公开(公告)号：US06423704B1

公开(公告)日：2002-07-23

申请号：US09739741

申请日：2000-12-18

Applicant: George D. Maynard ,  Tieu-Binh Le

Inventor： George D. Maynard ,  Tieu-Binh Le

IPC: A61K31551

Abstract: The present invention relates to novel 4-(1H-benzimidazol-2-yl)[1,4]diazepane derivatives of formula (1): and stereoisomers thereof, and pharmaceutically acceptable salts thereof which are useful as histamine receptor antagonists and tachykinin receptor antagonist. Such antagonists are useful in the treatment of allergic rhinitis, including seasonal rhinitis and sinusitis; inflammatory bowel diseases, including Crohn's disease and ulcerative colitis; asthma; bronchitis; and emesis.

公开(公告)号：US5864045A

公开(公告)日：1999-01-26

申请号：US67386

申请日：1998-04-27

Applicant: Timothy P. Burkholder ,  Elizabeth M. Kudlacz ,  Tieu-Binh Le

Inventor： Timothy P. Burkholder ,  Elizabeth M. Kudlacz ,  Tieu-Binh Le

IPC: A61K31/495 ,  A61P11/00 ,  A61P43/00 ,  C07D209/04 ,  C07D209/08 ,  C07D209/20 ,  C07D403/06 ,  C07D403/14

CPC classification number: C07D403/06 ,  C07D209/20 ,  C07D403/14

Abstract: The present invention relates to substituted piperazinone derivatives of formula (1) or stereoisomers, or pharmaceutically acceptable salts thereof and their use as tachykinin receptor antagonists. Such antagonists are useful in the treatment of tachykinin-mediated diseases and conditions disclosed herein including: asthma, cough, and bronchitis. The present invention also relates to intermediates useful in the preparation of compounds of formula (1).

Abstract translation: 本发明涉及式（1）的取代的哌嗪酮衍生物或其立体异构体或其药学上可接受的盐及其作为速激肽受体拮抗剂的用途。 这样的拮抗剂可用于治疗速激肽介导的疾病和本文公开的病症，包括：哮喘，咳嗽和支气管炎。 本发明还涉及可用于制备式（1）化合物的中间体。

公开(公告)号：US5672602A

公开(公告)日：1997-09-30

申请号：US640121

申请日：1996-04-30

Applicant: Timothy P. Burkholder ,  Tieu-Binh Le ,  Elizabeth M. Kudlacz

Inventor： Timothy P. Burkholder ,  Tieu-Binh Le ,  Elizabeth M. Kudlacz

IPC: C07D241/04 ,  A61K31/50 ,  A61P1/00 ,  A61P1/08 ,  A61P11/00 ,  A61P25/00 ,  A61P25/02 ,  A61P25/04 ,  A61P25/18 ,  A61P25/20 ,  A61P25/24 ,  A61P25/26 ,  A61P25/28 ,  A61P27/02 ,  A61P27/14 ,  A61P29/00 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07D241/08 ,  C07D309/12 ,  C07D403/06 ,  A61K31/495 ,  C07D403/04

CPC classification number: C07D403/06 ,  C07D241/08 ,  C07D309/12

Abstract: The present invention relates to substituted piperazine derivatives (herein referred to as compounds or compounds of formula (1)) or stereoisomers, or pharmaceutically acceptable salts thereof and their use as tachykinin receptor antagonists. Such antagonists are useful in the treatment of tachykinin-mediated diseases and conditions disclosed herein including: asthma, cough, and bronchitis.

Abstract translation: 本发明涉及取代的哌嗪衍生物（本文中称为化合物或式（1）的化合物）或其立体异构体或其药学上可接受的盐及其作为速激肽受体拮抗剂的用途。 这样的拮抗剂可用于治疗速激肽介导的疾病和本文公开的病症，包括：哮喘，咳嗽和支气管炎。

公开(公告)号：US08569535B2

公开(公告)日：2013-10-29

申请号：US12627546

申请日：2009-11-30

Applicant: Thomas Joseph Caulfield ,  Jennifer Williford Clemens ,  Robert S. Francis ,  Brian Scott Freed ,  Stanly John ,  Tieu-Binh Le ,  Brian Pedgrift ,  Antonio Daniel Ramos ,  Gerard Charles Rosse ,  Martin Smrcina ,  David Squire Thorpe ,  William Shelly Wire ,  Jianhong Zhao

Inventor： Thomas Joseph Caulfield ,  Jennifer Williford Clemens ,  Robert S. Francis ,  Brian Scott Freed ,  Stanly John ,  Tieu-Binh Le ,  Brian Pedgrift ,  Antonio Daniel Ramos ,  Gerard Charles Rosse ,  Martin Smrcina ,  David Squire Thorpe ,  William Shelly Wire ,  Jianhong Zhao

IPC: C07C229/00

CPC classification number: C07D333/78 ,  C07C233/52 ,  C07C233/63 ,  C07C233/81 ,  C07C235/42 ,  C07C235/54 ,  C07C235/62 ,  C07C235/84 ,  C07C237/42 ,  C07C255/13 ,  C07C255/57 ,  C07C311/09 ,  C07C311/29 ,  C07C317/44 ,  C07C323/62 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/10 ,  C07C2602/08 ,  C07C2602/10 ,  C07C2602/42 ,  C07C2603/26 ,  C07C2603/28 ,  C07C2603/74 ,  C07D213/81 ,  C07D307/79 ,  C07D333/68 ,  C07D401/04

Abstract: The present invention relates to novel compounds of the formula Ia: in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, wherein the substituents are as described herein. The inventive compounds have CXCR5 inhibitory activity, and are particularly useful in treating or preventing various inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis, lupus, Crohn's Disease, associated with the modulation of the human CXCR5 receptor.

Abstract translation: 本发明涉及式Ia的新化合物：其任何立体异构体形式或任何比例的立体异构形式的混合物或其生理上可接受的盐，其中取代基如本文所述。 本发明化合物具有CXCR5抑制活性，并且特别可用于治疗或预防与人CXCR5受体的调节相关的各种炎性疾病，例如类风湿性关节炎，多发性硬化，狼疮，克罗恩病。

公开(公告)号：US20100113462A1

公开(公告)日：2010-05-06

申请号：US12627546

申请日：2009-11-30

Applicant: Thomas J. CAULFIELD ,  Jennifer Williford CLEMENS ,  Robert S. FRANCIS ,  Brian S. FREED ,  Stanly JOHN ,  Tieu-Binh LE ,  Brian PEDGRIFT ,  Antonio D. RAMOS ,  Gerard Charles ROSSE ,  Martin SMRCINA ,  David S. THORPE ,  William WIRE ,  Jianhong ZHAO

Inventor： Thomas J. CAULFIELD ,  Jennifer Williford CLEMENS ,  Robert S. FRANCIS ,  Brian S. FREED ,  Stanly JOHN ,  Tieu-Binh LE ,  Brian PEDGRIFT ,  Antonio D. RAMOS ,  Gerard Charles ROSSE ,  Martin SMRCINA ,  David S. THORPE ,  William WIRE ,  Jianhong ZHAO

IPC: A61K31/196 ,  C07C229/50 ,  C07D215/38 ,  C07D241/36 ,  C07D401/04 ,  A61K31/47 ,  A61K31/498 ,  A61K31/4545 ,  A61P19/02 ,  A61P11/06

CPC classification number: C07D333/78 ,  C07C233/52 ,  C07C233/63 ,  C07C233/81 ,  C07C235/42 ,  C07C235/54 ,  C07C235/62 ,  C07C235/84 ,  C07C237/42 ,  C07C255/13 ,  C07C255/57 ,  C07C311/09 ,  C07C311/29 ,  C07C317/44 ,  C07C323/62 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/10 ,  C07C2602/08 ,  C07C2602/10 ,  C07C2602/42 ,  C07C2603/26 ,  C07C2603/28 ,  C07C2603/74 ,  C07D213/81 ,  C07D307/79 ,  C07D333/68 ,  C07D401/04

Abstract: The present invention relates to novel compounds of the formula I: wherein in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, wherein the substituents are as described herein. The inventive compounds have CXCR5 inhibitory activity are particularly useful in treating or preventing various inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis, lupus, Crohn's Disease, associated with the modulation of the human CXCR5 receptor.

Abstract translation: 本发明涉及式I的新化合物：其中任何立体异构形式或任何比例的立体异构形式的混合物或其生理上可接受的盐，其中取代基如本文所述。 本发明化合物具有CXCR5抑制活性，特别可用于治疗或预防与人CXCR5受体的调节相关的各种炎性疾病，例如类风湿性关节炎，多发性硬化，狼疮，克罗恩病。

公开(公告)号：US5861416A

公开(公告)日：1999-01-19

申请号：US795576

申请日：1997-02-06

Applicant: Timothy P. Burkholder ,  Tieu-Binh Le ,  Elizabeth M. Kudlacz ,  George D. Maynard

Inventor： Timothy P. Burkholder ,  Tieu-Binh Le ,  Elizabeth M. Kudlacz ,  George D. Maynard

IPC: C07D401/06 ,  C07D401/14 ,  C07D409/14 ,  C07D471/10 ,  A61K31/445 ,  C07D401/02

CPC classification number: C07D401/06 ,  C07D401/14 ,  C07D409/14 ,  C07D471/10

Abstract: The present invention relates to substituted pyrrolidinyl-3-yl-alkyl-piperidines, their stereoisomers, and pharmaceutically acceptable salts thereof and processes for preparation of the same. The compounds of the present invention are useful in their pharmacological activities such as tachykinin antagonism, especially substance P and neurokinin A antagonism, and the like. Compounds having the property of tachykinin antagonism are indicated for conditions associated with neurogenic inflammation and other diseases described herein.

Abstract translation: 本发明涉及取代的吡咯烷基-3-基 - 烷基 - 哌啶，其立体异构体及其药学上可接受的盐及其制备方法。 本发明的化合物可用于其药理活性如速激肽拮抗作用，特别是P物质和神经激肽A拮抗作用等。 表示具有速激肽拮抗作用的化合物用于与神经源性炎症和本文所述的其它疾病相关的病症。

公开(公告)号：US5661160A

公开(公告)日：1997-08-26

申请号：US487375

申请日：1995-06-07

Applicant: Timothy P. Burkholder ,  Tieu-Binh Le ,  Elizabeth M. Kudlacz ,  George D. Maynard

Inventor： Timothy P. Burkholder ,  Tieu-Binh Le ,  Elizabeth M. Kudlacz ,  George D. Maynard

IPC: C07D401/06 ,  C07D401/14 ,  C07D409/14 ,  C07D471/10 ,  A61K31/445

CPC classification number: C07D401/06 ,  C07D401/14 ,  C07D409/14 ,  C07D471/10

Abstract: The present invention relates to substituted pyrrolidinyl-3-yl-alkyl-piperidines, their stereoisomers, and pharmaceutically acceptable salts thereof and processes for preparation of the same. The compounds of the present invention are useful in their pharmacological activities such as tachykinin antagonism, especially substance P and neurokinin A antagonism, and the like. Compounds having the property of tachykinin antagonism are indicated for conditions associated with neurogenic inflammation and other diseases described herein.

公开(公告)号：US5840726A

公开(公告)日：1998-11-24

申请号：US878695

申请日：1997-06-19

Applicant: Timothy P. Burkholder ,  Elizabeth M. Kudlacz ,  Tieu-Binh Le

Inventor： Timothy P. Burkholder ,  Elizabeth M. Kudlacz ,  Tieu-Binh Le

IPC: A61K31/495 ,  A61P11/00 ,  A61P43/00 ,  C07D209/04 ,  C07D209/08 ,  C07D209/20 ,  C07D403/06 ,  C07D403/14 ,  C07D209/24

CPC classification number: C07D403/06 ,  C07D209/20 ,  C07D403/14

Abstract: The present invention relates to substituted piperazinone derivatives (compounds of formula (1)) or stereoisomers, or pharmaceutically acceptable salts thereof and their use as tachykinin receptor antagonists. Such antagonists are useful in the treatment of tachykinin-mediated diseases and conditions disclosed herein including: asthma, cough, and bronchitis. The present invention also relates to intermediates useful in the preparation of compounds of formula (1).

Abstract translation: 本发明涉及取代的哌嗪酮衍生物（式（1）的化合物）或其立体异构体或其药学上可接受的盐及其作为速激肽受体拮抗剂的用途。 这样的拮抗剂可用于治疗速激肽介导的疾病和本文公开的病症，包括：哮喘，咳嗽和支气管炎。 本发明还涉及可用于制备式（1）化合物的中间体。

公开(公告)号：US5648366A

公开(公告)日：1997-07-15

申请号：US477167

申请日：1995-06-07

Applicant: Timothy P. Burkholder ,  Tieu-Binh Le ,  Elizabeth M. Kudlacz ,  George D. Maynard

Inventor： Timothy P. Burkholder ,  Tieu-Binh Le ,  Elizabeth M. Kudlacz ,  George D. Maynard

IPC: C07D401/06 ,  C07D401/14 ,  C07D409/14 ,  C07D471/10 ,  A61K31/445

CPC classification number: C07D401/06 ,  C07D401/14 ,  C07D409/14 ,  C07D471/10

Abstract: The present invention relates to substituted pyrrolidinyl-3-yl-alkyl-piperidines, their stereoisomers, and pharmaceutically acceptable salts thereof and processes for preparation of the same. The compounds of the present invention are useful in their pharmacological activities such as tachykinin antagonism, especially substance P and neurokinin A antagonism, and the like. Compounds having the property of tachykinin antagonism are indicated for conditions associated with neurogenic inflammation and other diseases described herein.

公开(公告)号：US5597845A

公开(公告)日：1997-01-28

申请号：US262209

申请日：1994-06-20

Applicant: Timothy P. Burkholder ,  Elizabeth M. Kudlacz ,  Tieu-Binh Le

Inventor： Timothy P. Burkholder ,  Elizabeth M. Kudlacz ,  Tieu-Binh Le

IPC: C07D309/12 ,  A61K31/215 ,  A61K31/35 ,  A61K31/351 ,  A61K31/403 ,  A61K31/404 ,  A61K31/405 ,  A61P11/00 ,  A61P43/00 ,  C07C211/27 ,  C07C211/29 ,  C07C211/30 ,  C07C223/02 ,  C07C227/18 ,  C07C229/36 ,  C07C233/78 ,  C07C237/20 ,  C07C237/52 ,  C07C271/20 ,  C07C271/22 ,  C07D209/14 ,  C07D209/20 ,  C07D209/18 ,  C07D407/06

CPC classification number: C07C271/22 ,  C07C233/78 ,  C07C237/20 ,  C07C237/52 ,  C07D209/20

Abstract: The present invention relates to novel substituted alkyldiamine derivatives and pharmaceutically acceptable salts thereof which are useful tachykinin antagonists. Such antagonists are useful in the treatment of tachykinin-mediated diseases and conditions including asthma, cough, and bronchitis.

Abstract translation: 本发明涉及新的取代烷基二胺衍生物及其药学上可接受的盐，它们是有效的速激肽拮抗剂。 这种拮抗剂可用于治疗速激肽介导的疾病和病症，包括哮喘，咳嗽和支气管炎。