公开(公告)号：US08183238B2

公开(公告)日：2012-05-22

申请号：US12816612

申请日：2010-06-16

Applicant: Michelle M. Claffey ,  Amy B. Dounay ,  Matthew M. Hayward ,  Suobao Rong ,  Patrick R. Verhoest ,  Jamison B. Tuttle ,  Xinmin Gan

Inventor： Michelle M. Claffey ,  Amy B. Dounay ,  Matthew M. Hayward ,  Suobao Rong ,  Patrick R. Verhoest ,  Jamison B. Tuttle ,  Xinmin Gan

IPC: A61K31/52 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/4375 ,  A61K31/473 ,  A61K31/4741 ,  A61K31/506 ,  A61K31/501 ,  A61K31/517 ,  C07D473/30 ,  C07D473/20 ,  C07D413/12 ,  C07D405/10 ,  C07D401/10 ,  C07D401/04 ,  C07D471/04 ,  C07D215/58 ,  C07D221/10 ,  C07D413/10 ,  C07D491/048 ,  C07D487/04

CPC classification number: C07D215/60 ,  C07D401/04 ,  C07D401/12 ,  C07D405/04 ,  C07D471/04 ,  C07D491/04

Abstract: Compounds of Formula X: wherein A, X, Y, Z, R5, R6a, and R6b are as defined herein, and pharmaceutically acceptable salts thereof, are described as useful for the treatment of cognitive deficits associated with schizophrenia and other neurodegenerative and/or neurological disorders in mammals, including humans.

Abstract translation: 式X的化合物：其中A，X，Y，Z，R 5，R 6a和R 6b如本文所定义，及其药学上可接受的盐被描述为可用于治疗与精神分裂症和其它神经变性和/或其它神经变性相关的认知缺陷 包括人在内的哺乳动物的神经障碍。

公开(公告)号：US07825254B2

公开(公告)日：2010-11-02

申请号：US12037964

申请日：2008-02-27

Applicant: Patrick R. Verhoest ,  Christopher J. Helal ,  Dennis J. Hoover ,  John M. Humphrey

Inventor： Patrick R. Verhoest ,  Christopher J. Helal ,  Dennis J. Hoover ,  John M. Humphrey

IPC: C07D215/12 ,  A61K31/47

CPC classification number: C07D401/14 ,  C07D413/14

Abstract: The invention pertains to heteroaromatic compounds that serve as effective phosphodiesterase (PDE) inhibitors. In particular, the invention relates to said compounds which are selective inhibitors of PDE10. The invention also relates to intermediates for preparation of said compounds; pharmaceutical compositions comprising said compounds; and the use of said compounds in a method for treating certain central nervous system (CNS) or other disorders.

Abstract translation: 本发明涉及用作有效磷酸二酯酶（PDE）抑制剂的杂芳族化合物。 特别地，本发明涉及作为PDE10的选择性抑制剂的所述化合物。 本发明还涉及制备所述化合物的中间体; 包含所述化合物的药物组合物; 以及所述化合物在治疗某些中枢神经系统（CNS）或其它疾病的方法中的用途。

公开(公告)号：US07429665B2

公开(公告)日：2008-09-30

申请号：US11326221

申请日：2006-01-05

Applicant: Patrick R. Verhoest ,  Christopher J. Helal ,  Dennis J. Hoover ,  John M. Humphrey

Inventor： Patrick R. Verhoest ,  Christopher J. Helal ,  Dennis J. Hoover ,  John M. Humphrey

IPC: C07D215/00 ,  A01N43/42

CPC classification number: C07D401/14 ,  C07D413/14

Abstract: The invention pertains to heteroaromatic compounds that serve as effective phosphodiesterase (PDE) inhibitors. In particular, the invention relates to said compounds which are selective inhibitors of PDE10. The invention also relates to intermediates for preparation of said compounds; pharmaceutical compositions comprising said compounds; and the use of said compounds in a method for treating certain central nervous system (CNS) or other disorders.

Abstract translation: 本发明涉及用作有效磷酸二酯酶（PDE）抑制剂的杂芳族化合物。 特别地，本发明涉及作为PDE10的选择性抑制剂的所述化合物。 本发明还涉及制备所述化合物的中间体; 包含所述化合物的药物组合物; 以及所述化合物在治疗某些中枢神经系统（CNS）或其它疾病的方法中的用途。

公开(公告)号：US20080214607A1

公开(公告)日：2008-09-04

申请号：US12037964

申请日：2008-02-27

Applicant: Patrick R. Verhoest ,  Christopher J. Helal ,  Dennis J. Hoover ,  John M. Humphrey

Inventor： Patrick R. Verhoest ,  Christopher J. Helal ,  Dennis J. Hoover ,  John M. Humphrey

IPC: A61K31/4709 ,  C07D215/14 ,  A61P25/36 ,  A61P25/00 ,  A61P3/04

CPC classification number: C07D401/14 ,  C07D413/14

Abstract: The invention pertains to heteroaromatic compounds that serve as effective phosphodiesterase (PDE) inhibitors. In particular, the invention relates to said compounds which are selective inhibitors of PDE10. The invention also relates to intermediates for preparation of said compounds; pharmaceutical compositions comprising said compounds; and the use of said compounds in a method for treating certain central nervous system (CNS) or other disorders.

Abstract translation: 本发明涉及用作有效磷酸二酯酶（PDE）抑制剂的杂芳族化合物。 特别地，本发明涉及作为PDE10的选择性抑制剂的所述化合物。 本发明还涉及制备所述化合物的中间体; 包含所述化合物的药物组合物; 以及所述化合物在治疗某些中枢神经系统（CNS）或其它疾病的方法中的用途。

公开(公告)号：US07087617B2

公开(公告)日：2006-08-08

申请号：US10839055

申请日：2004-05-05

Applicant: Jeffrey W. Corbett ,  Michael Dalton Ennis ,  Kristine E. Frank ,  Jian-Min Fu ,  Robert Louis Hoffman ,  Patrick R. Verhoest

Inventor： Jeffrey W. Corbett ,  Michael Dalton Ennis ,  Kristine E. Frank ,  Jian-Min Fu ,  Robert Louis Hoffman ,  Patrick R. Verhoest

IPC: A61K31/505 ,  C07D239/32

CPC classification number: C07D239/42 ,  C07D213/72

Abstract: This invention relates to compounds of Formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, or a pharmaceutically acceptable salt of a prodrug thereof. The compounds interact with CRF1 receptors, including human CRF1 receptors. This invention also relates to methods of using the compounds of the invention to treat a disorder or condition, the treatment of which can be effected or facilitated by antagonizing a CRF receptor, such as CNS disorders or diseases, particularly anxiety-related disorders such as anxiety, and mood disorders such as major depression.

Abstract translation: 本发明涉及式I化合物，其立体异构体，其药学上可接受的盐，其前药或其前药的药学上可接受的盐。 这些化合物与CRF1受体（包括人CRF 1受体）相互作用。 本发明还涉及使用本发明化合物治疗病症或病症的方法，所述疾病或病症的治疗可以通过拮抗CRF受体如CNS疾病或疾病，特别是焦虑相关疾病例如焦虑来实现或促进 ，以及心理障碍如重度抑郁症。

公开(公告)号：US07041672B2

公开(公告)日：2006-05-09

申请号：US10844004

申请日：2004-05-12

Applicant: Patrick R. Verhoest ,  Jeffrey W. Corbett ,  Michael Dalton Ennis ,  Kristine E. Frank ,  Jian-Min Fu ,  Robert Louis Hoffman

Inventor： Patrick R. Verhoest ,  Jeffrey W. Corbett ,  Michael Dalton Ennis ,  Kristine E. Frank ,  Jian-Min Fu ,  Robert Louis Hoffman

IPC: A61K31/4965 ,  C07D401/00 ,  C07D403/00 ,  C07D405/00 ,  C07D409/00

CPC classification number: C07D241/18 ,  C07D241/20 ,  C07D241/26 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D491/04 ,  G01N33/74 ,  G01N2333/5751 ,  G01N2500/02 ,  Y10S206/828

Abstract: Substituted aryl pyrazine derivatives of the formula I as defined herein, and their use in treating anxiety disorders, depression and stress related disorders are disclosed.

Abstract translation: 公开了本文定义的式I的取代的芳基吡嗪衍生物及其在治疗焦虑症，抑郁症和应激相关疾病中的用途。

公开(公告)号：US08487104B2

公开(公告)日：2013-07-16

申请号：US13307140

申请日：2011-11-30

Applicant: Amy B Dounay ,  Christopher J Helal ,  Jamison B Tuttle ,  Patrick R Verhoest

Inventor： Amy B Dounay ,  Christopher J Helal ,  Jamison B Tuttle ,  Patrick R Verhoest

IPC: C07D215/58

CPC classification number: C07D215/58

Abstract: The present invention relates to compounds 3-amino-1-hydroxy-2-oxo-1,2,3, 4-tetrahydroquinoline-7-carbonitrile, 3-amino-1-hydroxy-7-(2-methoxyethoxy)-3,4-dihydroquinolin-2(1H)-one, and 3-amino-1-hydroxy-7-[(1S)-2-methoxy-1-methylethoxy]-3,4-dihydroquinolin-2(1H)-one, including racemic mixtures and resolved enantiomers thereof, to pharmaceutically acceptable salts thereof, and to the treatment of cognitive deficits associated with schizophrenia and other psychiatric, neurodegenerative and/or neurological disorders in mammals, including humans.

Abstract translation: 本发明涉及3-氨基-1-羟基-2-氧代-1,2,3,4-四氢喹啉-7-腈，3-氨基-1-羟基-7-（2-甲氧基乙氧基） （1H） - 酮和3-氨基-1-羟基-7 - [（1S）-2-甲氧基-1-甲基乙氧基] -3,4-二氢喹啉-2（1H） - 酮，包括 外消旋混合物及其拆分的对映异构体，其药学上可接受的盐，以及治疗与哺乳动物（包括人）中的精神分裂症和其它精神病，神经变性和/或神经障碍有关的认知缺陷。

公开(公告)号：US06992087B2

公开(公告)日：2006-01-31

申请号：US10298193

申请日：2002-11-15

Applicant: Patrick R. Verhoest ,  Robert Louis Hoffman ,  Jeffrey W. Corbett ,  Michael Dalton Ennis ,  Kristine E. Frank ,  Jian-Min Fu

Inventor： Patrick R. Verhoest ,  Robert Louis Hoffman ,  Jeffrey W. Corbett ,  Michael Dalton Ennis ,  Kristine E. Frank ,  Jian-Min Fu

IPC: A61K31/4965 ,  C07D241/00 ,  C07D241/02 ,  B65D75/80

CPC classification number: C07D241/18 ,  C07D241/20 ,  C07D241/26 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D491/04 ,  G01N33/74 ,  G01N2333/5751 ,  G01N2500/02 ,  Y10S206/828

Abstract: Substituted aryl 1,4-pyrazine derivatives of formula I as defined herein and their use in treating anxiety disorders, depression and stress related disorders are disclosed.

Abstract translation: 公开了本文定义的式I的取代的芳基1,4-吡嗪衍生物及其在治疗焦虑症，抑郁症和应激相关疾病中的用途。

公开(公告)号：US08278295B2

公开(公告)日：2012-10-02

申请号：US12693480

申请日：2010-01-26

Applicant: Michelle M. Claffey ,  Christopher J. Helal ,  Patrick R. Verhoest

Inventor： Michelle M. Claffey ,  Christopher J. Helal ,  Patrick R. Verhoest

IPC: A01N43/00 ,  A01N43/90 ,  A61K31/00 ,  A61K31/519 ,  C07D487/00

CPC classification number: C07D487/04 ,  A61K31/13 ,  A61K31/27 ,  A61K31/444 ,  A61K31/445 ,  A61K31/473 ,  A61K31/519 ,  A61K31/55

Abstract: The invention provides PDE9-inhibiting compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, A, and n are as defined herein. Pharmaceutical compositions containing the compounds of Formula I, and uses thereof in treating neurodegenerative and cognitive disorders, such as Alzheimer's disease and schizophrenia, are also provided.

Abstract translation: 本发明提供抑制PDE9的式（I）化合物及其药学上可接受的盐，其中R 1，R 2，R 3，A和n如本文所定义。 还提供了含有式I化合物的药物组合物及其用于治疗神经变性和认知障碍如阿尔茨海默病和精神分裂症的用途。

公开(公告)号：US20120142729A1

公开(公告)日：2012-06-07

申请号：US13307140

申请日：2011-11-30

Applicant: AMY B. DOUNAY ,  Christopher J. Helal ,  Jamison B. Tuttle ,  Patrick R. Verhoest

Inventor： AMY B. DOUNAY ,  Christopher J. Helal ,  Jamison B. Tuttle ,  Patrick R. Verhoest

IPC: A61K31/4704 ,  A61P25/00 ,  A61P25/18 ,  A61P25/28 ,  A61P9/04 ,  A61P9/10 ,  A61P25/14 ,  A61P27/02 ,  A61P25/16 ,  A61P25/08 ,  A61P25/06 ,  A61P13/00 ,  A61P25/30 ,  A61P25/24 ,  A61P25/22 ,  A61P29/00 ,  A61P37/00 ,  A61P1/16 ,  A61P35/00 ,  A61P27/16 ,  A61P1/08 ,  C07D215/58

CPC classification number: C07D215/58

Abstract: The present invention relates to compounds 3-amino-1-hydroxy-2-oxo-1,2,3,4-tetrahydroquinoline-7-carbonitrile, 3-amino-1-hydroxy-7-(2-methoxyethoxy)-3,4-dihydroquinolin-2(1H)-one, and 3-amino-1-hydroxy-7-[(1S)-2-methoxy-1-methylethoxy]-3,4-dihydroquinolin-2(1H)-one, including racemic mixtures and resolved enantiomers thereof, to pharmaceutically acceptable salts thereof, and to the treatment of cognitive deficits associated with schizophrenia and other psychiatric, neurodegenerative and/or neurological disorders in mammals, including humans.

Abstract translation: 本发明涉及3-氨基-1-羟基-2-氧代-1,2,3,4-四氢喹啉-7-腈，3-氨基-1-羟基-7-（2-甲氧基乙氧基） （1H） - 酮和3-氨基-1-羟基-7 - [（1S）-2-甲氧基-1-甲基乙氧基] -3,4-二氢喹啉-2（1H） - 酮，包括 外消旋混合物及其拆分的对映异构体，其药学上可接受的盐，以及治疗与哺乳动物（包括人）中的精神分裂症和其它精神病，神经变性和/或神经障碍有关的认知缺陷。