公开(公告)号：US20080214616A1

公开(公告)日：2008-09-04

申请号：US11996126

申请日：2006-07-14

申请人： Larry Chris Blaszczak ,  Brian Michael Mathes ,  Shon Roland Pulley ,  Michael Alan Robertson ,  Scott Martin Sheehan ,  Qing Shi ,  Brian Morgan Watson ,  Michael Robert Wiley

发明人： Larry Chris Blaszczak ,  Brian Michael Mathes ,  Shon Roland Pulley ,  Michael Alan Robertson ,  Scott Martin Sheehan ,  Qing Shi ,  Brian Morgan Watson ,  Michael Robert Wiley

IPC分类号： A61K31/44 ,  C07D213/46 ,  A61K31/444 ,  A61P3/00

CPC分类号： C07D213/82 ,  C07D213/38

摘要： The present invention is directed to compounds of formula (I) or a pharmaceutically acceptable salt thereof; wherein A is (1); X is selected from CH, CF and N; R5 is selected from H, C1-C6 fluoroalkyl, and —OR12; R9 is selected from H —NR13C(O)R14 and —C(O)NR10R11; R12 is selected from H, C1-C6 alkyl and C3-C6 cycloalkyl, for use as inhibitors of the DPP-IV enzyme in the treatment or prevention of conditions including Type II diabetes.

摘要翻译： 本发明涉及式（I）化合物或其药学上可接受的盐; 其中A为（1）; X选自CH，CF和N; R 5选自H，C 1 -C 6氟代烷基和-OR 12; R 9选自H -NR 13 C（O）R 14和-C（O）NR 10 R 11; R 12选自H，C 1 -C 6烷基和C 3 -C 6环烷基，用于 作为DPP-IV酶的抑制剂，用于治疗或预防包括II型糖尿病的病症。

公开(公告)号：US06358972B1

公开(公告)日：2002-03-19

申请号：US09701934

申请日：2000-12-05

申请人： Sandra Ann Filla ,  Daniel James Koch ,  Brian Michael Mathes ,  Vincent Patrick Rocco

发明人： Sandra Ann Filla ,  Daniel James Koch ,  Brian Michael Mathes ,  Vincent Patrick Rocco

IPC分类号： A61K31435

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04

摘要： The present invention relates to a compound of formula (I): or a pharmaceutical acid addition salt thereof; which is useful for activating 5-HT1f receptors and inhibiting protein extravasation in a mammal.

摘要翻译： 本发明涉及式（I）化合物或其药用酸加成盐： 其可用于激活哺乳动物中的5-HT1f受体并抑制蛋白质外渗。

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.

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：US07417064B2

公开(公告)日：2008-08-26

申请号：US10532657

申请日：2003-10-24

申请人： Serge Louis Boulet ,  Sandra Ann Filla ,  Peter Thaddeus Gallagher ,  Kevin John Hudziak ,  Anette Margareta Johansson ,  Rushad E. Karanjawala ,  John Joseph Masters ,  Victor Giulio Matassa ,  Brian Michael Mathes ,  Richard Edmund Rathmell ,  Maria Ann Whatton ,  Chad Nolan Wolfe

发明人： Serge Louis Boulet ,  Sandra Ann Filla ,  Peter Thaddeus Gallagher ,  Kevin John Hudziak ,  Anette Margareta Johansson ,  Rushad E. Karanjawala ,  John Joseph Masters ,  Victor Giulio Matassa ,  Brian Michael Mathes ,  Richard Edmund Rathmell ,  Maria Ann Whatton ,  Chad Nolan Wolfe

IPC分类号： A61K31/381 ,  C07D333/64

CPC分类号： C07C217/20 ,  C07C217/34 ,  C07D333/54

摘要： There is provided a compound of formula (I) wherein A is selected from —O— and —S—; X is selected from C2-C8 alkyl, C2-C8 alkenyl, C3-C8 cycloalkyl and C4-C8 cycloalkylalkyl, each of which may be optionally substituted with up to 3 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n— where n is 0, 1 or 2, —CF3, —CN and —CONH2; Y is selected from phenyl, naphthyl, dihydrobenzothienyl, benzothiazolyl, benzoisothiazolyl, quinolyl, isoquinolyl, naphthyridyl, thienopyridyl, indanyl, 1,3-benzodioxolyl, benzothienyl, indolyl and benzofuranyl, each of which may be optionally substituted with up to 4 or, where possible, 5 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n— where n is 0, 1 or 2, nitro, acetyl, —CF3, —SCF3 and cyano; and when Y is indolyl it may be substituted or further substituted by an N-substituent selected from C1-C4 alkyl; Z is selected from H, OR3 or F, wherein R3 is selected from H, C1-C6 alkyl and phenyl C1-C6 alkyl; R1 and R2 are each independently H or C1-C4 alkyl; with the proviso that, when Z is H, then Y may not be optionally substituted phenyl or optionally substituted naphthyl.

公开(公告)号：US08133907B2

公开(公告)日：2012-03-13

申请号：US11996126

申请日：2006-07-14

申请人： Larry Chris Blaszczak ,  Brian Michael Mathes ,  Shon Roland Pulley ,  Michael Alan Robertson ,  Scott Martin Sheehan ,  Qing Shi ,  Brian Morgan Watson ,  Michael Robert Wiley

发明人： Larry Chris Blaszczak ,  Brian Michael Mathes ,  Shon Roland Pulley ,  Michael Alan Robertson ,  Scott Martin Sheehan ,  Qing Shi ,  Brian Morgan Watson ,  Michael Robert Wiley

IPC分类号： A61K31/4425 ,  A61K31/44 ,  C07D213/56 ,  C07D401/06

CPC分类号： C07D213/82 ,  C07D213/38

摘要： The present invention is directed to compounds of formula (I) or a pharmaceutically acceptable salt thereof; wherein A is (1); X is selected from CH, CF and N; R5 is selected from H, C1-C6 alkyl, C1-C6 fluoroalkyl, and —OR12; R9 is selected from H —NR13C(O)R14 and —C(O)NR10R11; R12 is selected from H, C1-C6 alkyl and C3-C6 cycloalkyl, for use as inhibitors of the DPP-IV enzyme in the treatment or prevention of conditions including Type II diabetes.

摘要翻译： 本发明涉及式（I）化合物或其药学上可接受的盐; 其中A为（1）; X选自CH，CF和N; R5选自H，C1-C6烷基，C1-C6氟烷基和-OR12; R 9选自H -NR 13 C（O）R 14和-C（O）NR 10 R 11; R12选自H，C1-C6烷基和C3-C6环烷基，用作DPP-IV酶的抑制剂，用于治疗或预防包括II型糖尿病的病症。

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：US07410982B2

公开(公告)日：2008-08-12

申请号：US10532765

申请日：2003-10-24

申请人： Serge Louis Boulet ,  Sandra Ann Filla ,  Peter Thaddeus Gallagher ,  Kevin John Hudziak ,  Anette Margareta Johansson ,  Rushad E. Karanjawala ,  John Joseph Masters ,  Brian Michael Mathes ,  Richard Edmund Rathmell ,  Maria Ann (nee Fagan) Whatton ,  Victor Matassa ,  Chad Nolan Wolfe

发明人： Serge Louis Boulet ,  Sandra Ann Filla ,  Peter Thaddeus Gallagher ,  Kevin John Hudziak ,  Anette Margareta Johansson ,  Rushad E. Karanjawala ,  John Joseph Masters ,  Brian Michael Mathes ,  Richard Edmund Rathmell ,  Maria Ann (nee Fagan) Whatton ,  Victor Matassa ,  Chad Nolan Wolfe

IPC分类号： A61K31/4365 ,  C07D409/02

CPC分类号： C07D275/04 ,  C07D215/20 ,  C07D217/02 ,  C07D217/04 ,  C07D217/24 ,  C07D277/62 ,  C07D333/54 ,  C07D471/04 ,  C07D495/04

摘要： There is provided a heretoaryloxy/thio 3-substituted propanamine compound of formula (I) wherein A is selected from —O— and —S—; X is selected from phenyl optionally substituted with up to 5 substituents each independently selected from halo, C1-C4 alkyl and C1-C4 alkoxy, thienyl optionally substituted with up to 3 substituents each independently selected from halo and C1-C4 alkyl, and C2-C8 alkyl, C2-C8 alkenyl, C3-C8 cycloalkyl and C4-C8 cycloalkylalkyl, each of which may be optionally substituted with up to 3 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl —S(O)n— where n is 0, 1 or 2, —CF3, —CN and —CONH2; Y is selected from dihydrobenzothienyl, benzothiazolyl, benzoisothiazolyl, quinolyl, isoquinolyl, naphthyridyl, and thienopyridyl, each of which may be optionally substituted with up to 4 or, where possible, up to 5 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n— where n is 0, 1 or 2, nitro acetyl, —CF3, —SCF3 and cyano; Z is selected from H, OR3 or F, wherein R3 is selected from H, C1-C6 alkyl and phenyl C1C6 alkyl; R1 and R2 are each independently H or C1-C4 alkyl; and pharmaceutically acceptable salts thereof.

公开(公告)号：US07410996B2

公开(公告)日：2008-08-12

申请号：US10533328

申请日：2003-10-24

申请人： Serge Louis Boulet ,  Sandra Ann Filla ,  Peter Thaddeus Gallagher ,  Kevin John Hudziak ,  Anette Margareta Johansson ,  Rushad E. Karanjawala ,  John Joseph Masters ,  Victor Giulio Matassa ,  Brian Michael Mathes ,  Richard Edmund Rathmell ,  Maria Ann Whatton ,  Chad Nolan Wolfe

发明人： Serge Louis Boulet ,  Sandra Ann Filla ,  Peter Thaddeus Gallagher ,  Kevin John Hudziak ,  Anette Margareta Johansson ,  Rushad E. Karanjawala ,  John Joseph Masters ,  Victor Giulio Matassa ,  Brian Michael Mathes ,  Richard Edmund Rathmell ,  Maria Ann Whatton ,  Chad Nolan Wolfe

IPC分类号： A61K31/381 ,  C07D333/64

CPC分类号： C07D275/04 ,  C07C217/16 ,  C07C217/30 ,  C07C217/48 ,  C07C323/32 ,  C07D307/86 ,  C07D333/54 ,  C07D333/62 ,  C07D475/04

摘要： There is provided a compound of formula (I) wherein A is selected from —O— and —S—; X is selected from phenyl optionally substituted with up to 5 substituents each independently selected from halo, C1-C4 alkyl and C1-C4 alkoxy, thienyl optionally substituted with up to 3 substituents each independently selected from halo and C1-C4 alkyl, and C2-C8 alkyl, C2-C8 alkenyl, C3-C8 cycloalkyl and C4-C8 cycloalkylalkyl, each of which may be optionally substituted with up to 3 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n— where n is 0, 1 or 2, —CF3, —CN and —CONH2; Y is selected from phenyl, naphthyl, dihydrobenzothienyl, benzothiazolyl, benzoisothiazolyl, quinolyl, isoquinolyl, naphthyridyl, thienopyridyl, indanyl, 1,3-benzodioxolyl, benzothienyl, indolyl and benzofuranyl, each of which may be optionally substituted with up to 4 or, where possible, up to 5 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n— where n is 0, 1 or 2, nitro, acetyl, —CF3, —SCF3 and cyano; and when Y is indolyl it may be substituted or further substituted by an N-substituent selected from C1-C4 alkyl; Z is selected from OR3 or F, wherein R3 is selected from H, C1-C6 alkyl and phenyl C1-C6 alkyl; R1 and R2 are each independently H or C1-C4 alkyl; and pharmaceutically acceptable salts thereof with the proviso that when Y is optionally substituted phenyl or optionally substituted 1,3-benzodioxolyl and Z is OR3 and X is optionally substituted phenyl then A is —S—.

公开(公告)号：US06953805B2

公开(公告)日：2005-10-11

申请号：US10451819

申请日：2001-12-20

申请人： Sandra Ann Filla ,  Kevin John Hudziak ,  Brian Michael Mathes ,  Paul Leslie Ornstein

发明人： Sandra Ann Filla ,  Kevin John Hudziak ,  Brian Michael Mathes ,  Paul Leslie Ornstein

IPC分类号： A61K31/00 ,  A61K31/47 ,  A61P25/00 ,  A61P25/06 ,  C07D401/04 ,  C07D401/06 ,  C07D401/14

CPC分类号： C07D401/14 ,  C07D401/04 ,  C07D401/06

摘要： The present invention provides novel compounds of Formula I or Formula II, or the pharmaceutically acceptable salts or prodrugs thereof, pharmaceutical compositions comprising an effective amount of a compound of Formula I or Formula II in combination with a suitable carrier, diluent, or excipient, and methods for treating neurological disorders and neurodegenerative diseases, particularly pain and migraine.

摘要翻译： 本发明提供式I或式II的新化合物或其药学上可接受的盐或前药，药物组合物包含有效量的式I或式II化合物与合适的载体，稀释剂或赋形剂的组合，和 治疗神经系统疾病和神经变性疾病，特别是疼痛和偏头痛的方法。