公开(公告)号：US20090131409A1

公开(公告)日：2009-05-21

申请号：US12255232

申请日：2008-10-21

申请人： John Francis Mehlmann ,  Joseph Theodore Lundquist, IV ,  Paige Erin Mahaney ,  Matthew Lantz Crawley ,  Callain Younghee Kim

发明人： John Francis Mehlmann ,  Joseph Theodore Lundquist, IV ,  Paige Erin Mahaney ,  Matthew Lantz Crawley ,  Callain Younghee Kim

IPC分类号： A61K31/55 ,  C07D487/04 ,  A61P3/00 ,  A61P9/00 ,  A61P25/00 ,  A61P35/00

CPC分类号： C07D487/04

摘要： Disclosed are chemical entities including compounds of Formula I and pharmaceutically acceptable salts thereof, wherein X is chosen from CN, CF3, CF2H, S(O)nR6, and S(O)2N(R9)R10; Y is chosen from CR11 and N; Z is chosen from O and NH; R3 is chosen from —C(O)R12 and —C(O)N(R9)R10; and n, R1, R2 and R4-R12 are defined herein; compositions comprising one or more such chemical entities; and methods of using one or more such chemical entities for modulating the activity of certain receptors (e.g., farnesoid X) or for the treatment or prevention of one or more symptoms of disease or disorder related to the activity of those receptors.

摘要翻译： 公开了包括式I化合物及其药学上可接受的盐的化学实体，其中X选自CN，CF 3，CF 2 H，S（O）n R 6和S（O）2 N（R 9）R 10; Y选自CR11和N; Z选自O和NH; R 3选自-C（O）R 12和-C（O）N（R 9）R 10; 且n，R 1，R 2和R 4 -R 12在本文中定义; 包含一种或多种这样的化学实体的组合物; 以及使用一种或多种这样的化学实体调节某些受体（例如法尼斯X）的活性或用于治疗或预防与这些受体的活性相关的一种或多种疾病或病症症状的方法。

公开(公告)号：US20110039824A1

公开(公告)日：2011-02-17

申请号：US12662971

申请日：2010-05-13

申请人： Joseph Theodore Lundquist, IV ,  Paige Erin Mahaney ,  Callain Younghee Kim ,  Matthew Lantz Crawley

发明人： Joseph Theodore Lundquist, IV ,  Paige Erin Mahaney ,  Callain Younghee Kim ,  Matthew Lantz Crawley

IPC分类号： A61K31/55 ,  C07D487/04 ,  A61P3/06 ,  A61P3/04 ,  A61P3/10 ,  A61P1/16 ,  A61P35/00 ,  A61P9/10 ,  C12N5/02

CPC分类号： C07D487/04

摘要： Provided are certain 1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate compounds which are useful for modulating the activity of nuclear receptors, such as farnesoid X receptors, and/or for the treatment, prevention, or amelioration diseases or disorders related to the activity of these receptors.

摘要翻译： 提供可用于调节核受体如法呢酯X受体的活性和/或用于治疗，预防的某些1,2,3,6-四氮杂吖庚因[4,5-b]吲哚-5-羧酸酯化合物 ，或与这些受体的活性相关的改善疾病或病症。

公开(公告)号：US20090137554A1

公开(公告)日：2009-05-28

申请号：US12255216

申请日：2008-10-21

申请人： John Francis Mehlmann ,  Joseph Theodore Lundquist, IV ,  Paige Erin Mahaney ,  Matthew Lantz Crawley ,  Callain Younghee Kim

发明人： John Francis Mehlmann ,  Joseph Theodore Lundquist, IV ,  Paige Erin Mahaney ,  Matthew Lantz Crawley ,  Callain Younghee Kim

IPC分类号： A61K31/55 ,  C07D487/04 ,  C07D491/20 ,  A61P3/04

CPC分类号： C07D487/04 ,  C07D491/20

摘要： Disclosed are chemical entities including compounds of Formula I and pharmaceutically acceptable salts thereof, wherein X is chosen from CN, CF3, CF2H, S(O)nR8, and S(O)2N(R9)R10; Y is chosen from CR11 and N; Z is chosen from O and NH; R3 is chosen from —C(O)R12 and —C(O)N(R9)R10; and n, R1, R2 and R4-R12 are defined herein; compositions comprising one or more such chemical entities; and methods of using one or more such chemical entities for modulating the activity of certain receptors (e.g., farnesoid X) or for the treatment or prevention of one or more symptoms of disease or disorder related to the activity of those receptors.

摘要翻译： 公开了包括式I化合物及其药学上可接受的盐的化学实体，其中X选自CN，CF 3，CF 2 H，S（O）n R 8和S（O）2 N（R 9）R 10; Y选自CR11和N; Z选自O和NH; R 3选自-C（O）R 12和-C（O）N（R 9）R 10; 且n，R 1，R 2和R 4 -R 12在本文中定义; 包含一种或多种这样的化学实体的组合物; 以及使用一种或多种这样的化学实体调节某些受体（例如法尼斯X）的活性或用于治疗或预防与这些受体的活性相关的一种或多种疾病或病症症状的方法。

公开(公告)号：US20080161366A1

公开(公告)日：2008-07-03

申请号：US11955195

申请日：2007-12-12

申请人： Casey Cameron McComas ,  Stephen Todd Cohn ,  Matthew Lantz Crawley ,  Andrew Fensome ,  Joel Adam Goldberg ,  Douglas John Jenkins ,  Callain Younghee Kim ,  Paige Erin Mahaney ,  Charles William Mann ,  Michael Anthony Marella ,  David John O'Neill ,  Joseph Peter Sabatucci ,  Eugene Anthony Terefenko ,  Eugene John Trybulski ,  An Thien Vu ,  Richard Page Woodworth ,  Puwen Zhang

发明人： Casey Cameron McComas ,  Stephen Todd Cohn ,  Matthew Lantz Crawley ,  Andrew Fensome ,  Joel Adam Goldberg ,  Douglas John Jenkins ,  Callain Younghee Kim ,  Paige Erin Mahaney ,  Charles William Mann ,  Michael Anthony Marella ,  David John O'Neill ,  Joseph Peter Sabatucci ,  Eugene Anthony Terefenko ,  Eugene John Trybulski ,  An Thien Vu ,  Richard Page Woodworth ,  Puwen Zhang

IPC分类号： A61K31/433 ,  C07D285/14 ,  A61P15/00 ,  A61P25/00 ,  A61P1/00 ,  A61P3/00

CPC分类号： C07D417/04 ,  C07D285/14 ,  C07D417/06

摘要： The present invention is directed to aminoalkyl-substituted aryl sulfamide derivatives of formula I: or a pharmaceutically acceptable salt, stereoisomer or tautomer thereof, which are monoamine reuptake inhibitors, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions, including, inter alia, vasomotor symptoms, sexual dysfunction, gastrointestinal disorders and genitourinary disorder, depression disorders, endogenous behavioral disorders, cognitive disorders, diabetic neuropathy, pain, and other diseases or disorders.

摘要翻译： 本发明涉及式I的氨基烷基取代的芳基磺酰胺衍生物：或其药学上可接受的盐，立体异构体或互变异构体，它们是单胺再摄取抑制剂，含有这些衍生物的组合物及其用于预防和治疗病症的方法 ，包括血管舒缩症状，性功能障碍，胃肠道疾病和泌尿生殖器疾病，抑郁症，内源性行为障碍，认知障碍，糖尿病性神经病，疼痛和其他疾病或病症。

公开(公告)号：US20090099164A1

公开(公告)日：2009-04-16

申请号：US12335144

申请日：2008-12-15

申请人： Callain Younghee Kim ,  Paige Erin Mahaney ,  Eugene John Trybulski ,  Puwen Zhang ,  Eugene Anthony Terefenko ,  Casey Cameron McComas ,  Michael Anthony Marella ,  Richard Dale Coghlan ,  Gavin David Heffernan ,  Stephen Todd Cohn ,  An Thien Vu ,  Joseph Peter Sabatucci ,  Fei Ye

发明人： Callain Younghee Kim ,  Paige Erin Mahaney ,  Eugene John Trybulski ,  Puwen Zhang ,  Eugene Anthony Terefenko ,  Casey Cameron McComas ,  Michael Anthony Marella ,  Richard Dale Coghlan ,  Gavin David Heffernan ,  Stephen Todd Cohn ,  An Thien Vu ,  Joseph Peter Sabatucci ,  Fei Ye

IPC分类号： A61K31/538 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/498 ,  A61K31/437 ,  A61P25/24 ,  A61P15/00 ,  A61P1/00 ,  A61P25/22 ,  A61P29/00 ,  A61K31/4184 ,  A61K31/404 ,  A61K31/4439

CPC分类号： C07D209/08 ,  C07D209/30 ,  C07D209/42 ,  C07D235/06 ,  C07D241/42 ,  C07D265/36 ,  C07D471/04

摘要： The present invention is directed to phenylaminopropanol derivatives of formula I: or a pharmaceutically acceptable salt thereof, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nervous system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, and combinations thereof.

摘要翻译： 本发明涉及式I的苯基氨基丙醇衍生物：或其药学上可接受的盐，含有这些衍生物的组合物及其用于预防和治疗由单胺再摄取改善的病症的方法，所述方法尤其包括血管舒缩症状（VMS） 特别是选自重度抑郁障碍，血管舒缩症状，压力和急迫性尿失禁，纤维肌痛，疼痛等的那些情况，特别是选自以下的那些病症：血管紧张素转换酶，抑制性功能障碍，性功能障碍，胃肠道和泌尿生殖系统疾病，慢性疲劳综合征，纤维瘤病综合征，神经系统疾病及其组合， 糖尿病性神经病变及其组合。

公开(公告)号：US07517899B2

公开(公告)日：2009-04-14

申请号：US11091885

申请日：2005-03-28

申请人： Callain Younghee Kim ,  Paige Erin Mahaney ,  Eugene John Trybulski ,  Puwen Zhang ,  Eugene Anthony Terefenko ,  Casey McComas ,  Michael Anthony Marella ,  Richard Dale Coghlan ,  Gavin David Heffernan ,  Stephen Todd Cohn ,  An Thien Vu ,  Joseph Peter Sabatucci ,  Fei Ye

发明人： Callain Younghee Kim ,  Paige Erin Mahaney ,  Eugene John Trybulski ,  Puwen Zhang ,  Eugene Anthony Terefenko ,  Casey McComas ,  Michael Anthony Marella ,  Richard Dale Coghlan ,  Gavin David Heffernan ,  Stephen Todd Cohn ,  An Thien Vu ,  Joseph Peter Sabatucci ,  Fei Ye

IPC分类号： A61K31/40 ,  A61K31/415 ,  C07D235/00 ,  C07D209/04

CPC分类号： C07D209/08 ,  C07D209/30 ,  C07D209/42 ,  C07D235/06 ,  C07D241/42 ,  C07D265/36 ,  C07D471/04

摘要： The present invention is directed to phenylaminopropanol derivatives of formula I: or a pharmaceutically acceptable salt thereof, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nervous system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, and combinations thereof.

摘要翻译： 本发明涉及式I的苯基氨基丙醇衍生物：或其药学上可接受的盐，含有这些衍生物的组合物及其用于预防和治疗由单胺再摄取改善的病症的方法，所述方法尤其包括血管舒缩症状（VMS） 特别是选自重度抑郁障碍，血管舒缩症状，压力和急迫性尿失禁，纤维肌痛，疼痛等的那些情况，特别是选自以下的那些病症：血管紧张素转换酶，抑制性功能障碍，性功能障碍，胃肠道和泌尿生殖系统疾病，慢性疲劳综合征，纤维瘤病综合征，神经系统疾病及其组合， 糖尿病性神经病变及其组合。

公开(公告)号：US20090093469A1

公开(公告)日：2009-04-09

申请号：US12335245

申请日：2008-12-15

申请人： Callain Younghee Kim ,  Paige Erin Mahaney ,  Eugene John Trybulski ,  Puwen Zhang ,  Eugene Anthony Terefenko ,  Casey Cameron McComas ,  Michael Anthony Marella ,  Richard Dale Coghlan ,  Gavin David Heffernan ,  Stephen Todd Cohn ,  An Thien Vu ,  Joseph Peter Sabatucci ,  Fei Ye

发明人： Callain Younghee Kim ,  Paige Erin Mahaney ,  Eugene John Trybulski ,  Puwen Zhang ,  Eugene Anthony Terefenko ,  Casey Cameron McComas ,  Michael Anthony Marella ,  Richard Dale Coghlan ,  Gavin David Heffernan ,  Stephen Todd Cohn ,  An Thien Vu ,  Joseph Peter Sabatucci ,  Fei Ye

IPC分类号： A61K31/5415 ,  C07D403/06 ,  A61K31/496 ,  C07D413/06 ,  A61K31/5377 ,  C07D209/04 ,  A61K31/404 ,  C07D401/06 ,  A61K31/4439 ,  A61K31/454 ,  C07D265/36 ,  A61K31/538 ,  C07D241/38 ,  A61K31/498 ,  C07D235/04 ,  A61K31/4184 ,  C07D471/04 ,  A61K31/437 ,  A61P29/00 ,  A61P25/00 ,  A61P25/24 ,  C07D409/06 ,  C07D209/96 ,  C07D279/16

CPC分类号： C07D209/08 ,  C07D209/30 ,  C07D209/42 ,  C07D235/06 ,  C07D241/42 ,  C07D265/36 ,  C07D471/04

摘要： The present invention is directed to phenylaminopropanol derivatives of formula I: or a pharmaceutically acceptable salt thereof, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nervous system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, and combinations thereof.

公开(公告)号：US07612210B2

公开(公告)日：2009-11-03

申请号：US11633207

申请日：2006-12-04

申请人： Paige Erin Mahaney ,  Madelene Miyoko Antane ,  Jerry Shunneng Sun

发明人： Paige Erin Mahaney ,  Madelene Miyoko Antane ,  Jerry Shunneng Sun

IPC分类号： C07D263/04

CPC分类号： C07C213/02 ,  C07B2200/07 ,  C07C59/72 ,  C07C235/34 ,  C07C2601/14 ,  C07D263/26 ,  C07D295/092 ,  C07D295/096 ,  C07D295/185 ,  C07C217/74

摘要： A process for the enantioselective synthesis of an (S)- or (R)-1-[2-dimethylamino)-1-(methoxyphenyl)ethyl]cyclohexanol and analogues or salt thereof are described. The method involves the steps of (a) reacting an (S) or (R) 4-benzyloxazolidinone with a mixed anhydride of a methyoxyphenylacetic acid under conditions which form a oxazolidinone, (4S)- or (4R)-4-benzyl-3-[methyoxyphenyl]acetyl]-oxazolidin-2-one, (b) treating the (4S)- or (4R)-4-benzyl-3-[(methoxyphenyl)acetyl]-1,3-oxazolidin-2-one with an aprotic amine base and titanium chloride in a chlorinated solvent under conditions which permit formation of the corresponding anion, (c) mixing the corresponding anion with titanium chloride and cylcohexanone under conditions which permit an aldol reaction to form the corresponding (4S)- or (4R)-4-benzyl-3-[(2R)-2-(1-hydroxycyclohexyl)-2-(methoxyphenyl)acetyl]-1,3-oxazolidin-2-one,(d) hydrolyzing the (4S)— or (4R)-4-benzyl-3-[(2R)-2-(1-hydroxycyclohexyl)-2-(methoxyphenyl)acetyl]-1,3-oxazolidin-2-one to form a chiral acid (2S or 2R)-(1-hydroxycyclohexyl)-methoxyphenyl)acetic acid, (e) coupling the chiral phenylacid to a secondary amine to form an amide, and (f) reducing the amide to form an (S) or (R) 1[2-dimethylamino)-1-(methoxyphenyl)ethyl]cyclohexanol or a salt thereof.

摘要翻译： 描述了（S） - 或（R）-1- [2-二甲基氨基）-1-（甲氧基苯基）乙基]环己醇及其类似物或其盐的对映选择性合成方法。 该方法包括以下步骤：（S）或（R）4-苄氧基恶唑烷酮与甲氧基苯乙酸的混合酸酐在形成恶唑烷酮，（4S） - 或（4R）-4-苄基-3 - [甲氧基苯基]乙酰基] - 恶唑烷-2-酮，（b）用（4S） - 或（4R）-4-苄基-3 - [（甲氧基苯基）乙酰] -1,3-恶唑烷-2-酮处理 非质子胺基和氯化钛在氯化溶剂中，在允许形成相应阴离子的条件下，（c）在允许醛醇缩合反应形成相应的（4S） - 或（ - ）的条件下将相应的阴离子与氯化钛和环己酮混合， 4R）-4-苄基-3 - [（2R）-2-（1-羟基环己基）-2-（甲氧基苯基）乙酰基] -1,3-恶唑烷-2-酮，（d）水解（4S） - 或 （4R）-4-苄基-3 - [（2R）-2-（1-羟基环己基）-2-（甲氧基苯基）乙酰基] -1,3-恶唑烷-2-酮以形成手性酸（2S或2R） - （1-羟基环己基） - 甲氧基苯基）乙酸，（e）将手性苯基酸偶联到仲胺以形成一个 （f）还原酰胺以形成（S）或（R）1 [2-二甲基氨基）-1-（甲氧基苯基）乙基]环己醇或其盐。

公开(公告)号：US07550456B2

公开(公告)日：2009-06-23

申请号：US12031187

申请日：2008-02-14

申请人： Eugene John Trybulski ,  Joseph Peter Sabatucci ,  An Thien Vu ,  Stephen Todd Cohn ,  Arthur Attilio Santilli ,  Lori Krim Gavrin ,  Fei Ye ,  Paige Erin Mahaney

发明人： Eugene John Trybulski ,  Joseph Peter Sabatucci ,  An Thien Vu ,  Stephen Todd Cohn ,  Arthur Attilio Santilli ,  Lori Krim Gavrin ,  Fei Ye ,  Paige Erin Mahaney

IPC分类号： A01N43/62 ,  C07D243/08

CPC分类号： C07D295/088 ,  C07D207/14 ,  C07D209/14 ,  C07D211/44 ,  C07D211/46 ,  C07D211/56 ,  C07D211/58 ,  C07D213/38 ,  C07D215/12 ,  C07D241/04 ,  C07D243/08 ,  C07D295/03 ,  C07D307/14 ,  C07D307/81 ,  C07D309/12 ,  C07D317/58 ,  C07D333/28 ,  C07D333/58

摘要： The present invention is directed to substituted aryl cycloalkanoyl derivatives, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromyalgia syndrome, nervous system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, and combinations thereof.

摘要翻译： 本发明涉及取代的芳基环烷酰基衍生物，含有这些衍生物的组合物及其用于预防和治疗由单胺再摄取改善的病症的方法，所述方法尤其包括血管舒缩症状（VMS），性功能障碍，胃肠道和泌尿生殖系统疾病 特别是选自重度抑郁障碍，血管舒缩症状，压力和急迫性尿失禁，纤维肌痛，疼痛，糖尿病性神经病变及其组合的那些病症，慢性疲劳综合征，纤维肌痛综合征，神经系统疾病及其组合。

公开(公告)号：US07419980B2

公开(公告)日：2008-09-02

申请号：US10963064

申请日：2004-10-12

申请人： Eugene John Trybulski ,  Paige Erin Mahaney ,  Lori Krim Gavrin ,  Joseph Peter Sabatucci ,  Gary Paul Stack

发明人： Eugene John Trybulski ,  Paige Erin Mahaney ,  Lori Krim Gavrin ,  Joseph Peter Sabatucci ,  Gary Paul Stack

IPC分类号： A61K31/497 ,  A61K31/4965 ,  C07D401/00 ,  C07D403/00 ,  C07D405/00 ,  C07D409/00 ,  C07D411/00 ,  C07D413/00 ,  C07D417/00 ,  C07D419/00 ,  C07D241/04 ,  C07D295/00

CPC分类号： C07D295/092 ,  A61K31/496 ,  C07D207/14 ,  C07D207/22 ,  C07D209/14 ,  C07D211/48 ,  C07D211/56 ,  C07D211/58 ,  C07D213/38 ,  C07D215/12 ,  C07D307/34 ,  C07D307/52 ,  C07D307/81 ,  C07D309/10 ,  C07D317/58 ,  C07D333/28 ,  C07D333/58 ,  C07D409/06

摘要： The present invention is directed to fused-aryl and heteroaryl derivatives, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nervous system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, and combinations thereof.

摘要翻译： 本发明涉及稠合芳基和杂芳基衍生物，含有这些衍生物的组合物及其用于预防和治疗由单胺再摄取改善的病症的方法，其中尤其包括血管舒缩症状（VMS），性功能障碍，胃肠道和 特别是选自重症抑郁障碍，血管舒缩症状，压力和急迫性尿失禁，纤维肌痛，疼痛，糖尿病性神经病变及其组合的那些病症，特别是选自下列的那些病症：泌尿生殖系统疾病，慢性疲劳综合征，纤维瘤病综合征，神经系统疾病及其组合 。