公开(公告)号：US10155716B2

公开(公告)日：2018-12-18

申请号：US15852922

申请日：2017-12-22

申请人： CAYMAN CHEMICAL COMPANY INCORPORATED

发明人： Gilles Chambournier ,  Gregory William Endres ,  Kirk William Hering ,  Victor Fedij ,  Hussein Mahmoud Mahmoud

IPC分类号： C07C29/09 ,  C07C59/72 ,  C07F7/18 ,  C07C41/26 ,  C07C51/09 ,  C07C51/347 ,  C07C51/41 ,  C07C45/29 ,  C07C51/00

摘要： The present invention provides amine salts of the prostacyclin analogue of Formula I and processes for generating these amine salts.

公开(公告)号：US09708287B2

公开(公告)日：2017-07-18

申请号：US14872419

申请日：2015-10-01

申请人： Cayman Chemical Company Incorporated

发明人： Mitchell A. deLong ,  Kalla Lynn Kvalnes ,  Raymond Boissy

IPC分类号： C07D335/02 ,  C07D309/10 ,  A61K8/49 ,  A61K8/69 ,  C07D309/12 ,  A61Q19/02 ,  A61K8/60 ,  C07D215/227 ,  C07D311/94 ,  C07D313/04 ,  C07D313/18 ,  C07D333/32 ,  C07D333/64 ,  C07D493/04 ,  C07H15/203 ,  C07D311/02 ,  C07D215/22 ,  C07D319/12 ,  C07D333/48 ,  C07D307/20 ,  A61K8/33

CPC分类号： C07D335/02 ,  A61K8/33 ,  A61K8/4926 ,  A61K8/4973 ,  A61K8/498 ,  A61K8/4986 ,  A61K8/602 ,  A61K8/69 ,  A61K2800/591 ,  A61Q19/02 ,  C07D215/22 ,  C07D215/227 ,  C07D307/20 ,  C07D309/10 ,  C07D309/12 ,  C07D311/02 ,  C07D311/94 ,  C07D313/04 ,  C07D313/18 ,  C07D319/12 ,  C07D333/32 ,  C07D333/48 ,  C07D333/64 ,  C07D493/04 ,  C07H15/203

摘要： Compounds that function, alone or in combination, as inhibitors of pigmentation for the improvement of mammalian skin are described herein. Specifically, the compounds of the present disclosure, namely chiral, non-racemic compounds, function as pigment formation inhibitors thereof to beautify skin and discourage the production of melanins. One or more products, consumer and otherwise, comprising the chiral, non-racemic compounds are disclosed herein. Methods of employing both the compounds of the present disclosure and the products incorporating the present compounds are also disclosed herein.

公开(公告)号：US20150322107A1

公开(公告)日：2015-11-12

申请号：US14801897

申请日：2015-07-17

申请人： Cayman Chemical Company, Incorporated ,  The Regents of the University of Michigan

发明人： Stephen Douglas Barrett ,  Daniel Austin Bochar ,  Levi Lynn Blazer ,  Fred Lawrence Ciske ,  Gregory William Endres ,  Jeffrey Keith Johnson ,  Gregory Scott Keyes ,  Ranjinder Singh Sidhu ,  Raymond C. Trievel ,  Margaret Lynn Collins

IPC分类号： C07H19/16 ,  G01N33/58

CPC分类号： G01N33/582 ,  C07D471/04 ,  C07D473/34 ,  C07D519/00 ,  C07H19/16 ,  G01N21/6428 ,  G01N2201/061 ,  G01N2333/91011

摘要： Assay methods may generally comprise forming homogeneous assay mixtures comprising target SAM-utilizing protein, fluorescent detection analyte, and test compound, incubating, and measuring FP or TR-FRET signal emitted in order to determine a measure of test compound-SAM-utilizing protein binding. Assay mixtures comprise a SAM-utilizing protein, and a fluorescent detection analyte that binds with the SAM-utilizing protein in the absence of test compound. Assay mixtures may further comprise a test compound. Assay mixture embodiments may generate FP or TR-FRET signal properties that are a function of the inherent binding interactions of both the test compound and the detection analyte with the SAM-utilizing protein. Fluorescent detection analytes comprise a fluorophore moiety, a covalent linker moiety, and a SAM-utilizing protein ligand moiety and could be utilized in FP or TR-FRET assays to measure test compound binding.

摘要翻译： 测定方法通常可以包括形成均匀的测定混合物，其包含目标SAM利用蛋白质，荧光检测分析物和测试化合物，孵育和测量发射的FP或TR-FRET信号，以确定测试化合物-SM利用蛋白质结合的量度 。 测定混合物包含SAM-利用蛋白质和在不存在测试化合物的情况下与SAM利用蛋白质结合的荧光检测分析物。 测定混合物可进一步包含测试化合物。 测定混合物实施方案可以产生FP或TR-FRET信号特性，其是测试化合物和检测分析物与SAM-利用蛋白的固有结合相互作用的函数。 荧光检测分析物包含荧光团部分，共价连接体部分和SAM-利用蛋白质配体部分，并且可用于FP或TR-FRET测定以测量测试化合物结合。

公开(公告)号：US09126973B2

公开(公告)日：2015-09-08

申请号：US14499763

申请日：2014-09-29

申请人： Cayman Chemical Company, Incorporated

发明人： Gregory W. Endres ,  Pil Heui Lee ,  Kirk Lang Olson ,  James Bernard Kramer ,  Fred Lawrence Ciske ,  Stephen Douglas Barrett

IPC分类号： A61K31/44 ,  C07D401/04 ,  C07D239/02 ,  C07D239/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D407/14 ,  C07D413/04 ,  C07D417/04 ,  A61K31/4439 ,  A61K45/06 ,  C07D417/14 ,  A61K31/506 ,  A61K31/5377

CPC分类号： C07D401/04 ,  A61K31/4439 ,  A61K31/506 ,  A61K31/5377 ,  A61K45/06 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D407/14 ,  C07D413/04 ,  C07D417/04 ,  C07D417/14

摘要： Multiheteroaryl compounds, their preparation, pharmaceutical compositions comprising these compounds, and their pharmaceutical use in the prevention and treatment of prostaglandin D2 mediated diseases and conditions that may be modulated by the inhibition of hematopoietic prostaglandin D synthase (H-PGDS).

摘要翻译： 多杂芳基化合物，其制备方法，包含这些化合物的药物组合物及其在预防和治疗前列腺素D2介导的疾病和可能通过抑制造血前列腺素D合成酶（H-PGDS）调节的病症）中的药物用途。

公开(公告)号：US20130079375A1

公开(公告)日：2013-03-28

申请号：US13666054

申请日：2012-11-01

申请人： Cayman Chemical Company, Incorporated

发明人： Gregory W. Endres ,  Pil Heui Lee ,  Kiurk Lang Olson ,  James Bernard Kramer ,  Fred Lawrence Ciske ,  Stephen Douglas Barrett

IPC分类号： C07D417/14 ,  A61K45/06 ,  A61K31/4439

CPC分类号： C07D401/04 ,  A61K31/4439 ,  A61K31/506 ,  A61K31/5377 ,  A61K45/06 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D407/14 ,  C07D413/04 ,  C07D417/04 ,  C07D417/14

摘要： Multiheteroaryl compounds, their preparation, pharmaceutical compositions comprising these compounds, and their pharmaceutical use in the prevention and treatment of prostaglandin D2 mediated diseases and conditions that may be modulated by the inhibition of hematopoietic prostaglandin D synthase (H-PGDS).

公开(公告)号：US20180141889A1

公开(公告)日：2018-05-24

申请号：US15874093

申请日：2018-01-18

申请人： CAYMAN CHEMICAL COMPANY INCORPORATED

发明人： Kirk William Hering ,  Gilles Chambournier ,  Gregory William Endres ,  Victor Fedij ,  Thomas James Krell, II ,  Hussein Mahmoud Mahmoud

IPC分类号： C07C51/347 ,  C07D301/00 ,  C07C205/57 ,  C07C45/29 ,  C07C41/44 ,  C07D303/14 ,  C07D317/22 ,  C07C51/41 ,  C07C51/09 ,  C07C41/26 ,  C07D301/32 ,  C07F7/18 ,  C07D303/16 ,  C07C59/72 ,  C07C43/23

摘要： The present invention provides processes for preparing a prostacyclin analogue of Formula I or a pharmaceutically acceptable salt thereof, wherein R10 is a linear or branched C1-6 alkyl. The processes of the present invention comprise steps that generate improved yields and fewer byproducts than traditional methods. The processes of the present invention employ reagents (e.g., the oxidizing reagent) that are less toxic that those used in the traditional methods (e.g., oxalyl chloride). Many of the processes of the present invention generate intermediates with improved e.e. and chemical purity; thereby eliminating the need of additional chromatography steps. And, the processes of the present invention are scalable to generate commercial quantities of the final compound.

公开(公告)号：US20150315114A1

公开(公告)日：2015-11-05

申请号：US14650234

申请日：2013-12-06

申请人： CAYMAN CHEMICAL COMPANY INCORPORATED

发明人： Kirk Willam HERING ,  Gilles CHAMBOURNIER ,  Gregory William ENDRES ,  Victor FEDIJ ,  Thomas James KRELL, II ,  Hussein Mahmoud MAHMOUD

IPC分类号： C07C51/347 ,  C07D303/16 ,  C07D301/00 ,  C07C41/44 ,  C07C205/57 ,  C07C45/29 ,  C07F7/18 ,  C07D301/32

摘要： The present invention provides processes for preparing a prostacyclin analogue of Formula (I) or a pharmaceutically acceptable salt thereof, wherein R10 is a linear or branched C1-6 alkyl. The processes of the present invention comprise steps that generate improved yields and fewer byproducts than traditional methods. The processes of the present invention employ reagents (e.g., the oxidizing reagent) that are less toxic that those used in the traditional methods (e.g., oxalyl chloride). Many of the processes of the present invention generate intermediates with improved e.e. and chemical purity; thereby eliminating the need of additional chromatography steps. And, the processes of the present invention are scalable to generate commercial quantities of the final compound.

摘要翻译： 本发明提供制备式（I）的前列环素类似物或其药学上可接受的盐的方法，其中R 10是直链或支链C 1-6烷基。 本发明的方法包括与传统方法相比产生提高的产率和较少的副产物的步骤。 本发明的方法使用与传统方法（例如草酰氯）中使用的试剂毒性相差的试剂（例如，氧化试剂）。 本发明的许多方法产生具有改进的e.e的中间体。 和化学纯度; 从而不需要额外的色谱步骤。 而且，本发明的方法是可扩展的，以产生商业数量的最终化合物。

公开(公告)号：US09908834B2

公开(公告)日：2018-03-06

申请号：US15583457

申请日：2017-05-01

申请人： CAYMAN CHEMICAL COMPANY INCORPORATED

发明人： Kirk William Hering ,  Gilles Chambournier ,  Gregory William Endres ,  Victor Fedij ,  Thomas James Krell, II ,  Hussein Mahmoud Mahmoud

IPC分类号： C07C41/26 ,  C07D303/16 ,  C07C51/347 ,  C07D301/00 ,  C07C45/29 ,  C07C41/44 ,  C07D301/32 ,  C07C205/57 ,  C07F7/18 ,  C07D317/22 ,  C07D303/14 ,  C07C51/09 ,  C07C51/41

CPC分类号： C07C51/347 ,  C07C41/26 ,  C07C41/44 ,  C07C45/29 ,  C07C51/09 ,  C07C51/412 ,  C07C205/57 ,  C07C2603/14 ,  C07D301/00 ,  C07D301/32 ,  C07D303/14 ,  C07D303/16 ,  C07D317/22 ,  C07F7/1804 ,  C07C59/72 ,  C07C43/23

摘要： The present invention provides processes for preparing a prostacyclin analog of Formula (I) or a pharmaceutically acceptable salt thereof, wherein R10 is a linear or branched C1-6 alkyl. The processes of the present invention comprise steps that generate improved yields and fewer byproducts than traditional methods. The processes of the present invention employ reagents (e.g., the oxidizing reagent) that are less toxic that those used in the traditional methods (e.g., oxalyl chloride). Many of the processes of the present invention generate intermediates with improved e.e. and chemical purity; thereby eliminating the need of additional chromatography steps. And, the processes of the present invention are scalable to generate commercial quantities of the final compound.

公开(公告)号：US20160289158A1

公开(公告)日：2016-10-06

申请号：US15036219

申请日：2014-11-07

申请人： CAYMAN CHEMICAL COMPANY INCORPORATED

发明人： GILLES CHAMBOURNIER ,  GREGORY WILLIAM ENDRES ,  KIRK WILLIAM HERING ,  VICTOR FEDIJ ,  HUSSEIN MAHMOUD MAHMOUD

IPC分类号： C07C59/72 ,  C07C45/29 ,  C07F7/18 ,  C07C51/00

CPC分类号： C07C59/72 ,  C07C29/09 ,  C07C41/26 ,  C07C45/298 ,  C07C51/00 ,  C07C51/09 ,  C07C51/347 ,  C07C51/412 ,  C07C2603/14 ,  C07F7/1804 ,  C07C43/23 ,  C07C35/37

摘要： The present invention provides amine salts of the prostacyclin analogue of Formula I and processes for generating these amine salts.

公开(公告)号：US20150323542A1

公开(公告)日：2015-11-12

申请号：US14801902

申请日：2015-07-17

申请人： Cayman Chemical Company, Incorporated ,  The Regents of the University of Michigan

发明人： Stephen Douglas Barrett ,  Daniel Austin Bochar ,  Levi Lynn Blazer ,  Fred Lawrence Ciske ,  Gregory William Endres ,  Jeffrey Keith Johnson ,  Gregory Scott Keyes ,  Ranjinder Singh Sidhu ,  Raymond C. Trievel ,  Margaret Lynn Collins

IPC分类号： G01N33/58 ,  G01N21/64 ,  C07D519/00 ,  C07D473/34 ,  C07D471/04

CPC分类号： G01N33/582 ,  C07D471/04 ,  C07D473/34 ,  C07D519/00 ,  C07H19/16 ,  G01N21/6428 ,  G01N2201/061 ,  G01N2333/91011

摘要： Assay methods may generally comprise forming homogeneous assay mixtures comprising target SAM-utilizing protein, fluorescent detection analyte, and test compound, incubating, and measuring FP or TR-FRET signal emitted in order to determine a measure of test compound-SAM-utilizing protein binding. Assay mixtures comprise a SAM-utilizing protein, and a fluorescent detection analyte that binds with the SAM-utilizing protein in the absence of test compound. Assay mixtures may further comprise a test compound. Assay mixture embodiments may generate FP or TR-FRET signal properties that are a function of the inherent binding interactions of both the test compound and the detection analyte with the SAM-utilizing protein. Fluorescent detection analytes comprise a fluorophore moiety, a covalent linker moiety, and a SAM-utilizing protein ligand moiety and could be utilized in FP or TR-FRET assays to measure test compound binding.