公开(公告)号：US20070270466A1

公开(公告)日：2007-11-22

申请号：US11810388

申请日：2007-06-04

申请人： Maria-Jesus Blanco-Pillado ,  Michael Cohen ,  Sandra Filla ,  Kevin Hudziak ,  Daniel Kohlman ,  Dana Benesh ,  Frantz Victor ,  Yao-Chang Xu ,  Bai-Ping Ying ,  DeAnna Zacherl ,  Deyi Zhang ,  Brian Mathes

发明人： Maria-Jesus Blanco-Pillado ,  Michael Cohen ,  Sandra Filla ,  Kevin Hudziak ,  Daniel Kohlman ,  Dana Benesh ,  Frantz Victor ,  Yao-Chang Xu ,  Bai-Ping Ying ,  DeAnna Zacherl ,  Deyi Zhang ,  Brian Mathes

IPC分类号： A61K31/4468 ,  A61K31/4523 ,  A61P25/06

CPC分类号： C07D211/58 ,  A61K31/4468 ,  A61K31/4523 ,  C04B35/632 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D409/12 ,  C07D409/14

摘要： The present invention relates to compounds of formula I: or a pharmaceutically acceptable acid addition salt thereof, wherein X is C(R3c)═ or N═; R1 is C2-C6 alkyl, substituted C2-C6 alkyl, C3-C7 cycloalkyl, substituted C3-C7 cycloalkyl, phenyl, substituted phenyl, heterocycle, or substituted heterocycle; R2 is hydrogen, C1-C3 n-alkyl, C3-C6 cycloalkyl-C1-C3 alkyl, or a group of formula II provided that when R1 is C2-C6 alkyl or substituted C2-C6 alkyl, R2 is hydrogen or methyl; R3a, R3b and, when X is —C(R3c)═, R3c, are each independently hydrogen, fluoro, or methyl, provided that no more than one of R3a, R3b, and R3c may be other than hydrogen; R4 is hydrogen or C1-C3 alkyl; R5 is hydrogen, C1-C3 alkyl, or C3-C6 cycloalkylcarbonyl, provided that when R3a is other than hydrogen, R5 is hydrogen; R6 is hydrogen or C1-C6 alkyl; and n is an integer from 1 to 6 inclusively. The compounds of the present invention are useful for activating 5HT1F receptors, inhibiting neuronal protein extravasation, and for the treatment or prevention of migraine in a mammal.

公开(公告)号：US20060287363A1

公开(公告)日：2006-12-21

申请号：US10569109

申请日：2004-09-03

申请人： Maria-Jesus Blanco-Pillado ,  Michael Cohen ,  Sandra Filla ,  Kevin Hudzlak ,  Daniel Kohlman ,  Dana Benesh ,  Frantz Victor ,  Yao-Chang Xu ,  Bai-Ping Ying ,  DeAnna Zacherl ,  Deyi Zhang ,  Brian Mathes

发明人： Maria-Jesus Blanco-Pillado ,  Michael Cohen ,  Sandra Filla ,  Kevin Hudzlak ,  Daniel Kohlman ,  Dana Benesh ,  Frantz Victor ,  Yao-Chang Xu ,  Bai-Ping Ying ,  DeAnna Zacherl ,  Deyi Zhang ,  Brian Mathes

IPC分类号： A61K31/4545 ,  A61K31/454 ,  C07D403/14

CPC分类号： C07D211/58 ,  A61K31/4468 ,  A61K31/4523 ,  C04B35/632 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D409/12 ,  C07D409/14

摘要： The present invention relates to compounds of formula I: (I) or a pharmaceutically acceptable acid addition salt thereof, where; X is C(R3c═ or N═; R1 is C2-C6 alkyl, substituted C2-C6 alkyl, C3-C7 cycloalkyl, substituted C3-C7 cycloalkyl, phenyl, substituted phenyl, heterocycle, or substituted heterocycle; R2 is hydrogen, C1-C3 n-alkyl, C3-C6 cycloalkyl-C1-C3 alkyl, or a group of formula II (II) provided that when R1 is C2-C6 alkyl or substituted C2-C6 alkyl, R2 is hydrogen or methyl; R3a, R3b, and, when X is C(R3c)═, R3c, are each independently hydrogen, fluoro, or methyl, provided that no more than one of R3a, R3b, and R3c may be other than hydrogen; R4 is hydrogen or C1-C3 alkyl; R5 is hydrogen, C1-C3 alkyl, or C3-C6 cycloalkylcarbonyl, provided that when R3a is other than hydrogen, R5 is hydrogen; R6 is hydrogen or C1-C6 alkyl; and n is an integer from 1 to 6 inclusively. The compounds of the present invention are useful for activating 5-HT1F receptors, inhibiting neuronal protein extravasation, and for the treatment or prevention of migraine in a mammal.

公开(公告)号：US20060211734A1

公开(公告)日：2006-09-21

申请号：US10552131

申请日：2004-04-14

申请人： Maria-Jesus Blanco-Pillado ,  Dana Benesh ,  Sandra Filla ,  Kevin Hudziak ,  Brian Mathes ,  Daniel Kohlman ,  Bai-Ping Ying ,  Deyl Zhang ,  Yao-Chang Xu

发明人： Maria-Jesus Blanco-Pillado ,  Dana Benesh ,  Sandra Filla ,  Kevin Hudziak ,  Brian Mathes ,  Daniel Kohlman ,  Bai-Ping Ying ,  Deyl Zhang ,  Yao-Chang Xu

IPC分类号： A61K31/4545 ,  A61K31/454 ,  C07D401/14 ,  C07D403/14

CPC分类号： C07D401/12 ,  C07D211/44 ,  C07D211/46 ,  C07D211/54 ,  C07D401/14 ,  C07D409/12 ,  C07D409/14

摘要： The present invention relates to compounds of formula 1: and pharmaceutically acceptable acid addition sails thereof. The compounds of the present invention are useful for activating 5-HT1F receptors, inhibiting neuronal protein extravasation, and for the treatment or preverition of migraine in mammals, particularly humans.

摘要翻译： 本发明涉及式1的化合物及其药学上可接受的酸加成口。 本发明的化合物可用于激活5-HT 1F受体，抑制神经元蛋白质外渗，以及在哺乳动物，特别是人中治疗或预防偏头痛。

公开(公告)号：US20050222206A1

公开(公告)日：2005-10-06

申请号：US10509770

申请日：2003-03-27

申请人： Michael Cohen ,  Daniel Kohlman ,  Sidney Liang ,  Vincent Mancuso ,  Yao-Chang Xu ,  Bai-Ping Ying ,  DeAnna Zacherl ,  Deyi Zhang ,  Frantz Victor

发明人： Michael Cohen ,  Daniel Kohlman ,  Sidney Liang ,  Vincent Mancuso ,  Yao-Chang Xu ,  Bai-Ping Ying ,  DeAnna Zacherl ,  Deyi Zhang ,  Frantz Victor

IPC分类号： A61K31/4545 ,  A61K31/506 ,  A61P15/00 ,  A61P15/10 ,  A61P17/14 ,  A61P25/06 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/32 ,  A61P25/34 ,  A61P43/00 ,  C07D401/06 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14 ,  C07D41/02

CPC分类号： C07D401/06 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14

摘要： The present invention relates to compounds of formula I: or pharmaceutically acceptable acid addition salts thereof, where; R1 is C1-C6 alkyl, substituted C1-C6 alkyl, C3-C7 cycloalkyl, substituted C3-C7 cycloalkyl, C3-C7 cycloalkyl-C1-C3 alkyl, substituted C3-C7 cycloalkyl-C1-C3 alkyl, phenyl, substituted phenyl, heterocycle, or substituted heterocycle; R2 is hydrogen, C1-C3 alkyl, C3-C6 cycloalkyl-C1-C3 alkyl, or a group of formula II R3 is hydrogen or C1-C3 alkyl; R4 is hydrogen, halo, or C1-C3 alkyl; R5 is hydrogen or C1-C3 alkyl; R6 is hydrogen or C1-C6 alkyl; and n is an integer from 1 to 6 inclusively. The compounds of the present invention are useful for activating 5-HT1F receptors, inhibiting neuronal protein extravasation, and for the treatment or prevention of migraine in a mammal. The present invention also relates to a process for the synthesis of intermediates in the synthesis of compounds of Formula I.

摘要翻译： 本发明涉及式I化合物或其药学上可接受的酸加成盐，其中： R 1是C 1 -C 6烷基，取代的C 1 -C 6亚烷基 烷基，C 3 -C 7环烷基，取代的C 3 -C 7环烷基，C 1 -C 3烷基， 取代的C 3 -C 3烷基，取代的C 3 -C 3烷基，C 1 -C 3烷基，C 3 -C 3 - 苯基，取代的苯基，杂环或取代的杂环; R 2是氢，C 1 -C 3烷基，C 3 -C 6烷基，C 3 -C 3烷基，C 3 -C 3烷基， 或者式II的基团R 3是氢或C 1 -C 6烷基， C 1 -C 3烷基; R 4是氢，卤素或C 1 -C 3烷基; R 5是氢或C 1 -C 3烷基; R 5是氢或C 1 -C 3烷基; R 6是氢或C 1 -C 6烷基; n为1〜6的整数。 本发明的化合物可用于活化5-HT 1F受体，抑制神经元蛋白质外渗，以及治疗或预防哺乳动物偏头痛。 本发明还涉及合成式I化合物中的中间体的方法。

公开(公告)号：US20070078169A1

公开(公告)日：2007-04-05

申请号：US10576762

申请日：2004-12-06

申请人： Daniel Kohlman ,  Frantz Victor ,  Yao-Chang Xu ,  Bai-Ping Ying ,  Deyi Zhang

发明人： Daniel Kohlman ,  Frantz Victor ,  Yao-Chang Xu ,  Bai-Ping Ying ,  Deyi Zhang

IPC分类号： A61K31/4439 ,  A61K31/44 ,  A61K31/277 ,  A61K31/165

CPC分类号： C07D213/73 ,  C07C233/80 ,  C07C2601/16 ,  C07C2601/18 ,  C07D213/61 ,  C07D213/75

摘要： The present invention relates to compounds of formula I: or a pharmaceutically acceptable acid addition salt thereof, where; X is —C(R4)═ or —N═; Ar is phenyl, substituted phenyl, heterocycle, or substituted heterocycle; R1 and R2 are independently hydrogen or C1-C3 alkyl; R3 is hydrogen, fluoro, or methyl; when X is —C(R4)═, R4 is hydrogen, fluoro, or methyl, provided that no more than one of R3 and R4 may be other than hydrogen; and R5 is hydrogen, methyl, or ethyl. The compounds of the present invention are useful for activating 5-HT1F receptors, inhibiting dural protein extravasation, and for the treatment or prevention of migraine in a mammal.

摘要翻译： 本发明涉及式I化合物或其药学上可接受的酸加成盐，其中： X是-C（R 4） - 或-N-; Ar是苯基，取代的苯基，杂环或取代的杂环; R 1和R 2独立地是氢或C 1 -C 3烷基; R 3是氢，氟或甲基; 当X是-C（R 4） - ）时，R 4是氢，氟或甲基，条件是R 3不超过一个 >和R 4可以不同于氢; R 5是氢，甲基或乙基。 本发明的化合物可用于活化5-HT 1F受体，抑制硬脑膜蛋白质外渗，以及治疗或预防哺乳动物偏头痛。

公开(公告)号：US20060009464A1

公开(公告)日：2006-01-12

申请号：US11225541

申请日：2005-09-13

申请人： Alexander Godfrey ,  Daniel Kohlman ,  John O'Toole ,  Yao-Chang Xu ,  Tony Zhang ,  Jeffrey McKelvy

发明人： Alexander Godfrey ,  Daniel Kohlman ,  John O'Toole ,  Yao-Chang Xu ,  Tony Zhang ,  Jeffrey McKelvy

IPC分类号： A61K31/496 ,  C07D403/02

CPC分类号： C07D295/088 ,  A61K31/495 ,  A61K31/496 ,  C07C45/004 ,  C07C45/29 ,  C07C45/40 ,  C07C45/515 ,  C07C45/59 ,  C07C45/68 ,  C07C49/563 ,  C07C49/577 ,  C07C49/583 ,  C07C49/86 ,  C07D213/74 ,  C07D295/104 ,  C07D295/108

摘要： A series of aryl piperazine compounds are effective pharmaceuticals for the treatment of conditions related to or affected by the serotonin 1A receptor; the compounds are particularly effective antagonists at that receptor, and are particularly useful for alleviating the symptoms of nicotine and tobacco withdrawal.

摘要翻译： 一系列芳基哌嗪化合物是用于治疗与5-羟色胺1 A受体相关或受其影响的病症的有效药物; 该化合物在该受体上是特别有效的拮抗剂，特别可用于缓解尼古丁和烟草戒断症状。

公开(公告)号：US20050282817A1

公开(公告)日：2005-12-22

申请号：US11184522

申请日：2005-07-19

申请人： Alexander Godfrey ,  Daniel Kohlman ,  John O'Toole ,  Yao-Chang Xu ,  Tony Zhang

发明人： Alexander Godfrey ,  Daniel Kohlman ,  John O'Toole ,  Yao-Chang Xu ,  Tony Zhang

IPC分类号： C07D295/08 ,  A61K20060101 ,  A61K31/395 ,  A61K31/495 ,  A61K31/496 ,  A61P1/00 ,  A61P3/04 ,  A61P9/00 ,  A61P15/10 ,  A61P25/00 ,  A61P25/06 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P25/34 ,  A61P43/00 ,  C07C20060101 ,  C07C45/00 ,  C07C45/29 ,  C07C45/40 ,  C07C45/51 ,  C07C45/59 ,  C07C45/68 ,  C07C49/355 ,  C07C49/563 ,  C07C49/577 ,  C07C49/583 ,  C07C49/86 ,  C07D20060101 ,  C07D213/74 ,  C07D295/04 ,  C07D295/088 ,  C07D295/092 ,  C07D295/10 ,  C07D295/104 ,  C07D295/108 ,  C07D401/04 ,  C07D521/00

CPC分类号： C07D295/088 ,  A61K31/495 ,  A61K31/496 ,  C07C45/004 ,  C07C45/29 ,  C07C45/40 ,  C07C45/515 ,  C07C45/59 ,  C07C45/68 ,  C07C49/563 ,  C07C49/577 ,  C07C49/583 ,  C07C49/86 ,  C07D213/74 ,  C07D295/104 ,  C07D295/108

摘要： A series of aryl piperazine compounds are effective pharmaceuticals for the treatment of conditions related to or affected by the serotonin 1A receptor; the compounds are particularly effective antagonists at that receptor, and are particularly useful for alleviating the symptoms of nicotine and tobacco withdrawal.