公开(公告)号：US07645780B2

公开(公告)日：2010-01-12

申请号：US11447789

申请日：2006-06-06

Applicant: Varghese John ,  Michel Maillard ,  James P. Beck ,  Eric T. Baldwin ,  Robert Hughes ,  Shon R. Pulley ,  Ruth T. TenBrink

Inventor： Varghese John ,  Michel Maillard ,  James P. Beck ,  Eric T. Baldwin ,  Robert Hughes ,  Shon R. Pulley ,  Ruth T. TenBrink

IPC: C07D213/56 ,  A61K31/44

CPC classification number: C07C233/36 ,  C07C235/10 ,  C07C235/74 ,  C07C271/24 ,  C07C311/05 ,  C07C327/30 ,  C07C2601/02 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2602/10 ,  C07D209/14 ,  C07D213/38 ,  C07D213/64 ,  C07D215/233 ,  C07D215/38 ,  C07D215/42 ,  C07D215/46 ,  C07D217/22 ,  C07D233/61 ,  C07D233/64 ,  C07D237/08 ,  C07D237/14 ,  C07D239/26 ,  C07D239/38 ,  C07D241/12 ,  C07D249/08 ,  C07D261/08 ,  C07D265/02 ,  C07D277/28 ,  C07D295/135 ,  C07D307/52 ,  C07D309/14 ,  C07D311/68 ,  C07D311/74 ,  C07D333/20 ,  C07D333/22 ,  C07D335/06 ,  C07D405/04 ,  C07D407/06 ,  C07D409/12 ,  C07D495/04

Abstract: Disclosed are compounds of the formula: where variables Z, X, R15, R2, R3, and Rc are defined herein. Compounds disclosed herein are inhibitors of the beta-secretase enzyme and are therefore useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal.

Abstract translation: 公开了下式的化合物：其中变量Z，X，R 15，R 2，R 3和R c在本文中定义。 本文公开的化合物是β-分泌酶的抑制剂，因此可用于治疗阿尔茨海默病和以哺乳动物中Aβ肽沉积为特征的其它疾病。

公开(公告)号：US20090253906A1

公开(公告)日：2009-10-08

申请号：US12417598

申请日：2009-04-02

Applicant: Bruce F. MOLINO ,  Shuang LIU ,  Peter R. GUZZO ,  James P. BECK

Inventor： Bruce F. MOLINO ,  Shuang LIU ,  Peter R. GUZZO ,  James P. BECK

IPC: C07D413/14 ,  C07D401/14 ,  C07D401/04 ,  C07D403/14 ,  C07D409/14 ,  C07D409/04 ,  C07D413/04 ,  C07D417/14 ,  C07D417/04

CPC classification number: 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

Abstract: 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.

Abstract translation: 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 ]吡啶基，吡唑并[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：US07265116B2

公开(公告)日：2007-09-04

申请号：US10917801

申请日：2004-08-13

Applicant: James P. Beck ,  Matt A. Curry ,  Mark A. Smith

Inventor： James P. Beck ,  Matt A. Curry ,  Mark A. Smith

IPC: A61K31/50

CPC classification number: C07D401/04 ,  C07D217/04 ,  C07D405/04 ,  C07D409/04 ,  C07D413/04

Abstract: Provided herein are compounds of the formula (I): wherein R1-R8 are as described herein, R4 being phthalazinyl, pyrazinyl, pyridazinyl, or quinoxalinyl. Such compounds are particularly useful in the treatment of a disorder which is created by or is dependent upon decreased availability of serotonin, norepinephrine, or dopamine.

Abstract translation: 本文提供了式（I）的化合物：其中R 1 -R 8如本文所述，R 4是酞嗪基，吡嗪基， 哒嗪基或喹喔啉基。 这样的化合物特别可用于治疗由5-羟色胺，去甲肾上腺素或多巴胺的可用性降低而产生或依赖于其的依赖性。

公开(公告)号：US06846813B2

公开(公告)日：2005-01-25

申请号：US09895843

申请日：2001-06-29

Applicant: James P. Beck ,  Andrea Gailunas ,  Roy Hom ,  Barbara Jagodzinska ,  Varghese John ,  Michel Maillard

Inventor： James P. Beck ,  Andrea Gailunas ,  Roy Hom ,  Barbara Jagodzinska ,  Varghese John ,  Michel Maillard

IPC: A61P25/28 ,  C07C215/28 ,  C07C233/78 ,  C07C235/84 ,  C07C239/20 ,  C07C243/22 ,  C07C243/28 ,  C07C271/16 ,  C07C271/18 ,  C07C275/24 ,  C07C311/03 ,  C07C311/08 ,  C07C311/13 ,  C07C311/16 ,  C07C311/37 ,  C07C317/44 ,  C07C323/60 ,  C07D211/60 ,  C07D215/12 ,  C07D223/10 ,  C07D277/04 ,  C07D295/13 ,  C07D303/36 ,  C07D307/52 ,  C07D307/54 ,  C07D333/24 ,  A61K31/33 ,  A61K31/495 ,  C07D241/00 ,  C07D241/04

CPC classification number: C07D295/13 ,  C07C215/28 ,  C07C233/78 ,  C07C235/84 ,  C07C239/20 ,  C07C243/22 ,  C07C243/28 ,  C07C271/16 ,  C07C271/18 ,  C07C275/24 ,  C07C311/03 ,  C07C311/08 ,  C07C311/13 ,  C07C311/16 ,  C07C311/37 ,  C07C317/44 ,  C07C323/60 ,  C07D211/60 ,  C07D215/12 ,  C07D223/10 ,  C07D277/04 ,  C07D303/36 ,  C07D307/52 ,  C07D307/54 ,  C07D333/24

Abstract: The present invention is disubstituted amines of formula (I) and disubstituted amines of formula (II) useful in treating Alzheimer's disease and other similar diseases.

Abstract translation: 本发明是式（I）的二取代胺和式（II）的二取代的胺，其可用于治疗阿尔茨海默病和其它类似疾病。

公开(公告)号：US06579885B2

公开(公告)日：2003-06-17

申请号：US10091949

申请日：2002-03-06

Applicant: James P. Beck ,  Matt A. Curry ,  Mark A. Smith

Inventor： James P. Beck ,  Matt A. Curry ,  Mark A. Smith

IPC: C07D21702

CPC classification number: C07D401/04 ,  C07D217/04 ,  C07D405/04 ,  C07D409/04 ,  C07D413/04

Abstract: Provided herein are compounds of the formula (I): wherein R1-R8 are as described herein, R4 being aryl or heteroaryl Such compounds are particularly useful in the treatment of a disorder which is created by or is dependent upon decreased availability of serotonin, norepinephrine or dopamine.

Abstract translation: 本文提供了式（I）的化合物：其中R 1 -R 8如本文所述，R 4是芳基或杂芳基。该化合物特别可用于治疗由5-羟色胺，去甲肾上腺素的可用性降低而产生或依赖于 或多巴胺。

公开(公告)号：US06245769B1

公开(公告)日：2001-06-12

申请号：US09145231

申请日：1998-09-01

Applicant: Argyrios G. Arvanitis ,  Paul J. Gilligan ,  James P. Beck ,  Rajagopal Bakthavatchalam

Inventor： Argyrios G. Arvanitis ,  Paul J. Gilligan ,  James P. Beck ,  Rajagopal Bakthavatchalam

IPC: A61K314192

CPC classification number: C07D471/04 ,  C07D487/04

Abstract: Corticotropin releasing factor (CRF) antagonists of Formula (I): and their use in treating psychiatric disorders and neurological diseases, anxiety-related disorders, post-traumatic stress disorder, supranuclear palsy and feeding disorders as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress in mammals.

Abstract translation: 式（I）的促肾上腺皮质激素释放因子（CRF）拮抗剂及其用于治疗精神疾病和神经系统疾病，焦虑相关疾病，创伤后应激障碍，核上性麻痹和进食障碍以及免疫学，心血管或心脏的治疗 与哺乳动物精神病理障碍和压力相关的疾病和结肠超敏反应。

公开(公告)号：US06174912B1

公开(公告)日：2001-01-16

申请号：US09138460

申请日：1998-08-21

Applicant: James P. Beck ,  Paul J. Gilligan

Inventor： James P. Beck ,  Paul J. Gilligan

IPC: A61K314162

CPC classification number: C07D487/04

Abstract: Corticotropin releasing factor (CRF) antagonists of Formulae (I) or (II): and their use in treating psychiatric disorders and neurological diseases including major depression, anxiety-related disorders, post-traumatic stress disorder, supranuclear palsy and feeding disorders as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress.

Abstract translation: 式（I）或（II）的促肾上腺皮质激素释放因子（CRF）拮抗剂及其用于治疗精神疾病和神经疾病，包括主要抑郁症，焦虑相关疾病，创伤后应激障碍，核上性麻痹和进食障碍以及 治疗与精神病理学障碍和应激相关的免疫学，心血管或心脏相关疾病和结肠超敏反应。

公开(公告)号：US4567138A

公开(公告)日：1986-01-28

申请号：US644647

申请日：1984-08-27

Applicant: James P. Beck ,  Carlos E. Luna

Inventor： James P. Beck ,  Carlos E. Luna

IPC: C12Q1/48

CPC classification number: C12Q1/48 ,  Y10S435/81

Abstract: A substrate solution comprising (a) a substrate selected from a group consisting of salts of L-.gamma.-glutamyl-p-nitroanilide and L-.gamma.-glutamyl-3-carboxy-p-nitroanilide; and (b) a polyol selected from a group consisting of alkyl polyols containing 2 to 10 carbon atoms and 2 to 10 hydroxy groups and polyethylene glycol having an average molecular weight of from about 200 to about 600.Also, a kit for the determination of .gamma.-glutamyltransferase activity of the type comprising (a) a buffered medium comprising a buffer and a .gamma.-glutamyl residue acceptor; and (b) a substrate solution; the buffered medium and substrate solution being adapted such that preselected aliquots thereof can react in the presence of .gamma.-glutamyltransferase to produce an absorbing cleavage product. The kit is characterized in that the substrate solution is as described above.In addition, a method for determining .gamma.-glutamyltransferase acitivity of the type comprising (a) contacting in any preselected order an aliquot of a buffered medium comprising a buffer and a .gamma.-glutamyl residue acceptor, an aliquot of a substrate solution, and an aliquot of a sample to be assayed to thereby form a cleavage product; and (b) measuring the absorbance of said cleavage product. The method is characterized in that the substrate solution is as described above.

Abstract translation: 一种底物溶液，其包含（a）选自由L-γ-谷氨酰 - 对硝基苯胺和L-γ-谷氨酰基-3-羧基 - 对硝基苯胺的盐组成的组的底物; 和（b）选自含有2至10个碳原子的烷基多元醇和2至10个羟基的多元醇和平均分子量为约200至约600的聚乙二醇。另外，用于测定 该类型的γ-谷氨酰转移酶活性包括（a）包含缓冲液和γ-谷氨酰残基受体的缓冲介质; 和（b）底物溶液; 缓冲介质和底物溶液适于使得其预选等分试样在γ-谷氨酰转移酶存在下反应以产生吸收性裂解产物。 该试剂盒的特征在于底物溶液如上所述。 另外，用于确定该类型的γ-谷氨酰转移酶活性的方法包括（a）以任何预先选择的顺序接触包含缓冲液和γ-谷氨酰残基受体的缓冲介质的等分试样，底物溶液的等分试样和等分试样 的待测样品，从而形成裂解产物; 和（b）测量所述切割产物的吸光度。 该方法的特征在于底物溶液如上所述。

公开(公告)号：US4211015A

公开(公告)日：1980-07-08

申请号：US870537

申请日：1978-01-18

Applicant: Thomas H. Adams ,  James P. Beck ,  Robert C. Menson

Inventor： Thomas H. Adams ,  James P. Beck ,  Robert C. Menson

IPC: A61K39/00 ,  A01N1/02 ,  A61K9/14 ,  A61K9/19 ,  A61K35/14 ,  A61K35/16 ,  A61K38/00 ,  A61K38/16 ,  B01D9/02 ,  B01D9/04 ,  C12N1/04 ,  C12N9/98 ,  F25C1/00 ,  F25D3/10 ,  F26B5/06 ,  G01N33/483

CPC classification number: F25D3/10 ,  A01N1/0278 ,  A61K35/16 ,  A61K9/19 ,  C12N1/04 ,  C12N9/98 ,  F25C1/00 ,  F26B5/065 ,  Y10T436/105831 ,  Y10T436/107497

Abstract: An improved method and apparatus is disclosed for producing frozen particulate compositions from liquid feedstock. A continuous stream of liquid feedstock is passed through an orifice and into a liquid freezant without the orifice contacting the freezant. Compositions produced by this improved method have low proportions of fine and large particles, yielding particularly beneficial results in the case of quality control materials. The compositions are advantageously employed in automated weighing and filling apparatus.

Abstract translation: 公开了用于从液体原料生产冷冻颗粒组合物的改进的方法和装置。 连续的液体原料流通过孔并进入液体冷冻剂中，而孔不接触冷冻剂。 通过该改进方法制备的组合物具有低比例的精细和大颗粒，在质量控制材料的情况下产生特别有益的结果。 组合物有利地用于自动称重和填充装置中。

公开(公告)号：US08741901B2

公开(公告)日：2014-06-03

申请号：US13540446

申请日：2012-07-02

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

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

IPC: A61K31/497 ,  C07D217/00

CPC classification number: 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

Abstract: 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.

Abstract translation: 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。