公开(公告)号：US07691884B2

公开(公告)日：2010-04-06

申请号：US11081784

申请日：2005-03-16

申请人： Anthony Frank Kreft ,  Derek C. Cole ,  Kevin R. Woller ,  Joseph R. Stock ,  George Diamantidis ,  Dennis M. Kubrak ,  Kristina M. Kutterer ,  William J. Moore ,  David S. Casebier

发明人： Anthony Frank Kreft ,  Derek C. Cole ,  Kevin R. Woller ,  Joseph R. Stock ,  George Diamantidis ,  Dennis M. Kubrak ,  Kristina M. Kutterer ,  William J. Moore ,  David S. Casebier

IPC分类号： A61K31/44 ,  A61K31/38 ,  A61K31/335 ,  A61K31/34 ,  C07D409/12 ,  C07D333/34 ,  C07D407/12 ,  C07D307/34

CPC分类号： C07D409/12 ,  C07D307/64 ,  C07D333/34

摘要： Compounds of Formula (I), wherein R1, R2, R3, R4, R5, R6, T, W, X, Y and Z are as defined herein are provided, together with pharmaceutically acceptable salt, hydrates and/or prodrugs thereof. Methods of using these compounds for determining β-amyloid levels in a subject are described.

摘要翻译： 提供其中R1，R2，R3，R4，R5，R6，T，W，X，Y和Z如本文所定义的式（I）化合物及其药学上可接受的盐，水合物和/或前药。 描述了使用这些化合物来测定受试者中的β-淀粉样蛋白水平的方法。

公开(公告)号：US07842718B2

公开(公告)日：2010-11-30

申请号：US12576513

申请日：2009-10-09

申请人： Anthony Frank Kreft ,  Derek Cecil Cole ,  Kevin R. Woller ,  Joseph Raymond Stock ,  George Diamantidis ,  Dennis Michael Kubrak ,  Kristina Martha Kutterer ,  William J. Moore ,  David S. Casebier

发明人： Anthony Frank Kreft ,  Derek Cecil Cole ,  Kevin R. Woller ,  Joseph Raymond Stock ,  George Diamantidis ,  Dennis Michael Kubrak ,  Kristina Martha Kutterer ,  William J. Moore ,  David S. Casebier

IPC分类号： A61K31/381 ,  C07D333/34

CPC分类号： C07D409/12 ,  C07D307/64 ,  C07D333/34

摘要： Compounds of Formula (I), wherein R1, R2, R3, R4, R5, R6, T, W, X, Y and Z are as defined herein are provided, together with pharmaceutically acceptable salt, hydrates and/or prodrugs thereof. Methods of using these compounds for inhibiting beta amyloid production and for treatment of Alzheimer's disease and Down's syndrome are described.

摘要翻译： 提供其中R1，R2，R3，R4，R5，R6，T，W，X，Y和Z如本文所定义的式（I）化合物及其药学上可接受的盐，水合物和/或前药。 描述了使用这些化合物抑制β淀粉样蛋白生成和治疗阿尔茨海默病和唐氏综合征的方法。

公开(公告)号：US07858658B2

公开(公告)日：2010-12-28

申请号：US12435442

申请日：2009-05-05

申请人： Anthony Frank Kreft ,  Lynn Resnick ,  Scott Christian Mayer ,  George Diamantidis ,  Derek Cecil Cole ,  Boyd Lynn Harrison ,  Minsheng Zhang ,  Molly Hoke ,  Tingzhong Wang ,  Rocco John Galante

发明人： Anthony Frank Kreft ,  Lynn Resnick ,  Scott Christian Mayer ,  George Diamantidis ,  Derek Cecil Cole ,  Boyd Lynn Harrison ,  Minsheng Zhang ,  Molly Hoke ,  Tingzhong Wang ,  Rocco John Galante

IPC分类号： A61K31/381 ,  C07D333/34

CPC分类号： C07D333/62 ,  C07D231/18 ,  C07D333/34

摘要： Compounds of Formula (I), are provided where T is CHO, COR8, or C(OH)R1R2; R1 and R2 are hydrogen, optionally substituted lower alkyl, CF3, optionally substituted alkenyl, or optionally substituted alkynyl; R3 is hydrogen or optionally substituted lower alkyl; R4 is (CF3)nalkyl, (CF3)n(substitutedalkyl), (CF3)nalkylphenyl, (CF3)nalkyl(substitutedphenyl), or (F)ncycloalkyl; n=1-3; R5 is hydrogen, halogen, CF3, diene fused to Y when Y=C, or substituted diene fused to Y when Y=C; W, Y and Z are C, CR6 or N where at least one of W, Y or Z are C; R6 is hydrogen, halogen, or optionally substituted lower alkyl; X is O, S, SO2, or NR7; R7 is hydrogen, optionally substituted lower alkyl, optionally substituted benzyl, or optionally substituted phenyl; and R8 is lower alkyl, CF3, or optionally substituted phenyl. Methods of preparing and using these compounds for inhibiting beta amyloid production and for treatment of Alzheimer's Disease and Down's syndrome are also described.

摘要翻译： 提供式（I）化合物，其中T是CHO，COR8或C（OH）R 1 R 2; R 1和R 2是氢，任选取代的低级烷基，CF 3，任选取代的烯基或任选取代的炔基; R3是氢或任选取代的低级烷基; R4是（CF3）n烷基，（CF3）n（取代烷基），（CF3）n烷基苯基，（CF3）n烷基（取代苯基）或（F）n环烷基; n = 1-3; 当Y = C时，R 5为氢，卤素，CF 3，与Y稠合的二烯，或Y = C时与Y稠合的取代二烯; W，Y和Z是C，CR 6或N，其中W，Y或Z中的至少一个是C; R6是氢，卤素或任选取代的低级烷基; X是O，S，SO 2或NR 7; R 7是氢，任选取代的低级烷基，任选取代的苄基或任选取代的苯基; 且R 8为低级烷基，CF 3或任选取代的苯基。 还描述了制备和使用这些化合物抑制β-淀粉样蛋白产生和治疗阿尔茨海默病和唐氏综合征的方法。

公开(公告)号：US20090227667A1

公开(公告)日：2009-09-10

申请号：US12435442

申请日：2009-05-05

申请人： Anthony Frank Kreft ,  Lynn Resnick ,  Scott Christian Mayer ,  George Diamantidis ,  Derek Cecil Cole ,  Boyd Lynn Harrison ,  Minsheng Zhang ,  Molly Hoke ,  Tingzhong Wang ,  Rocco John Galante

发明人： Anthony Frank Kreft ,  Lynn Resnick ,  Scott Christian Mayer ,  George Diamantidis ,  Derek Cecil Cole ,  Boyd Lynn Harrison ,  Minsheng Zhang ,  Molly Hoke ,  Tingzhong Wang ,  Rocco John Galante

IPC分类号： A61K31/381 ,  C07D333/34 ,  C07D333/62

CPC分类号： C07D333/62 ,  C07D231/18 ,  C07D333/34

摘要： Compounds of Formula (I), are provided where T is CHO, COR8, or C(OH)R1R2; R1 and R2 are hydrogen, optionally substituted lower alkyl, CF3, optionally substituted alkenyl, or optionally substituted alkynyl; R3 is hydrogen or optionally substituted lower alkyl; R4 is (CF3)nalkyl, (CF3)n(substitutedalkyl), (CF3)nalkylphenyl, (CF3)nalkyl(substitutedphenyl), or (F)ncycloalkyl; n=1-3; R5 is hydrogen, halogen, CF3, diene fused to Y when Y=C, or substituted diene fused to Y when Y=C; W, Y and Z are C, CR6 or N where at least one of W, Y or Z are C; R6 is hydrogen, halogen, or optionally substituted lower alkyl; X is O, S, SO2, or NR7; R7 is hydrogen, optionally substituted lower alkyl, optionally substituted benzyl, or optionally substituted phenyl; and R8 is lower alkyl, CF3, or optionally substituted phenyl. Methods of preparing and using these compounds for inhibiting beta amyloid production and for treatment of Alzheimer's Disease and Down's syndrome are also described.

摘要翻译： 提供式（I）化合物，其中T是CHO，COR8或C（OH）R 1 R 2; R 1和R 2是氢，任选取代的低级烷基，CF 3，任选取代的烯基或任选取代的炔基; R3是氢或任选取代的低级烷基; R4是（CF3）n烷基，（CF3）n（取代烷基），（CF3）n烷基苯基，（CF3）n烷基（取代苯基）或（F）n环烷基; n = 1-3; 当Y = C时，R 5为氢，卤素，CF 3，与Y稠合的二烯，或Y = C时与Y稠合的取代二烯; W，Y和Z是C，CR 6或N，其中W，Y或Z中的至少一个是C; R6是氢，卤素或任选取代的低级烷基; X是O，S，SO 2或NR 7; R 7是氢，任选取代的低级烷基，任选取代的苄基或任选取代的苯基; 且R 8为低级烷基，CF 3或任选取代的苯基。 还描述了制备和使用这些化合物抑制β-淀粉样蛋白产生和治疗阿尔茨海默病和唐氏综合征的方法。

公开(公告)号：US07547725B2

公开(公告)日：2009-06-16

申请号：US11818630

申请日：2007-06-15

申请人： Anthony Frank Kreft ,  Lynn Resnick ,  Scott Christian Mayer ,  George Diamantidis ,  Derek Cecil Cole ,  Boyd Lynn Harrison ,  Minsheng Zhang ,  Molly Hoke ,  Tingzhong Wang ,  Rocco John Galante

发明人： Anthony Frank Kreft ,  Lynn Resnick ,  Scott Christian Mayer ,  George Diamantidis ,  Derek Cecil Cole ,  Boyd Lynn Harrison ,  Minsheng Zhang ,  Molly Hoke ,  Tingzhong Wang ,  Rocco John Galante

IPC分类号： A61K31/381 ,  C07D333/10 ,  C07D333/34

CPC分类号： C07D333/62 ,  C07D231/18 ,  C07D333/34

摘要： Compounds of Formula (I), are provided where T is CHO, COR8, or C(OH)R1R2; R1 and R2 are hydrogen, optionally substituted lower alkyl, CF3, optionally substituted alkenyl, or optionally substituted alkynyl; R3 is hydrogen or optionally substituted lower alkyl; R4 is (CF3)nalkyl, (CF3)n(substituted alkyl), (CF3)nalkylphenyl, (CF3)nalkyl(substituted phenyl), or (F)ncycloalkyl; n=1-3; R5 is hydrogen, halogen, CF3, diene fused to Y when Y═C, or substituted diene fused to Y when Y═C; W, Y and Z are C, CR6 or N where at least one of W, Y or Z are C; R6 is hydrogen, halogen, or optionally substituted lower alkyl; X is O, S, SO2, or NR7; R7 is hydrogen, optionally substituted lower alkyl, optionally substituted benzyl, or optionally substituted phenyl; and R8 is lower alkyl, CF3, or optionally substituted phenyl. Methods of preparing and using these compounds for inhibiting beta amyloid production and for treatment of Alzheimer's Disease and Down's syndrome are also described.

摘要翻译： 提供式（I）化合物，其中T是CHO，COR8或C（OH）R 1 R 2; R 1和R 2是氢，任选取代的低级烷基，CF 3，任选取代的烯基或任选取代的炔基; R3是氢或任选取代的低级烷基; R4是（CF3）n烷基，（CF3）n（取代烷基），（CF3）n烷基苯基，（CF3）n烷基（取代苯基）或（F） n = 1-3; 当Y-C或Y-C与Y稠合时，R 5为氢，卤素，CF 3，二烯稠合至Y; W，Y和Z是C，CR 6或N，其中W，Y或Z中的至少一个是C; R6是氢，卤素或任选取代的低级烷基; X是O，S，SO 2或NR 7; R 7是氢，任选取代的低级烷基，任选取代的苄基或任选取代的苯基; 且R 8为低级烷基，CF 3或任选取代的苯基。 还描述了制备和使用这些化合物抑制β-淀粉样蛋白产生和治疗阿尔茨海默病和唐氏综合征的方法。

公开(公告)号：US07300951B2

公开(公告)日：2007-11-27

申请号：US10810517

申请日：2004-03-26

申请人： Anthony Frank Kreft ,  Lynn Resnick ,  Scott Christian Mayer ,  George Diamantidis ,  Derek Cecil Cole ,  Boyd Lynn Harrison ,  Minsheng Zhang ,  Molly Hoke ,  Tingzhong Wang ,  Rocco John Galante

发明人： Anthony Frank Kreft ,  Lynn Resnick ,  Scott Christian Mayer ,  George Diamantidis ,  Derek Cecil Cole ,  Boyd Lynn Harrison ,  Minsheng Zhang ,  Molly Hoke ,  Tingzhong Wang ,  Rocco John Galante

IPC分类号： A61K31/381 ,  C07D333/10 ,  C07D333/34

CPC分类号： C07D333/62 ,  C07D231/18 ,  C07D333/34

摘要： Compounds of Formula (I), are provided where T is CHO, CON, or C(OH)R1R2; R1 and R2 are hydrogen, optionally substituted lower alkyl, CF3, optionally substituted alkenyl, or optionally substituted alkynyl; R3 is hydrogen or optionally substituted lower alkyl; R4 is (CF3)nalkyl, (CF3)n(substitutedalkyl), (CF3)nalkylphenyl, (CF3)nalkyl(substitutedphenyl), or (F)ncycloalkyl; n=1-3; R5 is hydrogen, halogen, CF3, diene fused to Y when Y═C, or substituted diene fused to Y when Y═C; W, Y and Z are C, CR6 or N where at least one of W, Y or Z are C; R6 is hydrogen, halogen, or optionally substituted lower alkyl; X is O, S, SO2, or NR7; R7 is hydrogen, optionally substituted lower alkyl, optionally substituted benzyl, or optionally substituted phenyl; and R8 is lower alkyl, CF3, or optionally substituted phenyl. Methods of preparing and using these compounds for inhibiting beta amyloid production and for treatment of Alzheimer's Disease and Down's syndrome are also described.

摘要翻译： 提供式（I）的化合物，其中T是CHO，CON或C（OH）R 1 R 2 R 2; R 1和R 2均为氢，任选取代的低级烷基，CF 3，任选取代的烯基或任选取代的炔基; R 3是氢或任选取代的低级烷基; R 4是（CF 3）n烷基，（CF 3 N）N（S） （取代的烷基），（CF 3）n烷基苯基，（CF 3）n烷基（取代的苯基）或（C 3 -C 6）烷基 （F）环烷基; n = 1-3; 当Y-C时，R 5是氢，卤素，CF 3 O，与Y稠合的二烯，或Y-C时与Y稠合的取代的二烯; W，Y和Z是C，CR 6或N，其中W，Y或Z中的至少一个是C; R 6是氢，卤素或任选取代的低级烷基; X是O，S，SO 2或NR 7; R 7是氢，任选取代的低级烷基，任选取代的苄基或任选取代的苯基; 和R 8是低级烷基，CF 3或任选取代的苯基。 还描述了制备和使用这些化合物抑制β-淀粉样蛋白产生和治疗阿尔茨海默病和唐氏综合征的方法。

公开(公告)号：US20100120725A1

公开(公告)日：2010-05-13

申请号：US12691193

申请日：2010-01-21

申请人： Anthony Frank Kreft ,  Derek Cecil Cole ,  Kevin Roger Woller ,  Joseph Raymond Stock ,  Kristina Martha Kutterer ,  Dennis Martin Kubrak ,  Charles William Mann ,  William Jay Moore ,  David Scott Casebier

发明人： Anthony Frank Kreft ,  Derek Cecil Cole ,  Kevin Roger Woller ,  Joseph Raymond Stock ,  Kristina Martha Kutterer ,  Dennis Martin Kubrak ,  Charles William Mann ,  William Jay Moore ,  David Scott Casebier

IPC分类号： A61K31/655 ,  A61K31/18 ,  G01N33/53 ,  C07C303/00 ,  C09B29/00

CPC分类号： C07C311/40 ,  A61K31/18 ,  A61K31/335 ,  A61K31/34 ,  A61K31/357 ,  A61K31/4245 ,  A61K31/655 ,  C07C311/17 ,  C07C311/18 ,  C07C311/20 ,  C07C311/29 ,  C07C323/49 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2602/08 ,  C07C2602/42 ,  C07D209/16 ,  C07D307/52 ,  C07D319/06

摘要： Compounds of Formula I, wherein R1-R8 are defined herein are provided, together with pharmaceutically acceptable salts, hydrates, metabolites, and/or prodrugs thereof. Uses of these compounds for inhibiting beta amyloid production and for the prevention and treatment of Alzheimer's disease and Down's syndrome are also described.

摘要翻译： 提供其中R 1 -R 8在本文中定义的式I化合物及其药学上可接受的盐，水合物，代谢物和/或前药。 还描述了这些化合物用于抑制β淀粉样蛋白生成和预防和治疗阿尔茨海默氏病和唐氏综合征的用途。

公开(公告)号：US07399778B2

公开(公告)日：2008-07-15

申请号：US11035005

申请日：2005-01-13

申请人： Lynn Resnick ,  Donna M. Huryn ,  Joan E. Sabalski ,  Joshua D. Berkowitz ,  Anthony Frank Kreft ,  Dennis Martin Kubrak ,  Thomas Joseph Caggiano ,  Koi Michele Morris

发明人： Lynn Resnick ,  Donna M. Huryn ,  Joan E. Sabalski ,  Joshua D. Berkowitz ,  Anthony Frank Kreft ,  Dennis Martin Kubrak ,  Thomas Joseph Caggiano ,  Koi Michele Morris

IPC分类号： A61K31/415 ,  C07D233/00

CPC分类号： A61K31/416 ,  C07D231/12 ,  C07D409/12

摘要： Compounds useful for lowering beta amyloid levels are provided. The compounds have the structure of formula Ia: wherein, R1 is lower alkyl, substituted lower alkyl, phenyl, substituted phenyl, benzyl, substituted benzyl, benzyloxy, substituted benzyloxy, or SO2R5; R5 is phenyl, substituted phenyl, heterocycle, substituted heterocycle, alkyl, or substituted alkyl; R2 is lower alkyl, substituted lower alkyl, CF3, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, or cycloalkyl; R3 is hydrogen, lower alkyl, or substituted lower alkyl; R4 is phenyl, substituted phenyl, heterocycle, substituted heterocycle, thiophene, or substituted thiophene; R6 is hydrogen, lower alkyl, substituted lower alkyl, CF3, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, cycloalkyl, or substituted cycloalkyl; W, X and Y are independently CR7 or N; and R7 is hydrogen, halogen, lower alkyl, or substituted lower alkyl.

摘要翻译： 提供了可用于降低β淀粉样蛋白水平的化合物。 化合物具有式Ia的结构：其中R 1是低级烷基，取代的低级烷基，苯基，取代的苯基，苄基，取代的苄基，苄氧基，取代的苄氧基或SO 2， / 5> 5

公开(公告)号：US07671075B2

公开(公告)日：2010-03-02

申请号：US11528001

申请日：2006-09-27

申请人： Anthony Frank Kreft ,  Derek Cecil Cole ,  Kevin Roger Woller ,  Joseph Raymond Stock ,  Kristina Martha Kutterer ,  Dennis Martin Kubrak ,  Charles William Mann ,  William Jay Moore ,  David Scott Casebier

发明人： Anthony Frank Kreft ,  Derek Cecil Cole ,  Kevin Roger Woller ,  Joseph Raymond Stock ,  Kristina Martha Kutterer ,  Dennis Martin Kubrak ,  Charles William Mann ,  William Jay Moore ,  David Scott Casebier

IPC分类号： A61K31/18 ,  A61K31/34 ,  A61K31/357 ,  A61K31/4245 ,  C07C311/17 ,  C07D209/14 ,  C07D271/12 ,  C07D307/52 ,  C07D317/08

CPC分类号： C07C311/40 ,  A61K31/18 ,  A61K31/335 ,  A61K31/34 ,  A61K31/357 ,  A61K31/4245 ,  A61K31/655 ,  C07C311/17 ,  C07C311/18 ,  C07C311/20 ,  C07C311/29 ,  C07C323/49 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2602/08 ,  C07C2602/42 ,  C07D209/16 ,  C07D307/52 ,  C07D319/06

摘要： Compounds of Formula I, wherein R1-R8 are defined herein are provided, together with pharmaceutically acceptable salts, hydrates, metabolites, and/or prodrugs thereof. Uses of these compounds for inhibiting beta amyloid production and for the prevention and treatment of Alzheimer's Disease and Down's syndrome are also described.

摘要翻译： 提供其中R 1 -R 8在本文中定义的式I化合物及其药学上可接受的盐，水合物，代谢物和/或前药。 还描述了这些化合物用于抑制β淀粉样蛋白生成和预防和治疗阿尔茨海默病和唐氏综合征的用途。

公开(公告)号：US20080249150A1

公开(公告)日：2008-10-09

申请号：US12142306

申请日：2008-06-19

申请人： Lynn Resnick ,  Donna M. Huryn ,  Joan E. Sabalski ,  Joshua D. Berkowitz ,  Anthony Frank Kreft ,  Dennis Martin Kubrak ,  Thomas Joseph Caggiano ,  Koi Michele Morris

发明人： Lynn Resnick ,  Donna M. Huryn ,  Joan E. Sabalski ,  Joshua D. Berkowitz ,  Anthony Frank Kreft ,  Dennis Martin Kubrak ,  Thomas Joseph Caggiano ,  Koi Michele Morris

IPC分类号： A61K31/4196 ,  C07D409/02 ,  A61K31/415 ,  A61P25/28 ,  C07D231/12

CPC分类号： A61K31/416 ,  C07D231/12 ,  C07D409/12

摘要： Compounds useful for lowering beta amyloid levels are provided. The compounds have the structure of formula Ia: wherein, R1 is lower alkyl, substituted lower alkyl, phenyl, substituted phenyl, benzyl, substituted benzyl, benzyloxy, substituted benzyloxy, or SO2R5; R5 is phenyl, substituted phenyl, heterocycle, substituted heterocycle, alkyl, or substituted alkyl; R2 is lower alkyl, substituted lower alkyl, CF3, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, or cycloalkyl; R3 is hydrogen, lower alkyl, or substituted lower alkyl; R4 is phenyl, substituted phenyl, heterocycle, substituted heterocycle, thiophene, or substituted thiophene; R6 is hydrogen, lower alkyl, substituted lower alkyl, CF3, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, cycloalkyl, or substituted cycloalkyl; W, X and Y are independently CR7 or N; and R7 is hydrogen, halogen, lower alkyl, or substituted lower alkyl.

摘要翻译： 提供了可用于降低β淀粉样蛋白水平的化合物。 化合物具有式Ia的结构：其中R 1是低级烷基，取代的低级烷基，苯基，取代的苯基，苄基，取代的苄基，苄氧基，取代的苄氧基或SO 2， / 5> 5