公开(公告)号：US08481738B2

公开(公告)日：2013-07-09

申请号：US13293943

申请日：2011-11-10

Applicant: Graham Beaton ,  Mi Chen ,  Timothy Richard Coon ,  Todd Ewing ,  Wanlong Jiang ,  Richard Lowe ,  Willy Moree ,  Nicole Smith ,  Warren Wade ,  Liren Zhao ,  Yun-fei Zhu ,  Martin Rowbottom ,  Neil Ashweek

Inventor： Graham Beaton ,  Mi Chen ,  Timothy Richard Coon ,  Todd Ewing ,  Wanlong Jiang ,  Richard Lowe ,  Willy Moree ,  Nicole Smith ,  Warren Wade ,  Liren Zhao ,  Yun-fei Zhu ,  Martin Rowbottom ,  Neil Ashweek

IPC: C07D513/02 ,  C07D401/00

CPC classification number: C07D495/04 ,  C07C233/88 ,  C07C235/42 ,  C07C255/57 ,  C07D213/56 ,  C07D213/58 ,  C07D213/61 ,  C07D213/64 ,  C07D213/70 ,  C07D213/81 ,  C07D213/84 ,  C07D213/89 ,  C07D215/14 ,  C07D215/54 ,  C07D239/36 ,  C07D401/04 ,  C07D401/12 ,  C07D413/12 ,  C07D417/12

Abstract: GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein R1a, R1b, R1c, R1d, R2, R2a, and A are as defined herein, including stereoisomers, esters, solvates and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

公开(公告)号：US08263588B2

公开(公告)日：2012-09-11

申请号：US12594815

申请日：2008-04-04

Applicant: Graham Beaton ,  Mi Chen ,  Timothy Richard Coon ,  Todd Ewing ,  Wanlong Jiang ,  Jinghua Yu ,  Willy Moree ,  Warren Wade ,  Liren Zhao ,  Yun-fei Zhu ,  Martin Rowbottom ,  Neil Ashweek

Inventor： Graham Beaton ,  Mi Chen ,  Timothy Richard Coon ,  Todd Ewing ,  Wanlong Jiang ,  Jinghua Yu ,  Willy Moree ,  Warren Wade ,  Liren Zhao ,  Yun-fei Zhu ,  Martin Rowbottom ,  Neil Ashweek

IPC: C07D213/61 ,  C07D213/84 ,  C07D401/12 ,  C07D403/12 ,  A61K31/435 ,  A61P35/00

CPC classification number: C07D213/61 ,  C07D213/84 ,  C07D239/36 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12

Abstract: GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein R1a, R1b, R1c, R1d, R2, R2a, and A are as defined herein, including stereoisomers, esters, solvates, and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

Abstract translation: 公开了GnRH受体拮抗剂，其可用于治疗男性和女性中各种性激素相关病症。 本发明的化合物具有以下结构：其中R1a，R1b，R1c，R1d，R2，R2a和A如本文所定义，包括立体异构体，酯，溶剂化物和药学上可接受的盐。 还公开了含有本发明化合物与药学上可接受的载体组合的组合物，以及涉及其在有需要的受试者中拮抗促性腺激素释放激素的方法。

公开(公告)号：US20100184741A1

公开(公告)日：2010-07-22

申请号：US12594815

申请日：2008-04-04

Applicant: Neil Ashweek ,  Mi Chen ,  Timothy Richard Coon ,  Todd Ewing ,  Wanlong Jiang ,  Willy Moree ,  Martin Rowbottom ,  Warren Wade ,  Liren Zhao ,  Yun-fei Zhu ,  Jinghua Yu ,  Graham Beaton

Inventor： Neil Ashweek ,  Mi Chen ,  Timothy Richard Coon ,  Todd Ewing ,  Wanlong Jiang ,  Willy Moree ,  Martin Rowbottom ,  Warren Wade ,  Liren Zhao ,  Yun-fei Zhu ,  Jinghua Yu ,  Graham Beaton

IPC: C07D213/84 ,  A61K31/444 ,  C07D215/12 ,  C07D403/12 ,  A61K31/44 ,  A61K31/55 ,  C07D223/16 ,  A61K31/47 ,  A61P35/04 ,  A61P15/00

CPC classification number: C07D213/61 ,  C07D213/84 ,  C07D239/36 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12

Abstract: GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein R1a, R1b, R1c, R1d, R2, R2a, and A are as defined herein, including stereoisomers, esters, solvates, and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

Abstract translation: 公开了GnRH受体拮抗剂，其可用于治疗男性和女性中各种性激素相关病症。 本发明的化合物具有以下结构：其中R1a，R1b，R1c，R1d，R2，R2a和A如本文所定义，包括立体异构体，酯，溶剂化物和药学上可接受的盐。 还公开了含有本发明化合物与药学上可接受的载体组合的组合物，以及涉及其在有需要的受试者中拮抗促性腺激素释放激素的方法。

公开(公告)号：US20120122891A1

公开(公告)日：2012-05-17

申请号：US13293943

申请日：2011-11-10

Applicant: Graham Beaton ,  Mi Chen ,  Timothy Richard Coon ,  Todd Ewing ,  Wanlong Jiang ,  Richard Lowe ,  Willy Moree ,  Nicole Smith ,  Warren Wade ,  Liren Zhao ,  Yun-Fei Zhu ,  Martin Rowbottom ,  Neil Ashweek

Inventor： Graham Beaton ,  Mi Chen ,  Timothy Richard Coon ,  Todd Ewing ,  Wanlong Jiang ,  Richard Lowe ,  Willy Moree ,  Nicole Smith ,  Warren Wade ,  Liren Zhao ,  Yun-Fei Zhu ,  Martin Rowbottom ,  Neil Ashweek

IPC: A61K31/519 ,  C07D471/04 ,  C07D495/04 ,  A61K31/513 ,  A61K31/4375 ,  A61P13/02 ,  A61P5/08 ,  A61P17/00 ,  A61P15/08 ,  A61P1/00 ,  A61P35/00 ,  C07D239/36 ,  A61P15/00

CPC classification number: C07D495/04 ,  C07C233/88 ,  C07C235/42 ,  C07C255/57 ,  C07D213/56 ,  C07D213/58 ,  C07D213/61 ,  C07D213/64 ,  C07D213/70 ,  C07D213/81 ,  C07D213/84 ,  C07D213/89 ,  C07D215/14 ,  C07D215/54 ,  C07D239/36 ,  C07D401/04 ,  C07D401/12 ,  C07D413/12 ,  C07D417/12

Abstract: GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein R1a, R1b, R1c, R1d, R2, R2a, and A are as defined herein, including stereoisomers, esters, solvates and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

Abstract translation: 公开了GnRH受体拮抗剂，其可用于治疗男性和女性中各种性激素相关病症。 本发明的化合物具有以下结构：其中R1a，R1b，R1c，R1d，R2，R2a和A如本文所定义，包括其立体异构体，酯，溶剂化物和药学上可接受的盐。 还公开了含有本发明化合物与药学上可接受的载体组合的组合物，以及涉及其在有需要的受试者中拮抗促性腺激素释放激素的方法。

公开(公告)号：US08084614B2

公开(公告)日：2011-12-27

申请号：US12594809

申请日：2008-04-04

Applicant: Graham Beaton ,  Mi Chen ,  Timothy Richard Coon ,  Todd Ewing ,  Wanlong Jiang ,  Richard Lowe ,  Willy Moree ,  Nicole Smith ,  Warren Wade ,  Liren Zhao ,  Yun-fei Zhu ,  Martin Rowbottom ,  Neil Ashweek

Inventor： Graham Beaton ,  Mi Chen ,  Timothy Richard Coon ,  Todd Ewing ,  Wanlong Jiang ,  Richard Lowe ,  Willy Moree ,  Nicole Smith ,  Warren Wade ,  Liren Zhao ,  Yun-fei Zhu ,  Martin Rowbottom ,  Neil Ashweek

IPC: C07D213/00 ,  C07D211/70 ,  C07D233/00 ,  A61K31/44

CPC classification number: C07D495/04 ,  C07C233/88 ,  C07C235/42 ,  C07C255/57 ,  C07D213/56 ,  C07D213/58 ,  C07D213/61 ,  C07D213/64 ,  C07D213/70 ,  C07D213/81 ,  C07D213/84 ,  C07D213/89 ,  C07D215/14 ,  C07D215/54 ,  C07D239/36 ,  C07D401/04 ,  C07D401/12 ,  C07D413/12 ,  C07D417/12

Abstract: GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure, wherein R1a, R1b, R1c, R1d, R2, R2a, and A are as defined herein, including stereoisomers, esters, solvates and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

Abstract translation: 公开了GnRH受体拮抗剂，其可用于治疗男性和女性中各种性激素相关病症。 本发明的化合物具有以下结构，其中R1a，R1b，R1c，R1d，R2，R2a和A如本文所定义，包括其立体异构体，酯，溶剂合物及其药学上可接受的盐。 还公开了含有本发明化合物与药学上可接受的载体组合的组合物，以及涉及其在有需要的受试者中拮抗促性腺激素释放激素的方法。

公开(公告)号：US5625050A

公开(公告)日：1997-04-29

申请号：US221425

申请日：1994-03-31

Applicant: Graham Beaton ,  Eric F. Fisher

Inventor： Graham Beaton ,  Eric F. Fisher

IPC: C07D473/18 ,  A61K31/70 ,  A61K31/7042 ,  A61K31/7052 ,  A61K31/7064 ,  A61K31/7068 ,  A61K31/7072 ,  A61K31/7076 ,  A61K31/708 ,  A61K31/7088 ,  A61P31/12 ,  A61P35/00 ,  C07D405/04 ,  C07D473/34 ,  C07H19/06 ,  C07H19/16 ,  C07H21/00 ,  C07H21/02 ,  C07H21/04

CPC classification number: C07H19/06 ,  C07H19/16 ,  C07H21/00

Abstract: The present invention provides nuclease resistant 3'-carbon modified oligonucleotides that can be used in the field of nucleic acid therapeutics and diagnostics. The modified oligonucleotides of the present invention have at least one modified internucleotide linkage wherein the divalent oxygen moiety at the 3'-position of the internucleotide linkage is replaced by a tetravalent carbon moiety. The 3'-carbon modified internucleotide linkage is preferably a 3'-methylene or 3'-hydroxymethylene linkage. Also provided are a method and monomeric nucleoside and nucleotide intermediates for making the modified oligonucleotides of the present invention.

Abstract translation: 本发明提供可用于核酸治疗和诊断领域的耐核酸酶3'-碳修饰的寡核苷酸。 本发明的经修饰的寡核苷酸具有至少一个修饰的核苷酸间键，其中核苷酸间键的3'-位上的二价氧部分被四价碳部分代替。 3'-碳修饰的核苷酸间键优选为3'-亚甲基或3'-羟基亚甲基键。 还提供了用于制备本发明的修饰的寡核苷酸的方法和单体核苷和核苷酸中间体。

公开(公告)号：US20130040975A1

公开(公告)日：2013-02-14

申请号：US13572510

申请日：2012-08-10

Applicant: Graham Beaton ,  Mi Chen ,  Timothy Richard Coon ,  Todd Ewing ,  Wanlong Jiang ,  Jinghua Yu ,  Willy Moree ,  Warren Wade ,  Liren Zhao ,  Yun-fei Zhu ,  Martin Rowbottom ,  Neil Ashweek

Inventor： Graham Beaton ,  Mi Chen ,  Timothy Richard Coon ,  Todd Ewing ,  Wanlong Jiang ,  Jinghua Yu ,  Willy Moree ,  Warren Wade ,  Liren Zhao ,  Yun-fei Zhu ,  Martin Rowbottom ,  Neil Ashweek

IPC: C07D213/61 ,  C07D239/36 ,  A61K31/513 ,  C07D213/84 ,  A61K31/444 ,  C07D405/12 ,  A61K31/443 ,  C07C311/15 ,  C07D215/14 ,  C07D495/04 ,  A61P5/24 ,  A61P15/00 ,  A61P17/00 ,  A61P35/00 ,  A61P13/08 ,  A61P15/08 ,  A61K31/4418

CPC classification number: C07D213/61 ,  C07D213/84 ,  C07D239/36 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12

Abstract: GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein R1a, R1b, R1c, R1d, R2, R2a, and A are as defined herein, including stereoisomers, esters, solvates, and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

Abstract translation: 公开了GnRH受体拮抗剂，其可用于治疗男性和女性中各种性激素相关病症。 本发明的化合物具有以下结构：其中R1a，R1b，R1c，R1d，R2，R2a和A如本文所定义，包括立体异构体，酯，溶剂化物和药学上可接受的盐。 还公开了含有本发明化合物与药学上可接受的载体组合的组合物，以及涉及其在有需要的受试者中拮抗促性腺激素释放激素的方法。

公开(公告)号：US20100152207A1

公开(公告)日：2010-06-17

申请号：US12594809

申请日：2008-04-04

Applicant: Graham Beaton ,  Mi Chen ,  Timothy Richard Coon ,  Todd Ewing ,  Wanlong Jiang ,  Willy Moree ,  Martin Rowbottom ,  Warren Wade ,  Liren Zhao ,  Richard Lowe ,  Nicole Smith ,  Neil Ashweek ,  Yun-Fei Zhu

Inventor： Graham Beaton ,  Mi Chen ,  Timothy Richard Coon ,  Todd Ewing ,  Wanlong Jiang ,  Willy Moree ,  Martin Rowbottom ,  Warren Wade ,  Liren Zhao ,  Richard Lowe ,  Nicole Smith ,  Neil Ashweek ,  Yun-Fei Zhu

IPC: A61K31/519 ,  C07D213/56 ,  A61K31/4418 ,  C07D215/38 ,  A61K31/47 ,  C07D495/04 ,  C07C233/67 ,  A61K31/165 ,  C07D213/84 ,  A61K31/44 ,  C07D401/04 ,  A61K31/4439 ,  C07D213/62 ,  C07D239/02 ,  A61K31/505 ,  C07D401/12 ,  C07D413/12 ,  C07D403/02 ,  A61K31/444 ,  A61P15/00

CPC classification number: C07D495/04 ,  C07C233/88 ,  C07C235/42 ,  C07C255/57 ,  C07D213/56 ,  C07D213/58 ,  C07D213/61 ,  C07D213/64 ,  C07D213/70 ,  C07D213/81 ,  C07D213/84 ,  C07D213/89 ,  C07D215/14 ,  C07D215/54 ,  C07D239/36 ,  C07D401/04 ,  C07D401/12 ,  C07D413/12 ,  C07D417/12

Abstract: GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure, wherein R1a, R1b, R1c, R1d, R2, R2a, and A are as defined herein, including stereoisomers, esters, solvates and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

Abstract translation: 公开了GnRH受体拮抗剂，其可用于治疗男性和女性中各种性激素相关病症。 本发明的化合物具有以下结构，其中R1a，R1b，R1c，R1d，R2，R2a和A如本文所定义，包括其立体异构体，酯，溶剂合物及其药学上可接受的盐。 还公开了含有本发明化合物与药学上可接受的载体组合的组合物，以及涉及其在有需要的受试者中拮抗促性腺激素释放激素的方法。

公开(公告)号：US20050277645A1

公开(公告)日：2005-12-15

申请号：US11097963

申请日：2005-04-01

Applicant: Wilna (Willy) Moree ,  Graham Beaton ,  Jinghua Yu ,  Binfeng Li ,  Said Zamani-Kord

Inventor： Wilna (Willy) Moree ,  Graham Beaton ,  Jinghua Yu ,  Binfeng Li ,  Said Zamani-Kord

IPC: A61K31/137 ,  A61K31/415 ,  A61K31/421 ,  A61K31/4245 ,  A61K31/426 ,  A61K31/433 ,  A61K31/495 ,  A61K31/4965 ,  C07C209/50 ,  C07C217/48 ,  C07C229/34 ,  C07C255/42

CPC classification number: A61K31/426 ,  A61K31/137 ,  A61K31/415 ,  A61K31/421 ,  A61K31/4245 ,  A61K31/433 ,  A61K31/495 ,  A61K31/4965 ,  C07C217/48 ,  C07C229/34 ,  C07C255/42 ,  C07D237/08 ,  C07D241/12 ,  C07D263/10 ,  C07D271/10 ,  C07D277/28 ,  C07D285/12 ,  C07D403/10

Abstract: Compounds having the following structure: including stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein R1, R2a, R2b, R3, R4, R5a, R5b, L1, L2 and n are as defined herein. Pharmaceutical compositions containing one or more compounds of structure (I), as well as methods relating to the use thereof, including methods for treating insomnia, inducing sleep or inducing sedation or hypnosis, are also disclosed.

Abstract translation: 具有以下结构的化合物：包括立体异构体，前药和其药学上可接受的盐，其中R 1，R 2a，R 2b， R 3，R 4，R 5a，R 5b，L 1，L 3， SUB＆gt; 2＆gt;和n如本文所定义。 还公开了含有一种或多种结构（I）化合物的药物组合物，以及涉及其用途的方法，包括治疗失眠，诱导睡眠或诱发镇静或催眠的方法。

公开(公告)号：US06924284B2

公开(公告)日：2005-08-02

申请号：US10222749

申请日：2002-08-15

Applicant: Graham Beaton ,  Wilna J. Moree ,  Jaimie K. Rueter ,  Russell S. Dahl ,  David L. McElligott ,  Phyllis Goldman ,  Anthony J. Demaggio ,  Erik Christenson ,  Dan Herendeen ,  Kerry W. Fowler ,  Danwen Huang ,  Jaimie E. Bertino ,  Lisa H. Bourdon ,  David J. Fairfax ,  Qin Jiang ,  Helge A. Reisch ,  Ren Hua Song ,  Pavel E. Zhichkin

Inventor： Graham Beaton ,  Wilna J. Moree ,  Jaimie K. Rueter ,  Russell S. Dahl ,  David L. McElligott ,  Phyllis Goldman ,  Anthony J. Demaggio ,  Erik Christenson ,  Dan Herendeen ,  Kerry W. Fowler ,  Danwen Huang ,  Jaimie E. Bertino ,  Lisa H. Bourdon ,  David J. Fairfax ,  Qin Jiang ,  Helge A. Reisch ,  Ren Hua Song ,  Pavel E. Zhichkin

IPC: A61K31/502 ,  A61K31/5025 ,  A61K31/5377 ,  A61K41/00 ,  A61K49/00 ,  A61P9/00 ,  A61P9/10 ,  A61P25/00 ,  A61P25/14 ,  A61P25/16 ,  A61P25/28 ,  A61P35/00 ,  A61P43/00 ,  C07D237/32 ,  C07D237/34 ,  C07D241/44 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D237/52

CPC classification number: C07D401/12 ,  A61K41/0038 ,  A61K49/001 ,  C07D237/32 ,  C07D237/34 ,  C07D241/44 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04

Abstract: The present invention provides compounds comprising a bicyclic aryl moiety, such as 2H-phthalazin-1-one or derivatives thereof, compositions comprising the same, and methods for producing and using the same. In particular, the present invention provides compounds of the formula: or a pharmaceutically acceptable salt, a hydrate, a solvate, or a prodrug thereof; where Q1, Q2 and Y are those defined herein.

Abstract translation: 本发明提供包含双环芳基部分的化合物，例如2H-酞嗪-1-酮或其衍生物，包含它们的组合物，及其制备和使用方法。 特别地，本发明提供下式的化合物：或其药学上可接受的盐，水合物，溶剂化物或前药; 其中Q 1，Q 2和Y是本文定义的那些。