号： A61K31/166 ,  C07C233/78 ,  A61P25/06

CPC分类号： C07D311/96 ,  A61K31/166 ,  A61K31/343 ,  A61K31/351 ,  A61K31/352 ,  A61K31/357 ,  A61K31/385 ,  A61K31/41 ,  A61K31/4168 ,  A61K31/4196 ,  A61K31/421 ,  A61K31/426 ,  A61K31/438 ,  C07C279/22 ,  C07D207/20 ,  C07D209/54 ,  C07D209/96 ,  C07D211/70 ,  C07D221/20 ,  C07D233/50 ,  C07D249/14 ,  C07D257/06 ,  C07D263/28 ,  C07D277/18 ,  C07D303/06 ,  C07D305/14 ,  C07D307/94 ,  C07D309/06 ,  C07D309/20 ,  C07D317/12 ,  C07D319/14 ,  C07D327/04 ,  C07D335/04 ,  C07D339/06

摘要： This invention relates to a novel fluorene derivative having a characteristic structure in which guanidino group or the like functional group is linked to the fluorene structure via carbonyl group, or a salt thereof.The compound of the invention has an advantage in that it has high affinity for serotonin receptor subtypes, particularly for 5-HT2B receptor and 5-HT7 receptor, and shows excellent pharmacological effects in comparison with the conventional compounds which have only one of the antagonistic activities of 5-HT2B receptor and 5-HT7 receptor, this is useful as a prophylactic antimigraine agent having high safety and excellent effect.

摘要翻译： 本发明涉及具有胍基等官能团通过羰基与芴结构连接的特征结构的新型芴衍生物或其盐。 本发明的化合物具有的优点在于其对5-羟色胺受体亚型具有高亲和力，特别是对于5-HT 2B受体和5-HT 7受体，并且显示出优异的 与仅具有5-HT 2B受体和5-HT 7受体的拮抗活性的常规化合物相比，药理作用可用作预防性抗偏头痛 药剂安全性高，效果好。

公开(公告)号：US20090286766A1

公开(公告)日：2009-11-19

申请号：US12297275

申请日：2007-04-19

申请人： Keizo Sugasawa ,  Kenichi Kawaguchi ,  Takaho Matsuzawa ,  Ryushi Seo ,  Hironori Harada ,  Akira Suga ,  Tomoaki Abe ,  Hidenori Azami ,  Shunichiro Matsumoto ,  Takashi Shin ,  Masayuki Tanahashi ,  Toru Watanabe

发明人： Keizo Sugasawa ,  Kenichi Kawaguchi ,  Takaho Matsuzawa ,  Ryushi Seo ,  Hironori Harada ,  Akira Suga ,  Tomoaki Abe ,  Hidenori Azami ,  Shunichiro Matsumoto ,  Takashi Shin ,  Masayuki Tanahashi ,  Toru Watanabe

IPC分类号： A61K31/496 ,  C07D417/12 ,  C07D487/04 ,  C07D417/14 ,  C07D413/12 ,  C07D413/14 ,  A61K31/454 ,  A61K31/5377 ,  A61K31/551 ,  A61K31/55 ,  A61K31/541 ,  A61P13/00

CPC分类号： C07D277/56 ,  C07D263/34 ,  C07D263/48 ,  C07D413/04 ,  C07D413/12 ,  C07D413/14 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D471/10 ,  C07D487/08 ,  C07D491/08

摘要： 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.

摘要翻译： 本发明提供一种治疗或预​​防尿频，尿急，尿失禁，与膀胱过度活动，下尿路疾病如间质性膀胱炎和伴有下尿路疼痛的慢性前列腺炎以及伴有疼痛的各种疾病相关的尿失禁。 通过甲酰胺将唑环或吡唑环或吡啶环或吡啶环与吡唑或恶唑等唑类结合的新型偶氮甲酰胺衍生物被证实具有强的trkA受体抑制活性，被发现是用于治疗或预防较低 泌尿道疾病，伴有疼痛的各种疾病，其功效和安全性优异，从而完成了本发明。

公开(公告)号：US08163746B2

公开(公告)日：2012-04-24

申请号：US12297275

申请日：2007-04-19

申请人： Keizo Sugasawa ,  Kenichi Kawaguchi ,  Takaho Matsuzawa ,  Ryushi Seo ,  Hironori Harada ,  Akira Suga ,  Tomoaki Abe ,  Hidenori Azami ,  Shunichiro Matsumoto ,  Takashi Shin ,  Masayuki Tanahashi ,  Toru Watanabe

发明人： Keizo Sugasawa ,  Kenichi Kawaguchi ,  Takaho Matsuzawa ,  Ryushi Seo ,  Hironori Harada ,  Akira Suga ,  Tomoaki Abe ,  Hidenori Azami ,  Shunichiro Matsumoto ,  Takashi Shin ,  Masayuki Tanahashi ,  Toru Watanabe

IPC分类号： A61K31/5355 ,  A61K31/496 ,  A61K31/451 ,  A61K31/4535 ,  A61K31/426 ,  C07D413/14 ,  C07D211/32 ,  C07D211/46 ,  C07D277/24

CPC分类号： C07D277/56 ,  C07D263/34 ,  C07D263/48 ,  C07D413/04 ,  C07D413/12 ,  C07D413/14 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D471/10 ,  C07D487/08 ,  C07D491/08

摘要： 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.

摘要翻译： 提供治疗或预防与膀胱过度活动相关的尿频，尿急和尿失禁的药物，诸如间质性膀胱炎的下尿路疾病和伴有下尿路疼痛的慢性前列腺炎以及伴有疼痛的各种疾病。 通过甲酰胺将唑环或吡唑环或吡啶环或吡啶环与吡唑或恶唑等唑类结合的新型偶氮甲酰胺衍生物被证实具有强的trkA受体抑制活性，被发现是用于治疗或预防较低 泌尿道疾病，伴有疼痛的各种疾病，其功效和安全性优异，从而完成了本发明。