公开(公告)号：US07683076B2

公开(公告)日：2010-03-23

申请号：US10578413

申请日：2004-10-26

申请人： Axel Bouchon ,  Nicole Diedrichs ,  Achim Hermann ,  Klemens Lustig ,  Heinrich Meier ,  Josef Pernerstorfer ,  Elke Reiβmüller ,  Muneto Mogi ,  Hiroshi Fujishima ,  Masaomi Tajimi ,  Noriyuki Yamamoto

发明人： Axel Bouchon ,  Nicole Diedrichs ,  Achim Hermann ,  Klemens Lustig ,  Heinrich Meier ,  Josef Pernerstorfer ,  Elke Reiβmüller ,  Muneto Mogi ,  Hiroshi Fujishima ,  Masaomi Tajimi ,  Noriyuki Yamamoto

IPC分类号： C07D215/38 ,  A61K31/47

CPC分类号： C07D215/38

摘要： This invention relates to tetrahydro-quinolinylurea derivatives and salts thereof which are useful as active ingredients of pharmaceutical preparations. The tetrahydro-quinolinylurea derivative of the present invention has vanilloid receptor (VR1) antagonistic activity, and can be used for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urological diseases or disorders, such as detrusor overactivity (overactive bladder), urinary incontinence, neurogenic detrusor overactivity (detrusor hyperflexia), idiopathic detrusor overactivity (detrusor instability), benign prostatic hyperplasia, and lower urinary tract symptoms; chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, and inflammatory disorders such as asthma and chronic obstructive pulmonary (or airways) disease (COPD).

摘要翻译： 本发明涉及可用作药物制剂活性成分的四氢 - 喹啉基脲衍生物及其盐。 本发明的四氢 - 喹啉基脲衍生物具有香草素受体（VR1）拮抗活性，可用于预防和治疗与VR1活性有关的疾病，特别是用于治疗泌尿系统疾病或障碍，例如逼尿肌过度活动 膀胱过度活动），尿失禁，神经源性逼尿肌过度活动（逼尿肌hyperflexia），特发性逼尿肌过度活动（逼尿肌不稳定），良性前列腺增生和下尿路症状; 慢性疼痛，神经性疼痛，术后疼痛，类风湿性关节炎疼痛，神经痛，神经病，痛觉，神经损伤，局部缺血，神经变性，中风和炎性疾病如哮喘和慢性阻塞性肺（或气道）疾病（COPD）。

公开(公告)号：US07615557B2

公开(公告)日：2009-11-10

申请号：US10574122

申请日：2004-09-22

申请人： Axel Bouchon ,  Nicole Diedrichs ,  Achim Hermann ,  Klemens Lustig ,  Heinrich Meier ,  Josef Pernerstorfer ,  Elke Reissmuller ,  Jean De Vry ,  Muneto Mogi ,  Klaus Urbahns ,  Takeshi Yura ,  Hiroshi Fujishima ,  Masaomi Tajimi ,  Noriyuki Yamamoto ,  Yasuhiro Tsukimi ,  Hiroaki Yuasa ,  Jang Gupta ,  Fumihiko Hayashi

发明人： Axel Bouchon ,  Nicole Diedrichs ,  Achim Hermann ,  Klemens Lustig ,  Heinrich Meier ,  Josef Pernerstorfer ,  Elke Reissmuller ,  Jean De Vry ,  Muneto Mogi ,  Klaus Urbahns ,  Takeshi Yura ,  Hiroshi Fujishima ,  Masaomi Tajimi ,  Noriyuki Yamamoto ,  Yasuhiro Tsukimi ,  Hiroaki Yuasa ,  Jang Gupta ,  Fumihiko Hayashi

IPC分类号： A01N43/40 ,  A61K31/445 ,  A61K31/4965 ,  C07D295/00 ,  C07D241/04

CPC分类号： C07D295/215 ,  C07D211/62 ,  C07D401/04

摘要： This invention relates to a hydroxy-tetrahydro-naphthalene or an urea derivative formula (I) and salts thereof which are useful as active ingredients of pharmaceutical preparations, wherein A represents formula (II) or (III) wherein # represents the connection position to the molecule and Q1a, Q2a, Q3a and Q4a are defined, and E represents formula (IV) or (V) wherein # represents the connection position to the molecule and Q1b, Q2b, Q3b, Q4b, Q5b, R1b, na, ma, Xa and Ra are defined.

摘要翻译： 本发明涉及用作药物制剂活性成分的羟基 - 四氢 - 萘或脲衍生物式（I）及其盐，其中A表示式（II）或（III），其中＃表示与 分子和Q1a，Q2a，Q3a和Q4a，E表示式（IV）或（V），其中＃表示与分子的连接位置，Q1b，Q2b，Q3b，Q4b，Q5b，R1b，na，ma，Xa 和Ra。

公开(公告)号：US20100137361A1

公开(公告)日：2010-06-03

申请号：US12700417

申请日：2010-02-04

申请人： Axel BOUCHON ,  Nicole Diedrichs ,  Achim Hermann ,  Klemens Lustig ,  Heinrich Meier ,  Josef Pernerstorfer ,  Elke Reissmüller ,  Muneto Mogi ,  Hiroshi Fujishima ,  Masaomi Tajimi ,  Noriyuki Yamamoto

发明人： Axel BOUCHON ,  Nicole Diedrichs ,  Achim Hermann ,  Klemens Lustig ,  Heinrich Meier ,  Josef Pernerstorfer ,  Elke Reissmüller ,  Muneto Mogi ,  Hiroshi Fujishima ,  Masaomi Tajimi ,  Noriyuki Yamamoto

IPC分类号： A61K31/47 ,  A61P11/06 ,  A61P13/02

CPC分类号： C07D215/38

摘要： This invention relates to tetrahydro-quinolinylurea derivatives and salts thereof which are useful as active ingredients of pharmaceutical preparations.The tetrahydro-quinolinylurea derivative of the present invention has vanilloid receptor (VR1) antagonistic activity, and can be used for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urological diseases or disorders, such as detrusor overactivity (overactive bladder), urinary incontinence, neurogenic detrusor overactivity (detrusor hyperflexia), idiopathic detrusor overactivity (detrusor instability), benign prostatic hyperplasia, and lower urinary tract symptoms; chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, and inflammatory disorders such as asthma and chronic obstructive pulmonary (or airways) disease (COPD).

摘要翻译： 本发明涉及可用作药物制剂活性成分的四氢 - 喹啉基脲衍生物及其盐。 本发明的四氢 - 喹啉基脲衍生物具有香草素受体（VR1）拮抗活性，可用于预防和治疗与VR1活性有关的疾病，特别是用于治疗泌尿系统疾病或障碍，例如逼尿肌过度活动 膀胱过度活动），尿失禁，神经源性逼尿肌过度活动（逼尿肌hyperflexia），特发性逼尿肌过度活动（逼尿肌不稳定），良性前列腺增生和下尿路症状; 慢性疼痛，神经性疼痛，术后疼痛，类风湿性关节炎疼痛，神经痛，神经病，痛觉，神经损伤，局部缺血，神经变性，中风和炎性疾病如哮喘和慢性阻塞性肺（或气道）疾病（COPD）。

公开(公告)号：US20070167458A1

公开(公告)日：2007-07-19

申请号：US10574122

申请日：2004-09-22

申请人： Axel Bouchon ,  Nicole Diedrichs ,  Achim Hermann ,  Klemens Lustig ,  Heinrich Meier ,  Josef Pernerstorfer ,  Elke Reissmuller ,  Jean De Vry ,  Muneto Mogi ,  Klaus Urbahns ,  Takeshi Yura ,  Hiroshi Fujishima ,  Masaomi Tajimi ,  Noriyuki Yamamoto ,  Hiroaki Yuasa ,  Jang Gupta ,  Yasuhiro Tsukimi ,  Fumihiko Hayashi

发明人： Axel Bouchon ,  Nicole Diedrichs ,  Achim Hermann ,  Klemens Lustig ,  Heinrich Meier ,  Josef Pernerstorfer ,  Elke Reissmuller ,  Jean De Vry ,  Muneto Mogi ,  Klaus Urbahns ,  Takeshi Yura ,  Hiroshi Fujishima ,  Masaomi Tajimi ,  Noriyuki Yamamoto ,  Hiroaki Yuasa ,  Jang Gupta ,  Yasuhiro Tsukimi ,  Fumihiko Hayashi

IPC分类号： A61K31/495 ,  C07D211/40 ,  C07D241/04

CPC分类号： C07D295/215 ,  C07D211/62 ,  C07D401/04

摘要： This invention relates to a hydroxy-tetrahydro-naphthalene or an urea derivative formula (I) and salts thereof which are useful as active ingredients of pharmaceutical preparations, wherein A represents formula (II) or (III) wherein # represents the connection position to the molecule and Q1a, Q2a, Q3a and Q4a are defined, and E represents formula (IV) or (V) wherein # represents the connection position to the molecule and Q1b, Q2b, Q3b, Q4b, Q5b, R1b, na, ma, Xa and Ra are defined.

摘要翻译： 本发明涉及用作药物制剂活性成分的羟基 - 四氢 - 萘或脲衍生物式（I）及其盐，其中A表示式（II）或（III），其中＃表示与 分子和Q 1a，Q 2a，Q 3a和Q 4a定义，E表示式（IV ）或（V）其中＃表示与分子的连接位置和Q 1b，Q 2b，Q 3b，Q 4b α，α，α，α，α，α，α，α，α和R a a都被定义 。

公开(公告)号：US20070213363A1

公开(公告)日：2007-09-13

申请号：US10578413

申请日：2004-10-26

申请人： Axel Bouchon ,  Nicole Diedrichs ,  Achim Hermann ,  Klemens Lustig ,  Heinrich Meier ,  Josef Pernerstorfer ,  Elke Reissmuller ,  Mogi Muneto ,  Hiroshi Fujishima ,  Masaomi Tajimi ,  Noriyuki Yamamoto

发明人： Axel Bouchon ,  Nicole Diedrichs ,  Achim Hermann ,  Klemens Lustig ,  Heinrich Meier ,  Josef Pernerstorfer ,  Elke Reissmuller ,  Mogi Muneto ,  Hiroshi Fujishima ,  Masaomi Tajimi ,  Noriyuki Yamamoto

IPC分类号： A61K31/47 ,  C07D215/02

CPC分类号： C07D215/38

摘要： This invention relates to tetrahydro-quinolinylurea derivatives and salts thereof which are useful as active ingredi- ents of pharmaceutical preparations. The tetrahydro-quinolinylurea derivative of the present invention has vanilloid receptor (VR I) C antagonistic activity, and can be used for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for =the treatment of urological diseases or disorders, such as detrusor overactivity (overactive bladder), urinary incontinence, neurogenic detrusor oeractivity (detrusor hyperflexia), idiopathic detrusor overactivity (detrusor instability), benign prostatic hyperplasia, and lower urinary tract symptoms; chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, and inflammatory disorders such as asthma and chronic obstructive pul- monary (or airways) disease (COPD).

摘要翻译： 本发明涉及四氢喹啉基脲衍生物及其盐，其可用作药物制剂的活性成分。 本发明的四氢 - 喹啉基脲衍生物具有香草素受体（VR I）C拮抗活性，可用于预防和治疗与VR1活性相关的疾病，特别是用于治疗泌尿系统疾病或病症，例如 作为逼尿肌过度活动（膀胱过度活动），尿失禁，神经源性逼尿肌过敏反应（逼尿肌hyperflexia），特发性逼尿肌过度活动（逼尿肌不稳定），良性前列腺增生和下尿路症状; 慢性疼痛，神经性疼痛，术后疼痛，类风湿性关节炎疼痛，神经痛，神经病，痛觉，神经损伤，局部缺血，神经变性，中风和炎性疾病如哮喘和慢性阻塞性肺病（或气道）疾病（COPD）。

公开(公告)号：US20080045546A1

公开(公告)日：2008-02-21

申请号：US10575027

申请日：2004-10-02

申请人： Axel Bouchon ,  Nicole Diedrichs ,  Achim Hermann ,  Klemens Lustig ,  Heinrich Meier ,  Josef Pemerstorfer ,  Elke Reissmuller ,  Muneto Mogi ,  Takeshi Yura ,  Hiroshi Fujishima ,  Masanori Seki ,  Yuji Koriyama ,  Kayo Yasoshima ,  Keiko Misawa ,  Masaomi Tajimi ,  Noriyuki Yammoto ,  Klaus Urbahns ,  Fumihiko Hayashi ,  Yasuhiro Tsukimi ,  Jang Gupta

发明人： Axel Bouchon ,  Nicole Diedrichs ,  Achim Hermann ,  Klemens Lustig ,  Heinrich Meier ,  Josef Pemerstorfer ,  Elke Reissmuller ,  Muneto Mogi ,  Takeshi Yura ,  Hiroshi Fujishima ,  Masanori Seki ,  Yuji Koriyama ,  Kayo Yasoshima ,  Keiko Misawa ,  Masaomi Tajimi ,  Noriyuki Yammoto ,  Klaus Urbahns ,  Fumihiko Hayashi ,  Yasuhiro Tsukimi ,  Jang Gupta

IPC分类号： A61K31/519 ,  A61K31/44 ,  C07D211/68 ,  C07D213/06

CPC分类号： C07C275/32 ,  A61K31/167 ,  A61K31/17 ,  A61K31/357 ,  A61K31/42 ,  A61K31/433 ,  A61K31/4406 ,  A61K31/4409 ,  A61K31/4412 ,  A61K31/455 ,  A61K31/4706 ,  A61K31/472 ,  A61K31/517 ,  A61K47/54 ,  C07C233/29 ,  C07C233/75 ,  C07C235/24 ,  C07C235/38 ,  C07C235/56 ,  C07C235/64 ,  C07C237/04 ,  C07C275/30 ,  C07C275/38 ,  C07C2602/08 ,  C07C2602/10 ,  C07D209/18 ,  C07D213/40 ,  C07D213/56 ,  C07D213/89 ,  C07D215/46 ,  C07D217/22 ,  C07D239/94 ,  C07D261/14 ,  C07D285/06 ,  C07D317/66

摘要： This invention relates to tetrahydro-naphthalene and urea derivatives and salts thereof which are useful as active ingredients of pharmaceutical preparations. The tetrahydro-naphthalene and urea derivatives of the present invention have vanilloid receptor (VR1) antagonistic activity, and can be used for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urological diseases or disorders, such as detrusor overactivity (overactive bladder), urinary incontinence, neurogenic detrusor overactivity (detrusor hyperflexia), idiopathic detrusor overactivity (detrusor instability), benign prostatic hyperplasia, and lower urinary tract symptoms; chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, and inflammatory disorders such as asthma and chronic obstructive pulmonary (or airways) disease (COPD).

摘要翻译： 本发明涉及四氢萘和脲衍生物及其盐，其可用作药物制剂的活性成分。 本发明的四氢萘和脲衍生物具有香草素受体（VR1）拮抗活性，可用于预防和治疗与VR1活性相关的疾病，特别是用于治疗泌尿系统疾病或病症，如逼尿肌 过度活动（膀胱过度活动），尿失禁，神经源性逼尿肌过度活动（逼尿肌hyperflexia），特发性逼尿肌过度活动（逼尿肌不稳定），良性前列腺增生和下尿路症状; 慢性疼痛，神经性疼痛，术后疼痛，类风湿性关节炎疼痛，神经痛，神经病，痛觉，神经损伤，局部缺血，神经变性，中风和炎性疾病如哮喘和慢性阻塞性肺（或气道）疾病（COPD）。