公开(公告)号：US20140179648A1

公开(公告)日：2014-06-26

申请号：US14134793

申请日：2013-12-19

申请人： Shuang Liu ,  Bryan Cordell Duffy ,  John Frederick Quinn ,  May Xiaowu Jiang ,  Ruifang Wang ,  Gregory Scott Martin ,  He Zhao ,  Bruce Francis Molino ,  Peter Ronald Young

发明人： Shuang Liu ,  Bryan Cordell Duffy ,  John Frederick Quinn ,  May Xiaowu Jiang ,  Ruifang Wang ,  Gregory Scott Martin ,  He Zhao ,  Bruce Francis Molino ,  Peter Ronald Young

IPC分类号： A61K31/501 ,  C07D401/12 ,  A61K31/4439 ,  A61K45/06 ,  C07D413/14 ,  A61K31/496 ,  C07D237/04 ,  A61K31/50 ,  C07D413/04 ,  C07D417/04

CPC分类号： A61K31/5377 ,  A61K31/4375 ,  A61K31/4412 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/472 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/497 ,  A61K31/498 ,  A61K31/50 ,  A61K31/501 ,  A61K31/502 ,  A61K31/506 ,  A61K31/513 ,  A61K45/06 ,  C07D213/64 ,  C07D213/74 ,  C07D237/04 ,  C07D237/14 ,  C07D237/22 ,  C07D237/32 ,  C07D401/12 ,  C07D413/04 ,  C07D413/14 ,  C07D417/04 ,  Y02A50/467

摘要： The present disclosure relates to compounds, which are useful for inhibition of BET protein function by binding to bromodomains, and their use in therapy.

摘要翻译： 本公开涉及通过结合溴结构域可用于抑制BET蛋白功能的化合物及其在治疗中的用途。

公开(公告)号：US08741901B2

公开(公告)日：2014-06-03

申请号：US13540446

申请日：2012-07-02

申请人： Bruce F. Molino ,  Shuang Liu ,  Peter R. Guzzo ,  James P. Beck

发明人： Bruce F. Molino ,  Shuang Liu ,  Peter R. Guzzo ,  James P. Beck

IPC分类号： A61K31/497 ,  C07D217/00

CPC分类号： C07D417/04 ,  A61K31/4709 ,  A61K31/4741 ,  A61K31/4743 ,  A61K31/502 ,  A61K31/517 ,  A61K31/53 ,  C07D217/00 ,  C07D217/04 ,  C07D217/08 ,  C07D217/12 ,  C07D217/14 ,  C07D217/16 ,  C07D217/20 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D407/04 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D413/04 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04

摘要： The compounds of the present invention are represented by the chemical structure found in Formula (I): wherein: the carbon atom designated * is in the R or S configuration; and X is a fused bicyclic carbocycle or heterocycle selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted with substituents (1 to 4 in number) as defined in R14; with R1, R2, R3, R4, R5, R6, R7, R8, and R14 defined herein.

摘要翻译： 本发明的化合物由式（I）中所示的化学结构表示：其中：指定为*的碳原子为R或S构型; 并且X是选自苯并呋喃基，苯并[b]噻吩基，苯并异噻唑基，苯并异恶唑基，吲唑基，吲哚基，异吲哚基，吲嗪基，苯并咪唑基，苯并恶唑基，苯并噻唑基，苯并三唑基，咪唑并[1,2-a 吡啶并[1,5-a]吡啶基，[1,2,4]三唑并[4,3-a]吡啶基，噻吩并[2,3-b]吡啶基，噻吩并[3,2-b] 二氢苯并噻吩基，二氢苯并呋喃基，二氢苯并噻吩基，四氢萘基，喹啉基，异喹啉基，4H-喹啉基，9H-喹啉基，喹唑啉基，噌啉基，酞嗪基，喹喔啉基， 苯并[1,2,3]三嗪基，苯并[1,2,4]三嗪基，2H-色烯基，4H-色烯基和稠合的双环碳环或稠合双环杂环，其任选被如所定义的取代基（数目为1至4） 在R14; 本文定义的R1，R2，R3，R4，R5，R6，R7，R8和R14。

公开(公告)号：US08445494B2

公开(公告)日：2013-05-21

申请号：US12995771

申请日：2009-06-04

申请人： Jun Qiu ,  Qi Gao ,  Shuang Liu ,  Matthew Isherwood

发明人： Jun Qiu ,  Qi Gao ,  Shuang Liu ,  Matthew Isherwood

IPC分类号： A61K31/501 ,  C07D401/04 ,  A61P25/24

CPC分类号： C07F5/04 ,  C07C215/20 ,  C07C217/58 ,  C07C223/02 ,  C07D217/04 ,  C07D237/20 ,  C07D401/04 ,  C07D413/10 ,  C07F5/022 ,  C07F5/025

摘要： The present disclosure generally relates to a crystalline form of 6-[(4S)-2-methyl-4-(naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine. The present disclosure also generally relates to pharmaceutical compositions comprising the crystalline form, as well of methods of using a crystalline form in the treatment of depression and other conditions and methods for obtaining such crystalline form.

公开(公告)号：US20110160220A1

公开(公告)日：2011-06-30

申请号：US12995771

申请日：2009-06-04

申请人： Jun Qiu ,  Qi Gao ,  Shuang Liu ,  Min Hu ,  Yuh-Lin Allen Yang ,  Matthew Isherwood ,  Rasidul Amin

发明人： Jun Qiu ,  Qi Gao ,  Shuang Liu ,  Min Hu ,  Yuh-Lin Allen Yang ,  Matthew Isherwood ,  Rasidul Amin

IPC分类号： A61K31/501 ,  C07D401/02 ,  A61P25/24 ,  A61P25/22 ,  A61P29/00 ,  A61P3/04

CPC分类号： C07F5/04 ,  C07C215/20 ,  C07C217/58 ,  C07C223/02 ,  C07D217/04 ,  C07D237/20 ,  C07D401/04 ,  C07D413/10 ,  C07F5/022 ,  C07F5/025

摘要： The present disclosure generally relates to a crystalline form of 6-[(4S)-2-methyl-4-(naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine. The present disclosure also generally relates to pharmaceutical compositions comprising the crystalline form, as well of methods of using a crystalline form in the treatment of depression and other conditions and methods for obtaining such crystalline form.

摘要翻译： 本公开内容通常涉及6 - [（4S）-2-甲基-4-（萘基）-1,2,3,4-四氢异喹啉-7-基]哒嗪-3-胺的结晶形式。 本公开还通常涉及包含结晶形式的药物组合物，以及在治疗抑郁症和其它病症中使用结晶形式的方法以及获得这种结晶形式的方法。

公开(公告)号：US07317104B2

公开(公告)日：2008-01-08

申请号：US10864857

申请日：2004-06-09

申请人： Shuang Liu

发明人： Shuang Liu

IPC分类号： C07D211/72

CPC分类号： C07F13/005 ,  C07F9/58

摘要： Chelants and macrocyclic metal complexes thereof, methods of preparing the chelants and macrocyclic metal complexes, and radiopharmaceutical compositions comprising the macrocyclic metal complexes are disclosed. Methods of using the macrocyclic metal complexes as radiopharmaceuticals for the diagnosis of cardiovascular disorders, infectious diseases and cancer are also disclosed. Chelants as bifunctional chelators (BFCs) for the radiolabeling of target-specific biomolecules, such as proteins, peptides, peptidomimetics, non-peptide receptor ligands, enzyme inhibitors, and enzyme substrates are disclosed. Methods of using macrocyclic metal complexes containing the chelant-biomolecule conjugates as target-specific diagnostic radiopharmaceuticals that selectively localize at sites of disease and allow an image to be obtained of the loci using gamma scintigraphy are disclosed. Methods of use of the radiopharmaceuticals as imaging agents for the diagnosis of cardiovascular disorders, such as thromboembolic disease or atherosclerosis, infectious disease and cancer are further disclosed.

公开(公告)号：US20050201933A1

公开(公告)日：2005-09-15

申请号：US11124537

申请日：2005-05-06

申请人： Shuang Liu

发明人： Shuang Liu

IPC分类号： A61K51/04 ,  A61K51/08 ,  C07F9/6584 ,  C07F9/6587 ,  A61K51/00 ,  C07F5/00

CPC分类号： C07F9/6587 ,  A61K51/04 ,  A61K51/0482 ,  C07F9/6584

摘要： This invention relates to macrocyclic chelants comprised of one or two heteroatom-containing bridges, compositions containing them and their use in medicine, particularly in diagnostic imaging and radiotherapy. This invention relates especially to the use of metal chelates of the macrocyclic chelants as metallopharmaceuticals in Magnetic Resonance Imaging (MRI) and radiopharmaceuticals. This invention also relates to macrocyclic chelants as bifunctional chelating agents (BFC's) for the labeling of biologically active targeting molecules such as proteins, peptides, peptidomimetics, and non-peptide receptor ligands, with metal ions and radioisotopes.

摘要翻译： 本发明涉及由一个或两个含杂原子的桥组成的大环螯合剂，含有它们的组合物及其在医药中的用途，特别是在诊断成像和放射治疗中。 本发明特别涉及大环螯合物的金属螯合物作为磁共振成像（MRI）和放射性药物中的金属药物。 本发明还涉及用金属离子和放射性同位素标记生物活性靶向分子如蛋白质，肽，肽模拟物和非肽受体配体的双功能螯合剂（BFC's）的大环螯合剂。

公开(公告)号：US06916460B2

公开(公告)日：2005-07-12

申请号：US10663090

申请日：2003-09-15

申请人： Shuang Liu

发明人： Shuang Liu

IPC分类号： A61K51/04 ,  A61K51/08 ,  C07F9/6584 ,  C07F9/6587 ,  A61B49/00

CPC分类号： C07F9/6587 ,  A61K51/04 ,  A61K51/0482 ,  C07F9/6584

摘要： This invention relates to macrocyclic chelants comprised of one or two heteroatom-containing bridges, compositions containing them and their use in medicine, particularly in diagnostic imaging and radiotherapy. This invention relates especially to the use of metal chelates of the macrocyclic chelants as metallopharmaceuticals in Magnetic Resonance Imaging (MRI) and radiopharmaceuticals. This invention also relates to macrocyclic chelants as bifunctional chelating agents (BFC's) for the labeling of biologically active targeting molecules such as proteins, peptides, peptidomimetics, and non-peptide receptor ligands, with metal ions and radioisotopes.

公开(公告)号：US06800273B2

公开(公告)日：2004-10-05

申请号：US10342081

申请日：2003-01-14

申请人： Milind Rajopadhye ,  D. Scott Edwards ,  John A. Barrett ,  Alan P. Carpenter, Jr. ,  Thomas D. Harris ,  Stuart J. Heminway ,  Shuang Liu ,  Prahlad R. Singh

发明人： Milind Rajopadhye ,  D. Scott Edwards ,  John A. Barrett ,  Alan P. Carpenter, Jr. ,  Thomas D. Harris ,  Stuart J. Heminway ,  Shuang Liu ,  Prahlad R. Singh

IPC分类号： A61K5100

CPC分类号： C07D401/14 ,  A61K38/00 ,  A61K45/06 ,  A61K49/0002 ,  A61K49/227 ,  A61K51/082 ,  A61K51/088 ,  C07D401/12 ,  C07K7/06 ,  C07K7/08 ,  C07K7/64

摘要： The present invention describes novel compounds of the formula: (Q)d—Ln—Ch, useful for the diagnosis and treatment of cancer, methods of imaging tumors in a patient, and methods of treating cancer in a patient. The present invention also provides novel compounds useful for monitoring therapeutic angiogenesis treatment and destruction of new angiogenic vasculature. The pharmaceuticals are comprised of a targeting moiety that binds to a receptor that is upregulated during angiogenesis, an optional linking group, and a therapeutically effective radioisotope or diagnostically effective imageable moiety. The imageable moiety is a gamma ray or positron emitting radioisotope, a magnetic resonance imaging contrast agent, an X-ray contrast agent, or an ultrasound contrast agent.

摘要翻译： 本发明描述了新的下式化合物：可用于癌症的诊断和治疗，对患者肿瘤成像的方法，以及治疗患者癌症的方法。 本发明还提供了可用于监测治疗性血管生成治疗和破坏新的血管生成脉管系统的新型化合物。 药物由与血管发生期间上调的受体结合的靶向部分，任选的连接基团和治疗有效的放射性同位素或诊断上有效的可成像部分组成。 可成像部分是伽马射线或正电子发射放射性同位素，磁共振成像造影剂，X射线造影剂或超声造影剂。

公开(公告)号：US06713042B2

公开(公告)日：2004-03-30

申请号：US10081258

申请日：2002-02-22

申请人： Shuang Liu

发明人： Shuang Liu

IPC分类号： A61K5100

CPC分类号： A61K51/0491 ,  A61K51/04 ,  A61K51/0482 ,  A61K51/121

摘要： The invention relates to the use of ascorbic acid analogs as buffering reagents and chelating agents for the preparation of metalloradiopharmaceuticals. Also, invention relates to the use of ascorbic acid as a buffering reagent, a chelating agent, and a stabilizer for the preparation and stabilization of radiopharmaceuticals and processes for making and using the same.

摘要翻译： 本发明涉及抗坏血酸类似物作为缓冲试剂和螯合剂用于制备金属放射性药物的用途。 此外，本发明涉及抗坏血酸作为缓冲试剂，螯合剂和用于制备和稳定放射性药物的稳定剂的用途及其制备和使用方法。

公开(公告)号：US06537520B1

公开(公告)日：2003-03-25

申请号：US09599295

申请日：2000-06-21

申请人： Milind Rajopadhye ,  D. Scott Edwards ,  John A. Barrett ,  Alan P. Carpenter, Jr. ,  Thomas D. Harris ,  Stuart J. Heminway ,  Shuang Liu ,  Prahlad R. Singh

发明人： Milind Rajopadhye ,  D. Scott Edwards ,  John A. Barrett ,  Alan P. Carpenter, Jr. ,  Thomas D. Harris ,  Stuart J. Heminway ,  Shuang Liu ,  Prahlad R. Singh

IPC分类号： A61K5100

CPC分类号： C07D401/14 ,  A61K38/00 ,  A61K45/06 ,  A61K49/0002 ,  A61K49/227 ,  A61K51/082 ,  A61K51/088 ,  C07D401/12 ,  C07K7/06 ,  C07K7/08 ,  C07K7/64

摘要： The present invention describes novel compounds of the formula: (Q)d—Ln—Ch, useful for the diagnosis and treatment of cancer, methods of imaging tumors in a patient, and methods of treating cancer in a patient. The present invention also provides novel compounds useful for monitoring therapeutic angiogenesis treatment and destruction of new angiogenic vasculature. The pharmaceuticals are comprised of a targeting moiety that binds to a receptor that is upregulated during angiogenesis, an optional linking group, and a therapeutically effective radioisotope or diagnostically effective imageable moiety. The imageable moiety is a gamma ray or positron emitting radioisotope, a magnetic resonance imaging contrast agent, an X-ray contrast agent, or an ultrasound contrast agent.

摘要翻译： 本发明描述了新的下式化合物：可用于癌症的诊断和治疗，对患者肿瘤成像的方法，以及治疗患者癌症的方法。 本发明还提供了可用于监测治疗性血管生成治疗和破坏新的血管生成脉管系统的新型化合物。 药物由与血管发生期间上调的受体结合的靶向部分，任选的连接基团和治疗有效的放射性同位素或诊断上有效的可成像部分组成。 可成像部分是伽马射线或正电子发射放射性同位素，磁共振成像造影剂，X射线造影剂或超声造影剂。