公开(公告)号：US07608629B2

公开(公告)日：2009-10-27

申请号：US10552131

申请日：2004-04-14

申请人： Maria-Jesus Blanco-Pillado ,  Dana Rae Benesh ,  Sandra Ann Filla ,  Kevin John Hudziak ,  Brian Michael Mathes ,  Daniel Timothy Kohlman ,  Bai-Ping Ying ,  Deyi Zhang ,  Yao-Chang Xu

发明人： Maria-Jesus Blanco-Pillado ,  Dana Rae Benesh ,  Sandra Ann Filla ,  Kevin John Hudziak ,  Brian Michael Mathes ,  Daniel Timothy Kohlman ,  Bai-Ping Ying ,  Deyi Zhang ,  Yao-Chang Xu

IPC分类号： A61K31/4545 ,  C07D401/14

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-HT1F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：US6121201A

公开(公告)日：2000-09-19

申请号：US159233

申请日：1998-09-23

申请人： David A. Pulman ,  Bai-Ping Ying ,  Shao-Yong Wu ,  Sandeep Gupta ,  Masamitsu Tsukamoto ,  Takahiro Haga

发明人： David A. Pulman ,  Bai-Ping Ying ,  Shao-Yong Wu ,  Sandeep Gupta ,  Masamitsu Tsukamoto ,  Takahiro Haga

IPC分类号： A01N43/50 ,  A01N43/52 ,  A01N43/54 ,  A01N43/56 ,  A01N43/58 ,  A01N43/60 ,  A01N43/653 ,  A01N43/66 ,  A01N43/713 ,  A01N43/76 ,  A01N43/80 ,  A01N43/90 ,  C07D231/18 ,  C07D231/20

CPC分类号： C07D231/20 ,  A01N43/50 ,  A01N43/52 ,  A01N43/54 ,  A01N43/56 ,  A01N43/58 ,  A01N43/60 ,  A01N43/653 ,  A01N43/66 ,  A01N43/713 ,  A01N43/76 ,  A01N43/80 ,  A01N43/90 ,  C07D231/18

摘要： A compound represented by the formula (I) or its salt and herbicidal and desiccant use thereof: ##STR1## wherein X, Y are independently hydrogen, halogen, cyano, nitro, or (C.sub.1-6)haloalkyl;Z is oxygen or sulfur; andQ is ##STR2##

摘要翻译： 由式（I）表示的化合物或其盐和除草和干燥剂的用途：其中X，Y独立地为氢，卤素，氰基，硝基或（C 1-6）卤代烷基; Z是氧或硫; 而Q是

公开(公告)号：US20110034511A1

公开(公告)日：2011-02-10

申请号：US12892433

申请日：2010-09-28

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

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

IPC分类号： A61K31/4468 ,  C07D211/58 ,  C07D401/06 ,  C07D409/12 ,  C07D401/12 ,  C07D401/14 ,  A61K31/454 ,  A61K31/4545 ,  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.

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为C（R3c）=或N =; R 1是C 2 -C 6烷基，取代的C 2 -C 6烷基，C 3 -C 7环烷基，取代的C 3 -C 7环烷基，苯基，取代的苯基，杂环或取代的杂环; R 2是氢，C 1 -C 3正烷基，C 3 -C 6环烷基-C 1 -C 3烷基或式II基团，条件是当R 1是C 2 -C 6烷基或取代的C 2 -C 6烷基时，R 2是氢或甲基; R3a，R3b，并且当X是-C（R3c）= R3c时，R3c各自独立地为氢，氟或甲基，条件是R3a，R3b和R3c中不超过一个可以不是氢; R4是氢或C1-C3烷基; R5是氢，C1-C3烷基或C3-C6环烷基羰基，条件是当R3a不是氢时，R5是氢; R6是氢或C1-C6烷基; n为1〜6的整数。 本发明的化合物可用于活化5HT1F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。

公开(公告)号：US06479435B1

公开(公告)日：2002-11-12

申请号：US09779674

申请日：2001-02-09

申请人： David A. Pulman ,  Bai-Ping Ying ,  Shao-Yong Wu ,  Sandeep Gupta ,  Hiroshi Shimoharada ,  Masamitsu Tsukamoto

发明人： David A. Pulman ,  Bai-Ping Ying ,  Shao-Yong Wu ,  Sandeep Gupta ,  Hiroshi Shimoharada ,  Masamitsu Tsukamoto

IPC分类号： C07D40312

CPC分类号： C07D401/12 ,  A01N31/14 ,  A01N33/22 ,  A01N37/48 ,  A01N43/40 ,  A01N43/50 ,  A01N43/54 ,  A01N43/56 ,  A01N43/653 ,  A01N43/66 ,  A01N43/713 ,  A01N43/80 ,  A01N43/90 ,  A01N47/06 ,  C07D403/12 ,  C07D471/04 ,  C07D487/04 ,  C07D513/04

摘要： Diaryl ether compounds useful in the control of weeds are described. An exemplary compound is represented by the general formula (I): In this formula Q is represented by Q1 X and Y represent a hydrogen atom, halogen atom, cyano group, nitro group or (C1-6)haloalkyl group; R1 is halogen; R2 and R3 represent a hydrogen atom, a (C1-6)alkyl group or a (C1-6)haloalkyl group . Methods of making the compounds are also described.

摘要翻译： 描述了可用于控制杂草的二芳基醚化合物。 示例性化合物由通式（I）表示：在该式中Q由Q1X表示，Y表示氢原子，卤素原子，氰基，硝基或（C1-6）卤代烷基; R1是卤素; R2和R3表示氢原子，（C1-6）烷基或（C1-6）卤代烷基。 还描述了制备化合物的方法。

公开(公告)号：US06333296B1

公开(公告)日：2001-12-25

申请号：US09380830

申请日：1999-09-10

申请人： David A. Pulman ,  Bai-Ping Ying ,  Shao-Yong Wu ,  Sandeep Gupta ,  Hiroshi Shimoharada ,  Masamitsu Tsukamoto

发明人： David A. Pulman ,  Bai-Ping Ying ,  Shao-Yong Wu ,  Sandeep Gupta ,  Hiroshi Shimoharada ,  Masamitsu Tsukamoto

IPC分类号： C07D23946

CPC分类号： C07D401/12 ,  A01N31/14 ,  A01N33/22 ,  A01N37/48 ,  A01N43/40 ,  A01N43/50 ,  A01N43/54 ,  A01N43/56 ,  A01N43/653 ,  A01N43/66 ,  A01N43/713 ,  A01N43/80 ,  A01N43/90 ,  A01N47/06 ,  C07D403/12 ,  C07D471/04 ,  C07D487/04 ,  C07D513/04

摘要： Diaryl ether compounds useful in the control of weeds are described. An exemplary compound is represented by the general formula (I): In this formula Q is represented by Q9: X and Y represent a hydrogen atom, halogen atom, cyano group, nitro group or (C1-6)haloalkyl group. A1 and A2 are independently oxygen or sulfur atoms. R9 and R10 represent a hydrogen atom, a (C1-6)alkyl group, an acyl group, or a (C1-6)alkylsulfonyl group; or R9 and R10 may form a ring consisting of polymethylene, (CH2)m groups, where m is an integer of 2, 3, 4 or 5, together with the nitrogen atom of NR9R10, which may or may not have a (C1-6)alkyl substituent. Methods of making the compounds are also described.

摘要翻译： 描述了可用于控制杂草的二芳基醚化合物。 示例性化合物由通式（I）表示：在该式中Q由Q 9表示：X，Y表示氢原子，卤素原子，氰基，硝基或（C 1-6）卤代烷基。 A1和A2独立地是氧或硫原子。 R9和R10表示氢原子，（C1-6）烷基，酰基或（C1-6）烷基磺酰基; 或R 9和R 10可以形成由多亚甲基，（CH 2）m基团组成的环，其中m是2,3,4或5的整数，以及NR 9 R 10的氮原子，其可以具有或不具有（C1- 6）烷基取代基。 还描述了制备化合物的方法。

公开(公告)号：US06294503B1

公开(公告)日：2001-09-25

申请号：US09204060

申请日：1998-12-03

申请人： Sandeep Gupta ,  Shao-Yong Wu ,  Masamitsu Tsukamoto ,  Bai-Ping Ying ,  David A. Pulman

发明人： Sandeep Gupta ,  Shao-Yong Wu ,  Masamitsu Tsukamoto ,  Bai-Ping Ying ,  David A. Pulman

IPC分类号： A01N4384

CPC分类号： C07D413/04 ,  A01N43/84 ,  A01N43/90 ,  A01N47/20 ,  A01N47/22 ,  A01N53/00 ,  C07D471/04

摘要： Novel fused heterocycle compounds represented by the formula (I) are described. Q, R, W, —L—X—, Y, Z, and n are as defined in the disclosure. Also described are the processes for the manufacture of these compounds and agriculturally suitable compositions containing these as active ingredients which are useful as herbicides for general or selective pre-emergent or post-emergent control of undesired plant species.

摘要翻译： 描述由式（I）表示的新型稠合杂环化合物。 Q，R，W，-L-X-，Y，Z和n如本公开所定义。 还描述了制备这些化合物的方法和含有它们作为活性成分的农业合适的组合物，其可用作用于一般或选择性芽前或出苗后控制不需要的植物物种的除草剂。

公开(公告)号：US08748459B2

公开(公告)日：2014-06-10

申请号：US13363895

申请日：2012-02-01

申请人： Michael Philip Cohen ,  Daniel Timothy Kohlman ,  Sidney Xi Liang ,  Frantz Victor ,  Yao-Chang Xu ,  Bai-Ping Ying ,  DeAnna Piatt Zacherl ,  Deyi Zhang

发明人： Michael Philip Cohen ,  Daniel Timothy Kohlman ,  Sidney Xi Liang ,  Frantz Victor ,  Yao-Chang Xu ,  Bai-Ping Ying ,  DeAnna Piatt Zacherl ,  Deyi Zhang

IPC分类号： A61K31/445 ,  C07D401/06

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-HTlF 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烷基，C 3 -C 7环烷基，取代的C 3 -C 7环烷基，C 3 -C 7环烷基-C 1 -C 3烷基，取代的C 3 -C 7环烷基-C 1 -C 3烷基，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环烷基-C 1 -C 3烷基或式II的基团R 3是氢或C 1 -C 3烷基; R4是氢，卤素或C1-C3烷基; R5是氢或C1-C3烷基; R6是氢或C1-C6烷基; n为1〜6的整数。 本发明的化合物可用于激活5-HT1F受体，抑制神经元蛋白质外渗，以及用于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：US20120329820A1

公开(公告)日：2012-12-27

申请号：US13363895

申请日：2012-02-01

申请人： Michael P. Cohen ,  Daniel T. Kohlman ,  Sidney X. Liang ,  Frantz Victor ,  Yao-Chang Xu ,  Bai-Ping Ying ,  Deanna P. Zacherl ,  Deyi Zhang

发明人： Michael P. Cohen ,  Daniel T. Kohlman ,  Sidney X. Liang ,  Frantz Victor ,  Yao-Chang Xu ,  Bai-Ping Ying ,  Deanna P. Zacherl ,  Deyi Zhang

IPC分类号： A61K31/4545 ,  C07D409/14 ,  A61K31/506 ,  C07D405/14 ,  C07D417/14 ,  A61P25/06 ,  C07D401/06 ,  C07D401/14

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烷基，C 3 -C 7环烷基，取代的C 3 -C 7环烷基，C 3 -C 7环烷基-C 1 -C 3烷基，取代的C 3 -C 7环烷基-C 1 -C 3烷基，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环烷基-C 1 -C 3烷基或式II的基团R 3是氢或C 1 -C 3烷基; R4是氢，卤素或C1-C3烷基; R5是氢或C1-C3烷基; R6是氢或C1-C6烷基; n为1〜6的整数。 本发明的化合物可用于激活5-HT1F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：US07291632B2

公开(公告)日：2007-11-06

申请号：US10569109

申请日：2004-09-03

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

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

IPC分类号： A61K31/445 ,  C07D211/32 ,  C07D211/72 ,  C07D421/00

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.