公开(公告)号：US10112166B2

公开(公告)日：2018-10-30

申请号：US13471601

申请日：2012-05-15

申请人： Joshua Close ,  Haiyou Wang ,  Hsueh Sung Tung ,  Stephen A. Cottrell

发明人： Joshua Close ,  Haiyou Wang ,  Hsueh Sung Tung ,  Stephen A. Cottrell

IPC分类号： B03C5/00 ,  B01J8/10 ,  B01J8/00 ,  C07C17/275 ,  C07C17/278 ,  B03C1/033 ,  B01J23/745

摘要： Disclosed is a method for capturing and recycling iron catalyst used in the production of haloalkane compounds and more particularly, to an improved process for the manufacture of the compound 1,1,1,3,3-pentachloropropane (HCC-240fa), in which an electromagnetic separation unit (EMSU) is used to facilitate the reaction. When energized, the EMSU functions to remove all iron particles from the reactor effluent; when de-energized, the iron particles captured by the EMSU can be flushed back into the reactor for re-use in the continued production of HCC-240fa. The present invention is also useful in the manufacturing processes for other haloalkane compounds such as HCC-250 and HCC-360.

公开(公告)号：US20120305454A1

公开(公告)日：2012-12-06

申请号：US13471601

申请日：2012-05-15

申请人： Joshua Close ,  Haiyou Wang ,  Hsueh Sung Tung ,  Stephen A. Cottrell

发明人： Joshua Close ,  Haiyou Wang ,  Hsueh Sung Tung ,  Stephen A. Cottrell

IPC分类号： B03C1/00

CPC分类号： B01J8/10 ,  B01J8/005 ,  B01J8/0075 ,  B01J23/745 ,  B03C1/0335 ,  B03C5/00 ,  B03C2201/02 ,  B03C2201/18 ,  C07C17/275 ,  C07C17/278 ,  Y02P20/584 ,  C07C19/01

摘要： Disclosed is a method for capturing and recycling iron catalyst used in the production of haloalkane compounds and more particularly, to an improved process for the manufacture of the compound 1,1,1,3,3-pentachloropropane (HCC-240fa), in which an electromagnetic separation unit (EMSU) is used to facilitate the reaction. When energized, the EMSU functions to remove all iron particles from the reactor effluent; when de-energized, the iron particles captured by the EMSU can be flushed back into the reactor for re-use in the continued production of HCC-240fa. The present invention is also useful in the manufacturing processes for other haloalkane compounds such as HCC-250 and HCC-360.

摘要翻译： 公开了一种用于捕获和再循环用于制备卤代烷烃化合物的铁催化剂的方法，更具体地说，涉及制备化合物1,1,1,3,3-五氯丙烷（HCC-240fa）的改进方法，其中 使用电磁分离单元（EMSU）来促进反应。 当通电时，EMSU用于从反应器流出物中除去所有铁颗粒; 当断电时，由EMSU捕获的铁颗粒可以冲洗回反应器，以便在继续生产HCC-240fa时重新使用。 本发明也可用于其它卤代烷烃化合物如HCC-250和HCC-360的制备方法。

公开(公告)号：US20120310021A1

公开(公告)日：2012-12-06

申请号：US13481121

申请日：2012-05-25

申请人： Joshua Close ,  Haiyou Wang ,  Hsueh Sung Tung

发明人： Joshua Close ,  Haiyou Wang ,  Hsueh Sung Tung

IPC分类号： C07C17/275

CPC分类号： C07C17/275 ,  B01J23/745 ,  B01J23/94 ,  B01J31/0257 ,  B01J35/023 ,  B01J37/04 ,  B01J38/00 ,  B01J2231/32 ,  C07C17/278 ,  Y02P20/584 ,  C07C19/01

摘要： Disclosed is a process for the manufacture of haloalkane compounds, and more particularly, an improved process for the manufacture of the compound 1,1,1,3,3-penta-chloropropane (HCC-240fa), which mitigates the formation of by-products from vinyl chloride (CH2═CHCl). The present invention is also useful in the manufacture of other haloalkane compounds such as HCC-250 and HCC-360. One embodiment of the invention comprises a method for mitigating 1,1,3,3,5,5-hexachloropentane and 1,1,1,3,5,5-hexachloropentane formation in the HCC-240fa manufacturing process, in which FeCl3, is introduced to a reactor only after the start-up phase has ended and a continuous operation has started. In a preferred embodiment, “pre-chelated” FeCl3, which is concentrated in a catalyst recovery column, is introduced to reactor after the continuous operation has started.

摘要翻译： 公开了一种制备卤代烷烃化合物的方法，更具体地说，涉及制备化合物1,1,1,3,3-五氯丙烷（HCC-240fa）的改进方法，其减少副产物的形成， 氯乙烯（CH 2 = CHCl）的产物。 本发明也可用于制备其它卤代烷烃化合物如HCC-250和HCC-360。 本发明的一个实施方案包括在HCC-240fa制造方法中减轻1,1,3,3,5,5-六氯戊烷和1,1,1,3,5,5-六氯戊烷形成的方法，其中FeCl 3， 仅在启动阶段结束并且连续运行已经开始之后被引入反应器。 在优选的实施方案中，将浓缩在催化剂回收塔中的预螯合的FeCl 3在连续操作开始之后引入反应器。

公开(公告)号：US08835702B2

公开(公告)日：2014-09-16

申请号：US13481121

申请日：2012-05-25

申请人： Joshua Close ,  Haiyou Wang ,  Hsueh Sung Tung

发明人： Joshua Close ,  Haiyou Wang ,  Hsueh Sung Tung

IPC分类号： C07C17/26 ,  C07C17/272 ,  C07C17/278 ,  B01J35/02 ,  B01J31/02 ,  B01J38/00 ,  B01J23/745 ,  C07C17/275 ,  B01J23/94 ,  B01J37/04

CPC分类号： C07C17/275 ,  B01J23/745 ,  B01J23/94 ,  B01J31/0257 ,  B01J35/023 ,  B01J37/04 ,  B01J38/00 ,  B01J2231/32 ,  C07C17/278 ,  Y02P20/584 ,  C07C19/01

摘要： Disclosed is a process for the manufacture of haloalkane compounds, and more particularly, an improved process for the manufacture of the compound 1,1,1,3,3-penta-chloropropane (HCC-240fa), which mitigates the formation of by-products from vinyl chloride (CH2═CHCl). The present invention is also useful in the manufacture of other haloalkane compounds such as HCC-250 and HCC-360. One embodiment of the invention comprises a method for mitigating 1,1,3,3,5,5-hexachloropentane and 1,1,1,3,5,5-hexachloropentane formation in the HCC-240fa manufacturing process, in which FeCl3, is introduced to a reactor only after the start-up phase has ended and a continuous operation has started. In a preferred embodiment, “pre-chelated” FeCl3, which is concentrated in a catalyst recovery column, is introduced to reactor after the continuous operation has started.

摘要翻译： 公开了一种制备卤代烷烃化合物的方法，更具体地说，涉及制备化合物1,1,1,3,3-五氯丙烷（HCC-240fa）的改进方法，其减少副产物的形成， 氯乙烯（CH 2 = CHCl）的产物。 本发明也可用于制备其它卤代烷烃化合物如HCC-250和HCC-360。 本发明的一个实施方案包括在HCC-240fa制造方法中减轻1,1,3,3,5,5-六氯戊烷和1,1,1,3,5,5-六氯戊烷形成的方法，其中FeCl 3， 仅在启动阶段结束并且连续运行已经开始之后被引入反应器。 在优选的实施方案中，将浓缩在催化剂回收塔中的“预螯合的”​​FeCl 3在连续操作开始后引入反应器。

公开(公告)号：US08722946B2

公开(公告)日：2014-05-13

申请号：US13481111

申请日：2012-05-25

申请人： Joshua Close ,  Haiyou Wang ,  Hsueh Sung Tung

发明人： Joshua Close ,  Haiyou Wang ,  Hsueh Sung Tung

IPC分类号： C07C17/275

CPC分类号： C07C17/278 ,  B01J23/745 ,  B01J35/023 ,  C07C17/275 ,  C07C19/01

摘要： Disclosed is a process for the manufacture of haloalkane compounds, and more particularly, to an improved process for the manufacture of the compound 1,1,1,3,3-pentachloropropane (HCC-240fa), which mitigates the formation of by-products. The present invention is also useful in the manufacture of other haloalkane compounds such as HCC-250 and HCC-360. One embodiment of the process comprises a method and system for avoiding the formation of polyvinyl chloride during the production of HCC-240fa from CCl4, in which vinyl chloride (VCM) is fed into a reactor as a vapor instead of as a liquid, using a diffusing device to further increase the contact surface between VCM vapor and CCl4.

摘要翻译： 公开了一种制备卤代烷烃化合物的方法，更具体地说，涉及制备化合物1,1,1,3,3-五氯丙烷（HCC-240fa）的改进方法，其减少了副产物的形成 。 本发明也可用于制备其它卤代烷烃化合物如HCC-250和HCC-360。 该方法的一个实施方案包括在CCl 4生产HCC-240fa期间避免形成聚氯乙烯的方法和系统，其中将氯乙烯（VCM）作为蒸气而不是作为液体加入到反应器中，使用 扩散装置进一步增加VCM蒸气与CCl4之间的接触面。

公开(公告)号：US20120310020A1

公开(公告)日：2012-12-06

申请号：US13481111

申请日：2012-05-25

申请人： Joshua Close ,  Haiyou Wang ,  Hsueh Sung Tung

发明人： Joshua Close ,  Haiyou Wang ,  Hsueh Sung Tung

IPC分类号： C07C17/275

CPC分类号： C07C17/278 ,  B01J23/745 ,  B01J35/023 ,  C07C17/275 ,  C07C19/01

摘要： Disclosed is a process for the manufacture of haloalkane compounds, and more particularly, to an improved process for the manufacture of the compound 1,1,1,3,3-pentachloropropane (HCC-240fa), which mitigates the formation of by-products. The present invention is also useful in the manufacture of other haloalkane compounds such as HCC-250 and HCC-360. One embodiment of the process comprises a method and system for avoiding the formation of polyvinyl chloride during the production of HCC-240fa from CC14, in which vinyl chloride (VCM) is fed into a reactor as a vapor instead of as a liquid, using a diffusing device to further increase the contact surface between VCM vapor and CC14.

摘要翻译： 公开了一种制备卤代烷烃化合物的方法，更具体地说，涉及制备化合物1,1,1,3,3-五氯丙烷（HCC-240fa）的改进方法，其减少了副产物的形成 。 本发明也可用于制备其它卤代烷烃化合物如HCC-250和HCC-360。 该方法的一个实施方案包括在CC14生产HCC-240fa期间避免形成聚氯乙烯的方法和系统，其中将氯乙烯（VCM）作为蒸气而不是作为液体加入到反应器中，使用 扩散装置进一步增加VCM蒸气与CC14之间的接触面。

公开(公告)号：US10442819B2

公开(公告)日：2019-10-15

申请号：US15532549

申请日：2015-12-01

申请人： Christian Fischer ,  Stephane L. Bogen ,  Matthew L. Childers ,  Francesc Xavier Fradera Llinas ,  J. Michael Ellis ,  Sara Esposite ,  Qingmei Hong ,  Chunhui Huang ,  Alexander J. Kim ,  John W. Lampe ,  Michelle R. Machacek ,  Daniel R. McMasters ,  Ryan D. Otte ,  Dann L. Parker, Jr. ,  Michael Reutershan ,  Nunzio Sciammetta ,  Pengcheng P. Shao ,  David L. Sloman ,  Feroze Ujjainwalla ,  Catherine White ,  Zhicai Wu ,  Yang Yu ,  Kake Zhao ,  Craig Gibeau ,  Tesfaye Biftu ,  Purakkattle Biju ,  Lei Chen ,  Joshua Close ,  Peter H. Fuller ,  Xianhai Huang ,  Min K. Park ,  Valdimir Simov ,  David J. Witter ,  Hongjun Zhang

发明人： Christian Fischer ,  Stephane L. Bogen ,  Matthew L. Childers ,  Francesc Xavier Fradera Llinas ,  J. Michael Ellis ,  Sara Esposite ,  Qingmei Hong ,  Chunhui Huang ,  Alexander J. Kim ,  John W. Lampe ,  Michelle R. Machacek ,  Daniel R. McMasters ,  Ryan D. Otte ,  Dann L. Parker, Jr. ,  Michael Reutershan ,  Nunzio Sciammetta ,  Pengcheng P. Shao ,  David L. Sloman ,  Feroze Ujjainwalla ,  Catherine White ,  Zhicai Wu ,  Yang Yu ,  Kake Zhao ,  Craig Gibeau ,  Tesfaye Biftu ,  Purakkattle Biju ,  Lei Chen ,  Joshua Close ,  Peter H. Fuller ,  Xianhai Huang ,  Min K. Park ,  Valdimir Simov ,  David J. Witter ,  Hongjun Zhang

IPC分类号： A61K31/351 ,  A61K31/4353 ,  A61K31/5355 ,  A61K31/551 ,  C07D471/04 ,  C07D471/14 ,  C07D498/08 ,  C07D471/08 ,  C07D498/04 ,  C07D498/10 ,  A01N43/00

摘要： The present invention is directed to tricyclic compounds of formula (I) which are inhibitors of one or more mutant IDH enzymes: (I). The present invention is also directed to uses of the tricyclic compounds described herein in the potential treatment or prevention of cancers in which one or more mutant IDH enzymes are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such cancers.

公开(公告)号：US08026260B2

公开(公告)日：2011-09-27

申请号：US12084268

申请日：2006-10-30

申请人： Joshua Close ,  Richard W. Heidebrecht, Jr. ,  Solomon Kattar ,  Thomas A. Miller ,  David Sloman ,  Matthew G Stanton ,  Paul Tempest ,  David J. Witter

发明人： Joshua Close ,  Richard W. Heidebrecht, Jr. ,  Solomon Kattar ,  Thomas A. Miller ,  David Sloman ,  Matthew G Stanton ,  Paul Tempest ,  David J. Witter

IPC分类号： A61K31/4439 ,  A61K31/415 ,  A61K31/423 ,  A61K31/425 ,  A61K31/4245 ,  C07D401/02 ,  C07D271/10 ,  C07D277/20 ,  C07D231/10

CPC分类号： C07D401/12 ,  C07D231/40 ,  C07D409/04 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12

摘要： The present invention relates to a novel class of histone deacetylase inhibitors with aryl-pyrazolyl motifs. The compounds of this invention can be used to treat cancer. The compounds of this invention are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The present invention further provides pharmaceutical compositions comprising the compounds of this invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the compounds of this invention in vivo.

摘要翻译： 本发明涉及新一类具有芳基 - 吡唑基基序的组蛋白脱乙酰酶抑制剂。 本发明的化合物可用于治疗癌症。 本发明的化合物适用于选择性诱导终末分化，阻止肿瘤细胞的细胞生长和/或凋亡，从而抑制这些细胞的增殖。 因此，本发明的化合物可用于治疗具有以肿瘤细胞增殖为特征的肿瘤的患者。 本发明进一步提供包含本发明化合物和这些药物组合物的安全给药方案的药物组合物，其易于遵循，并且其在体内导致治疗有效量的本发明化合物。

公开(公告)号：US20080124402A1

公开(公告)日：2008-05-29

申请号：US11666525

申请日：2005-10-25

申请人： Yuntae Kim ,  Joshua Close ,  Mark E. Duggan ,  Barbara Hanney ,  Robert S. Meissner ,  Jeffrey Musselman ,  James J. Perkins ,  Jiabing Wang

发明人： Yuntae Kim ,  Joshua Close ,  Mark E. Duggan ,  Barbara Hanney ,  Robert S. Meissner ,  Jeffrey Musselman ,  James J. Perkins ,  Jiabing Wang

IPC分类号： A61K33/16 ,  C07D213/02 ,  A61K31/44 ,  A61K31/56 ,  A61K38/16 ,  A61K31/59 ,  A61P19/10 ,  A61P19/08 ,  A61K31/66 ,  A61K31/4535 ,  A61K33/10 ,  A61K33/06

CPC分类号： C07D213/64 ,  A61K31/44 ,  C07D213/74

摘要： Compounds of structural formula (I) are modulators of the androgen receptor (AR) in a tissue selective manner. These compounds are useful in the enhancement of weakened muscle tone and the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HIV-wasting, prostate cancer, benign prostatic hyperplasia (BPH), abdominal adiposity, metabolic syndrome, type II diabetes, cancer cachexia, Alzheimer's disease, muscular dystrophies, cognitive decline, sexual dysfunction, sleep apnea, depression, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

摘要翻译： 结构式（I）的化合物是以组织选择性方式的雄激素受体（AR）的调节剂。 这些化合物可用于增强弱化肌张力和治疗由雄激素缺乏引起的疾病或可由雄激素给药改善的疾病，包括骨质疏松症，骨质减少，糖皮质激素诱导的骨质疏松症，牙周病，骨折，骨重建后的骨损伤 手术，肌营养不良，虚弱，老化的皮肤，男性性腺机能减退，女性绝经后症状，动脉粥样硬化，高胆固醇血症，高脂血症，肥胖，再生障碍性贫血和其他造血障碍，炎性关节炎和关节修复，艾滋病毒消耗，前列腺癌，良性前列腺增生 ），腹部肥胖，代谢综合征，II型糖尿病，癌症恶病质，阿尔茨海默氏病，肌营养不良症，认知衰退，性功能障碍，睡眠呼吸暂停，抑郁症，卵巢早衰以及自身免疫性疾病，单独或与其它活性剂组合。

公开(公告)号：US20140235641A1

公开(公告)日：2014-08-21

申请号：US14345982

申请日：2012-09-21

申请人： Jason Brubaker ,  Joshua Close ,  Tony Siu ,  Graham Frank Smith ,  Luis E. Torres ,  Hyun Chong Woo ,  Jonathan R. Young ,  Zhongyong Wei ,  Feng Shi

发明人： Jason Brubaker ,  Joshua Close ,  Tony Siu ,  Graham Frank Smith ,  Luis E. Torres ,  Hyun Chong Woo ,  Jonathan R. Young ,  Zhongyong Wei ,  Feng Shi

IPC分类号： C07D401/04 ,  C07D405/14 ,  C07D409/04 ,  C07D417/14 ,  C07D405/04 ,  C07D413/14 ,  C07D401/14

CPC分类号： C07D405/08 ,  C07D231/38 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/08 ,  C07D403/12 ,  C07D405/04 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D409/04 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14

摘要： The instant invention provides compounds of formula I which are JAK inhibitors, and as such are useful for the treatment of JAK-mediated diseases such as rheumatoid arthritis, asthma, COPD and cancer.

摘要翻译： 本发明提供了作为JAK抑制剂的式I化合物，因此可用于治疗JAK介导的疾病如类风湿性关节炎，哮喘，COPD和癌症。