公开(公告)号：US09290511B2

公开(公告)日：2016-03-22

申请号：US14358722

申请日：2012-11-15

申请人： XENTION LIMITED

发明人： David Madge ,  Fiona Chan ,  Derek Edward John ,  Simon D. Edwards ,  Richard Blunt ,  Basil Hartzoulakis ,  Lindsay Brown

IPC分类号： C07D495/04 ,  A61K31/519 ,  A61P9/06 ,  C07D491/048

CPC分类号： C07D495/04 ,  A61K31/519 ,  C07D491/048

摘要： The present invention provides compounds of formula (I): (Formula (I); wherein A, R1, R2, R3I, V, X, and Z are defined herein, which are potassium channel inhibitors. The invention further provides pharmaceutical compositions comprising the compounds of formula (I) and their use in therapy, in particular in treatment of diseases or conditions that are mediated by Kir3.1 and/or Kir3.4 or any heteromultimers thereof, or that require inhibition of Kir3.1 and/or Kir3.4 or any heteromultimers thereof.

摘要翻译： 本发明提供式（I）化合物：（式（I））其中A，R 1，R 2，R 3，V，X和Z如本文所定义，其为钾通道抑制剂。 式（I）化合物及其在治疗中的用途，特别是在治疗由Kir3.1和/或Kir3.4或其任何异源多肽介导的疾病或病症或需要抑制Kir3.1和/或Kir3 .4或其任何异源多聚体。

公开(公告)号：US09073834B2

公开(公告)日：2015-07-07

申请号：US14174241

申请日：2014-02-06

申请人： Xention Limited

发明人： Mushtaq Mulla ,  Derek Edward John ,  Richard John Hamlyn ,  Sasha Louise Garrett ,  Basil Hartzoulakis ,  David Madge ,  John Ford

IPC分类号： C07D403/12 ,  C07D413/12 ,  C07D401/12 ,  C07C317/40 ,  C07C311/21 ,  C07C311/46 ,  C07D207/12 ,  C07D209/08 ,  C07D211/16 ,  C07D211/44 ,  C07D213/40 ,  C07D213/71 ,  C07D231/12 ,  C07D231/18 ,  C07D231/56 ,  C07D233/61 ,  C07D233/84 ,  C07D265/30 ,  C07D265/36 ,  C07D271/08 ,  C07D277/36 ,  C07D277/46 ,  C07D285/135 ,  C07D307/79 ,  C07D311/70 ,  C07D317/62 ,  C07D319/18 ,  C07C317/32 ,  C07D211/34 ,  C07D233/64 ,  C07D285/12

CPC分类号： C07C311/21 ,  C07C311/46 ,  C07C317/32 ,  C07C317/40 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07D207/12 ,  C07D209/08 ,  C07D211/16 ,  C07D211/34 ,  C07D211/44 ,  C07D213/36 ,  C07D213/40 ,  C07D213/71 ,  C07D231/12 ,  C07D231/18 ,  C07D231/56 ,  C07D233/61 ,  C07D233/64 ,  C07D233/84 ,  C07D265/30 ,  C07D265/36 ,  C07D271/08 ,  C07D277/28 ,  C07D277/36 ,  C07D277/46 ,  C07D285/12 ,  C07D285/135 ,  C07D307/79 ,  C07D311/70 ,  C07D317/62 ,  C07D319/18 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12

摘要： The present invention provides a compound of formula (I) or its salts or pharmaceutically acceptable derivatives thereof wherein X1, R1, R2, R3, R4, and R5 are defined as set forth in the specification. The compounds are useful as potassium ion channel inhibitors.

摘要翻译： 本发明提供式（I）化合物或其盐或其药学上可接受的衍生物，其中X1，R1，R2，R3，R4和R5如说明书所述定义。 该化合物可用作钾离子通道抑制剂。

公开(公告)号：US20140206703A1

公开(公告)日：2014-07-24

申请号：US14008776

申请日：2012-03-29

申请人： John Ford ,  Derek Edward John

发明人： John Ford ,  Derek Edward John

IPC分类号： C07D495/04

CPC分类号： C07D495/04

摘要： The present invention relates to thienopyrimidine compounds which are potassium channel inhibitors. Pharmaceutical compositions comprising the compounds and their use in the treatment of arrhythmia are also described.

摘要翻译： 本发明涉及作为钾通道抑制剂的噻吩并嘧啶化合物。 还描述了包含该化合物的药物组合物及其在治疗心律失常中的用途。

公开(公告)号：US07544716B2

公开(公告)日：2009-06-09

申请号：US10537217

申请日：2003-11-28

申请人： Masaomi Tajimi ,  Toshio Kokubo ,  Masahiro Shiroo ,  Yasuhiro Tsukimi ,  Takeshi Yura ,  Klaus Urbahns ,  Noriyuki Yamamoto ,  Muneto Mogi ,  Hiroshi Fujishima ,  Tsutomu Masuda ,  Nagahiro Yoshida ,  Toshiya Moriwaki

发明人： Masaomi Tajimi ,  Toshio Kokubo ,  Masahiro Shiroo ,  Yasuhiro Tsukimi ,  Takeshi Yura ,  Klaus Urbahns ,  Noriyuki Yamamoto ,  Muneto Mogi ,  Hiroshi Fujishima ,  Tsutomu Masuda ,  Nagahiro Yoshida ,  Toshiya Moriwaki

IPC分类号： A61K31/17

CPC分类号： C07C275/32 ,  C07C2602/10 ,  C07D207/27 ,  C07D211/22 ,  C07D211/46 ,  C07D211/62 ,  C07D295/135

摘要： This invention relates to tetrahydro-naphthalene derivatives of formula (I) in which the variable groups are as defined in the specification and claims, and tautomeric and stereoisomeric forms and salts thereof which are useful as active ingredients of pharmaceutical preparations. The tetrahydro-naphthalene derivatives of the present invention have an excellent activity as VR1 antagonists and are useful for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urinary incontinence, urge urinary incontinence, overactive bladder, chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, inflammatory disorders, asthma and COPD. The compounds, pharmaceutical compositions containing them, and methods of treatment using them are disclosed and claimed.

摘要翻译： 本发明涉及式（I）的四氢 - 萘衍生物，其中可变基团如说明书和权利要求中所定义，以及其可用作药物制剂活性成分的互变异构体和立体异构形式及其盐。 本发明的四氢 - 萘衍生物作为VR1拮抗剂具有优异的活性，可用于预防和治疗与VR1活性相关的疾病，特别是用于治疗尿失禁，敦促性尿失禁，膀胱过度活动症，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，炎症性疾病，哮喘和COPD。 公开并要求保护所述化合物，含有它们的药物组合物和使用它们的治疗方法。

公开(公告)号：US07381840B2

公开(公告)日：2008-06-03

申请号：US10537482

申请日：2003-11-28

申请人： Masaomi Tajimi ,  Toshio Kokubo ,  Masahiro Shiroo ,  Yasuhiro Tsukimi ,  Takeshi Yura ,  Klaus Urbahns ,  Noriyuki Yamamoto ,  Muneto Mogi ,  Hiroshi Fujishima ,  Tsutomu Masuda ,  Nagahiro Yoshida ,  Toshiya Moriwaki

发明人： Masaomi Tajimi ,  Toshio Kokubo ,  Masahiro Shiroo ,  Yasuhiro Tsukimi ,  Takeshi Yura ,  Klaus Urbahns ,  Noriyuki Yamamoto ,  Muneto Mogi ,  Hiroshi Fujishima ,  Tsutomu Masuda ,  Nagahiro Yoshida ,  Toshiya Moriwaki

IPC分类号： C07C273/00

CPC分类号： C07D295/088 ,  C07C233/29 ,  C07C233/75 ,  C07C235/42 ,  C07C237/40 ,  C07C275/32 ,  C07C275/38 ,  C07C275/40 ,  C07C275/42 ,  C07C317/32 ,  C07C323/44 ,  C07C2602/10 ,  C07D207/27 ,  C07D211/22 ,  C07D211/46 ,  C07D211/62 ,  C07D295/135

摘要： This invention relates to tetrahydro-naphthalene derivatives and salts thereof which are useful as active ingredients of pharmaceutical preparations. They have the general formula (I) in which R1 represents hydrogen or C1-6 alkyl, and X represents —N(H)Y1, —(H)—C1-6 alkyleneY1, biphenyl or C1-6 alkyl substituted by biphenyl, and the group Y1 is an optionally substituted biphenyl. The tetrahydro-naphthalene derivatives of the present invention have excellent activity as VR1 antagonists and are useful for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urinary incontinence, overactive bladder, urge urinary incontinence, chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, inflammatory disorders, asthma and COPD.

摘要翻译： 本发明涉及四氢萘衍生物及其盐，其可用作药物制剂的活性成分。 它们具有其中R 1表示氢或C 1-6烷基的通式（I），X表示-N（H）Y 1， ， - （H）-C 1-6亚烷基，由联苯取代的联苯基或C 1-6烷基，以及基团 Y 1是任选取代的联苯。 本发明的四氢 - 萘衍生物作为VR1拮抗剂具有优异的活性，可用于预防和治疗与VR1活性相关的疾病，特别是用于治疗尿失禁，膀胱过度活动症，急迫性尿失禁，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，炎性疾病，哮喘和COPD。

公开(公告)号：US20150259282A1

公开(公告)日：2015-09-17

申请号：US14724195

申请日：2015-05-28

申请人： Xention Limited

发明人： Mushtaq MULLA ,  Derek Edward JOHN ,  Richard John HAMLYN ,  Sasha Louise GARRETT ,  Basil HARTZOULAKIS ,  David MADGE ,  John FORD

IPC分类号： C07C311/21 ,  C07D213/36 ,  C07D277/28 ,  C07D231/12 ,  C07D285/12 ,  C07D231/56 ,  C07D233/61

CPC分类号： C07C311/21 ,  C07C311/46 ,  C07C317/32 ,  C07C317/40 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07D207/12 ,  C07D209/08 ,  C07D211/16 ,  C07D211/34 ,  C07D211/44 ,  C07D213/36 ,  C07D213/40 ,  C07D213/71 ,  C07D231/12 ,  C07D231/18 ,  C07D231/56 ,  C07D233/61 ,  C07D233/64 ,  C07D233/84 ,  C07D265/30 ,  C07D265/36 ,  C07D271/08 ,  C07D277/28 ,  C07D277/36 ,  C07D277/46 ,  C07D285/12 ,  C07D285/135 ,  C07D307/79 ,  C07D311/70 ,  C07D317/62 ,  C07D319/18 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12

摘要： The present invention provides a compound of formula (I) or its salts or pharmaceutically acceptable derivatives thereof wherein X1, R1, R2, R3, R4, and R5 are defined as set forth in the specification. The compounds are useful as potassium ion channel inhibitors.

摘要翻译： 本发明提供式（I）化合物或其盐或其药学上可接受的衍生物，其中X1，R1，R2，R3，R4和R5如说明书所述定义。 该化合物可用作钾离子通道抑制剂。

公开(公告)号：US08088826B2

公开(公告)日：2012-01-03

申请号：US12103396

申请日：2008-04-15

申请人： Masaomi Tajimi ,  Toshio Kokubo ,  Masahiro Shiroo ,  Yasuhiro Tsukimi ,  Takeshi Yura ,  Klaus Urbahns ,  Noriyuki Yamamoto ,  Muneto Mogi ,  Hiroshi Fujishima ,  Tsutomu Masuda ,  Nagahiro Yoshida ,  Toshiya Moriwaki

发明人： Masaomi Tajimi ,  Toshio Kokubo ,  Masahiro Shiroo ,  Yasuhiro Tsukimi ,  Takeshi Yura ,  Klaus Urbahns ,  Noriyuki Yamamoto ,  Muneto Mogi ,  Hiroshi Fujishima ,  Tsutomu Masuda ,  Nagahiro Yoshida ,  Toshiya Moriwaki

IPC分类号： A61K31/17

CPC分类号： C07D295/088 ,  C07C233/29 ,  C07C233/75 ,  C07C235/42 ,  C07C237/40 ,  C07C275/32 ,  C07C275/38 ,  C07C275/40 ,  C07C275/42 ,  C07C317/32 ,  C07C323/44 ,  C07C2602/10 ,  C07D207/27 ,  C07D211/22 ,  C07D211/46 ,  C07D211/62 ,  C07D295/135

摘要： This invention relates to tetrahydro-Naphthalene derivatives and salts thereof which are useful as an active ingredient of pharmaceutical preparations. The tethrahydro—Naphthalene derivatives of the present invention have excellent activity as VR1 antagonist and useful for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urinary incontinence, overactive bladder, urge urinary incontienence, chronic pain, neuropathic pain, post-operative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, inflammatory disorders, asthma and COPD.

摘要翻译： 本发明涉及四氢萘衍生物及其盐，其可用作药物制剂的活性成分。 本发明的四氢萘衍生物作为VR1拮抗剂具有优异的活性，可用于预防和治疗与VR1活性相关的疾病，特别是用于治疗尿失禁，膀胱过度活动症，敦促性尿失禁，慢性疼痛，神经性疼痛 ，手术后疼痛，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，炎症性疾病，哮喘和COPD。

公开(公告)号：US20110048939A1

公开(公告)日：2011-03-03

申请号：US12940564

申请日：2010-11-05

申请人： David Geraint Owen ,  Nicholas Gerard Byrne

发明人： David Geraint Owen ,  Nicholas Gerard Byrne

IPC分类号： G01N27/403

CPC分类号： G01N33/502 ,  B01L3/5025 ,  B01L2300/0829 ,  B01L2300/0851 ,  B01L2300/0893 ,  B01L2300/16 ,  G01N27/28 ,  G01N33/48728 ,  G01N33/5438 ,  G01N33/6872 ,  G01N2500/04 ,  G01N2500/10 ,  Y10T29/49826

摘要： The present invention relates to a structure comprising a biological membrane and a porous or perforated substrate, a biological membrane, a substrate, a high throughput screen, methods for production of the structure membrane and substrate, and a method for screening a large number of test compounds in a short period. More particularly it relates to a structure comprising a biological membrane adhered to a porous or perforated substrate, a biological membrane capable of adhering with high resistance seals to a substrate such as perforated glass and the ability to form sheets having predominantly an ion channel or transporter of interest, a high throughput screen for determining the effect of test compounds on ion channel or transporter activity, methods for manufacture of the structure, membrane and substrate, and a method for monitoring ion channel or transporter activity in a membrane.

摘要翻译： 本发明涉及一种包括生物膜和多孔或穿孔基底，生物膜，基底，高通量筛选，结构膜和基底的制备方法以及筛选大量试验的方法的结构 化合物在短时间内。 更具体地说，涉及一种结构，该结构包括附着于多孔或多孔基底的生物膜，能够将高电阻密封粘附到诸如多孔玻璃的基底上的生物膜，以及形成主要具有离子通道或转运体 兴趣，用于确定测试化合物对离子通道或转运蛋白活性的影响的高通量筛选，用于制造结构，膜和底物的方法，以及用于监测膜中的离子通道或转运蛋白活性的方法。

公开(公告)号：US07846389B2

公开(公告)日：2010-12-07

申请号：US11133808

申请日：2005-05-20

申请人： David Geraint Owen ,  Nicholas Gerard Byrne

发明人： David Geraint Owen ,  Nicholas Gerard Byrne

IPC分类号： G01N33/567 ,  G01N27/00 ,  G01N27/07 ,  G01N27/08 ,  B01L3/00 ,  B01L9/00

CPC分类号： G01N33/502 ,  B01L3/5025 ,  B01L2300/0829 ,  B01L2300/0851 ,  B01L2300/0893 ,  B01L2300/16 ,  G01N27/28 ,  G01N33/48728 ,  G01N33/5438 ,  G01N33/6872 ,  G01N2500/04 ,  G01N2500/10 ,  Y10T29/49826

摘要： The present invention relates to a structure comprising a biological membrane and a porous or perforated substrate, a biological membrane, a substrate, a high throughput screen, methods for production of the structure membrane and substrate, and a method for screening a large number of test compounds in a short period. More particularly it relates to a structure comprising a biological membrane adhered to a porous or perforated substrate, a biological membrane capable of adhering with high resistance seals to a substrate such as perforated glass and the ability to form sheets having predominantly an ion channel or transporter of interest, a high throughput screen for determining the effect of test compounds on inn channel or transporter activity, methods for manufacture of the structure, membrane and substrate, and a method for monitoring ion channel or transporter activity in a membrane.

摘要翻译： 本发明涉及一种包括生物膜和多孔或穿孔基底，生物膜，基底，高通量筛选，结构膜和基底的制备方法以及筛选大量试验的方法的结构 化合物在短时间内。 更具体地说，涉及一种结构，该结构包括附着于多孔或多孔基底的生物膜，能够将高电阻密封粘附到诸如多孔玻璃的基底上的生物膜，以及形成主要具有离子通道或转运体 感兴趣的，用于确定测试化合物对宿主通道或转运蛋白活性的影响的高通量筛选，用于制造结构，膜和底物的方法以及用于监测膜中的离子通道或转运蛋白活性的方法。

公开(公告)号：US20100087428A1

公开(公告)日：2010-04-08

申请号：US12550860

申请日：2009-08-31

申请人： Mushtaq Mulla ,  Derek Edward John ,  Richard John Hamlyn ,  Sasha Louise Garrett ,  Basil Hartzoulakis ,  David Madge ,  John Ford

发明人： Mushtaq Mulla ,  Derek Edward John ,  Richard John Hamlyn ,  Sasha Louise Garrett ,  Basil Hartzoulakis ,  David Madge ,  John Ford

IPC分类号： A61K31/415 ,  C07D231/04 ,  C07D233/66 ,  C07D213/62 ,  C07D265/36 ,  A61K31/4164 ,  A61K31/44 ,  A61K31/538 ,  A61P19/02 ,  A61P17/06 ,  A61P37/00

CPC分类号： C07C311/21 ,  C07C311/46 ,  C07C317/32 ,  C07C317/40 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07D207/12 ,  C07D209/08 ,  C07D211/16 ,  C07D211/34 ,  C07D211/44 ,  C07D213/36 ,  C07D213/40 ,  C07D213/71 ,  C07D231/12 ,  C07D231/18 ,  C07D231/56 ,  C07D233/61 ,  C07D233/64 ,  C07D233/84 ,  C07D265/30 ,  C07D265/36 ,  C07D271/08 ,  C07D277/28 ,  C07D277/36 ,  C07D277/46 ,  C07D285/12 ,  C07D285/135 ,  C07D307/79 ,  C07D311/70 ,  C07D317/62 ,  C07D319/18 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12

摘要： The present invention provides a compound of formula (I) or its salts or pharmaceutically acceptable derivatives thereof wherein; X1 is selected from a group consisting of CH2, C(═O), C(═NH), NC(═O), R1 is selected from the group consisting of optionally substituted arylalkyl, and optionally substituted heteroarylalkyl R2 is selected from the group consisting of optionally substituted alkyl, optionally substituted aryl or heteroaryl or NR24R25 R3 is selected from the group consisting of hydrogen, halogen, hydroxyl, alkoxy, aryloxy, optionally substituted alkyl, optionally substituted amino, optionally substituted amino sulfonyl or nitrile; R4 is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted acyl, optionally substituted sulfonyl, optionally substituted sulfamoyl, optionally substituted aryl, optionally substituted arylalkyl, and optionally substituted heteroaryl R5 may be hydrogen, an optionally substituted alkyl, preferably CH3 or, NR4R5 may form an optionally substituted saturated or partially saturated 4-7 membered ring with the general formula (II). Wherein; X2 is C(═O), CH2, CH(R6) or C(R6)(R6), X3 is CH2, CH(R7), C(R7)(R7), NH, N(R8), O or S Each R6 independently represents optionally substituted amino, optionally substituted amino carbonyl, hydroxyl, optionally substituted acyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalky, optionally substituted aryl or optionally substituted heteroaryl; Each R7 independently represents optionally substituted amino, optionally substituted amino carbonyl, hydroxyl, optionally substituted acyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalky, optionally substituted aryl or optionally substituted hetero aryl R8 is optionally substituted acyl, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl; R24 and R25 are the same or different and each represents hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl, n=1 or 2 m=1, 2 or 3 With the proviso that when X1 is C═O and R5 is H then R4 is not: Or Or Where R4a, R5a and R6a are each independently H, C1-6alkyl, aryl, heteroaryl, cycloalkyl, or aryl-C1-6alkyl; R10a is H or C1-6alkyl; and R11a is C1-6alkyl or aryl-C1-6alkyl and when X1 is C═O or CH2 and R5 is H then R4 is not: Where q is 0 to 5, R3b is H, OH or alkoxy and R4b is NH2, phenyl or a C3-10 heterocycle. The compounds are useful as potassium ion channel inhibitors.