公开(公告)号：US07276631B2

公开(公告)日：2007-10-02

申请号：US11183700

申请日：2005-07-18

Applicant: Yong-Jin Wu ,  Huan He

Inventor： Yong-Jin Wu ,  Huan He

IPC: C07C243/00 ,  A01N31/00

CPC classification number: C07C217/52 ,  C07C2601/02 ,  C07C2601/08 ,  C07C2601/14

Abstract: The present disclosure relates to chemical compounds and their use in human therapy. A specific embodiment of the disclosure relates to compounds of Formula (I); or an isomer, a pharmaceutically acceptable salt or solvate thereof or a pharmaceutically acceptable formulation comprising said compounds are useful for the useful for the treatment or prevention of conditions mediated by tachykinins and/or selective inhibition of serotonin reuptake transporter protein. The compounds act as dual NK-1 antagonists and selective serotonin reuptake inhibitors.

Abstract translation: 本公开涉及化学化合物及其在人类治疗中的用途。 本公开的具体实施方案涉及式（I）的化合物; 或其异构体，药学上可接受的盐或溶剂合物或包含所述化合物的药学上可接受的制剂可用于治疗或预防由速激肽介导的病症和/或选择性抑制5-羟色胺再摄取转运蛋白。 该化合物作为双重NK-1拮抗剂和选择性5-羟色胺再摄取抑制剂。

公开(公告)号：US07138423B2

公开(公告)日：2006-11-21

申请号：US11183702

申请日：2005-07-18

Applicant: Yong-Jin Wu ,  Huan He ,  Joanne J. Bronson

Inventor： Yong-Jin Wu ,  Huan He ,  Joanne J. Bronson

IPC: A01N43/36 ,  A01N43/38 ,  C07D207/08 ,  C07D209/14

CPC classification number: C07D207/08 ,  C07D403/04

Abstract: The present disclosure relates to chemical compounds and their use in treatment of human diseases. A particular embodiment relates to compounds of Formula (I) or an isomer, a pharmaceutically acceptable salts or solvates thereof or a pharmaceutically acceptable formulation comprising said compounds are useful for the treatment or prevention of conditions mediated by tachykinins and/or selective inhibition of serotonin reuptake transporter protein. The compounds act as dual NK-1 antagonists and selective serotonin reuptake inhibitors.

公开(公告)号：US20060019992A1

公开(公告)日：2006-01-26

申请号：US11183699

申请日：2005-07-18

Applicant: Yong-Jin Wu ,  Huan He

Inventor： Yong-Jin Wu ,  Huan He

IPC: C07D211/26 ,  A61K31/445

CPC classification number: C07D225/02

Abstract: The present disclosure relates to chemical compounds and their use in human therapy. A specific embodiment relates to compounds of Formula (I) or an isomer, a pharmaceutically acceptable salt or solvate thereof and pharmaceutically acceptable formulations comprising said compounds useful for the treatment or prevention of conditions mediated by tachykinins and/or selective inhibition of serotonin reuptake transporter protein. The compounds act as dual NK-1 antagonists and selective serotonin reuptake inhibitors.

公开(公告)号：US06831080B2

公开(公告)日：2004-12-14

申请号：US10160582

申请日：2002-05-31

Applicant: Yong-Jin Wu ,  Li-Quang Sun ,  Jie Chen ,  Huan He ,  Alexandre L'Heureux ,  Pierre Dextraze ,  Jean-Paul Daris ,  Gene G. Kinney ,  Steven I. Dworetzky ,  Piyasena Hewawasam

Inventor： Yong-Jin Wu ,  Li-Quang Sun ,  Jie Chen ,  Huan He ,  Alexandre L'Heureux ,  Pierre Dextraze ,  Jean-Paul Daris ,  Gene G. Kinney ,  Steven I. Dworetzky ,  Piyasena Hewawasam

IPC: C07C23720

CPC classification number: C07D213/40 ,  C07C233/11 ,  C07C235/34 ,  C07D209/08 ,  C07D213/56 ,  C07D215/04 ,  C07D215/12 ,  C07D217/06 ,  C07D239/26 ,  C07D241/12 ,  C07D265/30 ,  C07D265/36 ,  C07D295/135 ,  C07D307/79 ,  C07D311/58 ,  C07D317/58 ,  C07D317/60 ,  C07D319/18 ,  C07D333/24 ,  C07D407/12 ,  C07D491/08

Abstract: There is provided novel cinnamide derivatives of Formula I: wherein R is C1-4 alkyl or trifluoromethyl; R1 is selected from the group consisting of pyridinyl, quinolinyl, thienyl, furanyl, 1,4-benzodioxanyl, 1,3-benzodioxolyl, chromanyl, indanyl, biphenylyl, phenyl and substituted phenyl in which said substituted phenyl is substituted with one or two substituents each independently selected-from the group consisting of halogen, C1-4 alkyl, C1-4 alkoxy, trifluoromethyl, trifluoromethoxy and nitro; R2 and R3 are each independently selected from the group consisting of hydrogen, C1-4 alkyl, and halogen; R4 is selected from the group consisting of di(C1-4 alkyl)amino, trifluoromethoxy and optionally substituted morpholin-4-yl, pyridinyl, pyrimidinyl, piperazinyl, and pyrazinyl with one or two substituents in which said substituent is independently selected from the group consisting of C1-4 alkyl, aminomethyl, hydroxymethyl, chloro or fluoro; R5 is hydrogen, chloro or fluoro; or R4 and R5 taken together are —CH═CH—CH═CH— or —X(CH2)mY— in which X and Y are each independently selected from the group consisting of CH2, (CH2)nN(R9)— and O, wherein m is 1 or 2; n is 0 or 1; and R6, R7, and R8 are each independently selected from hydrogen, chloro and fluoro; and R9 is selected from the group consisting of hydrogen, C1-4 alkyl, hydroxyethyl, C1-4 alkoxyethyl, cyclopropylmethyl, —CO2(C1-4alkyl), and —CH2CH2NR10R11 in which R10 and R11 are each independently hydrogen or C1-4 alkyl, which are openers of the KCNQ potassium channels and are useful in the treatment of disorders which are responsive to the opening of the KCNQ potassium channels.

Abstract translation: 提供式I的新颖的肉桂酰胺衍生物：其中R是C 1-4烷基或三氟甲基; R 1选自吡啶基，喹啉基，噻吩基，呋喃基，1,4-苯并二恶烷基，1,3-苯并二恶唑基，苯并二氢吡喃基，茚满基，联苯基，苯基和取代的苯基，其中所述取代的苯基被一个 或两个各自独立地选自卤素，C 1-4烷基，C 1-4烷氧基，三氟甲基，三氟甲氧基和硝基的取代基; R 2和R 3各自独立地选自氢，C 1-4烷基和卤素; R 4选自二（C 1-4烷基）氨基，三氟甲氧基和任选取代的吗啉-4-基，吡啶基，嘧啶基，哌嗪基和吡嗪基，其中一个或两个取代基独立地选自所述取代基 由C1-4烷基，氨基甲基，羟甲基，氯或氟组成的基团; R 5是氢，氯或氟; 或R 4和R 5一起为-CH = CH-CH = CH-或-X（CH 2）mY-，其中X和Y各自独立地选自CH 2，（CH 2）n N （R 9） - 和O，其中m为1或2; n为0或1; 和R 6，R 7和R 8各自独立地选自氢，氯和氟; 并且R 9选自氢，C 1-4烷基，羟乙基，C 1-4烷氧基乙基，环丙基甲基，-CO 2（C 1-4烷基）和-CH 2 CH 2 NR 10 R 11， 10>和R 11各自独立地是氢或C 1-4烷基，其是KCNQ钾通道的开放剂，并且可用于治疗对开放KCNQ钾通道有响应的病症。

公开(公告)号：US07098203B2

公开(公告)日：2006-08-29

申请号：US11183691

申请日：2005-07-18

Applicant: Yong-Jin Wu ,  Huan He

Inventor： Yong-Jin Wu ,  Huan He

IPC: A61P25/00 ,  A61K31/55 ,  C07D223/04

CPC classification number: C07D223/04

Abstract: The present disclosure relates to chemical compounds and their use in human therapy. In a specific embodiment, compounds of Formula (I) or an isomer, a pharmaceutically acceptable salt or solvate thereof or a pharmaceutically acceptable formulation comprising said compounds useful for the treatment or prevention of conditions mediated by tachykinins and/or selective inhibition of serotonin reuptake transporter protein. The compounds act as dual NK-1 antagonists and selective serotonin reuptake inhibitors.

Abstract translation: 本公开涉及化学化合物及其在人类治疗中的用途。 在具体实施方案中，式（I）化合物或其异构体，药学上可接受的盐或溶剂合物或药学上可接受的制剂，其包含用于治疗或预防速激肽介导的病症和/或选择性抑制5-羟色胺再摄取转运蛋白 蛋白。 该化合物作为双重NK-1拮抗剂和选择性5-羟色胺再摄取抑制剂。

公开(公告)号：US07045551B2

公开(公告)日：2006-05-16

申请号：US10719465

申请日：2003-11-21

Applicant: Yong-Jin Wu ,  Li-Qiang Sun ,  Huan He ,  Alexandre L'Heureux

Inventor： Yong-Jin Wu ,  Li-Qiang Sun ,  Huan He ,  Alexandre L'Heureux

IPC: A61K31/165 ,  A61K31/34 ,  A61K31/535 ,  C07D265/30 ,  C07D307/78

CPC classification number: C07D295/135 ,  C07C233/19 ,  C07C233/22 ,  C07C233/60 ,  C07C233/73 ,  C07C2601/08 ,  C07C2601/14 ,  C07D213/40 ,  C07D307/54 ,  C07D333/24

Abstract: The present invention provides novel aryl hydroxyethyl amides and related derivatives having the general Formula I wherein R1, R2, R3, R4, R5, R6, R7 and A are as defined in the specification, or a nontoxic pharmaceutically acceptable salt, solvate or hydrate thereof which are openers or activators of KCNQ potassium channels. The present invention also provides pharmaceutical compositions comprising said aryl hydroxyethyl amides and to the method of treatment of disorders sensitive to KCNQ potassium channel opening activity such as migraine or a migraine attack, bipolar disorders, epilepsy, acute and chronic pain and anxiety.

Abstract translation: 本发明提供了具有通式I的新型芳基羟乙基酰胺和相关衍生物，其中R 1，R 2，R 3，R 3， R 4，R 5，R 6，R 7和A如说明书中所定义，或无毒的药学上可接受的 盐，溶剂合物或水合物，它们是KCNQ钾通道的开放剂或活化剂。 本发明还提供包含所述芳基羟乙基酰胺的药物组合物和治疗对KCNQ钾通道开放活性敏感的疾病如偏头痛或偏头痛发作，双相情感障碍，癫痫，急性和慢性疼痛和焦虑的方法。

公开(公告)号：US20060020011A1

公开(公告)日：2006-01-26

申请号：US11183702

申请日：2005-07-18

Applicant: Yong-Jin Wu ,  Huan He ,  Joanne Bronson

Inventor： Yong-Jin Wu ,  Huan He ,  Joanne Bronson

IPC: A61K31/4439 ,  A61K31/416 ,  A61K31/405 ,  A61K31/4025 ,  C07D403/02 ,  C07D405/02 ,  C07D409/02

CPC classification number: C07D207/08 ,  C07D403/04

Abstract: The present disclosure relates to chemical compounds and their use in treatment of human diseases. A particular embodiment relates to compounds of Formula (I) or an isomer, a pharmaceutically acceptable salts or solvates thereof or a pharmaceutically acceptable formulation comprising said compounds are useful for the treatment or prevention of conditions mediated by tachykinins and/or selective inhibition of serotonin reuptake transporter protein. The compounds act as dual NK-1 antagonists and selective serotonin reuptake inhibitors.

Abstract translation: 本公开涉及化学化合物及其在治疗人类疾病中的用途。 一个具体实施方案涉及式（I）化合物或其异构体，其药学上可接受的盐或溶剂合物或包含所述化合物的药学上可接受的制剂可用于治疗或预防由速激肽介导的病症和/或选择性抑制5-羟色胺再摄取 转运蛋白。 该化合物作为双重NK-1拮抗剂和选择性5-羟色胺再摄取抑制剂。

公开(公告)号：US20060019944A1

公开(公告)日：2006-01-26

申请号：US11183700

申请日：2005-07-18

Applicant: Yong-Jin Wu ,  Huan He

Inventor： Yong-Jin Wu ,  Huan He

IPC: A61K31/55 ,  A61K31/495 ,  A61K31/445 ,  A61K31/40

CPC classification number: C07C217/52 ,  C07C2601/02 ,  C07C2601/08 ,  C07C2601/14

Abstract: The present disclosure relates to chemical compounds and their use in human therapy. A specific embodiment of the disclosure relates to compounds of Formula (I); or an isomer, a pharmaceutically acceptable salt or solvate thereof or a pharmaceutically acceptable formulation comprising said compounds are useful for the useful for the treatment or prevention of conditions mediated by tachykinins and/or selective inhibition of serotonin reuptake transporter protein. The compounds act as dual NK-1 antagonists and selective serotonin reuptake inhibitors.

Abstract translation: 本公开涉及化学化合物及其在人类治疗中的用途。 本公开的具体实施方案涉及式（I）的化合物; 或其异构体，药学上可接受的盐或溶剂合物或包含所述化合物的药学上可接受的制剂可用于治疗或预防由速激肽介导的病症和/或选择性抑制5-羟色胺再摄取转运蛋白。 该化合物作为双重NK-1拮抗剂和选择性5-羟色胺再摄取抑制剂。

公开(公告)号：US20060019943A1

公开(公告)日：2006-01-26

申请号：US11183691

申请日：2005-07-18

Applicant: Yong-Jin Wu ,  Huan He

Inventor： Yong-Jin Wu ,  Huan He

IPC: A61K31/55 ,  C07D223/04

CPC classification number: C07D223/04

Abstract: The present disclosure relates to chemical compounds and their use in human therapy. In a specific embodiment, compounds of Formula (I) or an isomer, a pharmaceutically acceptable salt or solvate thereof or a pharmaceutically acceptable formulation comprising said compounds useful for the treatment or prevention of conditions mediated by tachykinins and/or selective inhibition of serotonin reuptake transporter protein. The compounds act as dual NK-1 antagonists and selective serotonin reuptake inhibitors.

公开(公告)号：US07494986B2

公开(公告)日：2009-02-24

申请号：US11183699

申请日：2005-07-18

Applicant: Yong-Jin Wu ,  Huan He

Inventor： Yong-Jin Wu ,  Huan He

IPC: A01N43/00 ,  A61K31/33 ,  C07D225/00 ,  C07D295/00

CPC classification number: C07D225/02

Abstract: The present disclosure relates to chemical compounds and their use in human therapy. A specific embodiment relates to compounds of Formula (I) or an isomer, a pharmaceutically acceptable salt or solvate thereof and pharmaceutically acceptable formulations comprising said compounds useful for the treatment or prevention of conditions mediated by tachykinins and/or selective inhibition of serotonin reuptake transporter protein. The compounds act as dual NK-1 antagonists and selective serotonin reuptake inhibitors.

Abstract translation: 本公开涉及化学化合物及其在人类治疗中的用途。 具体实施方案涉及式（I）化合物或其异构体，药学上可接受的盐或溶剂合物和药学上可接受的制剂，其包含用于治疗或预防由速激肽介导的病症和/或选择性抑制5-羟色胺再摄取转运蛋白 。 该化合物作为双重NK-1拮抗剂和选择性5-羟色胺再摄取抑制剂。