公开(公告)号：US06964973B2

公开(公告)日：2005-11-15

申请号：US10299909

申请日：2002-11-18

Applicant: Lin Zhi ,  Barbara Pio ,  Luc Farmer

Inventor： Lin Zhi ,  Barbara Pio ,  Luc Farmer

IPC: A61K31/37 ,  A61K31/4025 ,  A61K31/404 ,  A61K31/407 ,  A61K31/416 ,  A61K31/4178 ,  A61K31/428 ,  A61K31/47 ,  A61K31/4704 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/517 ,  A61K31/536 ,  A61K31/5377 ,  A61K31/538 ,  A61K31/55 ,  A61P5/26 ,  A61P5/28 ,  A61P5/34 ,  A61P5/36 ,  A61P7/04 ,  A61P7/06 ,  A61P13/08 ,  A61P15/00 ,  A61P15/04 ,  A61P15/08 ,  A61P15/10 ,  A61P15/16 ,  A61P15/18 ,  A61P17/10 ,  A61P17/14 ,  A61P35/00 ,  A61P43/00 ,  C07D209/34 ,  C07D209/96 ,  C07D215/22 ,  C07D215/227 ,  C07D215/36 ,  C07D215/38 ,  C07D215/48 ,  C07D239/80 ,  C07D265/18 ,  C07D265/36 ,  C07D277/68 ,  C07D311/14 ,  C07D311/20 ,  C07D401/04 ,  C07D401/12 ,  C07D405/04 ,  C07D405/12 ,  C07D409/04 ,  C07D409/12 ,  C07D413/04 ,  C07D417/04

CPC classification number: C07D215/227 ,  C07D209/34 ,  C07D209/96 ,  C07D215/36 ,  C07D215/38 ,  C07D239/80 ,  C07D265/18 ,  C07D265/36 ,  C07D277/68 ,  C07D311/14 ,  C07D311/20 ,  C07D401/04 ,  C07D401/12 ,  C07D405/04 ,  C07D405/12 ,  C07D409/04 ,  C07D409/12 ,  C07D413/04 ,  C07D417/04

Abstract: The present invention is directed to compounds, pharmaceutical compositions, and methods for modulating processes mediated by AR and PR. More particularly, the invention relates to nonsteroidal compounds and compositions that are high affinity, high specificity agonists, partial agonists (i.e., partial activators and/or tissue-specific activators) and antagonists for AR and PR. Also provided are methods of making such compounds and pharmaceutical compositions, as well as critical intermediates used in their synthesis.

公开(公告)号：US5808139A

公开(公告)日：1998-09-15

申请号：US303138

申请日：1994-09-08

Applicant: I. Charles Pathirana ,  Christina S. Berger ,  Robert B. Stein ,  William Fenical ,  Todd K. Jones ,  Lawrence G. Hamann ,  Michael G. Johnson ,  Luc Farmer

Inventor： I. Charles Pathirana ,  Christina S. Berger ,  Robert B. Stein ,  William Fenical ,  Todd K. Jones ,  Lawrence G. Hamann ,  Michael G. Johnson ,  Luc Farmer

IPC: C07C69/96 ,  C07C69/76

CPC classification number: C07C69/96

Abstract: Non-steroidal compounds which are high affinity, high specificity ligands for progesterone receptors are disclosed. The compounds include synthetic derivatives of cyclocymopol and its diastereomers, spectroscopically and chromatographically pure (3R)-cyclocymopol monomethyl ether, which functions as a progesterone receptor antagonist, and spectroscopically and chromatographically pure (3S)-cyclocymopol monomethyl ether, which functions as a progesterone receptor agonist. Also disclosed are methods for employing the disclosed compounds for modulating processes mediated by progesterone receptors and for treating patients requiring progesterone receptor agonist or antagonist therapy.

Abstract translation: 公开了对于孕酮受体是高亲和性，高特异性配体的非甾体化合物。 这些化合物包括作为孕酮受体拮抗剂起作用的环胞膜及其非对映异构体的光谱和色谱纯的（3R） - 环戊砜单甲醚的合成衍生物，以及用作孕酮受体的光谱和色谱纯的（3S） - 环戊砜单甲醚 激动剂。 还公开了使用所公开的化合物调节由孕酮受体介导的过程和用于治疗需要孕酮受体激动剂或拮抗剂治疗的患者的方法。

公开(公告)号：US5688810A

公开(公告)日：1997-11-18

申请号：US464541

申请日：1995-06-05

Applicant: Todd K. Jones ,  Mark E. Goldman ,  Charlotte L.F. Pooley ,  David T. Winn ,  James P. Edwards ,  Sarah J. West ,  Christopher M. Tegley ,  Lin Zhi

Inventor： Todd K. Jones ,  Mark E. Goldman ,  Charlotte L.F. Pooley ,  David T. Winn ,  James P. Edwards ,  Sarah J. West ,  Christopher M. Tegley ,  Lin Zhi

IPC: C07D215/06 ,  C07D221/18 ,  C07D311/80 ,  C07D401/04 ,  C07D413/04 ,  C07D417/04 ,  C07D471/04 ,  C07D491/04 ,  C07D491/048 ,  C07D491/052 ,  A61K31/47 ,  C07D215/12 ,  C07D215/18 ,  C07D215/36 ,  C07D215/38

CPC classification number: C07D401/04 ,  C07D215/06 ,  C07D221/18 ,  C07D311/80 ,  C07D413/04 ,  C07D417/04 ,  C07D471/04 ,  C07D491/04

Abstract: Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.

Abstract translation: 公开了用于类固醇受体的高亲和力，高选择性调节剂的非甾体化合物。 还公开了掺入这种化合物的药物组合物，使用所公开的化合物的方法和用于治疗需要类固醇受体激动剂或拮抗剂治疗的患者的组合物，可用于制备化合物的中间体和用于制备类固醇受体调节剂化合物的方法。

公开(公告)号：US5686596A

公开(公告)日：1997-11-11

申请号：US459287

申请日：1995-06-02

Applicant: Ranjan Mukherjee

Inventor： Ranjan Mukherjee

IPC: C12N15/09 ,  C07H21/04 ,  C07K14/705 ,  C12N15/12 ,  C12P21/02 ,  C12P21/06 ,  C07K1/00 ,  C07K17/00

CPC classification number: C07K14/705

Abstract: A human peroxisome proliferation activated receptor gene is purified from the environment in which it naturally occurs, and preferably provided within an expression vector.

Abstract translation: 从其天然存在的环境中纯化人类过氧化物酶体增殖活化受体基因，优选在表达载体内提供。

公开(公告)号：US5506102A

公开(公告)日：1996-04-09

申请号：US144554

申请日：1993-10-28

Applicant: Donald P. McDonnell

Inventor： Donald P. McDonnell

IPC: G01N33/566 ,  C07K14/72 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12 ,  C12Q1/68 ,  G01N33/74

CPC classification number: C07K14/721 ,  C12Q1/6897 ,  G01N33/743 ,  G01N2333/723 ,  Y10S435/81

Abstract: Methods to screen for antagonists of steroid IR transcription as mediated by the PR-A isoform of the progesterone receptor are provided. Such cell-based methods include a cell in which PR-A is transcriptionally inactive containing asteroid IR other than PR, PR-A and a reporter vector that includes a promoter which is transcriptionally active in the presence of the steroid IR and an activator of said steroid IR, but is substantially transcriptionally inactive in the presence of PR-A. This cell is contacted with the activator of the steroid IR and a compound to be assayed, and the level of reporter product produced in the cell is measured and compared to the level of reporter product expressed in a similar cellular system absent PR-A as an indication of the potential antagonist activity of the compound being assayed. Also provided are an assay kit, a method of screening PR active compounds as ER antagonists and compounds that inhibit the transcriptional activity of asteroid IR in the presence of PR-A in a cellular context where PR-A is substantially transcriptionally inactive.

Abstract translation: 提供了筛选由孕激素受体的PR-A同种型介导的类固醇IR转录拮抗剂的方法。 这种基于细胞的方法包括其中PR-A转录失活的细胞，其含有除PR，PR-A之外的小行星IR，以及包含在类固醇IR存在下具有转录活性的启动子的报告载体和所述 类固醇IR，但在PR-A存在下基本上转录无活性。 将该细胞与类固醇IR的活化剂和待测化合物接触，并测量在细胞中产生的报道产物的水平，并与不存在PR-A的类似细胞系统中表达的报道产物的水平进行比较 所测化合物潜在的拮抗剂活性的指示。 还提供了测定试剂盒，在PR-A基本上转录无活性的细胞环境中，PR-A存在下抑制PR活性化合物作为ER拮抗剂和抑制小行星IR的转录活性的化合物的方法。

公开(公告)号：US11773110B2

公开(公告)日：2023-10-03

申请号：US17513093

申请日：2021-10-28

Applicant: Ligand Pharmaceuticals Incorporated

Inventor： Koc-Kan Ho ,  David Diller ,  Jeffrey J. Letourneau ,  Brian F. McGuinness ,  Andrew G. Cole ,  David Rosen ,  Cornelis A. van Oeveren ,  Jason C. Pickens ,  Lin Zhi ,  Yixing Shen ,  Bijan Pedram

IPC: C07D235/02 ,  C07D269/02 ,  C07D277/42 ,  C07D277/60 ,  C07D513/04 ,  A61K31/407 ,  A61K31/4168 ,  A61K31/4353 ,  A61P29/00 ,  A61P37/00 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04

CPC classification number: C07D513/04 ,  A61K31/407 ,  A61K31/4168 ,  A61K31/4353 ,  A61P29/00 ,  A61P37/00 ,  C07D235/02 ,  C07D269/02 ,  C07D277/42 ,  C07D277/60 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04

Abstract: Compounds and methods in the fields of chemistry and medicine are disclosed. Some of the disclosed embodiments include compounds, compositions and methods of using heterocycle amines. Some of the disclosed embodiments include heterocycle amines useful to treat inflammatory disorders.

公开(公告)号：US10604533B2

公开(公告)日：2020-03-31

申请号：US16015925

申请日：2018-06-22

Applicant: Ligand Pharmaceuticals Incorporated

Inventor： Koc-Kan Ho ,  David Diller ,  Jeffrey J. Letourneau ,  Brian F. McGuinness ,  Andrew G. Cole ,  David Rosen ,  Cornelis A. van Oeveren ,  Jason C. Pickens ,  Lin Zhi ,  Yixing Shen ,  Bijan Pedram

IPC: C07D213/02 ,  C07D401/04 ,  C07D471/04 ,  C07D513/04 ,  A61K31/407 ,  A61K31/4168 ,  A61K31/4353 ,  C07D235/02 ,  C07D269/02 ,  C07D277/42 ,  C07D277/60 ,  A61P29/00 ,  A61P37/00 ,  C07D417/12 ,  C07D417/14

Abstract: Compounds and methods in the fields of chemistry and medicine are disclosed. Some of the disclosed embodiments include compounds, compositions and methods of using heterocycle amines. Some of the disclosed embodiments include heterocycle amines useful to treat inflammatory disorders.

公开(公告)号：US10420748B2

公开(公告)日：2019-09-24

申请号：US15908504

申请日：2018-02-28

Applicant: LIGAND PHARMACEUTICALS INCORPORATED

Inventor： Keith B. Marschke ,  Lin Zhi

IPC: A61K31/4045 ,  A61K31/4152 ,  A61K45/06 ,  A61K31/41 ,  A61K31/4155 ,  A61K31/454 ,  A61N5/10 ,  G01N33/50 ,  A61K31/40 ,  A61K31/4015

Abstract: Some embodiments include methods for treating, preventing, reversing, halting, or slowing the progression of cancer, comprising administering to a subject in need thereof an effective amount of one or more chemotherapeutic agents, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition, wherein at least one of the chemotherapeutic agents is a cytotoxic granulocyte colony-stimulating factor receptor (GCFR) modulator. Methods are also disclosed for treating, preventing, reversing, halting, or slowing the progression of a hematopoietic disorder, comprising administered a therapeutically effective cytotoxic amount of a GCFR modulator to a subject in need thereof.

公开(公告)号：US09676809B2

公开(公告)日：2017-06-13

申请号：US15034757

申请日：2014-11-19

Applicant: Ligand Pharmaceuticals Incorporated

Inventor： Lin Zhi

IPC: C07H19/10 ,  C07H19/11

CPC classification number: C07H19/10 ,  C07H19/11

Abstract: Some embodiments of the present invention include nucleoside 5′-monophosphate derivative compounds, their preparation and their uses. In some embodiments, such compounds are useful to treat hepatitis C viral infections.

公开(公告)号：US09266874B2

公开(公告)日：2016-02-23

申请号：US14137318

申请日：2013-12-20

Applicant: Ligand Pharmaceuticals Incorporated

Inventor： Koc-Kan Ho ,  David Diller ,  Jeffrey J. Letourneau ,  Brian F. McGuinness ,  Andrew G. Cole ,  David Rosen ,  Cornelis A. van Oeveren ,  Jason C. Pickens ,  Lin Zhi ,  Yixing Shen ,  Bijan Pedram

IPC: C07D417/14 ,  C07D417/12 ,  A61K31/407 ,  A61K31/4168 ,  A61K31/4353 ,  C07D235/02 ,  C07D269/02 ,  C07D277/42 ,  C07D277/60 ,  C07D471/04 ,  C07D513/04

CPC classification number: C07D513/04 ,  A61K31/407 ,  A61K31/4168 ,  A61K31/4353 ,  A61P29/00 ,  A61P37/00 ,  C07D235/02 ,  C07D269/02 ,  C07D277/42 ,  C07D277/60 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04

Abstract: Compounds and methods in the fields of chemistry and medicine are disclosed. Some of the disclosed embodiments include compounds, compositions and methods of using heterocycle amines. Some of the disclosed embodiments include heterocycle amines useful to treat inflammatory disorders.

Abstract translation: 公开了化学和医学领域中的化合物和方法。 一些所公开的实施方案包括使用杂环胺的化合物，组合物和方法。 一些所公开的实施方案包括可用于治疗炎症性疾病的杂环胺。